Pre-erythrocytic stages of plasmodia. Role of specific and nonspecific factors

Protection against pre-erythrocytic stages of malaria is possible as demonstrated by the generation of resistance after immunization with irradiated sporozoites. However, mechanisms involved are more numerous and intricate than previously believed and it progressively appears that the role of the presumed target, the sporozoite, might be negligible compared with that of the hepatic stage. The comparative use of in vivo and in vitro models clearly demonstrates that the intrahepatocytic parasite can be the target of antibodies, cytokines, phagocytic and cytotoxic cells, nonspecific factors--mechanisms in part induced by the previous or subsequent developmental stages.     

遗传多样性在啮齿动物研究中的应用

遗传多样性是物种多样性和生态系统多样性的基础,也是生命进化和物种分化的前提,更是评价自然生物资源的重要依据.遗传多样性在种类繁多的啮齿动物研究中得到广泛应用,本文综述了啮齿动物遗传多样性在鼠害防控、啮齿动物起源和分化及进化历史、啮齿动物的适应潜力、种群数量动态和调节机制、保护生物学方面研究中的应用,提出今后应系统论证种群数量动态与遗传多样性之间的关系,并对啮齿动物遗传多样性进行长期监控.
     

Cellular damage in the rat heart caused by caffeine or dinitrophenol

1. Langendorff-perfusion of rat hearts with either 10 mM caffeine or 1 mM 2,4-dinitrophenol (DNP) caused severe ultrastructural damage to the myofilaments and mitochondria that was similar to that found in a standard Ca²⁺-paradox.2. This damage occurred in the presence and absence of extracellular Ca²⁺3. Creatine kinase (CK) release (indicative of sarcolemma breakdown) was not recorded unless the caffeine- or DNP-perfusion was preceded by Ca²⁺₀-depletion.4. It is concluded that: (i) the pathways leading to damage to the myofilaments and sarcolemma are independent; (ii) the CK release mechanism requires dual activation of Ca²⁺₀-depletion plus a rise in [Ca²⁺]_i; and (iii) current theories concerning the mechanisms underlying the genesis of the Ca²⁺-paradox are incorrect or incomplete.     

Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents.

Long chain fatty acid transport is selectively up-regulated in adipocytes of Zucker fatty rats, diverting fatty acids from sites of oxidation toward storage in adipose tissue. To determine whether this is a general feature of obesity, we studied [(3)H]oleate uptake by adipocytes and hepatocytes from 1) homozygous male obese (ob), diabetic (db), fat (fat), and tubby (tub) mice and from 2) male Harlan Sprague-Dawley rats fed for 7 weeks a diet containing 55% of calories from fat. V(max) and K(m) were compared with controls of the appropriate background strain (C57BL/6J or C57BLKS) or diet (13% of calories from fat). V(max) for adipocyte fatty acid uptake was increased 5-6-fold in ob, db, fat, and tub mice versus controls (p < 0.001), whereas no differences were seen in the corresponding hepatocytes. Similar changes occurred in fat-fed rats. Of three membrane fatty acid transporters expressed in adipocytes, plasma membrane fatty acid-binding protein mRNA was increased 9-11-fold in ob and db, which lack a competent leptin/leptin receptor system, but was not increased in fat and tub, i.e. in strains with normal leptin signaling capability; fatty acid translocase mRNA was increased 2.2-6.5-fold in tub, ob, and fat adipocytes, but not in db adipocytes; and only marginal changes in fatty acid transport protein 1 mRNA were found in any of the mutant strains. Adipocyte fatty acid uptake is generally increased in murine obesity models, but up-regulation of individual transporters depends on the specific pathophysiology. Leptin may normally down-regulate expression of plasma membrane fatty acid binding protein.     

Role of genetic factors in the formation of trace reactions in man

Trace processes due to presentation of visual nonverbal information, and the dynamics of the bioelectrical parameter (mean level of asymmetry of EEG-waves) were studies in 32 pairs of monozygote and 38 pairs of dizygote twins with twins method. Statistical processing of the data revealed a significant effect of genetic factors on the formation of individual variability of the characteristics of trace processes in humans. The results obtained showed that with increased functional load the intrapair similarity of trace reactions increased in monozygote twins and did not change or decrease in dizygote twins and in unrelated pairs. This fact is interpreted at a dependence of appearance of geneticly determined neurophysiological characteristics on the level of functional activity of the nervous system.     

Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite

Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation and oxidative stress. Although the drug has been assumed to act by preventing the up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction with reactive oxygen species. The antibiotic did not react with superoxide or ^•NO radicals, but peroxynitrite (PON) was scavenged in the range of ∼1 μm minocycline and below. The interaction of pharmacologically relevant minocycline concentrations with PON was corroborated in several assay systems and significantly exceeded the efficacy of other antibiotics. Minocycline was degraded during the reaction with PON, and the resultant products lacked antioxidant properties. The antioxidant activity of minocycline extended to cellular systems, because it prevented neuronal mitochondrial DNA damage and glutathione depletion. Maintenance of neuronal viability under PON stress was shown to be solely dependent on direct chemical scavenging by minocycline. We chose α-synuclein (ASYN), known from Parkinsonian pathology as a biologically relevant target in chemical and cellular nitration reactions. Submicromolar concentrations of minocycline prevented tyrosine nitration of ASYN by PON. Mass spectrometric analysis revealed that minocycline impeded nitrations more effectively than methionine oxidations and dimerizations of ASYN, which are secondary reactions under PON stress. Thus, PON scavenging at low concentrations is a novel feature of minocycline and may help to explain its pharmacological activity.     

Role of IL-6 in the pleurisy and lung injury caused by carrageenan.

In the present study we used IL-6 knockout mice (IL-6KO) to evaluate the role of IL-6 in the inflammatory response caused by injection of carrageenan into the pleural space. Compared with carrageenan-treated IL-6 wild-type (IL-6WT) mice, carrageenan-treated IL-6KO mice exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung myeloperoxidase activity and lipid peroxidation were significantly reduced in IL-6KO mice compared with those in IL-6WT mice treated with carrageenan. Immunohistochemical analysis for nitrotyrosine and poly(A)DP-ribose polymerase revealed a positive staining in lungs from carrageenan-treated IL-6WT mice. No positive staining for nitrotyrosine or PARS was found in the lungs of the carrageenan-treated IL-6KO mice. Staining of lung tissue sections obtained from carrageenan-treated IL-6WT mice with an anti-cyclo-oxygenase-2 Ab showed a diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-6WT mice. The intensity and degree of the staining for cyclo-oxygenase-2 and inducible nitric oxide synthase were markedly reduced in tissue sections obtained from carrageenan-treated IL-6KO mice. Most notably, the degree of lung injury caused by carrageenan was also reduced in IL-6KO mice. Treatment of IL-6WT mice with anti-IL-6 (5 microg/day/mouse at 24 and 1 h before carrageenan treatment) also significantly attenuated all the above indicators of lung inflammation. Taken together, our results clearly demonstrate that IL-6KO mice are more resistant to the acute inflammation of the lung caused by carrageenan injection into the pleural space than the corresponding WT mice.     

Role of genetic factors in the epidemic process in respiratory viral infections

Observations carried out during 1973-1979 indicate that persons, who are frequently ill, determine the incidence of influenza and acute respiratory diseases among various groups of adult population at all epidemic periods. In constantly observed groups of different ages such persons were the source of 60-85% of the outbreaks of acute respiratory diseases. The correlation between genotypic blood markers (the ABO and HLA systems) and susceptibility to respiratory viruses has been established.