Peripapillary choroidal thickness in patients with chronic obstructive pulmonary disease

Objective: To evaluate the peripapillary choroidal thickness of patients with chronic obstructive pulmonary disease (COPD) via enhanced depth imaging optical coherence tomography (EDI-OCT).

Materials and methods: A total of 80 patients with COPD (80 eyes) and 50 control subjects (50 eyes) were enrolled. Choroidal scans and the retinal nerve fiber layer (RNFL) thickness were obtained for all eyes using OCT.

Results: The average peripapillary choroidal thickness measurements of the COPD group (147.58?±?53.53?μm) were lower than the control group (160.84?±?44.73?μm) (p?=?0.068). Inferior segment thicknesses were significantly thinner than the other segments (p?<?0.05). Subfoveal choroidal thickness and RNFL thickness measurements of the COPD group were also lower than those of the control group (p?=?0.111).

Conclusion: Hypoxia in COPD seems to affect the choroidal thickness. Thinning of the choroid may be attributed to increased vascular resistance and reduced blood flow in patients with COPD. The possible effects of the disease to the eye may be clarified through the role of the choroidal vasculature in the blood supply of the anterior optic nerve head.     

紫杉醇化疗方案对乳腺癌患者血清Th1/Th2细胞因子水平的影响

目的探讨紫杉醇化疗方案对乳腺癌患者血清Th1/Th2细胞因子水平的影响。方法将100例乳腺癌术后辅助化疗患者随机(1︰1)分为2组,常规组行AC(阿霉素-环磷酰胺,每3周1次)-P(紫杉醇80mg·m~(-2),每周1次)方案化疗,剂量密集组,行AC(阿霉素-环磷酰胺每2周1次)-P(紫杉醇175mg·m~(-2),每2周1次)方案化疗,化疗前后观察患者血清细胞因子水平变化。结果常规组及剂量密集组化疗后患者血清IL-2、TNF-α及IFN-γ浓度均显著增高(P<0.05),血清IL-4、IL-6及IL-10水平显著降低(P<0.05)。结论常规组及剂量密集组均能够改善乳腺癌患者细胞免疫功能;剂量密集组较常规组具有更强的恢复细胞免疫为主的抗肿瘤免疫能力,且未显著增加毒性和不良反应。     

E2F3和AR在前列腺癌组织中的表达及意义

目的:检测E2F3、AR在前列腺组织中的表达水平,分析两者的表达与前列腺癌病理分级和临床分期的关系.方法:利用免疫组织化学方法检测50例前列腺癌组织、50例良性前列腺增生组织中E2F3、AR蛋白的表达;采用SPSS 13.0进行统计学处理.结果:E2F3在良性前列腺增生组织、前列腺癌组织中的阳性表达率分别为20.00％( 10/50)及66.00％(33/50),差异有统计学意义(P＜0.05),且在前列腺癌组织中的表达与肿瘤临床分期和病理恶性程度呈正相关(rs分别为0.471和0.329,P＜0.05).前列腺癌组织中AR表达水平低于良性前列腺增生组织(P＜0.05),且在前列腺癌组织中的表达与肿瘤临床分期和病理恶性程度呈负相关(rs分别为-0.403和-0.391,均P＜0.01).E2F3在前列腺癌组织中的表达与AR在前列腺癌组织中的表达无相关关系(rs=-0.017,P＞0.05).结论:E2F3在前列腺癌的发生、发展中起着重要作用.     

Enzyme supplementation of dry and wet wheat-based feeds for broiler chickens: performance and gut responses

To test whether the improvements in digestive efficiency due to either wetting of the food or inclusion of enzymes are accompanied by the same changes in gut function, foods with a high content of wheat were fed to broiler chicks from 1-42 d old. Twenty-four birds were caged individually while a further sixty-four were in group pens in experiments of 2 x 2 factorial design with two levels of enzyme (0 or 1 g/kg, designed for wheat) and two levels of water addition (0 and 1300 g/kg). Food intake and live-weight gain were significantly increased by wet feeding (from 89.3 to 153.4 g/d and from 39.7 to 65.4 g/d respectively), the differences increasing with age, while the enzyme had no significant effect (120.5 and 122.2 g/d and 51.9 and 53.1g/week respectively). The viscosity of digesta was greatly reduced both by wetting (from 4.40 to 2.64 kPa. s) and enzyme (from 4.47 to 2.57 kPa. s) but there was a significant interaction with age in which the viscosity was low throughout in the wet only, enzyme only and wet + enzyme treatments but declined with age from a very high level in the dry, no enzyme treatment (11.5 kPa. s at 14 d). While wetting increased weight and length of digestive tract and thickness of some parts of the gut, enzyme had no significant effect, tending to reduce gut wall thickness. Crypt cell proliferation rate (CCPR) was significantly reduced by wet feeding (from 39.4 to 28.7 cells/crypt per 2 h) and by enzyme supplementation (from 38.9 to 29.2 cells/crypt per 2 h). Therefore, while both wetting and enzyme addition to the food reduced digesta viscosity and CCPR to a similar extent, the former had marked stimulatory effects on food intake and weight gain while the latter had little effect. The mode of action of wet feeding is therefore deduced to be not primarily through its effects on viscosity and CCPR.     

The presence and antimicrobial susceptibilities of human-pathogen Vibrio spp. isolated from blue crab (Callinectes sapidus) in Belek tourism coast,Turkey

Monitoring of Vibrio species by blue crabs (Callinectes sapidus) was carried out during the winter period in a selected area of the Belek, Antalya Gulf. Eighty-three blue crabs were examined for Vibrio species. V. alginolyticus (30.1%), V. fluvialis (10.8%), V. damsela (9.6%), V. harveyi (3.6%), V. metschnikovii (3.6%) and V. vulnificus (2.4%) were isolated. V. vulnificus was the highest concentration (5 x 10(8) Vibrio ml(-1)) although it was only 2.4% isolated from blue crabs. The strains of different vibrio species were highly susceptible to doxycycline, tetracycline and ciprofloxacin.     

The contracting and relaxing responses of human internal mammary artery grafts harvested by two different methods

Perioperative spasm of internal mammary artery is a common experience in coronary artery bypass grafting. Many techniques were described of harvesting the internal mammary artery to prevent vasospasm. We investigated the comparison of the contracting and relaxing responses of human internal mammary artery grafts harvested by two different methods. Patients were divided into two groups depending on the harvesting technique. In the first and second groups arteries were harvested by classical and carbon dioxide insufflation techniques, respectively. In both groups, endothelial function of arteries was assessed by precontracting the rings with phenylephrine (10(-5)M) and dilatating them by cumulative acetylcholine (10(-8) to 10(-5)M) concentrations. Cumulative concentration-response curves for phenylephrine (10(-8) to 10(-4)M), noradrenaline (10(-9) to 10(-4)M), and 5-hydroxytryptamine (10(-9) to 10(-4)M) were obtained in all groups. Endothelial integrity of arteries were histopathologically evaluated. In both groups, acetylcholine caused concentration-dependent relaxations in rings precontracted with phenylephrine (10(-5)M). In arteries harvested by carbon dioxide insufflation technique, acetylcholine caused significantly higher relaxations compared to the rings obtained by classical technique (p<0.05). In all rings of study groups, phenylephrine, noradrenaline and 5-hydroxytryptamine caused concentration-dependent contractions. There was not any significant difference in concentration-dependent responses of these contracting pharmacological agents between the groups. Histopathological evaluation revealed no major arterial damage in both groups. Carbon dioxide insufflation technique does seem not only to protect the integrity of the endothelium and the whole vessel, but also prevent the possible vasospasm of the internal mammary artery segments.     

Allelic variants of cytochromes P450 2C modify the risk for acute myocardial infarction

SUMMARY: Cytochromes P450 (CYP) 2C8 and 2C9 are polymorphic enzymes responsible for the biosynthesis of vasoactive substances from arachidonic acid including endothelium-derived hyperpolarizing factor. Inter-individual differences in the action of these substances might be important in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI) and hypertension. This study describes the relationship between genetic variants of CYP2C8 and CYP2C9, and morbidity in myocardial infarction in a large Swedish patient material. The study included 1172 AMI patients and 1503 control subjects (matched by age, sex and residential area) who participated in the Stockholm Heart Epidemiology Program (SHEEP). Genotyping was performed by allelic discrimination using a 5'-nuclease assay for the CYP2C8 and CYP2C9 variants. To estimate associations to AMI risks, odds ratios (OR) with 95% confidence intervals (CI) were calculated. The frequencies of CYP2C8*1, 2C8*3, 2C9*1, 2C9*2 and 2C9*3 variants in the control group were 0.91, 0.095, 0.83, 0.11 and 0.065, respectively. The risk of AMI in the female individuals carrying the *2 or *3 variant alleles of CYP2C9 and that of all individuals carrying the *3 variant of CYP2C8 was higher [OR (95% CI): 1.3 (1.0-1.9), P = 0.09; 1.5 (1.0-2.2), P = 0.06 and 1.2 (1.0-1.5), P = 0.07, respectively] compared to the groups with CYP2C8*1 and CYP2C9*1. Possession of rare genetic variants of the CYP2C8 and CYP2C9 genes in females is associated with a modest increase in risk of AMI. This might be related to genetic differences in the formation of endogenous vasoregulating eicosanoids.     

Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes

Several-fold differences have been observed among patients in the biotransformation of cyclophosphamide. The aim of this study was to investigate the contribution of CYP2C9 and CYP2C19 and their polymorphisms to the variability of cyclophosphamide activation. The formation of 4-hydroxycyclophosphamide was studied in microsomes from a total of 32 different genotyped human livers, as well as in yeast microsomes expressing different genetic variants of CYP2C9 and CYP2C19. The kinetic data obtained in the yeast system revealed that the intrinsic clearance (V(max)/K(m)) of cyclophosphamide by CYP2C9.2 and CYP2C9.3 samples was approximately threefold lower than that by CYP2C9.1. However, in liver microsomes, there were no statistically significant differences in the intrinsic clearance of 4-hydroxycyclophosphamide formation between the group of seven CYP2C9*1/*1 livers and the remaining nine with one or two variant CYP2C9 alleles ( P>0.7). We found a statistically significant correlation ( r(s)=0.65, P=0.003) between 4-hydroxylation of cyclophosphamide and 5'-hydroxylation of R-omeprazole, a measure of CYP2C19 activity in human liver microsomes ( n=19). No correlation was found between 4-hydroxylation of cyclophosphamide and the formation rate of hydroxycelecoxib, mainly catalysed by CYP2C9 ( r(s)=0.17, P=0.55, n=32). In conclusion, based on the correlation with the formation of R-5'-hydroxyomeprazole, CYP2C19 may partly contribute to the bioactivation of cyclophosphamide in human liver microsomes, while the role of CYP2C9 appears minor.     

CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers

OBJECTIVE: This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. METHODS: Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C9*2 and *3 was carried out with PCR-RFLP. RESULTS: The frequencies of CYP2C9*1, *2, and *3 alleles were 0.74 (95%CI: 0.68-0.80), 0.16 (95%CI: 0.11-0.21) and 0.10 (95%CI: 0.06-0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3'-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C9*1/*3 (0.83+/-0.4, n=14, 95% CI for the difference: 0.02-0.4) and CYP2C9*2/*3 (1.10+/-0.5, n=4, 95% CI for the difference: 0.16-0.8) genotypes compared to CYP2C9*1/*1 (0.62+/-0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C9*3 variant. CONCLUSIONS: The frequencies of CYP2C9*1, *2, and *3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C9*3 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied     

Evaluation of the novel antiepileptic drug,AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 microg/kg/injection). When AWD 131-138 (10-100 microg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.