A comparison of the discriminative stimulus effects of delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats

Efforts to determine whether Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and anandamide elicit similar discriminative stimulus effects have yielded conflicting results. The difficulty in establishing a discriminative cue to anandamide may be due to its metabolic instability. Rats were trained to discriminate either Delta(9)-THC or O-1812, a metabolically stable anandamide analog, from vehicle to avoid this issue. O-1812 and Delta(9)-THC substituted for each other; however, both drugs were more potent in the O-1812-trained rats. Further, O-1812 only substituted for Delta(9)-THC at response rate decreasing doses. The CB(1) antagonist, SR141716A, blocked the discriminative stimulus effects of both drugs but augmented their rate effects. O-1839, a VR(1) agonist, failed to substitute for either cannabinoid. These results suggest that the discriminative stimulus effects of Delta(9)-THC and O-1812 are similar, but subtle differences also exist.     

Microalbuminuria as a predictor of early glomerular injury in children with sickle cell disease

Objective : A cross sectional study was carried out to determine the prevalence of microalbuminuria in the pediatric patients with sickle cell disease.Methods : The study was carried out on 64 pediatric patients aged less than 14 years with documented HbSS, HbAS and HbS beta thalassemia, Microalbuminuria was estimated using single radial immuno diffusion technique. Majority of the study subjects were of HbSS type. 38.5% had symptoms for >2 years. 18.8% of the study population had significant microalbuminuria (19.2% of SS types and 18.8% of Hb AS types).Result : Microalbuminuria excretion was significantly more in patients >9 years of age as compared to young patients (p<0.05). Mean serum creatinine levels did not show any significant difference in the various study groups.Conclusion : Microalbuminuria estimation is a very important clinical marker of preclinical glomerular damage in patients with sickle cell disease. Its estimation would help in the early detection of such patients and prompt initiation of therapy.     

The IMS Act 1992: need for more amendments and publicity

The IMS act was passed after a lot of thinking, discussions over pros and cons of childhood feeding practices and recommendations of WHA. We are not only legally bound by it, but it is also our moral responsibility to see that the act works. Already 9-10 years have passed but the results are not that encouraging. Most of our colleagues are unaware of the provisions and importance of this act. Making the law effective is very time consuming, costly, unaffordable and avoidable affair. We should not harp on multiplicity of legal opinions & loopholes to allow breaking the law in spirit if not in letter. We feel that most of our laws are paper tigers without any teeth, gathering dust by remaining present only in law books or journals. If we don't act now then there is every possibility that this act may also become one of the historical legal documents. Hence it is time for all of us to become an activist or counselor for BF. We should create awareness and public opinion about protection, promotion and support for BF. Be vigilant, form community watch group and report violations to the authorities. So that our country can become a proud nation of healthy, intelligent and emotionally stable children in the 21st century.     

Keith Edwards score for diagnosis of tuberculosis

Objective : To evaluate the applicability of Keith Edwards scoring system for the diagnosis of childhood tuberculosis.Methods. One hundred and one children aged 2 months to 12 years who fulfilled the inclusion criteria were evaluated with Keith Edwards score. The diagnosis of tuberculosis by Keith Edwards score and the definitive reference were compared.Results. Among the 65 children diagnosed as having tuberculosis by the definitive reference, 59 had a Keith Edwards score of >7. Four children had a score of >7 but were not suffering from tuberculosis. The sensitivity and specificity of this score have been found to be 91% and 88% respectively.Conclusion. In select population with indicative clinical features, Keith Edwards score can be a definitive guideline for the diagnosis of childhood tuberculosis. However, more studies are required for the validation of this clinical score before it can be used as a definitive diagnostic reference standard for tuberculosis.     

Long-term suppression of weight gain,adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes

Intracerebroventricular administration of recombinant adeno-associated virus (rAAV) encoding the rat leptin gene (rAAV-lep) to 24-d-old female and male rats suppressed postpubertal weight gain for extended periods by decreasing food consumption and adiposity, as reflected by lowered serum leptin, insulin, and FFA. Serum ghrelin levels were increased in young but not older rats. Central rAAV-lep therapy also increased energy expenditure through nonshivering thermogenesis in younger rats as shown by expression of uncoupling protein mRNA in brown adipose tissue. The sustained decrease in appetite seemingly resulted from attenuation of appetite-stimulating neuropeptide Y and enhancement of appetite-inhibiting melanocortin signalings in the hypothalamus. Neither the onset of pubertal sexual maturation nor reproductive cyclicity in adult female rats was affected by the sustained reduction in energy consumption and weight gain. These findings demonstrate that central leptin gene therapy in prepubertal rats is a novel therapy to control postpubertal weight gain, adiposity, and hyperinsulinemia for extended periods.     

Prognostic factors in childhood tuberculous meningitis

The risk factors affecting the outcome in 50 children with tuberculous meningitis were evaluated over a period of 20 months. Five children (10 per cent) had stage 1 disease, 29 (58 per cent) had stage II disease, and 16 (32 per cent) had stage III disease at admission. Seventeen cases (34 per cent) showed complete recovery, five (10 per cent) had mild, 14 (28 per cent) had moderate, and nine (18 per cent) had severe neurological sequelae. Five children (10 per cent) died. Younger age, tonic posturing, papilloedema, focal neurological deficit and stage at presentation were found to affect adversely the prognosis independently in children with tuberculous meningitis.     

Pyruvate prevents poly-ADP ribose polymerase (PARP) activation,oxidative damage,and pyruvate dehydrogenase deactivation during hemorrhagic shock in swine

The inadequate availability of fuel substrates and sharp decline in cellular ATP have been implicated in a cascade of events associated with cell death and organ failure during hemorrhagic shock (HS). In this in vivo swine model of severe prolonged HS, the effect of exogenous pyruvate administration on various markers of cell damage in brain and liver was examined. Thirty minutes after the start of controlled arterial hemorrhage, 30% sodium pyruvate, 10% saline, or 0.9% saline was administered via jugular vein. Four hours after the initiation of hemorrhage, tissue samples from brain and liver were obtained and examined for the cellular and molecular markers of cellular damage. Results of our study suggest that pyruvate prevents loss of total NAD content, cleavage of poly-ADP ribose polymerase (PARP), and inhibits lipid peroxidation in both the brain and liver of swine during prolonged severe HS. We conclude that there are multiple mechanisms by which pyruvate can possibly prevent cell damage caused during HS.     

Leptin expression in hypothalamic PVN reverses dietary obesity and hyperinsulinemia but stimulates ghrelin

OBJECTIVE: In order to circumvent the multiple peripheral effects of hyperleptinemia and leptin resistance, the efficacy of leptin transgene expression in the hypothalamic paraventricular nucleus (PVN) to reinstate the central energy homeostasis in obesity was examined. RESEARCH METHODS AND PROCEDURES: A recombinant adeno-associated viral vector encoding either leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP) was microinjected into the PVN of obesity-prone rats consuming a high-fat diet (HFD). RESULTS: rAAV-lep, and not rAAV-GFP, microinjection significantly reduced energy intake and enhanced energy expenditure, thereby resulting in normalization of weight and blood levels of leptin, insulin, free fatty acids, and glucose concomitant with enhanced ghrelin secretion during the extended period of observation. DISCUSSION: Thus, we show, for the first time, that amelioration of leptin insufficiency with enhanced localized leptin availability in the PVN alone can reverse dietary obesity and the attendant hyperinsulinemia and concurrently block the central stimulatory effects of elevated endogenous ghrelin on food intake and adiposity.