Metabolic disorders and adipose tissue insulin responsiveness in neonatally STZ-induced diabetic rats are improved by long-term melatonin treatment

Diabetes mellitus is a product of low insulin sensibility and pancreatic β-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid synthase. In conclusion, melatonin treatment was capable of ameliorating the metabolic abnormalities in this particular diabetes model, including insulin resistance and promoting a better long-term glycemic control.     

Clinical trial: transcutaneous interferential electrical stimulation in individuals with irritable bowel syndrome - a prospective double-blind randomized study

Background: The exact etiology of irritable bowel syndrome (IBS) remains unclear. Curative treatment is not available and current treatment modalities are mainly directed against the predominant symptoms. There are a few studies reporting the beneficial effects of transcutaneous electrical stimulation in patients with chronic constipation, gastroparesis, and functional dyspepsia. Aim: To investigate whether transcutaneous electrical stimulation is an effective procedure in IBS patients. Methods: IBS patients were randomly placed in vacuum interferential current (IFC) and placebo groups. Both treatments consisted of 12 sessions administered over 4 weeks. Symptoms due to IBS were documented via questionnaires, including the IBS Global Assessment of Improvement Scale, numeric rating scales, visual analogue scale, and IBS Quality of Life Scale at the beginning of, end of, and 1 month after the treatment. Results: Patients in the therapy (29 cases) and placebo (29 cases) groups were homogeneous with respect to demographic data and gastrointestinal system symptoms. When compared to the beginning scores, severity of abdominal discomfort, bloating, and abdominal distension and rumbling improved significantly in either interference or placebo groups at both the end of treatment and 1 month after treatment. In the IFC group, severity of symptoms continued to decrease significantly at 1 month after treatment when compared to scores at just the end of treatment, whereas in the placebo group severity of these symptoms did not change significantly on numeric severity scales. Also, the visual analogue scale of the first month after treatment continued to decrease significantly when compared to the level at the end of treatment in the IFC group. Total quality score increased significantly in the IFC group. Conclusions: Vacuum IFC therapy can significantly improve symptoms and quality of life in patients with IBS. It may represent a novel treatment modality for drug-refractory IBS patients.     

Malignant retroperitoneal fibrosis: MRI characteristics in 50 patients

ABSTRACT: We analyzed magnetic resonance imaging (MRI) morphologic patterns of retroperitoneal fibrosis (RF) to identify those able to distinguish malignant RF (mRF) from idiopathic RF (iRF). This retrospective study concerned 50 consecutive patients with MRI-based RF diagnoses, 35 of whom also had histologically proven RF. Previous radiotherapy, abdominal or pelvic surgery or infection during the preceding 6 months, vascular aneurysm (aorta or iliac artery), presence of retroperitoneal multiple nodular masses, or enlarged lymph nodes with a diameter >15 mm constituted exclusion criteria.Patients with mRF differed from those with iRF by age, smoking habits, and follow-up duration but not by clinical manifestations, inflammatory syndrome, or renal insufficiency. MRI-documented mRF extension along the aorta, from above the renal arteries to below the aortic bifurcation, was more frequent than iRF (47% vs. 0%; p = 0.001) but less frequent between the renal arteries and the aortic bifurcation (18% vs. 50%; p = 0.04); mRF extension behind the aorta was wider than iRF (5.0 vs. 2.5 mm; p = 0.03). Neither urinary tract nor vessel involvement differed. Medial ureteral attraction was significantly less frequent in mRF than iRF (24% vs. 83%; p < 0.001), according to univariate and multivariate analyses. An algorithm based on the most discriminant criteria (RF extending from above the renal arteries to below the aortic bifurcation and the absence of medial ureteral attraction) for mRF diagnosis had 82% sensitivity and 83% specificity. When applied to the 15 iRF patients without histologic data, specificity was 73%.This mRF decision tree, consisting of the 2 most discriminant MRI criteria, could be used as a supplementary argument to support RF biopsy.     

Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats

Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 μg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.