Crosstalk between cholesterol homeostasis and drug metabolism

Nowadays cardiovascular diseases are among the major causes of mortality in the developed world. High cholesterol level in blood and atherosclerosis play the main role in progression of cardiovascular diseases. Reducing serum cholesterol level has been shown to avoid deleterious effects, whereas in serious diseases it improves the outcome. A widely used, statin-based therapy induces a decrease in de novo cholesterol biosynthesis in the liver. Another possibility for lowering serum cholesterol level is to block the uptake of dietary cholesterol from intestine (e.g. ezetimibe). Coadministration of statins and cholesterol uptake inhibitors provides an efficient therapeutical strategy. Several therapeutic agents, reducing serum cholesterol level, are able to regulate the expression of not only cholesterogenic enzymes, but of the major drug metabolizing enzymes, cytochromes P450. The crosstalk between cholesterol homeostasis and drug metabolism is mediated by nuclear receptors, activating target genes in response of endogenous and exogenous ligands. Better understanding of the crosstalk between cholesterol homeostasis and drug metabolism is essential for developing an adequate strategy in therapy and in novel drug development.     

Is there a unique measuring method to assess obesity?

In the literature there is not available a uniformly accepted method for assessing the degree of obesity. AIM: To determine how far insulin resistance, serum levels of leptin and resistin are altered in persons categorized on the basis of body-mass index (BMI), body fat percentage, and abdominal circumference. METHODS: 101 volunteer boys and 115 girls participated in the studies. Body height was measured, body mass, abdominal circumference, and body composition were determined by InBody3 bioimpedance instrument. Body mass index and body fat percentage were calculated by the instrument. Concentrations of serum glucose, insulin, leptin, and resistin were determined. Insulin resistance was calculated using the homeostasis model: HOMA IR . RESULTS: Body fat percentage, serum levels of leptin and resistin were significantly higher in girls than in boys. Increases in BMI, body fat percentage, and abdominal circumference were associated with the significant elevation of both HOMA IR and serum leptin concentrations. In overweight boys categorized by body fat percentage as obese the serum leptin concentrations were significantly higher than in their non-obese counterparts. CONCLUSION: Determination of body composition would be important concerning the follow-up of biochemical changes occurring in the body during the course of both epidemiological studies and nutritional interventions.     

Vena portae obstruction as a cause of portal hypertension in a child with Turner syndrome

Cardiovascular and renal malformations are well-known in Turner syndrome. However, gastrointestinal bleeding is less frequent. The possible etiologies of gastrointestinal bleeding in Turner syndrome are intestinal teleangiectasia, inflammatory bowel disease and portal hypertension. The authors report a 3-year-old girl with Turner syndrome who presented with severe gastrointestinal bleeding requiring transfusion. The radiological examination indicated prehepatic portal hypertension as a reason for haematochezia. The liver biopsy demonstrated the anomaly of intrahepatic arteries and veins. In this report we describe a case of congenital portal vein obstruction and we reviewed liver abnormalities associated with Turner syndrome and causes of obstruction of vena portae in childhood.     

Vena cava superior syndrome: surgical treatment of the thrombosis of the superior vena cava after implantation of a hemodialysis catheter--a case report and review of the literature

One of the rare reasons of the non malignant superior vena cava syndrome is the thrombosis of superior vena cava. Obstruction or occlusion of central veins is one of the many complications of the more and more frequently used central venous catheters and pacemaker electrodes. The authors report a case of superior vena cava thrombosis resulting in dialysis catheter insufficiency in case of a young, uraemic, female patient wit Tesio catheter and the surgical treatment of it with the use of cardiopulmonary bypass during the operation. Apropos of this case, the authors outline the causes of malignant, non-malignant and iatrogenic superior vena cava syndrome, furthermore the conservative, surgical and catheter therapy of the syndrome.     

Multiple obliterative vascular disease. Challenge in diagnosis and in treatment

Currently, peripheral arterial disease is an underdiagnosed disorder. Several modifiable and non-modifiable risk factors have role in its development and progression. As system disorder it might be a part and an important predictor of fatal cardio- and cerebrovascular events. CASE REPORT: The authors describe the case of a 73-year-old male with multilocational vascular disorder, with simultaneously occurring carotid disease, critical limb ischaemia with aorto-bifemoral bypass, multiple infarction with mechanical complication, inoperable coronary disease and with implantable cardioverter defibrillator for ventricular arrhythmia. CONCLUSION: Peripheral arterial disease affects the whole vascular system and can progress into serious cardiac and cerebral manifestations causing the patient's death inspite of comprehensive treatment.     

Hospital and long-term prognosis of patients with non-ST-segment elevation myocardial infarction

The authors analyze some clinical data, hospital and long-term prognosis of 139 consecutive patients with non-ST-segment elevation myocardial infarction. A three-quarter-year long follow-up of patients was performed, and data were recorded by use of postal questionnaire. The follow-up was complete in 98% of the patients. The mean age was 78.6 and 71.4 years in the case of female and male patients, respectively. High percent of patients had comorbidity (diabetes mellitus, hypertension and previous ischemic heart disease). Coronary angiography was performed in 30 patients (22%) and revascularization in 29 of them. Hospital mortality was found in 15% and during follow-up 17% of the patients died. The patients who died during hospital stay and during the follow-up period were significantly older than patients who stayed alive. Some echocardiographic parameters were also found prognostically important: ejection fraction, end systolic diameter, segmental wall motion abnormality and severity of mitral regurgitation were found significantly different in patients alive and who died. The authors investigated the hospital discharge medications according to guideline recommendations. The authors emphasize that this quality indicator was much better in this patient population than the earlier published data. By the end of follow-up, similar percent of patients used these drugs as at the time of hospital discharge.     

Novel bradykinin-1 antagonists containing a (1,2,3,4-tetrahydro-isoquinolin-1-yl)acetic acid scaffold

A novel B(1) antagonist core was utilized and the effects of modification of its amide side chain on the biological activity were tested. The imino functional group of isoquinolin-1-ylacetic acid and its 6,7-dimethoxy variant was sulfonylated (4-toluenesulfonyl), while the acetyl side chain was converted to amides. Three of the synthesized compounds exhibited significant activity at the recombinant human B(1) receptors in binding tests and also in a functional assay.     

Inflammation a possible link between economical stress and coronary heart disease

Objective: To assess the relationship between economical stress, as an indictor of SES, and inflammation in women patients with coronary heart disease (CHD). Design: a cross-sectional study. Setting and participants: Two hundred and thirteen women patients recruited from two hospitals in Stockholm, Sweden; mean age 63 ± 8, range 35–75 years, hospitalised for acute myocardial infarction, coronary angioplasty or bypass surgery between 1996 and 2000, examined in a stable phase, 1 year and 5 months (±2.5 months) after the index event. Main outcome measures: Economical stress, and other SES indicators were assessed by questionnaires. Levels of high-sensitivity C-reactive protein (CRP) were measured by nephelometry and the concentrations of interleukin-6 (Il-6) and interleukin-1 receptor antagonist (Il-1ra) were determined by enzyme-linked immunoassay. Results: After controlling for the potential confounders, i.e. treatment, menstruational, marital and education status in addition to age, patients having economical stress showed higher levels of hsCRP (2.79 vs. 1.83 mg/l, p = 0.04), Il-6 (3.12 vs. 2.38 mg/l, p = 0.015) and Il-1ra (599 vs. 456 mg/l, p = 0.02). The association persisted after controlling for other measures of economical status, like personal and household income. According to our mediational analyses, lifestyle variables, especially BMI, could partly explain the observed association. Conclusion: High economical stress was associated with higher Il-6, CRP and Il-1ra levels in women with stable CHD. The direction of causality cannot be inferred from such a cross-sectional study however, our results raise the possibility that increased inflammatory activity is a mediator for the effect of economical stress on adverse outcomes after a coronary event.