Intense blue light therapy during the night-time does not suppress the rhythmic melatonin biosynthesis in a young boy.

OBJECTIVE: Melatonin is a hormone predominantly synthesized and secreted during the night by the pineal gland. Artificial light at night, especially its blue part, acutely suppresses the melatonin production. Th e aim of the present study was to find out, whether an intense blue light phototherapy of severe hyperbilirubinemia, may suppress the melatonin production during the night when the eyes will be properly protected by a sleep mask. METHODS: The main melatonin metabolite, 6-sulphatoxymelatonin was measured in urine in a nine-year old boy suffering from the Crigler-Najjar syndrome type I. The boy was treated during the sleep period with an intense blue light (to 1800 lx) 10 h/day, since his birth. During the phototherapy, his eyes were protected with a sleep mask. The concentration of 6-sulphatoxymelatonin was determined in the first morning urine and urine collected afternoon during the six days. The patient was exposed to phototherapy for three nights, two nights without and the last one with the treatment. The control urine samples were obtained from 8 healthy nine-year old boys. The level of 6-sulphatoxymelatonin was measured by radioimmunoassay and the data were normalized to urinary creatinine. RESULTS: A distinct melatonin production rhythm was found and 6-sulphatoxymelatonin concentration in urine of the patient was comparable with the values obtained by the control group. No differences in 6-sulphatoxymelatonin levels were found between the nights with and without the phototherapy applied. CONCLUSIONS: We conclude that the whole night treatment of hyperbilirubinemia with intense blue light has negligible side effect on the rhythmic melatonin production, when the eyes are sufficiently protected by the sleep mask.

[Effect of hypolipidemic treatment on the composition of bile and the risk or cholesterol gallstone disease]. / Vliv hypolipidemické lécby na slození zluce a riziko cholesterolove cholelitiáizy.

Obesity, diabetes mellitus type 2 and dyslipidemia, characterized by hypertriglyceridemia and low HDL-cholesterol levels, are risk factors for cholesterol gallstone disease. The common denominator of above-mentioned states is insulin resistance. Hypolipidemic treatment significantly influences not only the biliary lipid composition, but also other etiopathogenetic mechanisms of the disease. Three principal defects are involved in gallstone formation - cholesterol supersaturation, accelerated nucleation, and gallbladder dysmotility. The degree of cholesterol saturation in gallbladder bile is the most important predictor of cholesterol crystal formation. Cholesterol, lecithin and bile acids are the major components in bile. According to the molar ratios of the three main components, simple or mixed micelles, unstable unilamellar or multilamellar vesicles are formed in the bile. The cholesterol supersaturation of the gallbladder bile and cholesterol crystal formation from the unstable multilamellar vesicles initiates the onset of cholesterol cholelithiasis. The pool of unesterified cholesterol is the source for VLDL synthesis; together with HDL-cholesterol, it is also the source for cholesterol secretion into the bile. The main metabolic products of cholesterol degradation are bile acids, which are synthesized predominantly from LDL-cholesterol. The rate of the production of primary bile acids is principally regulated by cholesterol 7alpha-hydroxylase (CYP7A 1). The treatment of dyslipidemia with niacin and resins does not influence the saturation of bile with cholesterol or the incidence of cholelithiasis. The effects of ezetimibe in human patients with the respect of cholesterol cholelithiasis have not been published. The fibrate treatment is associated with increased cholesterol saturation of bile due to inhibition of CYP7A1 activity, enhanced flux of cholesterol via HDL and increased secretion of cholesterol into bile. The clinical studies describe cholesterol supersaturation in bile and increased frequency of cholelithiasis as well. The administration of pravastatin and simvastatin led to reduced cholesterol saturation indexes. The patients with endogenous hypertriglyceridemia and low HDL-cholesterol being administered with polyunsaturated fatty acids of n-3 family had decreased cholesterol concentration in bile. Other authors described beneficial effect of fish oil on the biliary cholesterol nucleation time, improvement of gallbladder sensitivity to cholecystokinin and the prevention of cholesterol gallstone formations caused by rapid weight loss.

[Oxidation stress, insulin resistance and endothelial dysfunction during the treatment of hyperlipidaemia]. / Oxidacní stres, inzulínová rezistence a endoteliální dysfunkce v prubehu lécby hyperlipidémie.

BACKGROUND: Hyperlipidaemia represents one of the major risk factors of the type 2 diabetes mellitus (DM2). In the pathogenesis of insulin resistance (IR) development glucose homeostasis impairment and their progression into DM2, oxidative stress and endothelial dysfunction (ED) may play an important role. Recent papers indicate the possibility to prevent the development of DM2 by HLP treatment, which is characterised by increased oxidation stress and ED. METHODS AND RESULTS: For the period of twelve months 46 patients with primary HLP (group S) (LDL-C > 4.1 mmol/l a TG < 3.5 mmol/l), were treated with atorvastatine 20 mg or simvastatine 40 mg. Patients with LDL-C > 4.1 mmol/l along with TG > 3.5 mmol/l were randomly divided into two groups. The SF group was treated with a combination of statin + 200 mg micronized fenofibrate each day, and group SR received together with statin a compound containing n-3 polyene fatty acids (PUFA n-3) in the daily dose of 3.6 g. After one year lasting therapy we found beside the positively influenced concentration of atherogenic lipids and lipoproteins in the group S and SF a significantly reduced concentration of conjugated dienes (CD) in LDL ( -21, resp. 16%, both P < 0.05); the test of KD kinetics in LDL in the group S has marginal increase of the lag phase (P = 0.06) and in the groups S and SR also a significant improvement of ED (increase by the flow of mediated vasodilation, FMD) by 20%, resp. by 18% (both P < 0.05) and in the SR group a significant decrease of microalbuminuria. We did not proved significant concentrations of insulin, C-peptide or indexes showing the degree of IR (HOMA and QUICKI) CONCLUSIONS: Long-lasting hypolipidemic treatment positively affected in our study the oxidative stress and ED, however, it did not resulted in changes of IR.

[Effect of n-3 polyunsaturated fatty acids on plasma lipid, LDL lipoperoxidation, homocysteine and inflammation indicators in diabetic dyslipidemia treated with statin + fibrate combination]. / Vliv vícenenasycených mastných kyselin rady n-3 na plazmatické lipidy, lipoperoxidaci LDL, homocystein a ukazatele zánetu u diabetické dyslipidémie, lécené kombinací statin + fibrát.

BACKGROUND: The aim of the study was to determine how addition of n-3 polyenic fatty acids (PUFA) to the present treatment with statin + fibrate combination in diabetic dyslipidemia effects plasma lipids and lipoproteins, LDL lipoperoxidation, glucose homeostasis, concentration of serum homocysteine and selected inflammation indicators. METHODS AND RESULTS: 24 patients with type 2 diabetes, who after the combined hypolipidemic treatment (pravastatin 20 mg + micronized fenofibrate 200 mg per day) cannot reach the recommended target values for long time, received for three consecutive months supplementation of 3,6 g PUFA n-3 per day or a placebo (olive oil). At the beginning of the study, after three months of PUFA supplementation and after another three months of placebo administration, concentrations of plasma lipids, composition of fatty acids, plasma phosphatidylcholine (PC), cholesterol esters (CE) and triglycerides (TG), concentration of tHcy, conjugated diens (CD) in LDL and selected inflammation indicators (IL-6, TNFalpha, VCAM-1) were determined. n-3 PUFA supplementation resulted in the significant decrease of tHcy concentration (-29%, P < 0.01) and TG (-28%, P < 0.05) in plasma. During the period of placebo administration, values returned to base line levels. CD concentration in LDL after n-3 PUFA increased by 15% (P < 0.15, not significant), meanwhile after the placebo containing oleic acid it decreased by 18% (P < 0.05). CONCLUSIONS: Our results show that n-3 PUFA supplementation together with statin + fibrate combination in DDL patients can significantly decrease the risk of cardiovascular diseases.

Chronomics: circadian lead of extrapineal vs. pineal melatonin rhythms with an infradian hypothalamic exploration.

A circadian rhythm is documented for plasma, pineal, and hypothalamic melatonin of male and female rats kept on staggered lighting regimens. Log[_10]-transformation of the data usually normalizes, when need be, the distribution of residuals from the 24-hour cosine curve fits. A tentative circadian acrophase chart is presented that shows a lead in circadian acrophase of duodenal over pineal melatonin. The use of antiphasic lighting regimens facilitates circadian studies that can be carried out for several days, thereby allowing the assessment of infradian components such as a circasemiseptan variation in hypothalamic melatonin documented herein. The results are qualified by the presence of a second extremum of a double magnetic storm at the start of mapping.

Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts--forecasts of geomagnetics.

A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international [arbitrary] units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.

Chromium levels in patients with internal diseases.

Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).

[Effect of fish oils on plasma lipid risk factors and esterified fatty acids in primary hyperlipoproteinemia]. / Vliv rybích oleju na plazmatické lipidové rizikové faktory a esterifikované mastné kyseliny u primárních hyperlipoproteinemií.

BACKGROUND: Some epidemiological, clinical and experimental studies have shown that intake of n-3 fatty acids (FA) lowers the incidence of coronary heart disease (CHD). The effects of fish oil and n-3 FA on the development of atherosclerosis include several factors such as the platelet-vascular wall interaction, modulation of eicosanoid metabolism as well as platelet aggregation and its survival time. There were also changes in the fibrinolytic system and cardiovascular reactivity observed. Effects of n-3 FA on lipid and lipoprotein metabolism exert antiatheromatous action as well. The aim of the study was to evaluate changes in plasma lipid risk factors for CHD in subjects with primary hyperlipoproteinemia (HLP) after the administration of fish oil rich in n-3 FA. METHODS AND RESULTS: A total of 82 patients (61 men and 21 women) were administered fish oil (3.5 g n-3 FA daily) for a period of 3 weeks. The group of hyperlipidemics included 9 patients with HLP IIA, 29 with HLP IIB, and 35 with HLP IV. Seven patients had HLP type V while two had HLP type III. Intake of fish oil led to a mild decrease in total plasma cholesterol which was significant in the whole group and in HLP type V. Triglyceride levels declined significantly in all HLP phenotypes, with the changes being most marked in HLP types IIB, IV, and V. We also observed a significant increase in cholesterol concentration in HDL and in the both HDL2 and HDL3 subfractions in the whole group and all HLP phenotypes as well. On the other hand no statistical significant changes were observed in LDL-cholesterol levels. The levels of apo B rose significantly only in HLP type V. A statistically significant increase was found in apo A-1 levels in the whole group and in the HLP IIB subgroup. Fish oil administration led to a mild reduction in diastolic pressure and uricemia. In part of patients fish oil induced decrease in lipoprotein(a) concentration was observed.

[The effect of fish oil on metabolic parameters in patients with type 2 diabetes mellitus associated with dyslipidemia]. / Ucinky rybích oleju na nekteré metabolické parametry nemocných s diabetes mellitus 2. typu a pruvodnou dyslipidémií.

BACKGROUND: The authors discuss the effect of administration of fish oils rich in n-3 fatty acids in diabetic patients type 2 and draw attention to the possible deterioration of glucose homeostasis. The objective of the investigation was to assess changes of the lipid and carbohydrate metabolism in type 2 diabetics with associated dyslipidaemia after enrichment of the diet with n-3 fatty acids. METHODS AND RESULTS: To 17 patients with type 2 diabetes and dyslipidaemia fish oil containing 5.5 g n-3 fatty acids per day was administered. After six weeks a decline of triglycerides was recorded (-47%, P < 0.01), free fatty acids (-27%, P < 0.01) and a rise of HDL2-cholesterol (25%, P < 0.05). The concentration of apo B, apo A-1, LDL- and HDL cholesterol did not change significantly. There were no significant changes of the blood sugar level, glycosylated haemoglobin and fructosamine. The insulin and C-peptide concentration on fasting (and after glucagon stimulation) did not change significantly. With regard to the HDL2-cholesterol and 18:0 fatty acid concentration in serum the group can be divided into responders (with a decline of glycosylated haemoglobin) and non-responders. The two groups have a reverse trend of blood sugar levels and insulinaemia and differ as to the metabolism of 18:1 n-7 acid. CONCLUSIONS: Enrichment of the diet with n-3 fatty acids in diabetics with dyslipidaemia has a favourable effect on the plasma lipid spectrum without causing deterioration of parameters of diabetes compensation. Among the group of patients some can be found where fish oil administration improves also glucose homeostasis.

[The effect of polyene phosphatidylcholine administration on lipid metabolism and glucose tolerance in patients with hyperlipoproteinemia IIB]. / Ovlivnení metabolismu lipidu a glukózové tolerance u pacientu s hyperlipoproteinémií typu IIB podáváním polyenového fosfatidylcholinu.

BACKGROUND: Up to now, clinical and experimental studies have brought only inconsistent data about the effectiveness of polyene phosphatidylcholine (PPC) in treatment of dyslipidemia. The aim of this randomized, double blind study was to verify the effects of the polyene phosphatidylcholine preparation Lipostabil forte R (Rhone-Poulenc-Röhrer, Köln, FRG), given orally in a daily dose 2.7 g for three months to patients with hyperlipoproteinemia type IIB and hypoalfacholesterolemia both on the plasma lipids, lipoproteins, apolipoproteins and the parameters of glucose tolerance. METHODS AND RESULTS: Administration of PPC to 30 patients with hyperlipoproteinemia type IIB and hypoalfacholesterolemia led to a significant rise of HDL-cholesterol, HDL3-cholesterol and plasma apolipoprotein A-I concentrations in comparison with the group treated with placebo. At the same time, plasma apolipoprotein B concentration slightly increased. Blood glucose, immunoreactive insulin and non-esterified fatty acid concentrations during the oral glucose tolerance test didn't change significantly after PPC administration. CONCLUSIONS: It seems PPC could be the appropriate supplement to the treatment of patients with decreased concentrations of HDL-cholesterol and plasma apolipoprotein A-I.

[Comparison of the effects of omega-3 polyunsaturated fatty acids and Olbetam (Acipimox) in the treatment of hypertriglyceridemia]. / Srovnání úcinku polyenových mastných kyselin rady omega-3 a preparátu Olbetam (Acipimox) v lécbe hypertriglyceridémie.

BACKGROUND: Hypertriglyceridaemia associated with low HDL-concentrations is considered an independent risk factor of ischaemic heart disease. The drug of choice in this disorder is nicotinic acid. The aim of the presented work was to compare the hypolipidaemic effect of fish oils rich in omega-3 fatty acids (Activepa 30-TGR, Hydromartens, Norway) with a nicotinic acid derivative, acipimox (Olbetam, Farmitalia Carlo Erba, Italy). METHODS AND RESULTS: The preparations were administered for a three-week period to two groups of patients with hypertriglyceridaemia and low HDL cholesterol levels. The groups had comparable body weights and baseline parameters of lipid metabolism. In the group treated with Olbetam (750 mg/day), 17x hyperlipoproteinaemia type IV and 6x IIB) after treatment significant changes of the following parameters were recorded: triglycerides (-18%; P < 0.001), HDL cholesterol (+19%; P < 0.01), HDL2 and HDL3 cholesterol (+33%; +14%; P < 0.001, P < 0.01), apo B (+25%; P < 0.01), apo A-I (+7%; P < 0.01), ratio of apoB/A-I (+17%; P < 0.01). Furthermore, there was s drop of the atherogenic index (total cholesterol/HDL cholesterol) by 22% (P < 0.001). In the group of subjects (17x type IV and 8x type IIB) whose diet was enriched with omega-3 fatty acids (3.5 g/day), the following parameters changed significantly: triglycerides (-44%; P < 0.001), the atherogenic index (-23%; P < 0.001), HDL cholesterol (+11%, P < 0.01), HDL2 and HDL3 cholesterol (+13%, +17%; P < 0.01, P < 0.05). Changes of apo B, apo A-I concentrations and their ratios were not significant. Comparison of the effect of the two preparations on the investigated parameters revealed a more marked rise of the HDL cholesterol (P < 0.05), apo B (P < 0.01) concentrations and the apo B/-A-I ratio (P < 0.05) during Olbetam treatment. As to the action of the two preparations on further investigated parameters (total and LDL-cholesterol), no significant differences found. CONCLUSIONS: The assembled results indicate that enrichment of the diet with fish oil rich in omega-3 fatty acids has a hypolipidaemic effect comparable to acipimox. It is thus feasible to use fish oils as a drug of first choice in the treatment of hypertriglyceridaemia associated with a reduction of HDL cholesterol concentration.

[The effect of the spectrum fatty acids in plasma lipids on the hypolipidemic effect of fish oils in hyperlipidemic patients]. / Vliv spektra mastných kyselin plazmatických lipidu na hypolipidemický úcinek rybích oleju u hyperlipidemiku.

The authors administered to a group of 60 patients with primary hyperlipoproteinaemia (HLP) HLP type IIA 9, IIB 16, type IV 35 (fish oil) (Activepa 30TG) rich in eicosapentaenic acid (EPA, 20:5-n-3) and docosahexaenic acid (DHA, 22:6n-3). Administration of fish oil, 10 g per day, for a period of 21 days led to a decline of the total cholesterol by 9.8%, triglycerides (TG) by 39.5% and a rise of HDL-cholesterol (HDL-C) by 12.8%. The concentration of LDL-C, apo B, and apo A-I did not change significantly. The content of individual fatty acids (FA) in phosphatidyl choline (PC) cholesteryl esters (CE) and plasma TG before treatment was used as an independent variable for discrimination analysis in relation to dependent variables such quintile 1 (Q1) and Q2 on the one hand and Q4 and Q5 differences of the above mentioned parameters on the other hand. The drop of TG after ingestion of n-3 FA correlates indirectly with concentrations of PC 20:5n-3, TG 18:3n-3 and TG 20:4n-6. The content of 20:0 and 20:1 in PC and 18:0 in TG are related to the rise of LDL-C after treatment. The drop of apo B is associated with the PC 22:6n-3 concentration. The rise of HDL-C and apo A-I is positively associated with the concentration of 16:1n-7 in PC and TG and negatively with the CE 16:0 content. The rise of HDL-C after treatment is moreover negatively influenced by concentrations of PC 18:3n-6 and TG 20:3n-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary n-3 fatty acids on the composition of cholesteryl esters and triglycerides in plasma and liver perfusate of the rat.

The effects of polyunsaturated fatty acids of the omega-3 family (PUFA n-3), (addition of fish oil), on the molecular composition of cholesteryl esters and triglycerides in plasma and liver perfusate of rats were studied. Rats fed a diet rich in saturated fatty acids (addition of lard) served as controls. Supplemention with PUFA n-3 not only decreases the plasma concentrations of free cholesterol, cholesteryl esters, and triglycerides, it also significantly alters the plasma composition of cholesteryl esters and triglycerides. Analyses of liver perfusate indicate a decrease in triglycerides secretion by in vitro perfused liver and reciprocal changes in relative contents of cholesteryl esters fractions with C(16) and C(20) acyl chains. This finding may be a result of chain-shortening of long-chain fatty acids probably in peroxisomal beta-oxidative system. Alterations in plasma cholesteryl esters and triglycerides composition of the fish oil group could be affected further by additional factors such as increased plasma cholesterol esterification activity and presence of triglyceride species of intestinal origin.