Doses Of Ascorbic Acid Research Articles

Selective recovery of gallium with continuous counter-current foam separation and its application to leaching solution of zinc refinery residues

Continuous counter-current foam separation with simultaneous injections of metal and surfactant solutions into the rising foam bed was applied to gallium(III) recovery from hydrochloric acid solutions. A nonionic surfactant, poly(oxyethylene) nonylphenyl ether, used in this study showed a strong affinity to gallium(III) and played a double role of foam-producer and metal collector. The method was applied to multi-metals solutions of gallium, iron, copper and zinc, and the effects of experimental parameters such as solution acidity, an air flow rate, and injection rates of metal and surfactant solutions, were discussed in terms of the percent recovery and the separation factor of gallium(III) and iron(III). Satisfactory results could be obtained in a single stage; under the optimized condition, the separation factor of gallium(III) was 67 over iron(III) and more than 1000 over the other metals, while keeping the gallium(III) recovery complete. Compared with our previous experiment of solvent extraction using the same surfactant as an extractant, where the separation factor of gallium(III) over iron(III) was found to be merely 1.2, the present method provides much better performance due to its unique contact mechanism between the metal and the surfactant. As a practical trial, the method was applied to an acid leaching solution of zinc refinery residue containing gallium along with vast amounts of zinc, iron, aluminum and arsenic. By optimizing the experimental parameters and reducing trivalent iron with the dose of ascorbic acid to the leaching solution, complete recovery of gallium was attained with negligible contamination from the other metals.

Inherited Neuropathies

Inherited peripheral neuropathies are among the most common hereditary diseases of the nervous system. Charcot-Marie-Tooth (CMT) disease, also known from previous classifications as hereditary motor and sensory neuropathy (HMSN), is certainly the most common inherited neuropathy. In the past several years, various treatments for CMT have been proposed, although specific therapies are not yet available. In clinical practice, rehabilitative strategies remain the most helpful therapeutic approach to these patients. There is still a lack of consensus on the best way to rehabilitate patients affected by CMT. Based on our personal experience and on a review of the literature, we first recommend the prescription of ankle-foot orthoses (AFO) for patients affected by CMT; the choice of which patient, which AFO, and when to apply it depends on the individual condition of each patient and on the experience of the physician/therapist. Second, adaptive equipment (eg, button hook, long-handled shoehorn, elastic shoe laces) is available to compensate for hand deformities, sensory loss, and weakness. Third, moderate to intense strength training and aerobic exercise are well tolerated by patients affected by CMT; further studies are needed to establish whether these approaches are effective in improving their motor function and strength. There is not enough evidence to recommend muscle stretching exercises or proprioceptive kinesiotherapy, although in our experience both approaches may be helpful in selected CMT patients to prevent tendon retractions, muscle tightening, and loss of strength, and to improve balance. There is growing knowledge of the underlying genetic defects and molecular pathophysiology in CMT. To date, only a few clinical trials in CMT patients have been performed. A neurotrophic factor, neurotrophin 3, was used in a small sample of CMT1A patients with promising results, but it has not been tested in a larger cohort and there is currently no reason to suggest this therapy for CMT1A neuropathy. Based on positive results in an animal model of CMT1A, three trials with ascorbic acid (AA) were completed in a large number of patients with this neuropathy, with results that were negative overall. Therefore, it is not possible to recommend the use of AA in CMT1A patients at this time, but the results of a larger Italian-UK study and an American trial with higher doses of AA are still awaited. It is important to remember that a superimposed inflammatory/disimmune process may complicate the course of the neuropathy; in this case, severe worsening (especially motor) in a matter of weeks or months is a "red flag" that should suggest immunosuppressive or immunomodulatory treatment such as steroids, intravenous immunoglobulin, or plasma exchange. In fact, steroid-sensitive cases of HMSN were described many years ago, well before the genetic diagnosis was available. Symptomatic treatment to reduce neuropathic and nociceptive pain, both of which have been reported in patients affected by CMT, should be prescribed according to recently published guidelines for the therapy of pain. No evidence suggests any specific surgical intervention or change in diet or lifestyle for patients affected by various types of CMT.

Ascorbic and Folic Acids Intervention in P. berghei Induced Oxidative Stress in Mice

This research attempts to examine the effects of ascorbic and folic acid intervention on the haematology, antioxidants molecules and enzymes of mice exposed to malaria infection. The study involves three groups of control (non-parasitized-nontreated), parasitized-nontreated (PnT) and parasitized ascorbic and folic acid treated (P+as+faT). Intervention with ascorbic and folic acids commenced for three days after parasitemia had been established in mice. Results from this study showed that ascorbic and folic acid intervention in malaria condition reduced (P<0.05) total protein, erythrocyte fragility (EF), increased (P<0.05) packed cell volume (PCV) in comparison with PnT and control mice groups. Lipid peroxidation product in serum, Superoxide dismutase (SOD) activity and Catalase (CAT) activity and reduced glutathione (GSH) reduced in parasitized mice administered with ascorbic and folic acid doses, as against those of control, whereas SOD activity in Control and CAT activity in PnT observed to increase and decrease, respectively. The extent of lipid peroxidation in kidney was effectively reduced by ascorbic and folic acid compared to PnT. In liver SOD activity, CAT activity, glucose-6-phosphate dehydrogenase (G6PD) activity significantly (P<0.05) reduced in P+as+faT as against PnT and control groups. From these observations therefore, we draw the conclusion that ascorbic and folic acids combination in malaria infection may reduce lipid peroxidation and stimulate cellular pathways that enhance the production of high concentrations of hydrogen peroxide.

Dietary modulation of immune responses by ascorbic acid in healthy and cadmium-induced immunocompromised chickens

Dietary modulation of immune responses by ascorbic acid in healthy and cadmium-induced immunocompromised chickens The assessment of immunological changes induced in chickens by feeding 50 mg cadmium per 1 kg of diet from hatching to 30 days of age was studied. Furthermore, the modulatory effects of different supplemental doses of ascorbic acid (100 and 1000 mg per 1 kg of diet) were investigated. The observed immunocompromise in chickens continuously exposed to cadmium resulted in a decreased growth rate and disturbance of immune responses, both on nonspecific and specific levels. The effect of supplements 100 and 1000 mg of ascorbic acid per 1 kg of diet differed. The low dosage of ascorbic acid had immunostimulative action in healthy cadmium-untreated chickens, provided correction of compromised immunity, and increased tolerance of the birds to subtoxic cadmium intake. In contrast, the higher supplement of ascorbic acid had a slight or no effect on healthy birds and either caused no significant shifts in immunological indices or manifested synergistic effect combined with cadmium.

Light and electron microscopic study of the toxic effect of prolonged lead exposure on the seminiferous tubules of albino rats and the possible protective effect of ascorbic acid

Background Lead has been long recognized as an occupational toxicant. Now, lead is considered to be one of the major environmental pollutants which have serious potential threat to human health. Reports of declining male fertility have renewed interest in the role of environmental and occupational exposures in the etiology of human infertility. Objectives The aim of the present work was to investigate the toxic effect of prolonged exposure to lead on albino rat’s seminiferous tubules and the possible protective effect of ascorbic acid (vitamin C) on lead toxicity. Methods The study was carried out on 40 adult male albino rats divided into three groups: a control group which comprised three subgroups; negative control which received no treatment and two positive controls receiving an oral daily dose of distilled water or ascorbic acid, respectively. Lead acetate – intoxicated group received lead acetate orally in a dose of 25 mg/kg b.w dissolved in distilled water for 3 months. While the protected group received ascorbic acid orally in a dose of 100 mg/kg b.w daily for 3 months, simultaneously with lead acetate in a similar dose to that of the intoxicated group. By the end of the experimental period, blood samples were collected for estimation of blood lead level. Fresh specimens were taken from the testis and processed for light and electron microscopic examination. Results Biochemical analysis demonstrated significant increase in the blood lead level in lead intoxicated group compared to the control group, while ascorbic acid – protected group revealed significant decrease in the blood lead level. Light microscopic examination of lead treated group revealed loss of normal archicture of the testicular tissue in the form of thin walled seminiferous tubules with wide lumen and vacuolations in the spermatogenic epithelium mostly separating primary spermatocytes from spermatogonia and surrounding nuclei of Sertoli cells. Apoptotic bodies were found among the basal part of the spermatogenic epithelium. Ultrastructural examination of the same group revealed degenerating cells with cytoplasmic vacuolations, apoptotic cells with heterochromatic nuclei and dense cytoplasm, irregularities in the basal lamina with increased collagen deposition and shrunken myoid cells. Late differentiating spermatids showed deformed head with widening of the subacrosomal space and redundant acrosome, in addition to the abnormalities in the tail of developing sperms. On the other hand, ascorbic acid – protected group showed amelioration of most of the degenerative changes depicted in the lead intoxicated group. Conclusion Lead had an injurious effect on the testis of the exposed animals. Simultaneous administration of ascorbic acid was efficient in preventing most of such toxic effect and decreasing the blood lead level. Therefore, ascorbic acid can be recommended for protection against lead intoxication.

High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure

The increased central sympathetic activity typically associated with chronic heart failure (CHF) is probably mediated by formation of reactive oxygen species (ROS) in the brain. Our objective was to undertake a trial to test our hypothesis that administration of the well-known antioxidant and ROS scavenger ascorbic acid, would reverse or reduce the sympathetic overactivity in CHF patients. In a prospective, randomized, placebo-controlled, double-blind, cross-over trial, 11 CHF patients were treated with ascorbic acid 2 g/day or placebo for 3 days. At the end of each treatment period, sympathetic nervous system activity was measured by microneurography for direct muscle sympathetic nerve activity (MSNA) recording, analysis of heart rate variability (HRV) and measurement of plasma norepinephrine concentrations. During ascorbic acid administration, plasma vitamin C levels were higher than during placebo (74·9 ± 6·0 μmol/L vs. 54·8 ± 4·6 μmol/L, P = 0·03). Ascorbic acid had no effect on sympathetic activity: MSNA (ascorbic acid: 66·8 ± 3·3 vs. placebo 66·9 ± 3·2 bursts/100 beats, P = 0·98). In addition, HRV and plasma norepinephrine levels did not differ. Short-term administration of the antioxidant ascorbic acid in CHF patients does not reverse the increased sympathetic activity as measured by microneurography, HRV and plasma norepinephrine levels. The use of higher oral dosages seems not feasible due to accompanying side effects.

Prospective role of ascorbic acid (vitamin C) in attenuating hexavalent chromium-induced functional and cellular damage in rat thyroid

Occupational exposure to toxic heavy metals may render industrial workers with thyroid-related problems. Here, we examined the role of ascorbic acid (vitamin C) against hexavalent chromium Cr (VI)-induced damage in rat thyroid gland. Potassium dichromate (K2Cr2O7) and ascorbic acid doses were 60 microg and 120 mg kg(-1) body wt (intraperitoneally [i.p.]) respectively. Treatment regimens were group I rats, saline treated control; group II, only K2Cr2O7; group III, ascorbic acid 1 hour prior K2Cr2O7; group IV, simultaneous doses of ascorbic acid and K2Cr2O7, and group V, a combined premix dose of ascorbic acid and K2 Cr2O7 (2:1 ratio). Blood samples were taken before dosing the animals and 48 hours post exposure to determine the serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. Toward end of experiment, rats were sacrificed and thyroid glands were processed to evaluate the extent of cellular insult. Results showed significantly increased TSH and decreased FT3 and FT4 concentrations in groups II, III and IV rats as compared to control levels (p < 0.05). In contrast, in group V rats, serum TSH, FT3 and FT4 concentrations neared control concentrations. Histopathologically, protective effect of ascorbic acid was found in group V rats only, where thyroid gland structure neared control thyroid except the follicular size that was decreased (p < 0.05). Follicular density was no different from control. Basal laminae were intact, interfollicular spaces were normal. Colloid retraction and/or reabsorption were reduced maximally. Epithelial cell height was no different from control; epithelial follicular index increased only 1.3 fold, whereas nuclear-cytoplasmic (N/C) ratio was decreased by 14% only. The study indicates that the ascorbic acid may have the potential to protect thyroid gland from chromium toxicity; however, the study warrants further in-depth experimentation to precisely elucidate this role.

Ascorbic acid plus gemcitabine (gem) and erlotinib (erl) in patients with metastatic pancreatic cancer (mPanc): Preliminary safety results.

e14659 Background: Intravenous ascorbic acid in pharmacologic concentrations, via production of extracellular hydrogen peroxide and reactive oxygen species, has selective cytotoxicity to cancer cells but not normal cells and tissues in vitro and in vivo. In this study we have evaluated safety and tolerability of ascorbic acid combined with gem/erl in patients with mPanc, and we now report preliminary safety results. Methods: This is the phase I, open label portion of a phase I/II trial. The primary objective is to determine safety and tolerability of intravenous ascorbic acid at three dosage levels with gem/erl. The secondary objective is to evaluate tumor free progression. Eligible patients were >18 yrs of age, life expectancy > 3 months, histologically confirmed mPanc and ECOG PS 0/1. All patients received intravenous ascorbic acid at three times weekly combined with gem 1,000 mg/m2 weekly for 7 weeks and erl 100 mg oral daily. After a week of rest and reevaluation, subsequent cycles consisted of gem 1,000 mg/m2 weekly times 3 with 1 week of rest. The study used a 3+3+3 design with three different ascorbic acid doses: 50 gm, 75 gm, and 100 gm infused over 90-minute duration. Safety and tolerability is based on dose-limiting toxicities (DLTs), and grade 3/4 combination chemotherapy related adverse events (AEs) deemed clinically significant by the investigator. Plasma levels of ascorbic acid, gem, and erl will be determined. The primary endpoint was incidence of DLTs. Results: No DLT has been reported for the first 5 DLT evaluable subjects. Accrual to part 1 continues. Five patients have enrolled in part 1; 4 patients were female. Mean age was 69 years (60-82); ECOG 0/1 = 4/1. No grade 4 or 5 treatment related DLTs were seen. Serious possible AEs included diarrhea (grade 3) in one pt and jaundice (grade 3) in 1 pt. One pt had partial response, 2 pts had stable disease, and 2 pts had disease progression. Conclusions: Ascorbic acid combined with gem/erl has been well tolerated and may in the future offer potential in pts with mPanc. The MTD has not yet been reached. Treatment-related AEs Number of pts Grade of toxicity Nausea/vomiting 1 1 Infection 0 Diarrhea 2 1, 3 Erythema 1 1 Thrombocytopenia 2 1, 2 Rash 1 1 Jaundice 1 3 No significant financial relationships to disclose.

The Effects of Ascorbic Acid Supplementation on Muscle Blood Flow in Aged Rats

During exercise aged individuals exhibit endothelial dysfunction and decreased levels of whole-limb blood flow, both of which may be linked mechanistically to age-related increases in reactive oxygen species (ROS). Ascorbic acid (AA) reduces levels of ROS and has been shown to alleviate vascular and hyperemic dysfunction at rest and during small muscle mass exercise in humans (Kirby et al. J Physiol., 2009). However, the effect of AA on vascular function and blood flow (BF) to individual muscles during dynamic whole-body exercise is not known. PURPOSE: To test the hypothesis that a single high-dose infusion of AA would increase BF to the hindlimb musculature of old rats at rest and during treadmill running. METHODS: 18 old (∼28 months) Fischer 344 × Brown Norway rats were randomized into rest (n=9) and exercise (n=9) groups. BF to the hindlimb (28 individual muscles and muscle parts) was evaluated via radiolabeled microspheres before and after intra-arterial AA administration (76 mg/kg in 3 ml heparinized saline, 30 minute infusion) at rest and during submaximal treadmill running (20 m/min, 5% grade). Total antioxidant capacity (TAC) and thiobarbituric acid reactive species (TBARS) were measured before and after AA to determine the ability of this dose of AA to increase levels of plasma antioxidants and decrease levels of ROS, respectively. RESULTS: At rest: AA increased TAC (∼37%, P < 0.05) but did not change TBARS (Pre: 6.8 ± 0.7 vs. Post: 7.0 ± 1.0 μM, P > 0.05). AA decreased total hindlimb BF (Pre: 25 ± 3 vs Post: 16 ± 2 ml/min/100g, P < 0.05) and BF to 8 of the 28 individual muscles that were evaluated. During exercise: TAC was increased (∼35%, P < 0.05) and TBARS were decreased (Pre: 9.8 ± 2.0 vs Post: 6.1 ± 0.5 μM, P < 0.05). However, there was no effect on either total hindlimb BF (Pre: 154 ± 14 vs. Post: 162 ± 13, P > 0.05) or BF to any of the individual muscles that were evaluated. CONCLUSIONS: Increased TAC via AA infusion reduces hindlimb muscle BF at rest but not during whole-body dynamic exercise. Thus, although this specific AA dose decreased TBARS, there was no evidence that AA supplementation increases blood flow to the locomotor muscles during whole-body exercise. Whether other doses of AA or alternative antioxidants provide beneficial outcomes in other models remains unknown. Support: AHA Grant 070090Z

High dose of ascorbic acid induces cell death in mesothelioma cells

Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

Protective effect of oral ascorbic acid (vitamin c) against acetaminophen- induced hepatic injury in rats

The incidence of acetaminophen-induced hepatotoxicity is reported to be on the increase, with limited therapeutic or chemoprophylactic options. In the present in vivo study, single daily oral doses (100 – 500 mg/kg) of ascorbic acid (ASC) were investigated for their protective effects againstacetaminophen (APAP)-induced hepatotoxicity in 4 groups of rats made up of 6 rats per group for 14 days. Also, effects of the doses on body weights taken on the 1st, 7th and 15th day of the experiment were also investigated. On the 15th day, blood samples for serum ALT, AST and FBG assay were collected through cardiac puncture under inhaled diethyl ether anaesthesia. Rat livers were also studied for histopathology. Results showed that treatment with APAP intraperitoneal injection induced significant (P

Endothelial nitric oxide synthase activity involves in the protective effect of ascorbic acid against penicillin-induced epileptiform activity

Ascorbic acid and nitric oxide are known to play important roles in epilepsy. The aim of present study was to identify the involvement of nitric oxide (NO) in the anticonvulsant effects of ascorbic acid on penicillin-induced epileptiform activity in rats. Intracortical injection of penicillin (500, International Units (IU)) into the left sensorimotor cortex induced epileptiform activity within 2–5 min. Thirty minutes after penicillin injection, nitric oxide synthase (NOS) inhibitor, N G-nitro- l-arginine methyl ester ( l-NAME, 100 mg/kg), neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI, 40 mg/kg), NO substrate, l-arginine (500 mg/kg) were administered with the most effective dose of ascorbic acid (100 mg/kg) intraperitoneally (i.p.). The administration of l-arginine significantly decreased the frequency of epileptiform activity while administration of l-NAME did not influence the mean frequency of epileptiform activity. Injection of 7-NI decreased the mean frequency of epileptiform activity but did not influence amplitude. Ascorbic acid decreased both the mean frequency and amplitude of penicillin-induced epileptiform activity in rats. The application of l-NAME partially and temporarily reversed the anticonvulsant effects of ascorbic acid. The results support the hypothesis of neuro-protective role for NO and ascorbic acid. The protective effect of ascorbic acid against epileptiform activity was partially and temporarily reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ascorbic acid needs endothelial-NOS/NO route to decrease penicillin-induced epileptiform activity.

Ascorbic Acid Potentiation of Arsenic Trioxide Anticancer Activity Against Acute Promyelocytic Leukemia.

IntroductionAcute promyelocytic leukemia (APL) is a malignant disorder of the white blood cells. Arsenic trioxide (As2O3) has been used as a therapeutic agent to treat APL and other tumors. Studies suggest that ascorbic acid (AA) supplementation may improve the clinical outcome of As2O3 for APL patients. Our aim was to use human leukemia (HL-60) APL-cells as an in vitro test model to evaluate the effect of physiologic doses of AA on As2O3-induced toxicity and apoptosis of HL-60 cells.MethodsHL-60 cells were treated either with a pharmacologic dose of As2O3 alone and with several physiologic doses of AA. Cell survival was determined by trypan blue exclusion test. The extent of oxidative cell/tissue damage was determined by measuring lipid hydroperoxide concentration by spectrophotometry. Cell apoptosis was measured by flow cytometry using Annexin-V and propidium iodide (PI) staining.ResultsAA treatment potentiates the cytotoxicity of As2O3 in HL-60 cells. Viability decreased from (58 ± 3)% in cells with As2O3 alone to (47 ± 2)% in cells treated with 100 µM AA and 6 µg/mL As2O3 with P < 0.05. There was a significant (P < 0.05) increase in lipid hydroperoxide concentrations in HL-60 cells co-treated with AA compared to As2O3 alone. Flow cytometry assessment (Annexin V FITC/PI) suggested that AA co-treatment induces more apoptosis of HL-60 cells than did As2O3 alone, but this was not statistically significant. Taken together, our experiment indicates that As2O3 induced in vitro cell death and apoptosis of HL-60 cells. Administration of physiologic doses of AA enhanced As2O3-induced cytotoxicity, oxidative cell/tissue damage, and apoptosis of HL-60 cells through externalization of phosphatidylserine.ConclusionsThese suggest that AA may enhance the cytotoxicity of As2O3, suggesting a possible future role of AA/As2O3 combination therapy in patients with APL.

A Randomized Phase II Trial of High-Dose Melphalan, Ascorbic Acid and Arsenic Trioxide with or without Bortezomib in Multiple Myeloma.

Abstract 2309Poster Board II-286 BackgroundThere is a role for novel preparative regimens in multiple myeloma to improve the outcome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto HCT). Bortezomib is an active agent in newly diagnosed or relapsed multiple myeloma, and has synergistic activity with melphalan. We conducted a randomized phase II trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA) and melphalan. Methodsauto HCT, with preparative regimen melphalan 100 mg/m2 IV on days -4 and -3, AA 1000 mg/day IV on days -9 to -3 and ATO 0.25 mg/kg IV on days -9 to -3. Patients were randomized to 3 arms; no bortezomib (arm 1), bortezomib 1 mg/m2 on days -9, -6 and -3(arm 2), and bortezomib 1.5 mg/m2 on days -9, -6 and -3 (arm 3). Primary endpoints were complete response (CR), NCI grade 4 toxicity, and overall survival (OS). ResultsIn arms 1, 2 and 3, median intervals between diagnosis and auto HCT were 12.2, 9.6 and 8.8 months; median follow up in all surviving patients was 20 months (range 10 to 31). CR+near CR rates in arms 1, 2 and 3 were 35%, 30% and 25%. Grade 3–4 toxicity was seen in 6 patients in arm 1 (mucositis 3, dyspnea 1, acute renal failure 1, pleural effusion 1), 6 patients in arm 2 (mucositis 3, diarrhea 1, pneumonia 1 and hydronephrosis 1) and 6 patients in arm 3 (pulmonary edema 2, mucositis 1, intestinal obstruction 1, low back pain 1, elevated transaminases 1). The most common adverse events were nausea, diarrhea and pedal edema. Grade 1–2 weight gain due to fluid retention was seen in 84%, 70% and 95% of patients in arms 1, 2 and 3. Median time to neutrophil engraftment (ANC >500/dl) was 10 days in each arm. Median OS has not been reached in any of the 3 arms. Median progression-free survival (PFS) times were18.6, 13.2 and 17.5 months. OS was significantly shorter in patients with relapsed disease (0.00001) and cytogenetic abnormalities at auto HCT (0.0002). ConclusionsAdding bortezomib to a preparative regimen of ATO, AA and high dose melphalan is safe and well tolerated in patients with multiple myeloma. There was no significant impact of adding bortezomib at either dose on the CR rate, grade 3-4 toxicity or OS.Table:Patient Characteristics and OutcomesArm 1 (n=19)Arm 2 (n=20)Arm 3 (n=19)Median Age615964Abnormal Cytogenetics2 (10%)5 (25%)8 (42%)Relapsed disease6 (32%)7 (35%)3 (16%)Prior ASCT201Months from Diagnosis to ASCT12.29.68.8Median CD34 106/kg4.24.13.6Median Days to Engraftment (ANC > 500)101010Maintenance Rx6 (32%)4 (20%)3 (16%)CR + VGPR7 (35%)6 (30%)5 (25%)Grade 3-4 AEs666Median PFS (months)18.613.217.5 Disclosures:Shah:Celgene, Amgen, Novartis, Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Qazilbash:Cephalon: Speakers Bureau.

Therapeutic Influence of Zinc and Ascorbic Acid Against Lead induced Biochemical Alterations

The influence of co-administration of zinc (10mg/kg, intraperitoneal [ip]) and ascorbic acid (10, 20 and 30mg/kg, ip) against lead (lead acetate; 35mg/kg, ip for 3days) induced biochemical alterations was studied in young albino rats. The results revealed significant fall in hemoglobin content, on the other hand significant raise in the activity of serum transaminases and serum alkaline phosphatase after lead administration. Significant increase in lipid peroxidation and decreased level of reduced glutathione in liver showed oxidative stress due to lead exposure. Total protein content in liver and kidney were diminished after lead exposure. Activity of acid phosphatase in liver and kidney and alkaline phosphatase in kidney was increased significantly. Zinc and ascorbic acid treatment showed moderate therapeutic efficacy when administered individually, whereas more pronounced protective effects were observed after combined therapy of zinc and different doses of ascorbic acid. The results thus, suggested that co-administration of zinc and ascorbic acid may be useful in restoration of lead induced biochemical alterations.

Ascorbic Acid Supplementation and Spermatogenesis in Nigerian Men

Background: The role of ascorbic acid as an antioxidant nutrient in the maturation of sperm cells has received considerable attention. A previous study from our laboratory showed reduced seminal and plasma ascorbic acid in subfertile patients. Method: Fifteen subfertile male patients mean age 36.4±0.9 years with sperm counts of 31.4±7, 08 x10 6 /cm 3 were given 200mg/day dose of ascorbic acid as supplement for four weeks and ten highly fertile male mean age 35.6±1.7 years with sperm count of 50.9±10.3 x10 6 /cm 3 volunteers were selected as controls. The biochemical parameters and anthropometric measurements were determined using standard methods. Result: Significant decreases were obtained in baseline sperm cell count (p<0.01), percentage (%) motility and %vitality (p<0.01), and the % of morphologically normal sperm cells (p<0.01) in the subfertile compared with the controls. The baseline plasma and seminal ascorbic acid concentrations were significantly reduced (p<0.001). The post-supplementation sperm cell count (p<0.001), % motility and %vitality (p<0.01) were significantly increased compared with the baseline values. Conclusion: The enhanced reversal of poor semen quality and semen ascorbic acid status with dietary supplementation of vitamin C in subfertile is a pointer to its positive role in the maintenance of sperm cell integrity. Further work is therefore required to elucidate our findings. Keyword: Ascorbic acid, high density lipoprotein, cholesterol, semen, infertility subfertile.

Lowering the Erythropoietin Requirement for Dialysis Patients with Functional Iron Deficiency Using Ascorbic Acid (Vitamin C)

AbstractBACKGROUNDHemodialysis patients with functional iron deficiency often require excess recombinant human erythropoietin (EPO). In a few small studies, ascorbic acid (AA) has been shown to reduce EPO requirements. The goal of this study was to determine the lowest effective and safe dose of AA for these patients.METHODSThis was an open‐labeled, prospective, single‐center study involving hemodialysis patients with serum ferritin &gt;500 ng/mL and transferrin saturation &lt;20%. Patients with C‐reactive protein (CRP) &gt;2 mg/dL were excluded. The study comprised of 4 consecutive phases: intravenous AA 100 mg (phase I), 200 mg (phase II), 300 mg (phase III), and oral AA 250 mg (phase IV). Oxalate and AA levels were obtained before and after each treatment phase.RESULTSA total of 8 patients were enrolled and 6 patients completed the study. Positive impact of AA supplementation on lowering the EPO requirement was mainly seen with the 300 mg dosage and maintained on oral supplementation. Neither the oxalate nor AA levels increased significantly during the study. Overall the patients tolerated both forms of ascorbic acid well.CONCLUSIONThe role of AA in reducing the EPO requirement appears promising. Larger studies are needed to examine the safety and confirm the efficacy of AA in these patients.

A gas chromatography–mass spectrometry method for the quantitation of N-nitrosoproline and N-acetyl- S-allylcysteine in human urine: Application to a study of the effects of garlic consumption on nitrosation

Biomarkers in urine can provide useful information about the bioactivation of chemical carcinogens and can be used to investigate the chemoprotective properties of dietary nutrients. N-Nitrosoproline (NPRO) excretion has been used as an index for endogenous nitrosation. In vitro and animal studies have reported that compounds in garlic may suppress nitrosation and inhibit carcinogenesis. We present a new method for extraction and sensitive detection of both NPRO and N-acetyl- S-allylcysteine from urine. The latter is a metabolite of S-allylcysteine, which is found in garlic. Urine was acidified and the organic acids were extracted by reversed-phase extraction (RP–SPE) and use of a polymeric weak anion exchange (WAX–SPE) resin. NPRO was quantified by isotope dilution gas chromatography–mass spectrometry (GC–MS) using [ 13C 5]NPRO and N-nitrosopipecolinic acid (NPIC) as internal standards. This method was used to analyze urine samples from a study that was designed to test whether garlic supplementation inhibits NPRO synthesis. Using this method, 2.4 to 46.0 ng NPRO/ml urine was detected. The method is straightforward and reliable, and it can be performed with readily available GC–MS instruments. N-Acetyl- S-allylcysteine was quantified in the same fraction and detectable at levels of 4.1 to 176.4 ng/ml urine. The results suggest that 3 to 5 g of garlic supplements inhibited NPRO synthesis to an extent similar to a 0.5-g dose of ascorbic acid or a commercial supplement of aged garlic extract. Urinary NPRO concentration was inversely associated with the N-acetyl- S-allylcysteine concentration. It is possible that allyl sulfur compounds found in garlic may inhibit nitrosation in humans.

The influence of different doses of α-tocopherol and ascorbic acid on selected oxidative stress parameters in in vitro culture of leukocytes isolated from transported calves

The objective of the study was to assess in vitro the influence of various doses of two different antioxidants, α-tocopherol and ascorbic acid, on protective mechanisms against ROS in white blood cells obtained from calves exposed to transport, and to compare these results with those obtained from non-transported animals. The concentrations of lipid peroxidation products in leukocytes and in the retained medium were assessed by determining the level of Thio Barbituric Acid Reactive Substances (TBARS). Total antioxidant status in the leukocytes and the medium were estimated using a ferric-reducing ability of plasma (FRAP) assay. Leukocyte viability was determined using the trypan blue reduction test. The study demonstrated that after bovine leukocytes (WBC) were incubated in vitro with α-tocopherol and ascorbic acid, peroxidation intensity decreased and total antioxidant capacity increased. The results of the study reveal that these antioxidants in concentrations over 0.1 mg/ml have a major impact on free radical activity on bovine white blood cells and on cell viability during transport of animals. Based on this study, we suggest that incubation of the leukocytes with antioxidants decreases the oxidative stress development, which can be helpful in protection of the immunological cells during bovine respiratory disease.

Comparison of peroxyl radical scavenging capacity of commonly consumed beverages

The antioxidant potential of commercial beverages against peroxyl radical was determined using the Total Oxyradical Scavenging Capacity (TOSC) assay. Peroxyl radicals generated from thermal homolysis of 2,2'-azobis-amidinopropane oxidize alpha-keto-gamma-methiolbutyric acid to ethylene, which is monitored by gas chromatography. The TOSC of each beverage is quantified from its ability to inhibit ethylene generation relative to a control reaction. Nine different beverages (green tea, jasmine tea, black tea, instant coffee, brewed coffee, cocoa mix, oolong tea, prune juice, and grape juice) were selected for this study. Their antioxidant capacities per a cup-serving (125 mL) were measured and compared to peroxyl radical scavenging capacity provided by a recommended daily dose of ascorbic acid (90 mg) dissolved in the same volume of water. The greatest antioxidant capacity was found in brewed coffee, which was followed, in decreasing order, by prune juice, instant coffee, green tea, cocoa mix, grape juice, jasmine tea, black tea, oolong tea, and ascorbic acid. There was an almost 7-fold difference in the TOSC between brewed coffee and ascorbic acid. The data suggest a potential role for commonly consumed beverages in lowering the risk of pathophysiologies associated with peroxyl radical-mediated events.