Amlodipine and glutathione cycle in hypercholesterolaemia

OBJECTIVE: Effects of amlodipine on lipid peroxidation and alterations in glutathione and related enzymes in blood and aortic tissue were investigated in a cholesterol-induced atherosclerotic rabbit model. METHODS AND RESULTS: New Zealand white male rabbits were fed with regular chow (group I), chow supplemented with I% cholesterol (group II), regular chow plus amlodipine 5 mg/kg/day p.o. (group III) and I% cholesterol diet supplemented with amlodipine (group IV) for 8 weeks. Cholesterol, malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-Rd) were determined in blood samples drawn before and after the experimental period. Aortic tissue was examined morphologically for atherosclerotic changes and tissue cholesterol, MDA, GSSG, GSH-PX, GSH-Rd and glutathione-S-transferase (GST) were measured. After 8 weeks, blood cholesterol, MDA, GSSG and GSH-PX were elevated in groups II and IV; GSH was reduced in group IV; MDA levels were higher in group II than in group IV. Aortic tissue investigations revealed higher cholesterol and MDA concentrations in group II than in group IV. Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group II. Histopathological alterations related to atherogenesis were less in group IV than in group II. CONCLUSIONS: Amlodipine reduced the increase in oxidative stress by inhibiting excessive MDA production. Accelerated glutathione redox cycle activity of erythrocytes from animals supplemented with amlodipine suggests that this drug may reduce oxidative stress by enhancing the glutathione system. However, this drug does not seem to affect the glutathione redox cycle in the aortic tissue.     

Increased soluble glycoprotein V concentration during the acute onset of unstable angina pectoris in association with chronic cigarette smoking

Platelet hyperactivity is important in the pathobiology of acute coronary syndromes. Glycoprotein V (GPV) is an integral membrane protein of platelets in the function of the GPIb-V-IX receptor for vWf/shear-dependent platelet adhesion in arteries. Soluble GPV is a novel marker of platelet activation. The aim of this study is to assess circulating soluble GPV levels in unstable angina pectoris (UA). Twenty-one patients (15 men, six women, aged 52+/-7 years) with UA pectoris were studied. The inclusion criteria were angina at rest lasting >20 min during the preceding 6 h, with transient ST segment depression and/or T wave inversion and no evidence of myocardial infarction detected with the use of cardiac troponin-T. Coronary artery stenosis was angiographically confirmed in all patients. Twenty age- and sex-matched healthy adults (14 men, six women, aged 48+/-7 years) served as controls. There were no significant differences among the studied groups with respect to age, sex, obesity, smoking, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and platelet counts. Plasma-soluble GPV concentrations were higher in the UA patient group (126+/-46 ng/ml) than those in the healthy controls (82+/-15 ng/ml) (P=0.001). There was a significant correlation only between plasma-soluble GPV levels and smoking (r=0.526, P=0.0001). Smoker UA patients had higher levels of soluble GPV than the non-smoker patients (139+/-40 vs. 113+/-50 ng/ml, respectively, P=0.02). However, soluble GPV levels were similar in smoker and non-smoker healthy controls (P=0.2). It is concluded that soluble GPV concentrations are significantly increased during the acute clinical course of unstable angina pectoris, indicating that soluble GPV may be useful marker of platelet activation in those patients. The level of the molecule is significantly affected from smoking in those patients.     

Comparison of the effects of continuous and intermittent portal triad occlusion (PTO) in rats

BACKGROUND/AIMS: It has previously been shown that prolonged ischemia of the liver had a mortal course and a method of intermittent occlusion of the hepatic pedicle was defined in order to minimize the damage to the liver. The present experimental study aimed to compare the effects of continuous and intermittent occlusion of the hepatic pedicle on the liver by measuring serum lactate, serum MDA malondialdehyde and glutathione levels and by evaluating the histologic changes in the liver tissue. METHODOLOGY: Thirty male Wistar albino rats weighing 300 +/- 50 g were divided into three groups of ten animals. Group 1 underwent a sham operation. Animals in group 2 underwent continuous portal triad occlusion (PTO group) for 30 minutes following laparotomy. The remaining ten animals in group 3 underwent intermittent occlusion consisting of 10 minutes of occlusion followed by 10 minutes of reperfusion for a total period of 30 minutes of ischemia. Blood samples were collected at the 1st and 6th postoperative hour for analytical evaluation. After sacrificing the animals, liver samples were obtained for histologic evaluation. RESULTS: The serum lactate levels were significantly higher in both portal triad occlusion groups than in the control at the 1st hour. While lactate levels also increased at the 6th hour in the continuous PTO group, it decreased to the level of control values in the intermittent PTO group. The difference between continuous and intermittent groups was also significant. Despite the unchanged malondialdehyde levels in the control group, malondialdehyde levels were significantly increased at the first and sixth hour in both PTO groups and the levels were also significantly higher than control values. Malondialdehyde levels of intermittent PTO groups at the first and sixth hour were both significantly lower than continue PTO groups. Whole blood glutathione levels were not changed in control groups with time, levels increased significantly in both PTO groups. Glutathione levels were higher than control values in both PTO groups at the first hour. While it turned to its basal value in intermittent PTO groups at the 6th hour, it was still significantly higher in the continuous PTO group. When both PTO groups were compared, glutathione levels were found to be significantly higher in the continuous group both at the first and sixth hour than in the intermittent PTO group. Histopathologic evaluation also showed that there was less damage in the intermittent PTO group than in the continuous PTO group. CONCLUSIONS: Our results show that continuous portal triad occlusion resulted in significant oxidative stress and cell damage as confirmed by increased serum lactate and blood malondialdehyde levels. The blood glutathione levels are increased due to a greater requirement in response to increased oxidative stress induced by portal triad occlusion. It is also confirmed that intermittent portal triad occlusion is safer as it causes less oxidative stress and cell damage so that its use is strongly suggested whenever portal triad occlusion is required.     

The relationship between self-monitoring of blood glucose control and glycosylated haemoglobin in patients with type 2 diabetes with and without diabetic retinopathy

BACKGROUND: Diabetes mellitus (DM) is a major health problem with long-term microvascular and macrovascular complications responsible for the majority of its mortality and morbidity. The development and progression of diabetic complications are strongly related to the degree of glycemic control. To decrease the occurrence of these complications, instruments for self-monitoring of blood glucose (SMBG) have been developed and have become widely used among diabetic patients. In this study, we determined the relationship between SMBG control and glycosylated haemoglobin (HbA(lc)) levels in patients with type 2 diabetes, with and without diabetic retinopathy. METHODS: Two hundred and sixty-seven type 2 diabetic patients (mean age [mean+/-S.D.]: 58.07+/-9.13 years, duration of diabetes: 8.63+/-6.8 years) participated in this study. Following an educational program on SMBG, glucometers and usage of oral antidiabetic agents or insulin, optic fundi were examined and HbA(lc) levels were measured at baseline and after 6 and 12 months. The patients were classified in three groups according to their funduscopic findings: without retinopathy (n=140, 52.4%), background retinopathy (n=75, 28.1%) and proliferative retinopathy (n=52, 19.5%). RESULTS: HbA(lc) levels at baseline, after 6 and 12 months were 9.09+/-2.69%, 7.47+/-1.78% and 7.12+/-1.4%, respectively, mean+/-S.D. The values decreased significantly after the education program (P<.001 for both values compared with baseline). The prevalence of retinopathy (both background and proliferative) was 0.8% in the group of diabetics with a mean HbA(lc) level <6%, 7.1% in those between 6.1% and 6.9%; 9.4% in those between 7% and 7.9%; 11.8% between 8% and 8.9%; and 70.9% in those exceeding a mean HbA(lc) level of 9%. There was a statically significant relationship between proliferative diabetic retinopathy and body mass index (BMI; P<.001). The same relationship was observed between duration of diabetes and diabetic retinopathy (P<.001), but not between sex and diabetic retinopathy (P=.46). CONCLUSIONS: Implementing a program of SMBG control in type 2 diabetic patients results in lower levels of HbA(lc) at 6 and 12 months. In the group without diabetic retinopathy at 6- and 12-month controls, the mean HbA(lc) concentration is less than 7%, but in the group with diabetic (background and proliferative) retinopathy, this value could not be reduced below 7%. These results imply that SMBG would allow us to maintain better metabolic control by improving HbA(lc) levels and we have always kept in mind that SMBG was a part of an educational program. On the other hand, improving glycemic control prevents the onset or progression of diabetic microvascular complications, such as diabetic retinopathy, nephropathy and neuropathy. Long-term clinical studies should be performed to determine cost-effectiveness and the effects of SMBG on diabetic complications, morbidity and mortality.     

Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria: relation to glomerular hyperfiltration

BACKGROUND: Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria. METHODS: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded. RESULTS: Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics. CONCLUSIONS: Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes.     

A meta-analysis and systematic review of computed tomography angiography as a diagnostic triage tool for patients with chest pain presenting to the emergency department

Background  

To assess clinical utility of computed tomography angiography (CTA) in the diagnosis of chest pain patients presenting to emergency departments (EDs), we conducted a meta-analysis of CTA in patients with suspected acute coronary syndromes (ACSs).     

Adenocarcinoma of the gallbladder associated with congenital choledochal cyst and anomalous pancreaticobiliary ductal junction. Case report.

In a 61-year-old woman, villous adenocarcinoma of the gallbladder was associated with a congenital choledochal cyst and anomalous pancreaticobiliary ductal junction. The patient had a history of congenital choledochal cyst treated by cystoduodenostomy 27 years previously. The condition was demonstrated by intraoperative cholangiography and histologically confirmed. Extended cholecystectomy, regional lymph node dissection, excision of the cyst and hepaticojejunostomy were performed successfully.     

The effect of sleeved arms on oscillometric blood pressure measurement

The authors measured the blood pressures of 36 subjects who had bare and sleeved arms to determine the effect of wearing sleeves on automatic oscillometric blood pressure measurements. They found no statistically significant effect of sleeves on the measurement of either systolic or diastolic blood pressure (p>0.15). However, based on confidence intervals of possible sleeve effects, the authors recommend repeating blood pressure measurements on bared arms when the sleeved-arm oscillometric measurements are at least 86 mm Hg diastolic or 135 mm Hg systolic. Presented in part at the annual meeting of the Society of General Internal Medicine, Seattle, Washington, May 1–3, 1991.     

Treatment with homodimeric interleukin-12 (IL-12) p40 protects mice from IL-12-dependent shock but not from tumor necrosis factor alpha-dependent shock.

The role of interleukin-12 (IL-12) was investigated in different shock models using anti-IL-12 reagents. IL-12 is composed of two disulfide-bonded subunits, p35 and p40. The IL-12 p40 homodimer (p40)2 has been shown to be a potent IL-12 antagonist in vitro. We investigated its in vivo inhibitory capacity in different shock models of mice. We could demonstrate that (p40)2 is able to protect mice from septic shock in primarily IL-12-dependent models such as the Shwartzman reaction and lipopolysaccharide (LPS)-induced shock, whereas (p40)2 has no effect in the tumor necrosis factor alpha-dependent LPS/D-GalN shock model. In IL-12-dependent shock models, (p40)2 inhibits IL-12-induced gamma interferon production and thereby interferes with the cascade of cytokine release, finally leading to death.