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Vitamin C and acute respiratory infections.

So far over 60 studies have examined the effects of vitamin C on the common cold. No effect on common cold incidence was observed in the six largest studies, indicating that vitamin C has no preventive effects in normally nourished subjects in the Western countries. There are, however, smaller studies reporting benefit. In three trials of subjects under heavy acute physical stress, common cold incidence decreased by on average 50%, and in four trials of British males common cold incidence decreased by on average 30% in the vitamin C groups. The dietary vitamin C intake in the UK is low, and consequently the benefit may be due to the correction of marginal deficiency, rather than high vitamin doses. Regular vitamin C supplementation (> or =1 g/day) has quite consistently reduced the duration of colds, but the size of the benefit has varied greatly. In the four largest studies the duration of colds was reduced only by 5%. In two of these studies, however, absence from school and work was reduced by 14-21% per episode, which may have practical importance. Three controlled studies recorded a reduction of at least 80% in the incidence of pneumonia in the vitamin C group, and one randomised trial reported substantial treatment benefit from vitamin C in elderly UK patients hospitalized with pneumonia or bronchitis. It seems that the preventive effects of supplementation are mainly limited to subjects with low dietary vitamin C intake, but therapeutic effects may occur in wider population groups. Further carefully designed trials are needed to explore the effects of vitamin C.

Ascorbic Acid↗

Effects of topical 10% ascorbate solution on established corneal ulcers after severe alkali burns.

When established corneal ulcers induced by alkali burning were treated with 10% ascorbate drops, no perforation occurred, in contrast to a 25% incidence in the control group. If perforations and descemetoceles were grouped together, these difference became insignificant (i.e., 14.2% ascorbate-treated vs. 25% control). Prolongation of descemetocele presence without perforation in the ascorbate-treated group indicated some therapeutic effect. We conclude that topical ascorbate does not substantially alter the outcome of established corneal ulcers.

Administration, Topical↗

Keeping central venous lines open: a prospective comparison of heparin, vitamin C and sodium chloride sealing solutions in medical patients.

OBJECTIVE: To prevent catheter occlusion, intermittently used central venous catheters are frequently sealed with vitamin C solution or heparin solution between use. The present study was designed to test the effectiveness of this approach and to compare the efficiency of sealing solutions. DESIGN AND SETTING: Prospective randomized study performed on a 9-bed medical ICU and on medical wards of an academic tertiary care center. PARTICIPANTS. Ninety-nine central venous line placements were prospectively included in the study and randomized into three treatment groups: sodium chloride 0.9%, vitamin C (200 mg/ml) and heparin (5000 IU/ml) sealing solutions. INTERVENTIONS AND MEASUREMENTS: Catheters were filled with the respective sealing solution and patency was tested once every 2 days using a standardized routine. Catheter patency was compared among the three groups using Kaplan-Meier statistics and log-rank testing. RESULTS: There was a significant difference in catheter patency between the three groups (p<0.03, log-rank test). A comparison of catheter survival between the catheters filled with heparin and those filled with sodium chloride, but not between those filled with vitamin C solution and with sodium chloride solution, exhibited significant differences in catheter patency (p<0.04, log-rank test). CONCLUSIONS: Local anticoagulation of intermittently used central venous catheters prolongs catheter patency. High-dose (5000 IU/ml) heparin solution is a useful anticoagulant for this purpose, while vitamin C solution does not prolong catheter patency.

Academic Medical Centers↗

[35S]cysteamine: facile synthesis, in vivo biokinetics, and subcellular distribution.

Whereas chemical radioprotection against external beams of ionizing radiation is well studied in radiobiology, the aspects relating to tissue incorporated radionuclides have received little attention. The increased use of radionuclides in diagnostic and therapeutic nuclear medicine, as well as the presence of both manmade and natural radioactivity in the environment, indeed call for such investigations. Our ongoing work on a variety of radioprotectors has revealed that cysteamine (MEA), S-2-aminoethylisothio uroniumbromide hydrobromide (AET), and others (e.g. ascorbic acid), protect spermatogonial cells in mouse testis from the effects of chronic irradiation with intratesticularly localized radionuclides. In these experiments, dose modification factors ranging from 2 to 4 and 10 to 14 were obtained using spermhead survival and induction of spermhead abnormalities, respectively, as the biological end points. Similar experiments were carried out by changing the mode of administration of cysteamine to oral intubation. In these studies a dose modification factor of approximately 3 was observed in the spermhead survival assay. In an effort to understand the protection offered by MEA, the present work describes a one-pot synthesis of high specific activity [35S]cysteamine from elemental [35S]sulphur and its use in determining the biokinetics and biodistribution of MEA following intratesticular (i.t.) or oral administration in mice.

Administration, Oral↗

Effects of antioxidants on coronary microvascular spasm induced by epicardial coronary artery endothelial injury in pigs.

OBJECTIVES: The effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury. METHODS: Balloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n = 12) and in pigs treated with oral ASC (3 g/day) (ASC group, n = 12) and ASC (3 g/day) plus GSH (1 g/day) (ASC + GSH group, n = 12). RESULTS: In the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18 +/- 17% to a decrease of 100% (that is, zero flow, 8 weeks, P < 0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC + GSH group, blood flow response to ACh was altered to a decrease of 45 +/- 17% (8 weeks, P < 0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4 +/- 12.5 signal intensities, P < 0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56 +/- 17%, P < 0.01 compared with the endothelial injury group). CONCLUSIONS: Chronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.

6-Ketoprostaglandin F1 alpha↗

LDL oxidation: therapeutic perspectives.

The peroxidation step of lipid transormation is considered to be essential in the pathogenesis of atherosclerosis. Although data concerning the mechanisms by which lipid peroxidation occurs in vivo are scarce, several lines of evidence suggest that some endogenous and exogenous compounds with antioxidant activity could have some beneficial effects in the prevention of atherosclerosis. Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) act as the most important hydrophilic and lipophilic antioxidants, respectively in vivo. Accordingly, animal and human studies suggest that these compounds may have some preventive effect against the development of clinical coronary heart disease. Many plant phenols and flavonoids may be important dietary antioxidants and it has been speculated that these compounds in red wine or in the Mediterranean diet could explain the 'French paradox'. Several studies show that antioxidants such as probucol and butylated hydroxytoluene can inhibit development of atherosclerotic lesions in Watanabe and cholesterol-fed rabbits. Some drugs such as beta-blockers, calcium antagonists, hypolipodemic drugs,...appear to have at least in vitro antioxidant effects but the clinical relevance of these properties remains unkonwn. Moreover, some interventions aimed to decrease the LDL-oxidative susceptibility have not been shown to attenuate atherogenesis when cholesterol levels remain markedly elevated.

Animals↗

Ascorbic acid: useful as a buffer agent and radiolytic stabilizer for metalloradiopharmaceuticals.

The goal of this study is to explore the use of ascorbic acid (AA) as a buffer agent and a radiolytic stabilizer for preparation and stabilization of radiolabeled DOTA-biomolecule conjugates. Results from a titration experiment show that 0.1 M AA solution has sufficient buffer capacity at pH 5.0 while 0.5 M AA solution is useful even at pH 6.0. The radiolabeling experiment using TA138, a DOTA-conjugated nonpeptide integrin alpha(v)beta(3) receptor antagonist, clearly demonstrates that AA is a good buffer agent for pH control and an excellent antioxidant for stabilization of metal-labeled diagnostic ((111)In) and therapeutic ((90)Y and (177)Lu) radiopharmaceuticals if the radiolabeling is performed at pH 5-6. There is no need for the additional stabilizer (e.g., gentisic acid) and buffer agent such as ammonium acetate. The anaerobic AA formulation described in this study is particularly useful for radiolabeling of small biomolecules, which are sensitive to the radiolytic degradation during radiolabeling.

Ascorbic Acid↗

Polymorphonuclear leukocyte-mediated cell and tissue injury: oxygen metabolites and their relations to human disease.

Reactive oxygen metabolic products derived from an activated NADPH oxidase present in the cell membrane of PMNs and mononuclear phagocytic cells play a critical role in the host's defense against bacterial infection. Recent studies have also demonstrated the ability of these toxic products to initiate eukaryotic cell injury and promote the development of the acute inflammatory responses. Experimental studies suggest that neutrophil-derived oxygen metabolites contribute to the development of the tissue injury associated with a variety of disease states, including emphysema, myocardial infarction, adult respiratory distress syndrome, immune complex-mediated vasculitis, and rheumatoid arthritis. Future studies to define further the mechanisms by which reactive oxygen-derived metabolic products mediate tissue injury will provide insight into the development of new therapeutic strategies for the modulation of disease states that are mediated by the recruitment and activation of PMNs.

Animals↗

Arsenic trioxide: a new immunomodulatory agent in the management of multiple myeloma.

Arsenic has been used as a medicinal for thousands of years. Several reports from China relative to its use mainly in acute promyelocytic leukemia, especially from the Shanghai group, has caused a resurgence in the investigation of the drug in the management of malignancies with focus on malignancies of hematologic origin. Arsenic is eliminated by many routes (urine, feces, sweat, milk, hair, skin, and lungs), although most is ultimately excreted in urine. Multiple myeloma is characterized by the clonal proliferation of malignant plasma cells in the bone marrow associated with bone loss, renal disease, and immunodeficiency. Preclinical evidence suggests an immunologic mechanism behind the therapeutic effects of As2O3 on myeloma cells. This appears to be achieved by a marked increase in lymphokine-activated killers mediated killing and up-modulation of CD38 and Cd54, two molecules involved in cell-cell interactions. Moreover, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoproliferative disorders. Preliminary clinical data in relapsed/refractory multiple myeloma suggest that As2O3 does have a role in the management of multiple myeloma; however, preclinical data show that the addition of ascorbic acid, and using As2O3 in combination with other active chemotherapeutic agents will enhance its role in managing the disease, and this is probably the position the drug will occupy in the armamentarium against myeloma.

Antineoplastic Agents↗

[Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease patients].

The therapeutic effectiveness of the pantothenic acid drugs: calciipantothenas and pantethine, was studied in 182 patients with coronary heart disease and stable angina of effort. It is shown that both the drugs produce favourable effects on certain parameters of hemodynamics, on the metabolism of lipids, riboflavin and ascorbic acid. It is recommended that the administration of calciipantothenas in a dose of 300 mg/day, during 3 weeks, be included into the combined treatment of coronary patients with no manifest disorders of lipid metabolism. Patients with manifest hyperlipidemia should be administered pantethine in a dose of 500 mg/day.

Adult↗

Toxicity, radiation sensitivity modification, and combined drug effects of ascorbic acid with misonidazole in vivo on FSaII murine fibrosarcomas.

Ascorbic acid (ASC) has been shown to radioprotect nonmalignant tissue and to enhance the effects of misonidazole (MISO) on hypoxic cells in vitro. Since ASC is minimally toxic, it is an interesting candidate for improving the radiotherapeutic gain factor in vivo. The in vivo radiomodifying effects of ASC on a C3H/fSed murine fibrosarcoma (FSaII), on normal skin, and on bone marrow were determined with the use of the tumor growth delay and TCD50 (i.e., radiation dose required to control 50% of treated tumors for a minimum of 120 days) assays and the RD50 (i.e., dose required to cause a peak skin reaction of 2 in 50% of treated hind limbs) and LD50 (i.e., whole-body radiation lethal dose) assays, respectively. ASC was buffered to pH 7.35 and delivered ip at a dose of 4.5 mg g-1 body weight. ASC did not modify tumor growth delay induced by radiation or the TCD50 [87.1 Gy (control) vs. 85.6 Gy (ASC)]. Normal tissues, however, were radioprotected by ASC. RD50 values for 2+ acute skin reactions were 46.4 and 55.7 Gy for control and ASC-treated subjects, respectively; LD50 (30 days) values were 7.2 and 8.5 Gy. The enhancement ratios for skin and bone marrow were 1.20 and 1.18, and 95% confidence limits were (1.07 ... 1.34) and (1.14 ... 1.23), respectively. The therapeutic gain factor was 1.22 calculated as the ratio of the TCD50 and the reference normal tissue (RD50 or LD50). When ASC and MISO were combined, ASC reduced the in vivo radiosensitizing effects of MISO.

Animals↗

SB 211475, a metabolite of carvedilol, a novel antihypertensive agent, is a potent antioxidant.

The antioxidant effects of SB 211475, a metabolite of carvedilol, a novel antihypertensive agent, were studied and compared with carvedilol and other antioxidants such as U78517F, U74500A and probucol. SB 211475 inhibited Fe(2+)-vitamin C-initiated lipid peroxidation, assessed as thiobarbituric acid reactive substance, in brain-homogenate with an IC50 of 0.28 microM. Under the same conditions, the IC50s of probucol, carvedilol, U74500A and U78517F were 50, 8.1, 0.71 and 0.16 microM, respectively. SB 211475 inhibited oxidation of human low density lipoprotein by mouse macrophages with an IC50 of 0.043 microM. In the same model, the IC50s of carvedilol, U78517F and probucol were 3.8, 0.15, and 0.80 microM, respectively. SB 211475 protected cultured bovine pulmonary artery endothelial cells against hydroxyl radical-initiated lipid peroxidation (IC50 = 0.15 microM) and cell damage (lactate dehydrogenase release, IC50 = 0.16 microM), and promoted cell survival with an EC50 of 0.13 microM. SB 211475 also protected endothelial cells against xanthine/xanthine oxidase-initiated cytotoxicity and protected rat cerebellar neurons from hydroxyl radical-mediated cell death (EC50 = 0.19 microM). Moreover, SB 211475 inhibited superoxide (O2-) release from human neutrophils stimulated by phorbol myristate acetate. These observations indicate that SB 211475 is a potent antioxidant and may potentially contribute to the therapeutic effects of carvedilol in vivo.

Adenosine Diphosphate↗

Medical resistance to innovation.

A certain amount of resistance to new ideas is normal and functional in science providing the innovations have a means of being tested. A number of differences between medicine and pure science are noted which can result in some medical innovations being ignored or rejected without an adequate assessment. Historical and current instances of resistance to innovation are given. Social-organizational factors in medicine appear to favor the acceptance of theoretically glamorous, pharmaceutical, and high technology innovations over simpler and less profitable ones.

Ascorbic Acid↗

Relationship between antioxidant capacity and oxidative stress in children with acute hepatitis A.

AIM: To investigate in children with acute hepatitis A. According to our knowledge, there are no data about the blood levels of malondialdehyde (MDA, an indicator of oxidative stress) and nonenzymic antioxidants in children with acute hepatitis A. METHODS: Whole blood MDA and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10 females, 9 males) children with acute hepatitis A and in 29 (13 females, 16 males) healthy control subjects. RESULTS: There was a statistically significant difference between patients and controls for all parameters (P < 0.05). Lipid peroxidation marker MDA was significantly elevated (P < 0.001), while antioxidants beta-carotene, retinol and GSH were significantly decreased (all P < 0.001) in patients compared to healthy subjects. In addition, alpha-tocopherol and ascorbic acid levels were significantly lower in patients when compared to age and sex matched controls (P < 0.05, P < 0.01, respectively). CONCLUSION: Our study shows that hepatitis A virus induces oxidative stress in children with hepatitis A. This finding could be taken into consideration to improve the therapeutic approach in acute hepatitis A.

Antioxidants↗

Antioxidants in the treatment of patients with renal failure.

Renal failure is accompanied by oxidative stress, which is caused by enhanced production of reactive oxygen species and impaired antioxidant defense. The suggested therapeutical interventions aimed at reducing oxidative stress in chronic renal failure patients are as follows: 1) the use of biocompatible membranes, ultrapure dialysate, and removal of endogenous foci of infection; 2) haemolipodialysis, and electrolysed reduced water for dialysate preparation; 3) administration of antioxidants (alpha-tocopherol, ascorbic acid, N-acetylcysteine, reduced glutathione); 4) substances possibly affecting oxidative stress indirectly (erythropoietin, sodium selenite). As currently available data have, as yet, provided rather limited evidence for the clinical benefit of antioxidant interventions, at present it is untimely to give practical recommendations with regard to antioxidant treatment of patients with renal failure.

Antioxidants↗

[Hypertrophic cardiomyopathy caused by cytochrome-oxidase deficiency].

Mitochondrial cytopathies are due to genetic anomalies in the oxidative phosphorylation enzymes (excepting Krebs cycle, pyruvate and certain other mitochondrial enzymes). Recently discovered, these diseases have a characteristic heterogeneous clinical expression because of the ubiquitous nature of this intracellular organelle. We observed a case in a 16-year-old girl who had cytochrome C oxidase deficiency. The child was born to non-consanguinous parents and had a healthy brother. The first manifestation of the disease was a systolic murmur heard at the age of 4 years. Progressively, exertion dyspnoea, lipothymia with cyanose led to the first echocardiography at 8 years revealing non-obstructive cardiomyopathy. Functional inadaptation of cardiac performance worsened requiring various symptomatic treatments. At the age of 16, the symptomatology included lower limb fatigue and the diagnosis of a metabolic disease was entertained. Phosphorylase A and B activity and phosphokinase activity were normal. High lactic acid levels after exertion suggested a mitochondrial enzyme deficiency. The diagnosis of cytochrome C oxidase deficiency was confirmed by spectrophotometric and polarographic assay of mitochondria from a peripheral muscle biopsy. Treatment with riboflavin, ascorbic acid, factor P, menadione, carnitine and iron sulfate has currently provided some symptomatic improvement. In patients with unexplained cardiomyopathy, the diagnosis of mitochondrial cytopathy should be entertained if oxidoreduction potentials (lactate/pyruvate ratio) are perturbed. The diagnosis is confirmed by enzyme studies of fresh muscle mitochondria. Currently therapeutic prospects are at best very poor. Genetic counselling may be advisable.

Adolescent↗