Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat. Lysyl oxidase catalyzes the crosslinking of collagen and elastin. Lysyl oxidase activity was measured and localized in rat liver during the evolution of hepatic fibrosis induced by CCl4. Enzyme activity measured with DL-[6-3H]-lysine-labeled collagen substrates in liver and plasma increased sharply after approximately 3 wk of injection, reached a maximum at 6 wk, and then decreased. The increase in activity correlated histologically with early connective tissue septa formation, and the magnitude of increase was significantly greater than that found for the intracellular collagen biosynthetic enzymes protocollagen prolyl hydroxylase and lysyl hydroxylase. Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space. However, it was not possible to correlate the distribution pattern with a particular liver cell type. These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition.


Ontogenetic appearance and disappearance of tyrosine hydroxylase and catecholamines in the rat embryo. The ontogenetic pattern of noradrenergic differentiation in rat embryonic autonomic neuroblasts was defined in vivo. Noradrenergic specialization was examined by documenting the immunohistochemical appearance of tyrosine hydroxylase [Tyr-OH; tyrosine 3-monooxygenase; L-tyrosine,-tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the development of histofluorescence due to catecholamine (CA). Tyr-OH and CA were undetectable in the dorsal neural crest or the ventrally migrating crest cells and first appeared at 12.5 days of gestation (36--37 somite stage) in sympathoblasts that had formed sympathetic ganglion primordia. Fluorescence intensity and the number of fluorescent cells increased progressively thereafter. In addition, Tyr-OH and CA transiently appeared in scattered presumptive neuroblasts in the gut. The enzyme and transmitter were first detectable at 11.5 days of gestation and thereafter decreased progressively so that, by 14.5 days, only rare cells were encountered. There was remarkable synchrony in the appearance and disappearance of Tyr-OH and CA. These observations suggest that a number of noradrenergic transmitter mechanisms develop simultaneously in the differentiating neuroblast. The relevance of these results to the elucidation of developmental regulatory mechanisms is discussed.


Bacteriorhodopsin: lipid environment and conformational changes. The polar lipids of the purple membrane were exchanged for different phosphatidylcholine species. The resulting complexes had the same protein to lipid-phosphorus ratio as the natural membrane, but only about 0.5-1.0 mole of original lipid was still present per mole of bacteriorhodopsin. In such complexes the bacteriorhodopsin photocycle is slowed down 10-20 times, but the strong protein-protein interaction is not abolished. Due to the slow rate of the photocycle we were able to measure in the light the ratio between net proton release and net accumulation of the last intermediate of the photocycle, the unprotonated M412. This ratio was not constant and equal to 1.0, as expected for a single deprotonation reaction, but varied with pH from 1.5 to 0.4. The variable ratio suggests that light-induced conformational changes occur in the nonchromophore part of the protein, which shift the pKa values of unidentified groups so as to cause binding or release of additional protons. A similar conclusion was drawn from experiments on the kinetics of proton transfer by bacteriorhodopsin in subbacterial particles of Halobacterium halobium and in reconstituted bacteriorhodopsin proteoliposomes. However, in this case light-induced association and dissociation of additional protons occurs simultaneously on different sides of the membrane.


Proteins containing reductively aminated disaccharides: chemical and immunochemical characterization. Synthetic glycoproteins can be prepared by reductive amination of proteins and reducing carbohydrates in the presence of sodium cyanoborohydride. The reaction proceeds readily in aqueous solution at pH 6--9 to give high degrees of substitution. The degree of substitution can be determined by amino acid analysis, as the 2 degrees amine linkage formed with the epsilon-amino groups of lysine is stable to acid-catalyzed protein hydrolysis conditions. Antisera have been obtained to bovine serum albumin conjugates containing reductively aminated cellobiose, lactose, and maltose. Preliminary experiments demonstrate that antiserum to the cellobiose-BSA conjugate is hapten-specific, and the structural features of the hapten recognized by the antibodies were established by hapten inhibition experiments. These studies demonstrate that antibodies recognize both the terminal beta-glucosyl and acyclic reduced glucosyl residues.


Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa. Adult male Swiss-Webster mice were housed either singly (isolated) or with a female (nonisolated). Aggressive behavior was evoked by introducing a group-housed male mouse (intruder) into the home cage of the isolated or nonisolated mouse (resident).d-Amphetamine, methamphetamine, methylphenidate, cocaine, and L-dopa decreased attack and threat behavior by resident mice, the isolates requiring 2--4 times higher drug doses for the antiaggressive effects than the nonisolates, d-Amphetamine, methamphetamine, and methylphenidate caused intruder mice to be more frequently attacked by their non-treated resident opponents, to escape more often, to assume the defensive upright posture less, and to move about more often. L-Dopa nonspecifically de creased all elements of agonistic and nonagonistic behavior, while the amphetamines and methylphenidate suppressed attacks, increased escapes, decreased upright postures, and increased nonagonistic locomotion. By contrast, cocaine's antiaggressive effects were remarkably specific, i.e., not accompanied by changes in other behavioral elements.


Effect of thoracentesis on arterial oxygen tension. The acute effects of thoracentesis on arterial oxygenation were observed in 19 studies on 17 patients. Arterial blood samples were obtained prior to, immediately after, and 1 h after thoracentesis. Unpredictable changes in the arterial oxygen tension, ranging from -22 to +19 mm Hg were found immediately following thoracentesis. It was concluded that significant hypoxemia may result from thoracentesis due to aberration of ventilation-perfusion relationships. It is further suggested that oxygen therapy be routinely administered during and immediately after the procedure.


Mean whole body intracellular pH in unanesthetized dogs: a revised method. An improved method of calculating the mean whole body intracellular pH (pHi) by means of DMO in unanesthetized dogs is described. The elemination of DMO from the body fluid is assumed to follow a simple exponential decay with a time constant k1. The distribution of DMO into the extracellular and intracellular water is described by an exponential function (1-exp(-k2t)). From experiments in 9 unanesthetized dogs it was found that k1 = 0.008 h-1 and k2 = 1.325 h-1. Mean pHi was 7.08 +/- 0.05 at Pa(c02) = 4.1 kPa (31 mm Hg). The average difference between arterial blood and pHi was 0.35. No statistically different pHi values were found with data from arterial or mixed venous blood. Even after 24 h the method still yields reasonable values for pHi.


The influence of low, normal and high Pa(O2) on the respiratory effects of Pa(CO2) oscillations in anaesthetised cats. The present study examines the influence of oxygen tension on the recurrent tidal volume changes caused by oscillations in arterial P(CO2). The oscillations have a period equal to two respiratory cycles, and are produced by giving alternately CO2 -enriched and CO2 -free gas mixtures. The results show alternation of the tidal volume with the same incidence (is greater than 50%) at low, normal and high oxygen tensions. However, the magnitudes of the breath-by-breath changes are significantly greater at low oxygen tension than at normal oxygen tension. Under high oxygen tension breath-by-breath tidal volume changes are indistinguishable from those at normal oxygen tension.


Respiratory characteristics of opossum (Didelphis virginiana) blood during chronic anemia. In five adult opossums (Didelphis virginiana), blood hemoglobin concentration was lowered from 12.3g% to 6.4g% by daily bleeding. Blood P50 rose significantly (P is less than 0.05) from 44.5 mm Hg to 47.4 mm Hg and the concentration of 2, 3-diphosphoglycerate (DPG) increased from 14.17 mumol/g Hb to 20.90 mumol/g Hb. The observed shift in blood oxygen affinity was of similar magnitude to that recorded in humans with a similar degree of anemia, but the concomitant rise in DPG concentration was greater in opossums than in humans. In the opossum the shift in P50 with anemia can be attributed entirely to the action of DPG as a non diffusible intraerythrocytic anion.


Oxygen transport in chicken embryos under hypothermal exposure. Fertile hens' eggs incubated for 16 days at 38 degrees C were abruptly exposed to a temperature of 30 degrees C for 2 h and then determinations of blood gas parameters and the O2 dissociation curve were performed. In addition, O2 uptake was measured. Under hypothermal exposure the O2 dissociation curve showed a marked leftward shift in accordance with the increase in pH. The O2 saturation in arterialized blood of the allantoic vein reached almost 100%, and the blood S(O2) of the allantoic artery also increased up to about 50% in contrast with about 20% in normothermal controls. The blood flow rate through the chorioallantoic capillary plexus seemed to be almost identical with that of normothermal embryos. Because of the increased O2 affinity and the decreased O2 consumption, the systemic venous O2 reserve should be raised by hypothermal exposure. In connection with this conjecture, the redistribution of blood flow and O2 quantity by hypothermal exposure were calculated using the same circulation model as used in normothermal embryos. The result came closer to fetal lambs than to normothermal embryos.


Comparison of efflux rates of hydrogen and lactate ions from isolated muscles in vitro. Relative rates of efflux of hydrogen and lactate ions from skeletal muscle in vitro were determined on isolated rat diaphragms and frog satorius muscles. After a period of lacate accumulation by stimulation in vitro, muscles were suspended in a small volume of Ringer solution for different time periods lasting up to 60 min. The pH change in the solution was monitored continuously. After the predetermined time period, samples of the muscle and the Ringer solution were analysed for lactate content. Results showed that in both types of muscles the rate of efflux of hydrogen ions exceeded that of lactate ions by factors of about 14 and 50 in the case of diaphragm and sartorius muscles respectively. Because of this difference observed in the efflux kinetics of hydrogen and lactate ions, it is evident that the lactate content of a body compartment does not represent the absolute hydrogen ion load of the same compartment, particularly during the early phase of the efflux process.


[Détermination of salivary pH by contact pH metry. Study of ph on the tongue and of the orifices of Wharton's and Stenon's ducts]. The authors describe an electrochemical technique for the measurement of salivary pH by contact. They present a critical study fo 167 cases. The values obtained are characteristic in terms of age and the site of determination (dorsal surface of the tongue, orifice of Wharton's or Stenon's ducts).


The electrical potential difference and impedance between CSF and blood in unanesthetized man. The electrical potential difference (PD) between cerebrospinal fluid (CSF) and blood has been studied extensively in animals. To obtain data from man the PD and impedance were recorded from the lumbar subarachnoid space of thirteen unanaesthetized patients with a presumably normal blood--brain barrier. The spontaneous PD ranged from 1 mV to 5 mV, CSF positive to blood. Hyperventilation and CO2-inhalation changed the PD with a mean slope of deltaPD/deltapHa of --4.16 mV/pH. The CSF-blood PD in unanaesthetized man is similar in direction to that found in dogs, goats and rats, but its sensitivity to change in arterial pH may be less.


A short duration renal acidification test. As earlier investigations of renal acidification capacity were poorly standardized it was considered important to develop a clinically useful method. The ability of the kidneys to acidify urine was studied in 19 normal persons by short ammonium chloride loading. Ammonium chloride was given in a dose of 150 mmol/m2 body surface in one of four different ways: whole tablets, crushed tablets, capsules and in solution. The degree of acidosis developed in each subject was measured in arterialized capillary blood samples. Urine was analysed for pH, titratable acid, ammonium ions (TA and NH4+) and phosphate. The excretion of TA, NH4+ and phosphate increased with the degree of acidosis in blood whilst urine pH decreased. The critical level appeared to lie around a base excess of -6 mmol/l below which all subjects could acidify their urine to a pH below 5.0. For clinical applications a frame of reference with tolerance limits is given for acidification capacity related to the degree of acidosis expressed as base excess.


Urine acidification capacity in renal stone formers. A short ammonium chloride loading test was used in the investigation of renal acidification capacity of 51 patients with idiopathic recurrent renal stones containing calcium. Many of these patients had suffered from prolonged and severe stone disease. In 31% of the patients an impaired acidification with varying degrees of severity was found. Eight patients had defects suggesting distal renal tubular acidosis (RTA). One case with the complete and two cases with the incomplete form of RTA were found. A further five patients, who were all able to acidify their urine to an acid pH, had milder defects in the excretion of titratable acid and/or ammonium ions which may indicate an early stage of distal tubular acidosis. Six patients were suspected of having a proximal acidification defect, as they showed delayed responses to the ammonium chloride induced acidosis.


Bicarbonate re-absorption in renal stone patients with acidification defects. A pathological renal response to ammonium chloride loading was found to be common in renal stone formers. In order to elicit further information about the impaired acidification capacity eight patients were investigated by bicarbonate loading. One patient with a mild acidification defect had normal tubular re-absorption of bicarbonate. Five of these eight patients with suspected proximal acidification defect and two patients with impaired distal acidification were found to have a low bicarbonate threshold and an increased, fractionated, bicarbonate excretion at a normal plasma bicarbonate level. Four of the patients with suspected, proximal, acidification defect reached a maximal re-absorption of bicarbonate (Tm) that was low, while three patients did not reach a Tm. These three factors indicate increased bicarbonate wastage from the kidneys. A constantly alkaline urine, such as exists in patients with proximal acidification defect may give rise to an increased risk of the precipitation of renal stones - primarily calcium-phosphate stones.


Immunofluorescent detection of nuclear double-stranded RNA in situ in Vero and mosquito cells. Double-stranded RNA (dsRNA) was detected in situ by indirect immunofluorescence with antibodies to dsRNA. It was seen in nuclei of Vero and Aedes albopictus cells, but not in BHK cells, KB cells, chick embryo fibroblasts, or HeLa cells. Reactive dsRNA was present in the nucleoplasm, but not in nucleoli or cytoplasm. Extracted RNA from the whole cell contained from 0.08 percent (BHK) to 0.46 percent (HeLa) dsRNA, as estimated by serological methods. This dsRNA, found in molecules having the size distribution of heterogeneous nuclear RNA, did not renature rapidly after denaturation. The quantity of dsRNA in total extracted RNA did not correlate with the presence or absence of nuclear staining in situ.


Sodium channel inactivation in squid axon is removed by high internal pH or tyrosine-specific reagents. In squid axon, internal alkalinization from pH 7.1 to pH 10.2 results in a reversible decrease of the maximum inward current and the steady state sodium channel inactivation. Similar effects were observed after treatment of the axon with tetranitromethane or after iodination with lactoperoxidase. These results suggest that a tyrosine residue is an essential component of the inactivation process in this nerve.


Histamine H1 receptor-mediated guanosine 3',5'-monophosphate formation by cultured mouse neuroblastoma cells. Incubation of cultured mouse neuroblastoma cells with histamine caused a rapid and marked increase in the formation of guanosine 3',5'-monophosphate (cyclic GMP) by these cells. Receptor agonists for H1, but not H2, caused this effect which was reduced by H1 but not by H2 or muscarinic acetylcholine receptor antagonists. These results indicate that activation of H1 receptors in these cultured nerve cells stimulated cyclic GMP formation.


Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Silicone pellets containing d-amphetamine base were implanted subcutaneously in rats. These pellets release amphetamine continuously for at least 10 days. Several days after implantation, swollen dopamine axons concomitant with large decreases in tyrosine hydroxylase activity were observed in the caudate nucleus. Decreased tyrosine hydroxylase activity was still present 110 days after pellet removal in the caudate but not in several other brain regions, nor in the caudate of rats injected with an equivalent amount of amphetamine in daily injections. This implies that continuous amphetamine administration has a selective neurotoxic effect on dopamine terminals in the caudate.


Kainic acid lesions of the striatum dissociate amphetamine and apomorphine stereotypy: similarities to Huntingdon's chorea. Kainic acid lesion of cell bodies in the dorsal striatum enhanced the stereotypy-producing effects of d-amphetamine without affecting the sterotypy produced by the direct receptor agonist apomorphine. This pattern of results parallels that found in patients suffering from Hungtington's chorea, thus strengthening the parallels between the kainic acid animal model and the human disease state initially suggested on biochemical gounds. The present results further suggest a dissociation of the mechanisms involved in the production of stereotypy by these two drugs, perhaps in terms of differential involvement of the striato-nigral negative feedback loop.


Posterior spinal fusion with Harrington instrumentation using "balanced" anesthesia. In our experience nitrous oxide-oxygen-morphine-curare anesthesia has proved preferable because of the need for swifly awakening patients after instrumentation to ascertain neurologic status. Adjunctively, doxapram has been used to awaken patients in a predictably short time span. To prevent massive blood loss, hypotension has been attained by pentolinium, trimethaphan camsylate, and sodium nitroprusside.


Filariasis in West Kalimantan (Borneo), Indonesia. A survey was carried out among persons residing in 8 villages in the Province of West Kalimantan, Indonesia to determine the prevalence of filariasis. Finger tip blood smears were obtained at night from over 3,000 people and microfilariae of Brugia malayi were found in 108 (3.5%) and Wuchereria bancrofti in 10 (0.3%). Most B. malayi (96 carriers) was found in Kakap, a village near the coast, 20 km from the provincial capital of Pontianak. Nine of 10 cases of W. bancrofti were located in Pahauman, a village 130 km northeast of the provincial capital. Periodicity studies indicate the strain of B. malayi to be subperiodic. In Kakap 18% of 226 persons examined had a clinical history of filariasis and elephantiasis was seen in 13%. This is the first report of rural bancroftian filariasis in the area. A few Mansonia species of mosquitoes were examined but none were infected with filarial larvae.


Cation and hydrogen ion effect on canine acid and gastrin output. Differential stimulating effects on the parietal cell of dogs by calcium, magnesium and sodium were noted only at an alkaline pH. Acid inhibited the parietal cell, and antral perfusion did not cause gastrin stimulation at any pH level. The pH of the milieu of the parietal cell appears to be a more critical regulator of acid secretion than physiologic antral gastrin variation.


A new model for the study of septic shock. Septic shock was produced in 28 healthy mongrel dogs by injecting 10(8) Escherichia coli organisms per kilogram into the gallbladder following division of the cystic artery and duct. Based upon the circulatory responses and the mortality, two distinct groups emerged. In one, the cardiac index decreased significantly, and the total peripheral resistance was elevated. In the other, the cardiac index increased significantly, and the total peripheral resistance was significantly lower. The average survival time in the former group was three days and, in the latter, five days. The physiopathology of this model is remarkably similar to that of human septic shock. Studies are planned to further describe this model to increase its utility in the study of septic shock.


Pus, deoxyribonucleic acid, and sputum viscosity. On 100 sputum specimens selected from patients suffering  from chronic bronchitis, bronchiectasis, asthma, and cystic fibrosis total deoxyribonucleic acid (DNA) content has been related to macroscopic type, to total dry weight yield, and to the apparent viscosity of the secretion at 1350 s-1: since DNA may be present, either as fibres or within cells, in one-third of the specimens the contribution of each form to the apparent viscosity was assessed. The effect on sputum viscosity of the addition of DNA in vitro has also been studied. Whereas between mucoid, mucopurulent, and purulent macroscopic types a significant difference in total DNA and dry weight yield has been found, viscosity was not significantly correlated with purulence. Similarly, the concentration of either cells or fibres correlated significantly with total DNA but not with viscosity. The in vitro addition of DNA to sputum caused a significant increase in its viscosity, and reasons for the differences between the iv vivo and in vitro effect are discussed. Certain constituents of purulent sputum tend to increase viscosity and others to reduce it, and the influence of these varies in the several diseases studied.


Androgen concentration and partial characterization of 5alpha reductase in the epididymis of the rhesus monkey. The 5alpha reductase activity ofthe monkey epididymis was studied. The enzyme was found in particulate subcellular fractions, its distribution closely resembling that of the microsomal marker enzyme NADPH: cytochrome c reductase, suggesting an association of 5alpha reductase with membranes of the endoplasmic reticulum. Maximal enzyme activity was found at pH 5.4 and at 32--37 C. The crude nuclear preparation had a Km: 0.315 x 10(-6)M and Vmax: 168 pmoles/mg protein/h. The microsomal enzyme had a Km: 0.243 x 10(-6)M and Vmax: 828 pmoles/mg protein/h. Neither enzyme preparation was affected by addition to the incubation media of dihydrotestosterone (DHT) or 5alpha-androstane-3alpha,17beta-diol. The endogenous androgen concentration in the epididymides of 2 different monkeys, in ng/g wet weight was: DHT 20.81 +/- 1.98; T: 9.0L +/- 2.83; diol: 3.03 +/- 0.41.


Study of complex marine sterol mixtures by mass-analyzed ion kinetic energy spectrometry. Mass-analyzed ion kinetic energy spectrometry (MIKE) is shown to be an efficient and rapid method for the analysis of complex sterol mixtures. The method has been applied to the study of the free sterol fractions of five marine and one freshwater invertebrates.


Influence of experimental cryptorchidism on cholesterol side-chain cleavage enzyme and delta5-3beta-hydroxysteroid dehydrogenase activities in rat testes. Testicular cholesterol side-chain cleavage enzyme (CSCCE) and delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activities were assessed 12 hours and 2, 4, 8, 16, and 32 days after surgical induction of bilateral cryptorchidism in adult rats. Within 12 hours after surgery CSCCE activity (expressed as dpm of isocaproic acid-14C formed from cholesterol-26-14C/3 hours/testis) was significantly reduced (P less than 0.01) in cryptorchid testes to approximately 55% of sham-operated control values and remained depressed at less than 50% of control activities 2, 4, 16, and 32 days after surgery. Cryptorchid testis delta5-3beta-HSD activity (measured by a pregnenolone substrate-depletion assay and expressed as mumoles of products/30 minutes/testis) did not differ from controls (P greater than 0.05) 1/2, 2, or 4 days after translocation of testes to the abdominal cavity. By day 8 of cryptorchidism, however, delta5-3beta-HSD activity was reduced to 60% of control values (P less than 0.05) and continued to decline to approximately 30% of controls during the remainder of the experimental period. These observed alterations in enzyme activities suggest an impairment in the ability of cryptorchid rat testes to synthesize androgens and further indicate that testicular CSCCE is more acutely sensitive to the cryptorchid milieu than delta5-3beta-HSD.


Lack of correlation between splenic and marrow hematopoiesis following irradiation or irradiation and transplantation in mice. Differences were seen in the relative importance of spleen and marrow in early erythroid regeneration of lethally irradiated mice given spleen or marrow cell transplants compared with that in sublethally irradiated mice with surviving endogenous hematopoietic cells. Radioactive iron uptake was predominantly in the spleen of mice with transplants and in the marrow of endogenously recovering mice. Visable spleen colony counts increased from day 4 to day 7 and plateaued through day 10 in the transplant system, but shoed a small abortive rise with a 5-day peak, followed by a steady increase from days 6 to 10 in the endogenous system. Comparisons of peroxidase-positive cells (granulocytes) in the marrow of femurs and humeri and iron uptake in marrow and spleen suggested that repopulation of the marrow and spleen were independent, while that of different areas of the marrow was interrelated. The interrelationship of the rate of marrow regeneration was closer in the endogenous than in the transplant system.


Human red cell content of cyclic nucleotides and cations upon beta-adrenergic blockade. The content of cyclic nucleotides (cAMP, cGMP) and Mg2+, Zn2+,Na+ and  K+ was determined in human erythrocytes and after beta-adrenergic blockade in healthy individuals. The figures for cAMP and cGMP were 4.20 and 3.36 nmoles/ l intracellular volume, respectively. Only slight effects on the cyclic nucleotide content as well as on cation content were seen upon beta-blockade in the erythrocytes. It is concluded that the single determination of red cell cAMP is not a sufficient indicator of beta-adrenergic blockade. The determination of cAMP in combination with cGMP, Zn2+ and Na+ might reflect a beta-adrenergic blockade.


Denervation supersensitivity of the urethra to alpha-adrenergics in the chronic neurogenic bladder. The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholineR and a group of 10 control subjects. A supersensitive response to the administration of an alpha-stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of alpha-adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of alpha-adrenergic predominance in the urethra which is now believed to be dually innervated.


[Content of adenine nucleotides and creatinephosphate in brain, myocardium, liver and skeletal muscle under combined action of hypercapnia, hypoxia and cooling]. Cooling of rats under conditions of hypercapina and hypoxia induced no changes in the content of adenine nucleotides in the brain and skeletal muscles and decreased their concentration in the liver and myocardium. The content of creatine phosphate increased in the brain, but had no changes in the other tissues. 48 hours after cooling the amount of adenine nucleotides in the brain was higher as compared with the initial values, that was due to an increase in the ATP concentration; in the other tissues the contents of adenine nucleotides did not differ from that of the intact rats. The repeated action (48 hours after the first influences) caused no changes in the contents of adenine nucleotides in skeletal muscles and decreased them in the myocardium and liver. In the brain their amount and the content of creatinephosphate were increased as related to the intact rats. In the brain and myocardium the level of NADPH decreased after the first action and 48 hours after impact it restored up to the inital values. After repeated impact the level of NADPH in the brain restored up to initial values, in the myocardium it was increased.


Uropharmacology: VII. Ganglionic stimulating and blocking agents. A classification of the various ganglionic stimulants and blockers is presented, and their pharmacologic effects on the urinary bladder and urethra are discussed. Ganglionic stimulating drugs are of considerable interest in investigational work but are not presently used therapeutically. Ganglionic blockers include hexamethonium, tetraethylammonium, mecamylamine emepronium, pentolinium, chlorisondamine, and pemipidine. Of the numerous ganglionic blocking drugs that have appeared on the therapeutic scene, only mecamylamine, pentolinium, and trimethaphan are currently official.


[Immobilized form of Streptomyces griseus proteases complex]. The immobilized form of proteases complex of Str. griseus actinomycete is obtained by means of glutaric aldehyde with aminoethyl cellulose. Hydrolysis of synthetic substrates showed that the system of peptide hydrolases is bound, but the ratio of activities as compared to the initial proteolytic complex changes, pH-optimum of the total proteolytic activity, pH- and temperature optima of stability are not changed with immobilization. On the whole no essential stabilization of the complex was observed. After five repeated cycles of the immobilized form utilization of the activity loss accounts for 40-60%.


[Biochemical and hematological changes in the blood of horses after the "Velká Pardubická" steeple chase]. Blood parameters were studied in two groups of horses in the "Velká Pardubická" steeple-chase in 1974, 1975 and 1976. After the race, the levels of lactate showed a manifold increase; an increase was also ascertained in the levels of glucose, sodium, potassium, haemoglobin, in the haematocrit value and in the number of erythrocytes. The following parameters significantly dropped: the levels of acid-base balance - pH, base excess, bicarbonate levels. It was proved that the values of the same parameters in horses during training were incomparably lower. It is advisable to examine horses thoroughly during training and to use the results of training for the evaluation of their condition before difficult races.


Automated antibody detection in a low ionic strength (glycine) medium. Modifications were introduced into the low ionic strength system of Lalezari. Glycine was added in place of acidified glucose and the sensitisation and aggregation phases were segregated. In the automated glycine system a stable baseline is readily obtained as strong cell aggregation, with risk of cell adhesion to coil walls, is restricted to the last few turns of the aggregation phase. The automated glycine system is sensitive to a concentration of 0.0015 microgram/ml of anti-D diluted in saline and to 0.006 microgram/ml of anti-D in serum. Antibodies of a broad range of specificity are detectable.


[Protein inhibitor of cyclic nucleotide phosphodiesterase in the retina in hereditary degeneration]. Thermostable protein fraction from retina of rats with hereditary retinal dystrophy (Hunter and Campbell strains) did not inhibit cyclic nucleotide phosphodiesterase. At the same time an inhibitory component, found in retina of Wistar rat, rabbit, frog and lamprey, was similar to the component from bovine retina. Quantity of the inhibitory component in normal rat retina decreased considerably within postnatal period (12 days--3 months). Thermostable proteins, isolated from Campbell rat retina, differed from that of Hunters' one by electrophoretic properties while both preparations were dissimilar to the protein of normal rat. Protein bands, containing inhibitory component from dystrophic rat retina, appear to be less distinct as compared to those of normal rat. These proteins, eluated from the bands of Campbell rats, activated phosphodiesterase but the preparations from Hunter rats did not influence on it.


[Increase in tryptic digestibility of dietary proteins in the stomach]. The trypsin assailability of food proteins (bread, dried milk and egg powder pastes) subjected for different periods of time to the action of the gastric juice directly in the stomach was studied by taking account of the specific topography of its content. It is shown that foodstuffs proteins can be increasingly assailable with trypsin as a result of the action exerted upon them in the stomach by the secretion of its glands. For different food proteins and at different time after feeding the animals as well as in different layers of the gastric contents this effect manifests itself dissimilarly. The trypsin assailability of food proteins increases in the layer near the mucosa and in the antral layers of the gastric contents. A higher trypsin assailability of food proteins is directly related to the level of the proteins hydrolysis in the stomach, to the acidity of the gastric contents and, especially, to its proteolytic activity.


[Dynamics and mechanism of mineral metabolic disorders in excessive phosphorus content in the diet]. Keeping rats on a ration with a 1:3 proportion of calcium and phosphorus for 2 weeks results in hyperprosphatemia, hypocalcemia and renal calcinosis with uremia. When putting these animals on a food ration with the calcium and phosphorus ratio of 1:1 the concentration of these elements in the blood quickly returns back to normal, while renal calcinosis continues for the whole period of observation (7 months). The growing animals are more sensitive to a phosphorus excess than are the adult ones. An excessive consumption of phosphorus leads to its increased excretion with the urine with concurrent diminution of the calcium excretion. The blood and urine pH then experiences no change, whereas the ability of the turned inside out segments of the small intestine to absorb calcium as against the concentration gradient (active transport) in vitro not only does not diminish, but initially even goes up. It is suggested that the excess phosphorus content in the food ration tends to directly derange absorption of calcium in the intestines, this resulting in the development of hypocalciemia, hyperparathyroidism and calcinosis of the viscera and tissues.


Metabolism of atenolol in man.

Metabolism of atenolol in man. 1. The disposition and metabolism of 1-(4-carbamoyl[14C]methylphenoxy)-3-isopropylaminopan-2-ol (atenolol, Tenormin) has been studied in man following oral and intravenous doses. 2. Approx. 50% of an oral dose was eliminated in urine; the major radiolabelled component was atenolol (approx. 90%). Faecal extracts also contained largely unchanged atenolol, with small amounts of more polar metabolites. Biliary excretion of atenolol and its metabolites is not a major route of elimination in man. Metabolism of the compound is not extensive and route-dependent modes of metabolism do not appear to complicate the position. 3. Atenolol appeared to be the only major radiolabelled component in blood. 4. Oral doses of atenolol are incompletely absorbed (range 46-62%), even when formulated as a solution. 5. 1-[4-(C-Carbamoylhydroxymethyl)phenoxy]-3-isopropylaminopropan-2-ol was a minor urinary metabolite, which has only one tenth the activity of the parent compound as a beta-adrenergic blocking agent in the rat. 6. Pharmacological activity in man appears to be due to atenolol alone.


On the evolution of an oligocephalic enzyme. glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains of Salmonella typhimurium. (1) A procedure has been described for the purification of two glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains TAX6trpR782 and trpAB1653trpR782 of Salmonella typhimurium. (2) The native enzymes tend to aggregate forming polymers of molecular weights 333,000 in the case of TAXtrpR782 and 220,000 and larger than 1X10(6) in the case of trpAB1653trpR782. In the presence of sodium dodecyl sulfate the polymer of trpAB1653trpR782 dissociates into a single component with molecular weight of 72,000. (3) In contrast to anthranilate phosphoribosyltransferase of the wild type component II, the glutamine-chorismate-amidotransferase-free proteins do not complex with component I. They do however show catalytical similarities with the wild type with respect to anthranilate phosphoribosyltransferase activity.


[Analytical data of flunitrazepam (rohypnol), a new benzodiazepine-derivative, in special consideration of its metabolites (author's transl)]. The article describes analytical data (TLC, GLC, IR, UV and MS) of flunitrazepam, 7-amino-flunitrazepam, desmethylflunitrazepam, 3-hydroxyflunitrazepam, 7-amino-desmethyl-flunitrazepam and many other benzodiazepine-derivatives, especially aminobenzophenones. Also extraction from biological specimen is reported.


[On the distribution of myxobacteria in the temperate South America (author's transl)]. 60 soil samples from Southern Chile, mainly from forests and grassland, yielded six species of myxobacteria. In forest soils Myxococcus coralloides and Myxococcus fulvus occur frequently, in grassland soils Myxococcus coralloides and Archangium gephyra are predominating. Myxococcus virescens, Melittangium lichenicola, and Cytobacter fuscus have been observed rarely. It is pointed out that due to climate factors a high soil acidity causes the low nuber of myxobacter species. A comparison with the number of species in substrates from important plant formations over various climates is given.


[Neuraminidase activity of nonpathogenic Neisseria]. It was revealed earlier by the authors that N. meningitidis of the principal serological groups A, B, and C possessed neuraminidase activity. In the present work it was shown that this sign was genus-specific, and that this property was also possessed by the representatives of nonpathogenic neisseria habituating in the nasopharynx, However, the enzymatic activity in nonpathogenic neisseria was less pronounced than in meningococci, and required more prolonged contact of the enzymatic-substrate mixture for its detection. There was revealed a direct relationship between the neuraminidase activity and the growth phase of the microorganisms, whose maximum coincided with the exponential phase of bacterial growth, this apparently being associated with the extracellular character of its origin.


[Study of hemosensitization characteristics for the purpose of standardizing erythrocyte flagellin diagnostica]. The work is devoted to the study of conditions required for the purpose of creation of standard and the most active preparations of erythrocytic H-diagnostic agents. The dependence of binding of the H-antigen by erythrocytes on the pH and the ionic power of the medium was investigated. It was demonstrated that in the process of erythrocyte sensitization with flagellin of great importance were electrostatic, hydrogen, and hydrophobic powers.


[Method of culturing typhoid microorganisms with automatic regulation of glucose feed]. A system of oxygen-glucose inverse relationship is not acceptable for cultivation of typhoid bacilli with a high reproductive rate and glucose utilization. The elaborated method of automatic glucose supply during typhoid bacilli cultivation permits to lead the process under the optimal conditions by pH and the residual glucose concentration.


[Acid-base balance during dosed fasting of schizophrenic patients with residual manifestations of organic lesions of the central nervous system]. The indices of acid-alkaline blood balance was studied in the dynamics of dosed hungering in 29 patients with sluggish schizophrenia and 16 patients with residual signs oforganic lesions of the CNS. There were differences in the pH index, standard and buffer bicarbonates alkaline deficiency which indicated to different degrees of acidosis in this group of patients. Significant differences in the acid-alkaline indices during hunger were seen in the different groups of patients depending upon the existence or absence of hypothalamic disorders (without consideration of their nosological affinity). The existence of hypothalamic disorders requires a more careful consideration when prescribing hunger therapy (the first session should not exceed 10-14 days).


Polymorphism of the cobalt-activated acylase in human tissues. A method was elaborated for obtaining polyacrylamide gel zymograms of the cobalt-activated acylase after electrophoresis. Two fractions of the acylase showing activity towards N-chloroacetyl-gamma-L-glutamyl-beta-naphthylamide were found in human kidney, liver and intestine. The two fractions isolated from liver differ in substrate specificity, heat resistance, response to metal ions, inhibition by deaminated dipeptides, and in molecular weight. They differ also from other N-acylamino acid amidohydrolases: aminoacylase (EC 3.5.1.14) and aspartoacylase (EC 3.5.1.15).


[Measurements and calculations on aglycon liberation from highly masked CMT selectines with beta-glucuronidase at pH 6. Realization of the principle of transport form-activity in anti-cancer drugs: theory of selectivity]. The authors describe methods and results on the aglycon liberation from several glucuronides using beta-flucuronidase in vitro. The glucuronides examined are prototypes of new potent anticancer drugs (so-called CMT selectines). Basing on the knowledge of the values and parameters involved theoretical considerations result in evaluation of the anticipated selective action of CMT selectines in artificially hyperacidified cancer tissues compared to normal tissues. The equations derived from certain mathematical simplifications are presented. The calculated high selectivity S approximately 20 can only be realized in vivo if the "masking index" s as to toxic action and renal clearance of a chosen CMT selectine is greater than 20. In fact, the hitherto known CMT selectines exhibit sufficiently high masking indices that the realization of a true transportation form/active form principle using different cancerotoxic agents as aglycones can be assumed.


[Effect of rapid changes of the oxygenation state and other external parameters on the long-term behavior of the energy metabolism in the erythrocyte]. The red blood cell when transported through the circulatory system is exposed to a steady (approximately periodical) change of environmental conditions causing a permanent fluctuation of its important metabolic parameters. In a simple theoretical model it is demonstrated that a rapid oscillation of such parameters may stabilize a metabolic state which will collapse when this oscillation breaks off. The hypothesis is advanced that parameter oscillations caused by the physiological function of the red blood cell may be of importance for the maintenance of its energy metabolism and that the break-off of these oscillations may be a potential cause for the metabolic collapse, e.g. in stored blood.


Reversibility of the blood-brain barrier dysfunction induced by acute hypertension. An acute hypertensive episode of short duration (less than 3 min) induced by i.v. injection of angiotensin in rats resulted in a blood-brain barrier dysfunction that was rapidly reversible. Thus, no macroscopic extravasation was seen when Evans blue was given 10 or 20 min after angiotensin. A faint fluorescence (Evans blue-albumin) was seen in the walls of some intracerebral arterioles in a few rats given the tracer 10 min after angiotensin.


[Adult metachromatic leucodystrophy (author's transl)]. A new adult case of metachromatic leucodystrophy (MLD) is reported. The earliest clinical signs are psychiatric in contra-distinction with the prevalent neurological signs observed in infantile or juvenile MLD. Although the occurrence of psychiatric features in adolescents or adults does not at first suggest MLD, it is easy to ascertain the diagnosis by combining the enzymatic assay of arylsulfatase A on leucocytes or cultured fibroblasts with the morphological study of nerve bundles. Such a discovery has of course a major importance in genetic counselling.


Measurement of cerebral blood flow in the fetal lamb with a note on the flow-distribution. The cerebral blood flow was measured in the acutely exteriorized fetal lamb by 133Xenon washout and microsphere distribution techniques. The measurements were performed at different blood gas levels. Regional cerebral blood flow was calculated from the microsphere distribution for five different parts of the brain. This gave estimates for blood flow in both the grey and white matter of the hemispheres, which were in close agreement with the cerebral blood flow estimated by the 133Xe washout technique. The microsphere distribution shows that the fetal cerebral hemisphere has a low blood flow compared to the basel parts of the brain and that this difference is increased during hypoxia and hypercarbia.


Identification of beta-adrenoceptors and histamine receptors in the cat nasal vasculature. The responses of the nasal capacitance vessels of the cat were recorded following intra-arterial injections of beta-adrenoceptor agonists and histamine H1-and H2-receptor agonists. Isoprenaline evoked vasodilation and propranolol (beta-adrenoceptor antagonist) caused a parallel shift to the right of the isoprenaline log dose-response curve. Histamine, 2-(2-aminoethyl)pyridine (H1-agonist) and 4-methylhistamine (predominantly H2-agonist) all evoked vasodilation. Metiamide (H2-antagonist) produced a further small parallel shift to the right of the histamine log dose-response curve after the administration of mepyramine (H1-antagonist). It is concluded that the nasal capacitance vessels of the cat contain beta 2-adrenoceptors and H1-and H2-histamine receptors.


Alprenolol fails to antagonize the metabolic changes following repeated thyroxine injections in the rat. Repeated injections of rat with 1-thyroxine (50 microgram/kg daily for 5 five-day weeks) retarded the weight gain of the animals and increased the absolute and relative size of the heart, adrenals and interscapular brown adipose tissue. In the myocardium and thigh muscle, thyroxine treatment resulted in elevated activity of oxidative enzymes, succinate dehydrogenase, malate dehydrogenase and citrate synthase, while the activities of glycolytic enzymes remained unchanged. Glycogen content of the heart was decreased following thyroxine regime. In the brown fat, on the other hand, thyroxine injections resulted in a reduction of the activity of oxidative enzymes. This reduction can be accounted for by the decreased protein (enzyme) content of the tissue due to deposition of fat. Furthermore, thyroxine treatment delayed the body cooling of the rats swimming in water at 25 degrees C and enhanced hyperthermic response to injected noradrenaline. All these changes, which were not observable in rats treated with daily alprenolol (20 mg/kg) injections, were as pronounced in rats injected with alprenolol together with thyroxine as in rats injected with thyroxine only. It is concluded that beta blockers do not antagonize the metabolic changes due to hyperthyroidism.


Acute and long-term salt depletion and beta-blockade: plasma renin activity response and its relation to blood pressure reduction in long-term treatment. The changes in plasma renin activity (PRA) during short-term salt depletion (and peroral furosemide on the first day) and after bolus injection of propranolol were compared to the change during long-term treatment with diuretic and with propranolol in 19 patients with benign primary hypertension. A highly significant correlation was found between PRA on short-term and long-term salt depletion (r=0.02). A highly significant correlation was likewise found between initial PRA and decrement of PRA after bolus injection of or long-term treatment with propranolol. Only a weak inverse correlation was found between PRA reached during short-term salt depletion or long-term diuretic treatment and the fall in diastolic BP during long-term treatment (r=0.60). No significant correlation was found between decrease in PRA on propranolol (bolus/long-term) and diastolic BP reduction. It is concluded that the short-term PRA response to salt depletion and propranolol in the individual patient gives a good prediction of the PRA level on long-term diuretic or propranolol treatment, but is of no value in predicting the BP reduction during treatment.


Stereochemical studies of hydrogen incorporation from nucleotides with fatty acid synthetase from Brevibacterium ammoniagenes. The biosynthesis of fatty acids from malonyl-CoA and acetyl-CoA was investigated with an enzyme preparation which was purified 100-fold from Brevibacterium ammoniagenes. Fatty acids synthesized in the presence of D2O and stereospecifically deuterated NADPH and NADH were isolated and analyzed by mass chromatography to examine the localization of deuterium in the molecule. The following results were obtained: 1) HB hydrogen of NADPH was used for beta-ketoacyl reductase. 2) HB hydrogen of NADH was used for enoyl reductase. 3) Hydrogen atoms from water were found on the even-numbered methylene carbon atoms (2-hydrogen atoms per carbon atom) and some were also found on the odd-numbered methylene carbon. 4) Hydrogen atoms from NADPH were found on odd-numbered methylene carbon atoms (1-hydrogen per carbon). 5) Hydrogen atoms from NADH were also found on the odd-numbered methylene carbon atoms, but the number of incorporated hydrogen atoms was less than expected. The exchange of HB hydrogen of NADH with water catalyzed by enoyl reductase was suspected. 6) The exchange of methylene hydrogen atoms of malonyl-CoA with proton of water was suggested by 13C NMR analysis.


Studies on the function of the activator of sulphatase A. The activator of sulphatase A is necessary for the enzymic degradation of sulphatides to cerebrosides at ionic concentrations in the physiological range (1). Activation is probably due to the reversible formation of a one-to-one complex between activator and sulphatides (1,2). Formation of this complex is partly inhibited by cerebrosides due to competitive binding (2), as well as by phospholipids (e.g. lecithin or phosphatidylserine). Inhibition of the complex formation between activator and sulphatides by cerebrosides and phosphatidyl-serine depends on the concentration of the lipids and is of the same order of magnitude as the inhibition (by these lipids) of the enzymic degradation of sulphatides in the presence of activator (1). Moreover the degradation rate of sulphatides increases with the concentration of activator-sulphatide complex in the reaction mixture (1) indicating that the activator-sulphatide complex is the substrate for the enzyme in the degradation of sulphatides by sulphatase A.


Renal consequences of narcotic abuse.

Renal consequences of narcotic abuse. Heroin addiction is associated with several severe and occasionally fatal renal complications. Acute renal failure consequent to rhabdomyolysis and myoglobinuria, when treated supportively, carries a good prognosis. Staphylococcal or other bacterial septicemia may in itself prove fatal and is associated with a proliferative immune complex, acute glomerulonephritis, which generally follows the course and prognosis of septicemia. The necrotizing angiitis reported in heroin addicts still is largely undefined. Focal and segmental glomerular sclerosis is the most common pathologic finding in the syndrome of heroin-associated nephropathy (HAN). Typically, HAN presents with massive proteinuria and progresses rapidly to renal failure. Presumptive evidence supports the premise that heroin or its vehicles elicits immunologically mediated renal damage. The antigen still is unidentified. Removing the antigenic challenge by stopping heroin injection apparently interdicts the progression of renal disease. Renal transplantation can be effectively accomplished in patients with HAN without early recurrence if patients discontinue the use of heroin.


The effect of cyclophosphamide and methotrexate on the 'field effect' or unresponsiveness observed in the rat and mouse GvHR. The Field effect is the decreased biological response to a second challenge in the graft versus host reaction (GvHR). Treatment of recipeint rats or mice during the initial GvHR by methotrexate or cyclophosphamide effected the secondary unresponsivienss. Methotrexate and cyclophosphamide demonstrated different temporal responses indicating different mechanisms of their immunosuppresdive activities.


Conditions for the formation of cyclic compounds between pyridoxal phosphate and 5-hydroxytryptamine or 5-hydroxytryptophan. 5-Hydroxytryptamine (5HT) and 5-hydroxytryptophan (5HTP) form cyclic compounds (probably of the tetrahydro-beta-carboline type) with pyridoxal phosphate (PLP). In the first step of reaction a Schiff's base is formed; during incubation it is transformed into a cyclic compound with a maximum absorption spectrum at 330 nm. The degree of cyclization depends on pH and substrate concentrations. One mole of 5HT or 5HTP reacts with one mole of coenzyme. The velocity of cyclization increased with an excess of either 5HT (5HTP) or PLP, without any change in the mole to mole ratio. The formation of cyclic compounds was confirmed by the use of isotopes, separation from substrates being achieved by high-voltage electrophoresis.


Effect of prior antibiotic therapy on concentrations of bacteria in CSF. A prospective study was done to determine the effect of prior antibiotic therapy on concentrations of bacteria in CSF at the time of diagnosis. Concentrations of Haemophilus influenzae type b in CSF of partially treated patients were significantly smaller than in CSF of untreated patients. This was also true of patients with meningococcal meningitis, but no difference was observed between patients with pneumococcal meningitis. The identification of H influenzae by Gram stain of CSF was significantly decreased by prior antibiotic therapy. Measurable levels of antibiotic (penicillins, aminoglycosides) were present in CSF of ten of 23 patients. Two partially treated patients were diagnosed by detection of meningococcal antigen in CSF by counterimmunoelectrophoresis although cultures of CSF were sterile. Both of these patients had measurable levels of penicillin in CSF. These data indicate that prior antibiotic therapy significantly decreases the concentration of H influenzae type b and meningococcus in CSF and therefore decreases the usefulness of CSF Gram stain. Partial therapy may sterilize the CSF of some patients.


Effect of bile acids and pH on the release of enteropeptidase in man. Bile acids increase the release of human enteropeptidase as well as other brush-border enzymes (alkaline phosphatase, leucine aminopeptidase) from duodenal mucosa, as had been shown earlier in experimental animals. The action of bile acids is independent of their known enhancing effect on enteropeptidase activity. The pH of duodenal juice is an important, hitherto unrecognized, factor in the release mechanism of brush-border enzymes. All of the above enzymes tested were released to a markedly greater extent at pH 8.2 than 6.3, regardless of the presence or absence of bile acid. Contrary to some results obtained with animal tissue, by other investigators, our experiments with human duodenal mucosa indicate that enteropeptidase, under all conditions tested, is released at a rate considerably greater than that for alkaline phosphatase or leucine aminopeptidase. The looser association of enteropeptidase with cellular components relative to that of other brush-border enzymes, as indicated by our observations, may be related to the unique function of enteropeptidase as the trigger enzyme of protein digestion.


The pediatric corner: the varied manifestations of Crohn's disease in children and adolescents. Thirty children less than 15 years of age with Crohn's disease are reported. The mean age of onset was nine years and five months. Delay in diagnosis may stem from the varying modes of presentation. The mean delay in diagnosis was two years. Chronic diarrhea and/or recurrent abdominal pain associated with extraintestinal manifestations, particularly abnormalities of growth and development suggests the possibility of Crohn's disease in the pediatric age group. Involvement of the terminal ileum occurred in 29 of the 30 patients. In addition, colonic disease occurred in 13 and jejunal involvement in one. Four patients presented with an acute onset of their disease. A favorable response to either medical or surgical therapy occurred in all four. Twenty-six patients had an insidious onset and tended to have a chronic course despite either medical and/or surgical therapy. Thirteen patients had an intestinal resection, with recurrence occurring in three from 1-4 years postoperatively. To date there has been one death.


Effect of a new antacid on basal and meal-stimulated gastric secretion. Our study of the comparative neutralizing effectiveness of four antacids on the acidity and pH of the basal gastric secretion in 32 patients showed that using the conventional doses of two tablets of Rolaids, two tablets of Di-Gel, 15 ml. of Maalox liquid or two tablets of Conquel, they are equal in their acid neutralizing capacity. The duration of action for 45-60 minutes. Conquel, in a dose of two tablets, was a potent buffer for the peptone-meal stimulated secretion. The duration of action lasted for longer than two hours.


Granulomatous ileocolitis preceded by three years of pauciarticular arthritis. The case of a 12-year old male is presented in whom pauciarticular arthritis preceded the clinical onset of granulomatous ileocolitis by three years. Before the onset of gastrointestinal symptoms, the patients' clinical diagnosis was juvenile rheumatoid arthritis. This case stresses the importance of including inflammatory bowel disease in the differential diagnosis of pauciarticular arthritis in children.


The influence of maternal psychological stress on the fetus. The effects of maternal agitation, induced by exposure to bright light, upon fetal well-being were studied in pregnant rhesus monkeys at 139 to 148 days of gestation. Fetuses were classified as "healthy" or "asphyxiated" according to their initial acid-base state. Following variable periods of maternal excitement, a decrease in heart rate and arterial oxygenation was seen in all fetuses. Recovery occurred more rapidly in the healthy group, after maternal sedation was achieved, either by removing the stimulus or by additional administration of pentobarbital, 5 to 20 mg. intravenously. The beneficial effects of meternal sedation on the fetus have thus been demonstrated.


Gastric HCO3--secretion in the guinea pig. Measurement of gastric intraluminal PCO2 and pH in the anesthetized guinea pig enabled simultaneous determination of total H+ and HCO3- gastric secretions. There was quantitative agreement between the release of CO2 and decrease in HCO3- after intragastric instillation of HCl. The basal rate of HCO3- secretion (approximately 40 mueq-h-1) was, in most cases, smaller than spontaneous H+ secretion, but gastric net secretory output was alkaline (HCO3- greater than H+) after inhibition of acid secretion with histamine H2-receptor antagonists (cimetidine 20 mg-kg-1 or metiamide 35 mg-kg-1). Carbachol (1-2 microgram-kg-1) stimulated secretion of both HCO3- and H+; only the latter response was sensitive to the histamine antagonists. Atropin (100 microgram-kg-1) blocked stimulation of HCO3- secretion but did not affect the basal output of HCO3-. An increase in HCO3- secretion was associated with an equivalent increase in net Na+ influx and an increase in the net influx of Cl- with H+ plus K+. Intragastric neutralization of H+ by HCO3- is likely to occur at the mucosal surface and may protect the mucosa from the damaging effects of intraluminal acid.


Acetylsalicylic acid hydrolase of gastric mucosa. Acetylsalicylic acid hydrolase activity of rabbit fundic gastric mucosa has been isolated from the soluble 100,000 X g supernate. The enzymatic activity was partially purified by ammonium sulfate precipitation. The Km for acetylsalicylate was 2 mM and pH optimum was 8.6. The activity was insensitive to ionic strength, slightly inhibited by inclusion of 100 mM Cl-, and demonstrated no requirement for Ca2+ or Mg2+. Acetylsalicylic acid esterase was markedly inhibited by sodium cholate and sodium dodecyl sulfate. The enzyme was insensitive to sulfhydryl reagents with the exception of p-chloromercuribenzenesulfonic acid, which markedly inhibited the enzyme. Diisopropyl fluorophosphate (DFP) inhibited enzymatic activity with a Ki of 9 X 10(-9)M. Eserine was also inhibitory with a Ki of 0.25 mM. Inhibition by DFP at low concentration and by eserine at millimolar concentrations suggests that this enzyme is related to the group of aliphatic esterases. Identification of potent inhibitors will enable studies to define the role of this enzyme with the use of experimental preparations in which systemic toxicity can be avoided.


Alterations of glucose metabolism during perfusion of rat lung with paraquat. Isolated perfused rat lungs were used to investigate effects of paraquat on lung glucose metabolism. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate buffer, pH 7.4, containing albumin and 5.5 mM radiolabeled D-glucose. Control lung glucose utilization, estimated from rate of 3H2O production from [5-3H]glucose, was 44 mumol/h-g dry wt. Pentose cycle activity, based on 14CO2 specific yields at the end of perfusions with [1-14C]- and [6-14C]glucose, was 14% of glucose utilization. During perfusion with 1.5 mM paraquat, glucose utilization increased 28%, 14CO2 production via the pentose cycle increased 182% (P less than 0.005), CO2 production via mitochondrial metabolism increased 39% (P less than 0.02), and the rate of lactate production increased 28% (P less than 0.05). Pyruvate production and the lactate-to-pyruvate ratio were not significantly altered. The data indicate that interaction of paraquat with the lung results in increased turnover of cytoplasmic NADPH and increased mitochondrial metabolism, but no significant change in cytoplasmic redox state. The findings are compatible with intracellular enzymatic reduction of paraquat by an NADPH-requiring reductase.


Human platelet MAO in drug-free and medicated schizophrenic patients. The authors compared platelet monoamine oxidase activity in drug-free chronic and acute schizophrenic patients, medicated chronic schizophrenic patients, and normal controls. A significant decrement in MAO activity was found only in medicated chronic schizophrenic patients. The possible mechanism for this finding is discussed.


[The importance of age dependent changes of the organism for therapy (author's transl)]. Molecular and supramolecular mechanisms of ageing involve biochemical, physiological and morphological alterations of organs. Furthermore physiological disturbances are superimposed by pathological mechanisms of ageing. As a result the number of diseases in higher age increases as well as there are a lot of therapeutical problems. The following paper tries to reveal that physiological and pathological changes of different organs (heart, kidney, lung, brain) influence the therapy of older man. The results demonstrate that it is necessary to stimulate the research of pharmacodynamics and kinetics in the higher age.


[Contribution to wet and dry weights of mesenchymal and parenchymatous organs of humans and rats during the course of life (author's transl)]. The wet and dry weights of parenchymatous (lung, heart, liver, kidney) and of mesenchymal organs (aorta, skin, xiphoid cartilage) of humans and rats (both sexes) were investigated during the course of life. Furthermore, these investigations were done on the following rat organs: brain (divided in cerebrum as well as in cerebellum plus pons), spleen, rib cartilage, testis and ovar. The water content of these tissues and organs of both species was calculated by means of their wet and dry weights. The dry weights of the investigated parenchymal and mesenchymal organs of both species remain constant during the whole course of life (pastly until the high senile age)--using freeze-drying. The same is true for the water content: constancy without significant decrease during the investigated life periods and without sex dependent differences.


[Correlations between age, risk factors for arteriosclerosis and endocrine functions (author's transl)]. In 377 males and 528 female factory workers basal serum levels of glucose, neutralfat, cholesterol, Na, K, Ca and LH, FSH, TSH, Prolactin, GH, Insulin, total corticoids and testosteron were determined. Mean values and standard deviations as well as correlations between mean basal hormone levels and other serum parameters, blood pressure and relative body weight (Broca Index) and partial correlations excluding age and relative body weight were calculated. Basal serum levels of LH, FSH, GH and prolactin show age and sex dependent secretion patterns. In men serum insulin-, GH- and total corticoid levels correlate positive significant with glucose and cholesterol levels, relative body weight and blood pressure, which possibly shows, that these hormones may play a role in the development of degenerative heart and blood vessel diseases. Testosteron levels and parameters of fat metabolism, relative body weight and diastolic blood pressure correlate negative significant. Obviously testosteron has a protective effect against arterioslcerotic lesions. In women insulin and GH do not have the same importance as in men. Prolactin serum and cholesterol level correlate negative significant. In postmenopausal women LH and FSH serum levels correlate positive significant with glucose and cholesterol levels, blood pressure and relative body weight, the so called risk factors for arteriosclerosis.


[Linguistics of ageing, linguistic Gerontology--Why? (author's transl)]. Intercourse between the young and the old is accompanied by difficulties in finding the right word. Authentic observations will be presented. These every-day experiences have prompted the search for the felicity conditions of verbal interaction between members of different age groups. This concern is called linguistics of ageing (or, etatolinguistics). It is called linguistic gerontology (or, gerontolinguistics) if older people are involved in the verbal interactions to be investigated. Papers from the fields of intelligence psychology, language psychology, and language sociology have indeed reported differences in verbal scores between groups of different ages. What has not been answered as yet, however, is the question whether these differences are, or may be, responsible for the difficulties arising in verbal interaction between different age groups. A review of hypotheses as to why verbal scores differ between different age groups in the way they do will reveal that this problem has not as yet been solved either. In conclusion, a programme for further research will be outlined.


[On the social situation of sick old women (author's transl)]. By explaining the social situation of the patients in a Berlin hospital for chronic and geriatric diseases, it is demonstrated that financial security and social status of old woman patients are much worse than those of old men. Examples are mentioned to demonstrate which were--and still are--the main causes--that in their earlier years women were paid less for their work and were discriminated because of their sex. If for the future the situation of old women is to be improved, the emancipation of women must advance today.


[Analyses of space available in homes and day centers for the aged, as well as nursing homes for elderly people, in the FRG. Booking and occupation rate in homes and nursing homes for the aged (author's transl)]. Further intention of the survey having been conducted to show the consequences of the "Heimmindestverordnung" (draft dated Nov. 1974) was to obtain a review of the density of occupancy related to housing for the elderly. In homes for the old the rate of one-bed-rooms significantly increased during the last 15 years, whereas the respective quota for rooms with two, three, or more beds showed a decreasing tendency. In nursing homes density also decreased: the rate of one- and two-bed-rooms increased and the respective frequency of rooms equipped with four and more beds decreased from 55% to 13%. Regarding the density of occupancy also the other data collected such as related to variables as association the investigation-unit belongs to, commencement of operation, federal state, size of community led to some striking findings.


[Consumer information activities in old age (author's transl)]. The following feature occupies with consumer information activities in old age. These informations are partial results of a study that was carried out in the Institut für Sozialforschung und Gesellschaftspolitik in Cologne by order of the Arbeitsgemeinschaft der Verbraucher and which deals with chances of consumer policy for people in old age (Naegele 1977). The paper's major elements are, first, essential sources of information of old people (source of supply itself, communication with relatives and friends before buying, written informations), and second, favourite sources of consumer informations to protect and to acquaint old consumers.


[Working conditions and job-requirement of older industrial blue collar workers and the consequences in employment problems (author's transl)]. In the following passage the reduced vocational capacity of older workers will be discussed as a consequence of the intended high-capacity of workers as well as the non--human working--conditions in industry. The reduced personal sanity and working capacity of older workers point out the high rate of handicaps and the incapacity of vocational engagement. Problems of employment--and this could be pointed out by the high rates of unemployment amongst older workers--does not signify prejudice but indicates the low profitableness of older workers in the capitalistic production system. Finally discussed will be the contribution of a monetary--conpensatoric against a more prophylactic social policy for a better solution of the vocational problems of older blue-collar workers.


[The effects of the social security system on the life situation of old people (author's transl)]. The situation of old people is determined by the system of Social Security in a various way. A point of most importance are effects of pensions etc. on the distribution of income. It is shown, that distribution of old-age pensions follows the same scheme, which is dominating in the distribution of primary income. This is due to the basic principles of the Social Security System, which intensify inequality.


[Maintenance payments to the elderly (author's transl)]. The question of the extent older people sustain their livelihood through financial contribution from their children is important sociopolitically inasmuch as claims for payments under the Federal Social Welfare Scheme (Bundessozialhilfegesetz) can only be made where no such private financial support can be given by those next of kin responsible in law. It has been established that in approximately every 14th household in the Federal Republic such maintenance payments are made to at least one member of the older generation (either parents and/or parents-in-law). Seen together with the findings of other inquiries it appears justifiable to assume that these payments are more often remunerations recompensed either materially or otherwise by the older generation rather than a genuine alternative to (necessary) public welfare support. It must therefore be assumed that onesided private financial support carries the odium of "private relief" for the recipients, in which case it would run contrary to the intentions of social legislation.


[Measuring nursing needs of older people related to actual nursing time in institutions for the aged (author's transl)]. A great many of the elderly people are in need of care. In offering services accordingly it is necessary to acquire relevant data. The following article gives results of a study which determined 1) the real amount of given nursing care and 2) the measured amount of nursing needs of these patients. The research was done at 10 nursing stations with 210 persons. The results make clear 1) that need of care must be seen in a multidemensional perspective and 2) that much of the psychological and social needs of the patients are not yet satisfied.


[Environment and selfsufficiency of elder man (author's transl)]. The problems of environment of elderly people are concentrated in social area and in the intimate living space, which can not be maintained sufficiently because of increasing age and decreasing performance. The consequences of mobility in industrial revolution scattered families and also deprived old men of their helpers. Inadequate living rooms and absence of technical comfort especially in the houses of the very aged men produce intense dependence of the own individual performance. Medical data of the spontaneous elected performance informe about the amount of the requirements of daily working capacity. They show low requirements of stress. Spontaneous working load was below of the level of medical well tolerated effort. In healthy men no signs of overloading have been registrated. Seldom removal in old age pensions before the age of eighty is indicated by illness but frequently social motivation predominates. On the contrary considerable insufficiency in social and medical providing exist after acut illness, what is to improve by special hospitals for rehabilitation of older people and by a grid of social stations. By this method it might be possible to save a great amount of money by governments that now has to be payed for exorbitant expansive assistance which is medical not indicated.


[On postoperative azotemia in geriatric surgery: significance, risk groups, possibilities of prophylaxis (author's transl)]. 1032 Interventions on geriatric patients beeing more than 70 years old between 1966 and 1975 demonstrate the significance of azotemia in the postoperativ stage of the disease appears as well as its dependence upon prehospital factors, type and localisation also on the extension and duration on the intervention in each single case. Since it is hardly possible to exert an influence on the preliminary stress due to the old age and on the dysfunction determined by involution of the parenchymatose organs important for the course of the postoperative stage, a particular emphasis should be laid upon the prophylactic aspekt to the purpose of an appropriate screening against vegetativ-visceral, renally effective shock reflexes (hepatorenal syndrome) and on the other, usually extra-renal factors (PH 203R, splanchnic block). Further possibilities: considerate elimination of pain and general anesthesia, purpuseful and quick operative technique, improvement of the apparatus and instruments, after-treatment specific for the given case so as one consisting of a prophylaxis against pneumonia through a rapid reactivation of the operated person. However, regardless to all the professional advance made in this field, the primary human approach to the aged patient and to his life expectancy should be made due allowance for.


Ketamine sequelae. Evaluation of the ability of various premedicants to attenuate its psychic actions. The ability of a number of drugs to abolish the emergence delirium and unpleasant dreams which follow anaesthesia induced with 2 mg/kg ketamine was studied. These included three benzodiazepines, droperidol and 'neurolept' combinations and four commonly-used premedicants. When given intravenously 10 min before induction of anaesthesia flunitrazepam and lorazepam gave best results. In a subsequent study, these two benzodiazepines and diazepam were given intravenously 30-40 min before induction of anaesthesia. There was no doubt that 4 mg lorazepam gave the greatest protection and is worthy of further study in this respect.


Ketamine-iorazepam. Attenuation of psychic sequelae of ketamine by lorazepam. The intravenous, intramuscular and oral administration of 4 mg lorazepam given to adults will effectively reduce the psychic sequelae of ketamine to acceptable limits.


[The solutibility of local anaesthetics in cerebrospinal fluid and the dependency of the process on the hydrogene ion concentration (author's transl)]. Reports on in vitro precipitation of local anesthetics suggested the possibility of a damaging effect on nervous tissue with spinal anesthesia. The present assays showed that the solubility of local anesthetics in aqueous media decreases with rising pH-levels. The partial pressure of CO2 determines the pH-level of the cerebrospinal fluid, the level ranging at about 7.35 + 0.011 (95% range: 7.327-7.371). The solubilities calculated for a pH of 7.371 (at 37 degrees C) are as follows: Bupivacaine.HCl 0.83+/-0.10 mh/ml Carticaine.HCl 27 +/-2.8 mg/ml Lidocaine.HCl 24 +/-1.3 mg/ml Mepivacaine.HCl 14.8 +/- 0.2 mg/ml Tetracaine.HCl 1.4 +/- 0.12 mg/ml.


[pH of the cerebro spinal fluid during subdural block (author's transl)]. This study was initiated by other authors who found that bupivacaine precipitated together with spinal fluid in vitro and who assumed that during spinal anaesthesia complications might be possible. Under the influence of several local anaesthetic agents the pH of the spinal fluid and in 160 cases the precipitation was examined. There was no precipitation. The experimental conditions were nearly in vivo conditions. The results differed clearly from those in vitro. While in vitro bupivacaine precipitated from a pH higher than 7.37 in concentrations higher than 0.8 mg/ml [2], the pH of the spinal fluid in vivo was lower than 7.35 continually and the concentration of bupivacaine not higher than 0.3 mg/ml. This means that the border of bupivacaine precipitation is by far not reached in vivo and that complications therefore are not possible.


[Changes of circulation, blood gases, acid-base-and metabolism during neurolept-analgesia with and without beta-receptor blockers in electro coagulation of Gasser's ganglion (author's transl)]. The cardiovascular, blood gas, acid-base and metabolic changes occurring during operative stress were studied in 10 elderly, metabolically healthy patients, suffering from idiopathic trigeminal neuralgia, who underwent electrocoagulation of the gasserian ganglion under neuroleptanalgesia. In a group of 12 patients undergoing the same operative procedure and anesthesthetic management, we investigated the effects of administration of a beta blocking agent on these parameters. Intraoperative rises of blood pressure and tachycardia were prevented by intravenous administration of 0.4 mg Pindolol (Visken), whereas increases in the blood glucose levels at the end of the operation were the same. The increase of glycerol, free fatty acids and ketone bodies was markedly reduced after pretreatment with the beta blocker compared with the controlgroup. In the patients without beta blocker treatment pH and standard bicarbonate at the end of the operation were lower as the result of the stimulation of ketogenesis.


Acid aspiration during laparoscopy.

Acid aspiration during laparoscopy. The prophylactic efficacy of pre-operative antacid administration was shown by comparing the pH and volumes of gastric contents in 50 female patients treated with 10 ml of Mist. Magnesium Trisilicate B.P.C. with that of 50 controls. Routine antacid prophylaxis was advocated for all patients undergoing pelvic laparoscopy as intra-operative conditions increase the risk of pulmonary acid aspiration.


Placental transfer of lidocaine: effects of fetal acidosis. To investigate whether fetal acidosis increases the placental transfer of lidocaine, resulting in higher fetal blood levels of the drug, lidocaine was infused intravenously into ten pregnant ewes to maintain plasma levels of 2-4 microgram/ml. After maternal-fetal equilibrium was reached, the fetus was made acidotic by infusing lactic acid intravenously. Fetal blood pH decreased from 7.35 to 7.10. With fetal acidemia, fetal blood lidocaine levels increased significantly from 1.60 +/- 0.11 microgram/ml to 2.72 +/- 0.26 microgram/ml. The fetal-maternal lidocaine ratio increased from 0.76 to 1.21. Correction of the acidosis by bicarbonate infusion returned the fetal-maternal ratios to control values. It is concluded that acidosis in the fetus may result in trapping of ionized lidocaine in the fetal circulation and increase the transfer of lidocaine across the placenta.


Hemoglobin Creteil: oxygen transport by erythrocytes. In-vitro and in-vivo studies in a high oxygen-affinity mutant hemoglobin. Hemoglobin Hb) Creteil alpha2beta(2)89 (F5) Ser leads to Asn is a high oxygen-affinity variant that has a low cooperativity, a decreased Bohr effect, and does not interact with diphosphoglycerate (DPG) (1). This hemoglobin variant was silent by routine electrophoresis. Careful analyses of the oxygen dissociation curves of erythrocytes, determined at varying pH and Pco2 in fresh and DPG-depleted cells, gave extensive information on the abnormal function of the mutant hemoglobin. From the O2 dissociation curves of the erythrocytes of the heterozygous subject it appeared that Hb Creteil is inappropriate for O2 transport to the tissues because it remained completely saturated with O2 at normal physiologic levels of Po2. In-vivo measurements showed that only one half of the total hemoglobin present actually participated in oxygen transport. Polycythemia should therefore be maintained within clinically tolerable limits because it helps to keep arterial Po2 and Pvo2 close to their normal values and thus protects the individual from a permanent increase in blood flow.


Cold injuries in Kashmir, December 1971. A total of 847 cases of cold injury occurred within the short space of 2 weeks during the Indo-Pakistan conflict in Kashmir in December 1971. The management of these cases and their end results are described. A combination of drugs consisting of low-molecular-weight dextran, an anti-inflammatory agent, and a vasodilator was tried with encouraging results. A conservative attitude towards ablation of necrosed tissues paid good dividends.


A disorder of biogenic amines in dihydropteridine reductase deficiency. A severe deficiency of dihydropteridine reductase (DHPR) in liver, brain, and cultured skin fibroblasts was demonstrated in a child with hyperphenylalaninemia and an atypical form of phenylketonuria. DHPR is required for regeneration of the cofactor, tetrahydrobiopterin. The cofactor is essential in hydroxylation of aromatic amino acid precursors in the biosynthesis of neurotransmitters, serotonin, dopamine, and norepinephrine. In gray tissue at brain biopsy, dopamine was low at 3 ng per gram of tissue, serotonin was barely detected, and norepinephrine appeared high at 1600 ng per gram. In cerebrospinal fluid, homovanillic acid (HVA) was low normal at 33 ng/ml, 5-hydroxyindoleacetic acid (5-HIAA) was low at 4.2 ng/ml, and after a high dose of oral probenecid there was impaired accumulation of HVA to 128 ng/ml and 5-HIAA to 22.4 ng/ml. When the patient was 22 months of age, treatment with hydroxylated aromatic amino acid precursors was initiated, and after three months HVA and 5-HIAA levels were increased in CSF. The apparent restoration of biogenic amines in brain appears to have delayed the rate of neurological deterioration. DHPR activity in cultured skin fibroblasts of children with persistent hyperphenylalaninemia should permit early diagnosis and early treatment of this disorder.


Stability of antibiotics and amino acids in two synthetic L-amino acid solutions commonly used for total parenteral nutrition in children. The stability and interaction at 29 degrees C of ampicillin, carbenicillin, gentamicin, and polymyxin B were examined in a common electrolyte solution, invertose darrow, and in two synthetic l-amino acid solutions, one commercial (vamin with fructose; Vitrum) and the other a neonatal preparation modified for use in newborn infants. The concentration of amino acids was measured before and after the addition of these antibiotics. The concentration of antibiotics was measured over a 24-h period with a microbiological method. The concentration of ampicillin in invertose darrow fell 52%, and in vamin with fructose it fell 69%, whereas in the neonatal preparation the fall was only 22%. The concentration of carbenicillin in vamin with fructose fell 37%, and in the neonatal preparation it fell 31%. The combination of ampicillin or carbenicillin with gentamicin or polymyxin B did not influence the activity of the penicillins. The concentration of gentamicin and polymyxin B was unchanged in all solutions over a 24-h period. With the exception of cystine, the concentration of all amino acids remained constant after 24 h in the neonatal preparation with and without the different combinations of antibiotics. For cystine there was a fall of 20 to 30%.


Chloramphenicol resistance in Streptococcus pneumoniae: enzymatic acetylation and possible plasmid linkage. Clinical isolates of Streptococcus pneumoniae resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of S. pneumoniae in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be O-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a "cured" clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in S. pneumoniae.


Irreversible effects of serum proteins on beta-lactam antibiotics. The chromogenic cephalosporin nitrocefin (87/312) demonstrates rapid and visible instability to serum from many species. This phenomenon was distinct from serum binding, being significantly slower. Destruction of another cephalosporin, 10485, by serum appeared to account for some anomalous results during investigation into its human pharmacokinetics. Many cephalosporins of very different structures also showed serum instability, unrelated to their degrees of serum binding as measured by plate assay. Extrapolation could not be made from one species to another with regard to either binding or instability. Small changes in the chemical structures of the 3- and 7-substituents of the cephalosporins made profound changes in their susceptibility to serum attack. The decomposition is pH dependent, occurring more slowly at acid pH, and is due to a high-molecular-weight component of serum that resists boiling for several minutes. Isoelectric focusing of serum from several animal species gave various species-specific bands that decomposed nitrocefin. The inactivation of nitrocefin was not entirely parallel with that of 10485 and was inhibited by it. All other beta-lactam compounds tested also inhibited the reaction, much greater concentrations usually being necessary when the inhibitor was stable to serum. The complex that causes breakdown of the beta-lactam compounds is not necessarily the same as the one causing serum binding. It is postulated that serum may affect most other beta-lactam antibiotics in a similar way, although in most cases, this only occurs to a very slight extent.


Antimicrobial susceptibility patterns of Streptococcus pneumoniae. Fifty clinical isolates of Streptococcus pneumoniae received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests. No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin. This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin. An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance. Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms. Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade. However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy.


Susceptibility of skin and throat strains of group A streptococci to rosamicin and erythromycin. The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 mug of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 mug of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.


The action of lecithin monolayers on mosquitoes I. General observations. Monolayers of pure egg-lecithin at maximum equilibrium pressure were tested against eight species of mosquito in the laboratory, Anopheline larvae were prevented from surfacing and died in water of low dissolved oxygen content, but culicine larvae survived. The pupae of all species except Culex p. fatigans were killed. Effects on floating eggs, pupal-adult eclosion and adult behaviour are also reported.


The action of lecithin monolayers on mosquitoes. II. Action on the respiratory structures. Experiments on the interaction between the water surface and the respiratory structures of larvae and pupae of five species of mosquitoes showed that in the presence of a lecithin monolayer, a stable, soap-bubble type film is formed which prevents the insect from surfacing. Subsequently, wetting of the hydrophobic areas takes place. In pupae, buoyancy is lost through flooding of the ventral air space.


Hypotensive action of beta-blocking drugs injected into the cerebral ventricle of the rat. Pindolol, propranolol, practolol, N-isopropyl-p-nitrophenyl-ethanolamine (INPEA), d and l-alprenolol were injected into the lateral cerebral ventricle of the anaesthetized rat. Except for INPEA, which has no action at the doses used, these various beta-blocking agents produce a dose-related fall in blood pressure. D-alprenolol and practolol seem to be the least active of the hypotensive agents. Our results show some relationship between the beta-blocking potency of the drugs studied and the hypotension induced when they were injected in the lateral ventricle.


Ganglion blocking effects of streptomycin. The effects of streptomycin on the postganglionic compound action potential, presynaptic nerve terminal spike and preganglionic nerve action potnetial were studied in rabbit and rat superior cervical gnaglia. Streptomycin had a dose-dependent, blocking effect on the postganglionic action potential. The drug was found to have a preferential blocking effect on the first spike, S1, of the compound postganglionic action potential, but the second, S2, major spike was depressed at higher concentrations. At 1 mg/ml, streptomycin reduced the amplitude of the presynaptic nerve terminal action potential, but had no significant effect on the action potential recorded from the cervical sympathetic preganglionic nerve. Increasing the concentrations of Ca++ in the bathing solution antagonized the blocking effect of the antibiotic on the postganglionic action potential. The results are interpreted as indicating that ganglionic blockade by streptomycin is due, mainly, to a presynaptic effect which results in a decreased release of acetylcholine.


An experimental non-invasive animal technique for measuring nasal airway resistance: I. Adrenergic and antihistaminic agents. A non-invasive technically simple and sensitive method is described for the determination of nasal airway resistance (NAR). Aerosolized saline elicited a +/- 7% change in baseline NAR, duration 2 minutes, whereas aerosolized histamine increased NAR, duration is greater than 30 minutes. Aerosolized phenylephrine, norepinephrine, and oxymetrazoline elicited dose related decongestive response in a naris subjected to prior congestion (aerosolized histamine). Both H1 and H2 receptors are involved in the congestive response to intranasal histamine.


[Nonspecific aorto-arteritis. Anatomo-pathological study of 18 cases]. The present study comprises a pathological review of 18 necropsy cases with nonspecific aorto-arteritis (Takayasu's disease), autopsied at the Instituto Nacional de Cardiología of Mexico up to 1976. There were 11 females and 7 males with an average age at the time of death of 21.5 years. A comparison according to the distribution and extention of arterial lesions disclosed that our cases are often less classical than those described from Japan. The principal arterial changes were stenosis, occlusion, dilatation and aneurysm formation in the aorta, its branches and main pulmonary artery. More often than not the aorta was extensively involved. The aortic arch syndrome and renovascular hypertension were almost equally present in this serie and an unusual high incidence of coronary artery involvement (33%) leading to myocardial infarction (50%) also was observed. The significance of the intrapulmonary vascular changes in Takayasu's arteritis is discussed.


Age-dependence of renal tubular reabsorption of nitrofurantoin. Nitrofurantoin is rapidly excreted in adult rats. However, in 5 to 15 days old rats the renal excretion of nitrofurantoin is diminshed by a high rate of reabsorption. Because nitrofurantoin has a pKa of 7.2 its tubular reabsorption is influenced by the urine pH but is independent of urine flow. About 50% of an administered dose of nitrofurantoin is recovered as metabolites in the urine of both young and adult rats. Probenecid blocks the active tubular secretion of nitrofurantoin independently of age and reduces its rate of renal clearance. Induction of drug metabolizing enzymes by pretreatment with phenobarbital was without effect either on the metabolism or renal excretion of nitrofurantoin nor could the renal excretion of this drug be diminished by repeated administration. The age-dependent difference in the rate of renal excretion of nitrofurantion is due to the high rate of tubular reabsorption in the young animals. This study provides experimental support for the therapeutic use of nitrofurantoin in the neonatal period.


Hypersensitivity to salicylazosulfapyridine: renal and hepatic toxic reactions. Salicylazosulfapyridine has been used for a number of years as therapy for ulcerative colitis. Reported toxicities are usually minor. This case report represents an acute allergic reaction to the drug. Characterized by fever, rash, eosinophilia, nephritis, and hepatitis. Resolution occurred with discontinuation of salicylazosulfapyridine. Although similar reactions have been reported with the antimicrobial sulfonamides, none has been fully described with salicylazosulfapyridine, a combination of a sulfonamide and salicylate.