Superior Role of Waist Circumference to Body-Mass Index in the Prediction of Cardiometabolic Risk in Dyslipidemic Patients.

Coronary risk evaluation by conventional factors (age, gender, smoking, blood pressure and cholesterol) may further be specified by facets of the metabolic syndrome, namely insulin resistance, hypertriglyceridemia and obesity. Although obesity is usually defined as elevated body mass index (BMI), recent data indicate a superior role of waist circumference or hypertri-glyceridemic waist (HTGW) over BMI in the assessment of cardiometabolic risk. In dyslipidemic patients, the specific contributions of risky waist, HTGW or BMI have not been evaluated as yet. 686 dyslipidemic subjects (322 males and 364 females) were enrolled into a cross-sectional study. In each subject basic antropometry (i.e. waist circumference, HTGW, BMI) and laboratory parameters of lipid profile and insulin resistance were determined. Cardiometabolic risk was given by fulfilling the criteria (harmonized definition) of metabolic syndrome. The significance of risky waist, HTGW and BMI were assessed by comparing the respective predictive values for the presence of metabolic syndrome. Dyslipidemic patients with risky waist, HTGW or high BMI have a more atherogenic lipid profile and higher insulin resistance compared to those without risky waist, HTGW or high BMI. Risky waist is stronger predictor of metabolic syndrome (PPV 66 %, NPV 90 %) and thus posesa greater cardiometabolic risk than higher BMI per se does (PPV 42 %, NPV 97 %). The contribution of triglycerides (i.e. HTGW) to these predictive values is marginal (PPV 66 %, NPV 92 %). The present results highlight the superior role of waist circumference as a screening tool over BMI for the evaluation of cardiometabolic risk in dyslipidemic subjects. HTGW brings little additional benefit in risk stratification. Lower BMI proved to be optimal for identifying the subjects with inferior risk.

[Modes of tissue blood perfusion assessment by microdialysis - a review of current knowledge]. / Zpusoby hodnocení krevní perfuze tkání pomocí intersticiální mikrodialýzy - prehled soucasných znalostí

Microdialysis is a dynamically evolving method utilized for monitoring of tissue metabolism and barrier function, pharmacological studies and to estimate local blood perfusion in situ. The present review summarizes current knowledge of the last of the aforementioned applications on a characterization and comparison of two approaches used - microdialysis flow-indicator dilution technique and continuous metabolic monitoring. Currently, the use of metabolic indicators, which enable sensitive and complex evaluation of perfusion-induced changes in the tissue, is preferred. Despite the methods numerous advantages the measurement of tissue blood perfusion by microdialysis remains centralized in the area of clinical research, for the present. For wider acceptance and exercise in the routine clinical practice, more validating studies ought to be conducted and situations identified, where microdialysis could replace the current methods.

Alendronate lowers cholesterol synthesis in the central nervous system of rats - a preliminary study.

Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w.) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated water. In the alendronate group significant reductions of cholesterol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system.

Cholesterol synthesis in central nervous system of rat is affected by simvastatin as well as by atorvastatin.

OBJECTIVE: There is evidence to suppose that cholesterol-lowering drugs such as statins might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present study was to investigate possible influence of two lipophilic statins (simvastatin and atorvastatin) on cholesterol synthesis in selected parts of rat central nervous system (CNS). METHODS: Three groups of rats were orally treated with simvastatin (10 mg/kg b.wt.), atorvastatin (10 mg/kg b.wt.) or vehicle (aqua) for 9 days. At the end of experiment, brains (for basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the incorporation of deuterium from deuterated water. ANOVA with Fisher's LSD Multiple-Comparison Test and Kruskal-Wallis test were applied for statistical evaluation. P < 0.05 was considered statistically significant. RESULTS: Significant reductions of cholesterol synthesis rate were detected in both experimental groups (vs. controls) in all studied localisations. Both drugs elicited comparable effects on cholesterol synthesis rate irrespective of the examined tissue. CONCLUSIONS: This study brings additional evidence of the role of statins in the CNS cholesterol synthesis. The finding that both statins were able to lower braincholesterol synthesis without altering plasma cholesterol supports the idea of their local action inthe brain. For comparison of the effects of statins in the spinal cord and selected parts of brain, the deuterium technique was utilised for the first time.

Impact of cardiopulmonary bypass on peripheral tissue metabolism and microvascular blood flow.

The aim of this study was to monitor and compare the changes in metabolism and blood flow in the skeletal muscles during cardiac operations performed with cardiopulmonary bypass (CPB) and operations without CPB (off-pump) by means of interstitial microdialysis (Figure 1). Surgical revascularization, coronary artery bypass grafting (CABG), was performed in 40 patients randomized to two groups. Twenty patients (On-Pump Group) were operated on using CPB, 20 patients (Off-Pump Group) were operated on without CPB. Interstitial microdialysis was performed by 2 probes of a CMA 60 (CMA Microdialysis AB, Solna, Sweden) inserted into the patient's deltoid muscle. Microdialysis measurements were performed at 30-minute intervals. Glucose, lactate, pyruvate and glycerol as markers of basic metabolism and tissue perfusion were measured in samples from the first probe, using a CMA 600 Analyzer (CMA Microdialysis AB). Blood flow through the interstitium was monitored by means of dynamic microdialysis of ethanol as a flow-marker in the dialysates taken from the second probe (ethanol dilution technique). Results in both the groups were statistically processed and compared. Both the groups were similar in respect of preoperative characteristics. Dynamic changes of interstitial concentrations of the measured analytes were found in both the patient groups (on-pump vs. off-pump) during the operation. There was no significant difference in dialysate concentrations of glucose and lactate between the groups. Significant differences were detected in pyruvate and glycerol interstitial concentrations, lactate/pyruvate ratio and lactate/glucose ratio between the on-pump vs. off-pump patients. In the Off-Pump Group, pyruvate concentrations were higher and the values of concentrations of glycerol lower. The lactate/pyruvate ratio and the lactate/glucose ratio, indicating the aerobic and anaerobic tissue metabolism status, were lower in the Off-Pump Group. There was no significant difference in dialysate concentrations of ethanol as a flow-marker during the surgery in either of the groups. There was no statistically significant difference between the groups (On-Pump Group vs. Off-Pump Group) comparing the postoperative clinical outcome (ICU stay, ventilation duration, length of hospital stay). The dynamic changes in the interstitial concentrations of the glucose, glycerol, pyruvate and lactate were found in both the groups of patients (On-Pump Group and Off-Pump Group), but there was no difference in local blood flow when the ethanol dilution technique was used. These results showed significantly higher aerobic metabolic activity of the peripheral tissue of patients in the Off-Pump Group vs. the On-Pump Group during the course of cardiac revascularization surgery. Results suggest that extracorporeal circulation, cardiopulmonary bypass, compromises peripheral tissue (skeletal muscles) energy metabolism. These changes have no impact on the postoperative clinical outcome; no significant difference between the groups was found.

Differential effects of statins and alendronate on cholinesterases in serum and brain of rats.

Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer's disease. Cholesterol plays an important role in Alzheimer's disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug.

Colon submucosal microdialysis: a novel in vivo approach in barrier function assessment - a pilot study in rats.

During shock, prognosis of a patient depends largely on intestinal barrier function. The potency of gut epithelium to represent an obstacle to toxins is determined by the blood supply. All established methods of mucosal function determination necessitate the functional involvement of bloodstream. Microdialysis allows monitoring of extracellular substances in the gut submucosa, but its potential use for gut barrier integrity assessment is unknown. Twelve rats underwent perfusion of the descending colon either with 20 % ethanol or control medium (vehicle). Both media contained equal amounts of a radioactive tracer substance ((51)Cr-EDTA). Mucosal permeability for (51)Cr-EDTA was assessed by microdialysate to luminal perfusate activity ratios. Sampling was performed using the colon submucosal microdialysis technique. The group subjected to ethanol treatment had profound macro- and microscopical alterations in perfused colonic segment associated with a significant increase in tracer permeability during ethanol exposure (2.354+/-0.298 % for ethanol as opposed to 0.209+/-0.102 % for control group, p 0.01), which remained elevated for 60 min after cessation of ethanol administration (3.352+/-0.188 % for ethanol compared to 0.140+/-0.0838 % for the control group, p 0.001). Submucosal microdialysis with radioactive tracer substance can be considered a feasible and advantageous alternative of gut barrier function estimation. Parallel monitoring of local tissue chemistry with this method remains a challenge in the future.