Melatonin inhibits insulin secretion and decreases PKA levels without interfering with glucose metabolism in rat pancreatic islets

The effect of melatonin (0.1 microM) on freshly isolated islets from adult rats was investigated. Melatonin caused a marked decrease of insulin secretion by islets in response to glucose. The mechanism involved was then examined. Melatonin did not interfere with glucose metabolism as indicated by the measurement of glucose oxidation. However, the content of the protein kinase A (PKA) catalytic alpha-subunit was significantly decreased in islets exposed to melatonin for 1 hr in the presence of 8.3 mM glucose, whereas that of the protein kinase C (PKC) alpha-subunit remained unchanged. Melatonin also inhibited forskolin-induced insulin secretion, a well known activator of adenylate cyclase (AC) activity. This may explain the low content of insulin found in islets incubated in the presence of melatonin for 3 hr. In fact, 3',5' -cyclic adenosine monophosphate (cAMP), a product of AC activity, stimulates insulin synthesis. These findings led us to postulate that a down-regulation of the PKA signaling pathway may be the mechanism involved in the melatonin inhibition of the process of glucose-induced insulin secretion.     

Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain

Postoperative pain significantly impacts patient recovery. However, postoperative pain management remains suboptimal, perhaps because treatment strategies are based mainly on studies using inflammatory pain models. We used a recently developed mouse model of incisional pain to investigate peripheral and spinal mechanisms contributing to heat hyperalgesia after incision. Behavioral experiments involving TRPV1 KO mice demonstrate that, as previously observed in inflammatory models, TRPV1 is necessary for heat (but not mechanical) hyperalgesia after incision. However, in WT mice, neither the proportion of TRPV1 immunoreactive neurons in the DRG nor the intensity of TRPV1 staining in the sciatic nerve was different from that in controls up to 4 days after incision. This result was corroborated by immunoblot analysis of sciatic nerve in rats subjected to an incision, and is distinct from that following inflammation of the rat hind paw, a situation in which TRPV1 expression levels in sciatic nerve increases. In the absence of heat exposure, spinal c-Fos staining was similar between incised TRPV1 KO and WT mice. However, differences in c-Fos staining between heat exposed TRPV1 KO and WT mice after incision suggest that the incision-mediated enhancement of heat-evoked signaling to the spinal cord involves a TRPV1-dependent mechanism. Finally, heat hyperalgesia after incision was reversed by antagonism of spinal non-NMDA receptors, unlike inflammatory hyperalgesia, which is mediated via NMDA receptors . Thus, TRPV1 is important for the generation of thermal hyperalgesia after incision. Our observations suggest that all experimental pain models may not be equally appropriate to guide the development of postoperative pain therapies.     

Comparison of early postoperative functional levels following total hip replacement using minimally invasive versus standard incisions. A prospective randomized blinded trial

OBJECTIVE: To compare the results of single-incision minimally invasive total hip replacement (< or = 10 cm) to standard-incision (16 cm) total hip replacement in the early postoperative period with respect to functional and mobilizing ability (transfers, mobilizing, walking and stair assessment). SETTING: Orthopaedic wards of a regional orthopaedic centre. SUBJECTS: Two hundred and nineteen total hip replacement patients were tested between December 2003 and June 2004. INTERVENTIONS: Patients were randomized to either total hip replacement through a minimally invasive (< or = 10 cm) or standard incision (16 cm). A single surgeon performed all procedures using the same type of component fixation. Postoperative physiotherapy assessment and treatment was standardized. Analgesia was also standardized. All patients, physiotherapy staff and assessors were blinded to the incision used. MAIN OUTCOME MEASURES: Patients were tested two days post operatively and were assessed for the following activities: transfer from supine to sit, transfer from sitting to standing, mobilizing, ascending and descending stairs and weight-bearing. RESULTS: The shorter incision offered no significant improvement in patient ability in relation to transfer from lying to sitting, transfer from sitting to standing, mobilizing or weight-bearing. Ascending/descending stairs gave a total time for the minimal incision of 38.7 s against 40.8 s for a standard incision. There was no difference in walking velocity between the standard incision and minimal incision groups two days post operatively (minimal incision = 0.26 m/s versus standard incision = 0.26 m/s) or six weeks post operatively (minimal incision = 0.90 m/s versus standard incision = 0.93 m/s). There was no difference between groups with respect to walking aids at six-week review. The mean length of stay for the minimally invasive approach was 3.65 days (SD 2.04) against 3.68 days (SD 2.45) for the standard approach. This was not significantly different. CONCLUSION: Total hip replacement performed through a minimally invasive incision of < or = 10 cm compared with a standard incision of 16 cm offers no significant benefit in terms of the rate or ability of patients to mobilize and perform functional tasks necessary for safe discharge.     

Factors that influence the spread of HIV/AIDS among students of the University of Botswana.

The results discussed in this report are part of a larger study conducted among the students of the University of Botswana regarding their knowledge, attitudes, and behaviors related to HIV/AIDS. The study triangulated survey methods and focus group discussions. Five main areas were investigated: knowledge and personal experiences of HIV/AIDS, sexual behavior and practices, perceptions about risky sexual behavior on campus, and factors that influence the spread of HIV. This article reports high levels of risky behaviors such as alcohol and drug abuse; unprotected sex; frequent change of sexual partners; sex for financial gain, for prestige, for good grades, to relieve stress, and because of peer pressure; and casual sex as part of socializing.     

The clinical value of daily routine chest radiographs in a mixed medical–surgical intensive care unit is low

Introduction  

The clinical value of daily routine chest radiographs (CXRs) in critically ill patients is unknown. We conducted this study to evaluate how frequently unexpected predefined major abnormalities are identified with daily routine CXRs, and how often these findings lead to a change in care for intensive care unit (ICU) patients.     

MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults

Background

Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults.

Objective

To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation.

Materials and methods

We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression.

Results

We included 36 patients (22 male, 14 female; age range 8–21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression.

Conclusion

Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease.     

Interprofessional mentoring: enhancing students' clinical learning

Interprofessional (IP) collaboration is recognized as critical for patient-centred care. The clinical setting is an ideal environment for students to learn the competencies required to effectively work with providers from other professions. To enhance traditional clinical placements, we propose an IP mentoring approach, defined as learning that takes place between providers and students who are from different disciplines or health professions. In IP mentoring, students have primary relationships with their preceptors, but also have interactions with providers from other professions. We implemented IP mentoring with the support of two faculties of nursing in Alberta, Canada who provided an IP clinical focus for interested fourth year students. We emphasized to providers and students that there are no prescribed interactions that comprise IP mentoring; experiences between providers and students are context-specific and often informal. Through our evaluation we demonstrated that in IP mentoring, provider commitment was important, students engaged in IP activities of varying complexity, and students learned about roles of other professions and how to work together to provide patient-centred care. IP mentoring is an effective learning strategy to enhance students' knowledge and skills in IP collaboration without radical changes to the structure of the placements or to the educational curricula.     

Comparative protection against liver inflammation and fibrosis by a selective cyclooxygenase-2 inhibitor and a nonredox-type 5-lipoxygenase inhibitor

In this study, we examined the relative contribution of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO), two major proinflammatory pathways up-regulated in liver disease, to the progression of hepatic inflammation and fibrosis. Separate administration of 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-236), a selective COX-2 inhibitor, and CJ-13,610, a 5-LO inhibitor, to carbon tetrachloride-treated mice significantly reduced fibrosis as revealed by the analysis of Sirius Red-stained liver sections without affecting necroinflammation. Conversely, combined administration of SC-236 and 4-[3-[4-(2-methylimidazol-1-yl)-phenylthio]]phenyl-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (CJ-13,610) reduced both necroinflammation and fibrosis. These findings were confirmed in 5-LO-deficient mice receiving SC-236, which also showed reduced hepatic monocyte chemoattractant protein 1 expression. Interestingly, SC-236 and CJ-13,610 significantly increased the number of nonparenchymal liver cells with apoptotic nuclei (terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive). Additional pharmacological profiling of SC-236 and CJ-13,610 was performed in macrophages, the primary hepatic inflammatory cell type. In these cells, SC-236 inhibited prostaglandin (PG) E2 formation in a concentration-dependent manner, whereas CJ-13,610 blocked leukotriene B4 biosynthesis. Of note, the simultaneous addition of SC-236 and CJ-13,610 resulted in a higher inhibitory profile on PGE2 biosynthesis than the dual COX/5-LO inhibitor licofelone. These drugs differentially regulated interleukin-6 mRNA expression in macrophages. Taken together, these findings indicate that both COX-2 and 5-LO pathways are contributing factors to hepatic inflammation and fibrosis and that these two pathways of the arachidonic acid cascade represent potential targets for therapy.