Bivalent Ligands Targeting Multiple Pathological Factors Involved in Alzheimer's Disease

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Doppler echocardiography in normally functioning replacement aortic valves: a review of 129 studies

Echocardiography is the technique of choice for the assessment of replacement aortic valves. Hemodynamic function depends on the design and size of the valve. This review summarizes the published information available to the end of 2005. The most obstructive valve was the caged-ball, followed by the stented porcine and single tilting-disc valves. The stented bovine pericardial valves were slightly less obstructive than these, and similar to the intra-annular bileaflet mechanical valves. Stentless valves appeared slightly less obstructive still, and similar to reduced-cuff mechanical bileaflet valves. Homografts were the least obstructive. Approximate guide thresholds suggesting obstruction were derived.     

In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn

Objectives:

To evaluate the ethanolic and aqueous extracts of Bauhinia variegata Linn. for in vitro antioxidant and antihyperlipidemic activity.

Materials and Methods:

Ethanolic and aqueous extracts of the stem bark and root of B. variegata Linn. were prepared and assessed for in vitro antioxidant activity by various methods namely total reducing power, scavenging of various free radicals such as 1,2-diphenyl-2-picrylhydrazyl (DPPH), super oxide, nitric oxide, and hydrogen peroxide. The percentage scavenging of various free radicals were compared with standard antioxidants such as ascorbic acid and butylated hydroxyl anisole (BHA). The extracts were also evaluated for antihyperlipidemic activity in Triton WR-1339 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by estimating serum triglyceride, very low density lipids (VLDL), cholesterol, low-density lipids (LDL), and high-density lipid (HDL) levels.

Result:

Significant antioxidant activity was observed in all the methods, (P < 0.01) for reducing power and (P < 0.001) for scavenging DPPH, super oxide, nitric oxide, and hydrogen peroxide radicals. The extracts showed significant reduction (P < 0.01) in cholesterol at 6 and 24 h and (P < 0.05) at 48 h. There was significant reduction (P < 0.01) in triglyceride level at 6, 24, and 48 h. The VLDL level was also significantly (P < 0.05) reduced from 24 h and maximum reduction (P < 0.01) was seen at 48 h. There was significant increase (P < 0.01) in HDL at 6, 24, and 48 h.

Conclusion:

From the results, it is evident that alcoholic and aqueous extracts of B. variegata Linn. can effectively decrease plasma cholesterol, triglyceride, LDL, and VLDL and increase plasma HDL levels. In addition, the alcoholic and aqueous extracts have shown significant antioxidant activity. By the virtue of its antioxidant activity, B. variegata Linn. may show antihyperlipidemic activity.     

A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury

In nonalcoholic fatty liver disease, the pathogenesis of progression from simple steatosis to steatohepatitis has not been fully clarified. Many factors, including oxidative stress and hepatic immune regulation, contribute to the inflammation in steatosis. Because regulatory T cells (Tregs) are important components of immune regulation, we have now investigated their role in the pathogenesis of nonalcoholic steatohepatitis. Wild-type C57BL/6 mice were fed a high-fat (HF) diet to induce steatosis, and the hepatic lymphocyte population was analyzed by flow cytometry. HF-induced steatosis was associated with the depletion of hepatic Tregs and led to up-regulation of the inflammatory tumor necrosis factor-alpha signaling pathway. When challenged by exogenous lipopolysaccharide, the HF-fed mice developed liver inflammation. In contrast, the adoptive transfer of Tregs decreased inflammation in HF-fed mice. In comparison with effector T cells, Tregs had a lower expression of Bcl-2 and, therefore, increased susceptibility to oxidative stress-induced apoptosis. The treatment of mice with the antioxidant Mn(III)tetrakis(4-benzoic acid)porphyrin chloride reduced Treg apoptosis, increased the number of hepatic Tregs, and decreased hepatic inflammation in HF-fed mice. CONCLUSION: Our results indicate that increased oxidative stress in a fatty liver causes the apoptosis of Tregs, reduces the number of hepatic Tregs, and leads to a lowered suppression of inflammatory responses. This scenario is likely one of the pathogenetic mechanisms that facilitate the transformation of simple steatosis into steatohepatitis when a fatty liver is exposed to second or third hits.     

Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells

In the 60% pancreatectomy (Px) rat model of beta-cell adaptation, normoglycemia is maintained by an initial week of beta-cell hyperplasia that ceases and is followed by enhanced beta-cell function. It is unknown how this complex series of events is regulated. We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. As PPAR-gamma activation is known to both lower proliferation and have prodifferentiation effects in many tissues, we studied PPAR-gamma actions in INS-1 cells. A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. Additional studies are needed to determine whether there is a regulatory role for PPAR-gamma signaling in the beta-cell adaptation following a 60% Px in rats.     

Simultaneous or sequential combined living donor-intestine transplantation in children

BACKGROUND: Since the report of the first successful living donor combined liver-intestine transplant in pediatric patients, three other cases have been performed. In this article, we describe surgical technique, outcome, and propose a broader application of this procedure using deceased donors. PATIENTS: Four children of mean age 15.5 months (11-24 months) and weight 9.5 kg (8-10.9 kg) affected by end-stage liver and intestinal failure underwent living donor combined liver-intestine transplant with a left lateral liver and a distal segment of jejunum. In one case, the organs were transplanted simultaneously and in three in staged procedures. In all cases the liver transplant was performed first. The intestine was always transplanted with systemic venous drainage. The biliary anastomosis was a duct-to-duct, a biliodigestive, or a combined one according to the biliary anatomy of the liver graft. The abdomen was routinely closed with a Vicryl mesh followed by a skin graft. A loop graft ileostomy was fashioned for protocol biopsies and taken down within 3 months. RESULTS: One intestine was lost to generalized ischemia. The child was promptly retransplanted with another living donor graft. All children are alive and well at an average follow-up of 30 months (18-54 months). CONCLUSIONS: Living donor combined liver-intestine transplant can be performed successfully with excellent early outcome. The in situ splitting technique here described can be applied to obtain grafts for small children from appropriate adult deceased donors.     

Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging

Introduction

Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI.

Methods

200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events.

Results

On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B = 0.02, SE = 0.02, p < 0.001). Routine TTE had a sensitivity of 21–24% and a specificity of 95–98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ = 0.91 and κ = 0.96) compared to TTE (κ = 0.74 and κ = 0.53).

Conclusion

LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large.     

Acute kidney injury following implementation of an enhanced recovery after surgery (ERAS) protocol in colorectal surgery

Purpose

Fluid management within Enhanced Recovery After Surgery (ERAS) protocols is designed to maintain a euvolemic state avoiding the negative sequelae of hypervolemia or hypovolemia. We sought to determine the effect of a recent ERAS protocol implementation on kidney function and on the incidence of postoperative acute kidney injury (AKI).

Methods

A total of 132 elective colorectal resections performed using our ERAS protocol were compared to a propensity-matched group prior to ERAS implementation. Fluid balance, urine output, creatinine, and blood urea nitrogen (BUN) were recorded for all patients, and the incidence of AKI was determined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Results

Implementation of our ERAS protocol decreased average postoperative length of hospital stay (5.5 vs 7.7 days, p <?0.0001) and time to return of bowel function (2.5 vs 4.1 days, p <?0.0001). The rate of postoperative AKI increased following implementation of the protocol (11.4 vs 2.3%, p <?0.0001). However, by the time of discharge, the average creatinine of ERAS patients who had experienced AKI had returned to their preoperative baseline values (p =?0.9037). Significant univariate predictors of AKI in ERAS patients were longer operative times (p <?0.01) and the diagnosis of diverticulitis (p <?0.01). Within our ERAS patients, AKI was associated with a prolonged postoperative length of hospital stay (p <?0.01).

Conclusions

Despite the proven benefits of the Enhanced Recovery After Surgery (ERAS) protocols, care should be taken during protocol implementation to monitor for and to prevent acute kidney injury.

     

Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II

INTRODUCTION: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Baseline predictors of temporal BMD changes (DeltaBMD) in AN, including 1) gastrointestinal peptides regulating food intake and appetite that have been related to bone metabolism and 2) bone turnover markers, have not been well characterized. We hypothesized that baseline levels of nutritionally regulated hormones and of bone turnover markers would predict DeltaBMD overall. METHODS: In a prospective observational study, lumbar and whole-body BMD was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Baseline body mass index, lean mass, nutritionally regulated hormones [IGF-I, cortisol, ghrelin, leptin, and peptide YY (PYY)], bone formation, and resorption markers were examined to determine nutritional and hormonal predictors of bone density changes. RESULTS: In a regression model, baseline ghrelin and PYY predicted changes in spine bone measures; and baseline ghrelin, cortisol, and PYY predicted changes in whole-body bone measures independent of baseline nutritional status. CONCLUSIONS: Neuroendocrine gastrointestinal-derived peptides regulating food intake are independent predictors of changes in bone mass in AN.