Physical exercise improves glucose metabolism and insulin sensitivity. Brain-derived neurotrophic factor (BDNF) enhances insulin activity in diabetic rodents. Because physical exercise modifies BDNF production, this study aimed to investigate the effects of chronic exercise on plasma BDNF levels and the possible effects on insulin tolerance modification in healthy rats. Wistar rats were divided into five groups: control (sedentary, C); moderate- intensity training (MIT); MIT plus K252A TrkB blocker (MITK); high-intensity training (HIT); and HIT plus K252a (HITK). Training comprised 8 weeks of treadmill running. Plasma BDNF levels (ELISA assay), glucose tolerance, insulin tolerance, and immunohistochemistry for insulin and the pancreatic islet area were evaluated in all groups. In addition, Bdnf mRNA expression in the skeletal muscle was measured. Chronic treadmill exercise significantly increased plasma BDNF levels and insulin tolerance, and both effects were attenuated by TrkB blocking. In the MIT and HIT groups, a significant TrkB-dependent pancreatic islet enlargement was observed. MIT rats exhibited increased liver glycogen levels following insulin administration in a TrkB-independent manner. Chronic physical exercise exerted remarkable effects on insulin regulation by inducing significant increases in the pancreatic islet size and insulin sensitivity in a TrkB-dependent manner. A threshold for the induction of BNDF in response to physical exercise exists in certain muscle groups. To the best of our knowledge, these are the first results to reveal a role for TrkB in the chronic exercise-mediated insulin regulation in healthy rats.

Hypoxic stimulation of the carotid body receptors (CBR) results in a rapid hyperglycemia with an increase in brain glucose retention. Previous work indicates that neurohypophysectomy inhibits this hyperglycemic response. Here, we show that systemic arginine vasopressin (AVP) induced a transient, but significant, increase in blood glucose levels and increased brain glucose retention, a response similar to that observed after CBR stimulation. Comparable results were obtained after intracerebral infusion of AVP. Systemic AVP-induced changes were maintained in hypophysectomized rats but were not observed after adrenalectomy. Glycemic changes after CBR stimulation were inhibited by pharmacological blockage of AVP V1a receptors with a V1a-selective receptor antagonist ([β-Mercapto-β,β-cyclopentamethylenepropionyl¹,O-me-Tyr², Arg⁸]-vasopressin). Importantly, local application of micro-doses of this antagonist to the liver was sufficient to abolish the hyperglycemic response after CBR stimulation. These results suggest that AVP is a mediator of the hyperglycemic reflex and cerebral glucose retention following CBR stimulation. We propose that hepatic activation of AVP V1a receptors is essential for this hyperglycemic response.

Urethrocutaneous fistulae (UCFs) represent one of the most frequent causes of morbidity after urethroplasty. Hypospadias can be repaired using different surgical techniques, but—regardless of technique—the incidence of UCF ranges between 10% and 40%. Surgical repair of UCF remains the treatment of choice, even if some patients need further surgery because of recurrences. Cyanoacrylates have been used as skin suture substitutes, and some evidence suggests a beneficial effect when these adhesives are used as an adjuvant in the management of UCF. Here we describe the results of management of UCF using 2-octyl cyanoacrylate (OCA) compared with surgical repair. A randomized clinical trial conducted from January 2008 to December 2012 included 42 children with UCF complications after urethroplasty for hypospadias. Twenty-one children were assigned to receive OCA as ambulatory patients and 21 were treated surgically. The main outcome variable was closure of the UCF. The estimated costs of both treatments were also calculated, as were absolute risk reduction (ARR), relative risk reduction (RRR) and number needed to treat (NNT) to prevent a surgical intervention. The mean numbers of UCF were 1.3 in the OCA group (n = 28) and 1.1 in the surgical group (n = 25) with no statistically significant difference. The external orifices measured were 2.96 ± 1.0 mm and 3.8 ± 0.89 mm, respectively (NS). Sixty per cent of the UCFs treated with cyanoacrylate were completely closed and 68% of the surgical group healed completely (NS). More than one reoperation to improve complications was needed in the surgical group (3.5 ± 1.2). The clinical significance of the therapeutic usefulness of OCA was demonstrated by an ARR of 0.08, RRR of 0.25 and NNT of 12 to avoid further surgical treatment. The total costs of adhesive applications and reoperations were $US 14,809.00 and $US 158,538.50, respectively. The results showed a similar success rate for both treatments. However, sealant use should be considered before surgical treatment because this is a simple outpatient procedure with a reasonable success rate. ClinicalTrials.gov Identifier: NCT02115191 . Date: April 13, 2014.

Objectives The study’s objective was to assess the association between the PRSS1 R122H and N29I and the SPINK1 N34S mutations and acute pancreatitis (AP) and recurrent pancreatitis in Mexican pediatric patients. Methods The N34S and R122H mutations were detected using polymerase chain reaction–restriction fragment length polymorphism, and the N29I mutation was detected using allele-specific polymerase chain reaction in 92 pancreatitis patients (58 AP and 34 recurrent pancreatitis patients) and 144 controls. Results We found 1 mutated allele in 4 (4.3%) of 92 pancreatitis patients and none in the controls. All 4 patients bearing mutations had AP, with a frequency of 6.8% (4/58). Three (5.2%) of 58 patients were heterozygous for the N34S mutation, and 1 (1.7%) of 58 patients was heterozygous for the N29I mutation. The comparison between the AP and control groups revealed both a significant number of patients carrying any mutations in the screened genes (P = 0.008) and bearing the N34S mutation (P = 0.023). Moreover, we found that the N34S G allele increased the risk of developing AP (odds ratio, 10.3; confidence interval, 1.1–248.8). Conclusions Patients bearing the N34S G allele exhibited a 10-fold increased risk of developing AP compared with controls, suggesting that the SPINK1 N34S mutation represents an etiologic risk factor for AP in our Mexican pediatric patients.