Iranian Journal of Pharmaceutical Research
Year:2012 | Volume:11 | Issue:4|Papers Count:33

A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin (VCM) nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM (X1), amount of emulsifier (X2), stirring rate (X3), volume of organic phase (X4) and volume of aqueous phase (X5), on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1: 2 drug to polymer ratio, 0.2 (%w/w) amount of emulsifier, 25 mL (volume of organic phase), 25 mL (volume of aqueous phase), 3 min (time of stirring) and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug loading (R2=90.82). The highest entrapment efficiency was obtained when the ratio of drug to polymer was 1: 3. Zeta (z) potential of the nanoparticles was fairly positive in molecular level. In vitro release study showed two phases: an initial burst for 0.5 h followed by a very slow release pattern during a period of 24 h. The release of VCM was influenced by the drug to polymer ratio and particle size and was found to be diffusion controlled. The best-fit release kinetic was achieved with Peppas model. In conclusion, the VCM nanoparticle preparations showed optimize formulation, which can be useful for oral administrations.

As global competition intensifies, research and development (R & D) organizations needto enhance their strategic management in order to become goal-directed communities for innovation and allocate their resources consistent with their overall R & D strategy. The world pharmaceutical market has undergone fast, unprecedented, tremendous and complex changes in the last several years. The pharmaceutical industry is today still one of the most inventive, innovative and lucrative of the so-called “high-tech” industries. This industry serves a dual role in modern society. On one hand, it is a growing industry, and its output makes a direct contribution to gross domestic product (GDP). On the other side, drugs, this industry’s major output, are an input in the production of good health. The purpose of this study is to evaluate R & D activities of pharmaceutical companies, and also to highlight critical factors which have influential effect on results of these activities. To run this study a valid questionnaire based on literature review and experts’ opinion was designed and delivered to 11 pharmaceutical companies. Empirical data show there is not acceptable situations considering of the factors that should be taken in to account by managers including, management commitment, human resource management, information technology and financial management. Furthermore, we concluded some interesting results related to different aspects of R & D management. In conclusion, managers must be aware about their performance in R & D activities, accordingly they will able to take a comprehensive policy in both national and within the company.

Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, I), a piperazine derivative, belongs to H1 antihistamine group of drugs that shows such pharmacological properties as anti-inflammatory, anti-allergic and anti-platelet effects, similar to other H1-receptor antagonists. In this study, two new tolyl and cumene derivatives of I (1-ethyl- 4- [(p-isopropylphenyl) (p -tolyl) methyl] -piperazine, II and 1- [3, 4-dichlorophenyl] -4- [[p-isopropylphenyl] [p-tolyl] methyl] -piperazine, III) were synthesized to investigate their acute and chronic anti-inflammatory activities in formalin and histamine-induced rat paw edema. In addition, the vascular permeability in formalin and histamine-induced paw edema, xylene-induced ear edema, and peritonitis due to acetic acid application into peritoneal cavity were measured. The cotton pellet-induced granuloma model was chosen for inducing chronic inflammation in rats. Findings proved reduction in formalin-induced rat paw edema and vascular permeability (acute inflammation) by I and II at 30 min after the injection. In addition, results in histamine-induced rat paw edema showed anti-inflammatory effects of all drugs started 60 min after the injection as these effects continued for a longer period by II and III comparing to I, as discussed above. In addition, the data on vascular permeability in xylene-induced ear edema and acetic acid-induced to peritoneal cavity confirmed that substitutions on cyclizine molecule were more effective and could decrease the vascular permeability and acute inflammation. However, the results from the cotton pellet-induced granuloma formation in rats revealed that none of the drugs (I-III) were effective to reduce the reactions and intermediates of chronic inflammation.

As there is no evidence of previous studies on evaluating the level of job satisfaction and the major causes of dissatisfaction among the pharmacists in Iran, this study was designed.This study is a cross-sectional descriptive analysis of pharmacists practicing in Tehranprivate-sector pharmacies. We selected a stratified random sampling using number of prescriptions as a variable for stratification. The questionnaire was divided into three sections containing the demographic characteristics, general health perception and job satisfaction.Of all the participants, 62% were the owners of pharmacies and 38% were pharmacists in charge (non-owner). Seventy-eight percent of respondents reported satisfaction about theirpsychological and physical state. Just 11% of pharmacists were financially satisfied and 49% felt relaxed at the workplace. There was no correlation between the satisfaction and owning the pharmacy or sex of respondents. Spearman›s correlation showed that the income satisfaction correlated negatively with age (p£0.001) and years of experience (p<0.05). Moreover, the average working hours was significantly higher among men compared to women (p<0.01) and among owners relative to non-owners (p<0.05).Overall, general health perception and quality of life among the respondents were atsatisfactory level. However, work-related satisfaction was not high enough and most interviewed pharmacists were financially dissatisfied.

This study was designed to elucidate the effect of ascorbic acid on salivary total antioxidant capacity in smokers.In this single blind crossover clinical trial, the whole unstimulated saliva of 30 smokers, who were randomly divided into two groups, was collected. In the first phase after the saliva collection, one group of patients took 500 mg of vitamin C powder, for 3 weeks. Then, saliva of all patients was collected. After a one-week wash-out period, vitamin C was given to the other group. The collection of saliva was done after 3 weeks. Total antioxidant capacity was measured. Statistic evaluation was performed by Repeated Measured ANOVA, Independent sample t-test and Covariate test.The mean of total antioxidant capacity with and without using vitamin C was 0.511±0.155 (U/mL) and 0.555±0.171 (U/mL), respectively. This variability was not significant (p=0.605). Oxidative stress from cigarette smoke was not decreased significantly with using vitamin C.

Stress-related mucosal damage (SRMD) is a significant cause of morbidity and mortality in critically ill patients due to the gastrointestinal blood loss. Prophylaxis of SRMD with proton pump inhibitors or histamine-2 blockers has gained widespread use in intensive care units. Both demonstrated to be effective in reducing clinically significant bleedings, while PPIs has shown to exert some anti inflammatory effects including the inhibition of producing pro-inflammatory cytokines. As cytokines have role in developing SRMD, the aim of this study was to evaluate the effect of PPIs on the inhibition of cytokine release following the critical illness.A total of 27 critically ill patients with risk factors of developing stress ulcer and intragastric pH<3.0 enrolled to this Randomized clinical trial study. Patients were randomly assigned in three treatment groups, group one received 40 mg of intravenous pantoprazole every 12 h for 48 h (four doses), group two received 80 mg of intravenous pantoprazole every 24 h continuous infusion for 48 h and the third group received 150 mg of ranitidine intravenously as 24 h continuous infusion for 48 h. Plasma and gastric juice samples were obtained at 0th, 12th, 24th and 48th h for the measurement of EGF, IL-1 b, IL-6, IL-10 and TNF-a.Pantoprazole infusion have decreased the plasma IL-1b concentrations (p=0.041). No other significant differences in concentrations of EGF, IL-6, IL-10 and TNF-a were detected.There were reverse correlations between the intragastric pH with gastric juice IL-1b and TNF-a concentrations and a direct correlation between the intragastric pH and gastric juice EGF in pantoprazole groups.Our data suggest that pantoprazole may have some anti-inflammatory effects on patients. However, the exact impact of this effect on patients should be assessed by further studies.

Background Granisetron is a first-generation 5-HT3-receptor antagonist that has shown efficacy in preventing postoperative nausea and vomiting (PONV). In this randomized double-blind parallel-group clinical trial, we assessed the efficacy of generic granisetron versus KytrilÒ, in the prevention of PONV in patients undergoing general anesthesia for gynaecological surgeries. Method One hundred and twenty patients who were supposed to undergo major gynaecological surgeries (myomectomy and hysterectomy) in Dr. Shariati Teaching Hospital, Tehran, Iran were randomly assigned to either single dose generic granisetron (40 mcg/kg), or KytrilÒ (40 mcg/kg) at the end of the surgery. Two episodes of emetic symptoms (nausea and vomiting) were recorded by a gynaecologist who had no knowledge of which treatment each patient had received. This gynaecologist observed the patients at three different intervals: 6, 12 and 18 h post surgery. At the end of the observation period each patient evaluated the satisfaction with the study drug, and the gynaecologist evaluated sedation of the patients. Results In the generic granisetron group 47 and 13 patients, and in the KytrilÒ group 45 and 15 patients underwent hysterectomy and myomectomy respectively. No difference was observed between two treatment groups regarding postoperative nausea and vomiting control during 18 hours after the drugs administration. Also there were no differences in the satisfaction with the study drug between the generic granisetron and KytrilÒ. No difference in sedation scores was observed between two groups. Conclusion Generic granisetron exerts efficacy against PONV after gynaecological surgeries which is non-inferior to that of KytrilÒ.

Intravenous chemotherapy is an important mean for the treatment of cancers. Infusion phlebitis (Ph) is a common and acute complication of chemotherapy. The frequency of Ph is about 70% in patients undergoing chemotherapeutic management. It can induce the pain, increase the risk of thrombophlebitis, lead to incomplete follow-up, and thereby, affect the patient’s health status. Respecting the great importance of these issues, it is essential to prevent Ph.This study conducted to determine the effect of external use of Sesame Oil (SO) in the prevention of Ph.Sixty patients with colon or rectum cancer, who admitted for chemotherapeutic management, enrolled in clinical trial and were randomly divided into two equal groups: Control and Intervention. Ten drops of SO was applied twice a day for 14 days externally in intervention group, whereas the control group received nothing. Incidence and grade of Ph was measured in both groups. Data was analyzed through independent t-test, X2, Fisher’s exact test, Mann-Whitney, and Lagrange survival using SPSS 16.The incidence of Ph was 10% and 80% in intervention group and control group, respectively.There was a significant difference between two groups (p<0.05). Ph was 8 times more frequent in control group (R R=8, AR R=70%). In addition, there was statistically significant difference between the grade and incidence of Ph with SO and control group (p<0.05).According to these results, it seems that external use of SO is effective, safe and well-tolerated for prophylaxis from Ph. Therefore, it can be suggested as a selected prevention method for reducing the complication.

Itching is one of the most common skin symptoms. Generalized pruritus occurs in 1-8% of pregnant women. It can create unpleasant feeling for these women especially at nights. Most pregnant women avoid using synthetic drugs because of their side effects. Peppermint is a plant which has been used as a traditional drug in Iran. It decreases skin’s temperature. This study was done to determine the effects of peppermint oil on symptomatic treatment of pruritus in pregnant women attending to Rasoul Akram Hospital in Rasht, 2011.In this triple-blind clinical trial, 96 randomly selected subjects diagnosed with pruritus gravidarum were studied (47 cases and 49 controls). A bottle containing 60 mL of peppermint oil 0.5% in sesame oil and identical placebos were provided to be taken twice a day during 2 weeks by the case and control groups, respectively. The severity of the itch was assessed and compared before and after the study by VAS system. The results were analyzed by SPSS. Statistical methods such as descriptive analysis, independent samples’ t-test, paired samples’ t-test and Chi-square were employed.The severity of the itch in the treated group with peppermint oil in comparison with theplacebo group, showed a significant statistical difference (p=0.003).In accordance with the results of this study, it seems that peppermint oil can be effective in reducing the severity of Pruritus Gravidarum. More studies with larger sample sizes arerequired to confidently declare the mentioned results.

With respect to the high incidence of hot flash in postmenopausal women and the controversies regarding its treatment, this double-blind clinical trial was conducted to determine the effects of Pimpinella anisum on hot flashes in these women referring to rural and urban health centers of Qazvin Province in 2009.Seventy-two women with hot flashes were randomly selected according to the predetermined criteria and divided into two experimental and control groups. Their medical records at health centers were used for sampling. Each woman in the experimental group took a capsule containing 330 mg Pimpinella anisum 3 times a day while in the control group, women took 3 capsules, each containing 330 mg potato starch, over 4 weeks and after that, they were following up for 4 weeks. Before taking the capsules, they were assessed for 2 weeks about the frequency and severity of hot flashes. Data were collected through a questionnaire and an information form.Content validity method was used for validity of the tools. ANOVA and Student›s t-test were applied for statistical analysis.In the experimental group, the frequency and severity of hot flashes before the treatment were 4.21% and 56.21% and, after that, were 1.06% and 14.44% at the end of the fourth week respectively. No change was found in the frequency and severity of hot flashes in the control group.The frequency and severity of hot flashes was decreased during 4 weeks of follow up period. P. anisumis effective on the frequency and severity of hot flashes in postmenopausal women.

Determination of streptokinase activity is usually accomplished through two assay methods: a) Clot lysis, b) Chromogenic substrate assay. In this study the biological activity of two streptokinase products, namely StreptaseÒ, which is a native product and HeberkinasaÒ, which is a recombinant product, was determined against the third international reference standard using the two forementioned assay methods. The results indicated that whilst the activity of StreptaseÒ was found to be 101±4% and 97±5% of the label claim with Clot lysis and Chromogenic substrate assay respectively, for HeberkinasaÒ the potency values obtained were 42±5% and 92.5±2% of the label claim respectively. To shed some light on the reason for this finding, the n-terminal sequence of the streptokinase molecules present in the two products was determined. The results showed slight differences in the amino acid sequence of the recombinant product in comparison to the native one at the amino terminus. This finding supports those of other workers who found that n- terminal sequence of the streptokinase molecule can have significant effect on the activity of this protein.

The aim of the study is to examinein-vitro antioxidant and antimicrobial activity of the acetonic and methanolic extracts of the mushrooms Boletus aestivalis, Boletus edulis and Leccinum carpini. Antioxidant activity was evaluated by using free radical scavenging activity and reducing power. In addition, total content of phenol and flavonoid in extracts were determined as pyrocatechol equivalent, and as rutin equivalent, respectively. As a result of the study acetonic extracts from Boletus edulis was more powerful antioxidant activity with IC50 value of 4.72 mg/mL which was similar or greater than the standard antioxidants, ascorbic acid (IC50=4.22 mg/mL), BHA (IC50=6.42 mg/mL) and a-tocopherol (IC50=62.43 mg/mL). Moreover, the tested extracts had effective reducing power. A significant relationship between total phenolic and flavonoid contents and their antioxidative activities was significantly observed. The antimicrobial activity of each extract was estimated by determination of the minimum inhibitory concentration by using microdilution plate method against five species of bacteria and five species of fungi. Generally, the tested mushroom extracts had relatively strong antimicrobial activity against the tested microorganisms. The minimum inhibitory concentration for both extracts related to the tested bacteria and fungi were 1.25-10 mg/mL. The present study shows that tested mushroom species demonstrated a strong antioxidant and antimicrobial activity. It suggests that mushroom may be used as good sources of natural antioxidants and for pharmaceutical purposes in treating of various diseases.

Sericostoma pauciflorumStocks ex Wight (Family Boraginaceae) used against cancer, diabetes and known to be health promoter. Callus cultures have been established from the stem explants on Murashige and Skoog (MS) medium supplemented with 1.5 mg/L concentration of different growth hormone viz. kinetin (Kn), indole 3-acetic acid (IAA) and indole 3-butyric acid (IBA). At 6 weeks of age, these calli were harvested, dried and extracted successively in pet, ether, methanol and water. Extracts were dried, weighed (%) and analyzed for their bioefficacies. Antimicrobial activities were determined using agar well diffusion and antioxidant potentials by DPPH and FRAP methods. Among all the test extracts, the extract of stem callus raised on IBA found to be more effective whereas it’s pet. ether extract showed appreciable activity against both the test bacteria and fungi (S. aureus- IZ 14.00±0.57 mm and T. rubrum- 16.33±0.32 mm), followed by methanol extract (S. aureus- IZ 13.00±0.57 mm, A. niger and P. chrysogenum - IZ 16.66 mm in both). In antioxidant potentials, all aqueous extracts were more active where IBA and Kn extracts demonstrated 0.06 mg/mL IC50 value (% inhibition 93.30 and 92.70 respectively at 0.8 mg/mL concentration) with 366±6.69 and 343±3.34 ascorbic acid equivalent antioxidant potentials at 1 mg/mL concentration. Furthermore, the chemical profile of test extracts was carried out. The bioactive secondary metabolites, b-sitosterol and caffeic acid was isolated from culture tissue of 6 weeks-old callus, and their identification and confirmation was carried out by color reaction, TLC behavior and IR spectrum techniques.

Mycoplasmosis caused by mycoplasma has immensely reduced the performance of commercial animal husbandry, along with prevalence and increase of drug resistance in mycoplasma, thus new agents and therapies are urgently needed. Triclosan is a broad spectrum antimicrobial agent with a favorable safety profile. In the present study, we tested the antimycoplasmal activity of triclosan alone, as well as thein-vitro interaction of triclosan and the fluoroquinolones, gatifloxacin (GAT), moxifloxacin (MXF), levofloxacin (LVX), sparfloxacin (SPX), ciprofloxacin (CIP), enrofloxacin (EFX), and norfloxacin (NOR), against five mycoplasma species. This study demonstrated that triclosan had antimycoplasmal activity against both fluoroquinolones-sensitive species and a fluoroquinolones-resistant species isolated from clinic, with minimum inhibitory concentrations (MICs) of 16.0-64.0 mg/mL and 64.0 mg/ mL, respectively. A synergistic antimycoplasmal effect between triclosan and GAT, MFX or EFX against the five mycoplasma species was observed, with modulation factors (MFs) of 4-8, 4-16, 8-32, respectively, and fractional inhibitory concentration indexes (FICIs) of 0.375- 0.500, 0.350-0.500, 0.281-0.375, respectively. The combination of triclosan with LVX, SPX, CIP or NOR displayed either synergistic activity or indifference against the same mycoplasma species with MFs of 2-64, 4-16, 2-16, 2-64, respectively, while FICI values range from 0.516- 0.750, 0.500-0.625, 0.306-0.750, and 0.615-0.750, respectively. No antagonism was observed for any drug combination against any of the species tested. To the best of our knowledge, this is the first report that triclosan has synergistic activity with fluoroquinolones against mycoplasma species.

In this study, we have examined the antioxidant activity and total phenolic content of different extracts (including water, methanol, water: methanol and acetone) ofNerium oleander L. grown in the north of Iran by employing various in-vitro assay, i.e. DPPH free radical scavenging, reducing power and total antioxidant capacity through the Mo (VI) reduction. The extracts showed different levels of efficacy in each assay in a dose-dependent manner. Methanolic and aqueous methanolic extracts with the highest amount of total phenolic (by using the Folin-Ciocalteu phenol reagent method), were the most potent antioxidant in all of the assays that were used. According to the results of present study, Nerium oleander L. flowers were found to serve as a potential source of natural antioxidants.

The objective of this research was to study the biological activities of various extracts and the chemical composition of the essential oil Trigonella monantha C. A. Mey. subsp. monantha by gas chromatography (GC) and gas chromatography-mass spectroscopy (GC-MS), from the compounds derived from the aerial parts. The overall results of T. monantha tests allow us to conclude various extracts [hexane extract (HE), methanol extract (ME) and chloroform extract (CE)] of the test total phenolic, ABTS and DPPH while also testing b-carotene largest property antioxidant. The property antioxidant shows the extracts of both mechanisms of electron transfer and the hydrogen transfer it has gone through. The antimicrobial activity of the extracts of both samples was determined against seven Gram-positive and Gram-negative bacteria. The strongest activity exhibited by the T. monantha of ME was determined to be 49.58 mg/mL and was exhibited by ME.

Germination is one of the most effective processes to improve the quality of legumes. Vitamins and some other compounds that might be considered beneficial as antioxidants, often change dramatically during the course of germination. Antioxidants might be defined as compounds which are capable of preventing, delaying or retarding the development of rancidity or other flavor deterioration in foods or as protective factors against the oxidative damage in the human body. In this research, three different solvents were employed to extract the phenolic compounds present in chickpea seeds and sprouts. Total phenolic contents were measured by Folin Ciocalteau method and the antioxidant activity was determined by two different methods including the assay of hydroxyl radical scavenging activity and the oven test method. For the later, different concentrations of extracts (0.02, 0.04, 0.06, 0.08 and 0.1% w/w) were added to tallow and the stabilities of the treatments were determined. Peroxide value and induction period measurements were used as means to evaluate the antioxidant activities. The results indicated that germination process modifies the antioxidant activity. Although the amount of phenolic compounds was higher when acetone solvent was employed, methanolic extract indicated better hydroxyl radical scavenging activity. The evaluation of the antioxidant activity of the extracts activity was concentration-dependent by delaying the indicated oxidation and increased when higher concentrations of the extracts were applied. Therefore, chickpea sprout flour or extract might be used as a source of natural antioxidants in functional foods or in the formulation of the oil-based supplements or medicine in the form of capsule.

This study was carried out to evaluate the antimicrobial and antioxidant effectiveness of methanolic extract and different fractions (n-butanol, ethyl acetate, chloroform and n-hexane) of C. intybus seeds. The antimicrobial activity was determined by the disc diffusion method and minimum inhibitory concentration (MIC) against a panel of microorganisms (four bacterial strains, i.e. P. multocida, E. coli, B. subtilis and S. aureus and three fungal strains, i.e A. flavus, A. niger and R. solani). The results indicated that seeds extract and fractions of C. intybus showed moderate activity as antibacterial agent. While Antifungal activity of C. intybus seeds extract/fractions was very low against A. flavus and A. niger while mild against R. solani. The C. intybus seeds extract/fractions contained appreciable levels of total phenolic contents (50.8-285 GAE mg/100 g of Dry plant matter) and total flavonoid contents (43.3-150 CE mg/100 g of Dry plant matter). The C. intybus seed extract/fractions also exhibited good DPPH radical scavenging activity, with IC50 ranging from 21.28-72.14 mg/mL. Of the C. intybus seeds solvent extract/fractions tested, 100% methanolic extract and ethylacetate fraction exhibited the maximum antioxidant activity. The results of the present investigation demonstrated significant (p<0.01) variations in the antioxidant and antimicrobial activities of C. intybus seeds solvent extract/fractions.

This manuscript is the result of ethnobotany and ethnopharmacology survey on the Hezar Mountain in SE of Iran. Traditional botanical medicine is the primary mode of healthcare for most of the population of this region. The plants were collected in and around Hezar mountain from 2008-2010. The authors have conducted an interview of total 75 informants, The traditional uses of 92 species belonging to 35 vascular plant families and 78 genera have been recorded. The largest number of medicinal species came from Lamiaceae (15.2%). The most common preparations were decoction and infusion. These species are utilized to treat several ailments which the most common of them are digestive disorders of the gastrointestinal tract, (25.4%), renal and genital disorders (13%), respiratory tract system disorders (11.8%), and heart-blood circulatory system disorders (10.2%) respectively.

Inflammation is one of the symptoms of many common and harmful diseases. As it is incurable through chemical drugs, the study on this ailment using new methods and drugs seems necessary. In addition, the adverse effects of the present anti-inflammatory drugs like NSAIDS and Glucocorticoid appeared in the long time use make such study more demanded. Accordingly, in this study we examined the effects of aerial organs’ extract and seed of a plant commonly used in Iranian traditional medicine named Dill on the inflammation caused by plantar injection of formalin in rats and compared them with Diclofenac-gel.One of the methods used for the inflammation assessment is injecting formalin in the rat paw and then measuring the paw volume by the new plethysmometer (weighing method). The assessment is done at a specific time on day for 8 days and then recorded.This study includes 3 groups of 6 male rats: Formalin, Dill-Oil and Diclofenac-gel groups.The Dill-Oil group received 2 g of Dill-Oil, containing 100 mg Dill-extract and the Diclofenac group received 2 g gel containing, 20 mg Diclofenac Na.Data were analyzed with SPSS 17 using ANOVA, Kruskal-Wallis, and Repeated-Measures.The average paw volumes changes in these groups after Formalin-induced inflammation on 1st day, were 0.31 (standard error (SEM)=0.02), 0.30 (SEM=0.01) and 0.32 (SEM=0.05) respectively, with no significant difference.Regarding the peak of inflammation on the 2nd day, it was indicated that the average inflammations in Formalin, Dill-Oil and Diclofenac-gel groups were 0.44 (SEM=0.03), 0.15 (SEM=0.04) and 0.36 (SEM=0.08), respectively.The paw volume changes in groups receiving Dill-oil and Diclofenac-gel, after the daily formalin injection in 8 days compared to the blank group, had a significant decrease (p<0.001). The Dill group showed even more decrease in the paw volume compared to the Diclofenac one.The results of paw volume measurement analyzed by the Plethysmometer manifest that the Dill-Oil is able to decrease the paw volume significantly.

We have shown that buspirone, a partial agonist of 5-hydroxytryptamine 1A (5-HT1A) receptors, improves motor dysfunctions induced by 6-hydroxydopamine (6-OHDA) and haloperidol in rats. The present work extends these findings by investigating the role of 5-HT1A receptors on catalepsy-like immobilization in rats, a model of Parkinson’s disease. Catalepsy was induced by unilateral infusion of 6-OH-dopamine (8 mg/2 mL/rat) into the central region of the substantia nigra, compact part (SNc) and assayed by bar-test method 5, 60, 120 and 180 min after the drugs administration. The involvement of 5-HT1A receptors in 6-OHDA-induced catalepsy was studied through intraperitoneal (0.25, 0.5 and 1mg/Kg IP) and intrasubstantia nigra, compact part (10 mg/rat, intra-SNc) injection of 8-hydroxy-2- [di-n-propylamino] tetralin (8-OHDPAT) as well as administration of 1- (2-methoxyphenyl) -4- [4- (2-pthalimmido) butyl] piperazine hydrobromide (0.1, 0.5 and 1 mg/Kg, NAN-190, IP). NAN-190 (1 mg/Kg, IP) and 8-OHDPAT (1 mg/Kg, IP and 10 mg/rat, intra-SNc) increased and decreased 6-OHDA-induced catalepsy respectively. In normal (non 6-OHDA-lesioned) rats, NAN-190 (1 mg/Kg, IP) increased the elapsed time in bar-test while 8-OHDPAT did not produce any significant effect. The anticataleptic effect of 8-OHDPAT (1 mg/Kg, IP) was reversed markedly by co-injection with NAN-190 (1 mg/Kg, IP). These findings suggest that 5-HT1A receptors are involved in 6-OHDA-induced catalepsy-like immobilization.

Platelet aggregation inhibitory effect and anticoagulant properties of fractions separated from the venoms of Cerastes persicus fieldi and Echis carinatus were investigated.The partial fractionation was performed on a Sephadex G-100 column. Two fractions separated from Cerastes persicus fieldi showed anti platelet aggregation activity on ADP (200 mM) -induced platelet aggregation (ca 80% inhibition). Attempts to measure the antiplatelet aggregation activity of crude Echis carinatus venom and its fractions were not successful due to the protein coagulation of the plasma samples after the addition of venom. Anticoagulant activities of venoms were also evaluated. Total venom of Echis carinatus showed anti coagulant activity in PT test, while its fractions showed procoagulant activity.

The aim of this study was to define the electrocardiogram (ECG) changes following the moderate to severe CO intoxication in rats, and also evaluating the effect of erythropoietin (EPO) on observed cardiac disturbances. The growing literature on erythropoietin effect on cardiac ischemia led us to question its effect on cardiotoxicity due to the carbon monoxide poisoning.Wistar rats were exposed to three different concentrations of CO (250 PPM, 1000 PPM or 3000 PPM). EPO was administrated (5000 IU/Kg, intraperitoneal injection) at the end of CO exposure and then the animals were re-oxygenated with ambient air. Subsequently ECG recording, heart rate and carboxyhemoglobin values were evaluated.ECG changes following the CO intoxication included ST segment elevation and depression, T wave inversion and first-degree AV block. Ischemic ECG changes reduced significantly in EPO-treated animals.In the present study, for the first time, EPO was investigated for the management of cardiac complications due to the CO poisoning. Our results showed that EPO could inhibit ischemic changes of ECG after the CO poisoning.

Osteonecrosis (ON) is characterized through the impairment of osseous blood flow thatleads to the collapse of femur head. Corticoid-induced ON in rats and lipopolysaccharide (LPS) -induced in rabbits are useful models to assess the efficacy of potential treatments on this disease. D-003 inhibits the mevalonate pathway, lipid peroxidation and prevents osteoporosis in rats through increasing the osteoclast apoptosis. This study investigated the effects of D-003 on corticoid- and LPS-induced ON in rats and rabbits.Corticoid-induced ON: Rats were randomized into five groups. A negative control and four groups treated with prednisolone 6 mg/Kg: a positive control and three treated with D-003 (5, 25 and 200 mg/Kg) for 80 days. All positive controls presented ON areas. D-003 significantly reduced the numbers and proportions of ON lesions, as compared to the positive control group.LPS-induced ON in rabbits: Rabbits were randomized into five groups: a negative control and four injected with a single intra-venous injection of LPS (10 mg/Kg) including a positive control and three with D-003 (5, 25 and 200 mg/Kg) for 30 days. ON was seen in all positive controls. The incidence of ON and the number of ON lesions in the groups treated with D-003 (25 and 200 mg/Kg) was significantly lower compared to the positive controls. LPS injection significantly increased the size of bone marrow fat cells in positive controls and such increase was significantly decreased by D-003. In conclusion, D-003 reduced ON lesions in corticoid-and LPS-induced ON and also the size of bone marrow fat cells in rabbits with LPS.

Considering the high rate of epilepsy today, with respect to the insufficiency of the availabletherapies, new strategies and methods are recommended for medical treatment of epileptic patients. Therefore, the present study experimentally investigated the anticonvulsant effect of a herbal medicine candidate brassica nigra, by using kindling method. Sixty male mice were randomly selected and divided into six experimental groups (n=10) including: 1-control, 2-pentylentetrazole (PTZ) -kindled mice, 3-positive control group received valproate (100 mg/Kg) as anti-convulsant drug, 4-5 and 6 received brassica nigra seed extract in three doses (75, 150 and 300 mg/Kg, IP). All groups except for the control ones were kindled by 11 period injections of PTZ (35 mg/Kg, IP). In the 12th injection, all groups except for the control group were tested for PTZ challenge dose (75 mg/Kg). However, the exhibited phases of seizure (0-6) were observed and noted till 30 min after the PTZ injection. At last, the brains of all the mice were removed and then malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) levels of the brain tissues were determined. Statistical analysis of the data shows that the seed extract could reduce the intensity, improvement and duration of seizure. In addition, the brassica nigra extract increased the SOD and NO levels and decreased the MDA level in the brain tissues. Attained results show that the extract of Brassica nigra seed can be used in grand mal seizure treatment. Moreover, the antiepileptic effect of this extract is probably caused by its antioxidant properties and acts via enzyme activity mechanism.

Hepatoprotective Effect of Otostegia persica Boiss. Shoot Extract on Carbon Tetrachloride-Induced Acute Liver Damage in Rats In this study, the hepatoprotective effect of the methanol extract of aerial parts (shoot) fromOtostegia persica Boiss (Golder) was investigated against the carbon tetrachloride (CCl4) -induced acute hepatotoxicity in male rats. Liver damage was induced through the oral administration of 50% CCl4 in liquid paraffin (2.5 mL/Kg bw, per os) 60 min after the administration of the methanol extract of O. persica shoot (in 200, 300, 400 mg/Kg bw doses) and assessed using biochemical parameters (plasma and liver tissue malondialdehyde (MDA), transaminase enzyme levels in plasma [aspartate transaminase (AST), alanine aminotransferase (ALT)] and liver glutathione (GSH) levels). Results show that the methanol extract of O. persica shoot is active at 300 mg/Kg (per os) and it possess remarkable antioxidant and hepatoprotective activities. Additionally, histopathological studies verified the effectiveness of this dose of extract in acute liver damage prevention.

In the present study, we examined the antioxidative activities of Satureja khuzestanica essential oil (SKE) and possible protective effect of SKE on lipid profile, atherogenic index and liver enzyme markers in Alloxan-induced Type 1 diabetic rats. Thirty male rats were randomly divided into three groups, group one as control, group two diabetic untreatment, and group three treatments with SKE by 500 ppm in drinking water, respectively. Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of fasting blood glucose (FBG), triglyceride (TG), cholesterol (C), low density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), atherogenic index and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) of all groups were analyzed. Data were analyzed through non-parametric Man Whitney test (using SPSS 13 software) and p<0.05 was considered significant. SKE inhibited significantly the activities of ALT and ALP and decrease FBG, TG, C, LDL and VLDL. HDL level was significantly increased when treated with the extract. The activities of AST stayed unaltered. Moreover, total antioxidant capacity of SKE was 3.20±0.40 nmol of ascorbic acid equivalents/g SKE. This study showed that SKE is a source of potent antioxidants. The findings of the present study also suggest that SKE exert beneficial effects on the lipid profile, atherogenic index and liver enzymes activity in Alloxan-induced Type 1 diabetic rats.

The aim of the current study is to evaluate the potential mechanism of antidiabetic action of the essential oil of Artemisia sieberi and its effects on some hematological and biochemical parameters in alloxan induced diabetic rats. Extraction of the essential oil from aerial parts of A. sieberi was preformed by hydrodistillation. Fifty rats were divided into five groups. Groups I and II normal rats given 1 mL/day of dimethyl sulfoxide and 80 mg/kg BW of this oil extract, respectively. Groups III, IV and V diabetic rats given 1 mL/day of dimethyl sulfoxide, oil extract (80 mg/kg BW) and metformin (14.2 mg/kg BW), respectively. Several hematological and biochemical parameters were assessed. Oral administration of the extract resulted in a significant reduction in the mean values of blood glucose, glucagon, cholesterol, triglyceride, LDL-C, ESR, urea, uric acid, creatinine accompanied by an increase in the mean values of the total protein, albumin, insulin, HDL-C, neutrophile count and PCV in diabetic rats. No significant changes in these parameters were found in the control group. The effects produced by this extract were closely similar to a standard antidiabetic drug, metformin. In conclusion, the present study indicates that the essential oil extract of A. sieberi appears to exhibit cardioprotective, nephroprotective and hepatoprotective activities in alloxan induced diabetic rats.

Due to the anti-diabetic and antioxidant activity of green tea epigallocatechin-gallate(EGCG), this research study was conducted to evaluate, for the first time, the efficacy of chronic treatment of EGCG on alleviation of hyperalgesia in streptozotocin-diabetic (STZ-diabetic) rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and diabetic and sodium salicylate (SS) -treated control and diabetic groups. For induction of diabetes, STZ was intraperitoneally injected (IP) at a single dose of 60 mg/Kg. EGCG was orally administered daily at doses of 20 and 40 mg/Kg for seven weeks, one week after diabetes induction. Finally, hyperalgesia was assessed using standard formalin, hot tail immersion and paw pressure tests. Meanwhile, markers of oxidative stress in brain were measured. Diabetic rats showed a marked chemical, thermal and paw pressure hyperalgesia, indicating that the development of diabetic neuropathy and EGCG treatment at a dose 40 mg/Kg significantly ameliorated the alteration in hyperalgesia (p<0.05) in diabetic rats as compared with untreated diabetics. EGCG treatment (40 mg/Kg) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation (p<0.05) and nitrite (p<0.05) content and reversed the reduction of antioxidant defensive enzyme superoxide dismutase (p<0.05). The results may suggest therapeutic potential of EGCG for the treatment of diabetic hyperalgesia through the attenuation of oxidative stress.

In this study, it was surveyed to know whether an oral single dose of oleuropein could mimic the cardiac preconditioning in rats’ hearts or whether its prolonged oral administration could protect the heart against the aconitine-induced arrhythmia in rats.Eighty male Wistar rats were divided into two series (n=8 in each group). In the first series, all groups (except the control (Con) group) were given a single oral dose of oleuropein (20 mg/Kg) 1, 3, 24 and 48 h before the infusion of aconitine. In the second series, except the Con group, the other four groups were given oral oleuropein (20 mg/Kg/day) for 3, 7, 14 and 28 days, before the infusion of aconitine. Electrocardiogram was recorded to monitor arrhythmia.Data of the first series showed that the initiation time of arrhythmia, the initiation of ventricular tachycardia (VT), the numbers of reversible ventricular fibrillation (VF) and the death time had no significant difference compared with Con group. In the second series, a significant protection was occurred only in the 28 days group that was evident with increased initiation time of arrhythmia, increased initiation time of VT, and increased the number of reversible VF and death time in compared to the Con group.The findings of this study show that the oral administration of a single dose of oleuropein could not mimic the preconditioning effects in rat hearts, but the prolonged administration of oleuropein for about four weeks could protect the heart against aconitine-induced arrhythmia.

The lack of authentic standards has limited the quantitative analysis of herbal drugs in biological samples. The present work demonstrated a practicable strategy for the assay of herbs and their metabolites independent of authentic standards. A liquid chromatography– electrospray ionization–mass spectrometry (LC–ESI–MS) method for the qualitative and quantitative determination of the metabolites after oral administration of Rhizome coptidis and Zuojinwan preparation in rat urine has been developed. Urine samples, extracted with a protein precipitation procedure were separated on a C18 column using a mixture of water (containing 0.1% formic acid) and acetonitrile (30: 70, v/v) as mobile phase. The detection was performed via MS with electrospray ionization interface in positive selected reaction monitoring (SRM) mode. One urine sample after administration was selected as ‹standard›. The method validation was carried out according to a conventional method which was calibrated by authentic standards. The fully validated method was applied to the pharmacokinetic study of 2, 9-demethyljateorhizine-3-sulfate, 13-methoxyjateorhizine-3- glucoronide and 6-methyljateorhizine-5-glucoronide in rat urine. The results could provide evidence to explain the combination of Rhizome coptidis and Evodiae fructus in terms of elimination.

This study intended to assess the efficacy of acute administration of natural honey on cardiac arrhythmias and infarct size when it is used during the normothermic ischemia in isolated rat heart.During 30 min of regional normothermic ischemia followed by 120 min of reperfusion, the isolated hearts were perfused by a modified drug free Krebs-Henseleit solution (control) or the solution containing 0.125, 0.25, 0.5 and 1% of freshly prepared natural honey (test groups), respectively. Cardiac arrhythmias were analyzed and determined through the recorded ECGs. The infarct size was measured using computerized planimetry package.At the ischemic phase, honey (0.25 and 0.5%) decreased the number and duration of ventricular tachycardia (VT), total number of ventricular ectopic beats (VEBs), duration and incidence of reversible ventricular fibrillation (VF) and total VF (p<0.05 for all). During the reperfusion, concentrations of 0.125, 0.25 and 0.5% lowered the number of VT (p<0.05), duration of reversible VF (p<0.01) and total number of VEBs (p<0.05). In addition, VT duration was reduced significantly with honey 0.125 and 0.25%. Moreover, the infarct size was 45.6±3.4% in the control group, while the perfusion of honey (0.125, 0.25 and 0.5%) reduced it to 14.8±5.1 (p<0.001), 24.6±7.3 (p<0.01) and 31.4±7.3% (p<0.05), respectively.Regarding the results, it is concluded that the acute administration of natural honey in normothermic ischemia conditions can protect the rat heart as the reduction of infarct size and arrhythmias. Conceivably, the antioxidant and free radical scavenging activity, the reduction of necrotized tissue and the providence of rich energy source are more important mechanisms in cardioprotective effects of natural honey.

Despite all modern surgical techniques, skin flap that is considered as the main method inmost reconstructive surgeries puts the skin tissue at danger of necrosis and apoptosis derived from ischemia. Therefore, finding a treatment for decreasing the apoptosis derived from flap ischemia will be useful in clinic.In present study, we evaluated the effect of azelaic acid 20% and finasteride on expression of BCL-2 and bax proteins after the skin flap surgery. For this purpose, 21 rats were entered in three groups including control, azelaic acid 20% and finasteride, all experienced skin flap surgery and then flap tissue was assessed for determining the expression of proteins in 5 slicesprepared from each rat that were graded between – to+++scales.Both azelaic acid and finasteride increased the expression of BCL-2 protein (p<0.05) and decrease the expression of bax protein (p<0.05).These results suggested an antiapoptotic role for finasteride and azelaic acid in preserving the flap after the ischemia reperfusion insult.