Search

Our group previously reported that 6-h fasting increased both insulin II mRNA expression and insulin level in rat hypothalamus. Given that insulin effects on central glucose metabolism are insufficiently understood, we wanted to examine if the centrally produced insulin affects expression and/or regional distribution of glucose transporters, and glycogen stores in the hypothalamus during short-term fasting. In addition to determining the amount of total and activated insulin receptor, glucose transporters, and glycogen, we also studied distribution of insulin receptors and glucose transporters within the hypothalamus. We found that short-term fasting did not affect the astrocytic 45 kDa GLUT1 isoform, but it significantly increased the amount of endothelial 55 kDa GLUT1, and neuronal GLUT3 in the membrane fractions of hypothalamic proteins. The level of GLUT2 whose presence was detected in neurons, ependymocytes and tanycytes was also elevated. Unlike hepatic glycogen which was decreased, hypothalamic glycogen content was not changed after 6-h fasting. Our findings suggest that neurons may be given a priority over astrocytes in terms of glucose supply even during the initial phase of metabolic response to fasting. Namely, increase in glucose influx into the brain extracellular fluid and neurons by increasing the translocation of GLUT1, and GLUT3 in the cell membrane may represent the first line of defense in times of scarcity. The absence of co-localization of these membrane transporters with the activated insulin receptor suggests this process takes place in an insulin-independent manner.

Introduction: Coagulase-negative staphylococci (CoNS) are increasingly resistant nosocomial pathogens. We aimed to analyze the prevalence of CoNS isolates in clinical settings, the evolution of antimicrobial resistance of CoNS, and antibiotic consumption in a hospital., Methodology: This retrospective cohort study was carried out at a tertiary healthcare facility over 17 months. Identification of isolated cultures and antibiotic susceptibility testing were performed using the Vitek2 system. Of 1,217 isolates, 209 were obtained from 193 patients who had symptoms of nosocomial infections. Data were analyzed by descriptive statistics. Antibiotic consumption in the hospital is expressed in defined daily doses/100 patient days., Results: Sixty-one percent of patients were admitted to the internal medicine ward, while others were admitted to the surgical ward. Forty-four percent of Gram-positive isolates were from wound swabs, and 26% were from blood. The predominant Gram-positive bacteria were CoNS. Antibiotic resistance of CoNS was highest against beta-lactam antibiotics, macrolides, and tetracyclines. Tigecycline, linezolid, and vancomycin produced the highest activities against CoNS in in vitro conditions, and consumption of linezolid and tigecycline increased in the same period., Conclusion: There are just a few remaining therapeutic options for the treatment of CoNS according to our results; vancomycin, linezolid, and tigecycline might be considered as first-choice antibiotics, but such a hypothesis should be supported with a pharmacoeconomic analysis. Unfortunately, novel antimicrobial agents are still unavailable and/or too expensive in developing countries. However, inappropriate use of those antibiotics may lead to the rapid development of resistant strains in the near future.

Fat mass and obesity associated protein (Fto) is a nucleic acid demethylase, with a preference for thymine or uracil, according to the recent structural data. This fact suggests that methylated single-stranded RNA, rather than DNA, may be the primary Fto substrate. Fto is abundantly expressed in all hypothalamic sites governing feeding behavior. Considering that selective modulation of Fto levels in the hypothalamus can influence food intake, we set out to investigate the effect of 48 h fasting on the Fto expression in lateral hypothalamic area, paraventricular, ventromedial and arcuate nucleus, the regulatory centres of energy homeostasis. We have demonstrated that 48 h fasting causes not only an increase in the overall hypothalamic levels of both Fto mRNA and protein, but also alters Fto intracellular distribution. This switch happens in some neurons of paraventricular and ventromedial nucleus, as well as lateral hypothalamic area, resulting in the majority of the enzyme being localized outside the cell nuclei. Interestingly, the change in the Fto intracellular localization was not observed in neurons of arcuate nucleus, suggesting that fasting did not universally affect Fto in all of the hypothalmic sites involved in energy homeostasis regulation. Both Fto mRNA and catechol-O-methyltransferaze mRNA were upregulated in the identical time-dependent manner in fasting animals. This fact, combined with the knowledge of the Fto substrate preference, may provide further insight into monoamine metabolism in the state of disturbed energy homeostasis.

Leptin is produced by white adipose tissue and other cell types and is involved in both short- and long-term appetite control. Here we studied effects of starvation on serum, pituitary and hypothalamic levels of leptin during 72 h period. Each of the starved groups was sacrificed simultaneously with the group of ad libitum fed animals. The progression of the discrete starvation response phases was monitored by testing the blood glucose, free fatty acid, urea and corticosterone levels. Starvation caused biphasic increase in corticosterone and free fatty acid levels, and significant but transient decrease in urea and glucose levels. Starvation also abolished diurnal rhythm of changes in leptin concentrations in serum and hypothalamic and pituitary tissues. Only 6 h starving period was sufficient to lock serum leptin at low levels, whereas 12 h were needed to silence leptin production/secretion in hypothalamus for the whole examined period. In contrast, leptin production by pituitary tissues of starved animals required 24 h to reach minimum, followed by full recovery by the end of starvation period. These results indicate the tissue specific pattern of leptin release and suggest that the locally produced leptin could activate its receptor in pituitary cells independently of serum levels of this hormone.