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Opposite effects of vitamin C on migration and procoagulant activity of mononuclear leukocytes from malignant pleural effusion
Journal of Experimental and Clinical Cancer Research (Italy), 1996, 15/4 (375-380)
Cumulative evidence has shown fibrinolytic process to be a key event in breast cancer growth and invasion. In this work we examined in vitro vitamin C influence on mononuclear (MN) leukocytes random migration ability, as well as its procoagulant activity (PCA), as proposed opposing force in tumor progression. Malignant pleural effusion (PE) of breast cancer patients (n = 8) was used as source of MN leukocytes. PEMN cells (65-83% macrophages) exhibited basal PCA (10-245 mU/106 cells) which significantly increased during 4-44 hrs incubation period. Vitamin C (100, 500 microg/ml) significantly reduced PEMN cells motility while their PCA was simultaneously enhanced. Similar effects were obtained with LPS (5 microg/ml), a well-known stimulator of macrophage PCA. These results suggest that vitamin C beneficial effect on malignancies may be a consequence of both immobilization of MN leukocytes in loco and stimulation of coagulation pathway in their surroundings. These effects may prove useful in opposite harmful fibrinolytic activity in cancer tissues.
Inhibitory effect of vitamin C on the mutagenicity and covalent DNA binding of the electrophilic and carcinogenic metabolite, 6-sulfooxymethylbenzo(a)pyrene
CARCINOGENESIS (United Kingdom), 1994, 15/5 (917-920)
6-Sulfooxymethylbenzo(a)pyrene has recently been shown to be a strong hepatocarcinogen in infant male B6C3F1 mice and appears to be an ultimate carcinogenic metabolite of 6-hydroxymethylbenzo(a)pyrene and possibly of benzo(a)pyrene and 6-methylbenzo(a)pyrene. It produced high levels of aralkyl DNA adducts in the livers of B6C3F1 mice and also exhibited strong direct mutagenicity toward Salmonella typhimurium TA98 without metabolic activation. In the present study we found that ascorbic acid significantly reduced the bacterial mutagenicity and in vitro covalent DNA binding of 6-sulfooxymethylbenzo(a)pyrene. Ascorbic acid forms a mutagenically inactive covalent adduct with 6-sulfooxymethylbenzo(a)pyrene, which appears to account for its novel protective mechanism against this reactive sulfuric acid ester. It seems likely that the formation of this adduct involves aralkylation of an ascorbic acid anion by a presumed carbo cation derived from the electrophilic sulfuric acid ester.
Few aspects of bacterial colonies in the stomach during the treatment with acidoinhibitors
BOLL. CHIM. FARM. (Italy), 1992, 131/8 (302-303)
On this paper are stated the reasons why a prolonged gastric-acid inhibition causes bacterial and/or mycotic colonizations in the stomach. Instead, the surgical operations, that now became obsolete, are only casual occasions of intragastric colonizations. This paper ends with some rules to be followed in order to avoid risks connected to a pH increase, and with a short hint to two important vitamins (i.e. Vitamin C and Vitamin E) for the complementary treatment of ulcerous patients.
The prevention and management of pressure ulcers
Pressure ulcers are a common problem for older persons. Complications associated with pressure ulcers include infection and even death for some patients. Pressure is the primary pathogenic factor, but shearing forces, friction, and moisture are also important. Immobility, nutritional status, and age-related factors seem to be significant risk factors. Preventive care includes use of assessment tools to identify high risk patients, frequent repositioning, air or foam mattresses that reduce pressure over bony prominences, as well as careful attention to optimizing the overall patient condition. When pressure ulcers do develop, the treatment plan should include adequate nutrition including protein, vitamin C, and zinc supplements as indicated; systemic antibiotics for sepsis, cellulitis, osteomyelitis, or the prevention of bacterial endocarditis; and local wound care that eliminates necrotic tissue, decreases bacterial load, and provides a physiologic, pressure-free environment allowing the wound to heal. Specialized beds may be considered in some patients, particularly those with larger ulcers. Surgery is an option in older persons who are operative candidates. For some patients with pressure ulcers, appropriate treatment goals may focus on providing comfort rather than curing the ulcer.
The inhibition of bacterially mediated N-nitrosation by vitamin C: Relevance to the inhibition of endogenous N-nitrosation in the achlorhydric stomach
CARCINOGENESIS (United Kingdom), 1989, 10/2 (397-399)
It has been suggested that endogenously formed N-nitroso compounds are involved in the aetiology of gastric cancer. In the model of gastric carcinogenesis postulated by Correa, gastric atrophy is an important early stage in the progression to carcinoma which results in the loss of stomach acidity, and colonization of the stomach by bacteria. As a consequence of the metabolic activity of these bacteria intragastric nitrite (a precursor to N-nitroso compounds) and possibly carcinogenic N-nitroso compounds become elevated, which may hasten the progression to carcinoma. Vitamin C has been shown to be an effective inhibitor of acid-catalysed N-nitroso compound formation, in vivo and in vitro, and this has been attributed to its relatively rapid reaction with nitrite in contrast to the slower rates of reaction of nitrite with secondary amines. However, N-nitroso compound formation in the achlorhydric stomach must proceed by mechanisms which operate at neutral pH values. One potential mechanism involves the enzymatic catalysis of N-nitrosation by a subpopulation of the bacteria colonizing the achlorhydric stomach which catalyse these reactions and in particular denitrifying organisms. In this study, we examined the effect of vitamin C on the formation of N-nitrosomorpholine from morpholine and nitrite when mediated by cells of an actively N-nitrosating denitrifying bacterium (Pseudomonas aeruginosa, BM1030) at neutral pH. Despite the fact that vitamin C ordinarily shows little reactivity towards nitrite at neutral pH it did prove to be a potent inhibitor of bacterial N-nitrosamine formation. This study provides some justification for the use of vitamin C as an inhibitor of endogenous N-nitrosation regardless of gastric pH.
Activation of serum complement leads to inhibition of ascorbic acid transport (42530)
Ascorbic acid is transported into 3T6 fibroblasts by a carrier-mediated, energy-dependent saturable active process with a K(m) of 112 muM and V(max) of 158 pmole/min/mg protein. The transport is dependent on extracellular Nasup + concentration which reduces the K(m). It was recently observed in this laboratory that bovine serum contained a heat-labile factor which, after interaction with bacterial endotoxin (lipopolysaccharides), inhibited ascorbic acid transport (J.J. Alleo and H. Padh, Proc Soc Exp Biol Med 179:128-131, 1985). We report here that the inhibition of ascorbic acid transport by endotoxin is mediated by the activation of serum complement. This was done by examining the activation of complement by other activators like zymosan and immunocomplexes (e.g., albumin and antibodies to albumin). Ascorbate transport was inhibited by the mixture of unheated serum and the activators. No inhibition was observed with serum devoid of C3 (component 3 of the complement). When C3-deficient serum was reconstituted by the addition of purified C3, the endotoxin-induced inhibition of ascorbate transport was restored. The implication of these findings is that in spite of a normal intake and blood level of the vitamin, tissues may not be getting adequate vitamin C during disease states when the complement in serum is activated. In other words, what may be considered an adequate intake of vitamin C under health conditions may not be adequate under disease conditions.
Effects of vitamins A, C, and E on aflatoxin Bsub 1-induced mutagenesis in Salmonella typhimurium TA-98 and TA-100
The effects of retinoids (vitamin A analogs) and vitamins C and E on the aflatoxin Bsub 1-(AFBsub 1)-induced mutagenesis in Salmonella typhimurium TA-98 and TA-100 were investigated. The bioassay was performed under conditions that permitted the effects of vitamins on carcinogen metabolism to be assessed separately from effects on the expression of the mutated bacterial cell. Both retinoic acid and retinol inhibited (up to 50%) AFBsub 1-induced mutagenesis in S. typhimurium TA-98, but only retinol inhibited (up to 75%) mutagenesis in TA-100. Retinoic acid inhibition of mutagenesis in S. typhimurium TA-98 was pronounced over a wide concentration range (i.e., 2 x 10sup -sup 1sup 0 to 2 x 10sup -sup 8 M); however, at the higher concentrations (i.e., 2 x 10sup -sup 8 to 2 x 10sup -sup 6 M range) the predominant effect was the inhibition of the metabolism of AFBsub 1 to its mutagenic metabolites. Vitamin E was more potent in inhibiting the expression of AFBsub 1-induced mutagenesis than vitamin C. However, the major inhibitory effects of vitamin E were related to the metabolism of AFBsub 1, whereas vitamin C was inhibitory at both metabolic and the post-metabolic levels of the AFBsub 1 mutagenesis assay. The results of these investigations suggest that vitamins A, C, or E inhibit both AFBsub 1 metabolism to its mutagenic metabolites as well as the expression of AFBsub 1-induced mutated bacterial cells.
Cyclosporine A-induced oxidative stress in rat hepatocytes
Journal of Pharmacology and Experimental Therapeutics (USA), 1997, 280/3 (1328-1334)
In man the immunosuppressive drug Cyclosporine A (CsA) has been used successfully in organ transplantation and in the treatment of autoimmune disorders. The drug, however, causes side effects which occur mainly in the kidney but also in the liver. The mechanisms leading to the hepatic side effects are not yet fully understood. Because reactive oxygen production is a common mechanism of drug toxicity, the goal of this study was to evaluate whether CsA induces oxidative stress in rat fiver cells. In primary rat hepatocyte 2O-h cultures, CsA caused a concentration-dependent increase of free reactive oxygen species, thiobarbituric acid reactive substances, loss of protein thiols and decrease of molar ratios of glutathione and glutathione disulfide in the range of 0 to 50microM CsA. The weakening or enforcement of the cellular glutathione state by the glutathione synthesis inhibitor buthionine sulfoximine or the glutathione disulfide -reducing agent dithiothreitol either increased or inhibited the CsA cytotoxicity, as determined by lactate dehydrogenase release. CsA also decreased the level of endogenous antioxidant ascorbic acid and increased its oxidation product dehydroascorbic acid. Supplementation of the cell cultures with ascorbic acid significantly reduced the CsA toxicity. The antioxidant DL-alpha-tocophero l-polyethylene-glycol- 1000- succinate partly decreased CsA-mediated reactive oxygen species formation, totally decreased thiobarbituric acid reactive substances formation, prevented the loss of protein-bound sulfhydryl groups and in addition totally inhibited the CsA cytotoxicity. The present data provide good evidence that oxidative stress is part of the mechanism by which CsA causes toxicity in rat liver cells.
Bronchial reactivity and dietary antioxidants
Thorax (United Kingdom), 1997, 52/2 (166-170)
Background - It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. Methods - The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. Results - Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than five-fold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. Conclusions - This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.
Blocking effect of vitamin c in exercise-induced asthma
Archives of Pediatrics and Adolescent Medicine (USA), 1997, 151/4
Objective: To determine if vitamin C (ascorbic acid) has a protective effect on the hyperreactive airways of patients with exercise-induced asthma (EIA). Designs: All the patients underwent pulmonary function tests at rest, before and 1 hour after receiving 2 g of oral ascorbic acid. They were then randomly assigned in a double-blind manner to receive 2 g of ascorbic acid or a placebo 1 hour before a 7-minute exercise session on a treadmill. Pulmonary function tests were performed after an 8-minute rest. This procedure was repeated 1 week later, with each patient receiving the alternative medication. Settings: A university hospital. Participants: Twenty patients with asthma (13 males and 7 females), with ages ranging from 7 to 28 years (mean, 13.8 years). All patients who had a decline of at least 15% in their forced expiratory volume in 1 second after a standard exercise test on a motorized treadmill received a diagnosis of EIA. Main Outcome Measures: All patients were advised to stop using their regular asthma medication or bronchodilator 12 hours before the test. Pulmonary function tests were performed in the same ambient conditions on all patients. Results: All patients received a diagnosis of EIA. Ascorbic acid administration did not change the results of pulmonary functions at rest after 1 hour. In 9 patients, a protective effect on exercise-induced hyperreactive airways was documented. Four of 5 patients who received ascorbic acid and documented a protective effect on EIA continued to receive ascorbic acid, 0.5 g/d, for 2 more weeks with the same protective effect. Conclusions: The efficacy of vitamin C in preventing EIA cannot be predicted. However, vitamin C may have a protective effect on airway hyperreactivity in some patients with EIA.
Socioeconomic status and lung cancer incidence in men in The Netherlands: Is there a role for occupational exposure?
Journal of Epidemiology and Community Health (United Kingdom), 1997, 51/1 (24-29)
Study objective - To evaluate the influence of occupational exposure to carcinogens in explaining the association between socioeconomic status and lung cancer. Design - A prospective cohort study. Data on diet, other lifestyle factors, sociodemographic characteristics and job history were collected by means of a self administered questionnaire. Follow up for incident cancer was established by record linkage with a national pathology register and with regional cancer registries. Setting - Population originating from 204 municipalities in The Netherlands. Participants - These comprised 58,279 men aged 55-69 years in September 1986. After 4.3 years of follow up there were 470 microscopically confirmed incident lung cancer cases with complete data on dietary habits and job history. Measurements and main results - Estimation of occupational exposure to asbestos, paint dust, polycyclic aromatic hydrocarbons, and welding fumes was carried out by two experts, using information on job history from the baseline questionnaire. Socioeconomic status was measured by means of highest attained level of education and two indicators based on occupation. In the initial multivariate analyses of socioeconomic status and lung cancer, adjustment was made for age, smoking habits, intake of vitamin C, betacarotene and retinol, and history of chronic obstructive pulmonary disease or asthma. Additional adjustment for occupational exposure to the four carcinogens mentioned above did not change the inverse association between the level of education and lung cancer risk (initial model: RR highest/lowest level of education = 0.53; 95% CI 0.34,0.82; additional model: RR highest/lowest level of education = 0.53; 95% CI 0.34,0.84). Nor was the association between the two occupation based indicators of socioeconomic status and lung cancer risk influenced by occupational exposure to carcinogens. The effect of occupational exposure on the association between the level of education and lung cancer risk did not differ between ex-smokers and current smokers. Conclusions - Occupational exposure to asbestos, paint dust, polycyclic aromatic hydrocarbons, and welding fumes could not explain the inverse association between socioeconomic status and lung cancer risk. More research which explicitly addresses possible explanations for the association between socioeconomic status and lung cancer risk is needed.
Asthma but not smoking-related airflow limitation is associated with a high fat diet in men: Results from the population study 'Men born in 1914'
Monaldi Archives for Chest Disease (Italy), 1996, 51/1 (16-21)
The purpose of this study was to investigate whether there is an association between asthma and the intake of food with pro-oxidant or antioxidant activity (fat, alcohol, iron, zinc, and vitamins A and C), and to analyse whether any such association is specific to asthma or is found in airflow limitation in general. This study deals with 478 men, who were randomly selected from all the men born in Malmo in 1914. They were investigated using spirometry and their medical, occupational and dietary history was recorded in 1982-1983, at the age of 68 yrs, as part of the cohort study 'Men born in 1914'. Asthma was defined as a past or present physician's or nurse's diagnosis of asthma and airflow limitation was defined as a forced expiratory volume in one second/vital capacity ratio (FEV1/VC) of less than 70%, The relative risk of having asthma or airflow limitation as related to dietary intake at the age of 68 yrs was analysed after adjustments for smoking history and body mass index. Asthma was reported in 21 men and was not related to smoking history. Asthma was more common in men with a high fat intake (relative risk of asthma 1.74 for a 10% increase in fat intake, 95% confidence interval for the relative risk 1.13-2.68). The consumption of alcohol was higher for current smelters than ex-smelters and nonsmokers, and the intake of carbohydrates, vitamin C and iron was lower. Airflow limitation without asthma was present in 156 men and was related to smelting but not to dietary intake. Men with asthma had a significantly higher intake of fat than men without asthma. This difference appeared to be specific to asthma and was not found in airflow limitation in general.
[Prevention of cerebrovascular insults]
Schweiz Med Wochenschr (SWITZERLAND) Nov 12 1994
Cerebrovascular infarction is the third leading cause of mortality following coronary heart disease and malignancies. WHO studies show that more than half of patients admitted for cerebrovascular infarction were not treated for hypertension. The risk factors for coronary heart disease and cerebrovascular infarction are not identical. Patients with systolic and diastolic hypertension, atrial fibrillation, stenosis of the carotid artery, and smoking, have a significantly elevated risk for cerebrovascular accidents. Hypercholesterolemia and diabetes are less important risk factors. Risk factors amendable by adequate nutritional intake are low supply of carotene and vitamin C. Homocysteineemia appears to be a risk factor that may be influenced by appropriate nutrition. Antihypertensive therapy is the most important primary and secondary preventive measure. No smoking and adequate dietary intake are also important. Primary prevention with low dose salicylic acid (ASA) is recommended in the presence of additional cardiovascular risk factors. The benefit of low dose anticoagulant therapy in atrial fibrillation without symptoms is not fully established. In subjects with atrial fibrillation with cerebrovascular events anticoagulants are superior to ASA. Surgical treatment of significant stenosis of the carotid artery is indicated. In secondary prevention of thromboembolic events, low dose ASA is recommended. A valuable alternative in case of side effects is available in ticlopidine.
Diminished production of malondialdehyde after carotid artery surgery as a result of vitamin administration
Medical Science Research (United Kingdom), 1996, 24/11 (777-780)
The objective of this study was to establish the antioxidative effect of the vitamins E, C and retinyl palmitate (vitamin A), contained in a multivitamin solution, in carotid artery revascularisation surgery. 57 patients, 67.84 plus or minus 5.72 years of age, 39 men and 18 women, were divided into a control group (27 subjects) and a group with 30 subjects (mean age 68.46 plus or minus 5.09 years) who received the vitamin treatment immediately before the start of reperfusion of the brain. The control group (mean age 67.14 plus or minus 6.37 years) received physiological sodium chloride as placebo. All of the patients suffered from ischaemic cerebrovascular insufficiency manifested as TIA (transitory ischaemic attack) due to haemodynamically significant stenosis of the extracranial part of the ICA (internal carotid artery). Oxidative burst was measured by malondialdehyde (MDA) - thiobarbituric acid reactive substances (TBARS) perioperatively before and 0.5, 1, 2 and 3 h after revascularisation. In the control group MDA-TBARS significantly increased from 0.91 plus or minus 0.49 to 1.15 plus or minus 0.41 nmol mL-1 (p < 0.003) 1 h after reperfusion onset and returned to baseline after 2-3 h. In the vitamin-treated group MDA-TBARS steadily decreased during the reperfusion period (1.11 plus or minus 0.39, 0.91 plus or minus 0.42, 0.81 plus or minus 0.29, 0.78 plus or minus 0.39, 0.72 plus or minus 0.24 nmol mL-1). The significant difference in MDA-TBARS between control and treatment groups, 1 h after the start at reperfusion was 1.15 plus or minus 0.41 vs 0.81 plus or minus 0.29 nmol mL-1; (p < 0.001). As an indirect parameter of reperfusion injury 13% (4/30 patients) of the patients in thetreatment group suffered... The perioperative use of antihypertensive drugs was 20% (6/30) in the treatment group, as compared to 78% (21/27) in the control group. These results suggests that vitamin treatment prior to reperfusion might be of beneficial effect, alleviating lipid peroxidation and leading to a better clinical course as regards the central nervous system.
Effect of antioxidants on postoperative hyperamylasemia in coronary bypass surgery
Pancreas (USA), 1996, 13/3 (236-240)
Antioxidants may reduce pancreatic cellular injury after coronary artery bypass grafting (CABG). Twenty patients (Group A) received vitamin E (600 mg/day) for 28 days and vitamin C (2 g/day) and allopurinol (600 mg/day) for 2 days before and 1 day after CABG. Seventeen patients (Group C) received all drugs for 3 days, and 25 (Group B) and 19 (Group D) patients served as corresponding controls. The pre- and postoperative pancreatic isoamylase (P- amylase), creatinine, and antioxidant concentrations were measured. Serum hyperamylasemia was highest on the first postoperative day and occurred in 73% of the patients. After surgery serum P-amylase increased in all study groups and urine P-amylase decreased. Postoperative serum hyperamylasemia, whether primarily renal or pancreatic, cannot be decreased by pretreatment with allopurinol, vitamin C, and vitamin E.
[Anemia with hypersideroblastosis during anti-tuberculosis therapy. Cure with vitamin therapy]
Nouv Rev Fr Hematol (FRANCE) Apr 14 1978, 20 (1) p99-110
The unusual occurrence of microcytic anemia with hypochromia, high iron blood levels and excess of sideroblasts in the bone marrow, observed during the treatment of tuberculosis with isoniazid and rifampicine is reported. Three particularities were noted. First, in our experience, the occurrence of this type of anemia has never been noted previously as a result of these two drugs. Secondly, the improvement of the blood abnormalities was obtained by the combined use of vitamin B6 and vitamin C. Thirdly, the anemia was associated with neuropathy, characterized by areflexia and dysesthesia, which improved with vitamin B6 therapy (but not with vitamin C). Some mechanisms are discussed as being possibly the origin of this kind of anemia, particularly a lack of vitamin B6 resulting from a massive urinary loss of pyridoxal induced by isoniazid as well as both a tissue depletion and an overconsumption of this vitamin. The anemia may be the consequence of a deficiency of hemoglobin synthesis involving probably the first step of the biosynthesis of heme.
Interactions between folate and ascorbic acid in the guinea pig.
J Nutr (UNITED STATES) Apr 1982, 112 (4) p673-80
Possible interactions between folic acid (folate) and ascorbic acid (AA) have been suspected because megaloblastic anemia is occasionally observed in scorbutic patients, and it may or may not respond to folate treatment. Male weanling guinea pigs were fed diets containing high levels of folate and AA or diets deficient in one or both vitamins. A total of 36 animals, including 9 controls, were studied. When anorexia began to appear in the deficient groups, all animals were killed by exsanguination, and tissue samples (blood, liver, adrenal, kidney, spleen, and intestinal mucosa) were removed for AA and folate analyses. Folate and AA deficiency lowered tissue folate and AA levels, respectively. AA deficiency, either alone or in combination with folate restriction, did not affect tissue folate levels, nor did AA deficiency significantly exacerbate the anemia and leukopenia caused by folate deficiency. However, there was an unexpected decrease in AA levels in the liver and adrenal glands with folate deficiency. Although AA does not appear to be needed for normal folate metabolism, the lower AA levels associated with a folate deficiency are indicative of an interaction between the two vitamins.
Survival in patients with amyotrophic lateral sclerosis, treated with an array of antioxidants.
J Neurol Sci (NETHERLANDS) Aug 1996, 139 Suppl p99-103
Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis (ALS) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration. Our customary prescription sequence was N-acetylcysteine (NAC); vitamins C and E; N-acetylmethionine (NAM); and dithiothreitol (DTT) or its isomer dithioerythritol (DTE). Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid (DMSA). NAC, NAM, DTT, and DTE were administered by subcutaneous injection or by mouth or by both routes, the other vitamins and DMSA by mouth alone. The hospital pharmacy supplied NAC and NAM injections fluid as 100 ml bottles of 5.0 and 5.85% solutions, respectively. DTT was delivered in special double-walled capsules of 200 mg. DTT/DTE injection fluid was added to the NAC and NAM bottles, the final DTT/DTE concentrations never exceeding 0.5%. DMSA was provided in 250 mg capsules. All of the 36 patients used NAC and DTT/DTE; 29 also used vitamins C and E; 21 also used NAM; and 7 also used DMSA, DMSA, NAM, vitamins C and E were tolerated well. In many patients, DTT, DTE, NAC and NAM induced pain, redness and swelling at the injection sites in that order of decreasing frequency. DTT and DTE did often and NAC did sometimes cause gastric pain, nausea and other abdominal discomfort. Comparison of survival in the treated group and in a cohort of untreated historical controls, disclosed a median survival of 3.4 years (95% confidence interval: 3.0-4.2) in the treated and of 2.8 (95% confidence interval 2.2-3.1) years in the control patients. This difference may be explained by self-selection of our highly motivated treated group and by its initial survival of diagnosis for an average of 8.5 months before onset of treatment. We conclude that antioxidants neither seem to harm ALS patients, nor do they seem to prolong survival.
Autoimmune disease and allergy are controlled by vitamin C treatment
IN VIVO (Greece), 1994, 8/2 (251-258)
The present study was started to investigate the problem of whether or not vitamin C administration may help control autoimmune disease and allergy by stimulating the glucocorticoid mechanism of a patient with an immune disorder. Our study was expected to give an answer to the long-lasting enigma of endocrinology - why is the adrenal cortex so rich in the vitamin C content? Our investigation represents the complex of experimental and clinical study. A healthy male volunteer served as the test subject in the experimental study, and we investigated the effect of vitamin C injection or infusion treatments on the eosinophil count and 5 plasma steroids in plasma on the one hand, and also tested the effect of vitamin C treatments on diuresis and 17-hydroxycorticoids (17-OHCS) excretion on the other hand. In the clinical study, the effect of the vitamin C infusion treatment on immune disorders was assessed in 4 patients with autoimmune disease. Results obtained are as follows: 1) the vitamin C injection or infusion treatments induced an increase of plasma glucocorticoid activity with a delay of about 2 hours, as assessed in terms of the eosinophil count and plasma cortisol concentration. 2) Within 2 hours after vitamin C challenge, however, a remarkable decline of plasma cortisol was found to proceed without any corresponding change of the eosinophil count, a finding to suggest the presence of some cortisol absorber, of which the function was triggered by vitamin C. 3) The same vitamin C treatments also accelerated diuresis and 17-OHCS excretion. 4) The vitamin C infusion treatment produced clinical improvements in 4 patients with autoimmune diseases, of whom one patient with rheamatoid arthritis was freed from glucocorticoid addiction by intensinve use of the vitamin C infusion treatment. Thus, the experimental study and the clinical study both support an enhancing effect of vitamin C infusion treatment on the glucocorticoid mechanism of the host. The mechanism of action of vitamin C is discussed in the light of recent progress in molecular biology.
Vitamin C and the genesis of autoimmune disease and allergy (Review)
In Vivo (Greece), 1995, 9/3 (231-238)
The purpose of this review paper is to present relevant information for assessing the validity of our clinical investigation on the clinical usefulness of vitamin C infusion treatment tested in the control of autoimmune disease and allergy. Firstly, we describe the historical background of this study and then present the results of both experimental and clinical investigations as regards the therapeutic effect of vitamin C infusion treatment for the control of immune disorders including diabetes mellitus. Secondly, we discuss the interdisciplinary nature of our studies in the light of recent progress in clinical vitaminology endocrinology and immunology. Thirdly, we suggest the possibility that the use of out vitamin C infusion treatment may be beneficial in the clinical management of AIDS, of which the immunological background data are in favor of the participation of an autoimmune mechanism in the genesis of this disease. Finally, we stress the importance of paradigm change in the achievement of a breakthrough in natural science.
Is Linus Pauling, a vitamin C advocate, just making much ado about nothing?
IN VIVO (Greece), 1994, 8/3 (391-400)
Clinical use of vitamin C has been the subject of much debate in both the USA and Japan. We examine a number of topics to clarify the reasons for the confrontation of opinion between the pros and the cons as to the medical usefulness of this vitamin. We refer to our own experiences on the use of vitamin C infusion treatment for the control of either diabetes mellitus or autoimmune disease and allergy to show the importance of pharmacological considerations in the assessement of the effect of vitamin C. We also refer to a number of scientific debates to prove that a shift of paradigm is indispensable for getting a full comprehension of the benefits of vitamin C including the control of both diabetes mellitus and autoimmune disease/allergy complex.
Asthma and vitamin C
Objective. To define what role vitamin C may or may not play in the treatment of asthma. Data Sources. A comprehensive literature search of relevant English-language papers identified through a Medline search and from bibliographies of the identified papers. Study Selection. We identified papers and studies pertaining to vitamin C in asthma and allergy and analyzed these studies according to their design, inclusion and exclusion criteria, population studied, variables or factors tested, method of intervention or treatment with vitamin C, and results and conclusions. We reviewed our data and divided it based on significant or insignificant roles of vitamin C in asthma and allergy. Results. From our review, we found a number of studies that support the use of vitamin C in asthma and allergy. Significant results include positive effects on pulmonary function tests, bronchoprovocation challenges with methacholine or histamine or allergens, improvement in white blood cell function and motility, and a decrease in respiratory infections. Our review also revealed several studies that did not support a beneficial role in vitamin C in asthma and allergy. These studies did not report improvements in pulmonary function tests or bronchoprovocation challenges. No benefit was noted in these studies when testing cutaneous reactivity or specific immunologic factors and levels. Conclusions. Clearly from our review, the role of vitamin C in asthma and allergy is not well defined. The majority of the studies were short term and assessed immediate effects of vitamin C supplementation. Long term supplementation with vitamin C or delayed effects need to be studied. Although, the current literature does not support a definite indication for the use of vitamin C in asthma and allergy, the promising and positive studies revive curiosity and interest. With a large portion of health care dollars being spent on alternative medicine and vitamin C in particular, further studies are needed to define its role.
The effect of vitamin C infusion treatment on immune disorders: An invitation to a trial in AIDS patients (Review)
INT. J. ONCOL. (Greece), 1994, 4/4 (831-838)
We tested the therapeutic effect of vitamin C infusion treatment in patients with autoimmune disease or allergy, and found the trial to be a big success. The above clinical studies served to prove the validity of our speculation that vitamin C with its strong affinity for endocrine cells may enhance the function of the endocrines, and that the endocrines thus activated will in turn exert a beneficial influence on either autoimmune disease or allergy - a disease entity that is known to be responsive to glucocorticoid treatment. Experimental studies that have been conducted in parallel with our clinical studies were in agreement with our interpretation about the mechanism of vitamin C action - a finding which appears to be promising for a trial in AIDS patients. We next investigated the prospect of vitamin C infusion therapy in AIDS patients in the light of the historical development of natural science including microbiology, epidemiology and population ecology. Accumulated data were in support of the notion that AIDS is more akin to autoimmune disease than to venereal disease. Usefulness and limitation of vitamin C infusion treatment in the general crisis of the 20th Century world are discussed in relation to the population problem.
Chromium dermatitis and ascorbic acid
Fisher lists more than 50 occupations in which exposure to chromate causes dermatitis. Allergic contact dermatitis from chromates is the major problem faced by industries using chromium salts. An effective barrier cream has been sought to prevent penetration into the skin. The first recognition of such a substance was the report by Rajka et al. that 5% and 10% ascorbic acid could protect guinea pigs from the irritant action of 20% dichromate solutions. We report a severe case of chromium dermatitis which went on to complete recovery with the use of 10% ascorbic acid ointment. Effect of protective ointments with ion-exchanger on the results of patch tests with potassium dichromate in subjects sensitive to chromium compounds.
Colds and vitamin C
Cold symptoms, arising from upper respiratory inflammation, were analysed. The evidence that cold symptoms can be divided into Catarrhal and Toxic complexes is presented. It is shown that in 25% of patients these complexes are associated to form Whole Cold complexes and that Toxic or Catarrhal complexes tend to occur in the other 75% of patients, their frequency being sex dependent. Etiologically colds may have a viral or allergic origin. Common colds occur predominantly between August and April and allergic colds are most common in the summer from April to September. House dust mite sensitivity gives rise to characteristic cold symptoms which occur throughout the year. Alterations in ascorbic acid metabolism are associated with the presence of cold symptoms. A specific test for diagnosing the antigenic sensitivity responsible for the allergic cold symptoms is described. Catarrhal symptoms arise from localised respiratory inflammatory lesions and Toxic symptoms arise as a result of dissemination of viral particles or antigen into general body tissues where inflammatory and immunological response occurs. Ascorbic acid utilisation is increased during common and allergic colds for implementation of tissue defence mechanisms.
Vitamin C metabolism and atopic allergy
The procedure for carrying out the Leucocyte Ascorbic Acid Uptake Direct Antigen Challenge Test (LAADACT) is described. Leucocytes from normal individuals, when incubated in a buffered medium containing ascorbic acid, increase their ascorbic acid concentration by about 80%. When leukocytes from atopic individuals are incubated in a medium containing the antigen to which they are sensitive, as shown by positive skin test, the leucocyte uptake ascorbic acid is significantly reduced. Addition of antigen, to which atopic or normal individuals are not sensitive, to the incubation mixture does not reduce leucocyte ascorbic acid uptake. Measurement of ascorbic acid uptake into leucocytes is a relatively simple, routine, laboratory procedure. The LAADACT, therefore, provides a quick and accurate blood test for diagnosing sensitivity to specific antigens, and measuring relative antigenic sensitivities. The underlying mechanism of the LAADACT is discussed.
Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking.
Agents Actions (SWITZERLAND) May 1975, 5 (2) p164-73
Acetaldehyde is a toxic substance common to heavy drinking of alcohol and heavy smoking of cigarettes. It has been implicated thereby in diseases of the cardiovascular, respiratory, and central nervous systems. Protection against acetaldehyde toxicity (i.e. anesthesia and lethality) was studied in rats by oral intubation of test compounds 30-45 minutes prior to oral intubation of a standardized oral LD 90 dose (18 millimoles/kilogram) of acetaldehyde. Animals were monitored for anesthesia (loss of righting reflexes) and lethality for 72 hours. A total of 18 compounds was tested. L-ascorbic acid at 2 millimoles/kilogram (mM/kg) showed moderate protection against anesthesia and marked protection against lethality. Greatest protection against anesthesia and lethality was obtained at 2 m M/kg with each of the following: L-cysteine, N-acetyl-L-cysteine, thiamin-HCl, sodium metabisulfite, and L-cysteic acid. A combination of L-ascorbic acid with L- cysteine, and thiamin-HCl at reduced dose levels (2.0, 1.0 and 0.3 mM/kg, respectively) gave virtually complete protection. A detailed literature review is presented of the rationale and significance of these findings. Our findings could point the way to a possible build-up of natural protection against the chronic body insult of acetaldehyde arising from heavy drinking of alcohol and heavy smoking of cigarettes.
Adrenal function and ascorbic acid concentrations in elderly women.
Gerontology (SWITZERLAND) 1978, 24 (6) p473-6
Tetracosactrin (Synacthen) tests were performed on 19 elderly women who had leucocyte ascorbic acid (LAA) levels of less than 15 microgram/108 WBC. 9 were then given a daily dose of 200 mg ascorbic acid orally for 2 weeks while the other 10 were left untreated. Following this, tetracosactrin tests were repeated in both groups. All initial plasm cortisol responses to tetracosactrin were within normal limits. Treatment with ascorbic acid produced no changes in these. This suggests that the low LAA levels often found in old people do not result in adrenal insufficiency.
Ascorbate and urate are the strongest determinants of plasma antioxidative capacity and serum lipid resistance to oxidation in Finnish men
Atherosclerosis (Ireland), 1997, 130/1 (223-233)
Copper-induced plasma lipoprotein oxidation resistance has usually been determined innsity lipoprotein (LDL) fractions, that do not contain water-soluble antioxidants present in blood plasma. The aim of this study was to find the main determinants of the measurements of copper-induced lipid oxidation istance (lag time) in whole serum and plasma total peroxyl radical trapping capacity (TRAP) in a population sample of smoking (n = 25) or non-smoking (n = 26) middle aged men at high risk of cardiovascular diseases. Smokers had significantly lower plasma ascorbic acid values, but only slightly lower alpha-tocopherol, beta-carotene and serum urate values than non-smokers. Plasma ascorbic acid concentration explained 23.5% of the lag time variation (standardized regression coefficient beta = 0.48; P = 0.004) in smokers and 5.6% in non-smokers. Serum urate concentration was the strongest determinant of lag time in non-smokers (beta = 0.64, P < 0.001). In addition, serum albumin, lipid standardized alpha-tocopherol and serum high density lipoprotein (HDL) cholesterol entered the multivariate regression model for lag time. For plasma TRAP, only urate and ascorbic acid entered the multivariate regression model. Lag times in serum and in isolated very low density lipoprotein (VLDL) and LDL fraction did not correlate, but the maximal rate of these reactions correlated significantly. These results confirm that lipid peroxidation resistance in serum or plasma are associated with ascorbic acid, urate, alpha-tocopherol, albumin and HDL concentrations. The measurement of lipid oxidation resistance in whole serum might be more physiological than in isolated lipoprotein fraction, as the effects of water-soluble antioxidants are not artificially removed.
Oxidized low density lipoproteins in atherogenesis: Role of dietary modification
Annual Review of Nutrition (USA), 1996, 16/- (51-71)
The development of atherosclerosis is a complex and multistep process. There are many determinants in the pathogenesis of this condition, with different factors presumably playing key roles at different times in the evolution of the atherosclerotic plaque. It has been suggested that oxidation of low density lipoproteins (LDL) by cells in the artery wall leads to a proatherogenic particle that may help initiate early lesion formation. For this reason, understanding the determinants of LDL susceptibility to oxidation is essential for developing therapeutic strategies to inhibit this process. Oxidation of LDL begins with the abstraction of hydrogen from polyunsaturated fatty acids; thus, LDL fatty acid composition undoubtedly contributes to the process of LDL oxidation. Since dietary fatty acids influence the fatty acid composition of LDL and cell membranes, the amount and type of fat in the diet may effect susceptibility of LDL and cells to oxidative damage. Additionally, since cell membrane fatty acid composition also influences cellular formation of reactive oxygen species, dietary fatty acids may help determine the prooxidant activity of artery wall cells. Both cells and lipoproteins contain a variety of antioxidants that provide protection against oxidative stress. A major source of these antioxidants is the diet. Enrichment of the diet with foods high in such antioxidants as vitamin E, beta-carotene, or vitamin C, or supplementation of the diet with antioxidant vitamins, may inhibit oxidation and the process of atherosclerosis.
Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers
Atherosclerosis (Ireland), 1996, 124/1 (75-81)
In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely corrrelated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.
The role of free radicals in disease
Australian and New Zealand Journal of Ophthalmology (Australia), 1995, 23/1
Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.
Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: The diet and antioxidant trial on atherosclerosis (DATA)
Cardiovascular Drugs and Therapy (USA), 1995, 9/6
The effects of administration of guava and papaya fruit (100 g/day), vegetables, and mustard oil (5 g/day) (group A); antioxidant vitamins C (50 mg/day) and E (30 mg/day) plus betacarotene (10 mg/day) (group B); a high-fat (5-10 g/day) (group C); or a low-fat (4-5 g/day) diet (group D) were compared over 24 diet weeks in a randomized fashion, while all groups of rabbits (five in each of four groups) received a hydrogenated fat diet (5-10 g/day) for a period of 36 weeks. After 12 weeks on the high fat diet, each group of rabbits had an increase in blood lipoproteins. The fruit and vegetable-enriched prudent diet (group A) caused a significant decline in blood lipids at 24 and 36 weeks, whereas the lipid levels increased significantly in groups C and D. Group A also had a significant rise in vitamin E (2.1 Umol/l), C (10.5 Umol/l), A (0.66 Umol/l), and carotene (0.08 Umol/l) and a decrease in lipid peroxides (0.34 nmol/ml at 36 weeks, whereas the levels were unchanged in groups C and D. Group B rabbits had a significant and greater increase than group A in plasma vitamins E, C, A, and carotene; a rise in HDL cholesterol; and a greater decrease in lipid peroxides after 24 and 36 weeks of treatment. After stimulation of lipid peroxidation in all rabbits, 3 of 5 group C and 2 of 5 group D rabbits died due to coronary thrombosis, whereas in groups A and B there were no deaths, indicating that antioxidant therapy can provide protection against lipid peroxidation and free radical generation. Aortic lipids and sudanophilia, indicating atherosclerosis, were significantly higher in groups C and D than in groups A and B. Fatty streaks and atheromatous and fibrous plaques were noted in all the rabbits in groups C and D. Intimal fibrosis and medial degeneration were also present in the group C rabbits. While group A (36.4 plus or minus 4.4 microm) and group B (37.1 plus or minus 4.2 microm) rabbits had minimal coronary artery plaque sizes, group C (75.4 plus or minus 10.6 microm) and group D rabbits (69.5 plus or minus 6.2 microm) had significantly greater plaque sizes. Aortic plaque sizes were also greater in groups C and D than in groups A and B. It is possible that combined therapy with antioxidant vitamins C, E, and carotene, and a diet rich in antioxidants, could independently inhibit free radical generation and the development of atherosclerosis.
Effect of vitamin E, vitamin C and beta-carotene on LDL oxidation and atherosclerosis
Canadian Journal of Cardiology (Canada), 1995, 11/SUPPL. G (97G-103G)
OBJECTIVE: The oxidative modification of low density lipoprotein (LDL) may be early step in atherogenesis. Furthermore, evidence of oxidized LDL has been found in vivo. The most persuasive evidence shows that supplementation of some animal models with antioxidants slows atherosclerosis. The purpose of this review is to examine the roles that vitamin E, vitamin C and beta-carotene may play in reducing LDL oxidation. DATA SOURCES: English language articles published since 1980, particularly from groups active in this field of research. STUDY SELECTION: In vitro, animal, and human studies on antioxidants, LDL oxidation, and atherosclerosis were selected. DATA SYNTHESIS: Vitamin E has shown the most consistent effects with regard to LDL oxidation. Beta-carotene appears to have only a mild or no effect on oxidizability. Ascorbate, although it is not lipophilic, can also reduce LDL oxidative susceptibility. CONCLUSIONS: LDL oxidizability can be reduced by antioxidant nutrients. However, more research is needed to establish their utility in the prevention of coronary artery disease.
Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo
A common feature of cigarette-smoke (CS)-associated diseases such as atherosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro- and macrovascular endothelium. A previous study, using a skinfold chamber model for intravital fluorescence microscopy in awake hamsters, has shown that exposure of hamsters to the smoke generated by one research cigarette elicits the adhesion of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and scanning electron microscopy, we now demonstrate in the same animal model that (i) CS-induced leukocyte adhesion is not confined to the microcirculation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstream of aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte adhesion to micro- and macrovascular endothelium and leukocyte-platelet aggregate formation are almost entirely prevented by dietary or intravenous pretreatment with the water-soluble antioxidant vitamin C (venules, 21.4 plus or minus 11.0 vs. 149.6 plus or minus 38.7 leukocytes per mm2, P < 0.01; arterioles, 8.5 plus or minus 4.2 vs. 54.3 plus or minus 21.6 leukocytes per mm2, P < 0.01; aortas, 0.8 plus or minus 0.4 vs. 12.4 plus or minus 5.6 leukocytes per mm2, P < 0.01; means plus or minus SD of n = 7 animals, 15 min after CS exposure). No inhibitory effect was observed by pretreatment of the animals with the lipid-soluble antioxidants vitamin E or probucol. The protective effects of vitamin C on CS-induced leukocyte adhesion and aggregation were seen at vitamin C plasma levels (55.6 plus or minus 22.2 microM, n = 7) that can easily be reached in humans by dietary means or supplementation, suggesting that vitamin C effectively contributes to protection from CS-associated cardiovascular and pulmonary diseases in humans.
Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of alpha-tocopherol and ascorbate.
Arterioscler Thromb Vasc Biol (UNITED STATES) Oct 1995, 15 (10) p1616-24
We assessed the antioxidant status and contents of unoxidized and oxidized lipids in freshly obtained, homogenized samples of both normal human iliac arteries and carotid and femoral atherosclerotic plaque. Optimal sample preparation involved homogenization of human atherosclerotic plaque for 5 minutes, which resulted in recovery of most of the unoxidized and oxidized lipids without substantial destruction of endogenous vitamins C and E and 87% and 43% recoveries of added standards of alpha- tocotrienol and isoascorbate, respectively. The total protein, lipid, and antioxidant levels obtained from human plaque varied among donors, although the reproducibility of replicates from a single sample was within 3%, except for ubiquinone-10 and ascorbate, which varied by 20% and 25%, respectively. Plaque samples contained significantly more ascorbate and urate than control arteries, with no discernible difference in the vitamin C redox status between plaque and control materials. The concentrations of alpha-tocopherol and ubiquinone-10 were comparable in plaque samples and control arteries. However, approximately 9 mol percent of plaque alpha-tocopherol was present as alpha-tocopherylquinone, whereas this oxidation product of vitamin E was not detectable in control arteries. Coenzyme Q10 in plaque and control arteries was only detected in the oxidized form ubiquinone-10, although coenzyme Q10 oxidation may have occurred during processing. The most abundant of all studied lipids in plaque samples was free cholesterol, followed by cholesteryl oleate and cholesteryl linoleate (Ch18:2). Approximately 30% of plaque Ch18:2 was oxidized, with 17%, 12%, and 1% present as fatty acyl hydroxides, ketones, and hydroperoxides, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacotherapy in Alzheimer's dementia: Treatment of cognitive symptoms Results of new studies
Fortschritte der Neurologie Psychiatrie (Germany), 1997, 65/3 (108-121)
Recent investigations have given new insights into pathogenetical determinants of Alzheimer's disease. Amyloid deposition and neurofibrillary tangles are no longer considered to be primary pathological changes. Neurobiological research tries to work out the etiopathogenital cascade that finally causes Alzheimer's disease. So far, several relevant pathogenetical factors have been detected, e.g. pertubated control of glucose breakdown, impairment of oxidative metabolism, impaired neuroprotection due to increased oxidative stress and non-enzymatic protein glycation as well as immunological disturbances. Thus, new strategies for the development of cognition-enhancing drugs are emerging. The authors review reports on agents, that are under investigation for the treatment of cognitive symptomatology in Alzheimer's disease. Some of these agents have already been used for treatment of other medical conditions, e.g. nimodipine, memantine as well as selegiline. Many of them are still experimental. Promising strategies include antioxidative agents (e.g. vitamin E, vitamin C, beta-carotin), acetylcholinesterase-inhibitors with central selectivity (e.g. ENA 713), M1- and M4-muscarinic receptor agonists (milameline) as well as sabeluzole, a benzothazide derivative that shows neurotrophic activities and anti-inflammatory substances like indomethacin.
Vegetable, fruit, and grain consumption to colorectal adenomatous polyps
American Journal of Epidemiology (USA), 1996, 144/11 (1015-1025)
Previous studies suggest that colorectal cancer risk decreases with higher intake of vegetables, fruits, and grains. Few studies, however, have examined these factors in relation to occurrence of colorectal polyps. The authors used case-control data from 488 matched pairs to evaluate associations of vegetables, fruits, and grains with polyps. Subjects were southern Californians aged 50-74 years who had a sigmoidoscopy in 1991-1993. Diet in the year before sigmoidoscopy was measured with a food frequency questionnaire. Frequent consumption of vegetables, fruits, and grains was associated with decreased polyp prevalence. Specifically, the adjusted odds ratio comparing the highest with the lowest quintile of intake for vegetables was 0.47 (95% confidence interval (CI) 0.29-0.76), for fruits was 0.65 (95% CI 0.40-1.05), and for grains was 0.55 (95% CI 0.33-0.91). The authors also found inverse associations for high carotenoid vegetables, cruciferae, high vitamin C fruits, garlic, and tofu (or soybeans). After further adjusting for potentially anticarcinogenic constituents of these foods, high carotenoid vegetables, cruciferous vegetables, garlic, and tofu (or soybeans) remained inversely associated with polyps. These findings support the hypothesis that high intake of vegetables, fruits, or grains decreases the risk of polyps and suggest that any protective effects might reflect nmeasured constituents in these foods.
Diet and risk of esophageal cancer by histologic type in a low-risk Group
International Journal of Cancer (USA), 1996, 68/3 (300-304)
In a hospital-based case-control study of esophageal cancer undertaken in Athens (1989-1991), 43 patients with incident esophageal squamous-cell carcinoma and 56 patients with incident esophageal adenocarcinoma were compared to 200 injury patients. Personal interviews were conducted in the hospital setting, and dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire. Nutrient intakes for individuals were calculated by multiplying the nutrient content of a typical portion size for each specified food item by the frequency with which the food was consumed per month and summing these estimates for all food items. Data were modeled through logistic regression, controlling for sociodemographic factors, tobacco smoking, consumption of alcoholic beverages and total energy intake. Consumption of vegetables and fruits as well as intake of vitamin A, vitamin C and crude fiber were inversely associated with esophageal cancer in general, but the respective associations were stronger for adenocarcinoma. There was evidence that added oils and fats and intake of polyunsaturated fat were positively associated with adenocarcinoma but inversely associated with squamous-cell carcinoma.
Vitamin status in patients with inflammatory bowel disease
Fernandez-Banares F.; Abad-Lacruz A.; Xiol X.; Gine J.J.; Dolz C.; Cabre E.; Esteve M.; Gonzalez-Huix F.; Gassull M.A.
Department of Gastroenterology, Hospital de Bellvitge 'Princeps
d'Espanya', Barcelona Spain
The status of water- and fat-soluble vitamins was prospectively evaluated in 23 patients (13 men, 10 women, mean age 33 plus or minus 3 yr) admitted to the hospital with acute or subacute attacks of inflammatory bowel disease. Protein-energy status was also assessed by means of simultaneous measurement of triceps skin-fold thickness, mid-arm muscle circumference, and serum albumin. Fifteen patients (group A) had extensive acute colitis (ulcerative or Crohn's colitis), and eight cases (group B) had small bowel or ileocecal Crohn's disease. Eighty-nine healthy subjects (36 men, 53 women, mean age 34 plus or minus 2 yr) acted as controls. In both groups of patients, the levels of biotin, folate, beta-carotene, and vitamins A, C, and B1 were significantly lower than in controls (p < 0.05). Plasma levels of vitamin B12 were decreased only in group B (p < 0.01), whereas riboflavin was lower in group A (p < 0.01). The percentage of patients at risk of developing hypovitaminosis was 40% or higher for vitamin A, beta-carotene, folate, biotin, vitamin C, and thiamin in both groups of patients. Although some subjects had extremely low vitamin values, in no case were clinical symptoms of vitamin deficiency observed. Only a weak correlation was found between protein-energy nutritional parameters and vitamin values, probably due to the small size of the sample studied. The pathophysiological and clinical implications of the suboptimal vitamin status observed in acute inflammatory bowel disease are unknown. Further studies on long-term vitamin status and clinical outcome in these patients are necessary.
Ascorbic acid metabolism in ulcerative colitis of bacterial origin
Husainov O.H.
Kaf. Infekts. Bol., Tadzhik. Medinst., Dushanbe USSR
Investigation of 39 patients suffering from acute bacterial dysentery and 25 with an exacerbation of the chronic form revealed disturbances of the vitamin C metabolism in all cases, manifested by a low content of the vitamin in the blood and its low excretion in the urine. The degree of the changes depended on the clinical manifestations of the disease. Administration of vitamin C in therapeutic doses corrected the vitamin deficiency in acute bacterial dysentery. In patients with exacerbations of chronic dysentery the indices of the ascorbic acid metabolism failed to reach the normal values, thereby indicating more prolonged and massive vitamin therapy.
Clinical study of vitamin influence in diabetes mellitus
Journal of the Medical Society of Toho University (Japan), 1996, 42/6 (577-581)
Vitamin deficiency is a result of an inadequale diet. Education on the importance of trace nutrients in diabetic patients with poor blood sugar control is examined. Those who prepare meals must consider the loss of vitamins in the process of cooking. Our study also suggested that marginal vitamin deficiency plays an indirect but important role in the development of diabetic complications. Vitamin C as altering total cholesterol (T-ch) and vitamin E as altering triglyceride (TG) could modify diabetic angiopathy. Pharmacologically, niacin might be responsible for the decrease in Lipoprotein (a) and vitamin C would inhibit the influence of rapid blood glucose control on diabetic retinopathy.
Vitamins and immunity: II. Influence of L-carnitine on the immune system.
Acta Vitaminol Enzymol (ITALY) 1982, 4 (1-2) p135-40
Vitamin A affects the antibody responses and may affect phagocytic function and properdin levels. Pyridoxine deficiency impairs nucleic acid synthesis and depresses antibody formation, delayed hypersensitivity reactions and the ability of phagocytes to kill bacteria. Pantothenic acid deficiency impairs antibody formation. Vitamin C deficiency increases the incidence of infection, primary by a negative influence on reparative processes. Deficiencies of other vitamins either have not been sufficiently studied or have a variable effect. Moreover, even substances which for their biosynthesis require an adequate vitamin supplementation may exert immunomodulatory influences. With this respect the authors report their results on the influence of L-carnitine on the immune system. L-carnitine increases the proliferative responses of both murine and human lymphocyte following mitogenic stimulation and increase polymorphonuclear chemotaxis. Furthermore, L-carnitine, even at minimal concentrations, neutralizes the lipid induced immunosuppression.
Protein/platelet interaction with an artificial surface: effect of vitamins and platelet inhibitors.
Thromb Res (UNITED STATES) Jan 1 1986, 41 (1) p9-22
Protein adsorption and platelet adhesion are two important biological processes arising at the blood-prosthetic interface. The effect of Vitamins and antiplatelet drugs to modulate the surface induced platelet adhesion to polycarbonate was investigated using washed calf platelets in presence and absence of fibrinogen. This study also demonstrated the effects of Vitamins and antiplatelet drugs towards protein adsorption to an artificial surface. It seems Vitamin B6, Vitamin E, combinations of Aspirin-Persantine, Aspirin-Vitamin C, a synthetic Polyelectrolyte and Galactosamine reduced the fibrinogen (fg) surface concentration from a mixture of proteins. These antiplatelet agents also enhanced the albumin surface concentration. This itself may be one of the parameters to reduce the platelet adhesion towards an artificial surface. A combination of Aspirin-Vitamin C-Vitamin B6-Vitamin E inhibited the fibrinogen surface binding, which might be beneficial to improve the blood compatibility of an artificial surface
Selected micronutrient intake and thyroid carcinoma risk
Cancer (USA), 1997, 79/11 (2186-2192)
BACKGROUND. Protection from thyroid carcinoma due to certain dietary factors was suggested by several studies, but the findings were relatively inconsistent. The role of micronutrients has not yet been systematically analyzed. To investigate the relationship between micronutrient intake and thyroid carcinoma risk, the authors used data from a case-control study conducted in northern Italy between 1986 and 1992. METHODS. The study included 399 incident, histologically confirmed thyroid carcinoma cases and 617 controls admitted to the hospital for acute, nonneoplastic, nonhormone- related diseases. RESULTS. Retinol intake showed a direct association with thyroid carcinoma risk, with odds ratios (ORs) of 1.39 (95% confidence interval (CI), 0.9-2.0) in the third quartile of consumption and 1.52 (95% CI, 1.0-2.3) in the highest quartile, whereas beta-carotene had an inverse relationship, with ORs of 0.63 (95% CI, 0.4-0.9) in the third quartile of consumption and 0.58 (95% CI, 0.4- 0.9) in the highest quartile compared with the lowest quartile. Some protection was observed for measures of vitamin C intake (with an OR of 0.72) and vitamin E (with an OR of 0.67) for the highest quartile of consumption, although the estimates were not statistically significant, and were reduced after adjustment for beta- cern in risk appeared for vitamin D, folate, calcium, thiamin, or riboflavin. The inverse relationship between beta- carotene and thyroid carcinoma was observed in both papillary and follicular carcinomas. CONCLUSIONS. In this study, a significant inverse association between beta-carotene and thyroid carcinoma was observed, and some protection against thyroid carcinoma from vitamins C and E was also suggested.


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Make your house the place to be on game day with an Authentic Street Signs® Cincinnati Bengals "Man Cave" Street Sign. Crisp customized lettering is enhanced with a deep embossed design, giving the sign a three-dimensional feel. Great for an office desk or a Bengals shrine, this sign proudly displays your love of your favorite team. A high quality steel and automotive paint finish replicates the style of an antique street sign.
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Proposed town code amendments to address chronic problem properties and blight in the neighborhoods of the town pushed a hot button at last night's Barnstable Town Council meeting.
Sixteen people stepped to the lectern to address the council on the proposals, generated by the Greater Hyannis Civic Association with the assistance of the town attorney's office.
Following a discussion, the council decided to continue the public hearing on the changes to the council's January 17 meeting.
Council president Frederick Chirigotis of Centerville said continuing the public hearing to January 17 will allow the council to hold one or more workshops in the interim to address concerns raised by councilors and members of the public about the code changes.
Councilor Jennifer L. Cullum of Hyannis, with the support of councilors James H. Cote of Osterville and Jessica Rapp Grassetti of Cotuit, sponsored the proposed code changes.
Laura T. Cronin of Hyannis, a member of the Greater Hyannis Civic Association, gave a presentation on the proposed changes, which are intended to address issues such as chronic problem properties, blight, noise and overcrowding.
The council opened its discussion with a public hearing on a proposed new chapter in the town code on so-called "chronic problem properties" that generate repeated police calls.
The chapter would allow the town, at the discretion of the police chief, to bill the owner of a property for police costs after the police respond to three felonies or misdemeanors at that property within a 12-month period.
Once an address is identified by the chief under the chapter as a "chronic problem property," the town collector will be empowered to bill the property owner for police costs and deposit the money in the general fund of the town.
Unpaid bills will be added to the real estate tax.
Failure to pay real estate taxes will render the property owner delinquent and the collector will move to foreclose on the property.
At last night's hearing, members of the public addressed not only the proposed chapter, but the other proposed code changes as well.
Hyannis resident Milton E. Berglund said an undue burden was being placed on town taxpayers by the cost of dealing with very few problem properties.
Mr. Berglund said the problem had been festering for years, and called on the town council to take action.Meg O. Loughran, president of the Centerville Civic Association, said the association supports the code changes.
Ms. Loughran said the code changes are long overdue.Hyannis resident Peter Cross said the code changes were not perfect, but represented a start to address longstanding problems. Barnstable Deputy Police Chief Craig Tamash, who addressed the council on behalf of the town police chief, Paul B. MacDonald, agreed.
But the proposed changes also drew criticism from the public.
West Barnstable resident Ronald R. Beaty said the proposed changes would stigmatize properties and deny them equal protection under the law.
Kristine P. Clark, representing the West Barnstable Civic Association, read a letter from the association that questioned aspects of several of the code changes, such as applying subjective judgments on the condition of properties.
Several town councilors said the proposed changes were too loose and needed to be tightened up.
"I would like to see these get as close to perfect as possible before we pass them," councilor Ann B. Canedy of Barnstable Village said.
Councilor John T. Norman of Marstons Mills questioned holding landlords responsible for the actions of their tenants.
Councilor June M. Daley of Marstons Mills said agreed with Mr. Norman.
Councilor Janet S. Joakim of Centerville said the "problem property" ordinance as written could have a negative impact on the victims of domestic abuse.
Councilor Thomas Rugo of Centerville questioned moving against properties that had generated police calls, but had not yet resulted in convictions or admissions of guilt.
But councilor James M. Tinsley Jr. of Hyannis called for passing the ordinances even if they were not perfect.
"One thing about politics: nothing gets done," Mr. Tinsley said.


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Chef Danny Boome Takes Your Comfort Food Menu to "Recipe Rehab"
Written on October 30, 2012 at 10:30 am , by Karla Walsh
Take one easy-on-the-eyes English chef, mix in a selection of all of our favorite comfort food meals, add two all-star cooks with an eye towards health and stir.
That's the formula for Recipe Rehab, a new TV show airing on ABC stations. Each episode of the show, hosted by Danny Boome (left), features one dish that traditionally is a calorie bomb (spaghetti with meatballs or macaroni and cheese, for example). Two accomplished gourmets duke it out in the kitchen to see who can create the most flavorful—and healthful—makeover.
We caught up with Boome to find out what makes this program stand out among all of the cooking shows on air and to learn how we can lighten up any of our favorite meals.
What do you think most home cooks do wrong in terms of the health factor of their meals?
Why do we always have to buy full-fat or full-sodium products? Swap in reduced-sodium and low-fat and use your spice rack frequently. It also helps if you buy seasonally. Butternut squash tastes so much better—and is way more affordable—now rather than during summer.
Great advice! There are a lot of food shows on TV. What convinced you to sign on to the Recipe Rehab team?
It's much fresher than the "stand and stir" shows. The competition adds energy, but it's still educational. We're not lecturing. You don't have to cut everything out, but we show viewers how to make good choices
Keep reading for Boome's greatest lessons learned on set, plus a winning "unfried" chicken recipe from the show.
Categories: Healthy Eating, Nutrition, The Fit Stop | Tags: celebrity chef, cooking tips, healthy recipe, low calorie fried chicken, Recipe Rehab
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Research is a key component of CHOP's Neonatal Airway Program. We are engaged in studies to improve patient outcomes and enhance the field of otolaryngology.
Some current research includes:
To schedule an appointment or referral, please call the Neonatal Airway Program at 215-590-2616 or contact us online.
Reviewed by: Neonatal Airway Program team
Date: May 2013


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12 Sep 2014
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Improved reading skills
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"The magnitude of the improvement observed in the study is extremely large and is therefore likely to be of real clinical importance.− Professor Stephen Jackson, School of Psychology, Nottingham University
On the timed single word-reading task, the improvement shown by the treatment group was more than twice as high than that shown by the placebo group."
"The average improvement of the children in this study on at least one test was 18 months.
On average the children showed an 11-month improvement in word recognition, and an improvement of 9 months on single word reading and 7 months on spelling."− School pilot - Feltham Community College
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A research study on a 6-weeks program with BrightStar technology and remedial teaching.
A Dutch study analyzed data from a group of young people who volunteered for a special, 6-week program.
Over a period of 3 years, a total of 209 people took part in the program which consisted of semiweekly 20 to 30-minute BrightStar sessions and a weekly 45-minute remedial teaching session.
Note: Statistical analysis of the effects of the BrightStar treatment. CQM, Eindhoven, the Netherlands (2011)
improvement on a spelling test (PI)10 months
improvement on a reading test (CITO)9 months
improvement on a Reading fluency test (EMTb)8+ months
improvement on a Word reading test (DMT)8+ months
improvement on a Non-Word reading test (Klepel)7 months
To evaluate the volunteers' reading and spelling capabilities, extensive initial and final assessments were administered.
After the program, the observed changes were analyzed and the effects determined.
The graph shows the average improvement (in months) in people aged 12 – 16 years on some of the key tests.
The labels refer to standardized education tests for reading, spelling and fluency in the Netherlands.
in reading & language skills.
we work in.
dedicated experience.


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Feb 26, 2013 | 03:40 PM
| Lisa Gordon
Sadoff Iron & Metal Co.,
scrap recycling,
Rolf Hadel,
Mark Lasky,
Lisa Gordon
Pittsburgh Sadoff Iron & Metal Co.s Rolf Hadel will retire after a career in the scrap recycling....
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Are you stocking more inventory today than 18 months ago?
We actually don't know who his investors are. At the point when we are ready, we will investigate further. There are just so many things to handle and there are a lot of items to be considered with the project."
-- Charles C. Mitchell, Barstow city manager


text:
Narrow your search
Michael Zuk, a Canadian dentist, has already bought one of John Lennon's teeth. Next step: clone the rest.
Researchers at National Taiwan University have created a wearable mouth sensor that can differentiate your bad habits, and send that information straight to your dentist.
The Bluetooth-enabled toothbrush, which became available as of last week, is embedded with a sensor to track brushing habits and enable users to send their oral hygiene particulars to dentists.
Enterprising Indonesian dentist modifies a standard dental drill to emit far more pleasant sounds than the standard ominous high-pitched whine.
Showa Hanako, a robotic dental patient created to help train dental students, gets more realistic, thanks to silicone parts from a Japanese sex doll maker.
A New York dentist is accused of making patients sign away their copyright to negative reviews and then billing a patient $100 a day for posting unhappy reviews on Yelp. The dentist is now being taken to court.
Robots get extra creepy this week as Japanese sexbots take day jobs as dental student test subjects and androids find a way to smell as bad as their human counterparts.
Robots just became a whole lot more real this week as Japanese sexdolls help dental students and robot armpits assault your senses. We also pay equal time to Darth Vader and Spock merchandise, and check out the forefront of giant burger technology.
Real estate search site Estately.com has arranged our great states from most to least scary based on things like bears, dentists, and yes, clowns.
Pen-like device is billed as the first of its kind for soft-tissue incision.


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It had been quite a hiatus since the DWTS Season 1 winner Kelly Monaco had been in the ballroom. She was ready to put on her dancing shoes again and have a new partner, Valentin Chmerkovskiy for the All-Star Season. The pair's chemistry was noticeable from the beginning as they danced a Cha Cha to "Bang Bang" by David Sanborn for Week 1.
Judges' Scores:
Carrie Ann: 7
Len: 7
Bruno: 7.5
Even Len, who is generally reserved, was impressed: "You weren't this good Season 1. Something's happened here. I thought the choreography was terrific and suited Kelly. I loved it...well done."
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text:
- 5/16/13 /
- Comment
Scarlett Johansson to Make Her Directorial Debut
Adapting a Truman Capote novel.
Skip to content, or skip to search.
Adapting a Truman Capote novel.
But security concerns got in the way.
How does one turn an untheatrical novel into a compelling play?
Another excuse to stay indoors.
Not that we didn't already know that.
delete this
Another excuse to stay indoors.
Scarlett Johansson — from Avenger to auteur?
Today's the 50th birthday of Capote's original novella.


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Author: Ed Roach (239 Articles)
For 25 years or so I have developed positioning strategies for small businesses that helps to differentiate them. I appreciate working with companies who see the value of going beyond mere slogans and have a desire to sell from compelling positions. Opportunities come to light in every discussion. I consult predominantly with small business and and implement the solutions developed. If you'd like some help in allowing your brand to lead contact me. I've just released my first printed book, "101 Branding Tips - Practical advice for your brand that you can use today." Get your copy from Amazon.com and the Amazon Kindle Bookstore. I can be contacted directly at: 519-324-9536 or email@example.com Blog: TheBrandCorral.com


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50th Anniversary Alumni Reunion
October 17-18, 2014
All alumni who were part of the UW Oshkosh Radio-TV-Film (RTF) program are invited back to campus for a special reunion as part of Homecoming 2014. Return to campus to help kick off a year-long celebration of 50 years of RTF program excellence.
RTF 50th Anniversary - RSVP Today from UW Oshkosh Radio-TV-Film on Vimeo.
Reunion Information
- Planning Committee: Get involved!
Planning to Attend?
- Pledge to be at the 50th Anniversary Alumni Reunion on Saturday, Oct. 18, 2014, please complete the following:
Please encourage fellow RTF alums to attend and bring photos and memorabilia to share on Saturday evening.
View and Comment RTF 50th Anniversary Flickr Gallery
Schedule of Events
Friday, October 17
- 1:00–3:00 p.m. Pro Perspectives: A Dialogue with Media Insiders Networking Event
- 5:00–8:30 p.m. UW Oshkosh Alumni Association Awards Dinner*
- 8:00 p.m. Alumni / Student Event – off campus, location TBA
Saturday, October 18
- 10:00–11:30 a.m. RTF Student/Alumni Breakfast Open House & Facility Tours
- Noon–1:30 p.m. Pregame Celebration at RTF Alumni Tent at Tent City.
- 1:30 p.m. Football game vs. UW-River Falls, J. J. Keller Field at Oshkosh Sports Complex
- 6:30–10:30 p.m. RTF Alumni Reunion* (program 8–8:30 p.m.), UW Oshkosh Alumni Welcome Center
*Preregistration required


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History |
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fixed a bug that wrote the first part of data if an IMAP4 data didn't end with CR+LF.
updated copyright.
fixed crashes when trying to fetch >64KB messages on IMAP4 via FreeCap on Win32.
reverted linebreak conversion.
removed CR+LF to LF conversion on receiving.
also log IMAP4 literal strings.
support literals in IMAP response.
changed the license of LibSylph from GPL to LGPL.
moved recv.[ch] to libsylph.
made error check of IMAP4 fetch more strict.
added wrappers for C library function that take pathname arguments.
improved portability.
replaced intl.h with glib/gi18n.h.
Initial import of Sylpheed (GTK2 version).


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Elkhart General Hospital's HME Summer Elective Program offers medical students, who have completed one year of study, an opportunity to spend eight to ten weeks working with EGH medical staff and personnel learning about the local health care system.
Students participate in various departments and specialties in the hospital, as well as private practice offices.
The HME Program is sponsored by the Indiana Health & Hospital Association (IHHA) and the Indiana State Medical Association and is endorsed by the Indiana University School of Medicine. This program operates independently from the Indiana University School of Medicine.
For more information on any of these programs, please call CME at 574-389-4826.


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