Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine.

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.     

High alveolar surface tension increases clearance of technetium 99m diethylenetriamine-pentaacetic acid.

The effect of high alveolar surface tension on alveolar epithelial permeability was studied in anesthetized closed-chest mongrel dogs. Alveolar surface tension was elevated by displacement of pulmonary surfactant from the alveolar hypophase by the aerosolized detergent dioctyl sodium sulfosuccinate (OT). After measurement of baseline hemodynamics, arterial blood gases, and airway pressure, the dogs were separated into groups: Group I inhaled a 1% solution of OT (15 mg/kg) in a vehicle of equal parts saline and ethanol; group II inhaled the same volume of vehicle without OT. The pulmonary clearance of technetium 99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) (half-time in minutes) was studied immediately after aerosol (OT and vehicle) delivery and compared with that of historical control values. No change was seen in arterial blood gases and airway pressure after vehicle inhalation, whereas OT caused a marked fall in arterial oxygen tension and increase in airway pressure. Vehicle inhalation effected only a slight increase in DTPA clearance, whereas OT significantly reduced half-time over control and group II. These data suggest that high alveolar surface tension increases alveolar epithelial permeability.     

Scientific and regulatory issues relevant to assessing risk for developmental neurotoxicity: an overview

The effects of chemical exposure on the developing nervous system have been documented in both humans and animals for a variety of agents. However, the comparability of these effects has not been carefully evaluated to determine the predictability of animal models to adverse effects in humans. A workshop sponsored by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse was held on April 11-13, 1989, to address the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity. Invited experts were asked to review the human and animal data on several agents that are known to cause developmental neurotoxicity in humans, including lead, methylmercury, selected abused agents, anticonvulsants, polychlorinated biphenyls (PCBs), ethanol and X-irradiation, and to make quantitative comparisons on a specific end point basis as well as on a functional category basis. In addition, they were asked to make quantitative comparisons when adequate dose-effect data were available. The data also were evaluated in the context of the proposed EPA developmental neurotoxicity testing battery to determine whether or not the battery would adequately detect the effects of each agent. Finally, four work groups were asked to reach consensus on issues relating to: 1) comparability of end points across species for developmental neurotoxicity; 2) testing methods in developmental neurotoxicity for use in human risk assessment; 3) weight-of-evidence and quantitative evaluation of data from developmental neurotoxicity studies; and 4) triggers for developmental neurotoxicity testing.     

Hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness

The hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness (CCB) were studied. We propose that there is a linkage between the two loci on the X-chromosome determining CCB and glucose-6-phosphate dehydrogenase (G6PD), based on our study of a high incidence of G6PD deficiency in 156 male cases with CCB. The CCB gene is closely linked with that of G6PD deficiency from our pedigree investigations. The rise in the frequency of eight or more whorls, the low value of atd angle and the presenting rate of real palmar patterns of the thenar, hypothenar and I, areas presented the hereditary traits of congenital color blindness.     

Biological activity of fluorinated 3,4-dihydroisoquinolines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 26, No. 1, pp. 44–45, January, 1992.     

N-unsubstituted glucosamine residues and other modifications in murein of the obligatory chemolithotroph Thiobacillus neapolitanus.

Purified murein from Thiobacillus neapolitanus was poorly digested by lysozyme. It's sensitivity to the enzyme greatly increased after N-acetylation. The murein was found to contain 30 to 35% glucosamine residues lacking N-acetyl groups. It also contained phosphomuramic acid. Further modifications included amidation of diaminopimelic acid in the peptide side chains and a low alanine content. None of these modifications were found in the murein of another sulphur bacterium, Thiobacillus versutus.     

An etiological study on fulminant viral hepatitis]

Viral markers were studied in 79 cases of viral hepatitis with hepatic failure. The results were shown as follows: 8 cases were positive for anti-HAV IgM (10.12%); 76 cases positive for HBsAg or anti-HBc IgM (96.20%) and 41 cases positive for anti-HCV antibodies (51.89%). Among those with anti-HCV positive, 35 cases were co-infected with HBV, 5 cases with HAV and/or HCV, only one was infected with HCV alone 2 cases were HD-Ag positive (2.52%) and one not identified (1.27%). With the reference of clinical findings, patients co-infected with HBV/HCV or anti-HBc IgM positive were more critical and usually entail higher mortality. In cases with HCV co-infections, the positive HBV replication markers seems to be reduced. Hepatic failure without HBV replicative markers had a high rate of hepatic coma as well as poor outcome.     

Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex.

The responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N-methyl-D-aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy.