A randomized clinical trial to assess the effect of zinc and vitamin D supplementation in addition to hypertonic saline on treatment of acute bronchiolitis.

BACKGROUND: Bronchiolitis, the most common cause of hospitalization in infancy has not yet a definitive treatment. This study was conducted to assess the effect of Zinc and vitamin D on treatment of infants with bronchiolitis. METHODS: In this double blind, randomized clinical trial, 94 infants aged 2 to 23 months, admitted in Mousavi Hospital in Zanjan, Iran, with the diagnosis of acute bronchiolitis were randomly assigned into 3 groups. The control group was only treated with hypertonic saline. The two case groups received either 100 unit/kg/day of Vitamin D or 20 mg/day of zinc in addition to hypertonic saline. Wheezing, duration of hospital stay, cough, cyanosis, respiratory distress and the respiratory rate in the first, third and seventh day of hospitalization were evaluated. RESULTS: There was no significant difference between groups in terms of age, sex, weight, passive smoking, wheezing, oxygen saturation, cyanosis and type of delivery. On the third day of hospitalization, the respiratory rate/min in the control group, the groups receiving vitamin D and zinc were 45.2 ± 10.7, 37.8 ± 3.9 and 41.1 ± 9.1 respectively and the result of repeated measure analysis didn't show any significant difference between the 3 groups (P = 0.562). Duration of hospitalization in the group receiving Vitamin D or zinc and in controls were 4.2 ± 2.6, 4.4 ± 2.2 and 5.1 ± 2.4 days respectively and this difference was not significant. Zinc receiving patients did not differ from the control group regarding to respiratory rate, cyanosis and wheezing. CONCLUSION: Vitamin D or zinc administration was not effective in reducing respiratory rate in children with bronchiolitis. Trial registration This project was approved by the Institutional Ethics Committee (IR, ZUMS.REC.1396.50), and registered on IRCT (IRCT20131217015835N7).

Effect of Zinc on Hyperbilirubinemia of Newborns, a Randomized Double Blinded Clinical Trial.

BACKGROUND: Jaundice is one of the most common causes of hospitalization in newborn infants. Zinc may have a possible role as a cofactor of enzymes in the metabolism of bilirubin and can prevent red blood cell destruction as an antioxidant agent. The present study aims to investigate the effect of zinc in the treatment of neonatal hyperbilirubinemia. Material&Methods: In this double-blind, randomized clinical trial, 112 healthy newborns with idiopathic neonatal hyperbilirubinemia were divided into two groups receiving zinc and placebo. The case and control group received 10mg of zinc and placebo daily. The total bilirubin levels in the second, third, fourth and fifth day and duration of hospitalization and phototherapy were compared. RESULTS: The mean total bilirubin value in the second to fifth days in the zinc group were 11.95±2.35, 9.49±1.79, 8.54±1.63 and 8.64±0.96 respectively, and in the placebo group were 12.95±2.73, 9.88±2.35, 9.5±2.9 and 10.16±0.86 respectively and there was no significant difference between two groups. The duration of phototherapy and hospitalization in the zinc and placebo groups did not show any significant difference. CONCLUSION: We did not find a significant reduction in serum bilirubin levels nor the duration of hospitalization in neonates receiving zinc sulfate compared to control group.

Role of vitamin E and D3 supplementation in Intra-Cytoplasmic Sperm Injection outcomes of women with polycystic ovarian syndrome: A double blinded randomized placebo-controlled trial.

BACKGROUND & AIMS: Ovulation induction has been proven to impose oxidative stress during ICSI treatment cycle. Also, data indicates that PCOS women show higher oxidative markers. Available data are not convincing about which antioxidant supplements have the potential to overcome oxidative stress in PCOS subjects. The aim of this trial was to investigate the possible role of combined vitamin E and D supplementation in the ICSI outcomes (oocyte number and quality, embryo number and quality, pregnancy rate) of PCOS subjects. METHODS: A total of 105 PCOS infertile women scheduled for ICSI were enrolled in a double-blinded RCT to treatment group (vitamin E, 400 mg/day - and vitamin D3, 50,000 IU/one in two weeks, n = 52) or placebo group (n = 53) for 8 weeks. The primary outcomes were implantation rate, pregnancy and clinical pregnancy rate. Secondary outcomes included oocyte quality, embryo quality, fertilization rate, alteration in serum MDA, TAC and vitamin D3 after treatment. Further, association between serum and follicular fluid Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), and serum vitamin D3 level were assessed. RESULTS: Pregnancy, clinical pregnancy and implantation rate were significantly higher in treatment group (P < 0.001). Data analysis in both groups revealed a significant increase in serum MDA compared to baseline and a significant decrease in serum TAC compared to baseline after treatment. Further analysis showed that there is a positive weak association between vitamin D level, implantation rate (P = 0.015) and increased clinical pregnancy (P = 0.037). No significant association was detected between either follicular fluid or serum MDA and TAC and ICSI outcomes. CONCLUSIONS: In conclusion, the findings of this trial do not add clinical support to the evidence that vitamins E and D3 may play a role in the success rate of IVF via an antioxidant mechanism. REGISTRY CODE: IRCT2014081018662N1.

Effects of Herbal Compound (IMOD) on Behavior and Expression of Alzheimer's Disease Related Genes in Streptozotocin-Rat Model of Sporadic Alzheimer's Disease.

Purpose: Sporadic Alzheimer's disease (AD) accounts for over 95% of cases. Possible mechanisms of AD such as inflammation and oxidative stresses in the brain motivate researchers to follow many therapies which would be effective, especially in the early stages of the disease. IMOD, the herbal extract of R. Canina, T. Vulgare and U. Dioica plant species enriched with selenium, has anti-inflammatory, immunoregulatory and protective effects against oxidative stress. Methods: In this study three AD-related genes, DAXX, NFκß and VEGF, were chosen as candidate to investigate the neuroprotective effect of the extract by comparing their expression levels in the hippocampus of rat model of sporadic AD, using qPCR in the herbal-treated and control groups. The therapeutic effects on learning and memory levels were evaluated by Morris Water Maze (MWM) test. Results: Gene expression results were indicative of significant up-regulation of Vegf in rat's hippocampus after treatment with the herbal extract comparing to model group (P-value= 0.001). The MWM results showed significant changes in path length and time for finding the hidden platform in all groups during test and the same change in the treated comparing to the control group in memory level. Conclusion: It could be concluded that the herbal extract may have significant effect on gene expression but not on behavioral level.

The Effects of Melilotus officinalis Extract on Expression of Daxx, Nfkb and Vegf Genes in the Streptozotocin-Induced Rat Model of Sporadic Alzheimer's Disease.

BACKGROUND: Possible mechanisms of Alzheimer Disease (AD) such as inflammation and oxidative stresses in the brain led us to investigate potential AD therapeutics of Melilotus officinalis, an herbal extract, with possible role as an anti-inflammatory and anti-oxidant agent. Among different genes which had important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF have shown significant statistical diversity in the brains of Alzheimer patients. METHODS: These genes were chosen to be investigated for neuroprotective effects of the extract by comparing the expression level in the hippocampus of Sporadic AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the treated and untreated groups. In addition, therapeutic effects at the behavioral, learning and memory level by Morris Water Maze (MWM) test were investigated. RESULTS: The results represented significant decreased expression in Daxx, Nfkb and Vegf genes in the SAD rat's model treated with the herbal extract compared to the Streptozotocin-induced (STZ-induced) rats. Furthermore, no significant changes were seen in swimming distance and time for finding the hidden platform in the herbal-treated compared to the STZ-induced group. In memory level, no significant changes were observed among treated and untreated groups. CONCLUSION: It seems that the herbal extract may have significant effect on Alzheimer-related gene expression changes but not on clinical levels.

Evaluating the role of maternal folic acid supplementation in modifying the effects of methylenetetrahydrofolate reductase (C677T and A1298C) gene polymorphisms in oral cleft children.

BACKGROUND: We studied the role of maternal folic acid supplementation in modifying the effects of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) gene polymorphisms in Iranian children with oral clefts. MATERIALS AND METHODS: Forty-seven newborn infants with orofacial cleft and their mothers were selected randomly. Mothers were matched regarding dietary folate intake. The genotyping on venous blood was carried out. Consistency between maternal and child genotypes was analyzed. RESULTS: Genotype consistency was not statistically significant in both C677T and A1298C gene variants (P > 0.05). CONCLUSION: Maternal folic acid consumption may not have any significant effect on modifying C677T and A1298C polymorphisms in children.

The Impact of Vitamin D Supplementation on Post-Partum Glucose Tolerance and Insulin Resistance in Gestational Diabetes: A Randomized Controlled Trial.

BACKGROUND: Hypovitaminosis D has been associated with the development of gestational diabetes mellitus (GDM) in many observational studies. OBJECTIVES: We report the first study of the impact of prenatal vitamin D supplementation on postpartum dysglycemia in GDM patients in a randomized clinical trial. PATIENTS AND METHODS: Women with GDM at 12 - 32 weeks of gestation were assigned randomly to either the intervention group (in which serum 25-hydroxy vitamin D [25OHD] levels were measured immediately, n = 48) or the control group (in which the serum was stored and assayed at 6 - 12 weeks post-partum, n = 48). Participants with initial serum 25OHD < 30 ng/mL in the intervention group were instructed to take a total of 700,000 IU vitamin D3 during pregnancy. The primary outcomes were fasting plasma glucose (FPG), insulin, 2-h post 75 g glucose load plasma glucose (2-hPLG), homeostasis model assessment of insulin resistance (HOMA-IR), HbA1C, and 25 OHD at 6 - 12 weeks after delivery. RESULTS: The mean ± SD of serum 25OHD in the intervention group raised dramatically from 14.6 ± 6.3 to 32.4 ± 14.4 ng/mL, whereas no significant change occurred in the control group (from 17.7 ± 6.1 to 19.3 ± 9.6 ng/mL, P < 0.001). Thirteen participants developed dysglycemia in each group. Mean FPG, 2-hPLG, and HOMA-IR were not significantly different between the groups. There was no significant difference between the groups for maternal and neonatal outcomes. CONCLUSIONS: Although the high vitamin D supplementation dose in the present study (compared to the 400 IU/day dose usually recommended for pregnancy) safely increases the serum 25OHD, in GDM cases, the higher dose does not affect the plasma glucose level or insulin resistance at short term follow-up after delivery.

Neuroprotective Effects of Herbal Extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on Rat Model of Sporadic Alzheimer's Disease.

BACKGROUND: Sporadic Alzheimer's Disease (SAD) is caused by genetic risk factors, aging and oxidative stresses. The herbal extract of Rosa canina (R. canina), Tanacetum vulgare (T. vulgare) and Urtica dioica (U. dioica) has a beneficial role in aging, as an anti-inflammatory and anti-oxidative agent. In this study, the neuroprotective effects of this herbal extract in the rat model of SAD was investigated. METHODS: The rats were divided into control, sham, model, herbal extract -treated and ethanol-treated groups. Drug interventions were started on the 21(st) day after modeling and each treatment group was given the drugs by intraperitoneal (I.P.) route for 21 days. The expression levels of the five important genes for pathogenesis of SAD including Syp, Psen1, Mapk3, Map2 and Tnf-α were measured by qPCR between the hippocampi of SAD model which were treated by this herbal extract and control groups. The Morris Water Maze was adapted to test spatial learning and memory ability of the rats. RESULTS: Treatment of the rat model of SAD with herbal extract induced a significant change in expression of Syp (p=0.001) and Psen1 (p=0.029). In Morris Water Maze, significant changes in spatial learning seen in the rat model group were improved in herbal-treated group. CONCLUSION: This herbal extract could have anti-dementia properties and improve spatial learning and memory in SAD rat model.

Maternal Supplementary Folate Intake, Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and the Risk of Orofacial Cleft in Iranian Children.

BACKGROUND: The purpose of this study was to describe the association of MTHFR gene single nucleotide polymorphisms (C677T and A1298C) and maternal supplementary folate intake with orofacial clefts in the Iranian population. METHODS: In this case-control study, peripheral venous blood was taken from 65 patients with orofacial clefts and 215 unaffected controls for DNA extraction and kept in EDTA for further analysis. The genotyping was carried out using Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) and gel electrophoresis. Data were analyzed using Chi square test and logistic regression tests. RESULTS: Genotype frequencies of 677TT were reported to be 13.5 and 36.1% in controls and CL/P patients, respectively, which showed a significant difference compared to CC as reference (OR=4.118; 95% CI=1.997-8.492; p=0.001). Conversely, 1298CC with frequencies of 10.8 and 12.7% in controls and patients, respectively, showed no significant difference compared to AA (OR=2.359; 95% CI=0.792-7.023; p=0.123). Comparing patients whose mothers did not report the folate supplement intake during pregnancy, to controls, it was observed that lack of folate intake was a predisposing factor for having a child with oral clefts (OR=5/718, p=0.000). CONCLUSION: Children carrying the 677TT variant of the MTHFR gene may have an increased risk of CL/P. In addition, the finding that the risk associated with this allele was obviously higher when the mothers didn't use folic acid, supports the hypothesis that folic acid may play a role in the etiology of CL/P.

Post marketing surveillance on safety and efficacy of IMOD in Iranian patients with HIV/AIDS.

Acquired immune deficiency syndrome is one of the world's serious health problems. Immune-based therapy is a new approach in the treatment of HIV infected patients. IMOD™ with the ability to correct immune deficiencies has been introduced for the management of HIV infection. In the phase IV trial study the main objectives were to assess the possible side effects, evaluate its effect on CD4⁺ T lymphocyte count and patients' and physicians' satisfactions for 600 HIV infected patients in 13 centers during 2007. The observed adverse events in patients included: headache and vertigo (1.2%), nausea (1.2%), gastritis (1.2%), phlebitis (1%) and mild rash (1%); serious adverse events were not observed in any of IMOD™ recipients. Therefore it was not needed to terminate the treatment in any of patient. The results of this study demonstrated that daily prescription of IMOD™ significantly increases T lymphocyte CD4⁺ and total lymphocyte count in HIV-positive patients. In addition, nearly 90% of the patients and 70% physicians are satisfied by IMOD™ treatment.

Safety and efficacy of Setarud (IMOD TM ) among people living with HIV/AIDS: a review.

The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these limitations. Setarud (IMOD™) is a safe, naturally- derived immunomodulator that was introduced for treatment of HIV patients in Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A significant rise of CD4 count was observed in HIV patients treated by IMOD™ in clinical trial phases, which could be explained by its immunomodulatory effects. Anti-oxidative activity of compounds in IMOD™ might play a role in the clinical outcomes of patients treated with this drug. Moreover, IMOD™ may show improving activity upon lipid profile and liver metabolism. According to studies on IMOD™, it seems that IMOD™ has minor side effects. IMOD™ with international publication number WO 2007/087825 A1 is an herbal extract which includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency and is useful in treatment of HIV infection and AIDS.