ubiquinone and Acquired-Immunodeficiency-Syndrome

Zidovudine (ZDV) has been associated with 'ragged-red' fibre myopathy, due to its effects on myocyte mitochondria. Usually this is reversible with cessation of ZDV. We report a 52-year-old man, who in 1985 developed ragged-red fibre myopathy 14 years after diagnosis of HIV infection while on effective ZDV-based combination antiretroviral therapy (ART). He was treated with the mitochondrial anti-oxidant coenzyme Q10 and made an excellent recovery, without change of ARTs. This suggests a novel therapy for further investigation targeted at ZDV induced myopathy, potentially allowing continuation of antiviral treatments including ZDV.

Topics: Acquired Immunodeficiency Syndrome; Coenzymes; Drug Therapy, Combination; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Reverse Transcriptase Inhibitors; Treatment Outcome; Ubiquinone; Zidovudine

This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antifungal Agents; Atovaquone; Case-Control Studies; Cohort Studies; Cytochrome b Group; Female; Gene Amplification; Humans; Male; Middle Aged; Molecular Sequence Data; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Genetic; Retrospective Studies; Survival; Treatment Outcome; Ubiquinone

Hypothalamic digoxin, an isoprenoidal metabolite, is an endogenous regulator of membrane Na(+)-K(+) ATPase activity, immune activation and synaptic neurotransmission. The objective of this study was to assess the role of hypothalamic digoxin and hemispheric dominance in the pathogenesis of the acquired immunodeficiency syndrome (AIDS) and in the genesis of sexual orientation.. The isoprenoid-pathway-related cascade - (i) isoprenoidal metabolites - digoxin, dolichol and ubiquinone, (ii) tryptophan/tyrosine catabolic patterns, (iii) glycoconjugate metabolism, (iv) free radical metabolism and (v) membrane composition were assessed in AIDS (CDC stage - group IV - subgroup C), individuals with differing hemispheric dominance as well as in individuals with differing sexual orientation. Statistical analysis was done by Student's t test with modified degrees of freedom.. The HMG CoA reductase activity was increased with increased digoxin and dolichol levels and reduced ubiquinone levels in AIDS. The membrane Na(+)-K(+) ATPase activity and serum magnesium levels were reduced. The tryptophan catabolites (serotonin, quinolinic acid, nicotine and strychnine) were increased and the tyrosine catabolites (morphine, dopamine and noradrenaline) were reduced. The serum glycoconjugate metabolites were increased and lysosomal stability was reduced in AIDS. There was reduced incorporation of glycoconjugates into membranes and an increased membrane cholesterol:phospholipid ratio. Lipid peroxidation products and NO were increased while free radical scavenging enzymes and reduced glutathione were reduced. The biochemical patterns obtained in AIDS correlated with those obtained in right-hemispheric dominance and homosexuals/bisexual states.. Hypothalamic digoxin and right-hemispheric dominance is important in the predisposition to AIDS as well as homosexual/bisexual states.

Topics: Acquired Immunodeficiency Syndrome; Adult; Cell Membrane; Cerebral Cortex; Cholesterol; Digoxin; Dolichols; Down-Regulation; Enzymes; Erythrocytes; Free Radicals; Functional Laterality; Genetic Predisposition to Disease; Glycosaminoglycans; Humans; Hydroxymethylglutaryl CoA Reductases; Hypothalamus; Male; Risk Factors; Sexual Behavior; Signal Transduction; Sodium-Potassium-Exchanging ATPase; Ubiquinone; Up-Regulation

Coenzyme Q10 (CoQ10) is indispensable to biochemical mechanisms of bioenergetics, and it has a non-specific role as an antioxidant. CoQ10 has shown a hematological activity for the human and has shown an influence on the host defense system. The T4/T8 ratios of lymphocytes are known to be low in patients with AIDS, ARC and malignancies. Our two patients with ARC have survived four-five years without any symptoms of adenopathy or infection on continuous treatment with CoQ10. We have newly found that 14 ordinary subjects responded to CoQ10 by increases in the T4/T8 ratios and an increase in blood levels of CoQ10; both by p less than 0.001. This knowledge and survival of two ARC patients for four-five years on CoQ10 without symptoms, and new data on increasing ratios of T4/T8 lymphocytes in the human by treatment with CoQ10 constitute a rationale for new double blind clinical trials on treating patients with AIDS, ARC and diverse malignancies with CoQ10.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; CD4-Positive T-Lymphocytes; Coenzymes; Female; Humans; Leukocyte Count; Male; Middle Aged; T-Lymphocytes, Regulatory; Ubiquinone

Two situations required a modified determination of coenzyme Q10 (CoQ10) in human blood and organ tissue. Blood from patients with AIDS and cancer raised apprehensions about safety to an analyst, and the number of specimens for analysis is increasing enormously. A modified determination replaces silica gel-TLC with disposable Florisil columns, and steps were simplified to allow more analyses per unit time. Data from the modified determination are quantitatively compatible with data from older and tedious procedures. This determination was used for blood from 36 diverse patients with allergies. The mean CoQ10 blood level of these patients is not different from the mean level of so-called normal individuals, but approximately 40% (14/36) of these allergic patients had levels up to 0.65 micrograms/ml, which is the level of dying class IV cardiac patients. The biosynthesis of CoQ10 in human tissues is a complex process that requires several vitamins and micronutrients, so that countless vitamin-unsupplemented Americans may be deficient in CoQ10. The relationship of allergies to autoimmune mechanisms and immunity, and the established relationship of CoQ10 to immune states, may be a rationale for therapeutic trials of administering CoQ10 to patients with allergies who have low CoQ10 blood levels and are very likely deficient.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Chromatography, High Pressure Liquid; Coenzymes; Female; Humans; Hypersensitivity; Indicators and Reagents; Male; Middle Aged; Reference Values; Safety; Specimen Handling; Ubiquinone

AIDS patients (2 groups) had a blood deficiency (p less than 0.001) of coenzyme Q10 vs. 2 control groups. AIDS patients had a greater deficiency (p less than 0.01) than ARC patients. ARC patients had a deficiency (p less than 0.05) vs. control. HIV-infected patients had a deficiency (p less than 0.05) vs. control. The deficiency of CoQ10 increased with the increased severity of the disease, i.e., from HIV positive (no symptoms) to ARC (constitutional symptoms, no opportunistic infection or tumor) to AIDS (HIV infection, opportunistic infection and/or tumor). This deficiency, a decade of data on CoQ10 on the immune system, on IgG levels, on hematological activity constituted the rationale for treatment with CoQ10 of 7 patients with AIDS or ARC. One was lost to follow-up; one expired after stopping CoQ10; 5 survived, were symptomatically improved with no opportunistic infection after 4-7 months. In spite of poor compliance of 5/7 patients, the treatment was very encouraging and at times even striking.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; Coenzymes; HIV; Humans; Ubiquinone