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[The effect of drugs on laboratory diagnosis. The effect of ascorbic acid on selected automatic laboratory methods].

The paper presents further investigations for a critical survey on the influences of drugs on laboratory methods. In controversion to the meanings you can find in the literature that ascorbic acid is most one of the important drugs to interfere with laboratory results we couldn't see in our systematical experimental investigation such results. Only in very extremly cases it seems to be right. Selected parameters of clinical chemistry (glucose, lactic dehydrogenase, aspartal-aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumine, creatinine, butanol extractable iodine, ferrum) show under therapeutic conditions no influences of ascorbic acid, which can lead to diagnostic or therapeutic false interpretations. Above all the often mentioned example that glucose estimations in blood (reduction methods) can disturb if ascorbic acid is present, is abstracted in an uncritical manner how our experimental results may show.

Ascorbic Acid↗

Pretreatment with intravenous ascorbic acid preserves endothelial function during acute hyperglycaemia (R1).

1. Acute hyperglycaemia may impair endothelial function. Ascorbic acid (AA), administered intra-arterially, has been reported to improve endothelium-dependent vasodilatation during a forearm hyperglycaemic clamp. Using a randomized, double-blind, placebo-controlled, cross-over study, we investigated the potential for intravenous ascorbic acid to modify the endothelial response to acute systemic hyperglycaemia in humans. 2. Nine healthy male volunteers were recruited from the hospital staff. Endothelial function was determined by measuring the forearm blood flow responses to intrabrachial infusions of endothelium-dependent (ED) and endothelium-independent (EID) vasodilators. The endothelial function index (EFI) was derived from the ratio of ED and EID vasodilatation. Haemodynamic and endothelial function measurements were performed at baseline and then repeated 2 h after a systemic hyperglycaemic clamp (14 mmol/L). The subjects, studied on two separate occasions, were randomized to placebo or 2 g intravenous ascorbic acid prior to the initiation of hyperglycaemia. 3. After systemic hyperglycaemia with placebo pretreatment, the EFI fell from 1.08 +/- 0.21 to 0.74 +/- 0.13 (difference (95% confidence interval): 0.34 (0.20, 0.47); P < 0.001). When subjects were pretreated with ascorbic acid, the EFI was not affected by hyperglycaemia (1.11 +/- 0.21 to 1.12 +/- 0.17; P = 0.938). This difference between placebo and ascorbic acid was significant (P < 0.001). Plasma ascorbate concentrations decreased during hyperglycaemia and correlated directly with the reduction in the EFI (r = 0.798; P < 0.001). 4. Pretreatment with an intravenous bolus of ascorbic acid can prevent endothelial dysfunction during acute systemic hyperglycaemia. Therefore, ascorbic acid may have potential therapeutic use in clinical situations where acute hyperglycaemia may be a complication.

Acute Disease↗

The influence of ascorbic acid and lactose on the interaction of iron with each of cobalt and zinc during intestinal absorption.

The effect of ascorbic acid and lactose on the interaction between iron and each of zinc or copper during intestinal absorption was studied in normal and iron-deficient rats. It was found that addition of cobalt to the iron dose inhibited absorption of iron to 42% in normal rats and to 46.7% in iron deficient ones. The presence of zinc with the iron dose also inhibited absorption of iron to 34.6% in normal rats and to 32.2% in case of the iron deficient ones. The addition of ascorbic acid to the combined dose of Fe + Co enhanced absorption of iron by five times in normal and in iron deficient rats. In case of the combined dose of Fe + Zn the enhancement was four times in normal rats and six times in iron deficient ones. The addition of lactose to the combined dose of either Fe + Co or Fe + Zn corrected the inhibiting action of either cobalt or zinc on iron absorption. Based on these findings, it is recommended that ascorbic acid and lactose be added to therapeutic multimineral preparations.

Animals↗

Differential effects of acute administration of haloperidol and clozapine on ethanol-induced ascorbic acid release in rat striatum.

Antipsychotic drugs were initially considered to act predominantly through their antagonism at dopamine D(2)-like receptors. However, reports have demonstrated that the typical neuroleptic drug haloperidol and the atypical neuroleptic drug clozapine showed differential actions in clinical, behavioral and biochemical studies. Since ascorbic acid has a potential usefulness in psychological therapeutics, the present study investigates the actions of these two drugs on ethanol-induced ascorbic acid release in the striatum in order to help explain the different mechanisms of these drugs. The results showed that clozapine, at the doses of 15 and 30 mg/kg, i.p., had no effect on basal ascorbic acid release. However, a synergistic tendency at a dose of 15 mg/kg and a significant synergism at a dose of 30 mg/kg were observed on ascorbic acid release when clozapine was used with ethanol. In contrast, haloperidol, at the doses of 0.5, 1.0 and 2.0 mg/kg, i.p., administered alone did not affect the basal release of striatal ascorbic acid, and when used together with ethanol had neither a potentiating nor an antagonizing effect on ethanol-induced ascorbic acid release. Chlorpromazine, a nonselective dopamine receptor antagonist, at the dose of 5 mg/kg, i.p., affected neither the basal nor the ethanol-induced ascorbic acid release. Ritanserin, a 5-HT(2) receptor antagonist, at the dose of 1 mg/kg, s.c., significantly antagonized ethanol-induced ascorbic acid release. These results demonstrate that clozapine dose-dependently potentiates the stimulatory effect of ethanol on striatal ascorbic acid release and this effect of clozapine may not be related to its dopamine D(2) receptor antagonism.

Animals↗

Treatment of acute lead intoxication. A quantitative comparison of a number of chelating agents.

The efficacy of several chelating agents in alleviating acute lead intoxication has been investigated in male Swiss mice. The relative effectiveness of diethylenetriaminepentaacetic acid (DTPA), ethyleneglycolbis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), cyclohexanediaminetetraacetic acid (CDTA), L-cysteine, N-acetyl-L-cysteine (NAC), ascorbic acid, sodium diethyldithiocarbamate (DDC), 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-1-propanesulfonate (DMPS) in reducing lethality of lead was examined. Significant increases in survival were noted with CDTA, ascorbic acid, DMSA, and DMPS. Therapeutic effectiveness (TEF) was determined for these compounds; TEF for ethylenediaminetetraacetic acid (EDTA) and for 2,3-dimercaptopropanol (BAL) was also determined; CDTA (2.33) and EDTA (1.73) showed the highest values. In subsequent experiments, the effect of the chelating agents on the distribution and excretion of lead was investigated. Lead acetate trihydrate was administered subcutaneously at doses of 37.8 mmol/kg (LD50), and fifteen minutes later, chelators were given intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. EDTA, DTPA and CDTA were the most effective agents in increasing the urinary excretion of lead, whereas DTPA, CDTA, and DDC increased significantly the fecal excretion of lead. EDTA, DDC, and CDTA were the most effective chelators in reducing the concentration of lead found in various tissues. On the basis of these results, CDTA may be considered as an alternative in the treatment of acute lead poisoning.

Animals↗

Ascorbic acid dynamics in the seriously ill and injured.

BACKGROUND: In addition to the known beneficial effects of ascorbic acid on wound healing and the immune response, it is also a potent extracellular antioxidant. Recent work in septic rats suggests that high-dose ascorbic acid total parenteral nutrition (TPN) supplementation may protect cells from free radical injury and improve survival. In this study, we determined ascorbic acid levels in the immediate post-injury/illness period and evaluated the ability of early short-term high levels of ascorbic acid in TPN to normalize plasma levels. MATERIALS AND METHODS: Ascorbic acid levels were determined in 12 critically injured patients and 2 patients with severe surgical infections. Each patient received TPN supplemented with increasing doses of ascorbic acid over a 6-day period. Therapeutic responses were determined by plasma and urine measurements using high-pressure liquid chromatography. RESULTS: The initial mean +/- SEM baseline plasma ascorbic acid concentration was depressed (0.11 +/- 0.03 mg/dl) and unresponsive following 2 days on 300 mg/day supplementation (0.14 +/- 0.03; P = 1.0) and only approached low normal plasma levels following 2 days on 1000 mg/day (0.32 +/- 0.08; P = 0.36). A significant increase was noted following 2 days on 3000 mg/day (1.2 +/- 0.03; P = 0.005). CONCLUSION: We confirmed extremely low plasma levels of ascorbic acid following trauma and infection. Maximal early repletion of this vitamin requires rapid pool filling early in the post-injury period using supraphysiologic doses for 3 or more days.

Adult↗

Effect of a new synthetic ascorbic acid derivative as a free radical scavenger on the development of acute pancreatitis in mice.

The therapeutic effects of CV 3611, a new synthetic free radical scavenger prepared from an ascorbic acid derivative, on choline deficient, ethionine enriched (CDE) diet induced acute pancreatitis in mice were evaluated and compared with those of superoxide dismutase. Time/course studies after subcutaneous injection of CV 3611 in normal mice showed a peak plasma concentration of mean (SEM) 0.54 (0.09) micrograms/ml at one hour, with a gradual decrease over the next 10 hours, while a peak concentration in pancreatic tissue of mean (SEM) 425 (33) ng/g tissue was achieved at three hours and the drug was undetectable at 12 hours. Survival rates and activities of pancreatic enzymes (amylase, lipase, elastase I) were compared in control mice and animals that received CV 3611 before or at the time of feeding the CDE diet. The survival rate was observed in a no treatment group and mice given pretreatment or treatment with CV 3611 or superoxide dismutase. The survival rate was significantly better in the treatment group given CV 3611 (p less than 0.02), but superoxide dismutase had no significant effect on survival. The increases in the three serum enzyme activities were significantly less at 48 hours in the groups given pretreatment or treatment with CV 3611 than in the no treatment group. These results indicate that CV 3611, which has been proved to pass through the cell membrane and to have a long half life in plasma and tissue, had an important therapeutic effect on the development of acute pancreatitis. They also suggest that oxygen derived free radicals may play an important role in the development of acute pancreatitis.

Amylases↗

Effect of peritoneal dialysis on plasma levels of ascorbic acid.

The effect of peritoneal dialysis on plasma ascorbate levels was investigated in 32 patients suffering from end-stage renal disease. Our studies demonstrated a high peritoneal clearance of ascorbic acid resulting in a significant loss into the dialysate. The quantity of ascorbic acid lost by patients undergoing peritoneal dialysis was proportional to the predialysis ascorbic acid levels. Since the ascorbic acid lost from the plasma during peritoneal dialysis is not adequately replaced by dietary consumption of vitamin C, patients undergoing chronic peritoneal dialysis should receive ascorbic acid supplementation as an important part of their therapeutic regimen.

Adult↗

Effect of some commonly prescribed drugs on certain chemistry tests.

Of the 44 commonly prescribed drugs listed only ascorbic acid, at the upper end of its therapeutic range, significantly affected any (glucose, uric acid) of the twenty-three more frequently requested tests measured in the clinical chemistry laboratory. Acetaminophen, acetylsalicylic acid, ascorbic acid, nitrofurantoin, methyldopa and tetracycline at five times the upper end of their therapeutic ranges individually produced consistently significant effects on one or more of the following tests: glucose, bilirubin, carbon dioxide, calcium, cholesterol, uric acid and aspartate aminotransferase. When drugs are added to lyophilized human serum and to fresh human serum in similar concentrations, their effects on clinical chemistry tests performed on these two different sera are not always the same.

Acetaminophen↗

"Nanobacterium sanguineum"--is it a new life-form in search of human ailment or commensal: overview of its transmissibility and chemical means of intervention.

Morphological, cultural, and immuno-histochemical characteristics of "Nanobacterium sanguineum" (NB) described in the literature are reviewed. NB is reported to be a motile, Gram negative organism that divides by binary fission within a calcium-coated slimy shell; this yeast-like shell replicates by budding. It measures between 20 and 200 nm with a unique structure containing 16S ribosomal RNA. NB has been observed by electron microscopy in coronary artery plaques (CAD) and in kidney stones (KS) found in renal diseases. On the basis of supportive literature, we suggest that NB is not only present in the human body but also has auxiliary association with human ailments without a specific etiological role; anti-NB antibody has been detected in subjects with calcified lesions and inflammation in diverse ailments including choriodecidual inflammation in pregnancy, ovarian cancers, arthritis and even Alzheimer's disease. More recent report on the detection and vertical transmission of NB antigen and anti-NB antibody in HIV-infected mothers supports the view that NB might be an important opportunistic infective agent contributing to HIV pathology; we note that the presence of viable and transmitting NB was not studied and suggest further studies to establish vertical transmission of NB in HIV-infected persons. On the basis of the foregoing we suggest that NB possibly exacerbates human ailments and raise the question: Is NB a new life-form in search of human ailment or a commensal organism? Recognizing the presence of NB in the human body, we discuss clinical trials, reported in the literature relevant to its eradication, with a rectal suppository containing very high amounts of disodium EDTA and tetracycline. We suggest that tetracycline in this formulation acted in combination with EDTA, more as a chelating agent than an antibiotic; oxytetracycline- a non-chelating form of tetracycline-does not inhibit or kill NB. Evaluation of anti-NB effect of orally administrable and potentially safer as well as therapeutically more acceptable chelating agent -ascorbic acid, acting alone or in combination with antibiotics-that eradicates another slime forming bacterium - Pseudomonas aeruginosa - in children with cystic fibrosis, is suggested.

Bacteria↗

Role of reactive oxygen species in male infertility.

Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly H2O2 and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of anti-oxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.

Antioxidants↗

In vitro antioxidant studies of Sphaeranthus indicus (Linn).

The free radical scavenging potential of the plant S. indicus was studied by using different antioxidant models of screening. The ethanolic extract at 1000 microg/ml showed maximum scavenging of the radical cation, 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS) observed upto 41.99% followed by the scavenging of the stable radical 1,1-diphenyl, 2-picryl hydrazyl (DPPH) (33.27%), superoxide dismutase (25.14%) and nitric oxide radical (22.36%) at the same concentration. However, the extract showed only moderate scavenging activity of iron chelation (14.2%). Total antioxidant capacity of the extract was found to be 160.85 nmol/g ascorbic acid. The results justify the therapeutic applications of the plant in the indigenous system of medicine, augmenting its therapeutic value.

Antioxidants↗

Natural treatment of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States, affecting approximately 14 percent of the population. CRS is a challenging condition to treat, partly due to its multifaceted, poorly understood pathophysiology. Treatment goals include maintaining open drainage and decreasing inflammation while improving tissue integrity and limiting causative factors. This review covers the etiology, pathology, and diagnosis of CRS, as well as mainstream and alternative treatments. Discussion of alternative therapeutics includes nutrients and botanicals (ascorbic acid, bromelain, N-acetylcysteine, quercetin, undecylenic acid, and Urtica dioica and other herbal medicines) and procedures (nasal irrigation and naso-sympatico treatments). The influences of diet and air quality on CRS are also discussed.

Chronic Disease↗

Inhibition of bacterially mediated N-nitrosation by ascorbate: therapeutic and mechanistic considerations.

Ascorbate is known to inhibit the acid-catalysed N-nitrosation reactions of nitrite in the normally acid stomach, suggesting a useful therapeutic application of this compound to reduce exposure to the carcinogenic products of such reactions. However, in the achlorhydric stomach, which is particularly predisposed to cancer, increased exposure to endogenous N-nitroso compounds may result from bacterially catalysed reactions. The mechanism of these bacterially mediated reactions is only just beginning to be understood, and, indeed, more than one such mechanism may exist. Despite its usual lack of reactivity towards nitrite at neutral pH, ascorbate proved to be a potent inhibitor of the bacterially mediated (Pseudomonas aeruginosa) nitrosation of morpholine, competing with morpholine for the nitrosating agent elaborated by the bacteria from nitrite (the kinetics of the inhibition were classically competitive). This and other data, particularly with regard to the dependence of the bacterially mediated reaction on amine pKa, are discussed in relation to the potential mechanisms of these bacterially mediated reactions.

Ascorbic Acid↗

The effect of ascorbic acid on a proliferating cell system.

Ascorbic acid, alone and in combination with copper sulphate, was injected into the sub-blastodermal space in the early chick embryo at 17 hours of incubation. There was a marked stunting of the embryonal axis. The absence of interphase cells indicate that ascorbic acid is lethal to the resting cell and results in a reversal of differentiation. Copper counteracts the effect of ascorbic acid and protects the blastoderm when given before ascorbic acid. A parallel action in neoplasia is of importance in the therapeutic use of this vitamin.

Animals↗