The exact causes of inflammatory bowel disease (IBD) are not yet fully defined. From a vast body of literature, we know that the immune response has long been involved in the pathogenesis of IBD, including both ulcerative colitis and Crohn’s disease. A variety of specific alterations can lead to immune activation and inflammation directed to the colon, as revealed by some animal models. Current research has focused on the role of antibodies in downstream events and mechanisms of autoimmunity and inflammation. It is not well known whether the production of antibodies is a serologic consequence of IBD, or if it is a result of barrier dysfunction induced by inflammation. Here, we present a new hypothesis to distinguish the complex links between genetic susceptibility, barrier dysfunction, commensal and pathologic microbial factors and inflammatory response (especially autoantibodies) in the pathogenesis of IBD. To ascertain the hypothesis, we developed a pilot model with the concept of the presence of antibodies against enteric bacterial antigens in IBD. Results confirmed our hypothesis. Our hypothesis suggests the possibility of subcutaneous vaccination of animals with administration of all or specific enteric bacterial antigens.
Inflammatory bowel disease rat model; Pathogenesis; Barrier dysfunction; Microbial factor
Iran; Sanction; Science
AIM: To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease (IBD) by conducting a meta-analysis.
METHODS: Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD. The search terms were: “herb” or “plant” or “herbal” and “inflammatory bowel disease”. Data were collected from 1966 to 2013 (up to Feb). The “clinical response”, “clinical remission”, “endoscopic response”, “endoscopic remission”, “histological response”, “histological remission”, “relapse”, “any adverse events”, and “serious adverse events” were the key outcomes of interest. We used the Mantel-Haenszel, Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects. For subgroup analyses, we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability.
RESULTS: Seven placebo controlled clinical trials met our criteria and were included (474 patients). Comparison of herbal medicine with placebo yielded a significant RR of 2.07 (95%CI: 1.41-3.03, P = 0.0002) for clinical remission; a significant RR of 2.59 (95%CI: 1.24-5.42, P = 0.01) for clinical response; a non-significant RR of 1.33 (95%CI: 0.93-1.9, P = 0.12) for endoscopic remission; a non-significant RR of 1.69 (95%CI: 0.69-5.04) for endoscopic response; a non-significant RR of 0.64 (95%CI: 0.25-1.81) for histological remission; a non-significant RR of 0.86 (95%CI: 0.55-1.55) for histological response; a non-significant RR of 0.95 (95%CI: 0.52-1.73) for relapse; a non-significant RR of 0.89 (95%CI: 0.75-1.06, P = 0.2) for any adverse events; and a non-significant RR of 0.97 (95%CI: 0.37-2.56, P = 0.96) for serious adverse events.
CONCLUSION: The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on endoscopic and histological outcomes, but the number of studies is limited to make a strong conclusion.
Herbal medicine; Inflammatory bowel disease; Efficacy; Relapse; Adverse events; Meta-analysis
Multiple sclerosis (MS) is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000). Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF β) and their copied biopharmaceuticals (CBPs) and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs).
A literature-based Markov model was developed to assess the cost-effectiveness of three INF βs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS) in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS). Disease progression transition probabilities for symptom management and INF β therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS). A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER) of cost/quality adjusted life year (QALY) for all available INF β products (brands, biosimilars and CBPs) were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model.
ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($) respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913.
The Markov pharmacoeconomics model determined that according to suggested threshold for developing countries by world health organization, all brand INF β products are cost effective in Iran except Avonex. The best strategy among INF β therapies is CBP intramuscular INF β-1a (Cinnovex). Results showed that a policy of encouraging accessibility to CBPs and biosimilars could make even high technology products cost-effective in LMICs.
Cost-Effectiveness; Decision analysis; Economic evaluation; Interferon beta; Markov model; Modeling; Switching
AIM: To study the clinical and laboratory characteristics of autoimmune hepatitis (AIH), and compare them with International Autoimmune Hepatitis Group (IAHG) criteria.
METHODS: Sixty consecutive patients with AIH attended the University Clinic at Tabriz University of Medical Sciences, Iran for a 12 mo period and were assessed in a case series study. Serological and biochemical evaluations were carried out in all patients. Autoantibodies, such as antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody (ALKM-1) type 1, and perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) were evaluated in these patients. A liver biopsy was performed after diagnosis of the disease. Patients were evaluated in terms of their signs and symptoms, and laboratory results and the degree to which they corresponded with the diagnostic criteria of IAHG. In this study, both a comprehensive diagnostic scoring system and a simplified diagnostic scoring system were employed for AIH.
RESULTS: Sixty patients, 20 male, 40 female, mean age 39.45 ± 17.50 years, participated in the study. Treatment began immediately after enrolment into the study. The percent distribution of the study population into definite and probable did not change after the treatment. The most common symptoms in descending order were fatigue (100%), icter (66.7%), abdominal discomfort (33.3%), abdominal distension (28.3%), dark urine (23.3%), edema (23.3%), hematemesis (20.0%), pruritus (20.0%), melena (11.7%) and pale stool (10.0%). At the physical examination, splenomegaly, ascites, hepatomegaly, epigastric tenderness and an abdominal mass were found in 50.0%, 16.7%, 13.3%, 5.0% and 3.3% of patients, respectively. Hypergammaglobulinemia was detected in 95.0% of cases. ALKM-1, P-ANCA, ANA and ASMA were positive in 71.4%, 66.7%, 42.4% and 19.4% of cases, respectively. Portal hypertensive gastropathy (45.0%), esophageal varices (41.7%) and cirrhosis (40.0%) were the most prevalent complications of AIH, and there was no evidence of primary sclerosing cholangitis, ulcerative colitis and overlap syndrome in these patients. According to IAHG criteria, 80.0% of cases had a definite diagnosis, 15.0% had a probable diagnosis and 5.0% had no AIH. The percent distribution of the study population into definite, probable and no AIH did not change after using the simplified diagnostic scoring system for AIH.
CONCLUSION: This research showed that the majority of cases in our study were appropriately diagnosed according to the IAHG criteria and simplified scoring system. Thus, these criteria are very useful.
Autoimmune hepatitis; International criteria; Diagnosis; Clinical; Paraclinical
Exemestane was approved in 2005 for adjuvant treatment of breast cancer. In this study, we aimed to assess whether it is cost-effective in comparison to available alternatives.
Material and methods
To evaluate the efficacy of exemestane, a systematic review was conducted by searching electronic databases. The outcomes of interest were “clinical benefit”, “overall response” and “disease-free survival rate”. To evaluate the cost of treatments, costs of both domestic generic and imported brand medicines were taken into account, and the incremental cost-effectiveness ratio (ICER) was calculated for each comparison.
Regarding primary breast cancer, based upon available evidence, exemestane could not be considered as a cost-effective medicine either in generic or brand form compared with placebo (ICER: 119,100 and 215,525), with tamoxifen after 2-3 years of therapy (ICER: 35,150 and 82,400) and with sequential treatment by tamoxifen and exemestane (dominated because of lower effectiveness and higher cost). In metastatic breast cancer, exemestane was not considered a cost-effective treatment compared with both anastrozole and megestrol acetate (dominated) and was highly cost-effective compared with tamoxifen (ICERs: 2,208 and 4,326 dollars per one more patient with an overall response for generic and brand medicines) although even in this case it was not cost-effective in terms of the 1-year survival rates (dominated).
Regarding current evidence and related costs in terms of Iranian pharmaceutical market prices, exemestane could not be considered a cost-effective treatment in primary and advanced breast cancer compared with available alternatives. However, more evidence is still needed for more certain decisions.
systematic review; cost-effectiveness; anastrozole; letrozole; megestrol acetate; exemestane; evidence based medicine
Obesity is the most prevalent health problem affecting all age groups, and leads to many complications in the form of chronic heart disease, diabetes mellitus Type 2 and stroke. A systematic review about safety and efficacy of herbal medicines in the management of obesity in human was carried out by searching bibliographic data bases such as, PubMed, Scopus, Google Scholar, Web of Science, and IranMedex, for studies reported between 30th December 2008 to 23rd April 2012 on human or animals, investigating the beneficial and harmful effects of herbal medicine to treat obesity. Actually we limited our search to such a narrow window of time in order to update our article published before December of 2008. In this update, the search terms were “obesity” and (“herbal medicine” or “plant”, “plant medicinal” or “medicine traditional”) without narrowing or limiting search items. Publications with available abstracts were reviewed only. Total publications found in the initial search were 651. Total number of publications for review study was 33 by excluding publications related to animals study.
Studies with Nigella Sativa, Camellia Sinensis, Crocus Sativus L, Seaweed laminaria Digitata, Xantigen, virgin olive oil, Catechin enriched green tea, Monoselect Camellia, Oolong tea, Yacon syrup, Irvingia Gabonensi, Weighlevel, RCM-104 compound of Camellia Sinensis, Pistachio, Psyllium fibre, black Chinese tea, sea buckthorn and bilberries show significant decreases in body weight. Only, alginate-based brown seaweed and Laminaria Digitata caused an abdominal bloating and upper respiratory tract infection as the side effect in the trial group. No other significant adverse effects were reported in all 33 trials included in this article.
In conclusion, Nigella Sativa, Camellia Synensis, Green Tea, and Black Chinese Tea seem to have satisfactory anti-obesity effects. The effect size of these medicinal plants is a critical point that should be considered for interpretation. Although there was no report for side effect in these trials, we believe that safety of these plants still remains to be elucidated by further long-term studies.
Herbal medicine; Obesity; Systematic review
Poisoning morbidity and mortality is high in the developing world. Systems for care of poisoned patients differ markedly between countries. In this paper a comparison of two very different systems for the care of poisoned patients, is presented. Specifically, the role of poison centers and poison treatment centers in the US and Iran are contrasted. A systematic literature search was undertaken utilizing the PubMed, Scopus, and Google Scholar and the keywords “poison centers”, “treatment” “Iran” “United States of America” and 100 publications were identified. From these, relevant data were found in 23 publications. The information was double-checked and data were summarized herein.
We find that the system of the care of poisoned patients relies heavily on certified poison centers in the US and that only a few hospitals have well developed medical toxicology services. In contrast, in Iran, the poison center system is somehow less developed and the care of poisoned patients is provided in centralized high volume hospital poison units.
Although both the US and Iran have highly developed systems for the care of poisoned patients they are distinctly different. Comparative studies based on these systems could provide important data for developing countries with more rudimentary poison control and treatment facilities.
Iran; Poisoning Management; Review; USA
Phthalic acid esters (PAEs) have been employed in polymer materials as a plasticizer to form them more flexible, adhesive, and soluble. These compounds are mainly used in paints, varnishes, personal cares, cosmetics, paper coatings, and adhesives even in bottled waters, shampoo, body deodorant, hairspray, and gels. Phthalates are able to possess remarkable toxic variations depending on their structures. So far, Di-(2-EthylHexyl) Phthalate DEHP and Di-n- Butyl Phthalate DBP have been found to cause reproductive and developmental toxicities. The U.S. Environmental Protection Agency (EPA) classified DEHP as probable human carcinogen. To the best of our knowledge, phthalates showed diverse toxicity profiles according to their structures in the liver, kidneys, thyroid, and testes, which are involved in general toxicity. Furthermore, they are introduced as hormonally-active agents, because they can interfere with the endocrine system in human. Incidence of developmental abnormalities (like skeletal malformations and cleft palate, and undescended testes, lowering testes weight and anogenital distance) seems increasing via high exposure to phthalate metabolites. Although, increasing the capacity for phthalate free plasticizer productions is the first step to restrict the distribution of these toxic manmade compounds, finding the new ways for phthalate absorption from the soil in agricultural fields may have benefits. Also, evaluation and examination of diverse sources of medicinal and food plants to determine the level of phthalate accumulation in their organs are extremely recommended to avoid creating toxicity particularly in reproductive systems.
Pharmacists as one of health-care providers face ethical issues in terms of pharmaceutical care, relationship with patients and cooperation with the health-care team. Other than pharmacy, there are pharmaceutical companies in various fields of manufacturing, importing or distributing that have their own ethical issues. Therefore, pharmacy practice is vulnerable to ethical challenges and needs special code of conducts. On feeling the need, based on a shared project between experts of the ethics from relevant research centers, all the needs were fully recognized and then specified code of conduct for each was written. The code of conduct was subject to comments of all experts involved in the pharmaceutical sector and thus criticized in several meetings. The prepared code of conduct is comprised of professional code of ethics for pharmacists, ethics guideline for pharmaceutical manufacturers, ethics guideline for pharmaceutical importers, ethics guideline for pharmaceutical distributors, and ethics guideline for policy makers. The document was compiled based on the principles of bioethics and professionalism. The compiling the code of ethics for the national pharmaceutical system is the first step in implementing ethics in pharmacy practice and further attempts into teaching the professionalism and the ethical code as the necessary and complementary effort are highly recommended.
Pharmaceuticals; pharmacy ethics; pharmacy professionalism
Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.
AIM: To investigate the efficacy of Magliasa, a traditional Iranian formula, on experimental colitis.
METHODS: After botanical authentication of herbal ingredients, formulation of Magliasa, quantitative determination of total glucosinolates and total phenolic content, and analysis of the thin layer chromatography profile were performed. Colitis was then induced in male rats by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in all groups, aside from the Sham group. The experimental groups consisted of: the Sham group that received only normal saline; the Mag-50, Mag-100 and Mag-200 groups, which received 50, 100 and 200 mg/kg per day of Magliasa, respectively; the control group, which received vehicle water orally; the infliximab group, which received infliximab (5 mg/kg per day, subcutaneously); and the Dexa group, which received dexamethasone (1 mg/kg per day, orally). After completing the treatment period (2 wk), the rats were sacrificed, the colon was removed, its macroscopic and microscopic changes were recorded, and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), total antioxidant capacity, myeloperoxidase (MPO), and lipid peroxidation (LPO) were assessed in colon homogenate.
RESULTS: The mean value of total glucosinolates in one gram of Magliasa was 19 ± 1 μmol. The mean value of the total phenolic content was 293.8 ± 17.6 mg gallic acid equivalents per 100 gram of Magliasa. Macroscopic scores were significantly decreased in Mag-100 (1.80 ± 0.58, P = 0.019) and Mag-200 (1.20 ± 0.20, P = 0.001) compared to the control group (3.40 ± 0.24), although some inflammation and hyperemia were evident. Treatment of rats by dexamethasone (0.33 ± 0.21, P < 0.001) and infliximab (0.83 ± 0.31, P < 0.001) remarkably attenuated scores where mild hyperemia was observed macroscopically. In comparison to the control group (4.00 ± 0.32), only Mag-200 (1.60 ± 0.40) showed a significant decrease in colonic histopathological scores (P = 0.005). Minimal mucosal inflammation was observed in the Dexa group (0.67 ± 0.21, P < 0.001). The levels of TNF-α, IL-1β and MPO were significantly lower in all groups compared to the controls (P < 0.05). A significant decrease in LPO was seen in the Mag-200 (3.27 ± 0.77, P = 0.01) and Dexa (3.44 ± 0.22, P = 0.011) groups in comparison to the control group (6.43 ± 0.61). Only dexamethasone caused a significant increase in antioxidant power in comparison to the control group (346.73 ± 9.9 vs 228.33 ± 2.75, P < 0.001). Infliximab and different doses of Magliasa did not show any remarkable increase in antioxidant capacity (P > 0.05). The effect of Magliasa in all of mentioned parameters, except antioxidant capacity, was dose dependent.
CONCLUSION: The effects of Magliasa in TNBS-induced colitis are encouraging and warrant clinical trials for further confirmation.
Magliasa; Traditional Iranian medicine; Colitis; Neutrophil infiltration; Inflammatory cytokines; Oxidative stress
Besides the pathological states, diabetes mellitus may also alter the hepatic biotransformation of pharmaceutical agents. It is advantageous to understand the effect of diabetes on the pharmacokinetic of drugs. The objective of this study was to define the pharmacokinetic changes of tramadol and its main metabolites after in vivo intraperitoneal administration and ex vivo perfused liver study in diabetic rat model.
Tramadol (10 mg/kg) was administered to rats (diabetic and control groups of six) intraperitoneally and blood samples were collected at different time points up to 300 min. In a parallel study, isolated liver perfusion was done (in diabetic and control rats) by Krebs-Henseleit buffer (containing 500 ng/ml tramadol). Perfusate samples were collected at 10 min intervals up to 180 min. Concentration of tramadol and its metabolites were determined by HPLC.
Tramadol reached higher concentrations after i.p. injection in diabetics (Cmax of 1607.5 ± 335.9 ng/ml) compared with control group (Cmax of 561.6 ± 111.4). M1 plasma concentrations were also higher in diabetic rats compared with control group. M2 showed also higher concentrations in diabetic rats. Comparing the concentration levels of M1 in diabetic and control perfused livers, showed that in contrast to intact animals, the metabolic ratios of M1 and M5 (M/T) were significantly higher in diabetic perfused liver compared to those of control group.
The pharmacokinetic of tramadol and its three metabolites are influenced by diabetes. As far as M1 is produced by Cyp2D6, its higher concentration in diabetic rats could be a result of induction in Cyp2D6 activity, while higher concentrations of tramadol can be explained by lower volume of distribution.
The complex metabolic syndrome, diabetes mellitus, is a major human health concern in the world and is estimated to affect 300 million people by the year 2025. Several drugs such as sulfonylureas and biguanides are presently available to reduce hyperglycemia in diabetes mellitus. These drugs have side effects and thus searching for a new class of compounds is essential to overcome this problems.
A series of seven novel N-(4-phenylthiazol-2-yl)benzenesulfonamides derivatives were synthesized and assayed in-vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well-known antidiabetic agent, as a reference drug. Four of the compounds were
effective, amongst which 13 show more prominent activity at 100 mg/Kg p.o. The experimental results are statistically significant at p < 0.05 level.
Thiazole; Benzenesulfonamides; Antidiabetic Activity; Diabetes Mellitus
Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer’s disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.
The synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman’s method. Docking studies were performed to get better insight into interaction of compounds with receptor.
The in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM) was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.
In this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.
In spite of the extreme rise to the knowledge of nanotechnology in pharmaceutical sciences, there are currently limited experimental works studying the interactions between nanoparticles (NPs) and the biological system. Adjustment of size and surface area plays the main role in the reaction between NPs and cells leading to their increased entrance into cells through skin, gastrointestinal and respiratory system. Moreover, change in physicochemical reactivity of NPs causes them to interact with circulatory and cellular proteins differentially leading to the altered parameters of their biokinetics, including adsorption, distribution, translocation, transformation, and elimination. A direct relationship between the surface area, reactive oxygen species generating capability, and proinflammatory effects of NPs have been found in respiratory tract toxicity. Additionally, complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanodrugs have been well defined. Inhalation studies of some NPs have confirmed the translocation of inhaled materials to extra pulmonary organs such as central nervous system (CNS) via olfactory neurons and induction of inflammatory response. Injectable uncoated NPs have a tendency to remain on the injection site while the poly ethanol glycol (PEG)-coated NPs can be notably drained from the injection site to get as far as the lymph nodes where they accumulate. This confirms the existence of channels within the extracellular matrix for NPs to move along. Furthermore, induction of DNA strand breaks and formation of micronuclei have been recorded for exposure to some NPs such as single-walled carbon nanotubes.
In the recent years, most of the studies have simply outlined better efficacy of nanodrugs, but few discussed their possible toxic reactions specially if used chronically. Therefore, we emphasize that this part of the nanoscience must not be undermined and toxicologists must be sensitive to set up suitable in vivo or in vitro toxicity models. A system for collecting data about the relationships between NPs’ structure-size-efficacy-toxicity (SSET) should be specified with special regard to portal of entry and target organ.
Nanomedicine; Biokinetics; Nanotoxicology; Review
Medicinal plants are presumed to be natural sources of antioxidants that protect organisms
from oxidative stresses. The present investigation aims to study the anti-oxidative
stress activity of the Stachys lavandulifolia (S. lavandulifolia) plant. This trial was conducted
on 26 healthy human subjects. The study was done in a before after fashion. The
included subjects were asked to consume the prepared infusion from 3 g aerial parts of S.
lavandulifolia on a daily basis. Doses were administered in every morning and evening for
14 days. At the beginning and the end of the study, blood samples were acquired to determine
the level of cellular lipid peroxidation and the total content of serum antioxidants.
Biomarkers analyzed from samples obtained before start of treatment and 14 days post
treatment, were subjected to paired t test analysis. Total blood antioxidants
reached from 2.3 ± 0.84 µmol/ml to 3.3 ± 0.54 µmol/ml. The lipid peroxidation reduced
and reached from 8.38 ± 1.78 to 11.6 ± 2.64 nmol/ml. The results suggest that S. lavandulifolia
possesses marked anti-oxidative stress activity and it can be useful as a supplement
in the management of diseases related to oxidative stress (Registration Number:
Antioxidant Effects; Clinical Trial; Medicinal Plants; Oxidative Stress; Stachys
Acute kidney injury (AKI) is a common and life-threatening complication following coronary artery bypass graft (CABG). Neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C have shown to be good predictive factors for AKI. Recently, there has been a growing interest in the use of hypertonic saline in cardiac operations.
The purpose of this study was to evaluate the prophylactic anti-inflammatory effect of hypertonic saline (Group A) infusion versus normal saline (Group B) on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients.
This randomized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center, Tehran, Iran. After applying exclusion criteria, the effects of preoperative hypertonic saline (294 meq Na) versus normal saline (154 meq Na) infusion on serum NGAL and Cystatin C levels were investigated in three intervals: before surgery and 24 and 48 hours postoperatively. The probable intraoperative or postoperative confounders, including pump time, cross-clamp time, heart rate, systolic and diastolic blood pressures, central venous pressure, arterial pH, partial pressure of arterial oxygen, fraction of inspired oxygen, blood sugar, Na, K, Mg, hemoglobins, white blood cells, hematocrits, and platelets, were recorded and compared between the two groups of study.
The study population comprised 40 patients, including 25 (62.5%) males, at a, mean age ± SD of 61.75 ± 8.13 years. There were no statistically significant differences between the patients’ basic, intraoperative, and postoperative characteristics, including intraoperative and postoperative hemodynamic variables and supports such as inotropic use. Intra-aortic balloon pump use and mortality were not seen in our cases.
Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml. Moreover, 10 patients in Group A and 17 patients in group B showed a rise in serum Cystatin C levels above 1.16 mg/dl.
Patients with AKI had significantly elevated NGAL and Cystatin C levels (p value < 0.001), but there were no significant differences in the decrease in the NGAL level in the hypertonic saline group versus the normal saline group (230.91 ± 92.68 vs. 239.74 ± 116.58 ng/ml, respectively; p value = 0.792), or in the decrease in the Cystatin C level in the hypertonic saline group versus the normal saline group (1.05 ± 0.26 vs. 1.06 ± 0.31, respectively; p value = 0.874).
Pre-treatment of CABG patients with hypertonic saline had no significant effect on serum NGAL and Cystatin C levels compared to the normal saline-receiving group. Our present data, albeit promising, have yet to fully document outcome differences.
Acute, kidney injury; Coronary artery bypass; Cystatin C; Neutrophil gelatinase-associated lipocalin protein, rat; Saline solution, hypertonic
The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.
To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS).
By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed.
After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07).
Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.
Heart rate; APACHE II score; SOFA score; GCS score; Head injury
Nanotechnology is one of the premiere technologies available today, having expanded both as field of scientific study and in the public consciousness. Despite this growth, the drawbacks, limitations and potential safety hazards associated with the incorporation of nanotechnology into existing industries are still being learned. The noticeable point is that there is no enough data available yet to analyze global use of nanotechnology from a meta-perspective. Three challenges can be defined in light of nanotoxicology. One, materials that might prove to be significantly toxic must be identified. Two, a system for the categorization of NP materials must be codified and made available to toxicologists. Third, a better understanding of nanoparticles biological interactions must be obtained, in order to make the best use of the first two goals. For all three, it must be remembered that research standards need to be developed for the gathering of data on the nanoscale, as that level is where the NPs and the patient’s biosystems will be interacting.
As requiring toxicologists to become nanotechnology experts would not be feasible, to properly incorporate the care of nanotoxicity into the existing medical framework, a range of experts across multiple fields of study must work in close synchronization. The focus needs to be on mechanism-driven research to ensure a solid scientific foundation for the assessment of NP and their role in healthcare.
Current opinion; Nanotoxicology; Nanotechnology
Physician prescribing is the most frequent medical intervention with a highest impact on healthcare costs and outcomes. Therefore improving and promoting rational drug use is a great interest. We aimed to assess the effectiveness and cost-effectiveness of two forms of conducting prescribing audit and feedback interventions and a printed educational material intervention in improving physician prescribing.
A four-arm randomized trial with economic evaluation will be conducted in Tehran. Three interventions (routine feedback, revised feedback, and printed educational material) and a no intervention control arm will be compared. Physicians working in outpatient practices are randomly allocated to one of the four arms using stratified randomized sampling. The interventions are developed based on a review of literature, physician interviews, current experiences in Iran and with theoretical insights from the Theory of Planned Behavior. Effects of the interventions on improving antibiotics and corticosteroids prescribing will be assessed in regression analyses. Cost data will be assessed from a health care provider’s perspective and incremental cost-effectiveness ratios will be calculated.
This study will determine the effectiveness and cost-effectiveness of three interventions and allow us to determine the most effective interventions in improving prescribing pattern. If the interventions are cost-effective, they will likely be applied nationwide.
Iranian Registry of Clinical Trials Registration Number: IRCT201106086740N1Pharmaceutical Sciences Research Center of TUMS Ethics Committee Registration Number: 90-02-27-07
Intervention study; Rational drug use; Audit and feedback; Printed educational material; Iran
Selective serotonin reuptake inhibitors (SSRIs) are the most frequently used antidepressants during pregnancy. There are conflicting results about their influence on pregnancy outcomes. The goal of this study was to update our previous meta-analysis about pregnancy outcomes following exposure to SSRIs. For this purpose, all relevant databases were searched from 1990 to March 2012 for studies investigating the pregnancy outcomes following exposure to any therapeutic dosage of any SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine) during pregnancy. Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. A total of 25 studies met our criteria and were included in the meta-analysis. The odds ratio (OD) values are 1.87 (95% CI: 1.5 to 2.33, P< 0.0001) for spontaneous abortion, 1.272 (95% CI: 1.098 to 1.474, P = 0.0014) for major malformations, 1.192 (95% CI: 0.39 to 3.644, P= 0.7578) for cardiovascular malformations, and 1.36 (95% CI: 0.61 to 3.04, P= 0.4498) for minor malformations. The results demonstrated that SSRIs increase the risk of spontaneous abortion and major malformations during pregnancy while they don’t increase the risk of cardiovascular malformations and minor malformations. Our previous meta-analysis only showed an increase in the risk of spontaneous abortion following the use of SSRIs during pregnancy. This might be due to increase in the number of studies included or addition of two new SSRIs (citalopram and escitalopram). The message to researchers is to try considering SSRIs individually during pregnancy to reduce heterogeneity, although all are aware of inevitable limitations to study on pregnant mothers.
Selective serotonin reuptake inhibitors (SSRIs); Pregnancy outcome; Meta-analysis; Evidence-based medicine; Malformation; Systematic review
Magnesium has been known for its antioxidative and antiinflammatory properties in many studies. In this study two dosing regimens of magnesium were compared with a placebo control group in order to investigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma patients. Inflammatory and oxidative factors were measured in this trial.
45 trauma patients with systemic inflammatory response syndromes (SIRS) were randomly assigned into 2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g of MgSO4 over 4 hour infusion, and placebo group received saline alone. The initial and post magnesium sulfate injections levels of tumor necrosis factor alpha (TNF-α), total antioxidant power and lipid peroxidation were measured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level of microalbuminuria were also determined.
Repeated measurements illustrated that there was no significant difference in TNF-α, total antioxidant power and lipid peroxidation levels among groups during the period of analysis. The microalbuminuria at 36 hour post infusion of high dose group was lower than that of control group (p = 0.024). Patient’s mortality (28 day) was similar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing any complications.
No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive patients was found. Magnesium in high doses may be recommended for traumatic patients with SIRS status to prevent microalbuminuria.
Magnesium; Microalbumin; TNF-α; Oxidative stress; Trauma; Critical care