Explore the vast range of titles available.

Background: Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. Objective: To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. Setting: University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. Methods: Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. Results: Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0–60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0–10 min), second-phase insulin secretion (AUC 10–60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. Conclusion: Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.

We evaluated pathophysiological characteristics of the lower urinary tract dysfunction in a streptozotocin (STZ)-induced diabetic rat model. STZ (60 mg/kg) was injected intraperitoneally into male Wistar rats. In vitro bladder muscle strip experiments, in vivo cystometry, and simultaneous recordings of bladder pressure + urethral perfusion pressure (BP + UPP) with or without intravenous administration of L-arginine (300 mg/kg) or tadalafil (0.03 mg/kg) were performed at several time points. In vitro muscle strip experiments demonstrated that diabetic rats had significantly higher contractile responses to carbachol at 4–16 weeks, and a tendency for higher contractile responses to electrical field stimulation at 4–12 weeks, but this was reversed at 16 weeks. Diabetic rats had significant increases in voided volume, residual volume, bladder capacity, maximal voiding pressure, and amplitude and frequency of non-voiding contractions at 16 weeks. Tadalafil decreased the residual volume in diabetic rats. Diabetic rats had significantly higher UPP nadir and mean UPP during high-frequency oscillation at 16 weeks, which were reversed by tadalafil or L-arginine administration. The present results suggest that urethral relaxation failure, probably related to impairment of the NO/cGMP signalling pathway, rather than bladder contractile dysfunction may be a prominent cause for voiding dysfunction in STZ-induced chronic diabetic rats.

Sickle cell anemia and the β-thalassemia syndromes are prevalent disorders caused by mutations affecting the adult-globin (beta-globin) chain of hemoglobin A (the chains designated as α 2 β 2 ) 1 – 5 . Sickle cell anemia was the first disease to be characterized at the molecular level 3 – 5 . Definitive treatment for the underlying condition has not followed, however, except for bone marrow transplantation in the few patients for whom there are appropriate donors. Increased production or prolonged expression of fetal globin (γ-globin) in sufficient quantities can ameliorate both disorders 6 – 13 . Chemotherapeutic agents, including azacitidine, cytarabine, and hydroxyurea, have been . . .

Interleukin-2 (IL-2) and sodium butyrate allow rats to be cured of peritoneal carcinomatosis from colon cancer. We performed a phase I trial of IL-2 and high-dose arginine butyrate (ArgB) in patients with advanced metastatic colorectal cancer. From April to July 1997, six patients were included in the trail; they had a median age of 52 years, four had a performance status of 0, two had a performance status of 1 with normal biological functions. All patients had received at least two prior lines of chemotherapy. A fixed dose of 18 MIU/m2 IL-2,was administered by subcutaneous injection and ArgB was delivered via continuous intravenous infusion on days 1-6 with escalating doses starting at 2 g kg(-1) day(-1). The planned dose escalation was not possible because of toxicities. A daily ArgB dose of 2 g/kg was delivered for nine cycles. Level 2 (4 g/kg) could not be delivered in three of the six patients because of liver toxicity. The dose-limiting toxicities were fatigue and liver function disturbances. The maximum tolerated dose for ArgB was 3 g kg(-1) day(-1), in combination with IL-2 at 12 MIU m2 day(-1). No clinical response was seen. Pharmacokinetic analysis showed large intra- and interindividual variations. This schedule with a high dose of ArgB proved to be highly toxic with liver insufficiency. We will be running another trial with lower doses of ArgB calculated from the schedule used in the experimental model, starting at a dose of 20 mg kg(-1) day(-1) for ArgB and 200000 UI kg(-1) day(-1) IL-2, every 8 h.

Changes in corticotropin (ACTH) and glucocorticoid secretion have been described during disturbances of body fluid homeostasis and attributed to alterations in arginine vasopressin (AVP) secretion from magnocellular hypothalamic neurons. In order to further characterize the mechanisms involved in the interactions between body fluid alterations and pituitary adrenal function, we manipulated osmolality and volemia in sheep under stimulation of the pituitary-adrenal axis by acute injection of endotoxin. We have recently shown that endotoxin injection induces a long-lasting release of both corticotropin releasing hormone (CRH) and AVP into hypophysial portal blood, and an early stimulation of AVP secretion into peripheral vessels, thus suggesting a joint activation of magnocellular and parvocellular neurons of the PVN. We used the same experimental model to investigate the effect of combined volume loading and plasma dilution (achieved by 1-deamino-8-D-arginine (dDAVP) administration together with infusion of 2 liters of 2.5% glucose solution) on CRH, AVP, ACTH and cortisol responses to endotoxin stimulation. In volume-loaded animals, ACTH and cortisol responses to endotoxin were significantly blunted and we observed a parallel decrease in portal CRH and jugular and portal AVP levels. These data show that hypoosmolality and/or hypervolemia reduce(s) ACTH and cortisol response to stress in sheep as in other species. They strongly suggest that this reduction in ACTH and cortisol responses to endotoxin involve not only magnocellular hypothalamic neurons secreting AVP, as usually assumed, but also PVN parvocellular neurons secreting both CRH and AVP.