Continuing care of patients with cardiovascular risk in general practice: patients with dyslipidemia and their care

INTRODUCTION: The role of dyslipidemia is essential in the development of atherosclerosis, therefore continuing care of dyslipidemic patients is an extremely important task in cardiovascular prevention. AIMS: This study was aimed to investigate continuing care of dyslipidemic patients in general practices. Method of the study was a questionnaire survey, 397 patients of 39 general practices were involved into the study. RESULTS: The cause of their continuing care was hypercholesterolemia in 91.7%, hypertriglyceridemia in 69%, decreased HDL-C in 18.4%, and these alterations frequently occurred together. Hypertension in 77%, disturbances of carbohydrate metabolism in 41.7%, increased BMI in 43.2% were found. Patients were smokers in 26.5%, given up smoking in 13.2%. They had cardiovascular problems in 56.5%, cerebrovascular problems in 18.6% and peripheral vascular ones in 20.3%. Patients were treated with lipid lowering drugs in 87.7%, statins were used in 81.7%, fibrates in 29.6% and both of them in 11.5%. The main results of continuing care were: in the whole group frequency of cholesterol level > 5.2 mmol/l decreased by 13%, frequency of triglyceride level >1.7 mmol/l decreased by 4%; cholesterol target values were reached in 3% of patients with high cardiovascular risk, in 22.2% of patients with medium risk, and in 66.7% of patients with mild risk. CONCLUSIONS: These results suggest that there is a need for more intensive drug treatment of dyslipidemic patients to reach the target lipid levels, and for regular assessment of continuing care of these patients.     

Scurvy leads to endoplasmic reticulum stress and apoptosis in the liver of Guinea pigs

Insufficient ascorbate intake causes scurvy in certain species. Beyond its known functions, it has been suggested that ascorbate participates in oxidative protein folding in the endoplasmic reticulum (ER). Because redox imbalance in this organelle might cause ER stress and apoptosis, we hypothesized that this might contribute to the pathology of scurvy. Guinea pigs were divided into 7 groups: the control group was fed a commercial guinea pig food containing 0.1 g/100 g ascorbate for 4 wk, 5 groups consumed an ascorbate-free food for 0, 1, 2, 3, or 4 wk and 1 group was fed this scorbutic diet for 2 wk and then the commercial food plus 1 g/L ascorbate in drinking water for 2 wk. TBARS generation and the expression of some ER chaperones and foldases were determined in hepatic microsomes. The apoptotic index was assessed in histological sections. Although ascorbate, measured by HPLC, was undetectable in the livers of the guinea pigs after they had consumed the scorbutic diet for 2 wk, the microsomal TBARS level was elevated relative to the initial value only at wk 4. Western blot revealed the induction of GRP78, GRP94, and protein disulfide isomerase at wk 3 and 4. Apoptosis was greater than in the control, beginning at wk 3. None of the alterations occurred in the groups fed the commercial guinea pig food or ascorbate-free food followed by ascorbate supplementation. Therefore, persistent ascorbate deficiency leads to ER stress, unfolded protein response, and apoptosis in the liver, suggesting that insufficient protein processing participates in the pathology of scurvy.     

Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients

A study was undertaken to determine Al, Mg and P concentrations in 5 different brain regions of 3 control and 3 Alzheimer-diseased patients. One of the aims of this work was to evaluate the performance of applied analytical techniques. The digested samples were analyzed by inductively coupled plasma atomic emission spectrometry for Al, Mg and P. The dried samples were measured by instrumental neutron activation analysis for Al and Mg. The determination of human brain Al levels is complicated by the interfering reaction of P. We have previously worked out an analytical method which can eliminate this interference. The accuracy of the measured data was investigated by the analysis of biological standard reference materials. Our second goal was to study the possible elemental concentration changes in Alzheimer-diseased patients. Significantly higher Al and lower Mg and P values were found in some AD brain regions compared to the controls.     

Hepatitis C virus RNA in the skin eruption from patients with prurigo and chronic hepatitis C

Hepatitis C virus RNA in the skin eruption from patients with prurigo and chronic hepatitis C. Since the discovery of hepatitis C virus (HCV) in 1989, many cutaneous disorders have been observed in patients suffering from chronic HCV infection. The relationship between HCV infection and cryoglobulinemia and porphyria cutanea tarda is clearly established, however, the link between HCV and other skin diseases is still controversial. AIM: Two patients with intense pruritus and secondary prurigo in chronic C hepatitis have been presented. METHODS: The chronic hepatitis C of the patients were proved by elevated ALT and AST level, anti HCV (ELISA), HCV-PCR serological examination and liver biopsy. The skin lesions were accompanied by severe itching. According to clinical symptoms the patients suffered from prurigo simplex. RESULTS: HCV RNA in the skin specimen from the biopsy of the skin lesion was detected by RT PCR method, but the non affected skin specimen from the patients was HCV RNA negative. CONCLUSIONS: This report is a case of prurigo simplex with chronic C hepatitis proving a direct relation between the HCV infection and prurigo.     

Metastatic endophthalmitis following lung transplantation

Intraocular septic--bacterial, viral or fungal--metastasis originating from an infectious focus is very rare but serious complication. The authors performed one enucleation and one evisceration on two patients because of endophthalmitis secondary to pulmonary infection following lung transplantation. The pathogens were Pseudomonas aeruginosa and Mycobacterium xenopi respectively. With this case report the authors aim to draw attention to a rare, but serious ophthalmic complication of organ transplantation: endophthalmitis; its early care, to help prevent the need for enucleation.     

Glucose analog inhibitors of glycogen phosphorylases as potential antidiabetic agents: recent developments

Diabetes is among the largest contributors to global mortality through its long term complications. The worldwide epidemic of type 2 diabetes has been stimulating the quest for new concepts and targets for the treatment of this incurable disease. A new target is glycogen phosphorylase (GP), the main regulatory enzyme in the liver responsible for the control of blood glucose levels. One of several approaches to influence the action of GP is the use of glucose derivatives as active site inhibitors. This field of research commenced 10-15 years ago and, due to joint efforts in computer aided molecular design, organic synthesis, protein crystallography, and biological assays, resulted in glucopyranosylidene-spiro-hydantoin 16 (K(i) = 3-4 micro M) as the most efficient glucose analog inhibitor of GP of that time. The present paper surveys the recent developments of this field achieved mainly in the last five years: the synthesis and evaluation of glucopyranosylidene-spiro-thiohydantoin 18 (K(i) = 5 micro M) which has proven equipotent with 16, and is available in gram amounts; furanosylidene- and xylopyranosylidene-spiro-(thio)hydantoins whose ineffectiveness (K(i) > 10 mM) confirmed the high specificity of the catalytic site of GP towards the D-glucopyranosyl unit; "open" hydantoins like methyl N-(1-carboxamido-D-glucopyranosyl)carbamate 37 (K(i) = 16 micro M) and N-acyl-N'-(beta-D-glucopyranosyl)ureas among them the to date best glucose analog inhibitor N-(2-naphthoyl)-N'-(beta-D-glucopyranosyl)urea (35, K(i) = 0.4 micro M) which can also bind to the so-called new allosteric site of GP; C-(beta-D-glucopyranosyl)heterocycles (tetrazole, 1,3,4-oxadiazoles, benzimidazole (K(i) = 11 micro M), and benzothiazole). Iminosugars like isofagomine (45, IC(50) = 0.7 micro M), noeuromycin (53, IC(50) = 4 micro M), and azafagomine (54, IC(50) = 13.5 micro M) also bind strongly to the active site of GP, however, substitution on the nitrogens makes the binding weaker. The natural product five-membered iminosugar DAB (56) exhibited IC(50) approximately 0.4-0.5 micro M. Azoloperhydropyridines which can be regarded iminosugar-annelated heterocycles show moderate inhibition of GP: nojiritetrazole 12 (K(i) = 53 micro M) is the best inhibitor and fewer nitrogens in the five-membered ring weakens the binding. Physiological investigations have been carried out with N-acetyl-beta-D-glucopyranosylamine 6, spiro-thiohydantoin 18, isofagomine 45, and DAB 56 to underline the potential use of these compounds in the treatment of type 2 diabetes. Computational methods suggest to synthesize further anomerically bifunctional glucose derivatives which may be good inhibitors of GP.     

Blood substitutes--current evidence

The aim to find an artificial substitute for human blood has failed in the past 70 years and will most probably fail in the following future. Genomics, proteomics and posttranslational research have revealed that blood is our most complex and highly coordinated organ. Plasma substitutes can only promote a single function of plasma: the blood volume replacement. The even more complex coordination of the intraerythrocytic hemoglobin functions based on the allosteric structural changes induced by binding of O2, CO2 and NO can not be replaced safely by artificial oxygen carriers. Cell-free haemoglobin binds NO, which under physiological conditions coordinates O2 supply with the respiratory cycle and vasomotor function. The binding of NO to haemoglobin results in hypertonic crisis and in increase of leukocyte adherence and platelet aggregation. These complications may have a fatal outcome.     

Prevalence of the alpha-1 antitrypsin phenotype in Hungary

INTRODUCTION: Alpha-1-antitrypsin deficiency is one of the most common inherited metabolic disorders. The presence of PiZ and PiS alleles alpha-1-antitrypsin deficeing are associated with. The geographical distribution of PiZ and PiS is heterogenous in Europe. AIM: The aim of the study was to investigate the frequency of alpha-1-antitrypsin alleles with isoelectric focusing in 789 healthy Hungarian citizens and to compare the results to those obtained in other European countries. The measurements were done in the Laboratory of the Institute of Experts in Forensic Medicine. RESULTS: The frequency of PiM, PiZ and PiS alleles were 97.2%, 0.95% and 1.65% respectively. Therefore, the hypothetical prevalences of PiZZ and PiSS alleles are 1:10526 and 1:6060, respectively. CONCLUSION: These results do not differ significantly from those found in the neighbouring countries. Further investigation is needed to elucidate the possible role of alpha-1-antitrypsin phenotypes in the pathogenesis of chronic liver disorders and lung emphysema.