Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B-related cirrhosis

Abstract Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B-related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 μg/h, following a bolus injection of 250 μg. In systemic haemodynamics, the mean arterial pressure (MAP) increased ( P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P = 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion ( P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min ( P = 0.057) and 30 min ( P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus-related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.     

A FUNCTIONAL DECLINE MODEL FOR PREVALENT COHORT DATA

Longitudinal designs are often used for studying the natural history of diseases. Data sets typically consist of short series of repeated measures on prevalent cases. We propose a growth model approach to the analysis of follow-up data to describe functional decline and associated risk factors in disease progression. We illustrate the model with an application to longitudinal data that describe the time-evolution of cognitive decline in a cohort of patients with Alzheimer's disease.     

Methylprednisolone Inhibits the Expression of Glial Fibrillary Acidic Protein and Chondroitin Sulfate Proteoglycans in Reactivated Astrocytes

创伤后的神经胶质增生导致硫酸软骨素蛋白聚糖(CSPG)的显著表达,从而抑制轴突生长和再生。甲基强地松龙(MP),一种合成的糖皮质激素,在急性脊髓损伤(SCI)的治疗中有神经保护作用和抗炎效应。但是,MP对于CSPG在活性胶质细胞中的表达的作用尚不清楚。本文用a-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AM-PA)诱导星形胶质细胞再活化,用环噻嗪模拟SCI的兴奋性中毒刺激。AMPA治疗后,星形胶质细胞再活化的标志物-胶质纤维酸性蛋白(GFAP)、CSPG神经聚糖和磷酸盐的表达都显著上调。AMPA治疗星形胶质细胞的条件培养液强烈抑制大鼠背根神经节中神经元的轴突生长,但这种作用能被MP的预处理所逆转。此外,MP下调成年SCI大鼠中GFAP和CSPG的表达,对抗RU486的糖皮质激素受体(GR)和GR si RNA能逆转MP对GFAP和神经聚糖表达的抑制作用。这些结果提示,MP能在兴奋性中毒损伤后通过GR介导的星形胶质细胞再活化下调和GSPG表达抑制来改善神经修复,促进轴突生长。     

Protocatechuic Acid Inhibits Lung Cancer Cells by Modulating FAK,MAPK, and NF-κB Pathways

Cytotoxic effects of protocatechuic acid (PCA) upon 3 nonsmall cell lung cancer (NSCLC) cell lines, A549, H3255, and Calu-6 cell lines, were examined. PCA at 1, 2, 4, and 8 μM was used to treat these cells. Results showed that PCA dose-dependently reduced cell growth; and at 2–8 μM enhanced protein expression of Bax and cleaved caspase-3; as well as diminished Bcl-2 expression. This compound destabilized mitochondrial membrane via increasing caspase-3 activity, decreasing mitochondrial membrane potential and Na⁺-K⁺-ATPase activity in these cells. PCA treatments dose-dependently decreased protein expression of vascular endothelial growth factor and fibronectin, as well as lowered interleukin (IL)-6 and IL-8 release; and at 2–8 μM suppressed protein expression of basic fibroblast growth factor, matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PCA treatments dose-dependently downregulated nuclear factor kappa (NF-κ)B p50 and NF-κB p65 protein expression, and at 2–8 μM suppressed protein expression of p-p38, p-JNK, and p-focal adhesion kinase (FAK). Our data revealed that PCA declined FAK, mitogen-activated protein kinase, and NF-κB activation, which subsequently decreased the production of cytokines and growth factors, and consequently inhibited proliferation of 3 test NSCLC cells. These findings suggest that PCA could provide wide-ranging anti-NSCLC potency.     

Routine Blastocyst Culture and Transfer: 201 Patients' Experience

Purpose: The purpose was to compare the outcomes betweenday-5 blastocyst and day-2 embryo transfers. Methods: Infertile women who accepted the ovarian hyperstimulationand oocyte retrieval were divided: Group 1, day2 embryo transfer, group 2, cultured to day 5 in serum-freesequential culture medium and transfer. Early embryoquality and growth, blastocyst formation and quality,implantation rate (IR) and pregnancy rates (PR) weredetected. Results: Total blastocyst formation rate was 49.4%. Betterearly embryo quality (days 2, 3) and higher day 3 blastomerenumber possess higher blastocyst formation rate. The IR forday 2 and day 5 embryos were 10.8% and 22.2%, respectively.The PR in both groups were comparable (37.3% vs. 41.8%). Conclusions: Blastocyst transfer has higher IR and comparablePR as those of day 2 embryo transfer. Early embryoqualities and day 3 blastomere number are useful in predictingthe final blastocyst formation. Blastocyst formationrate is not related to maternal age, infertile causes, inseminationmethods, and early embryo number.     

Snake skin pattern gastropathy in cirrhotic patients

Gastric mucosal lesions are common in patients with cirrhosis. Among them, snake skin pattern gastropathy (SSPG) is the most distinguishing one. A prospective study was conducted to investigate the incidence of SSPG in cirrhotic patients, the relationship between the degree of portal pressure and SSPG, and the possible association of SSPG with serum levels of gastrin and pepsinogen I. SSPG was found to be significantly more common in 100 cirrhotic patients than in 100 age- and sex-matched healthy controls (41% vs 0%, P less than 0.0001). Hepatic venous pressure gradient and serum gastrin and pepsinogen I levels were measured in 21 cirrhotic patients with SSPG and 25 cirrhotics without SSPG. There was no significant difference in hepatic venous pressure gradient (16.1 +/- 4.4 mmHg vs 16.1 +/- 4.9 mmHg, P greater than 0.05), serum gastrin level (78.0 +/- 26.7 pg/mL vs 80.1 +/- 32.5 pg/mL, P greater than 0.05) and serum pepsinogen I level (69.5 +/- 26.6 ng/mL vs 65.2 +/- 26.1 ng/mL, P greater than 0.05) in cirrhotic patients with or without SSPG. In conclusion, SSPG is common in cirrhotic patients. Portal pressure per se may not be the only factor causing SSPG--other aggressive factors may be needed together to cause the gastropathy. There is no evidence of correlation between serum gastrin or pepsinogen I level and SSPG.     

Treatment with dextromethorphan improves endothelial function,inflammation and oxidative stress in male heavy smokers

Summary. Background: Dextromethorphan (DM) is reported to reduce the inflammation‐mediated degeneration of dopaminergic neurons. Objective: The goal of this study was to test if DM can improve the endothelial dysfunction and inflammatory markers in heavy smokers. Patients and methods: Forty habitual smoking healthy male volunteers (mean age, 31.5 ± 1.4 years) were randomly given either DM (120 mg day^?1) or a placebo for 6 months. We determined endothelial function using the brachial artery diameter changes in flow‐mediated dilatation (FMD) and measured their inflammatory and oxidative markers. A sex‐and‐age matched non‐smoking group (n = 20) was compared as normal parameters. Results: Habitual smokers showed impaired baseline endothelial function in FMD (smoking vs. non‐smoking: 6.3 ± 1.8 vs. 10.2 ± 2.3% respectively, P < 0.01). Without change in smoking behavior, lipid and metabolic parameters, a significant increase in FMD was found in the DM‐treated group (32%), accompanied by a decrease in high‐sensitivity C‐reactive protein (hs‐CRP), phospholipase A₂, matrix metalloproteinase‐3, interleukin 6 (IL‐6) and tumor necrosis factor‐α receptor II (TNF‐α RII) (all P < 0.05), but unchanged in von Willebrand factor (VWF)and plasminogen activator inhibitor‐1 (PAI‐1). An increase in plasma glutathione peroxidase and a decrease in spot urinary excretion of 8‐epi‐prostaglandin F_2a were found in DM‐treated smokers. Conclusions: Our study suggests that a 6‐month treatment with DM can improve endothelial function and attenuate vascular oxidative stress and inflammation markers in habitual smokers.     

Papulolinear Collagenoma with Arborizing Arrangement: Report of a Case

Abstract:  Connective tissue nevi of collagen type are now classified in four major subtypes. In addition to the clinicopathological features of papulolinear collagenoma, which is considered as a variant of isolated collagen harmatoma, the case we present has a unique arborizing pattern.