Chronic hypoxia differentially alters the responses of pulmonary arteries and veins to endothelin-1 and other agents.

The effects of chronic hypoxia on the responses of rat large pulmonary arteries and veins to vasoactive agents have been examined. Endothelin-1-induced contractions of pulmonary arteries and pulmonary veins were reduced by chronic hypoxia. In contrast, chronic hypoxia augmented sarafotoxin 6c-induced contractile responses in pulmonary veins but not in pulmonary arteries. Chronic hypoxia augmented the constrictor effect of phenylephrine in pulmonary arteries, but not in pulmonary veins. The thromboxane receptor agonist, U46619 (9,11-dideoxy-9alpha,11alpha-epoxy-methanoprostaglandin++ + f2alpha) contracted pulmonary arteries and pulmonary veins, and although maximal responses were not altered in chronically hypoxic preparations, the EC50 value in pulmonary arteries was increased following chronic hypoxia. The relaxant effects of acetylcholine and isoprenaline on pulmonary arteries were potentiated by chronic hypoxia. In contrast, ionomycin-mediated relaxations of pulmonary arteries and pulmonary veins were reduced, while sodium nitroprusside-induced relaxation of pulmonary arteries and veins were not altered by chronic hypoxia. Previous studied have looked primarily at the effects of chronic hypoxia on pulmonary arteries. This data provides evidence that chronic hypoxia also causes selective changes in the reactivity of large pulmonary veins.     

Genetics of Alkaloids in Papaver somniferum

Based on numerical and graphic analyses of 6 x 6 diallele cross progenies (n (2) = 36) over two environments, dominance was found to be most prevalent (in overdominance range without being inflated by non-allelic interactions) in parents for latex yield, and morphine, codeine, thebaine, and narcotine contents. However, the additive component was also significant for the former three traits. Dominant alleles mostly with positive effects were, by and large, asymmetrically distributed in parents except for narcotine content. Heritability estimates were moderate and corresponded with low genetic advance estimates for morphine, codeine, and thebaine contents. Ample genetic diversity among parents was reflected for all traits except narcotine content. On an overall basis, heterosis breeding was suggested to be a rewarding proposition for genetic improvement of the opium poppy ( PAPAVER SOMNIFERUM L.).     

Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil.

Synthetic benzodiazepines produce an anterograde amnesia, which can be reversed by selective benzodiazepine antagonists or inverse agonists. It has therefore been suggested that the memory-enhancing effects of the antagonists are due to antagonism of an endogenous "benzodiazepine-like" endocoid. If the memory-enhancing effects of the benzodiazepine antagonists are determined predominantly by the antagonism of such endogenous benzodiazepine-ligands, then it could be hypothesized that administration of an inverse agonist, which produces effects functionally opposite to those of benzodiazepine agonists, may also mimic the effects of benzodiazepine antagonists but not produce effects greater than those of the pure antagonists. The purpose of the present study was therefore to investigate the memory-enhancing effects of the benzodiazepine inverse agonist, ethyl-8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate (Ro 15-4513) in young HSD:(ICR)BR mice and to compare these effects with those of the benzodiazepine antagonist, flumazenil. Pretraining injections of flumazenil and Ro 15-4513 (2.5 and 10.0 mg/kg) enhanced equally, both the acquisition and the retention of a task for 1 week requiring mice to discriminate the correct arm of a T-maze, to avoid a mild electric shock. Pretreatment with Ro 15-4513 also dose-dependently protected the animals from experimental amnesia, induced by the cholinergic receptor antagonist, scopolamine in a second model of memory, in which mice were required to passively avoid a dark chamber after shock. In contrast, Ro 15-4513, injected prior to daily active avoidance sessions, failed to significantly improve either the acquisition or retention performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inheritance of Biomass Yield and Tropane Alkaloid Content in Hyoscyamus muticus

The nature of gene action for biomass yield and tropane alkaloid content was ascertained through diallel analysis in Egyptian henbane, HYOSCYAMUS MUTICUS L. Dominance variation was preponderant over additive genetic variance, dominance being in the overdominance range for both traits. On an overall basis, recessive alleles had a positive (i.e. increasing) effect on both the characters. However, the positive or negative effects of recessive or dominant alleles were genotype-specific. Hence, transgressive breeding was suggested for isolating segregants with dominant alleles for herb yield and with recessives for alkaloid content so as to achieve overall high yields of tropane alkaloid per unit area.     

Within-subject behavioral analysis of recent memory in aging mice

Two experiments addressed the utility of a T-maze, delayed reversal paradigm for assessment of recent memory impairment in aging C57BL/6NNia mice. This paradigm involved acquisition of a learning set for identification of the correct arm choice in a daily multiple-trial discriminated avoidance session. During each session, the correct arm was always opposite that entered on an initial "information trial" and maximal performance thus required a reversal (or "lose-shift") strategy. Once the learning set had been acquired, retention performance was examined following delays of varying length which were introduced following the information trial during each session. In the first experiment, acquisition and retention components of delayed reversal were considered in a cross-sectional study involving separate groups of mice aged 7, 10, 15, or 27 months. Analysis of acquisition components suggested that relative to young mice, the old mice were slower to acquire both the first reversal and the learning set. Analysis of the retention phase suggested that memory decay gradients for goal arm discrimination became more pronounced with increasing age, whereas decay gradients for the avoidance response were similar among the age groups. Correlational analysis of data for the old mice suggested independence of age-related deficits in the acquisition and recent memory components of the delayed reversal paradigm. In the second experiment, survivors from the previous 7- and 10-month-old groups were retested when 27 months of age. The cross-sectional and longitudinal data led to the same conclusions with regard to the effect of age on recent memory function. Overall, these results suggest that the delayed reversal paradigm will be a valuable tool in the analysis and evaluation of interventions potentially affecting age-related cognitive impairment.     

Neurobehavioral biomarkers of aging: influence of genotype and dietary restriction

Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important "neurobehavioral" markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.     

Meningoencephalitis in brucellosis

Human brucellosis, more specifically neurobrucellosis, is a less commonly reported disease in India; although, animal brucellosis and seroprevalence in specific areas is well reported. We are reporting 4 cases of neurobrucellosis presenting as meningoencephalitis. Diagnosis was confirmed by serological test and agglutination titre was > 1:320 in all the patients. All these patients had close contact with animals and history of raw milk ingestion was present in 3 cases. The aim of presenting these cases is to create awareness among physicians while treating meningitis in persons, engaged in occupations related to brucellosis or having a history of ingestion of raw milk or milk product.     

Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children's Cancer Group Study.

PURPOSE: The long-term survival of children between age 12 and 24 months with stage 4 neuroblastoma and nonamplified MYCN (MYCN-NA) has not been defined previously. PATIENTS AND METHODS: Survival for stage 4 MYCN-NA neuroblastoma patients enrolled onto Children's Cancer Group (CCG) protocols 321P2 (1986 to 1991) and 3891 (1991 to 1996) was analyzed. Treatment consisted of intensive alkylator-based induction chemotherapy with or without autologous bone marrow transplantation (ABMT) with or without 13 cis-retinoic acid. Survival was analyzed by age strata less than 12, 12 to 18, 18 to 24, and more than 24 months at diagnosis. Patients younger than 12 months were treated on the moderate-intensity CCG protocol 3881. RESULTS: Forty-three patients with stage 4 MYCN-NA disease enrolled onto CCG-321P2 (n = 17) or CCG-3891 (n = 26) were between 12 and 24 months of age at diagnosis. After a median follow-up of 94 months (range, 4 to 140 months), the 6-year event-free survival (EFS) for the 12- to 18-month age group was superior to that of the 18- to 24-month age group (74% +/- 8% v 31% +/- 12%; P = .008). The EFS for children older than 24 months with stage 4 MYCN-NA neuroblastoma was 23% +/- 3%, and for children younger than 12 months was 92% +/- 3%. CONCLUSION: Children diagnosed with stage 4 MYCN-NA neuroblastoma in the second year of life form a transitional group between infants and older children in terms of prognosis. Patients between 12 and 18 months of age have significantly better long-term survival than that of older children treated with intensive chemotherapy with or without ABMT. These patients may not benefit from additional intensification of therapy beyond that provided in earlier clinical trials and may even maintain this high survival rate with less intensive therapy.