Changes in hypothalamic gene expression associated with the arrest of pulsatile gonadotropin-releasing hormone release during infancy in the agonadal male rhesus monkey (Macaca mulatta)

This study examined whether changes in the levels of the messenger RNAs (mRNAs) encoding the gamma-aminobutyric acid (GABA) synthesizing enzymes, glutamate decarboxylase (GAD)65 and GAD67 and transforming growth factor-alpha (TGFalpha) in the hypothalamus are correlated with the arrest of pulsatile GnRH release during infancy in the agonadal male monkey. This experiment also provided the opportunity to examine changes in hypothalamic GnRH gene expression during this critical phase of primate development. Male rhesus monkeys were castrated at 1 week of age: four were killed 4-7 weeks after orchidectomy while pulsatile GnRH release was robust as reflected by high circulating LH levels, and four were killed at 12-15 months of age after establishing that pulsatile GnRH release had been arrested. GAD65, GAD67, TGFalpha, and GnRH mRNA levels were estimated using RNase protection assays employing homologous probes and the results were expressed relative to cyclophilin mRNA levels. GnRH peptide was measured by RIA. GAD65 and GAD67 mRNA levels in the hypothalamus of juveniles were significantly greater than those in neonatal monkeys. On the other hand, hypothalamic TGFalpha and GnRH mRNA (and peptide) levels in agonadal neonate and juvenile monkeys were indistinguishable. These results indicate that the molecular concomitants associated with bringing the hypothalamic GnRH pulse generator into check in agonadal neonatal males are not a mirror image of those previously reported at the time this neuronal network is reactivated at puberty when TGFalpha and GnRH gene expression increase and GAD65 and GAD67 mRNA levels remain unchanged. Thus, the neurobiological mechanism that reactivates pulsatile GnRH release at puberty is likely to involve more than a simple reversal of that underlying inhibition of the same network in late infancy.     

Macular serpiginous choroiditis

PURPOSE: To report a variant form of serpiginous choroiditis, that initially or predominantly involved the macular area. METHODS: Nine eyes of 6 patients with the macular form of serpiginous choroiditis were evaluated clinically and angiographically in a longitudinal fashion for a period of 12-36 months. The active stage and the recurrences were treated by oral and periocular cortico steroids; and two patients were supplemented with oral azathioprine. Most of these patients were referred to our center with varied diagnoses. RESULTS: In this group, 4 were male and 2 were female with an average age of 30.5 years. Three patients had bilateral macular lesions, two had typical serpiginous choroiditis in the fellow eye and the remaining one had unilateral macular involvement alone. The initial visual acuity was 6/60 or less in 60% eyes whereas the final visual acuity was 6/18 or better in 66% eyes. Angiographic findings were typical of serpiginous choroiditis characterised by early hypofluorescence followed by leakage and staining of the borders and the lesion itself without any evidence of choroidal ischaemia or retinal vascular abnormalities. CONCLUSION: The macular variant of serpiginous choroiditis can mimic many other macular pathologic lesions, thus posing a diagnostic dilemma. Because of its relentless destructive course, early diagnosis and prompt treatment is required to prevent sight-threatening complications.     

Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance

Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one of the major signals that relay the status of fat stores to the hypothalamus and plays a significant role in energy homeostasis. Understanding the mechanisms of leptin signaling in the hypothalamus during normal and pathological conditions, such as obesity, has been the subject of intensive research during the last decade. It is now established that leptin action in the hypothalamus in regulation of food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals, including NPY, MCH, galanin, orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3 pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role in leptin signaling in the hypothalamus. It is now established that central leptin resistance contributes to the development of diet-induced obesity and ageing associated obesity. Central leptin resistance also occurs due to hyperleptinimia produced by exogenous leptin infusion. A defective nutritional regulation of leptin receptor gene expression and reduced STAT3 signaling may be involved in the development of leptin resistance in DIO. However, leptin resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3 pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway, defects in other leptin signaling pathways may be involved in leptin resistance. We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of the mechanisms behind the development of central leptin resistance seen in obesity.     

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract

Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5μ) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-α(TNF-α), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-α in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.     

Outbreak of neonatal septicemia with multidrug resistantKlebsiella Pneumoniae

A nosocomial outbreak of neonatal septicemia due toK. pneumoniae occurred in nursery during June–July, 1991.Klebsiella pneumoniae (Klebocin type 314) was recovered from blood of 33(70.2%) of 47 neonates with septicemia. Multiple drug resistance was observed in all the cases. The same strain ofK. pneumoniae was recovered from the neonates and environment of nursery and labour room as well. The outbreak was attributable to environmental dissemination.     

Leprosy elimination campaigns in Orissa

Four Modified Leprosy Elimination Campaigns (MLECs) were conducted in Orissa by March 2003. Their impact on various leprosy indicators was analyzed. More than 70% of the people of the State were examined during these campaigns. The suspect rate decreased from 1.44% to 0.37% towards the fourth MLEC. About 15% of the suspects were clinically confirmed to be having leprosy. The total number of new cases detected during the MLEC years was on the decrease. A marked fall in new case-detection rate was observed during inter-MLEC years. This has resulted in fluctuation in the prevalence rate during the MLEC years, but the overall PR/10,000 population decreased from 12.18 in 1996-97 to 7.3 in March 2003. More than 40% of the total new cases and about 45% of total new child cases for the corresponding year were detected during the MLECs, and the proportion of total new case-detection was as high as 60.8% during the first MLEC. The proportion of female cases detected during succeeding MLECs improved and an almost equal number of female cases were detected during MLECs III and IV. Considering the present leprosy situation in Orissa and the effectiveness of MLECs in case-detection, it was recommended that such campaigns should be undertaken in select high prevalent blocks of the State at regular intervals, along with the strengthening of the integration of NLEP activities into primary health care activities.     

Risk factors of substance use among street children from Delhi

OBJECTIVE: To estimate the magnitude of and socio-demographic factors related to substance use among street children in Delhi. DESIGN: Observational study. METHODS: 115 male street children aged 6 to 16 years were interviewed at the time of their admission to an observation home. RESULTS: More than half of the subjects had indulged in substance use before coming to the observation home. The agents consumed were nicotine,inhalants, alcohol and cannabis. On application of multiple logistic regression, maltreatment of the child by family members was found significant predictor of substance use in the study group. CONCLUSION: Substance use in street children is associated with unstable homes and maltreatment.     

Impact of blast induced transitory vibration and air-overpressure/noise on human brain--an experimental study

Human response to blast induced ground vibration and air-overpressure/noise is a major concern of current mining activity. This is because the fact that mines are fast transgressing the habitats and people are getting educated. Consequently the response of humans is changing and expectedly will increase in days to come with no viable and economic alternative to blasting--an essential component of mining. The response of humans can be purely physiological or psychological in nature or combination of both depending upon the situation and conditions of mining. Where physiological response is documented in terms of effects on ears and lungs there is a meager amount or no literature available regarding effects of blasting on the brain. Moreover, the studies on transitory phenomenon like the effects of blasting on humans are rare in comparison to the whole body vibration studies. This study was designed to address the issues as a precursor to a major initiative. The preliminary investigations conducted with the monitoring of EEG responses of humans to vibration and air-overpressure/noise due to blasting revealed that there is no major response of the brain to transitory vibrations and noise.