Protective effect of melatonin on beta-cell damage in streptozotocin-induced diabetes in rats

The aim of the present study was the evaluation of possible protective effects of melatonin against beta-cell damage in streptozotocin-induced diabetes in rats. Malondialdehyde levels and glutathione peroxidase activity were measured in pancreatic homogenates. Pancreatic beta-cells were examined by immunohistochemical methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for induction of diabetes. Melatonin (200 microg/kg/day, ip) was injected for 3 days prior to administration of streptozotocin; these injections were continued until the end of the study (4 weeks). Streptozotocin induced a significant increase in malondialdehyde levels (p < 0.01) and a significant decrease in glutathione peroxidase activity (p < 0.05) in pancreatic tissue. Degeneration of islet cells and weak immunohistochemical staining of insulin was observed in diabetic rats. Treatment of diabetic rats with melatonin markedly reduced malondialdehyde production (p < 0.05) and increased glutathione peroxidase activity (p < 0.01) without affecting hyperglycemia. Increased staining of insulin and preservation of islet cells were apparent in the melatonin-treated diabetic rats. These data suggest that melatonin treatment has a therapeutic effect in diabetes by reduction of oxidative stress and preservation of pancreatic beta-cell integrity.     

The claw paw mutation reveals a role for Lgi4 in peripheral nerve development

Peripheral nerve development results from multiple cellular interactions between axons, Schwann cells and the surrounding mesenchymal tissue. The delayed axonal sorting and hypomyelination throughout the peripheral nervous system of claw paw (clp) mutant mice suggest that the clp gene product is critical for these interactions. Here we identify the clp mutation as a 225-bp insertion in the Lgi4 gene. Lgi4 encodes a secreted and glycosylated leucine-rich repeat protein and is expressed in Schwann cells. The clp mutation affects Lgi4 mRNA splicing, resulting in a mutant protein that is retained in the cell. Additionally, siRNA-mediated downregulation of Lgi4 in wild-type neuron-Schwann cell cocultures inhibits myelination, whereas exogenous Lgi4 restores myelination in clp/clp cultures. Thus, the abnormalities observed in clp mice are attributable to the loss of Lgi4 function, and they identify Lgi4 as a new component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation.     

Melatonin attenuates renal ischemia-reperfusion injury in nitric oxide synthase inhibited rats

Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.48+/-0.2mg/l serum) than in the control group (2.69+/-0.2mg/l serum). L-NAME (40 mgkg(-1) for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.     

Assessment of ischemia-modified albumin level in patients with recurrent pregnancy loss during the first trimester

Objective

The finding that ischemia-modified albumin (IMA) is increased in pre-eclamptic pregnancy suggests a role for IMA as a potential biomarker for abnormal placental development related to miscarriage. This study was undertaken to evaluate IMA levels in women with recurrent pregnancy loss (RPL).

Study design

This case-control study was performed between March 2008 and September 2009, at the Department of Obstetrics and Gynecology of Meram School of Medicine. Serum IMA and albumin concentrations were assessed in 43 women with a history of two or more unexplained first trimester miscarriages (group 1), and 42 healthy pregnant women (group 2) in the first trimester. IMA, adjusted IMA and albumin concentrations were compared between the groups. Statistical analysis was performed using Student's t-test and Mann-Whitney U test.

Results

IMA and adjusted IMA levels were significantly higher in women with RPL (1.11 + 0.08 and 1.09 + 0.09, respectively) compared to women in group 2 (0.88 + 0.10 and 0.88 + 0.11, respectively). Albumin levels in group 1 were significantly lower compared with group 2. There was a negative correlation between IMAand albumin levels in each group.

Conclusion

Maternal IMA levels appear to be elevated in women with early RPL. This finding may suggest that an abnormally high hypoxic intrauterine environment may be associated with abnormal placental development that contributes to early miscarriage.     

Uptake of dehydroascorbic acid in high-GSH and normal-GSH dog erythrocytes

Uptake of dehydroascorbic acid (DHA) was studied in two types of dog erythrocytes with high GSH and normal GSH levels. Compared with ascorbic acid uptake, DHA produced a much greater ascorbic acid accumulation in dog erythrocytes. Both dog erythrocytes showed a concentration dependence of DHA uptake, and cellular ascorbic acid concentrations were significantly higher in high-GSH cells than in normal-GSH cells. Glucose and cytochalasin B inhibited DHA uptake. This suggests that DHA enters dog erythrocytes predominantly by the facilitated glucose transporter, particularly by the Glut 1 glucose transporter. The rate of glucose uptake was quite similar in the two types of cells. Compared with normal-GSH cells, high-GSH cells were more resistant to oxidative stress induced by high concentration of DHA. As a rapid entry of DHA inflicts on cells a heavy demand for GSH for its reduction to ascorbic acid, high-GSH cells containing a larger reserve of GSH have an advantage over normal-GSH cells in both ascorbic acid accumulation and resisting oxidative stress produced by DHA.     

Immunoglobulin abnormalities and effects of enzyme replacement therapy in children with Gaucher disease

Hyperimmunoglobulinemia is documented in patients with Gaucher disease of all ages. We investigated the frequency of hyperimmunoglobulinemia in 12 pediatric patients with type I and III Gaucher disease and the effects of enzyme replacement therapy on these abnormalities. The incidence of hyperimmunoglobulinemia was 77%, 66%, and 60% at the diagnosis, before and after ERT, respectively. Immunoglobulin G abnormalities were the most commonly seen isotype abnormality. After enzyme replacement therapy normalization of IgA and IgM levels were recorded but decline in IgG levels was less likely to occur. This study indicated the higher frequency of hyperimmunoglobulinemia in pediatric Gaucher patients.     

Implementing patient question-prompt lists into routine cancer care

Objective

To examine the feasibility and acceptability of routine provision of patient question prompt lists (QPLs) to promote patient participation and patient-clinician communication in medical consultations.

Methods

Four cancer centres across NSW, Australia (two rural, two urban) were invited to participate, involving distribution of QPLs to patients seeing a medical or radiation oncologist, or palliative care clinician. Patients rated their satisfaction after their next consultation. Cancer specialists provided their views at the end of the study.

Results

Sixty-four percent (389/606) of patients attending consultations received a QPL. Of patients offered a QPL (426), 91% accepted. Of 139 patients surveyed post-consultation, 89% reported reading the QPL and, of these, 44% referred to the QPL during the consultation at least once. All of 10 cancer specialists providing their views post-implementation reported that QPL implementation in routine practice was feasible and did not strain resources.

Conclusions

Cancer patients and cancer specialists showed support for routine dissemination of the QPL.

Practice implications

For successful implementation of evidence-based tools we recommend promotion by local clinical champions, negotiation with clinic staff about dissemination methods, raised patient awareness through on-site project facilitators, media, consumer and support groups, and availability of resources in hard copy and via online sources.     

Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study

Background

Patients with osteoarthritis (OA) take a variety of health supplements in an attempt to reduce pain and improve function. The aim of this study was to determine the efficacy of methylsulfonylmethane (MSM) in treating patients with knee OA.

Methods

This study was a prospective, randomized, double-blind, controlled clinical trial. Forty nine men and women 45-90 (mean 68 ± SD 7.3) years of age with knee OA according to the American College of Rheumatology clinical criteria for OA of the knee and with radiographic confirmed knee OA were enrolled in the study and randomly assigned into 2 groups: One received MSM in doses of 1.125 grams 3 times daily for 12 weeks and the other received a placebo in the same dosing frequency. The primary outcomes were the WOMAC Osteoarthritis Index for pain, stiffness and physical function, the Aggregated Locomotor Function (ALF) test that evaluates each patient's physical function, the SF-36 quality of life health survey and the visual-analogue-scale (VAS) for pain. The secondary outcomes were Knee Society Clinical Rating System for Knee Score (KSKS) and Function Score (KSFS). Patients were assessed at baseline, 6 weeks and 12 weeks. All continuous variables were tested by the Kolmogorov-Smirnov test for Normal distribution. Changes within the groups and differences between the groups were calculated by repeated measures of analysis (ANOVA) with one nested variable.

Results

There were significant differences between treatment groups over time in WOMAC physical function (14.6 mm [CI: 4.3, 25.0]; p = 0.04) and in WOMAC total score (15.0 mm [CI: 5.1, 24.9]; p = 0.03). Treatment groups did not differ significantly in WOMAC pain (12.4 mm [CI: 0.0, 24.8]); p = 0.08) or WOMAC stiffness (27.2 mm [CI: 8.2, 46.2]; p = 0.08). There was a non-significant difference in SF-36 total score between treatment groups (11.6 [CI: 1.0, 22.1]; p = 0.54). A significant difference was found between groups in VAS for pain (0.7 s [CI: -0.9, 2.4]; p = 0.05). Secondary outcomes showed non-significant differences between the two groups.

Conclusions

Patients with OA of the knee taking MSM for 12 weeks showed an improvement in pain and physical function. These improvements, however, are small and it is yet to be determined if they are of clinical significance.

Trial Registration

ClinicalTrials.gov: NCT01188213

     

Melatonin protects against epirubicin-induced cardiotoxicity

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.     

A heroin epidemic at the intersection of histories: the 1960s epidemic among African Americans in Baltimore

In the drug field the fundamental epidemiological question-why illicit drug use, here, now, among these people-has still not been adequately answered. Drawing on the work of colleagues in medical anthropology, we attempt to move closer to an answer by developing a "trend theory." In this article we analyze a single case: the increase in heroin use and addiction among African Americans in the City of Baltimore in the 1960s. We found that the two most important historical processes behind the epidemic were (1) a changing distribution/supply system and (2) the mix of hope and despair that was part of the early civil rights movement.