Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness

Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma in children; however, the mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we examined the effects of in utero cigarette smoke exposure of Balb/c mice on airway responsiveness, as determined by Penh measurements. Animals exposed prenatally but not postnatally to cigarette smoke exhibited increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract. The increased airway hyperresponsiveness was not associated with increased leukocyte migration or mucous production in the lung but was causally related to decreased lung cyclic adenosine monophosphate levels, increased phosphodiesterase-4 enzymatic activity, and phosphodiesterase-4D (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung. Exposure of adult mice to cigarette smoke did not significantly alter airway responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase activity. These results suggest that prenatal exposure to cigarette smoke affects lung airway reactivity by modulating the lung cyclic adenosine monophosphate levels through changes in phosphodiesterase-4D activity, and these effects are independent of significant mucous production or leukocyte recruitment into the lung.     

Central leptin gene therapy blocks high-fat diet-induced weight gain,hyperleptinemia, and hyperinsulinemia: increase in serum ghrelin levels

Recombinant adeno-associated virus (rAAV), encoding either rat leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP, control), was injected intracerebroventricularly in rats consuming a high-fat diet (HFD; 45 kcal%). Caloric consumption and body weight were monitored weekly until the rats were killed at 9 weeks. Untreated control rats consuming regular rat diet (RCD; 11 kcal%) were monitored in parallel. Body weight gain was accelerated in rAAV-GFP + HFD control rats relative to those consuming RCD, despite equivalent kcal consumption. At 9 weeks, serum leptin, free fatty acids, triglycerides, and insulin were elevated in HFD control rats. In contrast, rAAV-lep treatment reduced intake and blocked the HFD-induced increase in weight, adiposity, and metabolic variables. Blood glucose was slightly reduced but within the normal range, and serum ghrelin levels were significantly elevated in rAAV-lep + HFD rats. Uncoupling protein-1 (UCP1) mRNA in brown adipose tissue (BAT), an index of energy expenditure through nonshivering thermogenesis, was decreased in rats consuming HFD. Treatment with rAAV-lep significantly augmented BAT UCP1 mRNA expression, indicating increased thermogenic energy expenditure. These findings demonstrate that central leptin gene therapy efficiently prevents weight gain, increased adiposity, and hyperinsulinemia in rats consuming an HFD by decreasing energy intake and increasing thermogenic energy expenditure.     

MR findings of primary Ewing's sarcoma of greater wing of sphenoid

Primary Ewing's sarcoma of the skull is a very rare entity. We report MRI findings in a case of Ewing's sarcoma of the greater wing of sphenoid in a 4-year-old patient. Magnetic resonance imaging showed markedly heterogenous signal intensity with areas of haemorrhage and necrosis. It also demonstrated the exact extent of tumour due to its multiplanar capabilities and was, therefore, helpful in planning surgery.     

The role of magnetic resonance cholangiopancreatography in patients with suspected biliary obstruction

Endoscopic retrograde cholangiopancreatography (ERCP) is an accepted and accurate procedure that combines the advantage of diagnosis of biliary obstruction with possible therapeutic endobiliary intervention. However, it is an operator-dependent and invasive procedure that is associated with complications and limitations. Magnetic resonance cholangiopancreatography (MRCP) is a unique noninvasive technique for the diagnosis of biliary obstruction. It is well suited to provide the information required to plan the optimal therapeutic approach for these patients. MRCP has the potential to replace or at least precede ERCP as the first-line imaging effort in the evaluation of suspected biliary obstruction. Significant advantages and some notable limitations inherent to the modality dictate its judicious use in appropriate circumstances. The present article reviews the utility of MRCP in evaluation of biliary obstruction, with brief reference to its principles and techniques.     

Novel Tcradiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit

A quinazolinone derivative as a novel non-peptidic CCK-B receptor antagonist designated as Qn-In, was synthesized, characterized by spectroscopic techniques and evaluated for radiopharmaceutical potential. The efficiency of labeling with ^99mTc was greater than 98% and the complex was stable for about 7 hours at 37°C in presence of serum. Affinity of Qn-In was determined to be in nanomolar range by competitive binding studies on cancer cell line MDA-MB-468. Bio-distribution of ^99mTc labeled Qn-In in mice was examined by intravenous administration and time-activity curves were generated. The ligand showed binding to most of the organs, known to express CCK-B receptor. The lack of uptake in brain may be due to the inability of the complex to cross the blood-brain barrier. Our results show that ^99mTc labeled Qn-In ligand provides a new template for further development of non-peptidic ligands for diagnosis and therapy of diseases related with CCK-B receptor.     

Bladder rehabilitation in spinal cord injury patients.

The relative efficacy of intermittent catheterisation, self or assisted, over indwelling catheterisation was studied on 44 patients of different extent of spinal cord lesions. All the surviving cases (9) of incomplete cord lesion became catheter free irrespective of the method of catheterisation. In these patients urine was also found to be infection free by the 5th week of admission. Twenty-seven cases of complete cord lesion (out of a total of 35) became catheter free, of whom 18 patients were on intermittent catheterisation (out of a total of 20) and 9 patients were on indwelling catheter (out of a total of 15 cases). In the later group incidence of urine infection was higher. Other complications like urethral trauma were comparable between patients with indwelling catheter and patients with intermittent, self or assisted, catheterisation.