Antihyperglycemic activity of phenolics from Pterocarpus marsupium

Glucose levels in rats with hyperglycemia induced by streptozotocin were determined after i.p. administration of marsupsin (1), pterosupin (2), and pterostilbene (3), three important phenolic constituents of the heartwood of Pterocarpus marsupium. Marsupsin and pterostilbene significantly lowered the blood glucose level of hyperglycemic rats, and the effect was comparable to that of 1,1-dimethylbiguanide (metformin).     

Lipid free radical generation and brain cell membrane alteration following nitric oxide synthase inhibition during cerebral hypoxia in the newborn piglet

Nitric oxide (NO) is reported to cause neuronal damage through various mechanisms. The present study tests the hypothesis that NO synthase inhibition by N(omega)-nitro-L-arginine (NNLA) will result in decreased oxygen-derived free radical production leading to the preservation of cell membrane structure and function during cerebral hypoxia. Ten newborn piglets were pretreated with NNLA (40 mg/kg); five were subjected to hypoxia, whereas the other five were maintained with normoxia. An additional 10 piglets without NNLA treatment underwent the same conditions. Hypoxia was induced with a lowered FiO2 and documented biochemically by decreased cerebral ATP and phosphocreatine levels. Free radicals were detected by using electron spin resonance spectroscopy with a spin trapping technique. Results demonstrated that free radicals, corresponding to alkoxyl radicals, were induced by hypoxia but were inhibited by pretreatment with NNLA before inducing hypoxia. NNLA also inhibited hypoxia-induced generation of conjugated dienes, products of lipid peroxidation. Na+,K+-ATPase activity, an index of cellular membrane function, decreased following hypoxia but was preserved by pretreatment with NNLA. These data demonstrate that during hypoxia NO generates free radicals via peroxynitrite production, presumably causing lipid peroxidation and membrane dysfunction. These results suggest that NO is a potentially limiting factor in the peroxynitrite-mediated lipid peroxidation resulting in membrane injury.     

Childhood thyroid cancer. Characteristics and long-term outcome in children irradiated for benign conditions of the head and neck

OBJECTIVE: To determine the characteristics and long-term outcome of radiation-induced thyroid cancer in children. DESIGN: Retrospective review of a cohort of 4296 irradiated patients who received childhood radiation treatment to the head and neck area at the same hospital. PATIENTS: Forty-one children who were younger than 20 years when thyroid cancer developed in them and 77 adults in whom thyroid cancer developed. All 118 cases were diagnosed before 1974 and were followed up for a median of 19.4 years. RESULTS: Children presented with clinically palpable lymph nodes more often than adults (30.7% vs 15.1%, P = .05) and had more recurrences (39% vs 16%, P = .05). Despite these frequent recurrences, only one patient (an adult) died of thyroid cancer. Seventy percent of the recurrences occurred during the first 10 years of follow-up, but recurrences continued after 20 years. The adults had previously identified factors that predicted the risk of recurrences, but none could be identified in the children. CONCLUSION: The presentation and relatively good outcome of radiation-induced thyroid cancer in children is similar to that in nonirradiated children. Frequent and late recurrences call for lifelong follow-up.     

Impairment of energy metabolism and excitotoxic cell death in Huntington disease

The gene for Huntington's disease is widely expressed in brain and yet the illness is characterized pathologically by a distinct regional pattern of cell death. Various theories for this selective vulnerability have been offered but the most compelling remains that of abnormal energy metabolism. These issues are reviewed.     

Update on the use of percutaneous nephrostomy/balloon dilation for the treatment of renal transplant leak/obstruction

PURPOSE: Retrospective evaluation of the efficacy of percutaneous nephrostomy and nephroureteral stent placement for treatment of post-transplant ureteral leak, and percutaneous nephrostomy and balloon dilation for treatment of post-transplant ureteral obstruction. PATIENTS AND METHODS: Data were reviewed for all patients who underwent percutaneous therapy for complications after renal transplantation between January 1985 and June 1995. A total of 61 patients with complications (leak, n = 17; obstruction, n = 44) had been treated. Patients underwent percutaneous nephrostomy followed by antegrade placement of a nephroureteral stent. In addition, all patients with obstruction also underwent ureteral balloon dilation. Follow-up ranged from 9 weeks to 24 months. Positive outcome was defined as nonsurgical closure of leak, significant improvement in renal function, and removal of the nephroureteral stent with maintenance of stable renal function. RESULTS: Regarding ureteral leak, 10 of 17 patients (59%) healed after treatment. Seven patients (41%) did not respond and went on to surgical repair. All patients with early (n = 13) ureteral obstruction (< 3 months after transplantation), had improved renal function (P < .025). Sixty-two percent of patients with early obstruction were cured (tube out with stable renal function) and 38% went to surgery for ureteral repair. In patients with late (n = 31) obstruction (> 3 months after transplantation), renal function improved in only 58% (P < .01). Only 16% of patients with late obstruction were cured (tube out with stable renal function). Ureteral obstruction was persistent in the remaining patients and did not respond to multiple balloon dilations. All complications were minor and included 23 of 61 (38%) patients with urinary tract infections and nine of 61 (14%) patients with limited hematuria. CONCLUSION: Percutaneous nephrostomy is very effective in improving renal function in patients with early obstruction. It is moderately successful in treating ureteral leak. Ureteral balloon dilatation is moderately effective for treatment of obstruction in the early (< 3 months) postoperative period. However, balloon dilation is minimally successful in curing ureteric obstruction occurring more than 3 months after transplantation.     

The Second Canadian Gastroesophageal Reflux Disease Consensus: moving forward to new concepts

Gastroesophageal reflux disease (GERD) is a disease with serious consequences that may result in significant impairment in quality of life and disease morbidity. Across all grades of severity of symptoms and severity of underlying esophageal disease, proton pump inhibitors (PPIs) provide therapeutic gains over prokinetics (PKs) or H2 receptor antagonists (H2RAs). The potential cost effectiveness of using medications with higher acquisition costs that may lower health care costs overall is often disregarded when conducting cost comparisons with medications having lower 'up-front' costs. Limiting therapy to less effective agents condemns many patients to protracted suffering, repeated physician visits and needless reinvestigation of symptoms that could have been resolved by appropriate initial therapy. Based on current data, use of any classification of symptom severity as a basis for selecting one class of therapeutic agents over another for first line therapy (i.e. PKs, H2RAs for 'mild' GERD, versus a PPI for 'severe' disease) is unwarranted.