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PubMed1993

Oral contraceptives. Are drug interactions of clinical significance?

There is a large quantity of literature on drug interactions with oral contraceptive (OC) steroids although their incidence is not known. The potential clinical significance of some interactions makes it important for all prescribing doctors and dentists to have some knowledge of the topic. Interactions may be divided into those in which OC effectiveness is impaired, causing breakthrough bleeding or pregnancy, those in which OC activity is enhanced by other drugs and those in which OCs interfere with the metabolism or activity of other therapeutic agents. Consideration of their pharmacology indicates that impairment of OC effect is most likely to be due to interference with ethinylestradiol. This is because this compound is sulphated in the gut wall, hydroxylated and glucuronidated in the liver, and undergoes enterohepatic recirculation. The progestogens are only metabolised in the liver and have no significant enterohepatic recirculation. Protein binding interactions are rarely of clinical importance. OC plasma concentrations may be reduced by induction of hepatic metabolism in the case of griseofulvin, rifampicin (rifampin) and several anticonvulsant drugs; valproic acid (sodium valproate) does not have this effect. Antibiotics may interfere with enterohepatic recirculation of ethinylestradiol and reduce plasma levels of active hormone. This is probably only of significance in a subgroup of women who may sometimes be suspected on history, but cannot be identified by any diagnostic test. Reasons for differences between case reports and formal studies of interactions with antibiotics are discussed. Plasma concentrations of ethinylestradiol may be increased by ascorbic acid (vitamin C) and paracetamol (acetaminophen) which compete with it for sulphation in the gut wall. Theoretically, problems may arise if these agents are stopped suddenly. Imidazole antifungal agents can inhibit ethinylestradiol metabolism and increase its plasma concentrations but the clinical significance of this is unknown. OCs have been shown to inhibit metabolism of many therapeutic drugs and increase their plasma concentrations. This may be of clinical significance in the case of benzodiazepines which are hydroxylated in the liver, but clinical effects are less certain with the other agents. OCs may induce metabolism of other drugs which are glucuronidated, including some benzodiazepines and analgesics. The clinical significance of this type of interaction is also unknown. It is suggested that all prescribers should remember to ask about OCs when taking a drug history and to consider the possibility of interactions with other drugs.

Anti-Bacterial Agents↗
PubMed2004

Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts.

Reactive oxygen species play a central role in myocardial ischemic injury and are a target for therapeutic intervention. Vitamin C is an essential antioxidant yet difficult to deliver in pharmacologic concentration to the myocardium. We found that adult rat cardiomyocytes accumulate vitamin C by transporting dehydroascorbic acid (DHA), the oxidized form of vitamin C, but do not transport ascorbic acid. Loading cells with vitamin C by DHA treatment resulted in resistance to hypoxia- and hypoxia/reoxygenation-induced cell death associated with the quenching of reactive oxygen species. When rats were injected with DHA before coronary occlusion, the ascorbic acid content in the heart was six to eight times higher than in untreated controls and myocardial infarction was reduced by 62%. DHA also provided significant protection when administered intravenously 2 h after coronary occlusion. In cardiomyocytes subjected to hypoxia/reoxygenation, DHA treatment resulted in decreased apoptosis associated with inhibition of Bax expression, caspase-3 activation, and cytochrome c translocation into the cytoplasm. DHA treatment also inhibited Jak2, STAT1, and STAT5 phosphorylation, and increased STAT3 phosphorylation, in hypoxic cardiomyocytes and ischemic myocardial tissue. Our findings suggest that DHA may be useful as a cardioprotectant in ischemic heart disease.

Animals↗
PubMed2001

Liposomal antioxidants in combating ischemia-reperfusion injury in rat brain.

Liposome-encapsulated antioxidants have been tested in vivo to prevent oxidative attack during cerebral ischemia and reperfusion. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. From the therapeutic point of view free chemical antioxidants were almost ineffective to protect cerebral tissues from those oxidative attacks. Thus an attempt has been made to prevent the oxidative damage due to the cerebral ischemic insult by the introduction of chemical antioxidants, ascorbic acid and alpha-tocopherol either encapsulated or intercalated in small unilamellar liposomes. The effectiveness of antioxidant-loaded liposomes was tested against an experimental in vivo rat model of global cerebral ischemia. Oxidative free radical attack on cerebral tissues by the ischemic insult and brief reperfusion was accounted for by the amount of diene production per unit of tissue protein. Diene production in ischemic reperfused rat brain increases almost twofold over that of the normal rats. Prevention of excess diene production has been attributed to rats when they were treated either with L-ascorbic acid-encapsulated liposomes or alpha-tocopherol intercalated liposomes 2 hours prior to the cerebral ischemic insult. Complete restriction of excess diene generation has also been achieved when a mixture of alpha-tocopherol and L-ascorbic acid-encapsulated liposomes were injected 3 hours before the ischemic infraction.

Animals↗
PubMed1999

Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell-free systems and inflamed human colorectal biopsies.

BACKGROUND: The therapeutic efficacy of 5-aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties. AIM: To compare in vitro the antioxidant effects of conventional drugs (5-aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4-aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N-acetylcysteine, glutathione, verapamil). METHODS: Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell-free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol-amplified chemiluminescence. RESULTS: 5-aminosalicylic acid and balsalazide were more potent antioxidants than 4-aminosalicylic acid or N-acetyl-5-aminosalicylic acid in cell-free systems. 5-aminosalicylic acid (20 mM) and balsalazide (20 mM) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4-aminosalicylic acid (20 mM). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 mM) inhibited chemiluminescence by 100% in cell-free systems and by 60% in rectal biopsies. N-acetyl cysteine (10 mM), and both oxidized and reduced glutathione (10 mM), completely inhibited chemiluminescence in cell-free systems, but not with rectal biopsies. CONCLUSIONS: The antioxidant effects of compounds varies between cell-free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy.

Adrenal Cortex Hormones↗
PubMed1993

Ascorbigen and other indole-derived compounds from Brassica vegetables and their analogs as anticarcinogenic and immunomodulating agents.

Searches for the natural compounds that determine the anticarcinogenic properties of a cruciferous-vegetable diet, revealed the products of alkaloid glucobrassicin biotransformations; among these, ascorbigen, an indole-containing derivative of L-ascorbic acid, was found to be the most abundant. Study of chemical properties of ascorbigen showed that it is capable of different transformations in acidic (including gastric juice) and slightly alkaline (including blood) media. The stable and unstable products of ascorbigen transformation determine the biological properties of the compound. The most important product of ascorbigen transformation in gastric juice is 5,11-dihydroindolo[3,2-b]-carbazole, with a binding affinity to the Ah receptor only 3.7 x 10(-2) lower than that of tetrachlorodibenzodioxin. This compound may be responsible for modifying P450 enzyme activities. Ascorbigen and its analogs are available synthetically. Their biological evaluation showed that some of the compounds of these series are immunomodulators. The most active is N-methylascorbigen, which demonstrates therapeutic effects (inhibition of tumor growth, protection of animals from bacterial and viral infections). The immunomodulatory activity of natural ascorbigen may be an additional factor of importance for the anticarcinogenic properties of a cruciferous-vegetable diet.

Adjuvants, Immunologic↗
PubMed2001

Chelating activity of advanced glycation end-product inhibitors.

The advanced glycation end-product (AGE) hypothesis proposes that accelerated chemical modification of proteins by glucose during hyperglycemia contributes to the pathogenesis of diabetic complications. The two most commonly measured AGEs, N(epsilon)-(carboxymethyl)lysine and pentosidine, are glycoxidation products, formed from glucose by sequential glycation and autoxidation reactions. Although several compounds have been developed as AGE inhibitors and are being tested in animal models of diabetes and in clinical trials, the mechanism of action of these inhibitors is poorly understood. In general, they are thought to function as nucleophilic traps for reactive carbonyl intermediates in the formation of AGEs; however alternative mechanisms of actions, such as chelation, have not been rigorously examined. To distinguish between the carbonyl trapping and antioxidant activity of AGE inhibitors, we have measured the chelating activity of the inhibitors by determining the concentration required for 50% inhibition of the rate of copper-catalyzed autoxidation of ascorbic acid in phosphate buffer. All AGE inhibitors studied were chelators of copper, as measured by inhibition of metal-catalyzed autoxidation of ascorbate. Apparent binding constants for copper ranged from approximately 2 mm for aminoguanidine and pyridoxamine, to 10-100 microm for carnosine, phenazinediamine, OPB-9195 and tenilsetam. The AGE-breakers, phenacylthiazolium and phenacyldimethylthiazolium bromide, and their hydrolysis products, were among the most potent inhibitors of ascorbate oxidation. We conclude that, at millimolar concentrations of AGE inhibitors used in many in vitro studies, inhibition of AGE formation results primarily from the chelating or antioxidant activity of the AGE inhibitors, rather than their carbonyl trapping activity. Further, at therapeutic concentrations, the chelating activity of AGE inhibitors and AGE-breakers may contribute to their inhibition of AGE formation and protection against development of diabetic complications.

Amines↗
PubMed1997

Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. II. Relationships to cardiovascular risk factors and prevalent cardiovascular disease.

Coagulation factor activity (fibrinogen, VII, VIII and IX), coagulation inhibitor activity (antithrombin, protein C, protein S), and coagulation activation markers (prothrombin fragment F1, 2; thrombin-antithrombin complexes) were measured in 746 men and 816 women aged 25-74 years, randomly sampled from the north Glasgow population in the Third MONICA Survey. After age-adjustment, significant associations with cardiovascular risk factors were observed. Serum cholesterol and triglyceride were associated with increases in factors VII and IX, as well as antithrombin, protein C and protein S; and with increased fibrinogen and factor VIII in women. Apart from factor VIII (related to blood pressure in men, but not in women), similar associations were observed for blood pressure and body mass index. Smoking status and/or smoking markers were related to fibrinogen, factor IX, antithrombin and protein S. Alcohol intake was related to protein S, and inversely to fibrinogen and antithrombin in men. Low social class was associated with fibrinogen, factor VIII, factor IX, and with antithrombin, protein S, and low protein C in men. Serum vitamin C was associated inversely with coagulation factors and coagulation inhibitors. The only associations of activation markers were with low serum vitamin C, and with alcohol consumption and low social class in men. Prevalent cardiovascular disease was associated only with fibrinogen. These associations of coagulation factors and inhibitors with cardiovascular risk factors are plausibly relevant to thrombotic risk in cardiovascular disease. In general, 'worse' values of risk factors are associated with increased plasma levels of both coagulation factors and inhibitors, without significant increase in coagulation activation markers. However, the association of lower serum vitamin C with increased coagulation activation markers is of potential therapeutic interest.

Adult↗
PubMed2001

Antioxidants in exercise nutrition.

Physical exercise may be associated with a 10- to 20-fold increase in whole body oxygen uptake. Oxygen flux in the active peripheral skeletal muscle fibres may increase by as much as 100- to 200-fold during exercise. Studies during the past 2 decades suggest that during strenuous exercise, generation of reactive oxygen species (ROS) is elevated to a level that overwhelms tissue antioxidant defence systems. The result is oxidative stress. The magnitude of the stress depends on the ability of the tissues to detoxify ROS, that is, antioxidant defences. Antioxidants produced by the body act in concert with their exogenous, mainly dietary, counterparts to provide protection against the ravages of reactive oxygen as well as nitrogen species. Antioxidant supplementation is likely to provide beneficial effects against exercise-induced oxidative tissue damage. While universal recommendations specifying types and dosages of antioxidants are difficult to make, it would be prudent for competitive athletes routinely engaged in strenuous exercise to seek an estimate of individual requirement. A new dimension in oxidant biology has recently unfolded. Although excessive oxidants may cause damage to tissues, lower levels of oxidants in biological cells may act as messenger molecules enabling the function of numerous physiological processes. It is plausible that some exercise-induced beneficial effects are actually oxidant-mediated. Such developments call for an even more careful analysis of the overall significance of types and amounts of antioxidants in diet. While these complexities pose significant challenges, experts agree that if used prudently, oxidants and antioxidants may serve as potent therapeutic tools. Efforts to determine individual needs of athletes and a balanced diet rich in antioxidant supplements are highly recommended.

Animals↗
PubMed1999

Hyperglycaemia: the bridge between non-enzymatic glycation and oxidative stress in the pathogenesis of diabetic complications.

It is generally accepted that high glucose levels for many years are a primary cause of most long-term complications in diabetic patients. Many studies suggest that the central features of diabetic complications are caused by the hyperglycaemia-accelerated formation of non-enzymatic glycated products. Non-enzymatic glycation, however, has been recently demonstrated to be linked to glucose auto-oxidative process. At the same time glycated proteins have been shown to be a source of free radicals. These findings raised the hypothesis of a link between oxidative stress and the development of diabetic complications. Some studies have recently demonstrated that antioxidants, such as vitamin C and E, may reduce in vitro and in vivo protein glycation. At the same time some antioxidants act as scavengers of the free radicals produced by non-enzymatic glycation in vitro. Such studies may lead to therapeutic approaches for limiting the damage from glycation and oxidation reactions and for complementing existing therapy for treatment of the complications of diabetes.

Ascorbic Acid↗
PubMedDate not supplied

Urinary oxalate excretion increases in home parenteral nutrition patients on a higher intravenous ascorbic acid dose.

BACKGROUND: Vitamin C can be metabolized to oxalate. Case reports have suggested an association between IV vitamin C and urinary oxalate excretion. Recently, the US Food and Drug Administration required the dose of vitamin C in IV multivitamin preparations to be increased from 100 mg to 200 mg/d. We compared the urinary oxalate excretion level in stable home total parenteral nutrition (TPN) patients receiving both doses of vitamin C. METHODS: Each participant provided a 24-hour urine sample for oxalate determination on the vitamin C dose (100 mg/d), and again after at least 1 month on the increased vitamin C dose (200 mg/d). A 2-day diet diary was completed covering the day before and the day of the urine collection and was analyzed for oxalate and vitamin C content. Comparisons were made using Student paired t test and Wilcoxon signed rank. RESULTS: Thirteen patients (7 males/6 females) aged 63.1 +/- 12.2 years who had no history of nephrolithiasis and had received TPN for 55.9 +/- 78.8 months were enrolled. The most common indication for TPN was short bowel syndrome (38.5%). Eight patients had an intact colon. Urinary oxalate excretion increased on the 200-mg vitamin C dose, from 0.34 +/- 0.13 to 0.44 +/- 0.17 mmol/d (mean increase = 0.10 mmol/d; p = .04; 95% confidence interval 0.004 to 0.19 mmol/d). Oral intake of vitamin C and oxalate did not differ between the 2 collection periods. CONCLUSIONS: In therapeutically used doses, IV vitamin C increases urinary oxalate excretion, potentially predisposing susceptible individuals to nephrolithiasis. This factor should be considered in patients receiving home TPN.

Adult↗
PubMed1994

[The concentration of ascorbic acid, glucose and cortisol in the blood plasma of sheep and the excretion of ascorbic acid in the urine after i.v. administration of the compound].

In lambs, adult female sheep and wethers the influence of the intravenous injection of ascorbic acid (AA) in a dose of 10, 20 or 30 mg/kg body weight (b.w.) on the concentration of AA in the plasma up to 420 minutes thereafter was analysed. Further the concentration of glucose respectively of cortisol in the plasma was determined in some experiments. The results can be used as a basis for investigations in sheep with infectious and parasitic diseases for the determination of the degree of the saturation of the body with AA. For therapeutic purposes the repeated application of a dose of 20 mg AA/kg b.w. is recommended. In wethers a dose dependent excretion of AA in the urine after an i.v. injection of a dose of 10, 20 or 30 mg/kg b.w. was observed. The injection of ACTH, cortisol, adrenaline and noradrenaline had no substantial influence on the concentration of AA in the plasma. In the course of 24 hours there was no alteration in the concentration of AA in the plasma.

Animals↗
PubMed1977

Inhibition of urease by miscellaneous ions and compounds. Implications for the therapy of infection-induced urolithiasis.

One hundred forty-eight drugs and other organic and inorganic substances were screened for their ability to inhibit the enzyme urease in an in vitro system modeled on infected urine. The reported urease-inhibiting properties of ascorbic acid, tetracyclines, and sulfanilamide were not confirmed. At least 50 per cent inhibition was observed in the presence of kanamvcin, hydroxguanidine, benzoquinone, 1,2-naphthaquinone-4-sulfonate, chloramine-T, N-bromoacetamide, copper, mercury, and fluoride. It is, however, unlikely that therapeutically effective concentrations can be attained in urine without giving dosages likely to result in toxic effects. Hydroxyurea, at the dose level used in cytotoxic therapy, may be expected to produce effective inhibition of bacterial urease in the urinary tract, providing renal function is unimpaired and providing urinary volume does not exceed 1 liter per 24 hr. Acetohydroxamic acid is potentially the most useful drug for the treatment of infection-induced urinary stone disease available at present.

Bacterial Infections↗
PubMed1982

Vitamin C and cancer: an overview.

The outcome of every cancer illness is determined to a significant extent by the inherent resistance of the individual patient to his or her disease. There is increasing recognition that resistance to cancer depends, to a certain extent, upon the availability of certain nutritional factors, of which ascorbic acid appears to be the most important. Ascorbic acid protects against the destructive effects of malignant invasiveness by stabilizing the ground substance and enhancing collagen encapsulation. It is also involved in the mechanisms of both cell-mediated and humoral immunity including the production of interferon, and other factors either known or thought to be involved collectively in host resistance to neoplasia. There is also some recent evidence suggesting that ascorbate exerts a selective cytotoxic effect against malignant cells. All these observations indicate that supplemental ascorbate should be of some therapeutic value in the treatment of cancer. Clinical trials conducted over the last decade are briefly reviewed, and the balance of evidence supports this contention. It is predicted that in the not-to-distant future, supplemental ascorbate will attain an established place in all comprehensive cancer treatment regimes.

Adenocarcinoma, Scirrhous↗
PubMed1992

Ascorbic acid prevents oxidative stress in glutathione-deficient mice: effects on lung type 2 cell lamellar bodies, lung surfactant, and skeletal muscle.

Glutathione deficiency in adult mice leads to lung type 2 cell lamellar body and mitochondrial damage; as reported here, these effects are associated with marked decrease of the levels of phosphatidylcholine (the main component of lung surfactant) in the lung and the bronchoalveolar lining fluid. Severe mitochondrial damage was also found in skeletal muscle. Treatment with ascorbate (1-2 mmol per kg of body weight per day), which led to greatly increased (approximately 2-fold) levels of lung and muscle mitochondrial glutathione, prevented damage to lamellar bodies and mitochondria as well as the decline of phosphatidylcholine levels in lung and alveolar lining fluid. The findings indicate that glutathione deficiency leads to depletion of lung surfactant and that this can be prevented with ascorbate. Administration of ascorbate spares glutathione and prevents cellular damage. Lamellar body degeneration in glutathione deficiency appears to be associated with oxidative damage to the perilamellar membrane, which contains the enzymes required for phosphatidylcholine synthesis. It is notable that although severe glutathione deficiency is lethal to newborn rats, which apparently do not synthesize ascorbate, adult mice are better able to survive such a deficiency because they can synthesize ascorbate. The present studies, which suggest that high doses of ascorbate may be of therapeutic value, emphasize that ascorbate and glutathione have actions in common and that they function together in a physiologically significant antioxidant system.

Animals↗
PubMed2005

Antitumor effect of nutrient synergy on human osteosarcoma cells U-2OS, MNNG-HOS and Ewing's sarcoma SK-ES.1.

Current treatment of osteosarcoma is associated with poor prognosis, especially due to the increased risk of developing other cancers with chemotherapy. Therefore, new, safe and effective treatment strategies are needed. We investigated the effect of a unique mixture of nutrients containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate (EGCG) on human osteosarcoma cell lines U-2OS, MNNG-HOS, and Ewing's sarcoma SK-ES-1 by measuring: cell proliferation, expression of matrix metalloproteinase-2 (MMP-2), MMP-9, and invasive and angiogenesis potential. Cell proliferation was evaluated by MTT assay, matrix metalloproteinases (MMP) expression by gelatinase zymography, VEGF expression by ELISA, and invasion through Matrigel. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) to study enhanced MMP and VEGF expression. The invasion of osteosarcoma U-2OS and MNNG-HOS cells through Matrigel was significantly reduced in a dose-dependent fashion, with 100% inhibition of invasion of U-2OS cells at 100 microg/ml, and MNNG cells at 50 microg/ml concentration of the synergistically acting nutrient mixture. Ewing's sarcoma SK-ES-1 cells were not invasive. Nutrient synergy (NS) exhibited a dose response antiproliferative effect on osteosarcoma U-2OS cells, reaching 67% at 1000 microg/ml of NS; no significant suppression of cell proliferation was seen with MNNG or Ewing's sarcoma cells. Zymography showed dose-dependent inhibition of MMP secretion by all three cell lines in the presence of NS. VEGF secretion by U-2OS cells was completely blocked at 500 microg/ml of NS. Our results suggest NS is an excellent candidate for therapeutic use in the treatment of osteosarcoma, by inhibiting cancer cell invasion, and secretion of MMPs and VEGF, all critical parameters for cancer control and prevention.

Arginine↗
PubMed2000

Virological and immunological effects of antioxidant treatment in patients with HIV infection.

BACKGROUND: Intracellular oxidative stress in CD4+ lymphocytes due to disturbed glutathione homeostasis may lead to impaired lymphocyte functions and enhanced HIV replication in patients with HIV infection, especially in those with advanced immunodeficiency. The aim of the present study was to assess whether short-term, high-dose antioxidant treatment might have effects on immunological and virological parameters in patients with HIV infection. MATERIALS AND METHODS: In this pilot study, we examined virological and immunological effects of antioxidant combination treatment for 6 days with high doses of N-acetylcysteine (NAC) and vitamin C in 8 patients with HIV infection. The following were assayed before, during and after antioxidant treatment: HIV RNA plasma levels; numbers of CD4+, CD8+, and CD14+ leukocytes in blood; plasma thiols; intracellular glutathione redox status in CD4+ lymphocytes and CD14+ monocytes; lymphocyte proliferation; lymphocyte apoptosis and plasma levels of tumour necrosis factor (TNF)alpha; soluble TNF receptors and neopterin in plasma. RESULTS: No significant changes in HIV RNA plasma levels or CD4+ lymphocyte counts in blood were noted during antioxidant treatment in the patient group. However, in the 5 patients with the most advanced immunodeficiency (CD4+ lymphocyte counts < 200 x 106 L(-1)), a significant rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level of 0.8 log, an enhanced lymphocyte proliferation and an increased level of intracellular glutathione in CD4+ lymphocytes were found. No change in lymphocyte apoptosis was noted. CONCLUSIONS: Short-term, high-dose combination treatment with NAC and vitamin C in patients with HIV infection and advanced immunodeficiency lead to immunological and virological effects that might be of therapeutic value.

Acetylcysteine↗
PubMed1987

Circadian monitoring of gastric juice mutagenicity.

The circadian monitoring of intragastric pH and of the mutagenicity of 440 gastric juice samples collected hourly from 22 subjects provided evidence that, irrespective of diagnosis and treatment, a weak yet consistent increase in revertants can be detected in his- Salmonella typhimurium strains during the 3-4-h periods following each meal. The recorded mutagenic activity was not related to the histidine content of gastric juice, was due to thermostable components and was not significantly inhibited by administration of vitamin C. Various genetic mechanisms were involved, which were different from those consequent to the artificial supplementation of gastric juice with sodium nitrite. Treatment with a histamine H2-receptor antagonist (famotidine), either at dinner or at bedtime, was followed by a nocturnal plateau of mutagenicity. However, such effect was not due to mutagenicity of the drug or of its derivatives, but to the therapeutic rise in pH associated with its antisecretory activity.

Adult↗