Short-term weight loss reverses obesity-induced microvascular endothelial dysfunction

Obesity is one of the major risk factors for cardiovascular diseases and its prevalence is increasing in all age groups, with the biggest impact observed in middle-aged and older adults. A critical mechanism by which obesity promotes vascular pathologies in these patients involves impairment of endothelial function. While endothelial dysfunction in large vessels promotes atherogenesis, obesity-induced microvascular endothelial dysfunction impairs organ perfusion and thereby is causally related to the pathogenesis of ischemic heart disease, chronic kidney disease, intermittent claudication, exercise intolerance, and exacerbates cognitive decline in aging. Reduction of weight via calorie-based diet and exercise in animal models of obesity results in significant improvement of endothelial function both in large vessels and in the microcirculation, primarily due to attenuation of oxidative stress and inflammation. Clinical data on the protective effects of weight loss on endothelial function is limited to studies of flow-mediated dilation assessed in brachial arteries. Currently, there is no guideline on testing the effects of different weight management strategies on microvascular endothelial function in obese patients. Here, we provide proof-of-concept that weight loss-induced improvement of microvascular endothelial function can be reliably assessed in the setting of a geriatric outpatient clinic using a fast, reproducible, non-invasive method: laser speckle contrast imaging-based measurement of endothelium-dependent microvascular responses during post-occlusive reactive hyperemia tests. Our study also provides initial evidence that short-term weight loss induced by consumption of a low-carbohydrate low-calorie diet can reverse microvascular endothelial dysfunction associated with obesity.     

Endovascular Management of Extra-cranial Supra-aortic Vascular Injuries

Supra-aortic vessel injuries are uncommon but can be life-threatening and surgically challenging. Trauma to these vessels may be blunt or penetrating, including iatrogenic trauma following the insertion of central venous lines, which may be preventable. Recent advances in technology have resulted in endovascular therapy becoming a common first-line treatment, and interventional radiologists now play a major role in the management of these vascular injuries. We review the literature on the endovascular management of these types of injuries and describe a spectrum of case-based extra-cranial supra-aortic vascular injuries managed at our institution and the range of imaging appearances, including active contrast extravasation, traumatic vessel occlusion, true aneurysms, pseudoaneurysms, and arteriovenous fistulae.     

Interrelationship of prolactin and its receptor in carcinoma of colon and rectum: A preliminary report

The prolactin receptors (PRLR) were correlated with circulating prolactin arious clinicopathologic parameters to investigate its prognostic value in patients with colorectal cancer. The prolactin (by radioimmunoassay) and its receptors (by radioligand method) were estimated in a total of 71 male patients with colorectal cancer enrolled at the Gujarat Cancer and Research Institute, Ahmedabad. The patients were followed for a period of 3 years. We have observed that 51% colorectal tumors were PRLR⁺. Significant correlation was not observed between presence/absence of PRLR and clinicopathologic variables. Dukes' D patients were lost to follow-up after 2–3 months; therefore, the results of prognostic significance were analysed only in patients with Dukes' A, B, and C (N = 64). Statistically significant difference in overall survival was not observed when the patients were subgrouped according to the presence/absence of PRLR and according to the cutoff level (i.e., 2%). PRLR⁺ hyperprolactinemic (Prolactin > 20.0 ng/ml plasma) patients had better overall survival than that of patients with PRLR^? hyperprolactinemia, although the difference was statistically nonsignificant. However, PRLR^? hyperprolactinemia patients had a more unfavourable prognosis than that of their counterparts. A similar trend was observed in patients with Dukes' B and C disease. Our preliminary study suggests an unequivocal finding, that PRLR^?with concomitant hyperprolactinemia probably characterises a subgroup of patients with aggressive colorectal cancer. © Wiley-Liss, Inc.     

Presurgical Serum Albumin Levels Predict Survival Time from Glioblastoma Multiforme

To determine whether serum albumin levels, before first surgery, predict time until death, 24 glioblastoma multiforme patients newly diagnosed at Ohio State University and Cleveland Clinic Foundation Hospitals between 1993 and 1995 were followed until 1996. Patients with presurgical serum albumin levels below 3.4mg/dL survived an average (median) of 62 days (95% confidence interval (CI): 34, 135 days) after surgery. Those with serum albumin levels of at least 3.4mg/dL survived an average of 494 days (95% CI: 241, 624 days). The association between serum albumin level and time until death persists when adjusted for demographic and treatment variables using Cox proportional hazards regression. Adjusted hazard ratios, by quartile of presurgical serum albumin level, are: 1.0, 1.2, 0.1, 0.1 (P-value for trend test=0.007). In addition to providing a prognostic indicator, presurgical serum albumin levels can be used to evaluate the success of randomization of clinical trials for glioblastoma multiforme therapies. Our findings are consistent with results seen for tumors at other sites. We speculate that our results may be attributable to an association between low serum albumin levels and physiological events associated with angiogenesis.     

Curculigoside augments cell-mediated immune responses in metastatic tumor-bearing animals

A positive modulation of immune system is necessary for preparing the body to fight against malignant tumor cells. In the present study, the stimulatory effect of Curculigoside on cell-mediated immune response against the metastasis of B16F10 melanoma cells was analyzed in C57BL/6 mice. Curculigoside is a phenolic glucoside present in the plant Curculigo orchioides Gaertn. (Family – Amaryllidaceae). Administration of Curculigoside enhanced the natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity in metastatic tumor-bearing animals, when compared to the untreated control animals. The compound was also found to be effective in reducing the levels of proinflammatory cytokines such as TNF-α, IL-1β, IL-6 and GM-CSF during metastasis. Besides these, levels of TH1 cytokines, such as IL-2 and IFN-γ, were significantly enhanced (p?相似文献   

National trends of acute kidney injury requiring dialysis in decompensated cirrhosis hospitalizations in the United States

Background and aims

Cirrhosis affects 5.5 million patients with estimated costs of US$4 billion. Previous studies about dialysis requiring acute kidney injury (AKI-D) in decompensated cirrhosis (DC) are from a single center/year. We aimed to describe national trends of incidence and impact of AKI-D in DC hospitalizations.

Methods

We extracted our cohort from the Nationwide Inpatient Sample (NIS) from 2006–2012. We identified hospitalizations with DC and AKI-D by validated ICD9 codes. We analyzed temporal changes in DC hospitalizations complicated by AKI-D and utilized multivariable logistic regression models to estimate AKI-D impact on hospital mortality.

Results

We identified a total of 3,655,700 adult DC hospitalizations from 2006 to 2012 of which 78,015 (2.1 %) had AKI-D. The proportion with AKI-D increased from 1.5 % in 2006 to 2.23 % in 2012; it was stable between 2009 and 2012 despite an increase in absolute numbers from 6773 to 13,930. The overall hospital mortality was significantly higher in hospitalizations with AKI-D versus those without (40.87 vs. 6.96 %; p < 0.001). In an adjusted multivariable analysis, adjusted odds ratio for mortality was 2.17 (95 % CI 2.06–2.28; p < 0.01) with AKI-D, which was stable from 2006 to 2012. Changes in demographics and increases in acute/chronic comorbidities and procedures explained temporal changes in AKI-D.

Conclusions

Proportion of DC hospitalizations with AKI-D increased from 2006 to 2009, and although this was stable from 2009 to 2012, there was an increase in absolute cases. These results elucidate the burden of AKI-D on DC hospitalizations and excess associated mortality, as well as highlight the importance of prevention, early diagnosis and testing of novel interventions in this vulnerable population.

     

Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice

Borneol, a bicyclic monoterpene, can easily cross the blood brain barrier and was found to possess gamma amino butyric acid (GABA) modulatory effect. The present study was aimed at investigating the antiepileptogenic effect of borneol in the pentylenetetrazole (PTZ)-induced kindling besides its ability to suppress oxidative stress and neuroinflammatory marker, glial fibrillary acidic protein (GFAP). Repeated administration of a subconvulsive dose of PTZ (35 mg/kg, i.p.) on every alternate day for 4 weeks produced kindling in mice. Borneol (5, 10, and 25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were given as a pretreatment prior to each PTZ injection during the progression of kindling. Oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and lipid peroxidation (LPO) were assessed at the end of the study. Neuronal damage was assessed by hematoxylin and eosin staining technique. GFAP was also evaluated in the hippocampus region of the brain by using immunohistochemistry. Borneol significantly suppressed the process of epileptogenesis in PTZ-kindled mice. The biochemical alterations induced by PTZ kindling were ameliorated in borneol-treated animals which was indicated by decreased LPO and increased SOD, GSH, CAT levels. The distinct neuronal damage observed in the kindled group was counteracted by borneol. Furthermore, it decreased the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the antiepileptogenic potential of borneol in the PTZ-induced kindling model of epilepsy, and thus, it could be a prospective molecule in the treatment of epilepsy.