Publications by authors named "Hadi Esmaily"

20 Publications

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Impact of educational intervention by community pharmacists on asthma clinical outcomes, quality of life and medication adherence: A systematic review and meta-analysis.

J Clin Pharm Ther 2021 Apr 5. Epub 2021 Apr 5.

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

What Is Known And Objective: Community pharmacists can play an important role in controlling chronic diseases. This study aimed to evaluate the effects of pharmacists' educational interventions in the community pharmacy settings on asthma control and severity, quality of life (QOL) and medication adherence.

Methods: Databases PubMed, Scopus and Web of Science were searched for evidence regarding asthma severity and control, QOL, and medication adherence after pharmacists' interventions in community pharmacy settings. Twenty-one studies were eligible for qualitative and quantitative analysis. Indices and questionnaires were used in the studies, such as Asthma-related quality of life (IAQLQ), Asthma Control Test (ACT), Perceived Control of Asthma Questionnaire (PCAQ), inhaler technique (IT), Asthma Control Questionnaire (ACQ), 36-Item Short Form survey (SF-36) and peak expiratory flow rate (PEFR). The outcomes were extracted, pooled and analysed as percentages, means, standard deviations and errors, and 95% confidence intervals (CIs).

Results And Discussion: Community pharmacists in all studies educated and followed up the asthmatic patients, addressing the outcome measures. Pharmacists underwent training courses of at least a day. Standardized mean differences for the indices were pooled as follows: IAQLQ -0.241 (95% CI, -0.362 to -0.121), ACT 0.14 (95% CI, 0.02 to 0.27), PCAQ -0.15 (95% CI, -0.28 to 0.01), IT 0.79 (95% CI, 0.05 to 1.54), ACQ -0.50 (95% CI, -0.69 to -0.30), SF-36 0.39 (95% CI, 0.16 to 0.62), PEFR 0.13 (95% CI, 0.01 to 0.26) and asthma symptoms score -0.34 (95% CI, -0.49 to -0.18).

What Is New And Conclusion: Pharmacists' educational interventions in community pharmacy settings could significantly improve asthma severity and control, QOL and medication adherence.
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http://dx.doi.org/10.1111/jcpt.13419DOI Listing
April 2021

Low Molecular-weight Hyaluronic Acid Versus Physiotherapy for the Treatment of Supraspinatus Tendinopathy: A Randomized Comparative Clinical Trial.

J Am Acad Orthop Surg 2021 Feb 15. Epub 2021 Feb 15.

From the Clinical Biomechanics and Ergonomics Research Center (Rezasoltani, Dadarkhah, Rousta, Vashaei), Faculty of Medicine, Aja University of Medical Sciences, Department of Clinical Pharmacy (Esmaily), School of Pharmacy, Shahid Beheshti University of Medical Sciences, and Pharmaceutical Sciences Research Center (Mohebbi), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: The tendons of the rotator cuff are major sources of shoulder pain. This study aimed to compare the effects of low molecular-weight hyaluronic acid with physiotherapy (PT) in patients with supraspinatus tendinopathy (ST).

Methods: We carried out a parallel two-group randomized comparative clinical trial in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. In total, 51 patients (31 women) aged 20 to 55 years with ST were randomly allocated to subacromial hyaluronate injection (n = 28) and PT (n = 23) groups. For the hyaluronate group, we administered a single injection of 2 mL (20 mg) hyaluronate 1% (500 to 700 kDa). For PT, we prescribed three sessions of treatment per week for 12 weeks, totaling 36 sessions including rotator cuff activation exercises. The primary outcome was shoulder pain in the visual analog scale. The secondary outcomes included the range of movement and the disability score of the shoulder, and a World Health Organization questionnaire on quality of life. We did the measurements at the baseline and at one, four, and 12 weeks after intervention.

Results: The results showed that both interventions were beneficial in the management of ST. However, hyaluronate was more effective in reducing shoulder pain at rest and during activities (both P < 0.001, effect size = 0.52 and 0.68, respectively). The two interventions similarly decreased patients' disability (P = 0.196). Hyaluronate improved shoulder motion and the quality of life better than PT.

Conclusion: In the treatment of ST, low molecular-weight hyaluronate is more effective than PT, at least for three months. Particularly, hyaluronate is more successful in alleviating pain.
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http://dx.doi.org/10.5435/JAAOS-D-20-01014DOI Listing
February 2021

High- Versus Low-Molecular-Weight Hyaluronic Acid for the Treatment of Rotator Cuff Tendinopathy: A Triple-Blind Randomized Comparative Trial.

Ann Pharmacother 2021 Feb 10:1060028021994297. Epub 2021 Feb 10.

Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Shoulder pain most commonly originates from the tendon structures of the rotator cuff.

Objective: We compared the clinical effects of high- versus low-molecular-weight (LMW) hyaluronic acid for the management of rotator cuff tendinopathy.

Methods: We carried out a parallel, triple-blind, randomized comparative trial at a teaching hospital. In total, 56 patients aged 16 to 70 years with rotator cuff tendinopathy were randomly allocated to 2 groups. We administered a single shoulder injection of either 1 mL of 1% high- (>2000 kDa) or 1 mL of 1% LMW hyaluronate (500-700 kDa) to the corresponding groups. The primary outcome was the intensity of shoulder pain. The secondary outcomes were range of motion and disability of the shoulder, and quality of life. We performed the measurements at baseline and at 1, 4, and 12 weeks postintervention. The pain measurements were repeated at the sixth month postintervention.

Results: Comparisons of baseline versus 3 months showed that both interventions were beneficial in the management of the tendinopathy (all values <0.05). However, between-group analyses did not indicate any clinically significant difference between the 2 medications. The pain, induration ( = 0.007), and inflammation at the site of the injection were less prominent for LMW hyaluronate.

Conclusion And Relevance: Both medications are effective for the treatment of tendinopathy. The benefits last at least for 3 months, and pain alleviation lasts partially for 6 months. The shoulder injection of LMW hyaluronate is more tolerable to the patient. Therefore, we recommend LMW hyaluronate as the first choice for the management of rotator cuff tendinopathy.
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http://dx.doi.org/10.1177/1060028021994297DOI Listing
February 2021

Ultrasound-Guided Injection of High Molecular Weight Hyaluronic Acid versus Corticosteroid in Management of Plantar Fasciitis: A 24-Week Randomized Clinical Trial.

J Pain Res 2020 14;13:109-121. Epub 2020 Jan 14.

Clinical Research Development Center, Shahid Modarres Hospital, Tehran, Iran.

Background And Aims: Plantar fasciitis (PF) is the leading cause of heel pain in adults. This study was designed to evaluate the effect of hyaluronic acid (HA) injection in reducing the symptoms of PF, compared with corticosteroid (CS) injection as a conventional treatment.

Methods: In this triple-blind, randomized, clinical trial, 75 patients who had the symptoms of PF for at least 3 months were randomly divided into two groups of 38 and 37 individuals. Then, each patient received either a single injection of high molecular weight (>2000 kDa) HA (1 mL HA 20 mg + 1 mL lidocaine 2%) or CS (1 mL methylprednisolone 40 mg + 1 mL lidocaine 2%) under the ultrasonography (US) guidance. Visual analog scale (VAS), foot ankle ability index (FAAI), pressure pain threshold (PPT), functional foot index (FFI), and plantar fascia thickness (PFT) were measured using US at baseline, 6 weeks and 24 weeks after the injection. Eventually, at the end of the treatment period, the patients' satisfaction was measured. Intention to treat analysis was used to assess the results.

Results: After 24 weeks of follow-up, results from 60 subjects were fully obtained; however, results of 73 patients included into intention to treat analysis in the sixth-week follow-up. In both groups, VAS, PFT and FFI decreased, while FAAI and PPT increased significantly ( <0.001). At the baseline and at the 24th-week, no significant difference between the two groups was observed in any of the variables. However, a comparison between the baseline and the sixth-week results shows a prominent decrease in PPT and PFT in the CS group compared to the HA group ( = 0.004 and = 0.011). Finally, there were no statistical differences between the two groups in treatment satisfaction ( = 0.618).

Conclusion: Both CS and HA were effective modalities for PF and can improve pain and function with no superiority in 24th-week follow-ups, although CS seems to have a faster trend of improvement in the short term.
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http://dx.doi.org/10.2147/JPR.S217419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969680PMC
January 2020

Vitamin D Usage Among Iranian Population: A Toxicity Crisis is on the Way.

Oman Med J 2019 Mar;34(2):174-175

Student Research Committee, Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.5001/omj.2019.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425062PMC
March 2019

Does Twice-weekly Cabergoline Improve Anthropometrical and Biochemical Profiles in Prediabetes? A Randomized Double-blind Clinical Trial Pilot Study.

Iran J Pharm Res 2015 ;14(Suppl):77-86

Islamic Azad University of Pharmaceutical Sciences Branch, Tehran, Iran.

Dopaminergic signaling is one of the regulatory pathways being investigated for its implication in glucose metabolism. The aim of this study was to determine the effect of cabergoline on biochemical and anthropometric parameters in prediabetes stage (impaired fasting glucose and impaired glucose tolerance). In this double blind, placebo-controlled, pilot study, 27 prediabetic adults were randomized to receive 0.25-mg cabergoline twice weekly for two weeks, followed by 0.5 mg twice weekly for next 14 weeks (n = 13) or placebo (n = 14). All subjects were advised to follow a 500 kcal-deficit energy diet. Fasting plasma glucose (FPG), oral glucose tolerance, glycated hemoglobin (A1c), fasting, and 2-h insulin were measured at baseline and at 16-week follow-up. Homeostasis model assessment (HOMA) 2 was calculated to estimate steady-state beta-cell function, insulin sensitivity, and insulin resistance. Our results showed significant reductions in fasting (P = 0.004) and 2-h plasma glucose (P = 0.01) after treatment, and significant improvements in beta-cell function (P = 0.03) and insulin resistance (P = 0.04) in the cabergoline group. The trend of non-significant A1c changes was decreasing in the cabergoline group versus an increasing trend in the placebo group. All anthropometric parameters were similar between the two groups. Our results revealed that twice-weekly cabergoline could improve glucose metabolism in prediabetes stage. Larger studies of longer duration are warranted to investigate the effect of cabergoline in preventing progression of prediabetes to type 2 diabetes mellitus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499429PMC
July 2015

Autoantibodies and an immune-based rat model of inflammatory bowel disease.

World J Gastroenterol 2013 Nov;19(43):7569-76

Hadi Esmaily, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran.

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.
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http://dx.doi.org/10.3748/wjg.v19.i43.7569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837255PMC
November 2013

Effects of Hypericum perforatum extract on rat irritable bowel syndrome.

Pharmacogn Mag 2011 Jul;7(27):213-23

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Context: In irritable bowel syndrome (IBS), disturbance of bowel motility is associated with infiltration of inflammatory mediators and cytokines into the intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa (TNF-α), and lipid peroxide.

Aims: Regarding promising anti-inflammatory and anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti-depressant effect, this study was designed to evaluate the effects of HP in an experimental model of IBS.

Settings And Design: IBS was induced by a 5-day restraint stress in rats. The HP extract was administered by gavage in doses of 150, 300, and 450 mg/kg for 26 days. Fluoxetine and loperamide were used as positive controls. Gastric emptying and small bowel and colon transit, besides the levels of TNF-α, MPO, lipid peroxidation, and antioxidant power, were determined in colon homogenates.

Statistical Analysis Used: Data were analyzed by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons.

Results: A significant reduction in small bowel and colonic transit (450 mg/kg), TNF-α, MPO, and lipid peroxidation and an increase in antioxidant power in all HP-treated groups (150, 300, and 450 mg/kg) were seen as compared with the control group. Gastric emptying did not alter significantly when compared with the control group. Treatment with loperamide (10 mg/kg) significantly inhibited gastric emptying and small bowel and colonic transit, while flouxetine (10 mg/kg) decreased gastric emptying, TNF-α, MPO, and lipid peroxidation and increased the antioxidant power of the samples in comparison with the control group.

Conclusions: HP diminished the recruitment of inflammatory cells and TNF-α following restraint stress not in a dose-dependent manner, possibly via inhibition of MPO activity and increasing colon antioxidant power, without any difference with fluoxetine. The HP extract inhibits small bowel and colonic transit acceleration like loperamide but has minimal effect on gastric emptying.
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http://dx.doi.org/10.4103/0973-1296.84235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173896PMC
July 2011

Amelioration of experimental colitis by a novel nanoselenium-silymarin mixture.

Toxicol Mech Methods 2011 Mar 20;21(3):200-8. Epub 2011 Jan 20.

Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran.

Background: Silymarin has intracellular antioxidant property and inhibits activation of nuclear factor-κB (NF-κB) in low concentrations and reduces tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 levels, cyclooxygenase (COX), and angiogenesis. Selenium is one of the necessary trace element nutrients for human and animals. Selenium nanoparticles (nano-Se) have more bioavailability with less toxicity.

Aims: To investigate the combination effect of silymarin and nano-Se on inhibition of NF-κB, proinflammatory cytokines, and oxidative stress biomarkers in the experimental colitis.

Methods: Trinitrobenzene sulfonic acid (TNBS) was used to induce colitis. After TNBS instillation, rats were distributed into six groups, containing silymarin and nano-Se alone or in combination, dexamethasone, negative control with no treatment and the last one was normal sham rats. All drugs were administered for 7 days. Colon samples were scored macroscopically and microscopically. The levels of activated NF-κB, IL-1β, TNF-α, myeloperoxidase (MPO), lipid peroxidation, protein carbonyl (PC), and the antioxidant power of the colon homogenates were determined.

Result: A significant decrease in NF-κB activity in treated groups was observed. The levels of TNF-α, IL-1β, MPO, lipid peroxidation, and PC were reduced and an improvement in antioxidant power of treated groups was seen. Combination of silymarin and nano-Se were more effective than each one alone in improvement of NF-κB, TNF-α, antioxidant power, and lipid peroxidation values, although this difference was not significant in other factors.

Conclusion: Co-administration of silymarin and nano-Se with a good antioxidant profile and inhibition of NF-κB is a possible candidate for better management of inflammatory bowel disease.
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http://dx.doi.org/10.3109/15376516.2010.547887DOI Listing
March 2011

Efficacy of Setarud (IMod), a novel drug with potent anti-toxic stress potential in rat inflammatory bowel disease and comparison with dexamethasone and infliximab.

Indian J Biochem Biophys 2010 Aug;47(4):219-26

Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The inflammatory bowel disease (IBD) is an idiopathic, immune-mediated and chronic intestinal condition. In the present study, the effect of Setarud (IMOD), a novel natural drug with known immunomodulatory, anti-inflammatory and antioxidant properties was investigated in experimental colitis in rats and compared with the dexamethasone and infliximab. Immunologic colitis was induced by intracolonic administration of a mixture of trinitrobenzene sulfonic acid (TNBS) and absolute ethanol in male Wistar rats. Animals were divided into 6 groups of sham (normal group), control (vehicle-treated), positive control (dexamethasone 1 mg/kg/day given orally and infliximab 5 mg/kg/day given subcutaneously) and 3 Setarud-treated groups (13.3, 20, 30 mg/kg/day given intraperitoneally). The treatment continued for 14 consecutive days and then animals were decapitated on the day 15 and distal colons were removed for macroscopic, microscopic, and biochemical assays. Biochemical markers, including TNF-alpha, IL-1beta, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS) were measured in the homogenate of colonic tissue. A remarkable reduction in macroscopic and histological damage scores was observed in the animals treated with Setarud. These findings were confirmed by decreased levels of TNF-alpha, interleukin-1beta, MPO activity and TBARS, and raised levels of FRAP in the colon tissue. These observations confirmed the immunomodulatory, anti-inflammatory and antioxidant properties of Setarud in experimental colitis, which was comparable to those of dexamethasone and infliximab.
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August 2010

The correlation between NF-κB inhibition and disease activity by coadministration of silibinin and ursodeoxycholic acid in experimental colitis.

Fundam Clin Pharmacol 2011 Dec 16;25(6):723-33. Epub 2010 Nov 16.

Faculty of Pharmacy, Shahid Beheshti University, Tehran 14155-6153, Iran.

NF-κB is one of the most important nuclear factors responsible for overexpression of proinflammatory cytokines. This is demonstrated by increased NF-κB activity and other dependent immune factors in inflammatory bowel disease (IBD). Anti-inflammatory effects of silibinin and ursodeoxycholic acid (UDCA) along with their NF-κB inhibitory property are thought to be beneficial in colitis. Trinitrobenzene sulfonic acid was used to induce colitis rat models. After instillation, 48 rats were treated with oral silibinin, UDCA alone or a combination of both. Intraperitoneal dexamethasone was used in the control group. After 12 days of treatment, colonic samples were tested for the severity of mucosal damage macroscopically and microscopically. The levels of activated NF-κB, IL-1β, TNF-α, myeloperoxidase, thiobarbituric acid reactive substances (TBARS), protein carbonyl, and the antioxidant power of the bowel homogenates were determined. The results indicated a significant reduction in NF-κB activity as well as the levels of IL-1β, TNF-α, TBARS, protein carbonyl, myeloperoxidase activity, and an improvement in antioxidant power of colitis in treated rats. Combination therapy resulted in a more prominent improvement in bowel antioxidant power and myeloperoxidase activity. In conclusion, combination of silibinin and UDCA by inhibition of NF-κB and other relevant inflammatory factors of colitis is a good candidate for management of Crohn's disease.
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http://dx.doi.org/10.1111/j.1472-8206.2010.00893.xDOI Listing
December 2011

Effect of Phlomis persica on glucose levels and hepatic enzymatic antioxidants in streptozotocin-induced diabetic rats.

Pharmacogn Mag 2010 Jul;6(23):219-24

Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Methanol extract of the aerial parts of Phlomis persica Boiss. (Lamiaceae) (PPE) was studied to evaluate the effects of antidiabetic potential, by measuring fasting blood glucose, insulin, total antioxidant power (TAP), using ferric reducing antioxidant power (FRAP), lipid peroxidation (using thiobarbituric acid reactive substances, TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) on streptozotocin-induced diabetes in rats. Male Wistar rats were randomly divided into five groups of six animals each. Oral administration of PPE at doses of 100 and 200 mg/kg once a day for 10 days resulted in a significant reduction in fasting blood glucose and an increase in serum insulin levels, in comparison with diabetic control group. It also prevented diabetes-induced loss in body weight. Hepatic TAP increased and TBARS decreased following PPE treatments. The extract at 100 and 200 mg/kg increased the activity of hepatic SOD, CAT, and GPx in diabetic rats. It is concluded that PPE has antidiabetic potential that is comparable with glibenclamide. In conclusion, the results of the present study show positive effects of P. persica on experimental diabetes and thus the antidiabetic effect of PPE is related to its potential to inhibit hepatocellular oxidative stress.
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http://dx.doi.org/10.4103/0973-1296.66940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950386PMC
July 2010

On the benefit of Teucrium in murine colitis through improvement of toxic inflammatory mediators.

Hum Exp Toxicol 2010 Apr 9;29(4):287-95. Epub 2010 Feb 9.

Faculty of Veterinary Medicine, Islamic Azad University, Karaj Branch, Iran.

Regarding the role of free radicals in pathogenesis of inflammatory bowel disease (IBD), we were interested to investigate the effects of Teucrium persicum with approved antioxidant and anti-inflammatory properties in an experimental model of colitis. Immunologic colitis was induced by rectal administration of a mixture of 2,4,6-trinitrobenzene sulphonic acid (TNBS) and ethanol through rubber cannula into rats. Three different doses of Teucrium (100, 200, and 400 mg/kg) were gavaged in a duration of 10 days to rats. Endpoint markers of colitis included macroscopic and microscopic examination of colon tissue and measuring colonic cells concentrations of tumor necrosis factor-alpha (TNF-alpha), interlukin-1beta (IL-1beta), total antioxidant power as ferric reducing antioxidant power (FRAP), myeloperoxidase (MPO), and lipid peroxidation as thiobarbitoric acid-reactive substance (TBARS). Teucrium at all doses improved both macroscopic and histological damages of rats with colitis. Teucrium reduced colonic MPO activity and concentrations of cellular lipid peroxides, TNF-alpha, and IL-1beta, with a concomitant increase in FRAP value in rats with colitis. It is concluded that beneficial effects of Teucrium in experimental colitis is mediated through its antioxidant and anti-inflammatory potentials. Examination of this herbal medicine in patients with IBD as a supplement would further reveal the potential of Teucrium.
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http://dx.doi.org/10.1177/0960327110361754DOI Listing
April 2010

Cellular cytotoxicity and in-vivo biodistribution of docetaxel poly(lactide-co-glycolide) nanoparticles.

Anticancer Drugs 2010 Jan;21(1):43-52

Tehran University of Medical Sciences, Iran.

Docetaxel (DTX) is one of the most effective antineoplastic drugs. However, its current clinical administration, formulated in tween80, causes serious side effects. This study is focused on preparation and evaluation of poly(lactide-co-glycolide) nanoparticles (NPs) containing DTX to remove tween80. Drug encapsulation efficiency, in-vitro drug release, cellular cytotoxicity, and in-vivo biodistribution of NPs in mice after intravenous administration were investigated. The average diameter of the NPs was approximately 172-178 nm with encapsulation efficiency of 68%. A burst release of approximately 30% (w/w) of the loaded drug followed by a sustained release profile was observed. Cellular mortality of the NPs was more than or at least as great as DTX free drug; for example, cell viability measured at 100 nmol/l drug concentration was decreased from 50.9% for DTX free drug to 15.9% for the NP formulation after 48 h incubation with T47D cells. The DTX plasma amount remained at a good level (13% of the initial dose) in the NP formulation compared with the DTX conventional formulation, which is approximately 0.5% of the initial dose, was present in plasma up to 2 h. Poly(lactide-co-glycolide) NPs containing DTX prepared in this study may be regarded as a suitable and superior formulation for the current formulation in the market containing tween80 with improved cancerous cell mortality and biodistribution characteristics.
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http://dx.doi.org/10.1097/CAD.0b013e328331f934DOI Listing
January 2010

Effect of dimethyl-beta-cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in rats.

J Pharm Sci 2008 Dec;97(12):5176-85

Aerosol Research Laboratory, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

The aim of this article is to prepare and characterize inhalable dry powders of recombinant human growth hormone (rhGH), and assess their efficacy for systemic delivery of the protein in rats. The powders were prepared by spray drying using dimethyl-beta-cyclodextrin (DMbetaCD) at different molar ratios in the initial feeds. Size exclusive chromatography was performed in order to determine protecting effect of DMbetaCD on the rhGH aggregation during spray drying. By increasing the concentration of DMbetaCD, rhGH aggregation was decreased from 9.67 (in the absence of DMbetaCD) to 0.84% (using DMbetaCD at 1000 molar ratio in the spray solution). The aerosol performance of the spray dried (SD) powders was evaluated using Andersen cascade impactor. Fine particle fraction values of 53.49%, 33.40%, and 23.23% were obtained using DMbetaCD at 10, 100, and 1000 molar ratio, respectively. In vivo studies showed the absolute bioavailability of 25.38%, 76.52%, and 63.97% after intratracheal insufflation of the powders produced after spray drying of the solutions containing DMbetaCD at 10, 100, and 1000 molar ratio, respectively in rat. In conclusion, appropriate cyclodextrin concentration was achieved considering the protein aggregation and aerosol performance of the SD powders and the systemic absorption following administration through the rat lung.
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http://dx.doi.org/10.1002/jps.21353DOI Listing
December 2008

Pattern of acute poisoning in Tehran-Iran in 2003.

Hum Exp Toxicol 2007 Sep;26(9):753-6

Loghman-Hakim Hospital Poison Center, Faculty of Medicine and Toxicological Research Center, Shaheed-Beheshti University of Medical Sciences, Tehran.

To characterize the poisoning cases admitted to the Loghman-Hakim Hospital Poison Center (a teaching reference hospital of poisoning) in Tehran, Iran. All admitted acutely poisoned patients from January to December 2003 were evaluated retrospectively. Information of socio-demographic characteristics, agents and cause of poisoning, and the mortality rate were collected from medical records of the hospital. During this period, 24 179 cases were referred to the emergency department that 10 206 of them were admitted. Of the admitted cases, 51% were male and 49% female. The majority (38%) of cases were in the age range of 21-30 years. Most (79%) of poisonings were intentional and 21% were unintentional. The most important agents of acute poisoning were drugs (69.13%) especially sedative-hypnotics followed by opioids (12.34%) and pesticides especially organophosphates (OPs) (6.21%). The mortality rate was 1.3% (318 patients). Death was mostly occurred by opioids (41.54%), followed by drugs (28%) and pesticides especially OPs (12%). The prevention and treatment of poisoning due to opioids, pesticides specially OPs and sedative-hypnotics drugs should merit high priority in the health care of the indigenous population of Tehran.
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http://dx.doi.org/10.1177/0960327107083017DOI Listing
September 2007

Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress.

Hum Exp Toxicol 2006 Dec;25(12):697-703

Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The aim of this study was to evaluate effects of acute exposure to various doses of diazinon, a widely used synthetic organophosphorus (OP) insecticide on plasma glucose, hepatic cells key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress in rats. Diazinon was administered by gavage at doses of 15, 30 and 60 mg/ kg. The liver was perfused and removed under anaesthesia. The activities of glycogen phosphorylase (GP), phosphoenolpyruvate carboxykinase (PEPCK), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were analysed in liver homogenate. Administration of diazinon (15, 30 and 60 mg/kg) increased plasma glucose concentrations by 101.43% (P = 0.001), 103.68% (P = 0.000) and 160.65% (P = 0.000) of control, respectively. Diazinon (15, 30 and 60 mg/kg) increased hepatic GP activity by 43.5% (P = 0.05), 70.3% (P = 0.00) and 117.2% (P = 0.02) of control, respectively. In addition, diazinon (30 and 60 mg/kg) increased hepatic PEPCK by 77.3% (P = 0.000) and 93.5% (P = 0.000) of control, respectively. Diazinon (30 and 60 mg/kg) decreased liver TAC by 38% (P = 0.046) and 48% (P = 0.000) of control, respectively. Also diazinon (30 and 60 mg/kg) increased hepatic cell liver lipid peroxidation by 77% (P = 0.05) and 280% (P = 0.000) of control. The correlations between plasma glucose and hepatic cells TBARS (r2 = 0.537, P = 0.02), between plasma glucose and ChE activity (r2 = 0.81, P = 0.049) and between plasma glucose and hepatic cells GP activity (r2 = 0.833, P = 0.04) were significant. It is concluded that the liver cells are a site of toxic action of diazinon. Diazinon increases glucose release from liver into blood through activation of glycogenolysis and gluconeogenesis as a detoxication non-cholinergic mechanism to overwhelm diazinon-induced toxic stress. The results are in accordance with the hypothesis that OPs are a predisposing factor of diabetes.
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http://dx.doi.org/10.1177/0960327106075064DOI Listing
December 2006

Protection by pentoxifylline of diazinon-induced toxic stress in rat liver and muscle.

Toxicol Mech Methods 2007 ;17(4):215-21

Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Medical Sciences/University of Tehran, Tehran, Iran.

ABSTRACT The effects of diazinon, pentoxifylline, and their combination therapy on plasma glucose, the key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress were studied in rat liver and muscle. Oxidative stress was determined by measuring the concentration of lipid peroxides and assessing total antioxidant capacity. Diazinon (60 mg/kg) and pentoxifylline (100 mg/kg) were administrated by gavage. Administration of diazinon increased blood glucose, hepatic glycogen phosphorylase (GP), and phosphoenol pyruvate carboxykinase (PEPCK) by 160.65%, 117.2%, and 93.5%, respectively, while it decreased plasma cholinesterase (ChE) by 53.82%. Diazinon-induced oxidative stress was demonstrated by decreased total antioxidant capacity and enhanced lipid peroxidation by 52.61% and 280% in liver and by 40.02% and 46.6% in muscle, respectively. Pentoxifylline increased plasma glucose, hepatic GP, and PEPCK by 98.65%, 60%, and 79.86%, respectively, while it did not change plasma ChE, liver and muscle lipid peroxides, and total antioxidant capacity. In combination therapy, pentoxifylline did not alter diazinon-induced change in muscle GP activity but restored a diazinon-induced increase in hepatic and muscle lipid peroxides by 39.18% and 42.35%, respectively. Pentoxifylline also recovered a diazinon-induced decrease in liver and muscle total antioxidant capacity and plasma ChE by 122.33%, 56.44%, and 115.62%, respectively. Pentoxifylline did not affect diazinon-induced hyperglycemia and increased hepatic GP and PEPCK or muscle GP activities. It is concluded that pentoxifylline is a good choice for the alleviation of acute toxic stress of diazinon in muscle and liver and ChE in plasma, while it is unable to recover diazinon-induced hyperglycemia.
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http://dx.doi.org/10.1080/15376510600943783DOI Listing
October 2012

Effect of Satureja khuzestanica essential oil on male rat fertility.

Fitoterapia 2006 Dec 6;77(7-8):495-9. Epub 2006 Jul 6.

Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Centre, Tehran University of Medical Sciences, Iran.

This study was undertaken to study the effect of Satureja khuzestanica essential oil (SKEO) in male rat fertility. SKEO was administered orally at doses of 75, 150, and 225 mg/kg/day for 45 days through drinking water. Treated and control rats were mated with female on day 45 of treatment. SKEO significantly improved all the parameters evaluated such as potency, fecundity, fertility index, and litter size. Moreover, concentrations of FSH and testosterone were significantly increased in SKEO-treated groups. Also the weights of testes, seminal vesicles, and ventral prostate weights were increased by SKEO (225 mg/kg). Histopathological analysis showed that in male rats treated with SKEO (150, 225 mg/kg) the number of spermatogonium, spermatid cords, Leydig cells, and spermatozoids was increased. Also in these groups, the Sertoli cells were hypertrophic.
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http://dx.doi.org/10.1016/j.fitote.2006.05.025DOI Listing
December 2006

Synthesis and analgesic activity of N-Arylhydrazone derivatives of mefenamic acid.

J Pharm Pharm Sci 2005 Sep 1;8(3):419-25. Epub 2005 Sep 1.

Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: A series of N-Arylhydrazone derivatives of mefenamic acid (a known non-steroidal anti-inflammatory drug) were synthesized in order to obtain new compounds with potential analgesic and anti-inflammatory activity.

Methods: The structures of all synthesized compounds were confirmed by means of infrared, proton magnetic resonance and mass spectroscopy. All compounds were evaluated for their analgesic and anti-inflammatory activities by abdominal constriction test (writhing test) and carrageenan-induced rat paw edema test respectively.

Results: Most of the synthesized compounds induced significant reduction in the writhing response when compared to control. Among them, compounds 11, 12, 15, 16, 19, 20, and 21 were significantly more potent than mefenamic acid in the writhing test. The anti-inflammatory activity of these 7 compounds were evaluated and compounds 11, 12, 16, 19 and 20 showed significant anti-inflammatory activity in comparison to control but their effect was weaker than mefenamic acid.

Conclusions: The antinociceptive relative activity of some of these newly synthesized compounds is greater than mefenamic acid but they are not potent anti-inflammatory agents.
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September 2005