beta-carotene and citroxanthin

Brugada syndrome (BrS), caused by ion channel abnormalities, is characterized by ST segment elevation and negative T waves in the right precordial electrocardiographic (ECG) leads recorded over the right ventricular outflow tract (RVOT). BrS is sensitive to body temperature and can lead to T-wave alternans (TWA), ventricular tachycardia, and sudden death. Recent studies in an isolated canine RVOT model of BrS demonstrated that reversal of the transmural gradient of repolarization caused the ECG characteristics and that major intraepicardial and transmural dispersion of action potentials (APs) initiated phase 2 reentry, premature ventricular activations, and tachyarrhythmias. Hypothermia enhanced the heterogeneity of the AP and promoted the origination of phase 2 reentry in the epicardium of the RVOT, but the prolonged AP duration frequently blocked reentry. Hyperthermia abbreviated the AP and facilitated the maintenance of reentry and tachyarrhythmias. Bradycardia promoted alternans in the phase 2 dome of the AP within the epicardium of the RVOT, resulting in TWA. The above phenomena were localized in the epicardium of the RVOT. Blockade of the transient outward current, I(to), reduced AP heterogeneity and prevented arrhythmias in the BrS model. In addition, epicardial activation delay led to fragmented QRS, a risk marker of prognosis in BrS. Body surface mapping in patients with BrS supported these experimental findings. In conclusion, the AP heterogeneity within the epicardium of the RVOT contributes to the ECG characteristics, temperature sensitivity, TWA, and arrhythmias in BrS, and body surface mapping and fragmented QRS can be effective predictors of risk in patients with BrS.

Topics: Animals; Arrhythmias, Cardiac; beta Carotene; Body Temperature; Brugada Syndrome; Calcium Channels; Electrocardiography; Electrophysiologic Techniques, Cardiac; Heart Conduction System; Heart Ventricles; Humans; Risk Assessment; Sodium Channels

There are significant differences among patients treated with warfarin in the dosage volumes necessary to reach an optimum therapeutic effect. Apart from the external influences (interactions with drugs and food), genetic predispositions play an important role. Polymorphysms of the P 450 2C9 cytochrome bear upon the speed ofbreaking down S-warfarin, polymorfysms VKORC1 bear on the volume and quality of epoxide reductase--an enzyme whose blockade is the crux of the mechanism how cumarin anticoagulants act. These two genes are responsible for at least 50% of the warfarin effect variability. Warfarin's effect is further determined by the genetic variants of gamma-carboxylase, prothrombin, factors VII and IX. In near future, further results of pharmacogenetic research and clinical studies can be expected. They study the impact of the findings in clinical practice.

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; beta Carotene; Biotransformation; Cytochrome P-450 CYP2C9; Humans; Mixed Function Oxygenases; Pharmacogenetics; Polymorphism, Genetic; Vitamin K Epoxide Reductases; Warfarin

A point mutation [technical knockout(25t) (tko(25t))] in the Drosophila gene coding for mitoribosomal protein S12 generates a phenotype of developmental delay and bang sensitivity. tko(25t) has been intensively studied as an animal model for human mitochondrial diseases associated with deficiency of mitochondrial protein synthesis and consequent multiple respiratory chain defects. Transgenic expression in Drosophila of the alternative oxidase (AOX) derived from Ciona intestinalis has previously been shown to mitigate the toxicity of respiratory chain inhibitors and to rescue mutant and knockdown phenotypes associated with cytochrome oxidase deficiency. We therefore tested whether AOX expression could compensate the mutant phenotype of tko(25t) using the GeneSwitch system to activate expression at different times in development. The developmental delay of tko(25t) was not mitigated by expression of AOX throughout development. AOX expression for 1 d after eclosion, or continuously throughout development, had no effect on the bang sensitivity of tko(25t) adults, and continued expression in adults older than 30 d also produced no amelioration of the phenotype. In contrast, transgenic expression of the yeast alternative NADH dehydrogenase Ndi1 was synthetically semi-lethal with tko(25t) and was lethal when combined with both AOX and tko(25t). We conclude that AOX does not rescue tko(25t) and that the mutant phenotype is not solely due to limitations on electron flow in the respiratory chain, but rather to a more complex metabolic defect. The future therapeutic use of AOX in disorders of mitochondrial translation may thus be of limited value.

Topics: Adenosine Triphosphate; Animals; beta Carotene; Ciona intestinalis; Drosophila; Drosophila Proteins; Electron Transport Complex I; Embryonic Development; Female; Genotype; Hormone Antagonists; Male; Mifepristone; Mitochondria; Mitochondrial Proteins; NADH Dehydrogenase; Oxidoreductases; Phenotype; Plant Proteins; Reactive Oxygen Species; Ribosomal Proteins

The incidence of venous thromboembolism (VTE) during childhood is low with two peaks - neonatal and adolescent age. This retrospective study is focused on clinical characteristics ofVTE during adolescence. The main goals are to assess the most frequent inherited and acquired risk factors and to evaluate the benefit of D-dimers in diagnostics of venous thromboemblism. The data of 18 adolescents were analysed--16 girls (88.9%), 2 boys (11.1%). In 9 patients (50%) thrombosis of the lower limb deep veins was diagnosed, six patients (33.3%) suffered from symptomatic pulmonary embolism (PE) and 3 patients (16.7%) from thrombosis at unusual sites. One patient had an idiopathic VTE, the mean number of the inherited and acquired risk factors was 2.6. The most frequent inherited risk factor was Leiden mutation of factor V (27.8%). The most frequent acquired risk factor was oral contraception (OC) in 12 out of 16 girls (75%). All of our patients on oral contraception had one or more additional risk factors. 10 out of 18 (55.6%) patients with VTE had elevated activity of factor VIII. The sensitivity of D-dimers was low (50%) in patients with distal lower limb thrombosis, but very high (100%) in patients with PE.

Topics: Adolescent; beta Carotene; Factor V; Female; Humans; Male; Pulmonary Embolism; Risk Factors; Thrombophilia; Venous Thromboembolism

Topics: Adaptor Proteins, Signal Transducing; beta Carotene; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Methylation; DNA Mismatch Repair; Genetic Testing; Humans; MutL Protein Homolog 1; Nuclear Proteins; Promoter Regions, Genetic; Proto-Oncogene Proteins B-raf

Renal carcinoma represents histologically heterogeneous group of malignant tumors, with various clinical aggressiveness. The frequency of p53 mutation in primal renal carcinoma is rare, although there are information about its heterogeneous accumulation. The loss of protein p16 expression in primal renal carcinoma is detected in 20-30% of the cases. The aim of this paper was to determine frequency of mutated protein p53 and expression of protein p16(INK4a) in renal carcinoma, to analyze their correlative relation and relation with the examined clinicopathological parameters.. The examination included 12 patients (66.7% men, 33.3% women), with patohistologically verified renal carcinoma. Expression of mutated form of protein p53 and protein p16 was determined in tissue samples, by immunohistochemical analysis using of mice monoclonical antibodies produced by DAKO, Denmark. In 9 (75%) of the cases was detected mutated protein p53, of whom 66.6% had higher histological gradus of tumor (G3-4) and higher pathological stadium of the disease (pT3a-b) at the same time. In 7 (58.3%) and 5 (41.7%) of the cases expression of protein p16, the loss of expression of protein p16 were detected respectively. A statistically significant positive correlation was determined between pathological stadium of disease (TNM) and the degree of tumor differentiation (G) (p = 0.834; p < 0.001), as well as between TNM and mitotic index (p = 0.622; p = 0.031).. A mutated form of protein p53 exists in 75% of the cases with the renal carcinoma and 66.6% of then have higher histological gradus of tumor and higher stadium of tumor disease at the same time. Coexpression of mutated protein p53 and protein p16(INK4a) in renal carcinoma is not statistically significant and it is not in correlation with clinicopathological parameters. Immunohistochemical analysis of mutated protein p53 in renal carcinoma can have predictive significance.

Topics: Aged; Aged, 80 and over; beta Carotene; Cyclin-Dependent Kinase Inhibitor p16; Female; Genes, p53; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Proteins; Tumor Suppressor Protein p53

Three all-trans epoxides of beta-carotene (beta-Car), namely, 5,6-epoxy-beta-carotene (5,6-EC), 5,8-epoxy-beta-carotene (5,8-EC) and 5,6,5',6'-diepoxy-beta-carotene (5,6,5',6'-DEC) were synthesized by treatment of beta-carotene with 3-chloroperoxybenzoic acid, were purified chromatographically, and were characterized. The relative potencies (mean +/- S.D.) of 1 microM compounds in inducing the differentiation of NB4 cells, a cell line that contains the chromosomal transposition t(15;17) characteristic of acute promyelocytic leukemia, after 4 days of incubation were: RA: 1.35 +/- 0.16, 5,6-EC: 0.29 +/- 0.01, 5,8-EC: 0.22 +/- 0.05, 5,6,5',6'-DEC: 0.11 +/- 0.02, beta C: 0.09 +/- 0.01, and the control: 0.06 +/- 0.01. The same order of potencies existed at other concentrations tested and at other incubation times. P values for the differences between the inducing activities of successive pairs of compounds at 1 microM were: RA vs. 5,6-EC, < 0.001; 5,6-EC vs. 5,8-EC, < 0.01; 5,8-EC vs. 5,6,5',6'-DEC, < 0.01; 5,6,5',6'-DEC vs. beta-Car, < 0.10; beta-Car vs. control, < 0.005. Similar P values were also obtained for studies at other concentrations and at other incubation times. The viable cell mass at 4 days was inversely proportional to the extent of differentiation (rs = -1.0). The inducing activities of all compounds were dose-dependent. Thus, the 5,6-monoepoxide of beta-carotene, which has not previously been studied as an inducer, showed higher activity in NB4 cell differentiation than the 5,8-monoepoxide, the 5,6,5',6'-diepoxide, or beta-carotene. Possible explanations of these observations are discussed.

Topics: beta Carotene; Cell Differentiation; Cell Survival; Epoxy Compounds; Humans; Leukemia, Promyelocytic, Acute; Tretinoin; Tumor Cells, Cultured

Topics: Administration, Oral; Animals; Avitaminosis; beta Carotene; Carotenoids; Ethers, Cyclic; Intestines; Kidney; Liver; Lung; Rats; Spleen; Vitamin A; Xanthines

Topics: beta Carotene; Vitamin A; Vitamins

Topics: beta Carotene; Vitamin A; Vitamins