Effect of calcium on the pellet height response of Tetrahymena cilia. The pellet height response (a measure of the increase in height of the pellet of cilia obtained by brief centrifugation in the presence of ATP as compared to the absence of ATP) of Tetrahymena cilia prepared by deciliation in the presence of Ca2+ is sensitive to the concentration of free Ca2+ during the pellet height assay. The magnitude of the increase in pellet height and the sharpness of the pellet boundary both increase markedly with increasing [Ca2+]. The half-maximal effect is attained at a free [Ca2+] of about 1.5 x 10(-7) M. The pellet height assay thus measures a Ca2+-sensitive component of the ciliary motile system. The possibility that this is the Ca2+-sensitive orientation system is discussed.


Biochemical characteristics, metabolism, and antitumor activity of several acetylated hexosamines. We have synthesized several potential inhibitors and/or modifiers of the carbohydrate portion of plasma membrane glycoconjugates. These include fluorinated and actylated analogs of D-glucosamine, D-galactosamine, and D-mannosamine. These compounds have been tested to determine their effects on both[14C] glucosamine and [3H] leucine incorporation into glycoconjugate and on cell growth and viability using P-288 murine lymphoma cells maintained in tissue culture. The most cytotoxic agent tested was 2-acetamido-2-deoxy-1,3,4,6-tetra-O-acetyl-beta-D-glucopyranose or simply beta-pentaacetylglucosamine which prevented cell growth at 10(-4)-10(-3) M. beta-Pentaacetylglucosamine cytotoxicity was correlated with its high lipid solubility, having an octanol/water partition coefficient of 0.424 as compared with 0.278 for the alpha-anomer and 0.017 for N-acetylglucosamine. In vitro metabolism studies with [4C]- and/or [3H]-labeled pentaacetylglucosamine have indicated intracellular de-O-acetylation leading to the biosynthesis of UDP-N-acetylglucosamine, followed by the incorporation of this sugar into cellular glycoprotein. Concomitant with the formation of increased amounts of this nucleotide sugar, intracellular UTP and CTP pools fell to one third normal within 3 h after the administration of 1 mM pentaacetylglucosamine. At present it is unclear whether the cytotoxicity of beta-pentaacetylglucosamine or other similar agents is due to alterations in nucleotide and nucleotide-sugar pools causing a decrease in energy charge and polynucleotide biosynthesis or is due to a direct effect on membrane glycoconjugate biosynthesis.


Possible involvement of GABA mechanisms in central cardiovascular and respiratory control. Studies on the interaction between diazepam, picrotoxin and clonidine. Various doses (0.1-1 mg/kg) of diazepam were given to chloralose anesthetized rats, with both systemic (i.p.) and central injections being tested. Arterial pressure, heart rate, respiration depth and frequency were recorded. Diazepam caused a dose-dependent decrease in the arterial pressure after systemic administration and also decreased it after central administration. However, only intraventricular but not intracisternal injections of diazepam were effective. The hypotensive effect of systemic diazepam was competitively counteracted by pretreatment with picrotoxin, a putative gamma-aminobutyric acid receptor blocking agent. The hypotensive effect of the centrally acting alpha-adrenoreceptor agonist clonidine was not influenced by picrotoxin pretreatment. The effect of diazepam on heart rate was inconsistent. Diazepam caused a reduction of respiratory frequency, which was not counteracted by picrotoxin pretreatment. It is concluded that central gabergic mechanisms are to some extent involved in the hypotensive effect of diazepam, probably at a supramedullary level. The hypotensive effect of a threshold dose of diazepam was blocked by a small dose of clonidine. Likewise, diazepam pretreatment could counteract the hypotension, bradycardia and respiratory frequency reduction caused by a threshold dose of clonidine. These results suggest that gabergic and/or other benzodiazepine-sensitive receptors may interact with alpha-adrenoreceptors in the control of central cardiovascular and respiratory mechanisms.


The temporal dimensions of anticonvulsant action of some newer benzodiazepines against metrazol induced seizures in mice and rats. In a time-distribution study, the anticonvulsant effects of four benzodiazepine compounds were compared with those of three standard antiepileptics against metrazol-induced seizures in mice and rats. Ethosuximide and trimethadione had the shortest duration of action in mice, but protected the rats up to 6 hr. Phenobarbitone, diazepam, flurazepam and nitrazepam protected the mice up to 12 hr, but the rats were effectively protected only up to 3-4 hr. Clonazepam, the most potent and effective agent, protected the mice from clonic-tonic seizures up to 18-20 hr and the rats up to 6-7 hr. Comparison of the PD50 from clonic seizure at the peak-effect hours revealed that the benzodiazepines were 16 to 96 times more potent than phenobarbitone on a molar basis, while phenobarbitone itself was 12 to 26 times more potent than ethosuximide and trimethadione. Tonic seizures and mortality were largely suppressed by all drugs until 18-20 hr in mice and 6-7 hr in rats. Seizure latency and mortality patterns varied from drug to drug but not in a dose-dependent manner.


Pharmacokinetics of nicotine in adult and infant mice. Experiments were done to compare the time-courses of the nicotine concentration in the blood, heart, and brain of infant and adult mice after small and large single doses of radioactive nicotine tartrate. In some experiments the nicotine receptors were blocked with mecamylamine or hexamethonium, and their effects on nicotine levels were measured. The nicotine-induced tremor was allowed visually, and its effects on the heart rate were measured by ECG. In adult mice the peak levels of brain nicotine occurred at 10 min, whereas in infant mice the brain nicotine levels were still rising at 20 min. In the latter the blood and heart nicotine levels were higher than the respective brain levels, and the nicotine level in the brain stem exceeded the hemisphere level. The results were reversed in adult mice. A remarkable accumulation of nicotine in the infant heart was measured. Pretreatment with mecamylamine lowered brain nicotine levels in adult mice, and in infant mice the nicotine levels in blood and heart were lowered as well. This pretreatment abolished the nicotine tremor and its effects on the heart rate similarly in both age groups. This suggests that the difference in nicotine levels after mecamylamine in infant and adult mice may not depend solely on possible differences in circulatory changes but can represent differences in "receptor population" as well. Hexamethonium did not abolish the central depressant effect of nicotine on the heart rate nor did it lower the brain nicotine levels. This supports the view that there is some correlation of the central effects of nicotine and its brain levels.


Metabolic effects of repeated short-term exposures to heat in the rat. Repeated daily exposures of rats to a hot ambient temperature (40-41 degrees C) for 20 days induced activation of the oxidative enzymes in the thigh muscle and of lactate dehydrogenase in the myocardium. Heat-stressed rats also showed increased tolerance to cold. These changes, it is suggested, are caused by the increased sympathetic activity bouts associated with the heat stresses. The interscapular brown adipose tissue, however, showed adaptive changes similar to those induced by warm acclimation. The activity of oxidative enzymes was decreased and the fat droplets became large and unilocular.


[Parathyreoid autoransplantation in secondary hyperparathyreoidism (author's transl)]. Subtotal Parathyreoidectomy offers no problem after surgery, nor after Kidney transplantation. But a recurrence needs extensive investigations for localisation of recurrent hyperplastic glands. The necessary reoperation is loaded with difficulties. After total Parathyreoidectomy hypocalcaemia is a severe complication. Therefore in patients awaiting Kidney transplants in a chronic dialysis program the procedure is not opportune. In 11 patients following total Parathyreoidectomy and autoplastic parathyreoid transplant, we found nearly normal parathyreoid hormone plasma levels. The advantage of this method is: The function of the autoplastic graft is testable and a possible recurrence is easily resectable.


[Gastroduodenostomy and duodenogastric reflux (author's transl)]. In 36 pigs the intragastric C14 bile acid reflux and the concentration of lysolecithin is measured following different types of hemigastrectomy and gastroduodenostomy. Termino-terminal, termino-lateral and supraduodenal termino-lateral anastomosisses were as well studied as an isoperistaltic jejunal transposition of 15 cm resp. 25 cm length.-After all types of direct gastroduodenostomy the amounts of intragastral C14 bile acids and lysolecithin were significantly elevated. An additional jejunal transposition decrease the reflux in relation to the length of the transposed jejunal segment. The importance of the duodenogastric reflex of bile acids and lysolecithin for the development of alkaline reflux gastritis and carcinoma of the gastric stump is discussed. For clinical purpose a replacement of the pyloric reflux barrier by a primary jejunal transposition in case of pylorectomy has to be discussed.


[Pancreatic juice and stress ulcers of the rat (author's transl)]. In 55 rats the role of pancreatic juice for the development of stress ulcers was stuided. After ligation of the common bile duct the stress ulcer incidence was significantly decreased. An additional pancreaticogastrostomy was followed by an even lower ulcer frequency. After pancreaticojejunostomy a higher ulcer incidence was found as after bile duct ligation alone. The role of a duodenogastric reflux for development of stress ulcers is discussed. The ulcerogenic property of bile acids and of the combination of bile and pancreatic juice, caused by lysolecithin, is demonstrated. Pancreatic juice doesn't work as an ulcerogenic substance, but possibly has a protective function by uffering the hydrochloric acid.


[Early complications and early mortality of various operative methods of gastrectomy (author's transl)]. From 1959-1976, 183 gastrectomies were performed in the Chirurgische Klinik of the University of Tübingen, for gastric carcinoma. The average mortality for the operations was 19.1%, postoperative complications occurred in 41% of the cases. The most frequent cause of death was failure of the oesophageal anastomoses. The two methods most commonly used, Longmire-Gütgemann's interposition of small intestine and oesophagojejunostomy with Braun's anastomosis, differ considerably in the complication rate and mortality. The interposition of small intestine, with almost indentical preoperative and intraoperative risk factors, an operative mortality of 4.4% and distinctly less danger of anastomotic failure was shown to be superior to the technically simple oesophagojejunostomy. The formation of an "artificial stomach" in gastrectomy is therefore to be preferred to all other surgical methods of reconstruction of the intestinal passage, not only because of the better late results but also because of the better early results.


[Influence of duodenal reflux on the epithelium of the gastroenteral anastomosis (author's transl)]. The cancerogenic effect of continous duodenal reflux on the gastric mucosa has been investigated in male Wistar-rats after gastrointestinal anastomosis. Groups of animals with gastroenterostomy without enteroenteral anastomosis and with Roux-en-y-anastomosis preventing duodenal reflux were treated with lower dosages of the cancerogenic Nitrosoguanidine. Proliferative mucosal alterations near the gastroenteral anastomosis were observed. In addition the gastric mucosa was characterized by adenomatous lesions caused by duodenal reflux. The changes detected were not influenced by Nitrosoguanidine and did not appear in cases of Roux-en-y-anastomosis.


Antimicrobial properties of some West African medicinal plants iv. Antimicrobial activity of xylopic acid and other constituente of the fruits of Xylopia aethiopica (Annonaceae). Xylopic acid and four other isolates from the fresh ripe fruits of Xylopia aethiopica a common ingredient in several Ghanaian folklore medicines and foods, have been examined for antimicrobial activity against five micro-organisms, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Xylopic acid and two other diterpene isolates were found to have antimicrobial properties.


Muscle-relaxant activity in Asian Strychnos species. A re-examination of two western Malaysian dart poisons. Two supposedly Strychnos-based Semai Senoi dart poisons from Western Malaysia, ipoh akar and lampong, and their accompanying plant materials have been re-investigated botanically, chemically, and pharmacologically. The two poisons contained tertiary and quaternary alkaloids, including strychnine and bis-quaternary dimeric bases, and also cardiotonic glycosides. The dominant pharmacological activity of the highly toxic ipoh akar poison was convulsant. The weaker lampong poison had muscle-relaxant activity of the curarizing type. The alkaloids of the two poisons were almost certainly derived from Strychnosignatii Berg. (S. ovalifolia Wall. ex G. Don) and not from S. vanprukii Craib to which the accompanying plant materials probably belong, while the cardiotonic glycosides of the two poisons came from Antiaris toxicaria Lesch. The quaternary alkaloids of both S. ignatii and S. vanprukii have muscle relaxant activity.


Baeocystin in psilocybe, conocybe and panaeolus. Sixty collections of ten species referred to three families of the Agaricales have been analyzed for the presence of baeocystin by thin-layer chromatography. Baeocystin was detected in collections of Psilocybe, Conocybe, and Panaeolus from the U.S.A., Canada, Mexico, and Peru. Laboratory cultivated fruitbodies of Psilocybe cubensis, P. semilanceata, and P. cyanescens were also studied. Intra-species variation in the presence of decay rate of baeocystin, psilocybin and psilocin are discussed in terms of age and storage factors. In addition, evidence is presented to support the presence of 4-hydroxytryptamine in collections of P. baeocystis and P. cyanescens. The possible significance of baeocystin and 4-hydroxytryptamine in the biosynthesis of psilocybin in these organisms is discussed.


Constituents of West African medicinal plants. XXI. Tiliafunimine, a new imino bisbenzylisoquinoline alkaloid from Tiliacora funifera. Tiliacora funifera (Menispermaceae) is a woody climber of Ghana and West Africa that has been used natively as a medicinal in the treatment of numerous ailments. Chromatography of an extract of the leaves of T. funifera afforded tiliafunimine (13) whose ir, uv, nmr, and mass spectra were characteristic of a trimethoxylated phenolic iminobisbenzylisoquinoline alkaloid. Reduction of tiliafunimine with sodium borohydride afforded the dihydro-derivative (14) which upon treatment with formalin gave thalrugosine (12). The final structural assignment of tiliafunimine (13) as an iminobisbenzylisoquinoline alkaloid was made by nmr and mass spectral considerations. Other alkaloids isolated from the same extract include the bisbenzylisoquinoline bases isotetrandrine (11) and thalrugosine (12).


Cactus alkaloids. XXXVI. Mescaline and related compounds from Trichocereus peruvianus. Agurell has previously detected (tlc, glc-ms) tyramine, 3-methoxytyramine, and two unknown alkaloids in the Peruvian cactus, Trichocereus peruvianus Br. and R. The presence of mescaline in other similar Trichocereus species prompted us to reinvestigate this species, which is commercially available in the United States. The nonphenolic alkaloid extracts yielded an abundance of crystalline mescaline hydrochloride (0.82% yield) and a trace of 3,4-dimethoxyphenethylamine (tlc-ms). Crystalline tyramine hydrochloride, 3-methoxytyramine hydrochloride, and 3,5 dimethoxy-4-hydroxphenethylamine hydrochloride were isolated from the phenolic alkaloid extracts; the last compound has not been previously crystallized from nature, although it is the immediate biosynthetic precursor of mescaline. Crystalline 2-chloromescaline hydrochloride was isolated drom the nonphenolic extracts; but, as determined by mass-analyzed ion kinetic energy spectrometry, this new compound is an extraction artifact. Both 2-chloromescaline and 2.6-dichloromescaline hydrochlorides were prepared synthetically from mescaline. This cactus species has a mescaline content equal or superior to peyote and should be legally controlled as an item of drug abuse.


Potential anticancer agents vi. Constituents of Ailanthus excelsa (Simaroubaceae). Ailanthione (1), glaucarubinone (2) and a mixture of glaucarubol 15-isovalerate (3) and 13,18-dehydroglaucarubol 15-isovalerate (4) were found to be the compounds responsible for the antitumor and cytotoxic activities of extracts of the root bark of Ailanthus excelsa (Simaroubaceae). The latter compound, 4, is new.


[Preparatory metabolism of p-hydroxybenzoic acid in Candida tropicalis]. A technique of experimental adaptation was used to obtain mutants of Candida tropicalis which were able to utilize p-hydroxybenzoic acid as the sole source of carbon and energy. The preparatory metabolism of p-hydroxybenzoic acid involves the following stages: PHBA leads to quinol leads to hydroxyquinol leads to maleylacetic acid leads to beta-ketoadipic acid. The enzyme system which catalyzes oxidative decarboxylation of PHBA mediates also oxidative decarboxylation of protocatechuic, beta-resorcylic and gallic acids, i.e. compounds having a hydroxyl group in para position with respect to the carboxyl of hydroxyl derivatives of benzoic acid. Benzoic, salicyclic and gentisic acids are not substrates of this enzyme system. A technique is proposed for rapid indentification of beta-ketoadipic acid by thin-layer chromatography. The authors believe that methods used to study preparatory metabolism, on the basis of the Stanier theory of "simultaneous adaptation", are not quite reliable and may lead to erroneous conclusions.


[Direct selection of Aspergillus terricola variants having different toxicity on a culture of fibroblasts]. A direct method is proposed to select less toxic mutants of Aspergillus terricola on a culture of fibroblasts. The conidia are first irradiated with UV, and then are used to grow colonies on the glass surface of tubes or flasks containing medium 199. The cells of fibroblasts are added thereupon and the two cultures are being grown together for 24--48 hours. The colonies which inhibit the growth of fibroblasts to a less extent are selected using microscopy. The method can be used for primarily selection of experimentally produced mutants of Aspergillus which form fibrinolytic enzymes possessing low toxicity.


[Microbiological leaching of zinc and lead ores of the Tekeli deposit]. In certain regions of the West Tekeli lead-zinc ore deposti, the number of Thiobacillus ferrooxidans cells reaches 10(6) per 1 ml of ore water. Spontaneous bacterial leaching of sulphide ore is confirmed by an increase in the concentration of ferric iron and zinc in ore water. As a result of this leaching, up to 40 per cent of zinc and 60 per cent of lead have been leached from lead-zinc ore within 271-286 days. Bacterial leaching of lead intermediate products has shown that the maximum rate of galenite oxidation is reached at 50--65 degrees C and the content of Fe3+ in a solvent being above 20 g per litre. Microbiological leaching can be used for selective extraction of zinc and lead. Zinc dissolves directly in the leaching bacterial solution while lead remains in the precipitate and is then dissolved under the action of concentrated NaCl solutions.


[The protective role of pigments against UV rays in fungi isolated from the mesosphere]. Five among six species of microorganisms isolated from the mesosphere contained pigments which made them more resistant to the action of UV as compared to pigmentless microorganisms in the atmosphere of Earth. UV irradiation in the atmosphere is supposed to select resistant pigmented forms, so that they predominate in the mesosphere. To confirm this assumption, mutants of Aspergillus niger, Penicillium notatum and Circinella muscae were sported by irradiating them four times and then subjecting to stepwise selection. These mutants either synthesized pigments at a very low rate or did not produce them at all. No significant differences were found by studying the biomass, mycelium and sporeforming organs of the parent cultures and their mutants. However, their resistance to UV was not the same. Addition of the pigment apsergillin, isolated from the conidia of Aspergillus niger, to a suspension of the pigmentless (mutant) conidia of Penicillium notatum, the spores of Circinella muscae, and the vegetative cells of Micrococcus albus, before their irradiation with UV, considerably increased their resistance to this factor.


[Pathways of assimilation of carbon oxides in carboxydobacteria Seliberia carboxydohydrogena and Achromobacter carboxydus]. Assimilation products of 14C-bicarbonate and carbon-14C oxide were studied in two carboxydobacteria Seliberia carboxydohydrogena and Achromobacter carboxydus which differed in their ability for chemolithoautrophous growth in the presence of hydrogen. The dynamics and composition of labeled products formed upon assimilation of 14C-bicarbonate in the presence of unlabeled carbon oxide by the two organisms, the composition of products formed upon assimilation of 14CO by suspensions of S. carboxydohydrogena Z-1062 during 5 minutes, and the dynamics and composition of labeled assimilates of A. carboxydus Z-1171 after incubation in the presence of 14CO, were found to be consistent with those expected in the action of the reductive pentose phosphate Calvin cycle. The similarity of products formed upon assimilation of 14CO2 and 14CO suggests that CO is first oxidized to CO2, and only is assimilated.


[Isolation and properties of new strains of obligate methanotrophs]. New strains of obligate methanotrophic bacteria which assimilate only methane or methanol as the source of carbon and energy have been isolated. According to their morphology, ultrastructure, cultural and physiologo-biochemical characteristics, the bacteria were classed as Methylobacter vinelandii, Methylobacter bovis, Methylobacter chroococcum and Mehylosinus sporium. A new species Methylocystis echinoides sp. nov. is described; it differs from other methanotrophs in certain morphological and physiological properties. The subspecies Methylosinus trichosporium var. methanolicum is recommended to be termed as Methylocytis methanolicus sp. nov.


[Biological elimination of nitrous oxide under oxidative conditions]. The process of biological N2O elimination under oxidative conditions has been discribed. It was performed by samples of soil, litter, water, ooze, sewage and compost. The process differs from denitrification, is not accompanied with dinitrogen formation and its rate is maximal at 15% of oxygen in the gaseous phase. Acetylene, an inhibitor of denitrification has no effect on elimination of nitrous oxide under oxidative conditions.


[The activity of enzymes involved in synthesis and hydrolysis of flavin adenine dinucleotide is Pichia guilliermondii studies at different levels of flavinogenesis]. The activity of FAD-pyrophosphorylase and FAD-hydrolase (nucleotidepyrophosphatase) was studied in extracts of Pichia guilliermondii ATCC 9058 capable of riboflavin over-production. The specific activity of the enzymes was highest at the logarithmic growth phase (2.6 and 3.8 mcmoles of FAD per 1 min per 1 mg of protein X10(-5), respectively), and did not increase upon the induction of riboflavin overproduction. A decrease in the content of hemin compounds and a low content of flavins in the cells of Pichia guilliermondii mutants had no considerable effect on the activity of the two enzymes. When the yeast was cultivated on a medium containing hexadecane, an increase in the content of FAD in the cells was not accompanied with a rise in the activity of FAD-pyrophosphorylase. The activity of the enzyme did not change when succinate and lactate, the substrates of FAD-containing enzymes, were used as the source of carbon. The activity of FAD-pyrophosphorylase increased only when iron-deficient cells of the yeast were grown or incubated on a medium containing glycine; this stimulation was inhibited by cycloheximide.


[The effect of trisporic acids on the composition of components of the cell wall in Blakeslea trispora Thaxter]. The cell wall of Blakeslea trispora was found to contain chitin similar to crustaceaous chitin in physico-chemical properties; this was confirmed by the data of IR spectroscopy and X-ray diffraction analysis. Trisporic acids, hormonal regulators of reproduction, hardly affected the content of chitin, xylan, and other polysaccharides of the cell wall of Blakeslea trispora, but increased the content of protein.


[Characteristics of growth and changes in the ultrafine structure of bacteria in the course of continuous cultivation on media containing ethanol]. A large number of bacterial strains assimilating chemical ethanol has been isolated using an original technique. Active growth of strains belonging to the genera Pseudomonas and, particularly, Acinetobacter was registered on mineral media containing ethanol. A mathematical model was constructed select a strain of Acinetobacter calcoaceticus K-9 during its continuous cultivation on media containing ethanol. The model makes it possible to determine conditions for producing a present amount of the biomass, the percentage of its yield, and the produc;iveness as a function of the dilution rate, temperature, and the concentration of ethanol and phosphoric acid in the medium. The main characteristics of the growth process in the studied factor space were established. The optimum conditions were calculated for growth of the strain with respect to each of the criteria. Under various conditions of bacterial growth, changes in the morphology and ultra-fine structure of the cells correlated with their physiological activity. The volume of the cells increased with the rate of dilution of the medium: the process can be described by a saturation curve. The presence of mesosomal structures is typical of the cells growing at low flow rates.


[Changes in the chemical composition of Bacillus popilliae vegetative cells in the course of their growth on a chemically defined medium]. The growth, development and changes in the chemical composition of Bacillus popilliae cells were studied in the course of their growth on a liquid chemically defined medium containing casein hydrolysate, complex vitamin mixtures and glucose. Growth of the culture on this medium was accompanied with diauxia which could be registered by changes in the rate of growth and synthesis of the main cellular polymers (DNA, RNA, protein, phospholipids). The rate of protein synthesis correlated with the specific growth rate which was maximal when the reserve substances of the cells or the compounds of partly digested biomass were used. The rate of protein synthesis in the experiment depended mainly on the protein synthesizing activity of RNA rather than on its content in the cells. The low rates of growth and protein synthesis, which suggest that the growth of the culture is being interested with in the course of utilization of the components of the nutrient medium, may account for the absence of spore formation by this strain on the medium used.


[Speroplast behavior in cultures of Thermus ruber]. Spheroplasts spontaneously originating in cultures of Thermus ruber, which are cultivated on potato-peptone media, are capable of growth and multiplication. They may reach 10 mc in diameter. Spheroplasts multiply by budding which can be preceded with inner division or budding; as a result 2--9 and more protoplast bodies are formed under the "envelope" of a spheroplast. Self-reproduction of spheroplasts is most active in a semiliquid potato-meat-peptone medium containing 0.2--0.3 per cent of agar. Microcolonies, which are clusters of spheroplasts in the process of budding, are formed at 45 degrees C in this medium during 1--2 days. Reversion of spheroplasts to rod-like cells occurs if L-lysine and/or DL-alpha-aline are added to the potato-peptone medium. Spheroplasts spontaneously produced by Thermus ruber are similar to the unstable type of L-form in their fine organization and behaviour in cultures.


[Influence of the composition of the medium and the duration of cultivation on the growth of Actinomyces spheroides and their biosynthesis of intracellular proteases and novobiocin]. The growth of Actinomyces spheroides 35 under different conditions and the biosynthesis of biomass, proteases and the antibiotic were studied with two types of growth medium: a control one and an optimized one. The rate of biomass accumulation was by 5--7 per cent higher on the latter medium than on the former one. The dynamics of accumulation was studied with novobiocin and proteases which hydrolyzed fibrin and casein. Fibrin hydrolyzing proteases were found to be synthesized under conditions that were unfavourable for the production of novobiocin. If the production of the antibiotic was supressed, the concentration of fibrinolytic proteases in the cultural broth increased almost proportionally. Such a relation has not been found for caseinolytic proteases.


[Chemcial aspects of the energy process in nitrate reduction in different representatives of soil microflora]. Chemical aspects of dissimilatory nitrate reduction were studied by mass spectrometry in the following soil bacteria: Bacillus filaris, Bacillus polymyxa and Pseudomonas denitrificans. Chemical peculiarity of this process in spore-forming soil bacteria is the simultaneous operation of two energy processes: denitrification and nitrate respiration. The first process is terminated by the formation of molecular nitrogen, the second, by the production of ammonia. The quantitative ratio between these processes demonstrates the advantage of nitrate respiration in the overall energy pathway of nitrate dissimilation. Pseudomonas denitrificans maintains the abilityfor intensive gas production as a result of denitrification upon long storage on artificial media: ca. 34 per cent of the nitrate nitrogen is reduced to gaseous forms of nitrogen.


[Transformation of L-tryptophan by Rhizobium phaseoli]. Transformation of L-tryptophan was studied in Rhizobium phaseoli 680. The culture was capable of oxidation decarboxylation, transamination and degradation of L-tryptophan. Four metabolites were identified: tryptamine, indolyl-3-pyruvic, indolyl-3-acetic and anthranilic acids. The fifth metabolite has not been yet identified.


[Monosaccharide composition of the exopolysaccharides of oligonitrophilic bacteria]. Exopolysaccharides from ten strains of oligonitrophilic bacteria were found to contain galactose, glucose and mannose. Strains belonging to the genus Mycobacterium contained also fucose, ramnose and three sugars that had not been identified: two of them were lipophilic and one had a lower Rf than ramnose. A correlation has been established between the composition of monosaccharides, their molar ratios in exocellular polysaccharides of oligonitrophilic bacteria, and the taxonomy of these microorganisms. Sporeforming bacteria belonging to the genus Bacillus produce polysaccharides which contain galactose, glucose and mannose at a ratio of 10:19: : (13--15). The molar ratio between the same sugars in exopolysaccharides of bacteria belonging to the genera Pseudomonas and Azotomonas is 10:(12--19) : (4--6). The ratio between galactose, glucose, mannose, fucose, ramnose, the unknown sugar and the sum of two lipophilic sugars in exocellular polysaccharides of the genus Mycobacterium is 10:(15--16) : (5--6) : (7--10) : (0.1--9) : (0.3--0.5) : (0.4--0.8).


[Isolation and characteristics of the lipid granules of Candida tropicalis yeasts]. Preparative isolation of lipid granules from the protoplasts of Candida tropicalis was conducted by a technique of flotation in a stepwise density gradient. Parameters were selected for decomposing the protoplasts under hypotonic and isotonic conditions which made it possible to preserve the lipid granules being isolated intact, as well as parameters of a density gradient and centrifugation. The specific content of lipids, proteins and low molecular weight compounds was assayed using labeled compounds in the lipid granules which were isolated from yeast cells cultivated on various carbon substrates (1-6(-14C)-glucose and 1(-14C-octadecane). The lipid composition of the spherosomes was determined. If the yeast was grown on glucose, lipids localized in the lipid granules were represented mainly by triglycerides whose carbon constituted 69 per cent of the total lipid carbon. If it was cultivated on n-octadecane, these lipids were represented by hydrocarbons (51 per cent) and triglycerides (22 per cent). The structures isolated possessed a small lipase activity. The specific lipase activity of the lipid granules was lower by 16 per cent than that of the cell protoplast.


[The effect of beta-ionine on biosynthesis of carotenes by Actinomyces chrysomallus var. carotenoides]. Biosynthesis of carotenoids by a growing culture of Actinomyces chrysomallus var. carotenoides is totally inhibited by beta-ionone added at different concentrations, at various time of the cultural growth, and in various combinations with oil. The inhibition of carotenoid synthesis by beta-ionone is of a specific character since the biomass growth under the same conditions does not increase.


[Conditions for formation of heteromorphic forms of Bacillus brevis and their cytology]. The conditions of formation of Bacillus brevis var. GB heteromorphous forms were studied both under natural conditions and in the course of action of various factors. Natural polymorphism of the culture is low. It increases as the temperature of cultivation is lowered down to 28 degrees C or when the culture is kept at 5--6 degrees C in a refigerator. The P- and S forms of dissociation display higher polymorphism than than P+ and R variants. Cytological investigation has shown that heteromorphous forms are very large and contain gigantic nuclear formations in the form of solid bodies or bands. The sharp increase in the size of the nucleoids, their aggregation and splitting (breaking down of a band into sepraate units, transverse division of large nucleoids), as well as the data of biochemical analysis suggest the polygenomic or polyenergid nature of the giant heteromorphous forms of Bacillus brevis var. GB.


[Morphological and physiological properties of Phoma tracheiphila (mal secco) (author's transl)]. The morphological and physiological characteristics of Phoma tracheiphila, the cause of "Mal Secco" in Mediterranian lemons is discussed. The structure and the characteristics of the spore, mycelium and pigment of this fungus were investigated in liquid and solid media. The growth rate was examined in different media with different pH by dry weight determination. The growth curve of P. tracheiphila was first studied in YPG, (pH 5.6) medium in the stationary and shaking culture conditions. During the course of these studies the microscobic observations and measurements were recorded. The results established that in further studies, it will be necessary to incubate P. tracheiphila at least 5 days for its growth. The optimal pH and temperature scale were found between 5.5--6.0 and 20--25 degrees C respectively.


[Formation of diploids by Aspergillus niger and their biosynthesis of citric acid]. Diploid organisms appeared spontaneously in heterokaryons of Aspergillus niger produced by crossing a beige mutant, which was adenine-deficient, and a green mutant requiring the addition of yeast autolysate. The frequency of diploidization increased two-fold under the action of colchicine (0.5%). The diploids became prototrophous, the colour of their conidia increased 1.5--2.4 times. The rate of production of citric acid by the diploid strains which had originated under the action of colchinine was 1.5 times higher than that of the parent haploid mutants.


[Fungal flora of Ankara air in the morning and evening (author's transl)]. The fungal flora in different areas parts of Ankara in morning and evening atmosfere are discussed. It was seen that Penicillium, and Mycelia sterilia were found more in evenings, when Cladosporium and Alternaria were found in higher concentrations in mornings. Aspergillus was found in evening air either in less or at least in same concentrations. The rate of Monilia in evenings and mornings showed variable concentration according to areas.


[Electron microscopic study of the cells of variants of Bacillus thuringiensis var. galleriae forming colonies with altered morphology]. Colonial-morphological variants of Bacillus thuringiensis var. Galleriae were studied by electron microscopy. The S variant was found to be asporogenous, whereas the R variant produced mature spores. Morphological modifications in the cell were followed in the course of sporulation. Spores were shown to have thin filamentous and tubular protrusions which had not been so far described in crystalliferous bacteria. Preparations from colonies of the R variant contained peculiar structures which resembled phage tails. A possible function of these structures is discussed.


[Factors causing short-term periodic changes in the numbers of bacteria in the superficial layer of sludge and in the water near the bottom]. Rhythmical temporal changes in the number of bacterial populations inhabiting the surface ooze layer and the water layer above it have been found to depend on two processes: (1) the ability of bacteria for periodic intensive growth followed by death of the cells and (2) the participation of zooplankton in consuming the bacterial cells for nourishment. The total bacterial number in samples depends on which of the two processes prevails.


[Antigenic relationship among Candida guilliermondii strains (author's transl)]. In this short communication the results of cross aglutination and absorption tests among three sandard Candida guilliermondii strains (C. guilliermondii CBS--566, C. guilliermondii var. carpophila CBS--5256, C. guilliermondii var. japonica CBS--6021) are given. It showed that these microorganisms have the same antigenic structure.


[Salmonella serotypes isolated recently in Ankara from children with enteritis (author's transl)]. The results of serotyping done on 859 Salmonellas isolated between 25/2/1975--6/4/1977 are reported. In the series presented here percentage of S. thyhimurium is very close to that reported by us (91.37%) previously (2) showing that it is still the predominating serotype; But the important observations of the present study are the rises of the new serotypes which took the second and third places namely S. montevideo and S. thompson, indicating that clinicians should be aware of their presence. Under the impression of these findings the authors suggest to include the reagents prepared by S. thyphimurium's (i), S. thompson's (k) and S. montevideo's (g, m, s) flagellar antigens in addition to the routine Widal test antigens in Ankara hospitals.


[Sensitivity of various strains of Candida to amphotericin B and nystatin (author's transl)]. In this article the sensitivity of 42 standard Candida strains to Amphotericin B and Nystatin have been examined. The in vitro experiments showed that the sensitivity of various Candida strains to the above mentioned drugs were different. Also it was observed that Nystatin was more effective against the Candida albicans strains.


[Antigenic relationship between Salmonella cholerae suis and various yeasts]. The common antigenic fraction of Candida albicans and Salmonella O 6, 7 antigens were published by Aksoycan and Kaffmann (1); Recently Aksoycan and Sağanak (4,6) showed the antigenic relationship between Salmonella O 6, 7 antigen and various Candida, Torulopsis species and some other yeasts. During their earlier studies Aksoycan and his colleagues showed also the antigen relationship between Saccharomycopsis ludwigii, Syringospora albicans, Syringospora claussenii, Syringospora stellatoidea, Metschnikowia, Torulopsis and Salmonella cholerae suis O 6, 7 antigen (2, 3, 4, 5, 6, 7, 8).


[Pseudomonas-like bacteria (group Ve biotype 1) isolated from a subdiaphragmatic abscess (author's transl)]. Pseudomonas like bacteria group Ve biotype I was isolated three times from the specimens taken by thorocenthessis from a patient with subdiaphragmatic abscess who was admitted to the Thoracic Diseases Clinic in the University of Ankara School of Medicine.


[Identification and differentiation of nonfermentative gram-negative bacteria in the clinical laboratory (author's transl)]. Identification of nonfermentative gram negative rods encountered in medical bacteriology exhibit some difficulties in the clinical laboratory. However, we believe that, if identification procedures are applied systematicaly and step by step more than 90% of nonfermentative gram negative bacteria can be identified within 72 hours.


[Psychrophilic pseudomonas from soil].

[Psychrophilic pseudomonas from soil]. A psychrophilic culture of Pseudomonas inhabiting soil was cultivated at a temperature close to the minimum one (0 degrees C) and at a temperature close to a maximum one 28 degrees C) for growth on the original and diluted MPB. No changes were found in the formation of biomass, RNA and DNA. The maximum possible biomass yield was attained sooner at 0 degrees C on a diluted medium than on an original medium. At a low temperature, the specific growth rate remained the same, but the content of RNA increased.


Esophageal obturator airway.

Esophageal obturator airway. The Esophageal Obturator Airway, a device designed for use in the management of cardiopulmonary arrest, obstructs the esophagus while simultaneously ventilating the lungs. The EOA was clinically tested in 29,000 patients with a low incidence of false entries and complications. Physiological studies indicated that vital capacity, blood gases, and pH were comparable to those obtained with the use of the endotracheal tube. Furthermore, the insertion of the EOA was more rapid (mean 6 sec vs 20 sec), more accurate (98 percent vs 48 percent), and easier to teach to paramedical personnel. It was concluded that whenever optimal conditions for endotracheal intubation are unavailable, the EOA should be first choice in the management of the airway in aneflexic, apneic patients. Specific contraindications are listed.


The clinical assessment of cardiovascular emergencies. Data are given for a 2-year study of fire department ambulance runs in Houston, Texas. Comparisons are made between those runs in which telemetry was used and those in which telemetry was not used. These data show an important relationship between the prognosis of patients who were recognized by emergency medical technicians as cardiac emergencies (and therefore received telemetry service) and those patients who were not identified as cardiac emergencies and did not receive telemetry service. Criteria used for clinical assessment and classification of emergencies are discussed. Emergency life-support systems with telemetry can have significant benefit for certain selected acute, recognizable cardiovascular emergencies, but the majority of ischemic heart disease fatalities do not appear to be deriving benefit from these systems.


Improvement of defibrillators for EMS use: a problem in engineering and medicine. Recent improvement in defibrillators has been limited mostly to decreased size and weight of portable units. An overview of the scientific literature indicates that the main limitation to further improvement in defibrillators is the lack of medical and physiologic information. Technology probably exists to change defibrillators if the manufacturers know what changes would be desirable. Clinical studies are needed for determining (a) more accurate quantitation of electrical dose for human use, (b) the relative effectiveness of different waveforms, (c) the toxicity and damage of electrical shocks to the heart, (d) the effects of drugs upon defibrillation threshold, (e) improvement of defibrillation techniques, (f) optimal placement and size of electrodes, and (g) the effects of cardiac disease on defibrillation threshold. Most of the needed studies are not technically difficult to carry out but they will be moderately expensive. In some cases special equipment may be needed or special techniques may have to be developed. The experimental animal studies appropriate as background for these clinical studies have been completed. With limited resources available, it is important to ask the most important questions first in order to develop improved defibrillation techniques and defibrillators.


Mast pneumatic trousers: a mechanical device to support blood pressure. Maintaining the oxygenation of the heart-brain-lung circulation system is vitally important in reducing morbidity and mortality in emergency medicine. Mast pneumatic trousers were developed that compress the abdomen and legs, thus transfusing more than 20 percent of the whole blood volume into the heart-brain-lung circulation. This report consists of the results of treatment of approximately 70 patients whose blood pressures were significantly reduced before application of the trousers. These patients, for the most part, were delivered to the hospital in relatively good clinical condition. Complications with this device have been few. There is a question of pulmonary compromise because of the increased intra-abdominal pressure. Hard data on the number of lives saved are difficult to obtain because of the complexity of the human system in determining which lives would or would not have been saved without long-term studies. However, it can be shown that there is a significant increase in blood pressure with the utilization of such devices. This, then, infers that lives probably were saved in specific patients.


Autotransfusion: current status.

Autotransfusion: current status. Autotransfusion is the collection of blood from a patient and the reinfusion of that same blood back to that patient. Historically, it has been used since 1818, and there have been many rebirths of this technique since its beginning. Many problems encountered have caused the technique to be abandoned; but as devices become refined, interest is restimulated. There are many advantages to autotransfusion including the preservation of an extremely important natural resource, blood. Expanding massive surgical procedures are increasing demands on blood supplies, and autotransfusion is a safe, logical way to decrease demands and save blood. Devices presently available are discussed and described.


Comprehension of therapy by non-English speaking hospital patients. A survey was made of 1,832 patients who attended the Outpatients' Pharmacy of The Royal Melbourne Hospital during a five-day period. We identified 280 patients who did not speak English as their native tongue; of these 257 (90%) answered a series of questions asked by a pharmacist. An interpreter was essential for communication with 73 of the 257, yet only 31 had been previously classified as requiring an interpreter. Sixty-five per cent of the sample had a good knowledge of drug doses, frequency and drug function. Of the remaining 90, 39 were uncertain of the correct dose, 38 could not state the function and 13 knew neither function nor dose. The proportion of poorly informed patients varied significantly between clinics. Although it is routine practice to place cautionary labels on medication containers, only 78% of the patients had knowledge of these special warnings. Many patients were accompanied by friends or children who spoke some English; however, their translations were sometimes inaccurate and misleading. To improve communication with non-English speaking patients, more trained interpreters should be available in the hospital.


Rationale and indications for microfiltration of blood in emergency medicine. Documentation in the literature shows that massive transfusions for severe, nonthoracic trauma contribute to development of progressive pulmonary failure in some patients. Further review shows embolic phenomena in cardiopulmonary bypass procedures contribute to a number of postoperative complitions. These complications are related to the numbers and physical characteristics of aggregates in banked whole blood and to the morphology of the pulmonary circulation. Many of these complications can be prevented or markedly attenuated by microfiltration of banked blood. It is concluded that all transfusions of banked whole blood and blood products should be administered through microfiltration units.


Reducing the pill swill: an audit of clinical pharmacy. A drug surveillance programme involving pharmacists in a general medical ward has been shown to reduce the number of drugs prescribed to patients and also to reduce the number of dispensing errors. The evidence presented suggests that continuing involvement of pharmacists in patient care at the ward level is required to maintain the improved prescribing habits.


Retinoblastoma in Victoria.

Retinoblastoma in Victoria. This paper reports all cases of retinoblastoma occurring in Victoria over a 20-year period between 1956 and 1976. It suggests that the natural history of treated retinoblastoma in an Australian community, is characterized by low mortality (8.3%), but significant morbidity. The most common problem in management of unilateral cases was one of diagnosis in contrast to bilateral cases, in which the problem was one of maintaining useful vision whilst at the same time eradicating a life-threatening tumour. Suggestions are made as to how management of retinoblastoma may be further improved, and the need for an active national register is discussed.


Renal failure and treatment of a methadone maintenance patient. A 30-year-old veteran heroin addict being treated with methadone maintenance suffered renal failure. He underwent haemodialysis, peritoneal dialysis and cadaveric renal transplantation while being maintained on methodone. This report illustrates long-term treatment of heroin addicts with renal failure.


The role of physical activity in the control of obesity. An exercise programme is an important part of the management of the obese patient. Exercise may increase both the specific dynamic action of food and the post-exercise metabolic rate, in addition to its direct caloric cost. Moderate daily exercise aids regulation of the appetite and may reduce the voluntary caloric intake of otherwise sedentary persons. Post-prandial activity may utilize more calories; therefore an adequate breakfast and avoidance of late night eating may be effective in weight control. A better tolerated and more nutritious diet may be allowed, and lean body weight better preserved, by combining exercise with a dietary programme. Regular exercise may also reduce some of the more serious life-threatening complications of obesity and poor dietary habits, allowing greater freedom in the pursuit of other pleasures.


Road trauma: who should be counted?

Road trauma: who should be counted? Fatalities associated with the use of road vehicles, as reported in two separate data series, are compared. The customarily used collection, Road Traffic Accidents Including Casualties, underreported the actual total of road trauma deaths in Australia for the decade 1965 to 1974 by almost 2000 cases (5.8%). Of this total, approximately half were attributable to duration of survival exceeding 30 days; the remainder could be accounted for by a quirk of definition which excluded "off-road" accidents (in car parks, domestic and farm premises, factories and shopping centres). Cases excluded increased from 1.7% in 1965 to 8.4% in 1974. In the interests of accurate countermeasure evaluation, some revisions are recommended.


A study of five year old children born after elective induction of labour. A controlled retrospective study of some short-term and long-term effects of elective induction of labour was conducted. There did not appear to be any increase in the incidence of maternal complications during labour, or of neonatal problems in the induced-labour group compared with the remainder of the mothers in the hospital. In the follow-up phase of the study, two treatment groups of children who were delivered after amniotomy and amniotomy plus the administration of oxytocin were compared with each other, and with a control group of children born after spontaneous labour. The children were assessed at the age of five years on verbal and non-verbal subtests of a standardized intelligence scale, tests of gross motor and fine motor coordination, and auditory and visual tests. A full physical examination was also performed. No statistically significant differences nor trends of clinical interest were found between the groups on any measure.


Drinking, smoking and drug-taking patterns in a predominantly lower socioeconomic status sample: comparison with Medicheck sample. The drinking, smoking, and drug-taking patterns of 9829 adult members of the Australian Workers Union in Sydney are compared with data collected through the Medicheck Referral Centre. Overall, the two sets of data are very similar, but the results of this survey point to the high prevalence of heavy alcohol consumption, and of regular drug-taking in young people.


Perinatal mortality in South Australia.

Perinatal mortality in South Australia. A study of the recorded causes of perinatal mortality has been made in South Australia for the years 1970 to 1973. The overall perinatal mortality was 22.16 per 1,000 births. Higher mortality was observed in babies of women resident outside the metropolitan area, of those aged under 20 and over 35 years, and of those not currently married. The most frequent causes of perinatal mortality were prematurity, placental insufficiency, congenital anomalies, maternal disorders and haemorrhage, in that order. Multiple pregnancy had a high perinatal mortality. Better recording systems with record linkage are required.


Multiple drug interactions with phenytoin. A 49-year-old female with chronic alcoholism and epilepsy, treated with phenytoin, began to convulse when treatment with disulfiram (an inhibitor of phenytoin metabolism) was discontinued. The patient at this stage was resistant to the large doses of phenytoin, apparently owing to induction of the metabolism of this drug by chronic alcohol intake. Later, a small (30%) increase in dose resulted in about a tenfold increase in plasma concentration of phenytoin and severe toxicity. The final dose of phenytoin required to maintain the plasma level within the therapeutic range suggested that the enzyme induction had decreased. The value of monitoring plasma concentrations of phenytoin is emphasized.


Induction of labour.

Induction of labour. The only justification for adding to the extensive literature on induction of labour is to bring together relatively inaccessible but relevant data for the general reader. Some of these data refer to current practice, and some to patients' experiences. The conflicting value systems of some doctors and some patients are also discussed. The writer, a self-confessed armchair critic, makes some suggestions about ways of reducing disagreement about elective induction of labour.


Health status of a group of narcotic addicts in a methadone treatment programme. This study, which arose out of a concern for the health status of narcotic addicts already in a treatment programme, has demonstrated that there is a severe level of impairment of general health. A summary of important findings is reported. Narcotic addiction leads to secondary medical morbidity and mortality, but health impairment also follows the gross disorder of living which has its roots in childhood, and early adolescent experience. Successful prevention and rehabilitation needs to be based on this knowledge.


Hospital records of hydatid disease in Victoria for 1970 to 1974. The records of hydatid disease in 10 Melbourne hospitals and 12 rural hospitals in Victoria from 1970 to 1974 have been studied. In a total of 183 in-patients, the final diagnosis of hydatid disease had been confirmed surgically in 81 first admissions and in 56 readmissions. In 24 cases it was confirmed by necropsy, but in only one of these was hydatid disease believed to have been the cause of death. Figures are given for the age distribution and the organs involved.


Methyldopa and renal stones: a retrospective study. A possible association between treatment with methyldopa and the occurrence of renal stones was sought by retrospectively comparing 54 hypertensive patients with calculi detected by X-ray examination with a control group matched for age and sex. Treatment with methyldopa was equally frequent in both groups. There was a significant excess of methyldopa use in a subgroup of 16 patients with bilateral calculi, but the drug could be the primary cause of stone formation in, at most, four of these patients. If methyldopa does cause renal stones, it is probably an uncommon event, but precipitation of the drug from the urine may worsen a tendency to stone formation, which will lead to a higher incidence of bilateral calculi.


Mortality from all causes, and from ischaemic heart disease, in the Australian capital cities. A comparison was made of mortality from all causes, and from ischaemic heart disease, in the six Australian capital cities, for the years 1970, 1971 and 1972. Both rates were significantly higher in Brisbane and Sydney than in the other cities. Ninety per cent of the excess deaths in Brisbane men, and a large part of the excess deaths in Brisbane women and Sydney people of both sexes, were due to coronary disease. There was no relationship between either total or coronary mortality, and water softness or its magnesium content. So far these differences are unexplained.


"Hot spot" myocardial scanning: experiences with a mobile nuclear camera in a coronary care unit. Twenty-nine patients with suspected or actual myocardial infarction have had myocardial "hot spot" scans with technietium 99m pyrophosphate, using a mobile nuclear camera in a coronary care unit. Nine patients with transmural infarcts had positive scans. Nine out of 12 patients thought to have had endocardial infarction had positive scans. Two patients who had had intramuscular injections presented with chest pain and abnormally high serum enzyme levels, but had negative scans. Myocardial radionuclide scanning with a mobile nuclear camera is a rapid, easy, repeatable, non-invasive method of helping to confirm or exclude the diagnosis of myocardial infarction and, used together with other available tests, is a valuable additional diagnostic aid.


Complications of intravenous therapy: reduction by buffering of intravenous fluid preparation. Local complicationn of intravenous infusions have become a common cause of morbidity in hospitals. Two consecutive groups of patients were studied: the patients in the first group had received standard non-buffered intravenous fluid preparations with pH from 3.6 to 6.0; the second group of patients received fluids which were buffered to a neutral pH. The incidence of local complications in the first group was high (58%), with phlebitis being the most common complication which occurred in 43% of patients. The addition of a buffer to the fluids just before the infusion reduced the incidence of all complications in the second group of patients to 28%, and that of phlebitis to 19%. It will be shown that the complications can be significantly reduced by buffering the infusion fluids.


Reversible acute renal failure in the nephrotic syndrome with minimal glomerular pathology. A case of minimal change glomerulonephritis, associated with the nephrotic syndrome and prolonged acute renal failure requiring two months of dialysis, is reported. Complete recovery of renal function occurred, but proteinuria recurred, responding to a course of steroids. Normal renal function without proteinuria has been observed for two years subsequently. The full return of renal function without specific therapy demonstrates that spontaneous recovery is possible in this rare complication of minimal change glomerulonephritis.


New evidence concerning smoking and health. In the last 20 years, and especially as a result of smoking and health studies, we have learned a great deal about the impact of all airborne substances on human health. We are now painfully aware of the many sources of toxic and carcinogenic agents in our air. New evidence shows a complex relationship existing for exposure from many sources of pollutants from the community, smoking and other personal habits. This new evidence indicates that these pollutants, especially those encountered in blue collar occupations, account for a far larger proportion of cancers of the lung and of other sites (and of other diseases) than has been heretofore thought to be the case.


Coronary artery surgery in South Australia 1970-1976. The South Australian population of approximately 1,245,000 is 9.2% of the total Australian population. The Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital is the only one such unit in the State which is equipped for open heart surgery, and coronary artery grafting was first undertaken there in December, 1970. From that time until the end of December, 1976, 701 patients underwent coronary artery grafting with an overall hospital mortality of 3.0%, and a late mortality of 3.2%. The principal indication for operation was incapacitating angina, and of the 628 patients who have been followed-up after operation for a minimum period of six months, 78.6% were judged by their cardiologist to be completely relieved of this symptom. A further 8.9% of patients were considered to be significantly improved. Coronary artery surgery has rapidly assumed a dominant role in our Unit so that, in 1976, of the 435 open heart operations which were performed, 267 (61%) were procedures which necessitated coronary artery grafting. The rate of increase has slowed considerably over the past 18 months, and it is expected that, with current operative indications, the proportion of coronary artery cases will not rise much above 60% of the open heart work load of the Unit.


Cancer detection in working women: a report on 7450 subjects. A cancer detection programme for women was devised in 1964 by the writer, who attended an increasing number of work centres, mostly on an annual basis. During 12 years 7450 women were examined, some of them more than once. There were 237 abnormal Papanicolaou smears (in 112 of which the histological diagnosis was carcinoma or moderate to severe dysplasia), and 18 carcinomas of the breast. Education about cancer, teaching of breast self-examination and general counseling were also carried out. The high detection rate of cancer emphasizes the need for such services to be taken to the women at risk, and suggests that annual Papanicolaou smears are still the ideal.


Microsurgical tubal anastomosis for sterilization reversal. A series of patients requesting sterilization reversal has been reviewed. Microsurgical tubal anastomosis has been successfully employed and offers improved surgical results. Minimization of the length of tube damaged at sterilization procedures is probably a major factor in determining pregnancy rates should subsequent reversal be desired.


Paraquat poisoning is not necessarily fatal. This paper describes a case of deliberate ingestion of paraquat successfully managed with gastric lavage, forced diuresis, haemodialysis, gastrointestinal purgation and the adminstration of specific adsorbents.


Lactulose in vincristine-induced constipation. Constipation which is resistant to the usual range of laxatives is a troublesome undesirable effect of vincristine. Lactulose in doses up to 25 ml thrice daily proved to be a simple and effective treatment in six patients with refractory vincristine-induced constipation, and a successful prophylactic in two other patients. Palatable, and without any serious undesirable effects, lactulose can improve the quality of life for patients with a malignant tumour which is responsive to vincristine.


A simplified approach to the treatment of hypertension. A new beta-adrenoreceptor blocking drug (timolol) was used in two clinical studies. In the first double blind study administration of hydrochlorothiazide and timolol reduced the mean (formula: see text) blood pressure by 23 mm Hg, compared with a fall of nine mm Hg with administration of hydrochlorothiazide and a placebo. Plasma potassium (K+) levels fell with the administration of hydrochlorothiazide alone, but rose back to control values when patients were given timolol. In the second study (patient blind), Moduretic (hydrochlorothiazide, 50 mg and amiloride, 5 mg) and timolol were given once daily. The mean blood pressure fell by 20 +/- 2 mm Hg allowing hypertension to be controlled by this once-daily regimen; the control persisted throughout the day. Plasma potassium (K+) levels fell slightly after treatment with Moduretic, but the fall was not as great as with hydrochlorothiazide. Of the 65 patients who entered these studies, 35 had not been previously treated and had diastolic blood pressure between 105 mm Hg and 130 mm Hg. In 18 patients the diastolic blood pressure was reduced below 95 mm Hg after treatment with a diuretic alone, in 15 patients treatment with a diuretic and timolol (5 mg to 20 mg) reduced the diastolic blood pressure below 95 mm Hg. In two patients, the diastolic blood pressure was between 95 mm Hg and 100 mm Hg. The response achieved with a relatively simple therapeutic regimen that can be administered once daily suggests that the therapy of most hypertensive patients could be supervised by paramedical personnel.


Analgesic nephropathy complicated by development of transitional cell carcinoma of the renal pelvis and ureter. A case is described of analgesic nephropathy with papillary necrosis, calcification, osseous metaplasia and the development of papillary transitional cell carcinoma of the renal pelvis and ureter. Seven similar cases are summarized, and the literature briefly reviewed with particular reference to aetiological factors and associated clinical findings.


The pharmacology of newer aminoglycosides, with a consideration of the application to clinical situations. This has been an overview of the pharmacology of tobramycin, a new potent aminoglycoside, particularly active against Pseudomonas aeruginosa. Close attention must be given to the administration of this compound, and to the administration of all aminoglycosides, if one is to achieve adequate serum and tissue concentrations without provoking a toxic renal or otic reaction. Differences in methods and dosage of administration depending upon age, status of renal function, and route of administration are discussed. The basic principles reviewed can be applied to all the agents in this class.


Principles of concomitant antibiotic therapy. There are five major disadvantages of the combined use of antibiotics: (i) antibiotic antagonism; (ii) a "false sense of security"; (iii) increased toxicity; (iv) suprainfection; and (v) increased cost. Four situations clearly require the use of antibiotic combinations: (i) to produce antibiotic synergism; (ii) to prevent the emergence of resistant organisms; (iii) to treat mixed infections, such as brain abscess, peritonitis, and pelvic infections; and (iv) to institute therapy for severe infections.


Tobramycin in the treatment of peritonitis. Tobramycin is a new aminoglycosidic aminocyclitol antibiotic which has a broad spectrum of activity against aerobic and facultative Gram-negative bacilli. It is particularly effective against Pseudomonas aeruginosa, including some strains of this organism which are resistant to gentamicin. The newer aminoglycosidic aminocyclitol antibiotics all consist of a "backbone" of 2-deoxystreptamine, to which are attached several amino-containing sugar groups. These agents inhibit protein synthesis in bacteria at the level of the ribosome and are bactericidal although the precise mechanism by which they kill bacteria is still not known. There are a number of processes by which bacteria can become resistant to the action of the aminoglycosidic aminocyclitol antibiotics. Among these, the ability of bacteria to produce inactivating enzymes (usually mediated by R-factors or plasmids) appears to be the most important in current clinical isolates of bacteria. Aminoglycosidic aminocyclitol antibiotics which are resistant to these enzymes may have an enhanced spectrum of activity.


Tobramycin in the treatment of severe and complicated urinary tract infections. Tobramycin is an aminoglycoside aminocyclitol antibiotic with pharmacological similarities to gentamycin. Twenty-one of 30 patients with a severe or complicated Gram-negative urinary tract infection were cured by treatment with a 5-day course of tobramycin. No side effects were noted. This drug should prove beneficial for the treatment of severe Gram-negative sepsis, and promises to be particularly valuable for infections due to Pseudomonas aeruginosa. Dosage schedules for administering tobramycin to patients with renal function impairment are presented, together with some observations on its intravenous injection by bolus. A single dose of tobramycin has proved effective for initiating the antibacterial treatment of patients with acute pyelonephritis. The important concept of the differing concentrations of an antibiotic in the urine from kidneys of unequal function is discussed.


Clinical study of the use of the new aminoglycoside tobramycin for therapy of infections due to gram-negative bacteria. Tobramycin, a new aminoglycoside antimicrobial, was evaluated as therapy for infections due to Gram-negative bacilli in 15 seriously ill patients with underlying diseases. Three of 10 patients with Gram-negative bacteraemia also had a urinary tract infection. Two patients had a respiratory tract infection, one had cellulitis, one had a urinary tract infection, and another had septic phlebitis. Twelve patients were cured of their infections. Eosinophilia was observed in one patient, and another developed superinfection with Staphylococcus aureus after 6 days of tobramycin therapy. There were five isolates of Escherichia coli, five of Klebsiella sp., two of Pseudomonas sp., and one each of Enterobacter agglomerans, Serratia marcescens and Enterobacter cloacae. The average serum concentration of tobramycin 2 hr after a parenteral dose of 1.0 to 1.5 mg/kg was 5.1 microgram/ml; higher concentrations of tobramycin were present in urine. Tobramycin proved to be an effective antimicrobial in these patients.


A special-purpose computer for on-line statistical analysis of the heart rate. At present electronic instruments, in particular measuring devices, are widely used in hospitals. However, the usage of information processing systems is mainly limited to academic hospitals because of the costs, the need of skilled staff, etc. In this paper a relatively simple special purpose computer is described for the on-line generation of the tachogram, histogram, and joint interval distribution of a continuously updated series of RR intervals. Moreover mean value and variance of this series are calculated. This instrument has been in clinical use in a nonacademic hospital for one year and has proven to be a useful aid in patient monitoring. Some suggestions for improvement are discussed.


An automatic, multi-function pressure cuff control unit. A fully automatic blood pressure cuff control system is described. The system is designed for use in the assessment of peripheral vascular disease and helps reduce the amount of operator attention required to carry out such measurements properly. It also provides repeatable control of specific functions, thereby eliminating a potential source of variability. The system incorporates a pneumatic control system, an integrated silicon pressure transducer, and a digital readout. The design, modes of operation, safety features, and use of the system are described.


Liver-specific lysosomal acid phosphatase deficiency (Apl) on mouse chromosome 17. Apl, a gene involved in the processing of lysosomal acid phosphatase in mouse liver, has been mapped on Chromosome 17. The gene order and map distances in per cent recombination of the loci studied are T (20.6 +/- 3.4) Pgk-2 (7.4 +/- 2.2) Apl. Thus, Apl is at least 7 cM distal to H-2 on this chromosome. In addition, strain-specific allelic variants for Apl have been demonstrated on cellulose acetate gels, a quick and inexpensive method of electrophoresis.


Extrachromosomal inheritance in Schizosaccharomyces pombe. IV. Isolation and genetic characterization of mutants resistant to chloramphenicol and erythromycin using the mutator properties of mutant anar-8. Spontaneous chloramphenicol (capr)- and erythromycin (eryr)-resistant mutants were isolated from strain ade7-50 h- and the antimycin-resistant mutant anar-8 ade 7-50 h- of Schizosaccharomyces pombe (Sch. p.). By mitotic segregation analysis all 154 capr- and 120 eryr-mutants derived from ade 7-50 h- proved to be recessive chromosomal, whereas all 108 capr- and 200 eryr-mutants originating from anar-8 were extrachromosomally inherited. The rate of spontaneous capr- and eryr-mutants was about hundredfold in anar-8 compared to ade 7-50 h-. Growth of capr- and eryr-mutants was not inhibited by chloramphenicol or erythromycin, respectively, in glucose-medium and only slightly in glycerol-medium at concentrations which completely inhibited anar-8. By mitotic segregation-, tetrad-, and mitotic haploidization-analysis the extrachromosomal inheritance of mutants derived from anar-8 was established. Segregational patterns of capr- and eryr-determinants during mitosis, meiosis, and mitotic haploidization of diploids are discussed.


Ribosomal proteins in the fungus Podospora anserina: evidence for an electrophoretically altered 60S protein in a cycloheximide resistant mutant. Proteins of cytoplasmic ribosomes of the Podospora anserina were analyzed by two dimensional gel electrophoresis. The numbers of proteins were estimated to be 28 in the small subunit and 41 in the large subunit. The L21 protein of the large subunit was found to migrate differently in a cycloheximide resistant mutant.


Molecular cloning of fragments of bacteriophage T4 DNA. Non-glucosylated T4 DNA was digested with R.EcoRI and the resulting fragments covalently joined to lambda vectors. The genetic content of each lambda-T4 hybrid was determined by marker-rescue tests. The isolation of many recombinants containing partial-digestion products of T4 DNA provided the overlapping sequences necessary to order fragments within the T4 genome. The present analyses include parts of the "early" region between genes 42 and 46, and much of the "late" region between genes 50 and 29. T4 cytosine-DNA digested to completion by R.EcoRI was used to identify the fragments of DNA within the lambda-T4 recombinants. The T4 cytosine-DNA was also sensitive to R.HindIII and R.Xho but not to R.BamH1.


A search for allelic recombination in Chinese hamster cell hybrids. Mutants resistant to 6-thioguanine were selected from CHO cells which were either temperature sensitive or proline requiring. These mutants were stable and had low levels of hypoxanthine guanine phosphoribosyl transferase (HGPRT). Hybrids were selected which were heteroallelic at the hgprt locus and complementation between the mutants used was not observed. Interallelic recombination at this locus would generate hgprt+ cells which could be selected in Littlefield's HAT medium. Selection experiments with hybrids containing three different pairs of mutants yielded no recombinants among populations of 4 x 106 - 2 x 107 cells. After treatment with the recombinagen mitomycin C, 3 putative recombinants were detected amongst 1.4 x 107 surviving cells from one hybrid. One of these strains was examined and shown to have a normal level of HGPRT and its heterozygosity at this locus was demonstrated by the segregation of colonies resistant to 6-thioguanine. It cannot be excluded that the rare hgprt+ colonies seen arose by mutation rather than by recombination. Mitotic allelic recombination therefore appears to be a much less frequent event in CHO cells than it is in lower eukaryotes. It is possible that mitotic recombination is effectively suppressed in mammalian cells to prevent the expression of deleterious recessive mutants.


Genetics and function of isocitrate lyase in Coprinus. Thirteen chromosomal loci have been identified which affect acetate metabolism in Coprinus. Mutants at only two loci, acu-l and acu-7, are deficient in isocitrate lyase (ICL) (EC 4.1.3.1) activity. acu-1 mutants are unable to induce ICL because they lack acetyl-CoA synthetase which is required to convert acetate to the metabolic inducer of ICL. acu-7 is the structural gene for ICL. This was shown by selecting temperature sensitive acu+ revertants resulting from a second mutation within the acu-7 gene. One such revertant was shown to produce an ICL protein which was more thermolabile than the wild type enzyme. Other workers have postulated that ICL activity is important during asexual morphogenesis in fungi. No evidence was found for this in Coprinus. The morphological mutant oidial, which produces abundant asexual spores even in submerged culture, had the same low uninduced level of ICL activity as the wild type. Moreover, an acu-7 mutation had no effect on the expression of the oidial phenotype.


Carbohydrate composition of purified human liver alpha-L-fucosidase. Human liver alpha-L-fucosidase was purified to apparent homogeneity and analyzed for carbohydrate content primarily by gas-liquid chromatography (glc). The enzyme is about 7% carbohydrate by weight and contains the following sugars (residues per 50, 000 molecular weight subunit): mannose (8.3), glucosamine (4.3) (presumably N-acetylated), sialic acid (1.6) and glucose (1.6). Galactose (0.8) and L-fucose (1.8) were also found but their presence may be due to artifacts of the purification procedure.


[Morbus Wilson--pathogenesis, diagnosis, therapy, and course (author's transl)]. During childhood, Wilson's disease becomes manifest mostly in the hepatic form. In children every case of cirrhosis of the liver, hemolysis with high levels of conjugated bilirubin in the serum, and otherwise in explicable tremor make it imperative to exclude or confirm the existence of Wilson's disease. A false diagnosis often delays the start of therapy with d-penicillamine and low-copper diet. The prognosis, which was still fatal a few years ago, has improved considerably thanks to new therapeutic possibilities.


An inverse relation between mitochondrial hexokinase content and phosphoglucomutase activity of rat tissues. The hexokinase: fumarase ratios of mitochondria isolated from ten tissues of the rat were determined, and compared with the tissue content of phosphoglucomutase and phosphorylase, taken as representatives of enzymes concerned with glycogen metabolism. A generally inverse relationship was found between the mitochondrial hexokinase: fumarase ratio and phosphoglucomutase levels. The cytochrome: fumarase ratios were relatively invariant in these same mitochondria. The results are interpreted as indicating a specialization of mitochondria, with increased amounts to hexokinase being associated with the mitochondria in tissues exhibiting less dependence on glycogen metabolism, as judged from phosphoglucomutase levels.


[Medium chain triglycerides in the feeding of praemature infants. Fat balance studies (author's transl)]. 18 72-H Fat balance studies were performed in 9 premature infants with birthweights between 1650 and 2400 gm. At the age of two and three weeks, they received alternatively, one of two formulas identical in composition except for the type of fat: 30% of the vegetable fat in the first formula had been substituted by medium chain triglycerides (MCT) in the second formula. On the MCT-containing formula, the fat absorption significantly improved in the same infants as compared to their fat absorption capacity on the vegetable fat formula. The absorption of individual fatty acids, calculated by gaschromatographic analysis of pooled stool samples, also improved for most of the fatty acids with the MCT-formula. There were no adverse changes in blood glucose concentrations or in acidbase status of the infants when being fed the MCT-containing formula.


[Morbus wilson--progressive fatal course of the hepatic form with apoplexy and abscess of the brain (author's transl)]. The onset with a hemolytic crisis, as often described in the literature, led to the diagnosis of Wilson's disease. Treatment was immediately started in the usual way with diet and d-penicillamin. But the disease had already caused serious liver damage and renal lesions, and the patient died fourteen weeks after diagnosis. Examination of further family members disclosed a cousine with impaired liver and kidney function, also suffering from the hepatic form of homozygous Wilson's disease.


[Kniest's syndrome (author's transl)].

[Kniest's syndrome (author's transl)]. The clinical picture of the Kniest's syndrome is described. The syndrome is a rare hereditary condition with generalized bone dysplasia, disproportional dwarfism, conduction deafness and severe myopia, retinal detachment, cataract and amaurosis.


Experimental mucormycosis in congenitally athymic (nude) mice. Athymic nude (nu/nu) mice and their phenotypically normal (nu/+) littermates displayed a similar susceptibility to acute lethal infection with Absidia corymbifera. Although the clinical manifestations of acute infection were also similar in both groups, the nude mice tended to develop more extensive lesions and were less effective in eliminating viable A. corymbifera spores than their heterozygous littermates. The results suggested that thymus-dependent processes did not play an essential role in primary resistance to mucormycosis.


Studies on mycoflora of salt marshes in Egypt. IV. Osmophilic fungi. Ninety-five species and seven varieties which belong to thirty-nine genera were isolated from 74 soil samples from salt marshes. At 28 degrees C, on 30% sucrose Czapek's agar, ninety species and four varieties which belong to thirty-six genera were encountered, from which A. niger, A. fumigatus A. terreus and P. notatum were the most frequent. On 60% sucrose Czapek's agar, sixty-three species and three varieties were recovered which belong to twenty-five genera, from which A. niger, A. fumigatus, Cladosporium herbarum and A. terreus were the most frequent. At 45 degrees C, on 30% sucrose, sixteen species and four varieties were identified but on 60% sucrose, fourteen species and three varieties were isolated. A fumigatus and A. niger were the most frequent on both sucrose concentrations. The results reveal that the soil samples poor in total osmophilic fungi (at 28 degrees C) were significantly higher in their content of total soluble salts, Na and K and significantly lower in the average number of species per soil samples than the rich ones; the difference was non-significant in case of organic matter.


Dimorphism in Ceratocystis minor var. barrasii. Ceratocystis minor var. barrasii, a fungus associated with the southern pine beetle, Dendroctonus frontalis, exhibits dimorphism which is influenced by the concentration of both carbon dioxide and phosphate. The mycelium produces blastospores from the tips and sides of its hyphae when the concentration of carbon dioxide is high, and these blastospores germinate if the concentration of phosphate is above about 10(-2) mM, whereas below this concentration they bud.


Effects of intravenous kainic acid, N-methyl-D-aspartate, and (--)-nuciferine on the cat spinal cord. Kainic acid (a rigid conformational analogue of glutamate), N-methyl-D-aspartate (the methylated derivative of aspartate), and (--)-nuciferine (an aporphine alkaloid with a depressant effect on glutamate-induced neuronal firing), which, so far, have been examined in microiontophoretic studies, were investigated in spinal cats for their effects on some spinal cord activities after intravenous injections. At low doses, kainic acid (0.3 mg kg-1) enhanced segmental monosynaptic but not polysynaptic ventral root reflexes and increased the excitability of motoneurones, whereas N-methyl-D-aspartate (3 mg kg-1) facilitated polysynaptic but not monosynaptic reflexes. Higher doses of the two amino acids depolarized motoneurones and primary afferent endings, enhanced monosynaptic reflexes and depressed polysynaptic reflexes. (--)-Nuciferine (1--10 mg kg-1) depressed monosynaptic but not polysynaptic ventral root reflexes in a dose-dependent manner and antagonized the effects of kainic acid but not of N-methyl-D-aspartate on the spinal cord. The results are consistent with the hypothetical excitatory transmitter role of glutamate in primary afferents and of aspartate in excitatory spinal cord interneurones; the findings also suggest that (--)-nuciferine may be used as a systemically effective, rather selective blocker of central glutamate receptors.


Lipophilicity and brain disposition of clonidine and structurally related imidazolidines. The apparent partition coefficients (P') of clonidine and 27 of its structurally related imidazolidines were determined in the octanol/buffer (pH = 7.4) system as a measure of lipophilic behaviour. Lipophilicity of the imidazolidines is limited to the free bases and the principle of additivity is valid for this series of structurally similar compounds. Brain concentrations of clonidine and a number of its derivatives, achieved at the moment of maximal decrease in blood pressure, were determined following intravenous administration of anaesthetized rats. These brain concentrations represent the maximally attainable values. The ratio of log brain concentration/dose administered intravenously, log (Cbrain/Ci.v.), was employed as a measure of the penetration ability of the imidazolidines into the brain. The octanol/buffer (pH = 7.4) system proved a satisfactory reference model in order to describe the transport process of the present imidazolidines from the blood to the brain. The penetration ability of these compounds into the brain could be expressed mathematically by a highly significant, parabolic relationship in log P'. Ideal lipophilic character for optimal brain concentrations is connected with a log P' value of 2.16.


Effects of mazindol, fenfluramine and chlorimipramine on the 5-hydroxytryptamine uptake and storage mechanisms in rat brain: similarities and differences. Mazindol and fenfluramine inhibited in vitro the uptake of 5-HT into rat forebrain synaptosomes, whether the synpatosomes were incubated in vitro with the drugs or obtained from animals pretreated in vitro. Chlorimipramine was also effective in this latter preparation. Dose-response relationships and time course of this effect for the various drugs were determined. Fenfluramine also caused release of 5-HT from preloaded synaptosomes in in vitro incubations. Mazindol did not. Brain 5-HT levels were measured after acute and chronic administration of mazindol, fenfluramine and chlorimipramine. Mazindol had no effect, fenfluramine was active in reducing brain 5-HT concentrations acutely and chlorimipramine only after chronic administration. Therefore, it seems that even a long lasting inhibition of the uptake, such as that induced by mazindol, is not sufficient, per se, to cause depletion of brain 5-HT.


Evidence for selective and long-lasting stimulation of "regulatory" dopamine-receptors by bromocriptine (CB 154). Bromocriptine, an ergot-derivate with DA-receptor stimulating properties in vivo, produces long-lasting hypomotility in mice not accustomed to the motility cage and decreases brain DOPAC and HVA without affecting brain DA. These effects are obtained with doses 25 times lower than those which produce hypermotility. The decrease of brain DOPAC is correlated to the hypomotility both on a dose- and on a time-basis. Potent neuroleptics as pimozide, benzperidol and droperidol, which are considered to be fairly specific DA-receptor blockers, antagonize the hypomotility and the decrease of brain DOPAC produced by bromocriptine. These effects are obtained with very low doses (0.05--0.3 mg/kg) of neuroleptics which per se do not affect motility or brain DOPAC. The maximal decrease of brain DOPAC and HVA produced by bromocriptine is similar to that produced by apomorphine and the combination of these drugs does not result in a further decrease of brain DOPAC or HVA. On the basis of these results it is postulated that bromocriptine decreases brain DA-turnover and produces hypomotility by acting on "regulatory" DA-receptors different from the post-synaptic ones of the "terminal" dopaminergic areas.


Substance P in rat brain synaptosomes.

Substance P in rat brain synaptosomes. 1. Rat brain synaptosomes were incubated under different conditions to study the release of substance P (SP). 2. Potassium ions and electrical field stimulation induced a loss of SP from synaptosomes. The release of SP by potassium in high concentrations (23.8 mM) was shown to be calcium dependent. 3. Substance P was retained in synaptosomes during incubation in 0.32 M sucrose at +4 degrees C up to 120 min. During incubation at 30 degrees C the SP content fell initially (30 min) but was gradually restored (120 min). 4. If these pre-incubated synaptosomes were reincubated for 45 min at 30 degrees C in potassium free Krebs-Ringer-phosphate buffer a further rise in their SP content occurred which was taken as indication that SP is being synthesized in synaptosomes. 5. The newly synthesized SP is presumably stored by binding to phosphatidyl serine until a sudden release is initiated by depolarization.


Inhibition of the algesic effect of bradykinin and acetylcholine by mepacrine. 1. The isolated perfused rabbit ear connected to the body by its nerve only was used to investigate the influence of mepacrine on the algesic effect of bradykinin and acetylcholine. For comparison, quinidine was included in this investigation. 2. Infusion of mepacrine or quindine (2-10 microgram/ml) into the rabbit ear reduces the algesic effect of bradykinin as well as of acetylcholine in proportion to the dose. 3. Infusion of postglandin E1 (10 ng/ml) in addition to mepacrine or quinidine restores theinhibited algesic effect of bradykinin more than that of acetylcholine. 4. Mepacrine and quinidine (10 microgram/ml) reduce the brief vasoconstriction elicited by bradykinin in the rabbit ear. 5. The results suggest that mepacrine or quinidine reduce the algesic effect of bradykinin primarily by inhibiting the release of E-type prostaglandins which sensitize pain receptors and secondarily by an unspecific antagonism (local-anaesthetic action). The effect of acetylcholine, however, appears to be reduced mainly by an unspecific antagonism.


Studies on the positive inotropic effect of dopamine in the guinea-pig heart. The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10(-6)-3X10(-6) M). The inotropic effect of dopamine was antagonized by practolol (3X10(-7)-10(-6) M), but not by phentolamine (3X10(-6)-10(-5) M); moreover the alpha-adrenoceptor blocking drug (10(-5) M) did not affect the curve for dopamine in the presence of practolol (3X10(-7) M). In preparations in which fast sodium channels were blocked by K+ -rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10(-4)-3X10(-4) M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors.


Peripheral and central muscarinic receptor affinity of psychotropic drugs. The muscarinic receptor affinity of 27 psychotropic and 5 anticholinergic substances was examined in 2 in-vivo and 2 in-vitro models. A highly significant correlation was obtained between the effect of all compounds examined on the atropine sensitive binding of 3H-PrBCM and the effect in the conventional guinea-pig ileum preparation. Antagonism of oxotremorine induced tremors in mice by anticholinergics and neuroleptics was also significantly correlated to the corresponding data obtained in the in-vitro tests. Due to very low potency in the physostigmine induced mortality test in mice too few ED50 values were obtained to perform statistical comparisons. It is concluded, that the conventional guinea-pig ileum model and the 3h-prBCM binding model are equally predictive as tests for antimuscarinic properties. When in-vivo anticholinergic data for neuroleptics are used it must be considered that a possible dopamine receptor blockade may diminish the antimuscarinic effect of the substance.


Release of noradrenaline by the ionophore X537A from normal and reserpinized guinea-pig atrium. The effects of ionophore X537A on the release of 3H-noradrenaline and its metabolites from the superfused guinea-pig left atrium were investigated. Concentrations of ionophore of 10 and 30 mocrometer greatly increased the release of tritium. Of the total increase in radioactivity elicited by X537A 44% was accounted for as noradrenaline and 50% was due to deaminated metabolites. The ionophore-evoked release of tritium was independent of the extracellular calcium ions and was not affected by agents which modify calcium movements such as verapamil, ryanodine, ruthenium red and tetracaine. X537A released 3H-noradrenaline from extragranular sites in MAO-inhibited atria from reserpine-treated animals and this release was also calcium independent. It is concluded that the ability of X537A to release noradrenaline from vesicular or cytoplasmic sites is not related to its ability to couple with and transport calcium ions through membranes. The ionophore might modify the ionic distribution outside and inside the neuronal membrane which would lead to leakage of the transmitter.


Effects of dihydroergotamine methanesulfonate on the microcirculation of the rat cremaster muscle. Effects of dihydroergotamine on the microcirculation of the rat cremaster muscle were investigated microscopically using colour photographic technique. 1. Dihydroergotamine 10(-4) g/ml constricted arterioles of the rat cremaster. 2. Dihydroergotamine 10(-4) g/ml produced a significant contraction of venules. 3. Dihydroergotamine 10(-4) g/ml markedly inhibited the contractile response of noradrenaline 10(-6) g/ml on arterioles of the rat cremaster. The results suggest that dihydroergotamine has an appreciable vasoconstrictive action, especially upon venules, and that dihydroergotamine also has an adrenergic alpha-receptor blocking action. By means of highly sensitive negative colour film we obtained a satisfactory photograph of the rat cremaster's circulation.


Effect of acetylsalicylic acid on experimentally induced arterial thrombosis in rats. Acetylsalicylic acid (ASA) was tested for its antithrombotic activity in the arterial system after prophylactic administration to rats, using a new standardized method. Damage of the vessel wall was produced by chilling a small segment of the left carotid artery. Dose related, significant results were obtained after 3 mg/kg orally. If higher doses (10 and 30 mg/kg) are administered, the formation of non-occlusive thrombi is inhibited by 70--90% on the basis of thrombus weight. As the frequency distributions show, there are significantly more zero-values in the ASA treated groups (total 50%) than in the control groups. However, the incidence of occlusive thrombi was not changed by ASA. The long-lasting effect of ASA in inhibition of platelet aggregation was confirmed. The formation of arterial thrombi is significantly inhibited after prophylactic administration of 30 and 10 mg/kg up to 48 h before initiation of thrombosis. After administration of 3 mg/kg orally, only insignificant effects were observed. Thus the duration of action depends on the dose used.


Histoautoradiography of central nervous system in rats with generalized tetanus due to 125I-toxin. Rats were injected i.v. with 125I-tetanus toxin. In autoradiographs of the spinal cord radioactivity was found over the pericarya and in the surroundings of the motoneurones whereas grain density was less over their nuclear region. In addition, pericarya in the lateral horn of the thoracic region and also the bipolar cells of the spinal ganglia contained radioactivity. The central part and the dorsal horns of spinal cord, and the white substance did not show any appreciable radioactivity. Within the medulla oblongata, clusters of large cells representing motor nuclei, as well as some fibre tracts close to them, contained 125I. Forebrain and cerebellum remained free. According to its histoautoradiographic appearance, generalized tetanus can be described best as a combination of multiple local tetani.


Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat. The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml.kg-1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure. In healthy rats saralasin (6 microgram.kg-1.min-1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng.kg-1.min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.