Iranian Journal of Pharmaceutical Research
Volume:17 Issue: 4, Autumn 2018

The present study was conducted to investigate the performance of different size reduction techniques including probe sonication, extrusion, and high pressure homogenization for nanosizing of niosomes. Also, the effects of cholesterol content and surfactant type on the size and poly dispersity index (PDI) of the formulations were evaluated. Various niosomal formulations composed of Brij 72, Span 60, or Tween 60 were prepared and then, to reduce vesicle size and minimize the PDI, the niosomes were treated by various post-processing procedures. Surfactant type showed a significant effect on the particle size of the niosomes. The particle size of Tween 60 niosomes was significantly larger than those of Span 60 and Brij 72 niosomes (P < 0.05), indicating that at the same cholesterol content, niosomes composed of a surfactant with a higher HLB value show larger particle size than those with a lower HLB value. The influences of cholesterol content as well as downsizing methods, on the particle size and distribution of niosomes were significantly dependent on the surfactant composition of the niosomes. Extrusion and probe sonication were found to be the most efficient methods for size reduction of the Tween 60 and Span 60 niosomes, while for downsizing of Brij 72 niosomes, all employed methods were efficient and resulted in the approximately similar size of about 200 nm. In conclusion, the selection of an efficient method for nanosizing of niosomes and also achievement of a desired size range, and homogeneity highly depends on the niosome composition, particularly on the employed surfactant type.

Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and might lead to development of cervical cancer. Lactoferrin (LF) is a member of the transferrin family, which has antiviral activity against HPV-16. LF is an important player in the defense against pathogenic microorganisms and has also been shown to have activity against several viruses including herpesvirus, adenovirus, rotavirus and poliovirus. Bovine LF has been reported to be a more potent inhibitor of HPV entry in compare to human LF. The goal of the present study is to formulate, evaluate and optimize transfersomal vesicles as a non-invasive transdermal delivery system which assumed to be a suitable for treatment of genital warts. Transfersomes have been prepared by two methods including reverse phase evaporation and thin film hydration with different ratios of cholesterol: lecithin: DOTAP in the presence of SDS or Tween 80. The transferosomes were then evaluated regarding size, polydispersity and LF loading. In vitro release studies in pH 5.3 and 7.4, stability evaluation in 4° C and 25° C and TEM imaging has been performed on optimized transferosomal lactoferrin. The optimized transferosomes were found to have 100 nm sizes with good polydispersity index and encapsulation efficiency of 91% for lactoferrin as well as sustained release of lactoferrin during 24 hours. Transferosomal lactoferrin efficacy was evaluated by MTT assay. It was seen that the viral inhibitory concentration (IC50) of transfersomal lactoferrin has been significantly improved to nearly one tenth in comparison to free lactoferrin.

Terpenes are active constituents of many pharmaceutical dosage forms with naturalproducts origin. One of the challenges in developing dosage forms with herbal originis their standardization as pharmaceutical products. GC-Mass is the most decisive andreliable technique to fulfill the requirements in this regard. In the present study, a reliable,rapid, and accurate method was developed for determination of 7 monoterpenoids in twoselected pharmaceutical dosage forms (rowatinex and rowachol soft gelatin capsules) by gaschromatography-mass spectrometry triple quadrupole selected ion monitoring GC/MS-TQSIM.The method was validated for various parameters such as precision, linearity, accuracy,solution stability, limit of detection, and quantification. The average recovery of terpens wasin the range of 91.6-105.7%. The method was proved to be repeatable with RSD in the rangeof 0.28-11.18 for all of the concentration levels. The developed method is simple, rapid, andsensitive and was applied for determination of alpha pinene, camphene, beta pinene, cineol,fenchone, borneol, trans-anethol and menthol in a few batches of rowachol and rowatinexcapsules purchased from local drug stores.

The aim of current study was to investigate the effect of Brij decoration of liposomes on in vitro and in vivo characteristics of the nanocarriers. Two hydrophilic Brij surfactants (Brij 35 and Brij 78) with almost similar molecular weight but differing in acyl chain were incorporated into liposomal bilayers at two percentages (5% and 10%). Conventional liposomes (CL) containing egg phosphatidylcholine and cholesterol as well as Brij-enriched liposomal dispersions were prepared and characterized. In vivo pharmacokinetics of various liposomal formulations and drug solution (six groups) was studied after intravenous administration to rats. Conventional and Brij enriched DOX liposomes had small size within 82-97 nm and showed homogenous distribution (PDI < 0.1). Drug encapsulation was higher than 97% in all liposomes. The drug release profiles proved sustained DOX release from various formulations. Based on the results of in vivo studies, all five liposomes increased drug exposure and plasma concentration in comparison to free drug. However, DOX liposomes enriched with 5% of either Brij 35 or Brij 78 showed higher AUC values and lower clearance. Overall, Brij surfactants (5% of bilayer lipids) could potentially be used to improve liposomal pharmacokinetic parameters.

Rapid and facile preparation of the cheap modified electrode materials is an important parameter in development of the efficient electrochemical sensor for industrial scale production and mass-market usage. In the present work, the carbon paste electrode modified with multi-walled carbon nanotubes (MWCNTs) was prepared for sensitive determination of lead (Pb) ion in the presence of bismuth (Bi) ion due to synergetic effect of carbon nano-materials and Bi on the voltammetric response. Investigations showed that in presence of Bi ion degassing of the test solution is not needed. Supporting electrolyte, required Bi concentration and accumulation time and potential were optimized for differential pulsed anodic stripping voltammetric tests. Under optimized conditions, modified carbon paste electrode showed sensitive voltammetric response in the range of 0.1-10 μM toward Pb ion. Moreover, efficiency of the developed method was evaluated for the determination of Pb ion in several water samples. The obtained recovery results of 92-97 % revealed good agreement between responses of this sensor and common spectroscopies techniques for the Pb ion analysis. The optimized system has high efficiency in reproducibility and repeatability of the results and applicability for the analysis of the various environmental water samples.

Introduction. Azithromycin is among the broad-spectrum antibiotics that is widely available in various environmental systems and could have destructive effects on the ecosystem and human health due to its bacterial resistance. In this study, removal of azithromycin from wastewater using an advanced oxidation process of ultraviolet light with and without persulfate was investigated and effective parameters for the management of each of the processes were evaluated. Material and method. The effect of different parameters including the concentration of Azithromycin antibiotic at levels 5, 15, 45 mgL-1; the concentration of persulfate at levels 1, 2, 4 mmol; pH at levels 5, 7, 9, contact time in 30, 60, 90 minute range of azithromycin removal was investigated. Ultraviolet light at a wavelength of 254 nanometers was used to irradiate of the reactor. Results and discussion. The results showed that azithromycin removal was significantly lower in the presence of ultraviolet radiation alone 58% with the removal efficiency than the case that ultraviolet radiation was used with sodium persulfate 98%. The best azithromycin removal conditions were obtained at the removal efficiency with the initial concentration of antibiotic 5 mgL-1, the concentration of persulfate 1mmol, the contact time 30 min and pH=7. The rate of decrease in the concentration of residual azithromycin is increasing with increasing sodium persulfate concentration and decreasing the initial azithromycin concentration. Conclusion. This research can help to apply the integrated use of advanced oxidation processes to idealize decomposition-resistant compounds removal processes and to better understand the parameters affecting the removal.

Some new diazo incorporated coumarin compounds were designed and synthesized to evaluate their anti-HIV activity. Overall, compounds were active against HIV at 100 μM. Additionally, no cytotoxic effect was observed at this concentration. The compound with 4-chlorobenzyl group indicated the best anti-HIV activity (52%). Docking studies using the later crystallographic data available for PFV integrase showed similar binding modes to HIV-1 integrase inhibitors. On the basis of these data, nitrogen atoms of 1,3,4-oxadiazole ring have been involved in the Mg2+ chelation and 4-chlorobenzyl group occupies the same position as 4-flourobenzyl group of raltegravir in the active site. In addition, in silico ADME assay demonstrated favorable physicochemical properties for the new designed compounds. Thus, synthesized structures could be introduced as a novel template for designing safe anti-HIV compounds with integrase inhibitory potential.

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazolewith atypical structure-activity relationship was designed, synthesized, and biologicalevaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that althoughthe pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directlyattached to the central ring, it is in the same direction of the sulfonamide group of Celecoxib,a known selective cyclooxygenase-2 inhibitor. Therefore effective hydrogen binding withArg513 is established. Also, additional hydrogen binding could form between NH ofanilino moiety of the 5b and Arg120. All of the compounds had selective inhibitory activityagainst cyclooxygenase-2 in micromolar concentrations comparable with the reference,Celecoxibe. Finally, compound 5b with the selectivity index 115 and IC50 of 0.71 μM againstcyclooxygenase-2 was the most potent one.

Production of nanoparticles has been attractive by biological based fabrication as an alternative to physical and chemical approaches due to exceeding need to develop safe, reliable, clean and eco-friendly methods for the preparation of nanoparticle for pharmaceutical and biomedical applications. In the present study, biogenic tellurium nanoparticles (TeNPs) were successfully prepared using potassium tellurite (K2TeO3, 3H2O) via an eco-friendly and simple green approach by exploiting extracellular enzymes and biomolecules secreted from Penicillium chrysogenum PTCC 5031 at room temperature for the first time. The biofabricated TeNPs were characterized by Atomic Force Microscope (AFM), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Energy Dispersive X-ray spectroscopy (EDX), and Fourier Transform Infrared (FT-IR) spectrum. The AFM and SEM images revealed that the TeNPs were fairly uniform in size with a spherical shape and superior monodispersity. Furthermore, the DLS indicated that the average hydrodynamic diameter of TeNPs was around 50.16 nm and polydispersity index (PdI) of 0.012. The EDX results depicted that TeNPs display an absorption peak at 3.8 keV, indicating the presence of the elemental tellurium. Additionally, the FT-IR analysis of TeNPs exhibited the presence of possible functional groups that may have a role as bioreducers and capping agents. Overall, the results strongly suggested that P. chrysogenum can be a potential nanofactory for the preparation of TeNPs due to several advantages including non-pathogenic organism, fast growth rate, and high capacity of elemental ions reduction, as well as facile and economical biomass handling.

Enterotoxigenic Escherichia coli (ETEC)-induced diarrhoea is the second most commoncause of death in children in the developing countries. Heat labile toxin (LT) is responsible forETEC-induced diarrhoea. In the present study, a novel live ETEC vaccine based on subunitB of LT (LTB) expression in attenuated PhoPc Salmonella strain was developed. Herein, weaimed to compare the in-vitro activity of promoters including constitutive tac, IPTG inducibletrc, and in-vivo-inducible (nirB and nirB78-23) in PhoPc. Additionally, the ability of theserecombinant PhoPc/pLTBs to induce LTB-specific antibody responses in BALB/c mice afternasal immunization was evaluated. In-vitro studies demonstrated that PhoPc has the abilityto produce rLTB. Furthermore, nirB promoter directed significantly more LTB expression inPhoPc/pnirBLTB under anaerobic condition without induction compared to the amount of rLTBsecreted by PhoPc/ptrcLTB in bacterial soup under uninduced condition (6.06 ± 0.05 vs. 1.4 ±0.46 μg/109 cfu, p < 0.01). In addition, the constitutive rLTB expression from tac promoter wasmore than its expression from uninduced trc promoter in bacterial soup (4.2 ± 0.92 vs. 1.4 ±0.46 (μg/109 cfu)) and pellet (27.4 ± 0.89 vs. 13.4 ± 1.42 (μg/109 cfu), p < 0.0001). However,the mice immunized with PhoPc/ptrcLTB elicited the superior anti-LTB responses among thePhoPc containing the examined prompters, which were significantly higher than those inducedby PhoPc/pnirB78-23LTB and PhoPc/pnirB, 6 weeks after the first immunization. Totally, itcould be concluded that in-vitro analysis of promoters for LTB expression in PhoPc may notnecessarily predict the recombinant PhoPc immunogenicity.

The efficacy of methotrexate (MTX) as an antimetabolite chemotherapeutic agent highly depends on its blood circulation half-life. In our previous study, different conjugates of MTX (MTX-PEG) were synthesized, their physicochemical properties were investigated and MTX-PEG5000 was finally selected as optimum drug-conjugate for further investigations. In the current work, first the stability of MTX-PEG5000 was studied at 37 °C and the results indicated its high stability in plasma (T1/2 = 144 h) and a relatively rapid degradation in tissue homogenate (T1/2 = 24 h). The study of protein binding pointed out that the conjugate is highly protein-bound (95%). The results of pharmacokinetic studies in mice indicated that MTX-PEG5000 had longer plasma distribution and elimination half-lives compared to free MTX (T1/2 α 9.16 min for MTX-PEG5000 versus 2.45 min for MTX and T1/2 β 88.44 for MTX-PEG5000 versus 24.33 min for MTX). Pharmacokinetic parameters also showed higher area under the curve (AUC) of conjugate compared to parent drug (12.33 mg.mL-1.min for MTX-PEG5000 versus 2.64 mg.mL-1.min for MTX). The biodistribution studies demonstrated that MTX-PEG5000 did not highly accumulate in liver and intestine and had a mild and balanced distribution to other organs. Also, the conjugate was measurable in tissues up to 48 h after injection and was detected in the brain, suggesting the possibility of delivering drug to brain tumors.

In this study, we assumed that treating animals with an antidepressant agents or voluntary running wheel exercise (RW) during adolescence may have protective effects against early life stress (ELS) which can impact on behavior and mitochondrial function. Evidence indicates that ELS has deleterious effects on brain and behavior and increases the risk of mental disorders such as depression.

Maternal separation stress (MS) model to male rats (postnatal day or PND2-PND14) were performed to determination of depressive-like behaviors using the forced swimming test, splash test and mitochondrial function in the hippocampus.

Treating MS rats with both RW and fluoxetine (5 mg/kg/day, i.p) during adolescence (PND30-PND60) produced antidepressant-like effects in animals and attenuated the negative effects of ELS on hippocampal mitochondrial function in adult male rats. The results of present study showed that (non) pharmacological treatments during adolescence are able to produce protective effects against long-lasting effects of ELS on behavior and mitochondrial function.

These results highlighted the importance of adolescence as an important stage of life and the long-lasting effects of ELS on hippocampal mitochondrial function which can suggest the possible involvement of abnormal mitochondrial function in pathophysiology of depression following experiencing ELS.

Emerging line research showed that silk nanoparticles (NPs) have toxicity on the fibroblastand Huvec cells without any toxicity recognized mechanisms. Recently, it suggested peripheralarterial disease confounds almost eight million Americans. Also, due to the main effect offibroblast in a production of extracellular matrix (ECM), adhesive molecules, glycoproteinsand various cytokines, it decided to define the toxicity mechanistic of silk NPs in fibroblastand Huvec cells based on oxidative stress markers. Therefore, it investigated whether silkNPs is able to induce any abnormality in the fibroblast and Huvec cells based on reliable anddocumented oxidative stress methods. Our results indicated that silk NPs (0.5, 1 and 2 mg/mL)induces cellular and mitochondrial dysfunction including an increase in ROS production, lipidperoxidation, mitochondria membrane potential (MMP) collapse, and oxidation of thiol groupswhich caused to cytochrome c release. Besides, lysosomal integrity damage and decreased inATP/ADP ratio proposed disruptive effect of silk NPs on the mitochondrial respiratory chainand cell death signaling induction.

Since the rose water is used in food, pharmaceutical, and cosmetic products, its microbiological control is necessary. Conventional pasteurization methods cause undesirable changes in taste, smell, medicinal properties and nutritional value with decreasing the amount of essential oil, because of high temperatures. In this study, the effects of the microwave power, temperature, ultrasound power, and ultrasonic exposure were evaluated during rose water pasteurization process on its chemical compositions and E. coli content. In order to determine the microbial inactivation by microwave and ultrasound, E. coli at a concentration of 2 × 106 per mL was inoculated to rose aromatic water. The results showed that each variable on the inactivation of E. coli and energy consumption per microbial reduction cycle had a significant effect. The optimum values of microwave power, temperature, ultrasound power, and ultrasound exposure time were obtained 326.24 W, 43.32 °C, 100 W and 4 min, respectively. The chemical composition assessment was done by GC/MS analysis. Phenethyl alcohol is one of the main components of rose water which was completely lost in the conventional pasteurization method, while in pasteurization process by combined method, it showed an acceptable decrease as compared with raw rose water. Furthermore, the proposed method caused minimal changes in the chemical compositions of the rose water as compared to the conventional heating methods.

The purpose of this study was to investigate the antimicrobial properties of a conventionalpoly methyl methacrylate (PMMA) modified with hydrothermally synthesised titaniumdioxide nanotubes (TNTs). Minimum inhibitory concentration (MIC), minimum bactericidalconcentration (MBC), and minimum fungicidal concentrations (MFC) for planktonic cellsof the TiO2 nanotubes solution against Lactobacillus acidophilus, Streptococcus mutans andCandida albicans were determined. The powder of conventional acrylic resin was modifiedusing 2.5% and 5% by weight synthesised titanium dioxide (TiO2) nanotubes, and rectangularshapedspecimens (10 mm × 10 mm × 3 mm) were fabricated. The antimicrobial propertiesof ultraviolet (UV) and non-UV irradiated modified, and non-modified acrylic resins wereevaluated using the estimation of planktonic cell count and biofilm formation of the threemicroorganisms mentioned above. The data were analysed by one-way analysis of variance(ANOVA), followed by a post-hoc Tukey’s test at a significance level of 5%. MIC, forStreptococcus. mutans, Lactobacillus. acidophilus, and Candida. albicans, MBC for S. mutansand L. acidophilus and MFC for Candida. albicans were obtained more than 2100 μg/mL.The results of this study indicated a significant reduction in both planktonic cell count andbiofilm formation of modified UV-activated acrylic specimens compared with the controlgroup (p = 0.00). According to the results of the current study, it can be concluded that PMMA/TiO2 nanotube composite can be considered as a promising new material for antimicrobialapproaches.

Comorbidty is common among psychiatric disorders including obsessive-compulsive disorder and schizophrenia with a high rate. Many studies suggested that the disorders may have same etiological bases. In this regard, shared pathways of glutamate, dopaminergic, and serotonin are the known ones. Here, the common significant genes are examined to understand the possible molecular origin of the disorders in terms of sequence and functional features. Exploring the underling mechanisms of OCD and schizophrenia is important to achieve a better treatment options. Methods of Cytoscape software following R statistical software were applied for this purpose. Needleman-Wunsch global alignment algorithm was used to determine pair-wise similarities followed by clustering methods, AGNES and PAM in R statistical programming software. The results indicate that ten genes are significantly common for the two disorders and PPI network analysis showed the important key genes in the interaction profile. ESR1 (estrogen receptor α) as a key hub-bottleneck gene regulates many underling mechanisms of the brain. Application of global alignments indicates some of the genes with sequence similarities also elucidate similar biological terms. It seems that evaluation of gender and OCD subtype in schizophrenia patients is another important feature that may elucidate the role of ESR1 in the comoribidty.

Vitamin D deficiency is associated with cardiovascular and metabolic diseases. Cardiovascular diseases, in turn, are responsible for mortality of patients with type 2 diabetes (T2D). We investigated whether a single parenteral dose of 25(OH) Vit D could improve the endothelial function in T2D patients with ischemic heart disease. A randomized, placebo-controlled, and double-blind trial was performed on 112 patients randomly divided into vitamin D (n = 55) and placebo (n = 57) groups. A randomization table was used to administer a single dose of either vitamin D (300000 IU) or a matching placebo, intramuscularly. The levels of 25(OH Vit D, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured at baseline and at 8 weeks. In the supplemented group, the level of serum 25(OH) Vit D was increased significantly (29.6 ± 20.8 vs. 44.5 ± 19.2 ng/mL; P < 0.05), whereas no changes were observed in the placebo group. Within the supplemented group, before and after vitamin D intervention no significant changes in the levels of ICAM-1 and VCAM-1 were observed. Expectedly, the level of 25(OH Vit D increased significantly in the supplemented group. The marginal means of the outcome variables (ICAM-1, VCAM-1, and 25(OH) Vit D) were compared between the groups using ANCOVA, adjusted for the baseline of each variable itself: no significant difference was seen in the markers of the endothelial function. A single parenteral dose of vitamin D in T2D patients with ischemic heart disease failed to show improvement in endothelial function.

Poor penetration of vancomycin into Central Nervous System (CNS) can lead to treatmentfailure. The aim of this study was to evaluate and compare CSF concentration and serumpharmacokinetics of high dose vancomycin by continuous infusion vs. intermittent infusion inpost neurosurgical meningitis patients. Twenty patients were divided into two groups. Patientsin intermittent infusion group received vancomycin as a loading dose of 25 mg/kg over twohours, followed by 25 mg/kg over two hours every 12 h. In the Continuous Infusion group,patients received vancomycin as a loading dose of 25 mg/kg over two hours, followed by 50mg/kg/day by continuous infusion. In the intermittent infusion group, mean ± SD of serumtrough, peak and CSF concentrations were 17.49 ± 2.46 mg/L, 41.33 ± 2.73 mg/L, and 4.83± 1.05 mg/L, respectively. Mean of CSF/trough% ratio was 27.39 ± 2.43%. A positive linearcorrelation was found between the serum trough levels and CSF levels (r = 0.970, P < 0.001).In continuous infusion group, mean ± SD of serum and CSF concentrations were 24.76 ± 2.02mg/L and 6.20 ± 1.31 mg/L respectively. Mean ± SD of CSF/serum% ratio was 24.84% ±3.54%. The serum and CSF levels revealed positive linear correlation (r = 0.902, P < 0.001).The mean of CSF concentration in CI group was 6.20 ± 1.31 mg/L which was significantlyhigher than II group (4.83 ± 1.05 mg/L, P < 0.019). CSF/serum ratio did not show anysignificant difference between the two groups. Continuous infusion of vancomycin makes itpossible to achieve faster and constant target level in serum but did not have any significanteffect on the penetration (CSF/Serum ratio) of vancomycin in to the CNS.

Due to the emerging antibiotic resistance of Acinetobacter, which is the leading cause of ventilator-associated pneumonia (VAP) in critically ill patients, there is an urgent need for studies comparing various antibiotic regimens for its treatment. In this single blinded randomized clinical trial, adult patients with VAP due to multi drug resistant Acinetobacter (MDRA), were randomly assigned to receive 9×109 unit loading dose of Colistin followed by 4.5×109 unit intravenously twice daily plus 750mg intravenous Levofloxacin daily or continuous infusion of Ampicillin/Sulbactam, 24g daily plus 750mg IV Levofloxacin daily. Dose and dosing interval were adjusted according to serum creatinine levels during the study. Clinical and microbiological cure, inflammatory biomarkers and possible adverse effects were recorded in participants. Twenty-nine patients were recruited (14 in Colistin and 15 in Ampicillin/Sulbactam groups). Three patient excluded in each group. Clinical response occurred in 3 (27%) and 10 (83%) in Colistin and Ampicillin-Sulbactam arms, respectively (P=0.007). Nephrotoxicity happened in 6 (54%) and 1 (8%) of cases in Colistin and Ampicillin-Sulbactam groups, (P=0.016). 14-day and 28-day survival rate were significantly higher in Ampicillin-Sulbactam group compared to Colistin arm with P values of 0.002 and 0.049, respectively. This study revealed that Levofloxacin plus high dose Ampicillin/Sulbactam as continuous infusion is more effective than Levofloxacin plus Colistin in patients with MDR Acinetobacter VAP with significantly lower risk of nephrotoxicity.

We conducted a double-blind randomized placebo controlled trial to evaluate the impact of Lemon balm (Melissa officinalis L.) on the bleeding and systemic manifestations of menstruation. A total of 90 students were randomly assigned to treatment or placebo group. Bleeding and systemic manifestations were evaluated with a menstrual pictogram and multidimensional verbal scale before and during 2 consecutive menstrual cycles respectively. Statistical tests showed that in both groups, the severity of the systemic symptoms associated with dysmenorrhea decreased significantly (P=0.001). Among the systemic symptoms, the mean severity of fatigue, the lethargy and nervous changes in the two groups decreased after the treatment, which was statistically significant. There was no significant difference between the two groups regarding fatigue in the three cycles, but there was a significant difference between the two groups regarding lethargy in the first cycle (p=0.05) and the second cycle (p= 0.001) after the treatment. The present study showed that M. officinalis decreases the severity of the systemic signs associated with menstruation. It showed that the herb does not increase the severity of bleeding and the duration of menstruation. However, it reduces the mean total score of the severity of all the systemic symptoms associated with dysmenorrhea.

Human resource management has increasingly become one of the most important challenging issues in the pharmaceutical industry in general and in developing countries in particular to increase the access of societies to needed medicines. In this study, an attempt was made to explore the challenges of human resource management practices surrounding pharmaceutical firms in Iran, as a developing country. To answer the research question, a qualitative descriptive study using thematic analysis was performed through 22 semi-structured interviews with the key informants of Iranian pharmaceutical industry.Extracted themes of interviews were categorized into three main groups namely ability, motivation, and opportunity challenges based on the AMO model and briefly discussed separately. This is the first study investigating HRM challenges in the pharmaceutical industry; the research contributes to developing knowledge of human resource practices and assist pharma managers with better understanding how well implement human resource practices.