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1. Single comb White Leghorn hens of an inbred line highly susceptible to fatty liver haemorrhagic syndrome (FLHS) were fed supplemented dietary ascorbic acid (200 mg/kg), alpha-tocopherol (75 mg/kg), or L-cysteine (3 g/kg, and 6 g/kg) for 28 d in order to evaluate the potential therapeutic effect of these compounds against the disease. 2. Supplementation of ascorbic acid, alpha-tocopherol, or a low level of L-cysteine (3 g/kg) did not significantly affect any of the hepatic variables evaluated. Hepatic glutathione was not increased by the supplementation of dietary L-cysteine. 3. L-cysteine supplemented at a level of 6 g/kg decreased hepatic dry matter and fat contents without affecting the hepatic malondialdehyde or the liver haemorrhagic score. 4. Because one of the predisposing factors of FLHS is a high hepatic fat content it was concluded that dietary supplementation of L-cysteine (6 g/kg) may be useful in the prevention of the disease.
The aim of this study was to evaluate the therapeutic efficacy of commonly used acaricidal drugs in India and also to assess the effect of ascorbic acid (AA) as adjunct therapy in 72 growing sheep with sarcoptic mange, aged 5-6 months and weighing 20.4-31.7 kg. Eight replicates of nine animals were formed based on sex, and day 0 body weight. Another set of 12 healthy sheep (5-6 months old) constituted the healthy control group. Drugs were applied locally on the affected parts daily and recovery changes in skin lesions were observed at the time of every application. L-Ascorbic acid was administered intramuscularly. Skin scrapings were collected daily from each group and examined for the presence of mites. Blood samples from each group were collected and analysed for total erythrocytes, leucocytes, haematocrit, haemoglobin and lymphocytes on 0, 14th and 28th day post-treatment (PT). Cell-mediated (CMI) and humoral immune (HI) responses were assessed on 0 and 28 days PT. Within groups treated with the drug alone, recovery in oil of Jatropha curcas group was faster and lesions were free from mites after the eighth application. For each drug, the recovery was faster with AA as an adjunct therapy when compared with the group treated with the drug alone. Within all groups, recovery in oil of J. curcas plus ascorbic acid (OJC-AA) group was fastest and the lesions were mite-free after three applications. The overall mean values were higher for all haematological parameters in OJC-AA group. Recovery with respect to suppressed CMI and HI responses during infection was also faster in this group. Gross and microscopic pathological studies revealed a marked adverse effect of infection on skin, kidney, spleen and liver. The OJC-AA group indicated faster recovery. It is concluded from this study that oil of J. curcas was found more efficacious in controlling sarcoptic mange in sheep and AA might be beneficial as adjunct in case of sarcoptic mange to get quick recovery with lesser applications of main therapy. However, the pharmacology of AA with reference to health of skin needs to be investigated.
The aim of this study was to evaluate the therapeutic efficacy of commonly used acaricidal drugs in India and also to assess the effect of ascorbic acid as adjunct therapy in 72 growing sheep with sarcoptic mange, aged 5-6 months and weighing 20.4-31.7 kg. Eight replicates of nine animals were formed based on sex, and day 0 body weight. Drugs were applied locally on the affected parts daily and recovery changes in skin lesions were observed at the time of every application. L-ascorbic acid was administered intramuscularly. Skin scrapings were collected daily from each group and examined for the presence of mites. Body weights were measured every 10th day from day 0 to 60. Nutrient digestiblity was evaluated by studying digestibility coefficients for dry matter, crude protein, ether extract, crude fibre, nitrogen free extract, total carbohydrates and nutrient balance (nitrogen, calcium and phosphorus) for a 30-day period. The liver function was evaluated by bromosulphophthalein (BSP) dye retention time. The animals were shorn on day 60 post-treatment (PT). Meat quality assesment was carried out by killing sheep at 60 days PT and estimating pH, water-holding capacity (WHC), tenderness, muscle colour, rib eye area and fat thickness. The lambs treated with oil of Jatropha curcas ascorbic acid had significantly (P < 0.05) greater mean daily body weight gains (63.29 g) than the infected untreated control (41.10 g). This was also higher than the mean daily weight gain in other treated groups. Infected untreated sheep showed significantly (P < 0.01) reduced digestibility coefficients for dry matter, crude protein, crude fibre, ether extract and total carbohydrate, but no significant differences for nitrogen-free extract. Treated sheep had significantly higher positive nitrogen, calcium and phosphorus balances compared with infested untreated sheep. Oil of J. curcas plus ascorbic acid (OJC-AA) treated group was better over all other treated groups with respect to nutrient digestibility. The BSP test revealed significant (P < 0.05) increase in BSP retention time in sheep with sarcoptic mange. Post -treatment, the BSP retention time decreased in all treated groups and the decrease was maximum in OJC-AA treated group. The carcasses of sheep treated with OJC-AA had significantly (P < 0.01) higher water holding capacity, rib eye area and back fat thickness than the untreated infected control group. The muscle pH and tenderness values were significantly lower in OJC-AA treated group post-slaughter than infested untreated control group. Muscle colour of OJC-AA treated group was maximum bright red. The lambs treated with OJC-AA had significantly (P < 0.05) greater clean fleece weight and fleece yield than the untreated infected group. It is concluded that OJC was the better therapy for sarcoptic mange of sheep and ascorbic acid as adjunct therapy is advisable. OJC-AA therapy may be better from the point of view of improving two most important production parameters in sheep, that is, wool yield and meat production.
The efficacy of a water-soluble bioflavonoid-ascorbic acid complex was evaluated in the treatment of fifty episodes of recurrent herpes labialis. Twenty episodes were treated with a complex of 600 mg. of water-soluble bioflavonoids and 600 mg. of ascorbic acid, administered in equal increments three times daily. Twenty episodes were treated with a complex of 1,000 mg. of water-soluble bioflavonoids and 1,000 mg. of ascorbic acid, administered in equal increments five times daily. Ten episodes were treated with a lactose placebo. The therapeutic regimen was maintained for 3 days after the recognition of the initial symptoms associated with recurrent herpes labialis. The water-soluble bioflavonoid-ascorbic acid complex was observed to reduce vesiculation and to prevent the disruption of the vesicular membrane. The therapeutic measure was found to be most effective when initiated during the prodomal stage of the disease process. Optimum remission of symptoms was observed in 4.2 +/- 1.7 days with the 600 mg. dosage of the water-soluble bioflavonoid-ascorbic acid complex. No adverse reactions were reported by any of the patients who participated in this investigation.
AIMS: The purpose of the present study was to investigate functional responses and nitric oxide synthase activity in the corpus cavernosum of young control, middle-aged control and middle-aged non-insulin dependent diabetic rats. METHODS: The animal groups were treated with ascorbic acid. RESULTS: Acetylcholine-mediated endothelium-dependent relaxation of cavernosal tissue was significantly attenuated from a maximum of 58.0 +/- 4.1% (1 mmol, n = 10) in young rats to 44.3 +/- 1.6% in aged-matched controls (P < 0.05) and to 23.3 +/- 2.8% in non-insulin-dependent diabetes mellitus rats (P < 0.01). These deficits in acetylcholine responsiveness were completely prevented by ascorbic acid treatment. Non-adrenergic non-cholinergic relaxations evoked by electrical field stimulation (0.5-64.0 Hz) in the corpus cavernosum of middle-aged control and non-insulin dependent (NID) diabetic rats are blunted and were not restored by ascorbic acid. The histochemical findings demonstrated a decrease of nicotinamide adenine dinucleotide phosphate-diaphorase staining in the cavernosal tissue obtained from middle-aged control rats and middle-aged diabetic rats. CONCLUSION: Partial correction by ascorbic acid may suggest the importance of reactive oxygen species and a therapeutic approach in impotent NID diabetic men.
A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.
Efforts are made to find therapeutic agents capable of minimizing genotoxicity of various natural and man-made compounds. The genotoxicity induced by mercury compounds remains controversial. Therefore we have investigated the genotoxic effect of mercuric chloride (MC; HgCl(2)) at three concentrations (1.052, 5.262 and 10.524 microM) and role of L-ascorbic acid (vitamin C) at a concentration of 9.734 microM on MC-treated short-term human leucocyte cultures. We assessed the proliferative rate index (PRI), sister chromatid exchange (SCE) and chromosomal aberrations (CAS) in control and MC-treated cultures with and without vitamin C supplementation. The results showed that MC has no effect on cell-cycle kinetics, but the frequency of SCE/cell was significantly higher in a dose-dependent manner than control values. HgCl(2) also significantly induced C-anaphases (abnormal mitosis) in blood cultures. These effects were prevented by the addition of vitamin C to MC-treated cultures. The data indicate the mutagenic activity of MC and the protective role of vitamin C on mercury-induced genotoxicity in human blood cultures is probably due to its strong antioxidant and nucleophilic nature.
The present experiment determined the effects of glutathione and ascorbic acid, the two most important hydrophilic antioxidants, on myocardial ischemia-reperfusion injury and evaluated their relative therapeutic values. Isolated rat hearts were subjected to ischemia (30 min) and reperfusion (120 min) and treated with ascorbic acid, glutathione monoethyl ester (GSHme), or their combination at the onset of reperfusion. Administration of 1 mM GSHme alone, but not 1 mM ascorbic acid alone, significantly attenuated postischemic injury (P < 0.05 versus vehicle). Most interestingly, coadministration of ascorbic acid with GSHme markedly enhanced the protective effects of GSHme (P < 0.01 versus vehicle). The protection exerted by the combination of GSHme and ascorbic acid at 1 mM each was significantly greater than that observed with 1 mM GSHme alone (P < 0.05). Moreover, treatment with GSHme alone or GSHme plus ascorbic acid markedly reduced myocardial nitrotyrosine levels, suggesting that these treatments attenuated myocardial peroxynitrite formation. These results demonstrated that 1) GSHme, but not ascorbic acid, exerted protective effects against ischemia-reperfusion injury; and 2) the protective effects of GSHme were further enhanced by coadministration with ascorbic acid, suggesting a synergistic effect between GSHme and ascorbic acid.
Several factors contribute to increased vascular permeability in diabetes mellitus, namely hyperglycaemia leading to increased production of diacylglycerol and thence protein kinase C, non-enzymatic glucosylation generating free radicals and lipid peroxides, sorbitol formation, loss of endothelial cell surface heparan sulphates, and the action of arachidonate derivatives that affect endothelial cell contractility. In view of the importance of oxidative damage, serious consideration must be given to therapeutic regimens that utilise vitamin E or ascorbic acid or D-myoinositol. Probucol is an available antioxidant whose properties have received insufficient attention. The oleate of monounsaturated oil diets is likewise anti-oxidant. Furthermore there is a possibility of replacing lost surface heparan sulphates.
OBJECTIVE: To report four cases of myositis ossificans progressiva, its form of presentation, in addition to new control and treatment options. DESCRIPTION: The authors describe four cases of myositis ossificans progressiva, presenting its clinical manifestations, evolution, and available forms of control and treatment. The main congenital anomalies associated with myosistis ossificans progressiva are described, namely: hallux valgus, clinodactyly, short thumbs, exostosis, and syndactyly. The evolution and therapeutic responses of clinical improvement to oral ascorbic acid and biphosphonate in patients 1 and 4 are also described; patient 1 had a better response after receiving intravenous biphosphonate, while patients 2 and 3 showed clinical improvement after the administration of oral ascorbic acid. COMMENTS: Ascorbic acid relieves the pain and improves psychism in patients with myositis ossificans progressiva. Intravenous biphosphonate is an alternative to patients with significant worsening of the disease, especially those with ambulatory restrictions. The orientation towards avoiding recurrent trauma in myositis ossificans progressiva patients is important.
From experience in six cases the anabolic steroid hormones, especially long-acting testosterone and estrogen preparations, are the treatment of choice in Paget's disease, as in postmenopausal osteoporosis. Details of the management of three patients over a period of four years are presented. Roughly 4 per cent of the population, mostly persons over 40, show some evidence of Paget's disease. Only a small number of them, however, have severe manifestations requiring treatment, such as pain, howing or fracture of the bones, pressure on nerves or heart failure. In rare cases malignant changes occur in the involved bone. Since the cause of Paget's disease is not known, treatment in the past has been largely empirical. Reifenstein and Albright had advocated the therapeutic use of calcium, vitamin D and ascorbic acid, and, in postmenopausal women, administration of estrogens; but with fractures or immobilization, intake of calcium-containing foods, such as milk, must be restricted to avoid dangerous piling up of calcium and kidney stones, and fluids must be forced. In recent years anabolic steroid hormones, principally oral androgens and estrogens, have been employed by Gordan and others to promote bone repair, lessen bone pain and decrease urinary excretion of calcium. While these hormones probably do not arrest the disease, they seem to stabilize it and bring relief of symptoms. More recently, Albright and Henneman demonstrated that very large doses of corticotropin (ACTH) or cortisone resulted in immediate cessation of bone pain, decrease in urinary excretion of calcium and histologic evidence of regression of the disease process. The large doses required, however, also produce dangerous side effects, such as psychosis and osteoporosis, indicating that such treatment probably should not be continued over long periods.
Reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, .OH, OX-) which are produced by stimulated alveolar macrophages (AM), neutrophils and eosinophils, play an important role in the pathogenesis of many acute and chronic lung diseases. With regard to a therapeutic application the influence of the antioxidants ascorbic acid (Vitamin C) and alpha-tocopheryl acetate (Vitamin E acetate) on the production of ROM by AM was investigated. The AM were isolated by bronchoalveolar lavage from patients with different lung disorders. The ROM were determined by means of chemiluminescence-measuring. alpha-Tocopheryl acetate solved in peanut oil causes a little increase of the yeast cell wall-induced chemiluminescence. Pure alpha-Tocopheryl acetate has no effect on the chemiluminescence. In contrast to alpha-Tocopheryl acetate the addition Vitamin C to the stimulated AM results in a strong diminution of the chemiluminescence signal. This result suggests that Vitamin C reduces the generation of ROM by AM. Therefore Vitamin C could be a suitable scavenger of radicals and oxidants in different lung diseases.
A fast and high yielding method of 188Re radiolabelling DD-3B6/22 Fab' is described. An inert atmosphere [N2(g)] and ascorbic acid was essential for preparation and storage of therapeutic levels (< or =2 GBq/mg) for up to 24 h. Immunoreactivity was greater than 75%. Pharmacokinetic studies in nu/nu mice demonstrated localisation of 188Re DD-3B6/22 Fab' was equivalent and correlated well with the behaviour observed for 99mTc DD-3B6/22 Fab' used to image ovarian cancer. Excellent stability at the target site in vivo supports the potential use of 188Re DD-3B6/22 Fab' in the therapy of ovarian cancer.
Ascorbic acid in a dose proportional to the human therapeutic dose (500 mg/day), when administered to Swiss albino mice along with a dietary concentration of aflatoxin B1, decreases the incidence of toxin-induced chromosomal abnormalities in the bone marrow cells. Treatment with the toxin alone (6 and 12 weeks) did not produce any differences in clastogenicity. The vitamins, when administered along with the toxin for 6 weeks, seemed to nullify more of the structural changes than of the mitotic disruptions. In 12-week treatment, more structural and fewer disruption-type abnormalities were found.
When 2 clinical strains of plasmid-mediated penicillin-resistant Staphylococcus aureus were treated with 1 mM sodium ascorbate for 6 h, 12-35% colony-forming units (CFU) irreversibly lost their ability to produce beta-lactamase. Agarose gel electrophoresis showed the disappearance of the plasmid bands from the lysates of colonies in which susceptibility to penicillin was induced by ascorbate treatment. Since ascorbic acid is a compound that is completely non-toxic, the possibility of its therapeutic use in the treatment of multiresistant bacterial diseases is proposed.
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