Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.     

玻璃体切除术治疗外伤性眼内炎62例

0　引言　外伤性眼内炎是眼外伤的常见并发症 ,对视力及眼球威协极大 .由于病原体随致伤物直接进入眼内 ,在眼内和玻璃体繁殖 ,产生剧烈炎症反应 ,对眼内组织造成严重破坏 .如不及时而有效的控制 ,终使视力丧失 ,眼球萎缩 .近年随着现代玻璃体手术的发展 ,外伤性眼内炎的治愈率明显提高 .现将我科收治的 6 2例报告如下 .1　对象和方法1 .1　对象 1 996 - 0 6 / 1 998- 0 6我院连续收治 6 2例外伤性眼内炎 ,其中男 5 0例 ,女 1 2例 ,年龄 2～ 45岁 ,平均 1 6 .5岁 .1 4岁以下儿童 38例 ,占 6 1 .3% .以致伤原因分类 :角膜穿通伤30例 ,巩膜穿…     

Changes of nitric oxide synthase activity and free methylarginines contents in regenerating rat liver after partial hepatectomy

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N^G-monomethyl-L-arginine (MMA) and N^G, N^G-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.     

Effect of hepatic cirrhosis on the pharmacokinetics of theophylline in rats

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t_1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Effect of the aryl substituent on antitumor activity of 2-substituted-1,4-dihydroxy-9,10-anthraquinones and 2-substitutedanthracene-1,4,9,10-tetraones

2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).     

Stereoselective synthesis of (±)-epibatidine analog: (±)-2β-(2-chloro-5-pyridinyl)-8-azabicyclo[3.2.1]octane

Stereoselective synthesis of (+/-)-epibatidine analog 2, which contains the 8-azabicyclo[3.2.1]octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3.     

PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.KEY WORDS: Microalbuminuria, Diabetes mellitus, Diabetic nephropathy, Chronic renal failure     

Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

Inhibition of excitotoxicity in cultured rat cortical neurons by a mixture of conjugated linoleic acid isomers.

Glutamate excitotoxicity, which is mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors, directly contributes to the neuronal cell loss associated with both acute insults and chronic neurodegenerative disorders. Conjugated linoleic acid (CLA) is a group of dienoic derivatives of linoleic acid shown to have anticarcinogenic and antioxidative activities. To evaluate the effect of a mixture of CLA isomers (cis-9, trans-11 and cis-10, trans-12 octadecadienoic acids) on glutamate- and NMDA-induced excitotoxicity, primary cultures of rat cortical neurons were treated for 15 min with 300 microM glutamate or NMDA in the presence of various concentrations of CLA. After the exposure, cell cultures were maintained at 37 degrees C for 18 h in minimum essential medium supplemented with glucose. Neuronal injury was measured by a colorimetric cell proliferation assay, and a qualitative assessment was made by phase-contrast microscopy. CLA inhibited glutamate- and NMDA-induced neuronal cell death in a concentration-dependent fashion with the most effective dose for neuroprotection being 500 microM. These results demonstrate that a mixture of CLA isomers exhibits protective action against glutamate- and NMDA-induced excitotoxicity.