Chronic intermittent hypoxia elicits distinct transcriptomic responses among neurons and oligodendrocytes within the brainstem of mice.

Chronic intermittent hypoxia (CIH) is a prevalent condition characterized by recurrent episodes of oxygen deprivation, linked to respiratory and neurological disorders. Prolonged CIH is known to have adverse effects, including endothelial dysfunction, chronic inflammation, oxidative stress, and impaired neuronal function. These factors can contribute to serious comorbidities, including metabolic disorders and cardiovascular diseases.

Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and Heart Failure.

Aberrant autonomic signaling is being increasingly recognized as an important symptom in neuromuscular disorders. The δ-sarcoglycan-deficient BIO TO-2 hamster is recognized as a good model for studying mechanistic pathways and sequelae in muscular dystrophy and heart failure, including autonomic nervous system (ANS) dysfunction. Recent studies using the TO-2 hamster model have provided promising preclinical results demonstrating the efficacy of gene therapy to treat skeletal muscle weakness and heart failure.

Gait disturbances in dystrophic hamsters.

The delta-sarcoglycan-deficient hamster is an excellent model to study muscular dystrophy. Gait disturbances, important clinically, have not been described in this animal model. We applied ventral plane videography (DigiGait) to analyze gait in BIO TO-2 dystrophic and BIO F1B control hamsters walking on a transparent treadmill belt.

Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations.

Plasma coenzyme Q10 (CoQ10) response to oral ingestion of various CoQ10 formulations was examined. Both total plasma CoQ10 and net increase over baseline CoQ10 concentrations show a gradual increase with increasing doses of CoQ10. Plasma CoQ10 concentrations plateau at a dose of 2400 mg using one specific chewable tablet formulation.

Assessment of coenzyme Q10 absorption using an in vitro digestion-Caco-2 cell model.

The feasibility of using a coupled in vitro digestion-Caco-2 cell uptake as a model for examining the digestive stability and absorption of coenzyme Q10 (CoQ10) from a variety of commercially available CoQ10 products was examined. The products were first subjected to simulated digestion to mimic their passage through the GI tract to generate micelles containing CoQ10, and the micelle fractions added to monolayers of Caco-2 cells to determine CoQ10 uptake. The data demonstrate enhanced uptake of CoQ10 from formulations containing solubilized forms of CoQ10 and also from a CoQ10-gamma-cyclodextrin complex as compared with pure CoQ10 powder or tablets based on CoQ10 powder.

Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics.

Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant.

Potential role of ubiquinone (coenzyme Q10) in pediatric cardiomyopathy.

Pediatric cardiomyopathy (PCM) represents a group of rare and heterogeneous disorders that often results in death. While there is a large body of literature on adult cardiomyopathy, all of the information is not necessarily relevant to children with PCM. About 40% of children who present with symptomatic cardiomyopathy are reported to receive a heart transplant or die within the first two years of life.

Bioavailability assessment of oral coenzyme Q10 formulations in dogs.

The purpose of this investigation was to compare the bioavailability of three coenzyme Q10 (CoQ10) formulations in dogs using an open, randomized, multiple-dose crossover design. The formulations included a powder-filled capsule (A, control) and two soft gelatin formulations (Q-Gel as the water-miscible form of CoQ10, B and Q-Nol as the water-miscible form of ubiquinol, the reduced form of CoQ10, C). Formulations were evaluated in pairs, allowing a washout period of 14 days prior to crossing over.

Dietary coenzyme Q10 and vitamin E alter the status of these compounds in rat tissues and mitochondria.

Vitamin E (VE) and coenzyme Q (CQ) are essential for maintaining functions and integrity of mitochondria, and high concentrations of these compounds are found in their inner membranes. This study was conducted to examine the interaction between exogenously administered CQ10 and VE in rats. Male Sprague-Dawley rats (12 mo old) were fed a basal diet (10 IU VE or 6.

Relative bioavailabilities of natural and synthetic vitamin E formulations containing mixed tocopherols in human subjects.

There are several reports in the literature on the relative bioavailabilities of RRR (natural) vs. all-rac (synthetic) forms of vitamin E in humans and animal models but none on the bioavailability of alpha-tocopherol in mixed vitamin E formulations. In the present study we examined the bioavailability of alpha-tocopherol in a typical commercially available product containing mixed tocopherols.

Relative bioavailability of coenzyme Q10 formulations in human subjects.

The relative bioavailability of typical commercially available forms of coenzyme Q10 (CoQ10) was compared with that of Q-Gel, a new solubilized form of CoQ10, in human subjects in two separate trials. In the first, standard softgel capsules containing CoQ10 suspension in oil, powder-filled hardshell capsules and powder-based tablets were tested along with Q-Gel using a daily dosage of 120 mg for three weeks. The baseline plasma CoQ10 values were all very tight (0.

Uptake and distribution of carotenoids, retinol, and tocopherols in human colonic epithelial cells in vivo.

Studies suggest that micronutrients such as the tocopherols, retinol, and the carotenoids have a chemopreventive action against colonic carcinogenesis and that they may be essential for the functioning and structural integrity of the gastrointestinal epithelium. In this study, we have determined the concentrations of tocopherols, retinol, and the carotenoids in human colonic epithelial cells using a noninvasive procedure developed in this laboratory (G.P.

Ascorbic acid and gastrointestinal cancer.

A literature review was made to critically evaluate the ability of ascorbic acid to modulate the incidence of gastrointestinal cancer. A comparison of preclinical, clinical, and epidemiological studies indicated that evidence for ascorbic acid as an inhibitor of carcinogenesis is stronger with regard to gastric cancer and weaker with regard to esophageal and colon/rectal cancer. Insufficient evidence currently exists regarding the oral cavity and the use of ascorbic acid in precancerous conditions such as polyposis and leukoplakia.

Renal excretion of ascorbic acid: effect of age and sex.

To determine if the lower plasma ascorbic acid concentrations observed in males compared to females, and in the elderly in general, might be due to differences in renal clearances of ascorbic acid, tubular maximum reabsorptions (TmAA) and renal thresholds for ascorbic acid were determined on older (10 male, 10 female, aged 70-86 years) and younger (3 male, 5 female, aged 26-59 years) subjects. The mean TmAA for men was 1.54 +/- 0.

Dietary fish oil-induced changes in the distribution of alpha-tocopherol, retinol, and beta-carotene in plasma, red blood cells, and platelets: modulation by vitamin E.

Healthy men (ages 24-57 y) were fed a controlled basal diet supplemented with 15 g/d of placebo oil (PO) for 10 wk followed by 15 g/d of fish-oil concentrate (FO) (fortified with 15 mg all-rac-tocopherol) for 10 wk without additional alpha-tocopherol and the last 8 wk with 200 mg alpha-tocopherol/d (FO+E). Compared with PO, FO raised plasma malondialdehyde; lowered alpha-tocopherol in plasma, red blood cells, and platelets; and raised plasma and platelet beta-carotene. Supplementation with additional alpha-tocopherol (FO+E) not only restored tocopherol concentrations but also reversed the rise in beta-carotene.

Uptake and bioconversion of alpha-tocopheryl acetate to alpha-tocopherol in skin of hairless mice.

The photoprotective effect of topically applied alpha-tocopheryl acetate (vitamin E acetate), a stable derivative of alpha-tocopherol (vitamin E), and its possible bioconversion to the active antioxidant species (alpha-tocopherol) was examined in skin tissue of female hairless mice (HRS/J) exposed to UV-B irradiation. Our results indicate that topically applied alpha-tocopheryl acetate is absorbed into and retained by skin tissue. Furthermore, skin tissue from UV-B-irradiated animals that received daily topical alpha-tocopheryl acetate treatments contained significantly higher levels (P < 0.

Correlation between the disintegration time and the bioavailability of vitamin C tablets.

The goal of this study was to examine if the current USP disintegration standard for vitamin C tablets (max. 30 min in water at 37 degrees C with disks) is adequate or if a tighter disintegration standard (e.g.

Relationship between serum lipid peroxidation products in hypercholesterolemic subjects and vitamin E status.

The relationship of serum lipid peroxidation products in hypercholesterolemic subjects to their vitamin E intake was examined in 15 such subjects with no other associated significant disease process in a 3 month trial with vitamin E supplementation. These patients with elevated serum cholesterol levels also have elevated thiobarbituric acid reactive substances (TBARS) and lipid oxidation products (LOPS). Vitamin E supplementation of 800 IU daily normalized the lipid peroxidation products but did not significantly change serum lipids.

Effects of ascorbic acid and pyridoxine supplementation on oxalate metabolism in peritoneal dialysis patients.

We studied the effect of vitamin C and B6 supplementation on oxalate metabolism in seven patients receiving chronic peritoneal dialysis therapy. The study was divided into three phases, each lasting 4 weeks. Plasma oxalate, total ascorbic acid, and pyridoxal-5'-phosphate (PLP) were measured at the end of each phase.

Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA).

To test whether alpha-tocopherol prevents restenosis following percutaneous transluminal coronary angioplasty (PTCA), we enrolled patients in a double-blind, placebo-controlled trial. Patients were randomized after successful PTCA to receive vitamin E in the form of dl-alpha-tocopherol, 1200 IU/day, orally vs an inactive placebo for 4 months. Patients' blood was analyzed at baseline and at 4 months post-PTCA for differences in plasma lipids, lipoproteins, apolipoproteins, alpha-tocopherol, retinol, beta-carotene and lipoperoxide concentrations.

Increased vitamin E intake restores fish-oil-induced suppressed blastogenesis of mitogen-stimulated T lymphocytes.

We sought to determine whether fish-oil supplementation would suppress blastogenesis in vitro of concanavalin A (ConA)-stimulated peripheral blood mononuclear cells (PBMCs) and, if so, whether it could be reversed with increased intake of vitamin E. Healthy males ate a controlled basal diet providing a total of 40% of energy from fat when fed in conjunction with 15 g/d of either placebo oil (PO) or fish-oil concentrate (FOC) fortified with 15 mg alpha-tocopherol/d for three periods. The subjects were supplemented with PO for 10 wk (PO), with FOC for 10 wk (FOC), and with FOC plus an additional 200 mg alpha-tocopherol/d for 8 wk (FOC+E).