Modulatory role of locus coeruleus and estradiol on the stress response of female rats

The activity of the hypothalamic-pituitary-adrenal axis is modulated by the norepinephrinergic system and, in females, also by the ovarian hormones. We investigated the role of ovarian steroids and the locus coeruleus (LC) on stress-induced corticosterone secretion in female rats. Ovariectomized rats without hormonal replacement (OVX) or treated with estradiol (OVE) or estradiol plus progesterone (OVEP) were subjected to jugular cannulation. Immediately after that, each hormonal treatment group was subjected to LC lesion or sham surgery or no brain surgery. After 24 h, blood samples of all 9 groups were collected before and after ether inhalation. Other four groups (OVX control, sham and lesioned, and OVE) were perfused for glucocorticoid receptor (GR) immunocytochemistry in hippocampal CA1 neurons and paraventricular nucleus (PVN). Estradiol replacement decreased while LC lesions increased stress-induced corticosterone secretion. The effect of LC lesion was potentiated with the removal of ovarian steroids. Since GR expression of lesioned animals decreased in the hippocampus, but not in PVN, we suggest that the effect of LC lesion on corticosterone secretion could be due to a reduction in the efficiency of the negative feedback system in the CA1 neurons. However, this mechanism is not involved in the estradiol modulation on corticosteroid secretion, as no change in GR expression was observed in estradiol-treated animals.     

Serological profile of Helicobacter pylori infection in the population of San Luis (Argentina)

We performed a seroepidemiological study of anti-Helicobacter pylori IgG by a commercial enzyme immunoassay kit (Meridian Diagnostics, USA) in 509 serum samples from 314 randomly selected asymptomatic subjects from among the population, and grouped into children (n = 124), adolescents (n = 74) and adults (n = 116), and in 195 serum samples from subjects presenting clinical gastric symptoms, grouped into children (n = 38) and adults (n = 157). The cut-off value was redefined and set at OD450 = 0.050. The percentage of seropositive individuals was not significantly different between the two groups of adults studied (75.9% and 80.2%, respectively) (p < 0.05), suggesting a high degree of contact with the microorganism in this region.     

Long-term modulation of Na+ and K+ channels by TGF-��1 in neonatal rat cardiac myocytes

Previous work shows that transforming growth factor-β1 (TGF-β1) promotes several heart alterations, including atrial fibrillation (AF). In this work, we hypothesized that these effects might be associated with a potential modulation of Na(+) and K(+) channels. Atrial myocytes were cultured 1-2?days under either control conditions, or the presence of TGF-β1. Subsequently, Na(+) (I(Na)) and K(+) (I(K)) currents were investigated under whole-cell patch-clamp conditions. Three K(+) currents were isolated: inward rectifier (I(Kin)), outward transitory (I(to)), and outward sustained (I(Ksus)). Interestingly, TGF-β1 decreased (50%) the densities of I(Kin) and I(Ksus) but not of I(to). In addition, the growth factor reduced by 80% the amount of I(Na) available at -80?mV. This effect was due to a significant reduction (30%) in the maximum I(Na) recruited at very negative potentials or I(max), as well as to an increased fraction of inactivated Na(+) channels. The latter effect was, in turn, associated to a -7?mV shift in V(1/2) of inactivation. TGF-β1 also reduced by 60% the maximum amount of intramembrane charge movement of Na(+) channels or Q(max), but did not affect the corresponding voltage dependence of activation. This suggests that TGF-β1 promotes loss of Na(+) channels from the plasma membrane. Moreover, TGF-β1 also reduced (50%) the expression of the principal subunit of Na(+) channels, as indicated by western blot analysis. Thus, TGF-β1 inhibits the expression of Na(+) channels, as well as the activity of K(+) channels that give rise to I(Ksus) and I(Kin). These results may contribute to explaining the previously observed proarrhythmic effects of TGF-β1.     

Glial hypothalamic inhibition of GLUT2 expression alters satiety,impacting eating behavior

Glucose is a key modulator of feeding behavior. By acting in peripheral tissues and in the central nervous system, it directly controls the secretion of hormones and neuropeptides and modulates the activity of the autonomic nervous system. GLUT2 is required for several glucoregulatory responses in the brain, including feeding behavior, and is localized in the hypothalamus and brainstem, which are the main centers that control this behavior. In the hypothalamus, GLUT2 has been detected in glial cells, known as tanycytes, which line the basal walls of the third ventricle (3V). This study aimed to clarify the role of GLUT2 expression in tanycytes in feeding behavior using 3V injections of an adenovirus encoding a shRNA against GLUT2 and the reporter EGFP (Ad‐shGLUT2). Efficient in vivo GLUT2 knockdown in rat hypothalamic tissue was demonstrated by qPCR and Western blot analyses. Specificity of cell transduction in the hypothalamus and brainstem was evaluated by EGFP‐fluorescence and immunohistochemistry, which showed EGFP expression specifically in ependymal cells, including tanycytes. The altered mRNA levels of both orexigenic and anorexigenic neuropeptides suggested a loss of response to increased glucose in the 3V. Feeding behavior analysis in the fasting‐feeding transition revealed that GLUT2‐knockdown rats had increased food intake and body weight, suggesting an inhibitory effect on satiety. Taken together, suppression of GLUT2 expression in tanycytes disrupted the hypothalamic glucosensing mechanism, which altered the feeding behavior.     

Variability in postheparin hepatic lipase activity is associated with plasma adiponectin levels in African Americans.

BACKGROUND: African Americans commonly have normal high-density lipoprotein cholesterol (HDL-C) and low triglyceride levels despite having insulin resistance and obesity. The higher than expected HDL-C levels are usually attributed to low levels of hepatic triglyceride lipase (HTGL) activity. Factors that regulate HTGL in African Americans are not well delineated. METHODS: In the current study, HTGL activity was examined in relation to indices of body fat (body mass index [BMI] and waist circumference [WC]), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR] index), and adipokines (adiponectin and leptin). Sixty-three African Americans (33 men, 30 women; median age 31 years, range 20-50 years; median BMI 28.6 kg/m2, range 19.7-54.7 kg/m2) had anthropometry and measurement of postheparin lipase activities (HTGL), plasma HDL-C, triglycerides, and plasma adiponectin. RESULTS: HTGL correlated strongly with HDL-C (r = -.52, p < .0001) and adiponectin (r = -.49, p < .001). HTGL increased with BMI and WC (r = .297, p = .018 and r = .301, p = .016, respectively). Adiponectin correlated strongly with HDL-C (r = .50, p < .0001) and triglycerides (r = -.493, p < .001). From multiple regression models, 28% of HTGL variability among African Americans can be explained by adiponectin levels in combination with gender and 35% of HTGL is explained with HDL-C included in the model. CONCLUSION: The data suggest that adiponectin is a significant metabolic concomitant of HTGL activity in African Americans.     

Allergen-dependent CD14 modulation and apoptosis in monocytes from allergic patients

BACKGROUND: CD14 is a most important monocyte surface molecule. Recently, it has been reported that there is an important relationship between CD14 and immunoglobulin E, and that regulation of CD14 expression is an effector mechanism mediating apoptosis of monocytes. OBJECTIVE: The present study was designed to determine whether specific allergens were able to modulate CD14 expression and apoptosis by monocytes from allergic patients or whether specific immunotherapy (IT) might affect these processes. METHODS: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood monocytes from both groups of asthmatic patients in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Monocytes from normal subjects were also challenged with allergens. Expression of CD14 on the monocyte surface was analyzed by flow cytometry, and soluble CD14 (sCD14) in culture supernatant by enzyme-linked immunosorbent assay. The three groups of subjects were challenged with allergens, and apoptosis was analyzed by flow cytometry. RESULTS: When monocytes from non-IT-treated asthmatic patients were cultivated with the allergens to which the patients were sensitive, a significant up-regulation on the monocyte surface was observed compared with results from the healthy group (P < 0.003) and from the IT asthmatic group (P < 0.003). A significantly higher sCD14 level was observed in the culture supernatant of the monocytes from the IT asthmatic group were observed compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (P < 0.001). A significantly higher apoptosis level was observed in monocytes from the IT asthmatic group compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (<0.001). CONCLUSIONS: We present evidence that the expression of CD14 on the surface of monocytes and the apoptosis of the same cells can be modulated by an allergen-dependent mechanism. These processes can be affected by IT.     

Effects of increased nerve growth factor plasma levels on the expression of TrkA and p75 in rat testicles

In addition to their well-known roles within the nervous system, the neurotrophins and their receptors regulate some functions in the reproductive system. In this study we used combined morphological and immunohistochemical techniques to investigate the presence and cellular localization in the rat testicle of the two receptors of nerve growth factor (NGF), i.e. TrkA and p75(NTR). Furthermore, to evaluate whether increased plasma levels of NGF affect the ageing process, 4-methylcathechol (4-MC), an inductor of NGF synthesis, was administered. Both TrkA and p75(NTR) were expressed in rat testicles, but the pattern and intensity of immunoreaction were marginally different between them. In adult rats TrkA was expressed in spermatozoa and spermatids, and p75 was expressed in spermatogonia. In newborn rats TrkA immunoreactivity was found in the Leydig cells, whereas p75 was detected in a cellular layer that surrounds the seminiferous tubules. In adult treated animals the immunoreaction for TrkA and p75(NTR) was also localized in the spermatocytes, whereas in newborn treated rats no changes in the pattern of immunoreaction was observed. The present findings suggest a role of the NGF/TrkA/p75 system in the physiology of reproduction, but the practical relevance of this remains to be established.     

X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability

Partial trisomy of the long arm of chromosome 10 is a well-defined but rare syndrome. Clinical features of this chromosomopathy are a distinctive dysmorphic appearance, developmental delay, growth retardation, and in some cases, abnormalities of the extremities and renal, cardiac and ocular anomalies. This report describes a neonate with symmetric growth retardation and multiple dysmorphic features, in whom chromosomal analysis revealed a partial trisomy of chromosome 10q with a monosomy of the 13q34 region. The phenotype shares many common features with previously published cases. In addition to the typical features, our case also shows renal hypoplasia with early renal insufficiency and some genital anomalies.