ascorbic-acid and Sclerosis

Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts.. In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validated by real-time PCR, western blotting and functional assays.. We found significant changes in the expression levels of almost 600 genes between collagen VI deficient and control fibroblasts. Highly regulated genes included extracellular matrix components and surface receptors, including integrins, indicating a shift in the interaction between the cell and its environment. This was accompanied by a significant increase in fibroblasts adhesion to laminin. The observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases.

Topics: Ascorbic Acid; Cell Adhesion; Down-Regulation; Extracellular Matrix; Fibroblasts; Gene Expression Profiling; Gene Regulatory Networks; Humans; Integrin alpha3; MicroRNAs; Muscular Dystrophies; Sclerosis; Signal Transduction; Up-Regulation; Wound Healing

Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney.. Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n=8) and a vitamin C-treated group (n=8). Long-Evans Tokushima Otsuka rats (n=8) were used as a control.. Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats.. By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy.

Topics: Albuminuria; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Kidney; Male; Oxidative Stress; Rats; Rats, Inbred OLETF; Sclerosis

Myringosclerosis, a common finding after myringotomy, has been recently associated with an increased production of oxygen free radicals. Ascorbic acid's proposed actions include collagen synthesis, antioxidation, and free radical scavenging. The effects of topical ascorbic acid on healing tympanic membranes were studied. Particular attention was given to detecting the presence of myringosclerosis. Twelve Sprague-Dawley rats were bilaterally myringotomized. Their ears were randomized into group A, which received topical ascorbic acid in Gelfoam, group B, which received topical saline solution in Gelfoam, and group C, which received no treatment. The tympanic membranes were harvested on day 13, after routine otomicroscopy. Under light microscopy, the connective tissue layer of the untouched side of the pars tensa was distinctly thicker in group A than in group B or group C. At this level, the extent of sclerotic lesions was significantly less in the ascorbic acid-treated group. It is inferred that topical ascorbic acid reduces the occurrence of myringosclerosis following tympanic membrane perforations in the rat.

Topics: Administration, Topical; Animals; Ascorbic Acid; Free Radical Scavengers; Male; Middle Ear Ventilation; Rats; Rats, Sprague-Dawley; Sclerosis; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

The authors' study show that intravenous He-Ne laser therapy (HNLT) in patients with stable angina of effort (functional class II-III) and postinfarction cardiosclerosis irrespective of ejection fraction increased plasma katalase and red cell vitamin A concentrations. HNLT aroused vitamin E concentration in red cells in anginal patients with intact ejection fraction whereas in those with reduced ejection fraction it elevated blood peroxidase, plasma vitamin A and E concentrations. For patients with postinfarction cardiosclerosis there were, respectively, higher levels of blood peroxidase, plasmic vitamin A, red cell vitamin E, plasmic SH-groups and blood peroxidase, plasmic vitamins A and E.

Topics: Adult; Angina Pectoris; Angioplasty, Balloon, Laser-Assisted; Ascorbic Acid; Catalase; Ceruloplasmin; Female; Helium; Humans; Isotopes; Male; Middle Aged; Myocardial Infarction; Myocardium; Neon; Physical Exertion; Sclerosis; Vitamin A; Vitamin E

Topics: Animals; Ascorbic Acid; Carbon Isotopes; Collagen; Fibroblasts; Granulation Tissue; Guinea Pigs; Hydroxyproline; Iron; Models, Biological; Oxygen; Partial Pressure; Proline; Rats; Sclerosis; Skin; Tritium

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Cholestanes; Cholesterol; Cortisone; Heart Diseases; Rats; Sclerosis; Vitamin D; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Multiple Sclerosis; Sclerosis