Dyslipidemia: clinical approaches, evaluation of methods and strategies for standardization

Disorders in lipid metabolism (dyslipidemia) can result to the chronic heart disease. The low density lipoprotein (LDL) is a critical subfraction of total cholesterol present in serum because it is directly linked to coronary heart disease (CHD). The growing awareness of the risks of CHD stipulates the need for more accurate and precise measurement of LDL cholesterol. Current approaches in diagnosing and monitoring CHD is largely dependent on calculated LDL (CLDL) value due to the inherent complexity of ultracentrifugation method. While friedwald's calculated formula may provide comparable values with ultracentrifugation method, it may provide a result which is different. This difference may be of clinical significance. The lipoprotein electrophoresis may be useful in measuring LDL cholesterol, in the diagnosis of type III hyperlipidemia (broad beta band) and when the triglyceride level exceeds 400 mg/dl. The result that compares the CLDL with that obtained by the electrophoresis showed a significant difference (P > or = 0.000) for LDL and insignificant difference (P = 0.068) for high density lipoprotein (HDL) cholesterol.     

Spectroscopic studies of the interactions of the pyrethroid insecticide fenvalerate with gramicidin

Fenvalerate is a pyrethroid insecticide which interacts with ionic channels. Using circular dichroism technique we have studied the interaction of fenvalerate with gramicidin, a model channel peptide which transports ions. In most organic solvents, gramicidin exists as a double helix except in trifluoroethanol where it exists as a channel forming single stranded beta6.3 helical monomer. In model lipid membranes, under certain experimental conditions, gramicidin exists as a channel forming single stranded beta6.3 helical dimer. Our results show that fenvalerate interacts more with the single stranded beta6.3 helical monomer or dimer than with the double helical form of gramicidin. This was further confirmed by an increase in the rate of gramicidin mediated proton transport in liposomes by fenvalerate, using the pH sensitive fluorophore, pyranine.     

The selective norepinephrine reuptake inhibitor, LY368975, reduces food consumption in animal models of feeding

PURPOSE: The present study evaluated the cytostatic and apoptotic effects of a 24-hr paclitaxel treatment in ovarian tumors. METHODS: Three-dimensional histocultures of surgical specimens from patients (n = 17) were used. The cytostatic effect was measured by inhibition of 96-hr cumulative DNA precursor incorporation and induction of apoptosis was determined by morphological changes. RESULTS: Paclitaxel produced partial inhibition of DNA precursor incorporation in about 40% of tumors (maximum inhibition of approximately 30%) and induced apoptosis in about 90% of tumors (maximum apoptotic index of approximately 15%). In responsive tumors, maximum cytostatic and apoptotic effects were achieved at < or = 1 microM with no further enhancement by increasing the drug concentration to 10 microM. In individual tumors, the apoptotic effect inversely correlated with cytostatic effect (r2 = 0.27, p = 0.031), and the maximal apoptotic index correlated with the LI for the untreated controls (r2 = 0.38, p < 0.01). More than 95% of apoptotic cells after paclitaxel treatment were labeled with DNA precursor. The incomplete cytostatic and apoptotic effects of paclitaxel and the link between DNA synthesis and apoptosis in ovarian tumors are similar to our previous findings in other human solid tumors. CONCLUSIONS: These findings suggest that (a) apoptosis is the major paclitaxel effect in advanced ovarian tumors, (b) tumor sensitivity to drug-induced cytostatic effect is opposite to sensitivity to apoptotic effect, (c) paclitaxel-induced apoptosis increases with increased cell proliferation and is completed after DNA synthesis, and (d) further increasing the dose to elevate plasma concentration beyond 1 microM may not improve treatment outcome.