Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress

To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concentrations were reduced by 15 and 6% in pre- and postmenopausal women, respectively (P < 0.01) after LGP supplementation. In addition, plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by approximately 15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidation was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F(2)-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process. Through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.     

Amnioinfusion in thick meconium

Objective : There are conflicting reports regarding the results of amnioinfusion in the management of meconium passagein utero. This study was done to evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labour.Methods : 196 women at term in early labour with meconium were randomized to receive either transcervical intrapartum amnioinfusion with saline (96) or routine obstetrical care (100). Transcervical amnioinfusion of one liter saline infused over 30–45 minutes. End points were relief of decelerations, incidence of vaginal delivery, presence of meconium below the neonatal cords, and X-ray evidence of meconium aspiration.Results : Amnioinfusion resulted in relief of decelerations in 75% of cases as compared to 7% in the control group. Eighty-eight percent of patients delivered vaginally as compared to 58% in the control group (p<0.001). Neonatal outcome was significantly better in the infusion group. The incidence of meconium below the vocal cords was reduced from 48% to 17% (p<0.004) using amnioinfusion with positive X-rays for meconium aspiration in only 12.5% versus 26% (p<0.5).Conclusions : We concluded that transcervical intrapartum amnioinfusion is a safe, simple and inexpensive technique that reduces operative intervention and improves neonatal outcome, and is of tremendous relevance in developing countries.     

Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury

Dilated cardiomyopathy is a life-threatening syndrome that can arise from a myriad of causes, but predisposition toward this malady is inherited in many cases. A number of inherited forms of dilated cardiomyopathy arise from mutations in genes that encode proteins involved in linking the cytoskeleton to the extracellular matrix, and disruption of this link renders the cell membrane more susceptible to injury. Membrane repair is an important cellular mechanism that animal cells have developed to survive membrane disruption. We have previously shown that dysferlin deficiency leads to defective membrane resealing in skeletal muscle and muscle necrosis; however, the function of dysferlin in the heart remains to be determined. Here, we demonstrate that dysferlin is also involved in cardiomyocyte membrane repair and that dysferlin deficiency leads to cardiomyopathy. In particular, stress exercise disturbs left ventricular function in dysferlin-null mice and increases Evans blue dye uptake in dysferlin-deficient cardiomyocytes. Furthermore, a combined deficiency of dystrophin and dysferlin leads to early onset cardiomyopathy. Our results suggest that dysferlin-mediated membrane repair is important for maintaining membrane integrity of cardiomyocytes, particularly under conditions of mechanical stress. Thus, our study establishes what we believe is a novel mechanism underlying the cardiomyopathy that results from a defective membrane repair in the absence of dysferlin.     

Colonoscopy polypectomy management in Glanzmann’s thrombasthenia

Glanzmann's thrombasthenia (GT) is a rare autosomal recessive bleeding syndrome characterized by abnormal Glycoprotein IIb/IIIa complex (GIIb/IIIa) on platelets with resultant abnormality in platelet aggregation. There is very little information regarding polypectomy management in GT. We report a single patient with this rare disease, who underwent sequential endoscopic management of large colon polyps. Polypectomy in our GT patient was complicated by immediate and delayed bleeding. Multiple clips used after standard cautery polypectomy for a polyp 10 mm or larger in our GT patient, was most effective in preventing immediate and delayed post-polypectomy bleeding than other known therapeutic approaches. We favor preemptive use of multiple clips in large polypectomy defects for GT patients and we may argue the added cost may be offset by the reduction in the need for blood products, and by averting or shortening potential hospitalizations.     

Significance of ER–Src axis in hormonal therapy resistance

The estrogen receptor (ER) is implicated in the progression of breast cancer. Despite positive effects of hormonal therapy, initial or acquired resistance to endocrine therapies frequently occurs. Recent studies suggested ERα-coregulator PELP1 and growth factor receptor ErbB2/HER2 play an essential role in hormonal therapy responsiveness. Src axis couples ERα with HER2 and PELP1, thus representing a new pathway for targeted therapy resistance. To establish the significance of ER–Src axis in PELP1 and HER2 mediated therapy resistance, we have generated model cells that stably express Src-shRNA under conditions of PELP1, HER2 deregulation. Depletion of Src using shRNA substantially reduced E2 mediated activation of Src and MAPK activation in resistant model cells. Pharmacological inhibition of Src using dasatinib, an orally available inhibitor substantially inhibited the growth of therapy resistant MCF7–PELP1, MCF7–HER2, and MCF7–Tam model cells in proliferation assays. In post-menopausal xenograft based studies, treatment with dasatinib significantly inhibited the growth of therapy resistant cells. IHC analysis revealed that the tumors were ERα positive, and dasatinib treated tumors exhibited alterations in Src and MAPK signaling pathways. Combinatorial therapy of tamoxifen with dasatinib showed better therapeutic effect compared to single agent therapy on the growth of therapy resistant PELP1 driven tumors. The results from our study showed that ER–Src axis play an important role in promoting hormonal resistance by proto-oncogenes such as HER2, PELP1, and blocking this axis prevents the development of hormonal independence in vivo. Since PELP1, HER2, and Src kinase are commonly deregulated in breast cancers, combination therapies using both endocrine agents and dasatinib may have better therapeutic effect by delaying the development of hormonal resistance.     

Lubiprostone used with polyethylene glycol in diabetic patients enhances colonoscopy preparation quality

AIM: To assess the additive effect of lubiprostone on the quality of colon preparation in diabetics given single-dosed polyethylene glycol electrolyte (PEG) for colonoscopy.METHODS: This was an investigator-initiated, single-center, single-blinded prospective trial comparing the efficacy of L + PEG to PEG alone on colon preparation quality in diabetics undergoing screening colonoscopy. The study was approved by our institution’s IRB. The PEG was given as a single-dose to address patient-compliance concerns voiced by our IRB with split-dosing. All patients received only clear liquids the day prior to colonoscopy. Experimental group (Grp L) received PEG + 1 dose L 2 h prior to and 2 h after PEG completion. Control group (Grp C) received only PEG the evening prior to the colonoscopy. Patients were randomly assigned to one of the 2 groups. The endoscopist was blinded to which colon prep was given and all colonoscopies were complete. Upon colonoscopy completion, the endoscopist rated the colon prep-quality by a validated 5-point Likert scale (1-excellent to 5-inadequate).RESULTS: Sixty patients were enrolled in the study; 30 Grp L and 30 Grp C. Overall, patients were excluded due to study non-completion in 12 (41%) Grp L and 5 (17%) Grp C, P = 0.04. Average colon preparation score Grp L = 2.47 and Grp C = 3.00, P = 0.09. Although this was not statistically significant, there was a trend towards improved colon prep in Grp L. Statistical significance may have been achieved if completion rates had been similar between both study groups.CONCLUSION: Use of 2-L capsules with PEG resulted in a trend towards improved colon prep over PEG alone in diabetic patients when given as a single-dose regimen.     

White piedra of scalp hair by Trichosporon inkin

White piedra is a rare fungal infection of hair and is reported to be all the more rare on scalp. Trichosporon inkin is usually associated with white piedra of pubic hair. We report a case of white piedra of scalp hair caused by T. inkin. This is the first case reported from India and the fifth case reported worldwide. A 50-year-old Muslim female presented with white knots over scalp hair. Diagnosis of Trichosporon was made by examining KOH mounts of epilated hair and Lactophenol Cotton Blue preparations of the growth in culture. Automated mini-API test (for biochemical profiles) and Electronmicroscopy studies (for cell wall structures) helped in identification of the species. Mini-API test was also positive for Cryptococcus curvatus which could be due to similarity in biochemical and physiological properties of the two species. Absence of C. curvatus on culture further supports this view. Topical antifungal therapy resulted in clinical clearance within 2 months. Higher incidence of scalp white piedra is observed in Muslim females; contributing factor being the custom of using a veil, leading to higher humidity and limited sunlight exposure.