Noninvasive measurement of potassium efflux as an early indicator of cell death in mouse embryos

Programmed cell death (apoptosis) occurs in nearly all cell types examined, including mammalian oocytes and embryos, where it may underlie some forms of infertility in humans. Although the molecular machinery participating in apoptosis have been intensely investigated, the accompanying physiological changes have not received similar attention. In this study, a novel electrophysiology technique has been employed to monitor real-time perturbations in the physiology of mouse embryos undergoing apoptosis evoked by hydrogen peroxide, diamide, and staurosporine. Despite differences in their mode of action, these agents evoked a similar early change in cellular physiology; namely, a pronounced, transient, potassium efflux through tetraethylammonium-sensitive potassium channels accompanied by cell shrinkage. Mouse zygotes exposed to 200 microM H(2)O(2) exhibited potassium efflux that elevated the potassium concentration of the media surrounding embryos by 1.4 +/- 0.1 microM. Pretreatment with tetraethylammonium inhibited this increase (0.2 +/- 0.1 microM). Our results indicate that potassium efflux through potassium channels and concurrent cell shrinkage are early indicators of cell death in embryos and that noninvasive measurements of potassium pathophysiology may identify embryos undergoing cell death prior to the manifestation of other morphological or molecular hallmarks of cell death.     

Anidulafungin: experimental therapy of fungal infections in animal models

We have reviewed the existing data on the efficacy of anidulafungin, which is the most recent echinocandin in the experimental treatment of fungal infections. The scarce published data practically only refers to disseminated and pulmonary aspergillosis and to disseminated candidiasis. Anidulafungin shows fungistatic activity against Aspergillus fumigatus, and fungicidal activity against Candida albicans and Candida glabrata.     

The role of cellular and humoral factors of body resistance in the development of experimental influenza-staphylococcal infections in mice

The clinico-experimental studies of mixed influenza-staphylococcal infection constantly point to the development of the aggravation of the infectious process due to the synergic action of the bacterial and viral infective agents. But, as shown by the authors of the present work, in those cases when the experimental infection with the virus was preceded by staphylococcal infection by 72 hours no synergism was observed. In cases of infection with adaptogenic virus the mortality rate of mice resulting from meningococcal infection was twice as low. The possible explanation of this fact is discussed.     

Decrease of core body temperature in mice by dehydroepiandrosterone

Dietary dehydroepiandrosterone (DHEA) reduces food intake in mice, and this response is under genetic control. Moreover, both food restriction and DHEA can prevent or ameliorate certain diseases and mediate other biological effects. Mice fed DHEA (0.45% w/w of food) and mice pair-fed to these mice (food restricted) for 8 weeks were tested for changes in body temperature. DHEA was more efficient than food restriction alone in causing hypothermia. DHEA injected intraperitoneally also induced hypothermia that reached a nadir at 1 to 2 hr, and slowly recovered by 20 to 24 hr. This effect was dose dependent (0.5-50 mg). Each mouse strain tested (four) was susceptible to this effect, suggesting that the genetics differ for induction of hypophagia and induction of hypothermia. Because serotonin and dopamine can regulate (decrease) body temperature, we treated mice with haloperidol (dopamine receptor antagonist), 5,7-dihydroxytryptamine (serotonin production inhibitor), or ritanserin (serotonin receptor antagonist) prior to injection of DHEA. All of these agents increased rather than decreased the hypothermic effects of DHEA. DHEA metabolites that are proximate (5-androstene-3beta, 17beta-diol and androstenedione) or further downstream (estradiol-17beta) were much less effective than DHEA in inducing hypothermia. However, the DHEA analog, 16alpha-chloroepiandrosterone, was as active as DHEA. Thus, DHEA administered parentally seems to act directly on temperature-regulating sites in the body. These results suggest that DHEA induces hypothermia independent of its ability to cause food restriction, to affect serotonin or dopamine functions, or to act via its downstream steroid metabolites.     

Ergosterol as a measure of living fungal biomass: persistence in environmental samples after fungal death

The membrane lipid ergosterol is found almost exclusively in fungi, and is frequently used by environmental microbiologists as an indicator of living fungal biomass, based on the assumption that ergosterol is labile, and therefore rapidly degraded after the death of fungal hyphae. We studied the degradation of ergosterol in environmental samples without living fungi. Under the conditions used in this study, ergosterol was very stable both when added as a pure compound and when associated with dead fungi. The decrease of ergosterol was at most 34% during 2 months when protected from sunlight. Presence of a natural bacterial assemblage did not enhance degradation over this time period, as compared to sterile controls. However, photochemical degradation was significant, and led to a 43% decrease of in ergosterol content during 24 h. These results suggest that ergosterol should be used cautiously as a biomarker for living fungi.     

Effects of successive carbon monoxide exposures on delayed neuronal death in mice under the maintenance of normal body temperature.

The 3 time carbon monoxide (CO) exposures potentiated the delayed neuronal death (DND) in comparison with that induced by single CO exposure. Deterioration of DND induced by CO exposures was observed when normal body temperature was maintained during the exposures, since CO exposure fell the body temperature to about 34 degrees C. Pretreatment with noncompetitive NMDA receptor antagonist, MK-801 (30 nmol/mouse), ameliorated DND induced by successive CO exposures under the maintenance of normal body temperature. These results suggest that the mice exposed successively to CO under the maintenance of normal body temperature is a useful hypoxic model.     

Patterns of parasitic infections of fishes in a water body with constant temperature

Patterns of parasitic infections of Schizothorax intermedius in two water bodies of North Tadjikistan (Central Asia), one with constant temperature during the whole year, the other with normal annual seasonal range of temperature fluctuations, have been studied. It has been shown that in the first water body fluctuations in occurrence of the parasites are insignificant and are not under the influence of water temperature.     

Fundal height as a predictor of early preterm triplet delivery.

The purpose of this study was to create graphs of fundal height parameters in triplet pregnancies compared with those in twin pregnancies, and to investigate whether larger fundal heights in triplet pregnancies would predispose them to earlier delivery (before 34 weeks). The subjects were 727 twin pregnant women and 133 triplet pregnant women, who delivered after 1984. Triplet pregnancies showed significantly higher fundal heights compared with twin pregnancies at each gestational age (weeks). In triplet pregnancies, a single fundal height measurement above the 90th percentile before 34 weeks yielded a sensitivity of 31.3% and specificity of 82.4% for delivery before 34 weeks, with a positive predictive value of 50.0% and a negative predictive value of 68.0%. After adjusting for each associated factor using logistic regression, the risk of preterm labour was not significantly associated with a single fundal height measurement above the 90th percentile recorded before 34 weeks.     

Cytokines in the treatment of fungal infections

The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon- has been very effective as a modulator of resistance against a variety of fungal infectionsin vitro. The effect of interferon- against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon- enhances the elimination ofCandida, and consequently the agent is not effective in severly granulocytopenic animals. Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed.Abbreviations CGD chronic granulomatous disease - G-CSF granulocyte colony-stimulating factor - M-CSF monocyte colony-stimulating factor - GM-CSF granulocyte-monocyte colony-stimulating factor - IFN- interferon-gamma - IL interleukin - LAK lymphokine-activated killer - LPS lipopolysaccharide - MDP muramyl dipeptide - NK natural killer - PMN polymorphonuclear leukocytes - rh recombinant human - ROI reactive oxygen intermediates - TNF tumor necrosis factor     

艾滋病患者侵袭性真菌感染的治疗

艾滋病患者由于严重免疫缺陷而易于并发各种机会感染和肿瘤。高效抗反转录病毒联合治疗(HAART)的出现明显改善了艾滋病患者的预后,提高了患者生存质量,随着HAART在临床的广泛使用,艾滋病患者出现各种机会感染包括侵袭性真菌感染的概率大大降低。然而,由于我国艾滋病患者明确诊断时大多处于疾病晚期,机体免疫功能极低;部分患者尽管接受了HAART,但是由于依从性、病毒耐药性等原因导致患者未能出现良好的应答反应,患者的免疫功能仍未能得到     

Effects of beta-endorphin on body temperature in mice at different ambient temperatures

The effect of intracerebroventricular injection of beta-endorphin (beta-END) on body temperature of mice was studied at ambient temperatures (Ta) of 10 degrees, 20 degrees and 31 degrees C. Doses between 0.1 and 10.0 microgram/mouse were studied. The lower (less than 1 microgram) doses of beta-END produced a hyperthermia at all Ta's studied. The higher doses of beta-END produced hyper- or hypothermia depending on the Ta. The subcutaneous injection of naloxone (1 mg/kg) antagonized the high dose hypothermic effects, but not the hyperthermic effect of beta-END. These data suggest that there may be different receptors and/or sites of action for high and low doses of beta-END.