Doppler measurements: a surrogate marker of liver fibrosis?

OBJECTIVE: The potential diagnostic value of performing Doppler measurements of liver vasculature to assess early stages of liver fibrosis has not been established. Due to the potential clinical impact, this study focused on the correlation between Doppler measurements and histologically proven liver fibrosis. METHODS: Forty-three consecutive patients with chronic viral hepatitis (79% hepatitis C) were enrolled. At the time of liver biopsy, two independent investigators measured maximum and mean blood flow velocity, resistance indices, vessel diameter and blood flow volume in the portal vein, hepatic artery and hepatic veins. All measurements were taken in triplicate. The mean values were correlated to the degree of liver fibrosis using the Ludwig score. RESULTS: Sixty-seven per cent of the patients in our study group had no or only mild fibrosis (Ludwig score stage I or II). Thirty-three per cent showed progressive fibrosis or cirrhosis (Ludwig score stage III or IV). There was a large overlap in the Doppler measurements and findings between the various disease stages. No significant changes of Doppler parameters were detected, even between patients with no or mild fibrosis and patients with severe fibrosis (Ludwig score stage III or IV). CONCLUSIONS: Doppler measurements of the portal vein, hepatic artery and hepatic vein(s) are not a valid surrogate marker of liver fibrosis. Nor are Doppler measurements a useful method to estimate the degree of liver fibrosis.     

Evaluation of a synthetic oligonucleotide probe for diagnosis of Plasmodium falciparum infections

A radiolabeled synthetic oligonucleotide was evaluated as a diagnostic probe specific for Plasmodium falciparum using blood samples lysed directly on nitrocellulose filters. The probe technique successfully diagnosed malaria in experimentally infected chimpanzees that had 0.001% parasitemias (50 parasites/microliter) as determined by blood smears, and in 1 chimpanzee whose blood smear was negative, but whose blood was culture-positive for P. falciparum. In a double blind study of 50 patient samples from the Philippines, the probe results correlated well with blood smear results when the autoradiographs were read after 4-8 hr exposure. The results indicate that the oligonucleotide probe may be useful in the rapid and specific diagnosis of P. falciparum infection.     

Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear factor erythroid 2-related factor 2 activation

One hallmark of Alzheimer's disease is the accumulation of amyloid beta-peptide (AP), which can initiate a cascade of oxidative events that may result in neuronal death. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is the major regulator for a battery of genes encoding detoxifying and antioxidative enzymes via binding to the antioxidant response element (ARE), it is of great interest to find nontoxic activators of Nrf2 rendering neuronal cells more resistant to AP toxicity. Using ARE-luciferase assay and Western blot, we provide evidence that the kavalactones methysticin, kavain, and yangonin activate Nrf2 time- and dose-dependently in neural PC-12 and astroglial C6 cells and thereby up-regulate cytoprotective genes. Viability and cytotoxicity assays demonstrate that Nrf2 activation is able to protect neural cells from amyloid beta-(1-42) induced neurotoxicity. Down-regulation of Nrf2 by small hairpin RNA as well as extracellular signal-regulated kinase 1/2 inhibition abolishes cytoprotection. We further give evidence that kavalactone-mediated Nrf2 activation is not dependent on oxidative stress production. Our results demonstrate that kavalactones attenuate amyloid beta-peptide toxicity by inducing protective gene expression mediated by Nrf2 activation in vitro. These findings indicate that the use of purified kavalactones might be considered as an adjunct therapeutic strategy to combat neural demise in Alzheimer disease and other oxidative stress-related diseases.     

The role of leptin and cortisol in hyperactivity in patients with acute and weight-recovered anorexia nervosa

Introduction

In food-restricted rats, leptin as well as corticotropin releasing factor attenuate semistarvation-induced hyperactivity (SIH). Results from studies in patients with anorexia nervosa (AN) showed an association between excessive physical activity (PA) and leptin. One recent report suggests a role for cortisol in PA. In this study, we assessed the relationships between PA and both, cortisol and leptin levels at the same time in patients with acute anorexia nervosa (acAN) in comparison to recovered patients (recAN).

Methods

Plasma leptin, plasma cortisol, body mass index (BMI), and expert-ratings of qualities of PA were assessed in 36 acAN patients, 27 recAN patients and 44 healthy control woman (HCW). Regression analyses were used to predict PA using BMI, leptin and cortisol levels as predictor variables.

Results

Leptin levels but not cortisol significantly contributed to the prediction of PA in acAN. In recAN PA was not elevated and not related to endocrine parameters but correlated positively with core eating disorder symptoms.

Conclusions

Our work lends support to the proposed inverse association between peripheral leptin levels and excessive physical activity in AN. This relationship is specific to the state of semistarvation. The role of additional mediators remains to be clarified.     

Schlauchmagenbildung in der Behandlung der morbiden Adipositas

Background

Surgery for morbid obesity is also becoming more important in Germany. Besides standard procedures such as the Roux-en-Y (RNY) bypass, sleeve gastrectomy seems to be a new option which is mainly related to gastric restriction, neurohumoral changes and other unknown factors. The results of sleeve gastrectomy have to be compared with other established procedures such as the RNY bypass according the complication rate, weight loss and improvement of weight-related comorbidities such as diabetes and hypertension.

Patients and Methods

Between May 2008 and August 2009 sleeve gastrectomy was performed in a total of 200 patients (136 female and 64 male) with an obesity grade II?CIII. The average age of the patients was 43 years (range 21?C72 years) and the average BMI 47.9?kg/m² (range 35.5?C75.3?kg/m²). Of the patients 70 (35%) were diabetics and 96 (48%) suffered from hypertension. In 14 cases the operation was planned using the transvaginal assisted (hybrid NOTES) technique.

Results

Laparoscopic sleeve gastrectomy was possible in all patients. Of the patients 3 (1.5%) suffered from postoperative complications, such as leakage from the suture line in 2 (1%) cases and in 1 case (0.5%) with hemorrhaging from the abdominal wall and subsequent pulmonary embolism resulting in a mortality rate of 1% (2 cases). In the 197 cases without complications the mean hospital stay was 3.5 days (range 2?C9 days). Using the transvaginal technique the number of trocars could be reduced by 1?C2 and in all cases the resected stomach was retrieved transvaginally. No complications occurred due to the vaginal access. Antidiabetic medication was stopped 3 months after the operation in 45 (64%) out of 70 diabetics and the need for antihypertension drugs was also reduced. The mean weight loss after 3, 6 and 12 months was 27.3%, 41% and 58%, respectively.

Conclusions

Sleeve gastrectomy seems to be an effective surgical option for the treatment of morbid obesity with a low complication rate. During the first year after the operation weight loss was excellent and weight-related comorbidities such as diabetes and hypertension improved significantly. The transvaginal hybrid NOTES technique can be performed but there is still need for additional trocars through the abdominal wall. Long-term results with respect to a durable weight loss and obesity-associated comorbidities are still lacking. The results of sleeve gastrectomy are at present comparable to those of a RNY bypass.     

Intraarticular injection of platelet‐rich plasma reduces inflammation in a pig model of rheumatoid arthritis of the knee joint

Objective

Treatment options for rheumatoid arthritis range from symptomatic approaches to modern molecular interventions such as inhibition of inflammatory mediators. Inhibition of inflammation by platelet‐rich plasma (PRP) has been proposed as a treatment for tendinitis and osteoarthritis. The present study was undertaken to investigate the effect of PRP on antigen‐induced arthritis (AIA) of the knee joint in a large animal model.

Methods

Six‐month‐old pigs (n = 10) were systemically immunized by bovine serum albumin (BSA) injection, and arthritis was induced by intraarticular BSA injection. PRP was injected into the knee joints of 5 of the animals after 2 weeks. An additional 5 animals received no systemic immunization (controls). Signs of arthritis were documented by plain histologic analysis, Safranin O staining, and immunohistochemistry analysis for type II collagen (CII), interleukin‐6 (IL‐6), and vascular endothelial growth factor (VEGF). Interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor α (TNFα), VEGF, and insulin‐like growth factor 1 (IGF‐1) protein content was measured by Luminex assay.

Results

In the pigs with AIA, plain histologic analysis revealed severe arthritic changes in the synovium. Safranin O and CII staining showed decreased proteoglycan and CII content in cartilage. Immunohistochemistry analysis revealed increased levels of IL‐6 and VEGF in synovium and cartilage, and protein concentrations of IL‐6, VEGF, IL‐1β, and IGF‐1 in synovium and cartilage were elevated as well; in addition, TNFα protein was increased in cartilage. Treatment with PRP led to attenuation of these arthritic changes in the synovium and cartilage.

Conclusion

We have described a porcine model of AIA. Experiments using this model demonstrated that PRP can attenuate arthritic changes as assessed histologically and based on protein synthesis of typical inflammatory mediators in the synovial membrane and cartilage.