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1.  Targeting metabolic disorders by natural products 
The most prevalent metabolic disorders are diabetes mellitus, obesity, dyslipidemia, osteoporosis and metabolic syndrome, which are developed when normal metabolic processes are disturbed. The most common pathophysiologies of the above disorders are oxidative stress, Nrf2 pathways, epigenetic, and change in miRNA expression. There is a challenge in the prevention and treatment of metabolic disorders due to severe adverse effects of some synthetic drugs, their high cost, lack of safety and poverty in some conditions, and insufficient accessibility for the general population in the world. With increasing interest in shifting from synthetic drugs to phytotherapy as an alternative treatment, there is still a gap in scientific evidences of plant-derived therapeutic benefits. One reason may be slow rate of translation of animal studies’ findings into human clinical trials. Since metabolic disorders are multifactorial, it seems that poly-herbal medications, or drug-herbal combination are needed for their treatment. However, further researches to determine the most effective plant-derived metabolites, and their cellular mechanism in order to set priorities for well-designed animal and clinical trials, and also more studies with strong scientific evidences such as systematic review and meta-analysis of controlled studies are needed.
PMCID: PMC4495701  PMID: 26157708
Metabolic disorders; Oxidative stress; Epigenetic; Natural products
2.  Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis 
Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.
We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.
A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I2 =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I2 = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I2 = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I2 = 0%).
The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.
PMCID: PMC4502493  PMID: 26180433
Duration of mechanical ventilation; duration of vasopressor therapy; early goal-directed therapy; length of hospital stay; length of Intensive Care Unit stay; overall mortality; sepsis; septic shock; severe sepsis
3.  On The Protection by The Combination of CeO2 Nanoparticles and Sodium Selenite on Human Lymphocytes against Chlorpyrifos-Induced Apoptosis In Vitro 
Cell Journal (Yakhteh)  2015;17(2):361-371.
Chlorpyrifos (CP) as an organophosphorus pesticide is thought to induce oxidative stress in human cells via producing reactive oxygen species (ROS) that leads to the presence of pathologic conditions due to apoptosis along with acetylcholinesterase (AChE) inhibition.This study aimed to evaluate the apoptotic effects of CP and to assess the protective potential of CeO2nanoparticle (CNP) and sodium selenite (SSe) by measuring cascades of apoptosis, oxidative stress, inflammation, and AChE inhibition in human isolated lymphocytes.
Materials and Methods
In the present experimental study, we examined the anti-oxidative and AChE activating potential of CNP and SSe in CP-treated human lymphocytes. Therefore, the lymphocytes were isolated and exposed to CP, CP+CNP, CP+SSe, and CP+CNP+SSe after a three-day incubation. Then tumor necrosis factor-alpha (TNF-α) release, myeloperoxidase (MPO) activity, thiobarbituric acid-reactive substances (TBARS) levels as inflammatory/oxidative stress indices along with AChE activity were assessed. In addition, the apoptotic process was measured by flow cytometry.
Results showed a significant reduction in the mortality rate, TNF-α, MPO activity, TBARS, and apoptosis rate in cells treated with CNP, SSe and their combination. Interestingly, both CNP and SSe were able to activate AChE which is inhibited by CP. The results supported the synergistic effect of CNP/SSe combination in the prevention of apoptosis along with oxidative stress and inflammatory cascade.
CP induces apoptosis in isolated human lymphocytes via oxidative stress and inflammatory mediators. CP firstly produces ROS, which leads to membrane phospholipid damage. The beneficial effects of CNP and SSe in reduction of CP-induced apoptosis and restoring AChE inhibition relate to their anti-oxidative potentials.
PMCID: PMC4503850  PMID: 26199915
Organophosphorus; Chlorpyrifos; Lymphocytes; Cerium Oxide Nanoparticles; Sodium Selenite
4.  Role of dietary polyphenols in the management of peptic ulcer 
Peptic ulcer disease is a multifactorial and complex disease involving gastric and duodenal ulcers. Despite medical advances, the management of peptic ulcer and its complications remains a challenge, with high morbidity and death rates for the disease. An accumulating body of evidence suggests that, among a broad reach of natural molecules, dietary polyphenols with multiple biological mechanisms of action play a pivotal part in the management of gastric and duodenal ulcers. The current review confirmed that dietary polyphenols possess protective and therapeutic potential in peptic ulcer mediated by: improving cytoprotection, re-epithelialization, neovascularization, and angiogenesis; up-regulating tissue growth factors and prostaglandins; down-regulating anti-angiogenic factors; enhancing endothelial nitric oxide synthase-derived NO; suppressing oxidative mucosal damage; amplifying antioxidant performance, antacid, and anti-secretory activity; increasing endogenous mucosal defensive agents; and blocking Helicobacter pylori colonization associated gastric morphological changes and gastroduodenal inflammation and ulceration. In addition, anti-inflammatory activity due to down-regulation of proinflammatory cytokines and cellular and intercellular adhesion agents, suppressing leukocyte-endothelium interaction, inhibiting nuclear signaling pathways of inflammatory process, and modulating intracellular transduction and transcription pathways have key roles in the anti-ulcer action of dietary polyphenols. In conclusion, administration of a significant amount of dietary polyphenols in the human diet or as part of dietary supplementation along with conventional treatment can result in perfect security and treatment of peptic ulcer. Further well-designed preclinical and clinical tests are recommended in order to recognize higher levels of evidence for the confirmation of bioefficacy and safety of dietary polyphenols in the management of peptic ulcer.
PMCID: PMC4458761  PMID: 26074689
Anti-inflammatory; Dietary supplement; Helicobacter pylori; Inflammatory cytokines; Natural medicine; Non-steroidal anti-inflammatory drugs; Peptic ulcer; Polyphenols; Ulcer healing
5.  The effect of sevoflurane versus propofol anesthesia on troponin I after congenital heart surgery, a randomized clinical trial 
The ischemic preconditioning phenomenon can save myocardium against move severe ischemic damages and reduce infarction size and furthermore a heart rhythm disturbance. In this study we examine relationship between troponin I (as a structural myocardial protein) level and anesthetic agents in the children.
Materials and Methods:
In this study 84 children under 12 years age before cardiac surgery were divided randomly into two groups of 42 each. For anesthetic maintenance sevoflurane with dose of 0.5-1 MAC was used in Group 1 and 100-150 mg/kg/min of intravenous propofol in Group 2 for maintenance of anesthesia. Troponin I level was assessed 2 before and 1 hour after anesthetic induction. Outcome measures included the serum cardiac troponin I level in children before and after surgery in two study groups.
There was no significant difference between two groups in indices and both groups were homogenous in this point of view. The troponin I level after surgery was significantly increased in two groups. In the sevoflurane group it was 0.04 ± 0.12 to 0.05 ± 0.09 ng/ml (P value = 0.003) and the propofol group was 0.12 ± 0.26 to 0.19 ± 0.38 ng/ml (P value = 0.001).
In this study two Anesthetic regimens were compared to assess the mean troponin I level before and after pediatric closed heart surgery, and it was shown that mean troponin level before and after surgery in the sevoflurane group was less than the propofol group. But this result was not statistically significant. These results indicate that although more protective effects of sevoflurane on myocardial injuries during pediatric cardiac surgery is predominant but this effect has no significant difference in the propofol group.
PMCID: PMC4434452  PMID: 26015912
Heart surgery; pediatric; propofol; sevoflurane; Troponin I
6.  The Prevalence of Magnetic Resonance Imaging Hyperintensity in Migraine Patients and Its Association with Migraine Headache Characteristics and Cardiovascular Risk Factors 
Oman Medical Journal  2015;30(3):203-207.
To determine the frequency of hyperintense foci in migraine patients and the relationship with migraine headache characteristics and cardiovascular risk factors.
Ninety patients with migraine headache (70 without aura and 20 with aura) were enrolled and interviewed. Information on their headache (severity, frequency, and mean disease duration) and other related data was obtained by completing a clinical checklist. Subsequently, brain magnetic resonance imaging (MRI) was performed and each patient was then evaluated for hyperintense lesions.
Of the 90 patients, 29 (32%) had silent hyperintense lesions on their MRI. The mean age of the patients with hyperintense foci was 41 years while those with no lesions was 33 years (p<0.010). Supratentorial hyperintense lesions represented the majority of lesions in the patients (n=46, 63%). Moreover, 56.3% of the lesions (n=41) were located within the right hemisphere. Cardiovascular risk factors such as smoking, serum cholesterol, oral contraceptive pills use, and body mass index (BMI) were not significantly different in these two groups (p>0.050). The lesions were found significantly more frequently in the patients who experienced chronic migraine (p=0.032).
Our study adds weight to the theory that disease duration has a key role in the formation of hyperintense brain lesions. Certain cardiovascular risk factors such as sex, smoking, serum cholesterol, and BMI, do not affect the presence or absence of such lesions, suggesting that the relationship between migraine and these lesions may be directly due to the effects of migraine itself.
PMCID: PMC4459160  PMID: 26171127
Migraine Disorders; Magnetic Resonance Imaging; White Matter; Migraine with Aura; Migraine without Aura
8.  Hypoglycemic and hypolipidemic activities of Salvia hydrangea in streptozotocin-induced diabetes in rats 
This study was to investigate the potential anti-diabetic effects of alcoholic extract of Salvia hydrangea in rats.
Materials and Methods:
Thirty five male Wistar rats were divided into five groups namely non-diabetic control, diabetic control, and three experimental diabetic that received either Salvia hydrangea extract for 21 days at the doses of 100 and 200 or glibenclamide at the dose of 10 mg/kg through gavage feeding. To induce diabetes, streptozotocin was injected intraperitoneally.
Insulin and HDL levels in the group receiving the high dose of the extract showed significant increase, whereas the amount of cholesterol in rats that received glibenclamide and the extract showed a significant decrease as compared to the diabetic control group (P<0.05). The blood glucose levels showed significant reduction in all experimental groups (P<0.05).
Consumption of the extract of the aerial parts of S. hydrangea which reduces blood fat and increases insulin may have beneficial effects on the symptoms of diabetes and hyperlipidemia.
PMCID: PMC4439459  PMID: 26019807
Diabetes; Glucose; Salvia hydrangea; Streptozotocin
9.  Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis 
AIM: To investigate the efficacy of probiotics in irritable bowel syndrome (IBS) patients.
METHODS: PubMed, Cochrane library, Scopus, Google Scholar, and databases were searched for literature published between September 2007 and December 2013. The applied Mesh terms were “probiotics,” “irritable bowel syndrome,” and “irritable bowel syndrome treatment.” The collected data contained24 clinical trials, of which 15 were eligible for meta-analysis and nine were reviewed systematically. All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement. The Jadad score was used to assess the methodological quality of trials. The quality scale ranges from 0 to 5 points, with a score ≤ 2 indicating a low quality report, and a score of ≥ 3 indicating a high quality report. Relative risk (RR), standardized effect size, and 95%CI were calculated using the DerSimonian-Laird method. The Cochran Q test was used to test heterogeneity with P < 0.05. Funnel plots were constructed and Egger’s and Begg-Mazumdar tests were performed to assess publication bias.
RESULTS: A total of 1793 patients were included in the meta-analysis. The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96 (95%CI: 1.14-3.36; P = 0.01). RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43 (95%CI: 1.13-5.21; P = 0.02). For adequate improvement of general symptoms in IBS patients, the RR of seven included trials (six studies) comparing probiotics with placebo was 2.14 (95%CI: 1.08-4.26; P = 0.03). Distension, bloating, and flatulence were evaluated using an IBS severity scoring system in three trials (two studies) to compare the effect of probiotic therapy in IBS patients with placebo, the standardized effect size of mean differences for probiotics therapy was -2.57 (95%CI: -13.05--7.92).
CONCLUSION: Probiotics reduce pain and symptom severity scores. The results demonstrate the beneficial effects of probiotics in IBS patients in comparison with placebo.
PMCID: PMC4356930  PMID: 25780308
Evidence-based medicine; Irritable bowel syndrome; Meta-analysis; Probiotics; Systematic review; Clinical trial
10.  In vitro protection of human lymphocytes from toxic effects of chlorpyrifos by selenium-enriched medicines 
Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used extensively in agricultural and domestic pest control, accounting for 50% of the global insecticidal use. In the present study, protective effects of two selenium-enriched strong antioxidative medicines IMOD and Angipars were examined in human lymphocytes treated with CP in vitro.
Materials and Methods:
Isolated lymphocytes were exposed to 12 µg/ml CP either alone or in combination with effective doses (ED50) of IMOD (0.2 µg/ml) and Angipars (1 µg/ml). After 3 days incubation, the viability and oxidative stress markers including cellular lipid peroxidation (LPO), myeloperoxidase (MPO), total thiol molecules (TTM), and total antioxidant power (TAP) were evaluated. Also, the levels of tumor necrosis factor-α (TNF-α), as inflammatory index along with acetylcholinesterase (AChE) activity and cell apoptosis were assessed by flow cytometry.
Results indicated that effective doses of IMOD and Angipars reduced CP-exposed lymphocyte mortality rate along with oxidative stress. Both agents restored CP-induced elevation of TNF-α and protected the lymphocytes from CP-induced apoptosis and necrosis.
Overall, results confirm that IMOD and Angipars reduce the toxic effects associated with CP through free radical scavenging and protection from apoptosis and necrosis.
PMCID: PMC4414995  PMID: 25945242
Angipars; Chlorpyrifos; Human lymphocytes; IMOD; OrganophosphorusOxidative stress
11.  Effects of ethanol extract of Salvia hydrangea on hepatic and renal functions of streptozotocin-induced diabetic rats 
A wide range of liver and kidney disorders are associated with diabetes and there is a mutual relationship between diabetes and these diseases. Herbal medicine with having abundant ingredients is one of these options. The goal of this study was to compare the effects of alcoholic extract of aerial parts of Salvia hydrangea with glibenclamide on functional tests of liver and kidney in diabetic rats induced by streptozotocin.
Materials and Methods:
In this study, 35 male Wistar rats were divided into five groups (n= 7 in each group): control, diabetic control, and three experimental diabetic groups. The controls had normal access to water and food, the diabetic control group was given drug solvent and the three experimental groups received ethanol extract of Salvia hydrangea at doses of 100 and 200 mg and glibenclamideat a dose of 10 mg/kg/BW by gavage, respectively. To induce diabetes, a single dose of streptozotocin (60 mg/kg/BW) was injected to rats intraperitoneally. Blood samples were collected at day 21 from all groups and the related blood factors were measured and analyzed.
The results showed that the levels of creatinine, urea, aspartate aminotransferase (AST), and fasting blood sugar (FBS) in all diabetic groups increased compared to the control group. In all experimental groups and the group which received glibenclamide,a significant decrease was shown compared to the diabetic group (p<0.05).
The consumption of alcoholic extract of aerial parts of Salvia hydrangea may have beneficial effects on the reduction of diabetic complications by lowering blood sugar without any adverse effects on the kidney and liver tissue.
PMCID: PMC4418063  PMID: 25949955
Diabetes; Liver; Kidney; Streptozotocin; Glibenclamide; Salvia hydrangea
12.  Pharmaceutical supply chain risk assessment in Iran using analytic hierarchy process (AHP) and simple additive weighting (SAW) methods 
Pharmaceutical supply chain is a significant component of the health system in supplying medicines, particularly in countries where main drugs are provided by local pharmaceutical companies. No previous studies exist assessing risks and disruptions in pharmaceutical companies while assessing the pharmaceutical supply chain. Any risks affecting the pharmaceutical companies could disrupt supply medicines and health system efficiency. The goal of this study was the risk assessment in pharmaceutical industry in Iran considering process's priority, hazard and probability of risks.
The study was carried out in 4 phases; risk identification through literature review, risk identification in Iranian pharmaceutical companies through interview with experts, risk analysis through a questionnaire and consultation with experts using group analytic hierarchy process (AHP) method and rating scale (RS) and risk evaluation of simple additive weighting (SAW) method.
In total, 86 main risks were identified in the pharmaceutical supply chain with perspective of pharmaceutical companies classified in 11 classes. The majority of risks described in this study were related to the financial and economic category. Also financial management was found to be the most important factor for consideration.
Although pharmaceutical industry and supply chain were affected by current political conditions in Iran during the study time, but half of total risks in the pharmaceutical supply chain were found to be internal risks which could be fixed by companies, internally. Likewise, political status and related risks forced companies to focus more on financial and supply management resulting in less attention to quality management.
PMCID: PMC4354976  PMID: 25838919
Pharmaceutical supply chain; Risk assessment; analytic hierarchy process (AHP) method; Simple additive weighting (SAW) method; Iran pharmaceutical industry
15.  Acknowledgement of manuscript reviewers 2014 
Contributing reviewers
The editors of DARU Journal of Pharmaceutical Sciences would like to thank all our reviewers who have contributed to the journal in Volume 22 (2014).
PMCID: PMC4323264
17.  The prevalence of female sexual dysfunction among migraine patients 
Iranian Journal of Neurology  2015;14(1):8-11.
Background: Female sexual dysfunction (FSD) defines as any disorder in the process of sexual contact including 6 main domains, desire, arousal, lubrication, orgasm, orgasm satisfaction and pain. This study was conducted to evaluate prevalence of sexual dysfunction disorder in women with migraine headache and also find the associated factors related to migraine characteristics.
Methods: A total of 69 eligible woman patients fulfilling criteria for migraine participated in this study. The Female Sexual Function Index (FSFI), a multi-dimensional self-report implement for appraisal of Female Sexual Function during the past month were utilized in this study. The information related to migraine including frequency, duration of headache attack, severity of headache according to visual analog scale (VAS) score and headache impact test (HIT) score were obtained using a self-administrated questionnaire.
Results: About 68.4% of patients had an FSFI score < 28. In domains of desire 73.7%, arousal 64.9%, lubrication 21.1%, orgasm 33.3%, satisfaction 17.5%, and pain 40.4% of patients reported some degree of dysfunction. Among variables related to migraine characteristics, only a significant association between frequency and sexual dysfunction were recorded (P < 0.05).
Conclusion: FSD is prevalent among migraine patients. The frequency of a migraine attack is associated with FSD. Serotonin mechanisms such as 5HT2, 5HT3 agonist have been hypothesized as a shared etiology for migraine and sexual dysfunction.
PMCID: PMC4395811  PMID: 25874050
Migraine; Female Sexual Dysfunction; Female Sexual Function Index Score
18.  Growing burden of diabetes in Pakistan and the possible role of arsenic and pesticides 
This review is undertaken to address the possible role of arsenic and pesticides in the prevalence of diabetes in Pakistan and to highlight a resourceful targeted research in this area.
A bibliographic search of scientific databases was conducted with key words of “epidemics of diabetes in Pakistan”, “diabetes in Asia”, “diabetes mellitus and environmental pollutants”, “diabetes mellitus and heavy metals”, “diabetes mellitus and pesticides”, “prevalence of pesticides in Pakistan”, and “heavy metals contamination of drinking water, “vegetables and fruits in Pakistan”. More than 200 articles were examined. Studies reporting the prevalence of diabetes mellitus (DM), pesticides and heavy metal contamination of drinking water, fruits and vegetables were included in the study. According to WHO 2011 report, about 12.9 million people are suffering from DM and the number is constantly increasing. Water pollution is a major public health threat in Pakistan. Most of the people in Pakistan are exposed to arsenic and pesticides either in drinking water or through vegetables, fruits, and other edible items with various concentrations above the WHO/FAO permissible limits. Being an agricultural country, a 1169% increase has been recorded with the use of different types of pesticides since last two decades, and almost similar rise in the burden of diabetes.
There is a growing global concern of arsenic and pesticides exposure with the incidence of DM. Besides other factors, the environmental attributors in the incidence of DM in Pakistan have not been conclusively elucidated yet which in turn deserve a resourceful targeted research.
PMCID: PMC4271443  PMID: 25530951
Arsenic; Diabetes mellitus; Environmental pollutants; Heavy metals; Pakistan; Pesticides; Review
19.  The Influence of Pregnancy and Lactation on Maternal Bone Health: A Systematic Review 
Osteoporosis is considered as an important public health problem especially in postmenopausal women. There are some hypotheses support the contributory effect of pregnancy and lactation on osteoporosis later in life. High calcium demand during pregnancy and lactation and low estrogenic state support those hypotheses. Numerous studies have investigated on the issue but there is no consensus about the contributory effect of pregnancy and lactation on osteoporosis. To explore the current state of fact, in the present study, all bibliographic databases were searched and all relevant studies on the topic of osteoporosis, lactation, and pregnancy were reviewed.
The review shows that despite of controversial results, pregnancy may have protective effect on bone especially if followed by lactation.
PMCID: PMC4266784  PMID: 25530765
bone loss; pregnancy; lactation; parity
20.  Haptoglobin Duplicon, Hemoglobin, and Vitamin C: Analyses in the British Women's Heart and Health Study and Caerphilly Prospective Study 
Disease Markers  2014;2014:529456.
Background. Haptoglobin acts as an antioxidant by limiting peroxidative tissue damage by free hemoglobin. The haptoglobin gene allele Hp2 comprises a 1.7 kb partial duplication. Relative to allele Hp1, Hp2 carriers form protein multimers, suboptimal for hemoglobin scavenging. Objective. To examine the association of haptoglobin genotype with a range of phenotypes, with emphasis on vitamin C and hemoglobin levels. Methods. We applied a quantitative PCR assay for the duplication junction to two population cohorts including 2747 British women and 1198 British men. We examined the association of haptoglobin duplicon copy number with hemoglobin and vitamin C and used the copy number to complete a phenome scan. Results. Hemoglobin concentrations were greater in those with Hp2,2 genotype, in women only (Hp1,1 13.45 g/dL, Hp1,2 13.49 g/dL, Hp2,2 13.61 g/dL; P = 0.002), though statistically there was no evidence of a difference between the sexes (z value = 1.2, P = 0.24). Haptoglobin genotype was not associated with vitamin C or any other phenotype in either cohort. Conclusions. Our results do not support association of haptoglobin genotype with vitamin C or with other phenotypes measured in two population cohorts. The apparent association between haptoglobin genotype and hemoglobin in the women's cohort merits further investigation.
PMCID: PMC4265517  PMID: 25525287
22.  Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women 
In spite of several studies, the impact of homocysteine level and folic acid supplementation on bone metabolism is yet to be recognized. In this registered clinical trial (IRCT2014042217385N1), we aimed to find out the power of 6-month folic acid supplementation on homocysteine level and bone metabolism.
Forty postmenopausal osteoporotic women (50 to 87 years) were enrolled in the study. All participants were randomized to receive folic acid 1 mg (n = 17) or placebo (n = 14). At baseline, 3 months, and finally 6 months post intervention, the level of homocysteine, vitamin B12, and bone biomarkers were measured.
Both groups were similar at baseline. The homocysteine decreased in both groups but statistically non-significant (P > 0.05). The changes of the serum level of vitamin B12, osteocalcin, and β cross laps were significant between groups after 6 months (P ≤ 0.05).
The trend of changes of bone biomarkers after 6 months folic acid supplementation shows that homocysteine concentration and/or folic acid supplementation have impact on the rate of bone metabolism. However, further investigations by larger sample size and differentiating age and gender are still needed to clarify the exact role of folate, homocysteine and vitamin B12.
PMCID: PMC4172791  PMID: 25223378
Homocysteine; Folic acid; BMD; Bone biomarkers; Osteoporosis; Clinical trial
23.  The effect of preoperative intravenous paracetamol administration on postoperative fever in pediatrics cardiac surgery 
Post-operative fever is a common complication of cardiac operations, which is known to be correlated with a greater degree of cognitive dysfunction 6 weeks after cardiac surgery. The aim of the present study was to examine efficacy and safety of single dose intravenous Paracetamol in treatment of post-operative fever in children undergoing cardiac surgery.
Materials and Methods:
In this randomised, double-blind, placebo-controlled clinical trial, 80 children, aged 1-12 years, presenting for open heart surgery were entered in the trial and randomly allocated into two groups: Placebo and Paracetamol. After induction of anaesthesia, 15 mg/kg intravenous Paracetamol solution was infused during 1 h in the Paracetamol group. Patients in placebo group received 15 mg/kg normal saline infusion during the same time. Since the end of operation until next 24 h in intensive care unit, axillary temperature of the two group patients was recorded in 4-h intervals. Any fever that occurred during this period had been treated with Paracetamol suppository (125 mg) and the amount of antipyretic drug consumption for each patient had been recorded. In order to examine the safety of Paracetamol, patients were evaluated for drug complication at the same time.
Mean axillary temperature during first 24 h after operation was significantly lower in Paracetamol group compared with placebo group (P = 0.001). Overall fever incidence during 24 h after operation was higher in placebo group compared with Paracetamol group (P = 0.012). Of Paracetamol group patients, 42.5% compared with 15% of placebo group participants had no consumption of antipyretic agent (Paracetamol suppository) during 24 h after operation (P = 0.001).
This study suggests that single dose administration of intravenous Paracetamol before paediatric cardiac surgeries using cardiopulmonary bypass; reduce mean body temperature in the first 24 h after operation.
PMCID: PMC4178333  PMID: 25298601
Cardiac surgery; paracetamol; paediatric; post-operative fever
24.  Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients 
Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress.
Materials and Methods:
Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days.
Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004).
Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients.
PMCID: PMC4268196  PMID: 25535502
Hypertonic saline; mannitol; oxidative stress response; traumatic brain injury patients
25.  Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis 
World Journal of Gastroenterology : WJG  2014;20(31):10876-10885.
AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.
METHODS: Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon.
RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO.
CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.
PMCID: PMC4138466  PMID: 25152589
Butyrate; L-carnitine; Colitis; Inflammatory bowel disease; Oxidative stress; Lactobacillus casei; Probiotic

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