Plastic properties of the vestibulo-ocular reflex in olivo-ponto-cerebellar atrophy. Disorders in vestibulo-ocular functions were studied in 4 patients with olivo-ponto-cerebellar atrophy (OPCA). The phenomenon of habituation, considered as a plastic property of the vestibulo-ocular reflex (VOR), was explored with a behavioural paradigm in these patients. When subjected to the habituation paradigm all patients presented a modified response opposite to that observed in normal subjects. The role played by the cerebellum in relation to VOR plasticity--well known in different experimental models--is analyzed. The hypothesis of a modification of the cerebellum's inhibitory action on vestibular nuclei neurons is put forward to explain the inversion of the VOR habituation phenomenon in these patients.


Effect of transcutaneous electrostimulation on noise-induced temporary threshold shift. The effect of transcutaneous electrostimulation around the ear before and during noise exposure on noise-induced temporary threshold shift (TTS) was examined in 26 volunteers. Electrostimulation reduced TTS in the majority of cases and the reduction was statistically significant. Two possible mechanisms for this reduction are proposed: stimulation of the olivocochlear bundle and alteration of cochlear blood flow. Transcutaneous electrostimulation may be useful for prevention or treatment of noise induced hearing damage and for treatment of tinnitus.


Noise-induced auditory loss: influence of genotype, naloxone and methyl-prednisolone. Inbred strains of mice have several advantages as models for human noise-induced hearing loss. However, the isogenic nature of inbred lines is very unlike the human condition, and may make this species less valuable as an auditory model. The present experiments start with two mouse genotypes having lifelong normal cochlear functions: The CBA/CaJ and the AUS/sJ inbred strains. These strains and their F1 hybrid offspring were examined for noise-induced elevation of the auditory brainstem response (ABR) threshold. The F1 line had an intermediate degree of loss and the most uniform high frequency cochlear loss. Methylprednisolone was found to protect the F1 from noise-induced losses, whereas naloxone did not.


Immunohistochemical localization of alpha-atrial natriuretic polypeptide in the rat cochlea. The localization of alpha-atrial natriuretic polypeptide (alpha-ANP) in the rat cochlea was studied by immunohistochemical technique, using a polyclonal antibody against synthetic rat alpha-atrial natriuretic polypeptide (alpha-rANP). The spiral ligament of the lateral cochlear wall exhibited pronounced immunoreactivity to atrial natriuretic polypeptide (ANP), whereas the stria vascularis displayed almost no immunoreaction. ANP immunoreactivity (IR) was also intense in the spiral limbus region. IR was observed in the fibroblast-like cells and in the extracellular matrix, in particular along its fibrous bundles, of both the spiral ligament and the spiral limbus. These results indicate that ANP may participate in the regulation of the water electrolyte balance at these sites, which may imply a role for ANP in the regulation of cochlear fluids.


Localization of type II, IX and V collagen in the inner ear. Types II and IX collagen are traditionally considered cartilage collagens; however, within the inner ear, types II and IX collagen have a more diverse distribution. In the adult gerbil, type II collagen is the major fibrillar component. In the otic capsule it is present surrounding the osteocytes embedded and branching in the periosteal layer, in the cartilaginous rests of the enchondral layer, and in the endosteal layer bordering the membranous labyrinth. In the regions of the sensory cells, type II collagen is found in the osseous spiral lamina, the connective tissue of the spiral limbus, the subepithelial tissue of the maculae in the vestibule and the cristae in the ampullae, and in the spiral ligament. It is present in the non-cartilaginous and acellular structures of the tectorial membrane over the cochlear hair cells and the vestibular membrane lining the semicircular canals. Type IX collagen, when present, in all cases co-localizes with type II collagen but is found in more limited regions. It is found only in the cartilaginous rests of the enchondral bone, the tectorial membrane and the vestibular membrane. Type V-like collagen, a connective tissue collagen, is found to have a complementary localization to types II and IX collagen within the interstitial bone of the otic capsule, the osseous spiral lamina and the tectorial membrane, but it is absent from the vestibular membrane. This report is the first documenting the co-localization of types II and IX collagen.(ABSTRACT TRUNCATED AT 250 WORDS)


Human embryonic organ of Corti in tissue culture and NSE expression. For the first time ever, the cochlear tissue of the human embryo has been successfully grown in vitro in two cases, and neuro-specific enolase (NSE) immunoreactivity was studied in one of these tissues. The outer hair cells were arranged in three rows, and the inner hair cells in one row and in better order than the outer hair cells. After NSE immunostaining, the outer spiral bundle, tunnel fiber, outer hair cells, inner hair cells, and the spiral ganglion cells showed positive staining. This data suggests that the human embryonic cochlea has nearly reached complete maturation by 16 weeks, and that the tissue of the Corti organ can be differentiated and matured in vitro.


Ultrastructural findings in the inner ear of Jackson shaker mice. The ultrastructural characteristics of the inner ear of Jackson shaker mice were analyzed. We used 12 Jackson shaker mutants (js/js) with ages ranging from 10 to 47 days and 10 heterozygotes of the Jackson shaker (js/+) with ages ranging from 10 to 30 days. The most striking findings observed were incomplete differentiation of the stereocilia of the outer hair cells and the maculae, although outer and macular hair cell cytoplasm, including the nerve terminals, became fully developed. Most outer hair cells did not show regular W-shaped configuration of the stereocilia throughout the entire turns of the cochlea except for a few hair cells. In many hair cells of the utricular and saccular maculae, the classical pipe organ configuration of the stereocilia was not observed. The Jackson shaker mice have been reported to have a gene abnormality on chromosome 11, and its gene locus was close to that of our new-mutant mice which showed deranged stereocilia of the outer and macular hair cells. Therefore, future studies can provide additional information on the cytodifferentiation of the stereocilia as a function of the gene on chromosome 11.


Expression of glycoconjugates in the human fetal cochlea. The distribution of glycoconjugates in the human fetal cochlea was analyzed using six biotinylated lectins: wheat germ agglutinin (WGA), abrus precatorius agglutinin (APA), ulex europaeus agglutinin I (UEA-I), ricinus communis agglutinin 120 (RCA120), helix pomatia agglutinin (HPA), concanavalin A (ConA). The tectorial membrane (TM) in the 11- and 15-week-old human fetuses was labelled with WGA, APA, RCA120 and ConA, but not with UEA-I and HPA. In the 19-week-old fetuses, the reaction of the TM decreased. In the 11-, 15- and 19-week-old fetuses, the surface of the greater and the lesser epithelial ridges were respectively labelled with WGA, APA and RCA120. Reissner's membrane was labelled with WGA, ConA, APA, RCA120 and HPA. WGA, RCA120 and APA strongly stained the stria vascularis, especially in the 15-week-old fetuses. HPA did not stain the 11-week-old fetal cochleas at all, while it stained the apical surface of the hair cells, Reissner's membrane, the cells within the stria vascularis and spiral osseous lamina in the 15-week-old fetuses. In the 19-week-old fetuses, the fluorescent reaction with HPA became decreased and the apical surface of the hair cells was not labelled with HPA at all. This result suggests that HPA reactive glycoconjugates may be related to the molecule responsible for stereociliary adhesion only during development.


Differences in hair bundles associated with type I and type II vestibular hair cells of the guinea pig saccule. Several studies have reported variations in shape and size of stereociliary bundles and in a limited number of observations have associated them to type I and type II hair cells. A systematic study has been undertaken for which a technique was developed in order to identify both cell types and their corresponding hair bundles. Numerous fissures were obtained in saccular epithelia and observed in scanning electron microscopy. Saccular type I and type II hair cells in the guinea pig were found to have distinctive hair bundles. The tallest stereocilia of almost all type I cells were longer than 6 microns, and were shorter in the striola compared to the periphery. In contrast, the tallest stereocilia of almost all type II cells were shorter than 6 microns and were not found to vary notably in size from the striola to the periphery. Hair bundles with stereocilia organized in straight or in staggered rows were found for both types of cells across the whole saccular epithelium, with no apparent particular distribution. Possible physiological significance of differences in hair bundles is discussed.


Periductal vessels of the endolymphatic duct. Light microscope was used to examine the rich vascular plexus surrounding the human endolymphatic duct, both in the periductal loose connective tissue and in the bony channels surrounding the bony vestibular aqueduct. We also performed computer-aided three-dimensional reconstruction on one serially sectioned region of the endolymphatic duct. We found an anastomotic and looping network of vessels residing in the loose connective tissue close to the epithelium of the endolymphatic duct. This network often received a vascular contribution from the vessels in the periaqueductal bony channels. These findings were verified by light microscopic examination of 50 temporal bone specimens. Concurrent with this finding, histologic examination also showed different characteristic features of the vascular system of the endolymphatic duct-proximal sac areas and of the more distal parts of the endolymphatic sac. These features include the arrangement, quantity, and contents of the periaqueductal bony channels, as well as the organization of the bone containing these periductal bony channels. Findings from this study help the understanding of the anatomy of the human endolymphatic duct. In addition, they support and supplement earlier observations of the structure of the endolymphatic duct. We suggest the possible existence of a periductal vasculature system, similar in pattern to that in the endolymphatic sac, but specialized to work with the duct to aid its function.


Ischemia of the endolymphatic sac.

Ischemia of the endolymphatic sac. A decrease in vascular density in the endolymphatic sac was suspected as a factor in the pathogenesis of endolymphatic hydrops in Meniere's disease. The present study was undertaken to explore this possibility by cutting the posterior meningeal artery and the sigmoid sinus above and below the external aperture of the vestibular aqueduct or by incision of the dura adjacent to the sinus in 18 guinea pigs. The lesions in the sac were greater in the segmental ablation of the artery and sinus and were consistently associated with the development of endolymphatic hydrops. Among the lesions shown in the sac epithelia, the intermediate portion was most often and most severely affected with a decrease in rugose formation and a flattening of the tall epithelial cells or replacement of epithelial cells by squamous type cells. A high correlation between the lesions in the intermediate portion and occurrence of hydrops suggests that the intermediate portion plays a greater role in the pathogenesis of endolymphatic hydrops. The sac luminal precipitates known to be increased in human Meniere's cases were decreased or absent in this study, which suggests that the increased amount is unlikely to be the cause of endolymphatic hydrops. The evidence supports the hypothesis that these substances are secreted by the endolymphatic sac. The limited sensory cell lesions seen in the cochleae and saccules are likely to be due to a temporary vascular ischemia and endolymphatic hydrops.


Adenylate cyclase modulation of ion permeability in the guinea pig cochlea: a possible mechanism for the formation of endolymphatic hydrops. The pathophysiological mechanisms leading to endolymphatic hydrops in Meniere's disease are unknown. Changes in ionic permeability of the cellular membranes between the endolymph and the perilymph, which alter the composition and osmolarity of the inner ear fluid, may be a major factor in the etiology of endolymphatic hydrops. To determine the possible involvement of adenylate cyclase in the formation of endolymphatic hydrops, we measured the endolymphatic K+, Na+, Cl- activities (AK, ANa, ACl) and the endocochlear potential (EP) by means of ion-selective microelectrodes while inner ear adenylate cyclase was activated by perilymphatic perfusion with forskolin. We observed a large ACl increase accompanied by an EP increase during forskolin (2 x 10(-4) M) perfusion and a delayed AK decrease after perfusion. No measurable ANa change was observed. These results suggest that adenylate cyclase may regulate Cl- permeability of the endolymph-perilymph barrier and that adenylate cyclase plays a critical role in acute endolymphatic hydrops in Meniere's disease by altering the osmolarity of the endolymph.


CT-scanning of ancient Greenlandic Inuit temporal bones. Additional morphological evidence of former infectious middle ear disease (IMED) was found by CT-scanning in 5 of 6 Greenlandic Inuit crania strongly suspected for former IMED due to earlier examination revealing either bilateral hypocellularity or asymmetry of the pneumatized area of the temporal bones. The CT-scans showed sclerosing and obliteration of the air cells and even destruction of the cellular septae, and a high degree of irregularity of the cells. Sclerosing of the surrounding bone tissue was also found. The findings in one cranium were dubious and could both be regarded as a congenital malformation or an infection in infanthood. CT-scan confirms and even adds to the results of conventional X-ray of temporal bones making hypotheses of paleopathology more reliable. The findings also support the environmental theory of pneumatization of the air cell system in the temporal bones.


Effects of various inflammatory mediators on eustachian tube patency. The effects of several inflammatory mediators on the patency of the Eustachian tube were evaluated in 15 mongrel dogs. Histamine, leukotriene C4(LTC4) and D4(LTD4), and platelet activating factor (PAF) were perfused through the Eustachian tube of anesthetized dogs at concentrations detected in human middle ear effusion of patients with otitis media. The patency of the Eustachian tube was then evaluated by perfusion pressure and opening pressure. Histamine at concentrations of more than 10(-5) M caused increased tubal resistance and opening pressure rapidly. LTC4 and LTD4 caused a rapid increase of tubal resistance and opening pressure at far lower concentrations, i.e. 10(-12) M. Doses of PAF over 10(-9) M may cause an increase in the opening pressure. These results indicate that various inflammatory mediators are capable of affecting the Eustachian tube function.


Laser-Doppler flowmetry compared to intravital microscopy for assessment of blood flow in the nasal mucosa of the rabbit. Laser-Doppler flowmeter (LDF) studies of the rabbit nasal mucosal microcirculation were compared with intravital videomicroscopy and with flow measured in single blood vessels in order to evaluate the applicability of the LDF technique. Access to the nasal mucosa for a microscope objective was gained surgically through the maxilla. Transillumination for microscopy was achieved through a prism inserted on the contralateral side of the septal cartilage. Blood flow changes were induced by the inhalation of N2, CO2 and O2 and by topically applying the vasoconstricting alpha-adrenoceptor agonist oxymetazoline. The effects were registered by LDF and direct visual observation. Flow in veins and capillaries was calculated using on-line cross-correlation, and off-line a computerized video-analysis system. LDF did not correlate to flow in single veins or capillaries but agreed well with the visual impression. LDF is considered a valuable method for the assessment of over-all blood flow changes in the nasal mucosa.


Newcastle disease viral infection in chicken nasal turbinate and maxillary sinus. Newcastle disease virus (NDV) B strain was inoculated intranasally and intrasinusly into unanesthetized chicken which were maintained on a standard commercial mash chicken diet until the age of 21 days after hatch. The lesions induced by NDV following intranasal inoculation usually produced a selective destruction of significant portions of the inner surface of the turbinate scroll, but sinus lesions, though sometimes present in NDV infection, were not common. The chicken sinus was infected by intrasinus inoculation. These results were supported by the amount of virus and mucociliary transport time in the turbinate and sinus. It is suggested that mucus hypersecretion of ostial gland and/or mucociliary activity in the sinus be one of the most important factors in protecting against chicken sinus infection.


Immunohistochemical detection of epidermal growth factor receptor in laryngeal squamous cell carcinomas. Laryngeal squamous cell carcinomas from 15 consecutive preoperatively irradiated patients were investigated for the expression of epidermal growth factor receptor (EGF receptor). The study was performed on frozen sections by means of the 5-layer APAAP technique employing an antibody recognizing the extracellular part of the EGF receptor. In sections from 9 of the patients with laryngeal squamous cell carcinoma, normal differentiated epithelia were included. Sections from 6 of these patients, in addition, contained dysplastic epithelia. Expression of EGF receptor-like material was demonstrated in the basal cell layer of normally differentiated laryngeal epithelial and in dysplastic epithelia. Fourteen of the squamous cell carcinomas proved EGF receptor positive. Nearly all cells in the poorly differentiated carcinomas showed positive staining with the antibodies. In moderately to well differentiated carcinomas a reduction in the extent of staining was seen in certain areas. Especially for the epithelial pearls, the staining reaction was localized to the undifferentiated cells in the periphery. This finding corresponds to the staining pattern observed in the basal cell layers of normal epithelial. The present investigation confirms the expression of EGF receptor-like material in normal laryngeal epithelial, dysplastic epithelial and squamous cell carcinoma. The staining pattern was similar to that observed in oral squamous cell carcinomas, predominantly varying inversely with cellular differentiation.


Relationship between PaO2 and lung volume during high frequency oscillatory ventilation. The relationship between oxygenation and lung volume during high frequency oscillatory ventilation (HFOV) was studied. We ventilated anesthetized, tracheostomized adult rabbits that were rendered surfactant-deficient by lung lavage. Lung volume was measured by the 'disconnection technique'. In the first experiment, HFOV was commenced after conventional mechanical ventilation (CMV) for 1 hr. In the absence of sustained inflation (SI), oxygenation improved with time during HFOV. In the second experiment, HFOV was instituted after CMV for 4 hr. In the absence of SI, all animals expired during the experimental period. In the third experiment we ventilated rabbits for 4 hr and then switched to HFOV. We applied SI first and increased mean airway pressure (MAP) by increments of 2 cmH2O every 15 min. However, there was little improvement in PaO2 despite the use of repeated SI and the increase in MAP. We conclude that oxygenation has a linear relationship to lung volume during HFOV, and that secondary lung injury due to long-term CMV impairs the response to HFOV. Therefore, it is important to minimize the risk of such secondary injuries before instituting HFOV.


Skin tests of pollen grains of taxodiaceae and cupressaceae in children with bronchial asthma. Atmospheric cedar pollen in the southern region of Okayama Prefecture (situated in south-western Japan) has been counted since 1988. Pollen of different species of the Taxodiaceae family (Cryptomeria japonica, Sequoia sempervirens and Metasequoia glyptostroboides) and Japanese juniper (Juniperus rigida) in the Cupressaceae family, which are propagated mainly in the southern region of Okayama Prefecture, were found among the atmospheric pollen. Scratch tests using the pollen extract from Taxodiaceae and Cupressaceae were performed on children with bronchial asthma. Forty (25%) and 30 (18.8%) of the 160 patients reacted positively to an allergen extract from the pollen grains of Japanese cedar (Cryptomeria japonica) and Japanese juniper, respectively.


The effects of rice bran broth bathing in patients with atopic dermatitis. We determined the effects of rice bran broth bathing therapy in 17 outpatients with atopic dermatitis. The rice bran broth used in this study was made in our hospital and distributed to the patients who dissolved it in the bathtub as a medicinal bath. In the case of one patient, redness and itching of the skin increased just after bathing. The patient subsequently discontinued therapy. We followed the other 16 patients who performed rice bran broth bathing for 2-5 months and examined their skin symptoms once a month. The efficacy of this therapy in alleviating skin symptoms was excellent in four of the 16 evaluated patients, good in seven, slightly effective in four, and ineffective in one. None of the 16 patients experienced negative effects of treatment. Recurrence of initial symptoms was not detected in any patient during rice bran broth bathing. Rice bran broth bathing therapy appears to be safe and clinically useful.


Possible role of Streptococcus pyogenes in mucocutaneous lymph node syndrome. XV. Potential utility of streptococcal pyrogenic exotoxin toxoid for the prophylaxis and treatment of MCLS. Mice made tolerant to streptococcal pyrogenic exotoxin (SPE) by neonatal inoculation with SPE emulsified in incomplete Freund's adjuvant demonstrated early thrombocytopenia followed by thrombocytosis. This state is the perfect counterpart of patients with mucocutaneous lymph node syndrome (MCLS). We have hypothesized that by inducing tolerance to SPE, the biological activities of the toxin might play leading roles in the pathogenesis of MCLS. In the present investigations, the efficacy of SPE on the prophylaxis and treatment of diseases caused by Streptococcus pyogenes (including MCLS) were monitored using the murine model system accompanied with a platelet-counting technique. The mice, rendered tolerant due to neonatal SPE inoculation and followed by immunization with SPE toxoid about 1 month prior to the provocative injections with SPE, demonstrated an almost complete lack of response to the provocation, keeping platelet counts within the normal range of values (except for a marginally significant thrombocytosis 7 days postprovocation). Moreover, anti-SPE titers of the sera from the mice sacrificed on day 35, at which point the observation was terminated, were proved to be markedly elevated when compared with controls. These findings seem to suggest that immunization with the toxoid could overcome tolerance, resulting in the production of an antitoxin. In a second experiment that examined the effect of administration with rabbit antiserum raised against the toxoid, the antiserum-treated mice demonstrated a transitory thrombocytosis on 7 days postprovocation with SPE, followed by an abrupt decrease in the number of platelets from day 10 onward.(ABSTRACT TRUNCATED AT 250 WORDS)


Urinary fibrin and fibrinogen degradation products and the origin of hematuria. We examined urinary fibrin and fibrinogen degradation product (U-FDP) concentrations in pediatric patients with hematuria using the rapid and highly-sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non-glomerular hematuria. If U-FDP concentrations less than 0.25 microgram/ml are accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U-FDP concentrations observed in patients with non-glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U-FDP concentrations of 0.25 microgram/ml or more had coexistent erythrocyte cylindruria, the U-FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U-FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria.


Nosocomial meningitis due to Campylobacter fetus subspecies fetus in a neonatal intensive care unit. We experienced a nosocomial outbreak of Campylobacter fetus subspecies fetus (C. fetus) meningitis in a neonatal intensive care unit. A cluster of three infants developed meningitis approximately 1-1.5 months after the index patient was admitted. Two asymptomatic intestinal carriers of C. fetus were detected during the outbreak. Our experience indicates that C. fetus can cause nosocomial meningitis in neonates, and asymptomatic carriers may play a role in the transmission of the organism.


A mosaic case of isodicentric chromosome 18. A case of mosaicism of isodicentric chromosome 18 is reported. Dicentric chromosome 18 occurs rarely and only five cases of isodicentric chromosome 18 have been documented. A high resolution banding method revealed that the karyotype of the patient was mos 46,XX/46,XX idic(18)(pter-->q21.3::q21.3-->pter), and the ratio of normal and abnormal clones was 1:1. The clinical manifestations, resembling those of trisomy 18 syndrome, were affected by both partial trisomy 18pter-->q21.3 and partial monosomy 18q21.3-->qter.


Myelodysplastic syndrome with partial deletion of the long arm of chromosome 5: first report of a case in a child. A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 x 10(3)/l with 3% atypical lymphocytes, and platelet count 17.7 x 10(4)/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases. These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-.


Atelosteogenesis type 3: the first patient in Japan and a survivor for more than 1 year. We report the first patient of atelosteogenesis type 3 (AO3) in Japan. The patient had multiple craniofacial abnormalities at birth, including ocular hypertelorism, a flat nasal bridge, micrognathia and a cleft palate. There was rhizomelic shortness of the limbs and a club-foot. The infant had short broad thumbs in the hands similar to those observed in the feet. There were no chromosomal abnormalities. Radiological examination demonstrated striking hypoplasia of the humerus with proximal rounding and distal tapering giving a 'drumstick' appearance, 'S'-shape configuration of the cervical spine, scoliosis and coronal cleft in the thoracolumbar vertebral bodies. The infant experienced recurrent apnea and persistent severe tracheomalacia, which necessitated tracheostomy at 5 months of age. Despite his multiple skeletal deformities and respiratory problems, this patient survived more than 1 year with motoneuronal developmental delay.


Spinal arachnoid cyst in a newborn infant. A male infant was born with asphyxia following a prolonged breech delivery at 39 weeks of gestation. He had a chylohemothorax from birth. Soon after birth he exhibited flaccid paraplegia with an absence of deep tendon reflexes in the lower extremities. At 17 days of age, magnetic resonance imaging (MRI) disclosed a hypodense area in the thoracic cord between C7 and Th4 in T1-weighted images, and spinal sonography revealed an echo-free space compressing the spinal cord in the same region observed with MRI. A spinal cyst was removed surgically at 24 days of age. The cyst was confirmed by pathology to be a true arachnoid cyst between C7 and Th4. The cause of this cyst may have been a spinal cord injury during the perinatal period.


Report of a Japanese girl with Marfan syndrome associated with insulin-dependent diabetes mellitus. A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.


Case report of an insulin-dependent diabetes multiplex family with a pair of identical twins. The following is a case of a family with a pair of identical twins and a family history of insulin-dependent diabetes mellitus (IDDM). A 2 year old identical twin was first admitted to our hospital and diagnosed as IDDM based on diabetic ketoacidosis. His father has been treated with insulin since the diagnosis of IDDM at the age of 17. All family members had the HLA-DR4 and DQA1*0301 alleles, which are strongly associated with IDDM. The DR-DQ haplotypes of the father and both twins were DR4-DQW8 (DQB1*0302), which increases susceptibility to IDDM. Islet cell antibodies were positive only in the index twin at the time of diagnosis. The co-twin was considered to have beta-cell dysfunction based on the result of an intravenous glucose tolerance test.


Familial occurrence of growth hormone deficiency and primary hypothyroidism. We examined endocrine function in three male siblings with growth hormone (GH) deficiency and primary hypothyroidism. Low GH responses to various provocative tests were revealed in all three. Exaggerated thyrotropin (TSH) responses to thyrotropin-releasing hormone increased basal TSH levels, and low free thyroxine levels were also found in all three. Additionally, a low testosterone response to human chorionic gonadotropin and low gonadotropin responses to luteinizing hormone-releasing hormone were noted in the youngest sibling. Skull X-ray films, computerized tomography and magnetic resonance imaging revealed no abnormalities of the pituitary gland or sella turcica. The GH gene was intact in all of the children and their parents. We diagnosed all siblings as having GH deficiency and primary hypothyroidism. This is the first report of familial occurrence of GH deficiency and primary hypothyroidism.


Intra-operative total enteroscopy for the management of Peutz-Jegher's syndrome. We present a case of Peutz-Jegher's syndrome in an 18 year old female who was followed for gastrointestinal polyps for 13 years from the age of 5 years. The patient was treated four times with surgical or endoscopic polypectomy for gastrointestinal polyps. At the age of 14 years, a combined surgical and endoscopic approach for the management of Peutz-Jegher's syndrome was carried out. A large polyp of the ileum required enterotomy for its removal, and another smaller polyp of the upper jejunum was identified and removed by intra-operative total enteroscopy via the anus. Intra-operative enteroscopy allows one to identify polyps that would previously have been missed. A more complete polypectomy can be performed using this technique, allowing the patient with Peutz-Jegher's syndrome a longer interval between laparotomies and a reduction in symptoms attributed to polyps.


The very low birthweight neonate with an interrupted aortic arch and dextrocardia. Type 1A interruption of the aortic arch complex accompanied by mirror-image dextrocardia with situs inversus was diagnosed by counter-current aortography through the radial artery. This technique is useful for aortography of the very low birthweight neonate.


[Effects of m-nifedipine on experimental myocardial metabolism and infarct size in rabbits]. The protective effects of m-Nif 15, 30 and 50 micrograms.kg-1 and of Nif 30 micrograms.kg-1 on experimental myocardial infarction and metabolism in rabbits were evaluated. Blood samples were collected simultaneously from the femoral artery and the coronary sinus for examining lactate and potassium balance. In the normal group (n = 8) and the sham ligated group (n = 5), the lactate balance were +17 +/- 1.0 and + 13 +/- 1.1% respectively and the potassium balance were +2.1 +/- 0.08 and +2.4 +/- 0.08%, respectively. After occlusion of the LAD, the lactate and K+ balance reduced to -196 +/- 60.2 and -83.0 +/- 8.2% respectively, and m-Nif produced a dose dependent improvement of both balance. After giving m-Nif 15, 30 and 50 micrograms.kg-1 i.v., the lactate balance improved to -60 +/- 9, -48 +/- 6.7 and -24 +/- 1.8% and the K+ balance went up to -32.2 +/- 2.1, -17.6 +/- 0.1, -3.3 +/- 0.06, respectively. In the mean time, Nif 30 micrograms.kg-1 i.v. improved the lactate and K+ balances to -52 +/- 8.6% and -36.4 +/- 3.1%. In another experiment, propranolol 1 mg.kg-1 i.v. improved the lactate balance to -18 +/- 1.2% while the K+ balance increased to +2.0 +/- 0.05%. The area of the myocardial infarct was measured by nitroblue tetrazolium (N-BT) technique 24 h after LAD occlusion.2+ angina pectoris.


[Effects of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on tension of rabbit aortic strips]. The purpose of the investigation was to determine the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) on the isolated rabbit aortic strips. The results showed that (1) the rabbit aortic strips with intact endothelium contracted in a dose-dependent manner to exogenous AA between the concentrations of 2.5 x 10(-6) mol/L and 4 x 10(-5) mol/L. EPA did not affect the tension of the relaxing strips, but inhibited the contractile response to AA (2 x 10(-5) mol/L), IC50 = 9.94 x 10(-6) mol/L. DHA showed no significant effect on the contractile response to AA. (2) In the endothelium-damaged rabbit aorta, the contraction of strips to AA was drastically diminished. The inhibitory effect of EPA on the contraction to AA was almost vanished. (3) The contraction of rabbit aortic strips to AA was shown to be abolished by indomethacin (1.5 x 10(-5) mol/L), a cyclooxygenase inhibitor. (4) Radioimmunoassay showed that exogenous AA increased the tissue levels of 6-keto-PGF1 alpha, TXB2 and their ratio. Lower dose of EPA (1.5 x 10(-6) or 1.5 x 10(-5) mol/L) did not affect the tissue levels of 6-keto-PGF1 alpha and TXB2. However, EPA at higher concentrations decreased the metabolites of AA significantly. These findings suggest that exogenous AA induces the contraction of rabbit aortic strips in vitro, which is related to the endothelial cells and mediated by the metabolites(s) of cyclooxygenase, likely endothelium-derived contracting factor (EDCF).(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of cinobufagin on the guinea pig vas deferens and its mechanism of action]. Cinobufagin, one of the active principles extracted from toad venom, was studied on the isolated vas deferens of the guinea pig. The preparation was suspended in a bath containing 10 ml Krebs solution. Isometric tension of vas deferens was recorded on polygraph with a force displacement transducer. Cinobufagin caused a long lasting contraction of the vas deferens of the guinea pig at concentrations of 15-50 mumol/L. The contraction was inhibited following reserpinization and cold storage treatment. The cinobufagin induced contraction was partly blocked by pretreatment with phentolamine and verapamil. These results suggest that the cinobufagin induced contraction of vas deferens might be related to an action which promotes release of NA from the adrenergic nerve terminals.


[Synthesis and analgesic action of 6,7-methylenedioxy-1(2H,4H)-acridone derivatives]. Thirteen derivatives of 6,7-methylenedioxy-1 (2H, 4H)-acridone were prepared. The structures of all the compounds synthesized were characterized by elemental analysis, IR and 1H NMR spectra. Compounds IIa, IIb, IId, IIe, IIf increased significantly the pain threshold using the hot-plate method.


[Synthesis of molluscacidal synergists]. Chemical molluscicides are useful in schistosomiasis control. A synergist can potentiate the efficacy and reduce the dosage of a molluscicide, thus decreasing the toxicity and environmental pollution. In order to search for potential molluscicidal synergists, 13 compounds of O,O-dialkyl-O-(2-substituted-3-benzofurylacetonitrile-alpha-oxi mino)phosphate or thiophosphate (VI1-13) and 2 compounds of O,O-dialkyl-O-(2-thienylacetonitrile-alpha-oximino)phosphate (X14,15) were prepared. Preliminary test demonstrated that compound X15 had strong synergic effect with sodium pentachlorophenol in combating mollusks. Compounds X14 and VI1,2,3,6,8,10,12,13, also showed some molluscicidal synergistic activity.


[Isolation and identification of two new taxane diterpenes from Taxus chinensis (Pilger)Rehd]. Two new taxane diterpenes were isolated from the stem barks of Taxus chinensis grown in Sichuan province of China. Their structures were elucidated by spectral analysis and chemical evidence as 1-hydroxy-7,9-dideacetyl baccatin I(1) and 7,9-dideacetyl baccatin VI(3).


[Revision of structure of peimisine].

[Revision of structure of peimisine]. From the bulbs of Fritillaria siechuanica cultivated in Sichuan province, 5 alkaloids including peimisine (III) were isolated. Structure of peimisine reported in reference (2) was revised as 2 based on 2D-NMR (1H-1H, 1H-13C COSY and NOE), and FR-5 was proved to be peimisine on the basis of their melting point and TLC behavior. It is worthy of noting that 1) configuration of the oxygen at the C-17 in hupehenisine 3 is possibly erroneous; 2) both songbaisine 4 (A or B) and peimisine 2 should be the same compound on the basis of comparison of their 13C NMR data (Table 3) and 1H NMR spectra; 3) configuration of the oxygen atom at C-17 in the jervine-type steroidal alkaloids can not be safely proved by their IR, MS and the chemical shifts of some protons such as the methyls without the X-ray diffraction analysis, or the NOE technique and the 13C NMR method.


[Studies on naphthoic acid esters from the roots of Rubia cordifolia L]. Four naphthoic acid esters including a new compound were isolated from the roots of Rubia cordifolia L. The new one was named as rubilactone and its structure was elucidated as 3'-carbomethoxy-4'-hydroxy-naphtho[1',2'-2,3] pyran-6-one (I) based on the physicochemical properties and spectrometric analyses (UV, IR, MS, 1HNMR and 13CNMR). The other three were 3'-carbomethoxy-4'-hydroxy-naphtho [1',2'-2,3] furan (II), dihydromollugin (III) and 3-carbomethoxy-2-(3'-hydroxy)isopentyl-1,4-naphthohydroquinone-1-O -beta-D-glucoside (IV).


[Anodic stripping voltammetry of promethazine hydrochloride with Nafion coated glassy carbon electrode]. This paper reports the determination of promethazine hydrochloride with Nafion coated glassy carbon electrode by anodic stripping voltammetry. There is a linear relationship between the concentration and peak height in the range of 4 x 10(-8)-5 x 10(-5) mol/L and 8 x 10(-5)-1 x 10(-3) mol/L for promethazine hydrochloride. The raw material and tablets of promethazine hydrochloride have been analysed and good results were obtained.


[Comparison of chemical constituents of essential oils from Elsholtzia splendens and cultivated Mosla chinensis by GC-MS analysis]. Xiangru (Labiatae) is a well-known drug used in Chinese traditional medicine. Chemical constituents of essential oils from Elsholtzia splendens and cultivated Mosla chinensis were compared by GC-MS/DS combination on SE-54 capillary column (30 m x 0.32 mm). Forty-three components were identified in Elsholtzia splendens Nakai ex F.Maekawa. The total content of the components in the essential oil was found to be 90.61%. Among them the major constituents are elsholtzia ketone (80.81%). Fifty components were identified in cultivated Mosla chinensis, with a total content of 93.91% in the essential oil. The major constituents are carvacrol (51.11%), thymol (22.00%), and etc.


[Construction and application of all-solid-state aconitine electrochemical detector in flow injection analysis]. A new kind of all-solid-state electrochemical detector for very toxic alkaloids such as aconitine, mesaconitine and hypaconitine has been studied. It exhibits Nernstian response for these alkaloids with a slope of 56 mV/decade over the concentration range of 3 x 10(-5)-1 x 10(-2) mol/L at pH 2-7 under the flow condition. Direct potentiometry for the determination of aconitine in Aconitum kusnezoffii Reichb., Aconitum carmichaeli Debx. and Xiaohuoluo Wan showed average recoveries of 98.5, 98.3 and 96.8% and relative standard deviations of 1.8, 2.4 and 3.5%, respectively. It can be used for the determination of very toxic alkaloids in the above mentioned samples by flow injection analysis. It also can be used for the study of the hydrolytic kinetics of aconitine.


[Bioavailability of a controlled-release suspension of phenylpropanolamine in healthy volunteers]. A high-performance liquid chromatographic analysis of phenylpropanolamine (PPA) in human plasma is presented. Using direct UV detection the method is sufficiently sensitive to 25 ng/ml for PPA. Single-dose pharmacokinetics of PPA in 10 healthy volunteers taking controlled release suspension (C) or tablet (T), each containing 150 mg PPA was compared. The study described here has shown that the (C) AUC(0-infinity)/(T) AUC(0-infinity) = 1.02 (P greater than 0.4). The controlled-release product of PPA is equivalent to PPA tablet.


[Dissolution rate and bioavailability of famotidine tablets]. An automated dissolution test system was used for the determination of the dissolution rate of famotidine tablets, and a mean cumulative dissolution rate of 97.40 +/- 0.31% in 15 min was obtained. To each of six healthy volunteers, 40 mg of famotidine tablets were administered orally, then an automated HPLC with switching column system was used to analyze famotidine in plasma. Variation of drug concentration vs time were fitted to curves. By comparison of calculated values with observed ones, the results could be described as one-compartment model in human. According to a statistic moment algorithm, the results of calculation showed that T1/2 = 2.92 h and Frel = 118.8%.


[Morphological and histological studies on the Chinese drug shan-dou-gen]. The Chinese drug "Shan-Dou-Gen" has been used for removing toxic heat, promoting the subsidence of swelling and soothing the sore throat since the ancient time. The authors made a survey of the drug "Shan-Dou-Gen" available in drug markets as well as the plant origin from the drug producing districts. The results showed that the drug "Shan-Dou-Gen" used in different regions in China at present are the roots or rhizomes derived from 9 species: Sophora tonkinensis Gagnep. (Leguminosae), Menispermum dauricum DC. (Menispermaceae), Indigofera amblyantha Craib (Leguminosae), I. carlesii Carib, I., fortunei Craib, I. decoa Lindl. var. ichangensis Y. Y. Fang et C. Z. Zheng, I. kirilowii Maxim. et Palibin, I. potaninii Craib, and Beesia calthaefolia (Maxim.) Ulbr. (Ranuculaceae). In this paper, the morphological characters of the crude drugs are described, compared and illustrated with photographs. The histological structures of the used parts are described, compared and illustrated with line drawings. The morphological and histological similarities and differences found among the above 9 species are summarized, and the key for the identification of the crude drugs is provided. As the drug "Shan-Dou-Gen" derived from different species has different actions and dosages, it is necessary to give different names to different species and use them correctly.


[Derivatives of arteannuin B with antileukemia activity]. Arteannuin B (I) was converted to hydroxy lactones (VII, VIII) by a mixture of formic acid and sulfuric acid. Compound VI and Compound VII both showed activity against leukemia P 388 cell in vitro. The rate of growth inhibition were 97.5% and 11.8% for (VI) and 80% and 52.6% for (VII) at the concentration of 10 and 1 micrograms/ml respectively. It seems that the antileukemia activity of 6-membered lactone is higher than that of 5-membered and the methylene group is necessary for the antileukemia activity.


Purification and partial characterization of anti-inflammatory peptide from pilose antler of Cervus nippon Temminck. An anti-inflammatory compound was purified and isolated from pilose antler of Cervus nippon Temminck by dialysis, gel filtration and ion-exchange chromatography techniques. HPLC and N-terminal amion acid analysis identified the compound as a homogeneous peptide. The peptide is composed of 68 amino acids and its molecular weight as determined by amino analysis, is about 7200.


[The antitumor effect of adriamycin conjugated with monoclonal antibody against gastric cancer in vitro and in vivo]. Adriamycin (ADM), an anthracycline cytotoxic agent, was conjugated with monoclonal antibody 3H11 against gastric cancer via the dextran bridge method. The conjugate 3H11-DEX-ADM, with molar ratio of 3H11 to ADM being 1:73, retained antibody activity to 86%. In the cytotoxicity assay, 3H11-DEX-ADM was shown to exhibit increased cytotoxicity against the target cell line BGC 823. Its IC50 was 3.75 fold less than that of free ADM. The antitumor effect of the conjugate was evaluated in tumor-bearing nude mice. The results indicate that the specific antibody conjugate 3H11-DEX-ADM can significantly inhibit the tumor growth. At the dosage level used in the present study (5 micrograms/mouse x 6), 3H11-DEX-ADM showed an inhibition rate of 51.5%, whereas only moderate inhibition rates were observed with free ADM and the control conjugate NIgG-DEX-ADM. In addition, experiment was performed to evaluate the combined cytotoxicity of 3H11-DEX-ADM and the conjugate of mitomycin C (3H11-HSA-MMC) at different ratios. It was shown that the combination has no synergistic effect when their IC50 was compared with that of the two conjugates used alone. The same result was observed on combinations of the two corresponding free drugs.


Effect of Ganoderma polysaccharides on T cell subpopulations and production of interleukin 2 in mixed lymphocyte response. Mixed lymphocyte response was used as a main model through all the experiments In a series of concentrations (25, 50, 100, and 200 micrograms/ml), Ganoderma polysaccharides (GL-B) promoted the production of interleukin 2 (IL-2) in a concentration-dependent manner after initiation of culture for 12 h and increased the total cell recovery as well as that of Lyt 2+ and L3T4+ cells after 4 days of culture. The data also show that the polysaccharides markedly enhanced the cytotoxicity of cytotoxic T lymphocytes, which was increased by 100% at the concentration of 200 micrograms/ml.


[Synthesis of oxazolidines from ephedrines as potential prodrugs]. Twenty three (-)- or (+)-2-(substituted phenyl)-3,4-dimethyl-5-phenyl- oxazolidines and five Schiff base derivatives of ephedrine were synthesized by cyclization or condensation with aromatic aldehydes, according to the structure-activity relationships and the pro-drug principle. Stereochemical structures were studied for these compounds by spectroanalysis method, and the kinetics of hydrolysis of the oxazolidines were also studied by UV spectra and HPLC methods. The oxazolidines were found to undergo a facile and complete hydrolysis at pH 7.40 and 37 degrees C and the half-lives of hydrolysis were determined. The relationship between structure and stability of the oxazolidine derivatives were discussed. The oxazolidine derivatives are more lipophilic and less basic than the parent ephedrines and their chemical and physical characters are more stable than those of the parent aromatic aldehydes. The stability of the oxazolidine derivatives is affected by the configurations of ephedrines and the positions or Hammett constants of the substituents in the aromatic aldehydes. These results indicate that oxazolidines can be considered as potential prodrugs for ephedrines.


[Synthesis and antitumor activities of 4-acylthiol-4-deoxy-4'-demethylepipodophyllotoxin analogues]. This paper describes the synthesis and antitumor activity of 4-acylthiol-4-deoxy-4'-demethylepipodophyllotoxin analogues. 4-Mercapto-4-deoxy-4'-demethylepipodophyllotoxin prepared from 4'-demethylepipodophyllo-toxin with H2S in the presence of BF3.Et2O, was acylated with different acids using diethyl cyanophosphonate and thus, corresponding 4-acylthiol-4-deoxy-4'-demethyl epipodophyllotoxin analogues were synthesized. These compounds were screened in L1210 leukemia and KB cells, and one compound has activity similar to etoposide, and others were generally weaker than etoposide and corresponding 4-acylamido-4-deoxy-4'-demethylepipodophyllotoxin analogues.


[Total synthesis of securinine].

[Total synthesis of securinine]. Securinine, an alkaloid having strychnine-like action was synthesized using 1,4-cyclohexanedione as the starting material through the following sequence of reactions: condensation with piperidine, reduction, cyclization catalyzed by mercuric acetate and intramolecular condensation, totally in eleven steps. The IR, 1HNMR and melting point of the synthetic product is identical with those of natural securinine.


[Phenyl glycosides from Curculigo orchioides]. One new phenyl glycoside and two new chlorophenyl glycosides were isolated from rhizomes of Curculigo orchioides (Chinese name: Xian Mao, Hypoxidaceae). Based on HRMS, FABMS, 1H-, 13C-NMR and other spectral data as well as chemical evidence, the structures of curculigoside B, curculigine B and C were elucidated to be 2-beta-D-glucopyranosyloxy-5-hydroxybenzyl-2'-methoxy-6'-hydroxybe nzoate (I),24-dichloro-3-methyl-5-methoxy-phenol-O-beta-D-apiofuranosyl (1-6)-beta-D-glucopyanoside (III) and 2,4,6-trichloro-3-methyl-5-methoxyphenol-O-beta-D-xylopyranosyl (1-6)-beta-D-glucopyranoside (IV), respectively.


[Anthraquinones isolated from Morinda officinalis and Damnacanthus indicus]. From chloroform extract of the root of Morinda officinalis, eight anthraquinones were isolated whose structures were deduced to be rubiadin (I), rubiadin-1-methyl ether (II), 1-hydroxyanthraquinone (III), 1-hydroxy-2-methylanthraquinone (IV), 1,6-dihydroxy-2,4-dimethoxyanthraquinone (V), 1,6-dihydroxy-2-methoxyanthraquinone (VI), 1-hydroxy-2-methoxyanthraquinone (VII) and physcion (VIII). Except for compound I and compound II, the other compounds, 1-hydroxy-2-hydroxymethylanthraquinone (IX), 1,3-dihydroxy-2-methoxy-anthraquinone (X), 1,4-dihydroxy-2-methylanthraquinone (XI), 1-methoxy-2-hydroxyanthraquinone (XII) and 1,4-dimethoxy-2-hydroxyanthraquinone (XIII), were isolated from chloroform extract of root of Damnacanthus indicus. Compound V, VI and XIII are new compounds.


[Determination of nifedipine by differential spectrophotometry]. This paper reports a new method for determining nifedipine based on the unstable character of nifedipine to light. The absorbance was measured at 350 nm before and after light irradiation. In this method, the contents of nifedipine in tablets were determined by differential absorbance (delta A) and the assay of nifedipine was not affected by other components. Calibration graph was linear in the range of 10-60 micrograms/ml for delta A. The precision of the method was: 1.3% within-day and 1.9% between-days. The average recovery for nifedipine was 99.69%. The method is not only better in specificity and repeatability but also simple and rapid, it would be a new way of assay for nifedipine.


[Studies on the dissolution and bioavailability of trimethoprim-sulfadiazine-sulfamethoxazole tablets]. A reverse-phase high performance liquid chromatographic method was established for the simultaneous determination of trimethoprim (TMP), sulfadiazine (SD) and sulfamethoxazole (SMZ) in dissolution media. Meanwhile, another reverse-phase high performance liquid chromatographic method was developed for the simultaneous determination of the three drugs mentioned above and their metabolites, N4-acetyl-SD and N4-acetyl-SMZ in serum. The in vitro dissolution and in vivo bioavailability of two commercial trimethoprim-sulfadiazine-sulfamethoxazole tablets (A and B) were studied. Drugs were released far more rapidly from A than from B. Significant difference (P less than 0.001) was observed between the T50 s of the same active principles released from A and B. The in vivo processes of all three active principles in 8 healthy subjects taking two tablets each could be described by one-compartment model with first-order absorption and elimination. Compared with A, the relative bioavailabilities of B were 0.83, 0.73 and 0.78 for TMP, SD and SMZ, respectively. Drugs were absorbed more rapidly from A than from B.


[Studies on pharmacokinetics of cisplatin-ethylcellulose microspheres for maxillary arterial embolization in dogs]. This paper reports the preparation and pharmacokinetic studies of DDP-EC-ms. The DDP-EC-ms were infused into the maxillary artery of dogs and DDP were infused into the vein as control. The concentration of DDP in peripheral venous blood and tissue was determined by FAAS. Results showed that the DDP level of DDP-EC-ms in the circulating blood was significantly lower than that in dogs given DDP intravenously. However, a significantly higher DDP concentration in tissues was found in dogs treated with DDP-EC-ms. These facts suggest that maxillary arterial embolization with DDP-EC-ms, which significantly reduced the systematic side effects and increased the level of DDP in the embolized local tissue, could achieve the purpose of targeted cancer therapy.


[Effects of anisodamine and atropine on the microvasculature of liver, skeletal muscle and foot-pad skin in anesthetized rats]. Rats were urethanised and kept in a constant temperature chamber. The surface temperature of various organs including the liver and the armpit skeletal muscle were monitored with a special mercury thermometer through a narrow hole on the skin cut with scalpel. The temperature of the foot-pad skin were measured using a thermometer as reported previously. After iv of anisodamine or atropine at doses of 12.5-50 micrograms/kg the temperature of the liver and the armpit skeletal muscle were significantly reduced in a dose-dependent manner but the skin temperature was increased. Temperature changes were observed 5 min after drug administration, reaching peak height at about 15 min and maintained for one hour or so. Isoprenaline, dopamine and aminophylline iv showed only a temperature-elevating effect, while serotonin and noradrenaline caused only a temperature-decreasing effect in all the three organs mentioned above. Although the functional significance of the opposite effects on the microcirculation of different tissues remain to be defined, the effects of atropine-like drugs must result in a redistribution of circulating blood and may have beneficial effects on the survival of some vital organs such as brain, lungs, kidneys ... especially in shock.


[Synthesis and antitumor activity of substituted benzaldehyde/cinnamicaldehyde selenosemicarbazones]. According to drug combination principle 26 substituted benzaldehyde/cinnamicaldehyde semicarbazones were synthesized. Twelve of which were not found in literature. The structures of the title compounds were confirmed by elemental and IR, UV, 1HNMR and MS analyses. Thirteen compounds were screened in vivo against Ehrlich ascites tumor cells. Four compounds (VIIf, VIIg, VIIh, VIIm) showed strong antitumor activity. The percent increase in life span were between 46.1%-91.1%. 3-Methoxy-4-hydroxy and 3-methoxy-4-acetyloxy-cinnamicaldehyde selenosemicarbazones showed stronger activity and less toxicity with increase of life span of 76.5% (300 mg/kg) and 91.1% (60 mg/kg), respectively. They were worthy to be studied further.


[A new skeleton bisditerpenoid alkaloid from Aconitum pukeense]. A novel bisditerpenoid alkaloid named pukeensine was isolated from Aconitum pukeense W. T. Wang (Ranunculaceae). Its proposed structure was suggested by spectral evidence. This bisditerpenoid alkaloid skeleton has not been found previously.


[Acuminatin from the aerial part of Epimedium acuminatum]. A new flavonol glycoside, C27H28O10, mp 151-152 degrees C (MeOH), named acuminatin (I), was isolated from the aerial part of Epimedium acuminatum Franch in addition to four known compounds. By means of UV, FAB-MS, EI-MS, 1HNMR, 13CNMR and chemical evidences, the structure of acuminatin was established as 6", 6"-dimethylpyrano (2", 3": 7, 8) 4'-methyl kaempferol-3-O-alpha-L-rhamnopyranoside. The known compounds were identified as kaempferol-3-O-alpha-L-rhamnopyranoside (II), quercitrin (III), hyperin (IV) and daucosterol (V).


[Effects of astragalus (ASI, SK) on experimental liver injury]. The saponins (ASI, SK) used in this study was extracted from the root of Astragalus membranaceous Bge and Astragalus sieversianus Pull. ASI and SK were found to protect liver from chemical injury induced by CCl4, D-galactosamine and acetaminophen in mice. The two saponins were shown to impede the elevation of SGPT level, decrease the MDA content and increase the GSH concentration in mouse liver. Obvious improvement of histological changes were also observed. The protective action of ASI and SK against the hepatotoxicity was also shown in experiments using primary cultured rat hepatocytes. The average value of GPT in the medium treated with different concentration of ASI and SK (0.00075-0.18 mmol/L) was lower than that in control. Analyzing through multiple linear correlation, we showed that the lowering of SGPT was negatively related to the increase of GSH, positively related to the decrease of MDA in mice given CCl4 or acetaminophen in combination with ASI or SK. These results indicate that the hepato-protective effects of ASI and SK may be due to their anti-oxidation activities, since the content of liver protein in mice given ASI or SK was more than that in the controls. Moreover, the level of hepatic microsomal cytochrome P-450 in all mice given the two saponins were significantly increased, the liver metabolism and immunoregulating action produced by ASI and SK may be also involved in their hepato-protective effects.


[Comparison of antiarrhythmic effects of IHC-72 (an iodonium-72), lidocaine and verapamil]. The antiarrhythmic actions of 3,6-dimethylamino-dibenzopyridonium edetate (IHC-72), lidocaine (Lid) and verapamil (Ver) on several models Were compared at equitoxic doses (equal fraction of LD50). The action of IHC-72 against aconitine induced arrhythmia was similar to that of Lid but stronger than that of Ver in anesthetized rats. The effect of IHC-72 on ouabain induced arrhythmia was also similar to that of Lid, but weaker than that of Ver in anesthetized guinea pigs. The activity of IHC-72 to raise electrical ventricular fibrillation thresholds (VFT) was weaker than that of Lid and Ver. The effects of IHC-72 in decreasing the incidence of ventricular premature beat(VP B), ventricular tachycardia (VT), ventricular fibrillation (VF) and shortening the duration of VT yielded by reperfusion were similar to those of Lid anf Ver in vivo.


[Effects erythropoietin on experimental anemia in rats with chronic renal failure]. Erythropoietin (EPO) is a glycoprotein hormone secreted by human kidney cells. Human EPO was induced from human embryo kidney cells, isolated and purified from medium by biochemical method in our laboratory. The hypoproliferative anemia in chronic renal failure (CRF) has been assumed to be the result of decreased EPO production by the damaged kidney and of the shortening of the survival of erythrocytes. In this study, CRF anemia was formed 9 weeks after the removal of five-sixths of the renal mass of rats. These anemic rats were divided into 6 groups: treated with different dosages of EPO or physiological saline. The results indicate that EPO has apparent effects on anemia in rats with CRF. It may stimulate erythropoiesis and improve the anemia state of rats with CRF. Hematological parameters (RBC, Hb, PLT, Ht and Rt) may be reverted to normal levels (P less than 0.001). The level of BUN and Cr were significantly decreased. The optimum dose of EPO was 1000 U/kg. All these results show that injection of EPO has therapeutic effect on anemia in rats with CRF. EPO showed no effect on normal rats.


[Studies on the tissue schizonticide of malaria parasite: synthesis of derivatives of 2-substituted phenoxyprimaquine, 4-methylprimaquine and quinoxaline]. 2-Substituted phenoxy-, 4-methyl-6-methoxy-8-aminoquinolines and 7-methoxy-5-aminoquinoxaline were condensed with 1-phthalimido-bromo-alkane to yield 2-substituted phenoxy-, 4-methyl-6-methoxy-8-(1-phthalimidoalkyl)-aminoquinolines (compounds 7-10 and 15-20) and 7-methoxy-5-(1-phthalimidoalkyl)aminoquinoxalines (28-30) which were subsequently reacted with hydrazine hydrate to give 2-substituted phenoxy-, 4-methyl-6-methoxy-8-(1-aminoalkyl)-aminoquinolines (11-14 and 22-27) and 7-methoxy-5-(1-aminoalkyl) aminoquinoxalines (31-33), respectively. The 2-substituted phenoxy-6-methoxy-8-aminoquinolines (4-6) were afforded by reduction of the corresponding 8-nitroquinolines (1-3) which were obtained by condensation of 2-chloro-6-methoxy-8-nitroquinoline and substituted phenols. Among them, compounds 25 and 24 were the most effective when evaluated in Plasmodium yoelii infected mice, no parasitemia was observed after a single oral dose of 10 mg/kg.


[Studies on the tissue schizonticide of malaria parasite: synthesis of 5-trieluoroacetyl-primaquine and its derivatives]. Primaquine was acylated with trifluoroacetic anhydride to give 6-methoxy-8-(4-trifluoroacetamido-1-methylbutyl) aminoquinoline (compound 2 in Table) and 5-trifluoro-acetyl-6-methoxy-8-(4-trifluoroacetamido-1-methylbutyl )- aminoquinoline (compound 6), bis (trifluoroacetyl) primaquine, which was subsequently hydrolyzed to yield 5-trifluoroacetyl-6-methoxy-8-(4-amino-1-methylbutyl)-aminoquinoline (compound 11), 5-trifluoroacetyprimaquine or trifluoroacetoprimaquine, coded M8506. Similarly, compounds 1, 3-5 and 7-10 were also prepared. Among them, compound 11 appeared to be the most effective by evaluation in mice infected with sporozoites of Plamodium yoelii. With intragastrical dosage of 0.75 mg/kg/d x 3 d of compound 11 to monkeys infected with sporozoites of P. cynomolgi, the radical cure rate of the compound was 92.3%, while that of primaquine was 55.6%. The acute toxicity of compound 11 was two times a low as that of primaquine in mice. The compound did not appear to have mutagenicity, embryotoxicity and chromosomal aberration. When rats received intragastrical doses of 15, 30 and 60 mg/kg/d of compound 11 for 14 and 28 consecutive days respectively, no change was found in histopathological examination at the two lower doses. However, reversible changes were observed at the highest dose. Compound 11, trifluoroacetoprimaquine, was shown to be a promising tissue schizonticide of malaria parasite.


[Study on the mass spectrometry of natural products. XI. The MIKES of fast atom bombardment mass spectra of sodium adduct ions of phenylpropanoid glycosides]. The fast atom bombardment (FAB) mass spectra and mass-selected ion kinetic energy spectra [MIKES] of sodium adduct ions [M + Na]+ of six phenylpropanoid glycosides have been studied. An intense sodium adduct appeared in their FAB mass spectra, which was more abundant than the corresponding protonated molecular ion [M + H]+ and may give more definite information about molecular weight of the sample. The MIKES of these [M + Na]+ ions provided a convenient way for sugar sequence analysis of such glycosides.


[Glycosides of phenolic acid and flavonoids from the leaves of Glycyrrhiza uralensis Ficsh]. Seven glycosidic constituents have been isolated from the dried leaves of Glycyrrhiza uralensis Ficsh. (Leguminosae). The Structures of these compounds have been identified as 1-O-protocatechuyl-beta-D-xylose (I), apigenin-6,8-di-C- beta-D-glucopyranoside (vicenin-2, II), isorhamnetin-3-O-rutinoside (narcissin, III) kaempferol-3-O-rutinoside (nicotiflorin, IV), kaempferol-3-O-beta-D- glucopyranoside (astragalin, V), quercetin-3-O-rutinoside (rutin, VI), and quercetin-3-O-beta- D-glucopyranoside (isoquercitrin, VII) by chemical method and spectroscopic analysis. Among these compounds, I is a new compound, named uralenneoside; III was reported for the first time in the genus; III to VII were isolated for the first time from the species. II to VII are known biologically active constituents.


[Triterpene constituents from Euphorbia nematocypha Hand-Mazz]. Seven triterpenoids have been isolated from the roots of Euphorbia nematocypha Hand-Mazz. through chromatography on 20% AgNO3-silica gel. One of them was identified as a new compound named nematocyphol on the basis of spectral data (IR, EIMS, 1H-NMR and 13C-NMR). Its structure was deduced as IVa. Other compounds were identified as nepehinol acetate (I), germanicol acetate (II), euphol (III), tanaxastanol (Va), 24-methylenecycloartanol (VIa) and nepehinol (VIIa). These compounds were obtained for the first time from this plant.


[Direct injection of plasma to determine gliquidone in plasma using HPLC column switching technique]. An automated clean up and concentration method by column switching is described for the assay of gliquidone, a hypoglycemic agent, in plasma. The system uses Merck Lichroprep RP2 (25-40 microns) as short precolumn packing material for on--line clean up and concentration. A Shimpack CLC--ODS (5 microns) is used as analytical column. Water is used as the pretreatment mobile phase and a mixture of methanol--isopropanol--0.2 mol/L ammonium acetate solution (61:5:34) is used as the analytical mobile phase. The plasma is diluted with a solution of 0.2 mol/L acetic acid and injected directly on the precolumn. The low speed of 0.2 ml/min of pretreatment mobile phase during transfer of plasma sample on the precolumn can get recovery of 80.7%. The detection is at 310 nm and the detection limit is 30 ng/ml plasma. The procedure is simple and automatic.


[Quality assessment of the traditional Chinese medicine gentian by chemical pattern recognition]. Methanol extracts of 38 samples of the traditional Chinese medicine gentian of different origin were prepared. Data reflecting their chemical constituents as a whole were obtained by HPLC. The Chinese Pharmacopoeia (1990) specified four species of the getiana as authentic. Some samples from the authentic and non-authentic gentian were used as the training set of pattern recognition. Chemical features of the gentian samples were selected from among the matching data of HPLC by the SIMCA program. Finally, the selected chemical features were displayed as stars in a semicircular polar coordinate system, resulting in a constellation graph. Quality assessment of the traditional Chinese medicine gentian was accomplished by recognizing the position and path of the stars in the constellation graph. The clusters of the gentian samples in the constellation graph obtained from the HPLC features were consistent with and complement to their plant taxonomy. The vivid graph demonstrated that pattern recognition via chemical constellation promises well a reliable method for assessing traditional Chinese medicines.


[Determination of ofloxacin in human plasma and studies of its pharmacokinetics using HPLC method]. Ofloxacin is a new broad-spectrum oral bactericidal antimicrobial agent. Its primary effect is the inhibition of bacterial DNA gyrase. This paper describes the development of a simple method for its determination using HPLC with UV detection. We used a Waters liquid chromatograph equipped with a Model 490 E multi-wavelength detector, a Model 510 pump and a U6K injector. The separation was performed on a Spherisorb C18 column (200 mm x 4.6 mm ID, 5 microns) with a mobile phase of methanol-0.01 mol/L phosphate buffer-0.5 mol/L tetrabutylammonium bromide (35:65:4, pH 2.50). The flow-rate was 1.0 ml/min and detection was at 294 nm. A specimen (0.2 ml) was spiked with the internal standard (norfloxacin) and deproteinized by adding 1.0 ml methanol. The precipitated mixture was shaken and then centrifuged at 3000 x g for 10 min, the supernatant was evaporated at 75 degrees C under a nitrogen stream. The residue was taken up with 0.4 ml of the mobile phase and 50 microliters aliquots were injected into the system. The minimal detectable concentration in plasma is 20 ng/ml. There is a linear relationship between the peak area ratio over the range of 0.5-4.0 micrograms/ml with r = 0.9999. The method has been applied to assay ofloxacin concentration in human plasma. The pharmacokinetic characteristics were studied.


[Transdermal properties of timolol and factors affecting its permeability in vitro]. V-C horizontal diffusion cell has been used to carry out the initial study of timolol across intact and stripped hairless mouse skin and human cadaver skin. Also, we have systematically studied the effect of some factors such as hydration time, medium pH value as well as various transdermal enhancers on the permeability of timolol in vitro. We investigated the determination method of timolol by RP-HPLC using YWG-C18 column with water-acetonitrile-triethylamine (87:13:1) as the mobile phase. The results indicated the feasibility of transdermal absorption of timolol. The permeabilities of timolol raised significantly with properly extending of hydration time, increasing of medium pH and with presence of various kinds of transdermal enhancers. With 10% propylene glycol and 1% azone were used conjunctly, they showed obviously synergistic effects. All these studies contributed theoretically and practically to the further development and utilization of timolol in the form of transdermal patch.


[Studies on the chemical constituents of Fritillaria thunbergii Miq. III. Isolation and identification of zhebeinone]. A new C- nor D-homo steroidal alkaloid named zhebeinone was isolated from the bulbs of Fritillaria thunbergii Miq. Its structure was determined by spectral analyses and chemical conversion as 5 alpha, 14 alpha-cevanine-3 beta, 20 beta-dihydroxy-6-one or C-27 epimer of peiminine.


[Structure of swertiapuniside from Swertia punicea Hemsl]. A new xanthone glycoside, swertiapuniside (V), has been isolated from the whole plant of Swertia punicea Hemsl. The structure was elucidated as 1,5,8-trihydroxy-3-methoxyxanthone-8-O-beta-D-glucopyranosyl (1-6)-O-beta-D-glucopyranoside by means of chemical and spectroscopic data. Four other known xanthones mangiferin (I), bellidifodin (II), 1,3,5,8-tetrahydroxyxanthone (III) and swertinolin (IV) were also identified.


[Antitumor activity of new antitumor antibiotic C1027 and its monoclonal antibody assembled conjugate]. C1027, a new macromolecular peptide antitumor antibiotic produced by Streptomyces globisporus C1027, shows extremely potent cytotoxicity to cultured cancer cells. The antibiotic is composed of an apoprotein and a chromophore and the latter serves as the active part of the compound. C1027 was separated into apoprotein and chromophore by methanol extraction and the separated parts can be reconstituted to form the active C1027 molecule in phosphate buffer. For determination of the specificity of C1027 reconstitution, the apoprotein was incubated with epirubicin and the chromophore was incubated with H16, a McAb directed against hepatoma cells. Notably, the reconstitution of C1027 occurred neither between apoprotein and epirubicin nor between chromophore and IgG molecule. In addition, bovine serum albumin showed no competition with C1027 apoprotein in binding to the chromophore. Various methods for linking C1027 to McAb were studied and two kinds of immunoconjugates have been prepared: (1) direct conjugate was made by linking C1027 to McAb, using SPDP as a linker agent, (2) assembled conjugate was made by linking and reconstitution, including 3 steps. Firstly, the chromophore was extracted with methanol and stored at -70 degrees C in drak. Secondly, the apoprotein was conjugated to McAb by SPDP and finally the extracted chromophore was added to the McAb-apoprotein conjugate. Determined by clonogenic assay, the IC50 values for hepatoma cells were 42 pmol/L, and 5.5 pmol/L, respectively, for direct conjugate and assembled conjugate. The IC50 value of M3-C1027 assembled conjugate prepared by linking the irrelevant McAb M3 to C1027 was 1,400 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)


[Rejection of physico-chemical indices for pathological matrix in a quantitative drug design]. In a quantitative drug design, correlation of coefficient matrix of physico-chemical indices Xi is often pathological when these indices are highly correlated. The regression equation of biological activity Y about these indices Xi obtained in this case is not stable. In this paper, a method is given to obtain a stable regression equation: giving a critical valne alpha and finding out the indices among which correlation coefficient is not less than alpha. The following are the rules to reject some of them. If Xi and Xj is highly correlated (magnitude of rij greater than or equal to alpha, rij is the correlation coefficient of Xi and Xj), and magnitude of rin greater than magnitude of rjn (rin and rjn are correlation coefficients of Xi and Xj about Y, respectively), than the index Xj is rejected, otherwise, Xi is rejected. Stable equation can be obtained by stepwise regression with the remaining indices.


[Preparation and biological activities of monoclonal antibody-streptonigrin immunoconjugates]. The clinic use of streptonigrin (114B), a highly active antitumor antibiotic, is limited by its detrimental effects on normal tissues. In an attempt to improve its specificity streptonigrin was conjugated to anti-human hepatoma monoclonal antibody 3A5 by four different chemical linkage methods. The first method was via water-soluble carbodiimide (EDCI) to create conjugates (1); in the second, an active ester of streptonigrin was applied as a reactive intermediate (2); and in the other two, spacers were put to use for coupling streptonigrin to McAb 3A5-Dextran T-40 (3) or McAb 3A5-bovin serum albumin (BSA) (4). The conjugates showed biological activities and UV spectral characteristics of streptonigrin and 3A5. As determined by clonogenic assay with human hepatoma BEL-7402 cells for 1 hour exposure, the IC50 for conjugate (2), conjugate (3) and streptonigrin were 0.355 ng/ml, 1.23 ng/ml and 22.4 ng/ml, respectively. The potency of conjugates (2) and (3) were 63-fold and 18-fold stronger than that of free streptonigrin. Clonogenic assay with KB cells which weakly react with 3A5 by Elisa showed that the potency of conjugate (2) and (3) were 11-fold and 13-fold weaker than free streptonigrin, respectively. The results suggest that the conjugates of McAb 3A5 and streptonigrin show specific cytotoxicity to target liver cancer cails. The linkage groups of streptonigrin were also discussed.


[Synthesis of O,O'-dialkyl-O''-(5-substituted-3-benzothienglyoxylonitrile oximino) phosphates and thiophosphates]. In order to search for potential molluscicidal synergists, eighteen O,O'-dialkyl-O''-(5-substituted-3-benzothienglyoxylonitrile oximino) phosphates and thiophosphates were synthesized. Preliminary biological screening showed that compounds I2,3,7,11,12 combined with sodium pentachlorophenate exhibited significant molluscicidal synergism against snails (Oncomelanis hupensis).


[Studies on chemical constituents of the roots of Lantana camara]. Six oligosaccharides (I-VI) and six iridoid glucosides (VII-XII) isolated from the ethanolic extract of Lantana camara roots were identified as stachyose (I), verbascose (II), ajugose (III), verbascotetracose (IV), alpha-D-galac-(1-[-6)-alpha-D-galac(-1](3)-6-D-gluc(V ) , alpha-D-galac-(1-6)-alpha-D-galac(-1]-(4)6-D-)gluc(VI) , theveside (VII), 8-epiloganin (VIII), shanzhsid methyl ester (IX), theviridoside (X), lamiridoside (XI) and geniposide (XII), on the basis of spectral analysis (1H-NMR, 13C-NMR, FD-MS, GC-MS), physico-chemical constants and preparation of derivatives. V and VI were new compounds named lantanose A and lantanose B, respectively. The others were isolated from this plant for the first time.


[System of crystal structure analysis on pc computer--NOMCSDP package]. The package of crystal structure analysis--NOMCSDP (Natural Organic Molecule Crystal Structure Determination Package) Version 1.0 has been developed on the widely used IBM PC computer. It can perform the whole task of X-ray crystal structure analysis, as well as can be used for computing crystal structure on neutron diffraction. NOMCSDP has many advantages--easy operation, less needs for specialized crystallographic knowledge, wide applicability of solving structure, and having all the necessary functions. The inexorable trend of X-ray crystal structure analysis in the course of realizing the wide spread use in determining molecular structure of natural products was discussed and the practical uses of NOMCSDP were illustrated with examples. We hope that this version will play active role in the process of promoting routine use of crystal structure analysis.


[Studies on the chemical constituents from Aralia elata]. Eight compounds have been isolated from the root bark of Aralia elata. Their structures have been identified by means of physico-chemical and spectral analysis. They are (6'-O-palmitoyl)-beta-sitosterol-3-O-beta-D-glucoside (A5), silphiosideA (A9), chikusetusaponin Ib (A11), araloside A (A12), araloside C (A15), acanthoside D (B1). Compound A10 is a new natural product, named as araloside A methyl-ester. 3-O-beta-D-glucopyranosyl (1----3)[beta-D-glucopyranosy (1----4)]-beta-D-glucopyranosyl-oleanolic acid-28-O-beta-D-glucopyranoside (A16) is a new compound, named as araloside G. Compounds A5, A9, A10, A11, A16, and B1 were isolated for the first time from the plant. 13C-NMR chemical shifts of compounds A9 and A15 were assigned for the first time.


[Studies on the analytical method of a new anti-arrhythmic guan-fu base A in rabbit plasma]. Guan-fu base A, a new antiarrhythmic alkaloid with a structure of C20-diterpenoid, was first isolated from the tuber of Aconitum coreanum (Levl.) Raipaics in China in 1966. An analytical method of GC-ECD has been established in this paper for the determination of its concentration in rabbit plasma in order to study its pharmacokinetics in preclinical pharmacology. Guan-fu base A and the internal standard alprenolol (ALP) was found to react rapidly and quantitatively with trifluoroacetic anhydride (TFAA) to produce derivatives GFA-TFAA and ALP-TFAA which were identified by GC-MSD. An optimal GC-ECD system for the separation and determination of the derivatives following the sample preparation was established. There was a wide linear range of the method from 10-2 x 10(4) ng/ml (r = 0.9984). The average recovery of Guan-fu base A from the spiked plasma was 97.52%. The coefficient of variation of between-day and within-day were less than 9% and 7%, respectively. The method was used to determine Guan-fu base A in the plasma of 15 rabbits following intravenous administration of 3 dosages of 0.4, 2 and 10 mg per kg of body weight.


[Reversed phase high performance liquid chromatography of tetracyclines]. The present paper describes a quantitative determination method of tetracyclines by reversed phase high performance liquid chromatography. The method used a Waters 10 C18 4.6 nm ID x 250 nm reversed phase column, with a mobile phase composed of 14% acetonitrile-3% dimethylformamide-83% water containing 0.02 mol/L citric acid (pH-2.5), the detector wavelength was set at 350 nm, and the flow rate was maintained at 1.0 ml/min. Demethylchlortetracycline, epi-demethylchlortetracycline, demethyltetracycline, epi-demethyltetracycline, tetracycline, epi-tetracycline, chlortetracycline and epi-chlortetracycline can be separated highly efficiently. The tetracyclines and their anhydro- products can be separated on the same column with 15% acetonitrile- 15% dimethylformamide- 70% 0.02 mol/L citric acid as the mobile phase, and detected at UV 270 nm.


[Obtaining natural light photostability of drugs from lamp light exposure experiments]. The photostability of vitamin B2, vitamin K3, zinc sulfadiazine and vesnarinone, and the equivalent influences of different light sources on the photostability of the above drugs were studied under natural light and lamp lights. From this study, the photostability of drugs under different light sources can be converted to each other, and the natural light photostability of drugs can be conveniently obtained from lamp light exposure experiments. The relationship between the surface reflectance of the above drugs and the cumulative illumination of different light sources can be formulated as R = A + B(Et) + C/(Et + D) accurately, and the cumulative illumination of different light sources irradiated on the above drugs can be converted to each other equivalently.


Determination of arctiin and arctigenin in Fructus Arctii by reverse-phase HPLC. The fruits of Arctium lappa L. is an often-used herbal drug in traditional Chinese medicine for the treatment of common cold caused by wind and heat. This drug contained many constituents, principally arctiin, with arctigenin in smaller amount. In this work, arctiin has been isolated from the fruits of Arctium lappa, and then enzymolyzed into arctigenin. The obtained arctiin and arctigenin were characterized and then used as standards for their determination in the crude drug by HPLC. The method is simple, rapid and accurate.


[Simultaneous determination of propafenone and its active metabolite in serum by high performance liquid chromatography]. A rapid, sensitive and simple high performance liquid chromatographic method for the simultaneous determination of propafenone (PPF) and its metabolites (5-hydroxypropafenone, 5-OHP; N-depropylpropafenone, NDP) in serum has been developed. Separation of PPF, 5-OHP and NDP was achieved by reversed phase chromatography using a mobile phase consisting of 57% methanol and 43% 10 mmol/L potassium dibasic phosphate (pH 2.7) at a flow rate of 1.0 ml/min on a 5 microns ODS-C18 column. The eluent was monitored at 254 nm. The method showed a good linearity. The recoveries of PPF, 5-OHP and NDP were found to be 99.54 +/- 2.13%, 100.02 +/- 3.66% and 100.48 +/- 3.10%, respectively. Precision studies for both within day and day-to-day at different concentrations provided RSD values of less than 5%. Some commonly used drugs can be determined in the same procedure without interference except phenytoin. This method is well adapted to the therapeutic monitoring of PPF treated patients, as well as for pharmacokinetic studies.


[Pharmacognostical studies on Baibu radix stemonae and allied drugs. IX. Determination and evaluation of total alkaloid content in the roots of Chinese Stemona spp]. An acid-dye colorimetric method was reported for the determination of total alkaloids in 53 samples of Baibu drugs from their growing destricts in 14 provinces and municipalities and its average recovery and its linear range were 96.1% (CV less than 4%) and 20-150 micrograms respectively. The relationship between the total alkaloid content, geographical origins and morphology were discussed. The results showed that: 1. the content of total alkaloids of stemona was 0.26-3.1%; 2. that of Stemona sessilifolia was 0.26-2.17% with the highest content of the sample from Nanyang country in Henan Province; 3. that of S. japonica was 0.83-1.43%; 4. that of S. tuberosa was 0.53-3.1% with the highest content of sample from Hengyang in Hunan Province; 5. that of S. parviflora was 0.22-0.74% with the highest content of sample from Qongzhong in Hainan Province; and 6. that of more yellow, solider and stronger samples was higher than that of any other samples. However, that of all bigger samples in shape was not higher than that of smaller ones.


[Surface activity of emulsifiers. Part IV. Determination of the contact angle at the interface of two liquids]. A method has been worked out for the determination of wetting contact angle formed at the interface of oil/water and/or aqueous and oleaginous solutions of surfactants, respectively. Contact angle proved to be an accurate and well reproducible index. The size of contact angle decreased logarithmically along with the concentration of tensids. Several samples of the emulsifier series tested, induced interfacial tension in 1-1.5%, and the wetting contact angle did not decrease further above this concentration. Correlation and a non-linear regression was found between the contact angle and the interfacial tension.


[Effect of interferon and interferon combined with 3-methylcholanthrene on the mixed function oxidase system in the liver of mice]. The authors have studied the effect of human interferon alpha alone, as well as its effect when co-administered with 3-methylcholanthrene, on the mixed function oxidase system (MFO) of mouse liver. The single interferon alpha treatment did not influence the activities of MFO. However it decreased significantly the enzyme-inducing effect of 3-methylcholanthrene during combined treatment.


Sensitive colorimetric determination of copper (II) ions in some chemicals and multivitamins. A sensitive and selective colorimetric method has been devised for the micro-determination of copper (II) ions in pure form, some chemicals and multivitamin preparations. The method depends on the formation of stable blue complexes in ammonia medium peaking at 615 nm between copper (II) ions, oxalyldihydrazide and one of the following aldehydes: 4-nitrobenzaldehyde, 2-nitrocinnamaldehyde and formaldehyde with minimum detection limits 0.1, 0.16 and 1.1 ppm, respectively. Several metal ions do not interfere. The optimum reaction conditions were studied and the results obtained were favorably comparable to the diethyldithiocarbamate method.


[Effect of pretreatment with immunomodulating agents on the outcome of lymphocytic choriomeningitis virus infection in athymic (nude) and euthymic mice]. Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP-4 (a synthetic tetrapeptide, thymopoietin sequence analog, Pharmaceutical Product's Factory Gedeon Richter, Budapest, Hungary) or with Mannozym (0.1% zymosan suspension, Institute for Serobacterological Production and Research, HUMAN, Budapest, Hungary), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently they stimulated the cellular immune response in euthymic mice, but the athymic mice, either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection. The results showed that the cellular immune response stimulating effect by both agents was thymus-dependent. Using these agents immunostimulatory effect can be realized only in the presence of the thymus or the T-dependent lymphoid system, respectively.


[Analytic and biological standardization of Prunus avium extracts]. Novicardine, the acetonic extract of P. avium peduncle which has advantageous cardiotonic effect, was standardized chemically and biologically. Flavonones, flavones, isoflavones and their glycosides were (methanolbuffer solution eluent, gradient elution) detected by reverse phase HPLC technique. It has been found that substances produced from different varieties of cherry peduncle originated from various lands, have the same components and their ratios are similar, but a contradictory statement could be made in the case of sour cherry. The allowed area ratios belonging to some ingredients were stated with reference to dihydrowogonine-7-O-glucoside. The biological experiments were performed on isolated heart preparations. In the organ bath with Locke's solution content the suspended left atrium and the papillary muscle were driven by rectangular electric impulses of 1 msec duration and of 1.7 Hz frequency, whereas the right atria were beating spontaneously. The result of experiments demonstrated that the standard Novicardine improves the contraction force of heart muscle by some 20-25%, and at the same time doesn't exert influence on the basic electrophysiological parameters and doesn't cause significant changes in heart rate. On the basis of investigation of substances having modified componentratio it was stated that extracts could be isolated which have cardiotonic effect four times stronger than that of Novicardine, on the other hand there were some extracts having negative inotropic effect. These effects were brought into connection with families of compounds (mainly glycosides and aglycones). It seems that the big variety of Novicardine can be assigned to the individual sensitivity of heart preparations, and the ratios of the above mentioned compounds.


Increase of blood glucose concentrations in diabetic patients with glucagon eyedrops. Hypoglycemic crisis is a common occurrence in diabetic patients. In order to reverse the hypoglycemia, glucagon eyedrops at concentrations of 2.5%, 5.0%, and 7.5% were instilled to the eyes of diabetic patients who were fasted overnight. The glucagon eyedrops raised the blood glucose efficiently in a dose-dependent manner and peaked at 30 min after drug instillation. At 2.5%, glucagon raised the blood glucose 0.83 mmol.L-1 which exceeded the minimal requirement of 0.56 mmol.L-1 increase in blood glucose level at hypoglycemic crisis. At 5.0% and 7.5%, glucagon eyedrops increased the blood glucose level further to 1.76 and 1.91 mmol.L-1, respectively. These results indicate that glucagon can be delivered effectively through ocular route to raise the systemic blood glucose for the treatment of hypoglycemic crisis.


Effects of permeation enhancers BL-9 and Brij-78 on absorption of four peptide eyedrops in rabbits. Systemic absorption of 4 peptide drugs through ocular route was enhanced by permeation enhancers, BL-9 and Brij-78. Gonadorelin (LHRH) was the smallest molecule (M(r) = 1200) and its systemic delivery was most efficiently enhanced by BL-9 (17.0-20.8 times) and Brij-78 (13.9-21.5 times). Although bombesin (M(r) = 1620), atrial natriuretic peptides (ANP) (M(r) = 3240), and adrenocorticotropic hormone (ACTH) (M(r) = 4540) had molecular weight ranged widely, their systemic absorption through ocular route was enhanced by BL-9 (6.1-8.3 times) and Brij-78 (6.5-9.0 times) in about the same degree. BL-9 enhanced systemic absorption of peptide drugs faster and reached peak peptide concentrations in 5-20 min. On the other hand, Brij-78 took 20-60 min to reach to peak concentration of peptide drugs in the blood. These results indicate that systemic delivery of peptide drug through ocular route is a feasible one particularly when the absorption enhancers are used.


Effect of dizocilpine maleate on monoamines and their metabolites in rat brain. Systemic (ip) injection of dizocilpine maleate (DM, 0.1 and 0.5 mg.kg-1) increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid but did not bring about any noticeable change in the dopamine (DA) level in the striatum and limbic area. DM also increased the levels of norepinephrine in the limbic area and 5-hydroxyindoleacetic acid in the hippocampus. Amphetamine increased DA level and reduced DOPAC level in the striatum and limbic area. The behavioral manifestations revealed that DM predominantly evoked circling behavior and ataxia. The results indicate that the mechanism of the behavioral effect of DM may be different from that of amphetamine.


Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity. Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effect of Ful on acetaminophen (AA)-induced hepatotoxicity in mice. Ful pretreatment (75-225 mg.kg-1, sc x 3 d) significantly decreased AA (500 mg.kg-1, ip)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Ful pretreatment (225 mg.kg-1, sc x 3 d) decreased hepatic cytochrome P-450, cytochrome b5, and NADPH-cytochrome c reductase by approximately 15-20%. Microsomes from Ful-pretreated mice, incubated in vitro with AA, produced less AA-glutathione. A 28% increase in urinary excretion of AA-glucuronide was observed in Ful (150 mg.kg-1, sc x 3 d) pretreated mice. Ful pretreatment had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronyltransferase activity towards AA. In summary, Ful pretreatment protects against AA-induced hepatotoxicity. One of the mechanisms for this protection appears to be the decreased AA toxic activation via P-450, as well as increased detoxication via glucuronidation of AA.


Protective effects of fulvotomentosides on cadmium-induced hepatotoxicity. Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effects of Ful on cadmium (CdCl2)-induced acute liver injury in mice. Ful pretreatment (150 mg.kg-1, sc x 3 d) remarkably decreased CdCl2 (3.7 mg Cd.kg-1, iv)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Distribution of Cd to 12 organs and hepatic subcellular fractions was determined 2 h after Cd challenge. Ful pretreatment did not produce a marked shift in the distribution of Cd to various organs, but markedly altered the hepatic subcellular distribution of Cd, with more Cd bound to metallothionein (MT) in the cytosol, less in the nuclear, mitochondrial, and microsomal fractions. Ful pretreatment produced a dose-dependent increase in hepatic MT as determined by the Cd.hemoglobin assay. In conclusion, Ful protected against Cd hepatotoxicity by inducing MT, which binds Cd in the cytosol and lowers the amount of Cd available to other critical organelles and proteins.


Neuroprotective effects of phencyclidine on acute cerebral ischemia and reperfusion injury of rabbits. Acute cerebral ischemia and reperfusion injury of rabbits was produced by permanently occluding the vertebral arteries and temporarily clamping the common carotid arteries for 30 min. Phencyclidine [1-(phenylcyclohexyl)piperidine, PCP] 40-80 micrograms.kg-1 icv 30 min before ischemia significantly attenuated the decrease of the total power of electroencephalogram (EEG) within 30 min of ischemia and improved the recovery of brain electric activity following reperfusion. PCP 20-80 micrograms.kg-1 dose-dependently suppressed the creatine kinase (CK) release during cerebral ischemia and reperfusion, and PCP 40-80 micrograms.kg-1 reduced brain ischemic damage. These improvements indicated that PCP has protective effects on acute cerebral ischemia and reperfusion injury.


Acetylcholine contents and muscarinic receptor levels in frontal cortex, corpus striatum, and hippocampus of reserpinized rats and mice. The acetylcholine (ACh) levels in rat and mouse frontal cortex increased 155% and 124%, respectively, 24 h after ip reserpine 3 mg.kg-1. Striatal ACh contents, however, were diminished by 47% in rats and 80% in mice. ACh contents elevated 50% and scopolamine (Scop) depleted the ACh by 47% in mouse striatum 12 h following reserpine. Receptor binding assay showed that 24 h after reserpine the Bmax of [3H]quinuclidinyl benzilate ([3H]QNB) binding to muscarinic receptors increased in frontal cortex (by 33% in rats, by 30% in mice) and decreased in striatum (31% in rats, 26% in mice). In mouse hippocampus the ACh contents, Bmax, and affinity of muscarinic receptors lowered 63%, 19%, and 26%, respectively. But these changes were not seen in rat hippocampus.


Protective effect of cycloprotobuxine-A against cardiac arrhythmias induced by ouabain. Cycloprotobuxine-A (CPB-A) 1-4 mg.kg-1 iv increased the dose of ouabain required to induce ventricular arrhythmias in guinea pigs. At the equitoxic doses (1/50 LD50), CPB-A was more potent than cyclovirobuxine-D and amiodarone. Pretreatment with reserpine (5 mg.kg-1 ip), vagotomy or pithing spinal cord did not prevent the action of CPB-A, which indicate that the protective effect of CPB-A may be due to its direct action on myocardium without the involvement of nervous system. In isolated guinea pig ventricular muscles, CPB-A 3 mumol.L-1 consistently decreased the amplitude of oscillatory afterpotentials (OAP) and blocked triggered activity elicited by ouabain. At 30 mumol.L-1, CPB-A abolished the appearance of OAP. It seems that one of the mechanisms for the anti-arrhythmic action of CPB-A was a decrease in the amplitude of OAP.