Topical isoniazid as a novel treatment for melasma: A randomized, double-blind, vehicle-controlled clinical trial.

INTRODUCTION: Melasma is a chronic hyperpigmentation disorder, and its treatment poses a challenge to dermatologists due to its chronicity and resistance to conventional therapies. Oral isoniazid is used for the treatment of tuberculosis. One of us had previously showed that topical isoniazid exerts a strong depigmenting action in animal models. In this clinical trial, we assessed the therapeutic effect of topical isoniazid on melasma. METHODS: Twenty female patients suffering from epidermal melasma were enrolled and divided equally into two groups. The treatment group received topical isoniazid 10%, and the control group received the cold cream vehicle as the placebo. All participants were advised to avoid sunlight and used SPF 50 sunscreen. Patients applied topical agents once daily at night for 3 months. The melanin and erythema indices were measured by colorimetric evaluations at baseline and after 4, 8, and 12 weeks of treatment. At these time points, the (mMASI) score was also determined, as was the subjective evaluation through Melasma Quality of Life Scale (MELASQOL) scores. Blood tests were performed to evaluate CBC and the liver enzymes. RESULTS: All patients completed the 12-week study. In the treatment group, a significant decrease in melanin index from 63.77 ± 6.27 at baseline to 55.92 ± 5.79 was recorded (p = 0.001). Very minimal clinical changes were also seen in the control group and melanin index was decreased from 62.65 ± 2.23 to 61.25 ± 2.34 (p = 0.004). Clinically significant differences were observed in the rate of changes between both groups. These findings indicate that topical isoniazid has significant depigmenting effects compared to the placebo (p = 0.001). The erythema index remained unchanged in both groups. In the treatment group, the mMASI score was 5.63 ± 3.28 at baseline and 2.13 ± 1.71 at the last follow-up, significantly reduced compared to the control group (p = 0.002). The MELASQOL score indicated a significant improvement in the quality of life in the treatment group. CONCLUSION: This clinical trial shows for the first time that topical isoniazid is effective in treating melasma. Further clinical trials are necessary to confirm the efficacy and tolerability of topical isoniazid in comparison with other skin-depigmenting compounds.

Topical ocular administration using thermosensitive chitosan-glycerophosphate-PRP hydrogels for improved ocular bioavailability.

PURPOSE: One of the difficulties in the pharmacy field is the delivery of drugs for the eyes. Topical therapy is one of the most common methods for treating eye diseases. Due to their unique properties, including biocompatibility and suitable degradation, hydrogels are appropriate for biological purposes. Platelet-rich plasma (PRP), as a designated concentration of platelets, is in a smaller volume than the plasma and is considered a rich source of growth factor that has been used in recent years, including applications in eye diseases including corneal wound healing, improvement of dry eye and post-LASIK syndrome. METHODS: The present study was performed to fabricate Chitosan (CS) and glycerophosphate (GP) based hydrogels that are temperature-sensitive for PRP and investigate their effect on ocular stem cells. RESULTS: CS-GP-based temperature-sensitive hydrogels containing PRP were successfully fabricated using CS and GP. This hydrogel is liquid at ambient temperature and a gel at ocular temperature. Rheology, FTIR, and SEM tests assessed the properties of the hydrogels. The results of the MTT test showed that the hydrogel made with the optimal formulation was not toxic to LSC cell lines. CONCLUSIONS: Given this, CS-GP-based hydrogels can be applied as a biocompatible formulation in ocular medication administration with increased bioavailability at the ocular surface and topical delivery of PRP.

Chitosan-sialic acid nanoparticles of selenium: Statistical optimization of production, characterization, and assessment of cytotoxic effects against two human glioblastoma cell lines.

According to the favorable antitumor properties of selenium, this study aimed to design a novel form of selenium nanoparticles (Se NPs) functionalized with chitosan (Cs) and sialic acid to assess their antitumor effects on the human glioblastoma cell lines (T98 and A172). Se NPs were synthesized in the presence of chitosan and ascorbic acid (Vc) and the synthesis conditions were optimized using response surface methodology. Se NPs@Cs were obtained with a monoclinic structure with an average diameter of 23 nm under the optimum conditions (reaction time = 30 min, chitosan concentration = 1 % w/v, Vc/Se molar ratio = 5). To modify Se NP@Cs for glioblastoma treatment, sialic acid was used to cover the surface of the NPs. Sialic acid was successfully attached to the surface of Se NPs@Cs, and Se NPs@Cs-sialic acid were formed in the size range of 15-28 nm. Se NPs@Cs-sialic acid were stable for approximately 60 days at 4 ℃. The as-synthesized NPs exerted inhibitory effects on T98 greater than 3 T3 > A172 cells in a dose- and time-dependent manner. Additionally, sialic acid ameliorated the blood biocompatibility of Se NPs@Cs. Taken together, sialic acid improved both the stability and biological activity of Se NPs@Cs.

Immobilization of Clostridium perfringens type D in calcium alginate beads: toxin production mimics free cell culture.

Background and Objectives: Cell-immobilization is used to maintain microbial culture to produce metabolites in repeated-batch or continuous fermentations, thereby reducing the time and resources spent on delivering mass production of microbe. The technique also enables shortening of the detoxification phase and the amount of formaldehyde required due to low incidence of viable bacteria in the extract. Materials and Methods: A solution of sodium alginate containing Clostridium perfringens cells was dropped into stirring CaCl solution via a sterile syringe needle. Optimizations resulted in reasonably uniform beads containing C. perfringens. Beads were externally stabilized by poly L-lysine, followed by immersion in a solution of Na-alginate to coat them with a new layer of alginate forming an alginate-PLL-alginate cortex. Results: This study proved successful in immobilizing C. perfringens cells inside uniform alginate microspheres. Cell loading and cell propagation inside the beads were measured. The cell loaded beads were cultivable in liquid media producing 550 minimum lethal doses per milliliter (MLD/ml) in a 72 h. Conclusion: The research paved the way for further investigations to optimize and establish an efficient bacterial encapsulation method. Thus, it seems possible to produce toxins from beads engulfing C. perfringens on larger scales via repeated-batch or continuous fermentation processes.

Hydrogel beads-based nanocomposites in novel drug delivery platforms: Recent trends and developments.

The present article evaluates the composition and synthesis of hydrogel beads. Hydrogels, owing to their known biocompatibility, are widely used in drug delivery as a host (or drug carrier). Hydrogels, owing to their physical, chemical and biological properties, are popular in many aspects. Hydrogels are crosslinked-hydrophilic polymers and commercialized/synthesized in both natural and synthetic forms. These polymers are compatible with human tissues, therefore can be potentially used for biomedical treatments. Hydrogels in drug delivery offer several points of interest such as sustainability, and sensitivity without any side-effects as compared to traditional methods in this field. Drugs can encapsulate and release continuously into the targets when hydrogels are activated/modified magnetically or by fluorescent materials. It is crucial to develop new crosslinked polymers in terms of "biocompatibility" and "biodegradability" for novel drug delivery platforms. In the event that the accomplishments of the past can be used into the longer terms, it is exceedingly likely that hydrogels with a wide cluster of alluring properties can be synthesized. The current review, offers an updated summary of latest developments in the nanomedicines field as well as nanobased drug delivery systems over broad study of the discovery/ application of nanomaterials in improving both the efficacy of drugs and targeted delivery of them. The challenges/opportunities of nanomedicine in drug delivery also discussed. SCOPE OF THE RESEARCH: Although several reviews have been published in the field of hydrogels, however many of them have just centralized on the general overviews in terms of "synthesis" and "properties". The utilization of hydrogels and hydrogel-based composites in vital applications have been achieved a great interest. In this review, our aim is to recap of the key points in the field of hydrogels such as; a) hydrogel nanocomposites, b) magnetic beads, c) biomedical applications, and d) drug delivery. In the same vein, these outlines will be expanded with emphasizing on the boon of magnetic beads and recent developments in this area.

Preparation of PLA/chitosan nanoscaffolds containing cod liver oil and experimental diabetic wound healing in male rats study.

Diabetes mellitus is one of the most common metabolic disorders. One of the important metabolic complications in diabetes is diabetic foot ulcer syndrome, which causes delayed and abnormal healing of the wound. The formulation of nanoscaffolds containing cod liver oil by altering the hemodynamic balance toward the vasodilators state, increasing wound blood supply, and altering plasma membrane properties, namely altering the membrane phospholipids composition, can be effective in wound healing. In this study, electrospinning method was used to produce poly lactic acid/chitosan nanoscaffolds as a suitable bio-substitute. After preparing the nanoscaffolds, the products were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Also optical properties of polymer and comparison between adsorption between single polymer and polymer-drug calculated with UV-Vis spectra. The structure and functional groups of the final products were characterized by Fourier-transform infrared spectroscopy (FT-IR) and energy dispersive spectroscopy (EDAX) as elemental analysis. The results showed that the optimum formulation of cod liver oil was 30%, which formed a very thin fiber that rapidly absorbed to the wound and produced significant healing effects. According to the results, poly lactic acid/chitosan nanoscaffolds containing cod liver oil can be a suitable bio-product to be used in treating the diabetic foot ulcer syndrome.

Formulation, Physiochemical, and Microbial Assay of Henna Oil Vaginal Suppository Formulated with Polyethylene Glycol Bases.

BACKGROUND: Persian Medicine is one of the oldest and richest complementary and alternative options in the field of medicine and has a comprehensive medical system. Henna oil is recommended in Persian Medicine for the treatment of numerous women's diseases such as cervicitis. To date, henna has been used for many medical purposes, including astringent, bleeding, cardioinhibitory, hypotension, and relaxation. Accordingly, the present study aimed to provide the formulation of a henna-oil-based vaginal suppository and examine its physicochemical and antimicrobial properties. METHODS: The present study was approved and performed in accordance with the regulations of Research Council, Kerman University of Medical Sciences, Kerman, Iran, in July 2016. Different percentages of henna oil, glycerin, and gelatin, as well as henna oil and polyethylene glycol 400 and 4000, were mixed to achieve a formulation with proper appearance features and, particularly, without any oil leakage from the suppository surface. Uniformity of weight, uniformity of content, disintegration time, and dissolution test of the suppositories were evaluated. The growth-inhibiting activity of the suppositories and aqueous extract of henna was evaluated against bacteria, including the Gram-positive bacterium Gardnerella vaginalis, Neisseria gonorrhoeae, and group B streptococcus. RESULTS: The formulations had a smooth appearance without any cracks or fractures. Disintegration times for glycero-gelatin and polyethylene glycol suppositories were 60 and 10 min, respectively. 40% of the drug was released from polyethylene glycol suppositories after 60 min, but glycero-gelatin suppositories had no release after three hours. Minimum inhibitory concentration (MIC) of suppositories and aqueous extract were 0.4 mg/mL and 0.01 mg/mL, respectively. CONCLUSION: Polyethylene glycol suppositories had acceptable physicochemical properties, and the henna extract and suppositories inhibited the three studied pathogens.

Safety and efficacy of Berberis integerrima root extract in patients with type 2 diabetes. A parallel intervention based triple blind clinical trial.

PURPOSE: To evaluate the safety and efficacy of methanol extract of Berberis integerrima root on type 2 diabetes compared to metformin. METHODS: In a parallel triple blind clinical trial, 80 type 2 diabetic patients,, were randomized into two groups (treated with Berberis integerrima root, 480 mg (oral), compared to control group treated with metformin 1000 mg daily). Efficacy was evaluated by fasting and prandial glucose and HbA1c and side effects confirmed by physical examination, biology and hematology tests and urinalysis on days 15, 45 and 90. They were followed for 3 months. RESULTS: Two hundred and eighteen patients were recruited and 80 (55female and 25 male) patients randomized in two groups and 60 patient were analysed. The mean age of patients was 51.8 ± 9.3 and 46.5 ± 10 in the experimental (Berberis integerrima ) and control (metformin) groups respectively (P = 0.02). The mean HbA1c at baseline was 8.1 ± 1.6% and 7.9 ± 1.6% for B. integerrima and metformin group respectively (P = 0.53), and there was no significant difference between the two groups (7.5 vs. 7.2) after 3 months (P = 0.34).Weight loss was observed in both groups compared to baseline.No adverse event led to preventing the study was reported. CONCLUSION: Berberis integerrima root not only was effective as much as metformin in reducing blood glucose and controlling type 2 diabetes but also, no specific side effect was reported (in short term).So, it might be an effective and safe complementary therapy in diabetic patients.Iranian Research and Clinical Trial (IRCT) registeration number; 201,207,191,774 N5.Funding: Vice chancellor for research, Physiology Research Center of Kerman University of Medical Sciences and the Exir pharmaceutical company.

Leishmanicidal effects of amphotericin B in combination with selenium loaded on niosome against Leishmania tropica.

The strategy for improving the treatment of leishmaniasis by the World Health Organization, is the development of new drugs and combination therapy. The aim of this survey was to investigate the effect of amphotericin B (AmB) in combination with selenium, in a simple or niosomal form, on Leishmania tropica (L. tropica) by in vitro advanced assays. In this study, a niosomal formulation of AmB with selenium was prepared and characterized based on size and morphology. Using MTT assay, macrophage model, flow cytometry, and qPCR, the cytotoxicity and efficiency of the niosomal formulation and simple form of combination were evaluated. No toxicity was reported for both the niosomal and simple form of the combination. The niosomal formulation significantly showed higher inhibitory effect on the promastigote and amastigote forms of L. tropica than simple combination form. Interleukin (IL)-10 significantly decreased while the level of IL-12 and metacasoase as Th-1 activator significantly increased (P < 0.001). The findings of this study indicated that niosomes are the stable carriers for this combination, easy to produce and provide promising results as an effective formulation in the inhibition of extracellular and intracellular forms of L. tropica in compared with simple combination form.

Serum levels of Organochlorine Pesticides and Breast Cancer Risk in Iranian Women.

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.

Niosomal formulation of amphotericin B alone and in combination with glucantime: In vitro and in vivo leishmanicidal effects.

This study aimed to evaluate the efficacy of glucantime and amphotericin B (AmB) encapsulated in niosome against cutaneous leishmaniasis (CL) using in vitro and in vivo models. The niosomal formulations of the drugs alone and in combination were prepared and characterized. Subsequent to the examination of their cytotoxicity, their efficacy was evaluated using an in vitro MTT assay, macrophage model, flow cytometry, and gene expression profiling. For evaluation of therapeutic effect of niosomal combination on the lesion induced by Leishmania major in inbred BALB/c mice, the size of lesions and number of parasites in spleen was assessed. The niosomal formulations demonstrated significantly greater inhibitory effects compared with the non-niosomal forms when the IC50 was considered. The niosomal combination showed an increase in the apoptotic values and gene expression levels of IL-12 and metacaspase and a decrease in the levels of IL-10 with a dose-response effect. The niosomal combination was also effective in reducing the lesion size and splenic parasite burden in mice. Our findings indicated that there is a synergistic effect between AmB and glucantime in niosomal form in the inhibition of intracellular and extracellular forms of L. tropica. Additionally, the in vivo results on L. major suggest that topical niosomal formulation could be useful in the treatment of CL.

Preparation of polyacrylamide/polylactic acid co-assembled core/shell nanofibers as designed beads for dapsone in vitro efficient delivery.

The main aim of this study is to synthesize and prepare polyacrylamide (PAM)/polylactic acid (PLA) co-assembled core/shell nanofibers in order to investigate an effective dapsone-loaded capability and dapsone-release in the aqueous medium. Dapsone (4,4-diamino-diphenyl sulfone) has high permeability and low solubility in water. In vitro release testing indicates that maximum incorporation of the dapsone nanoemulsions into core/shell nanofibrous structures were 77.71 after 400 min. Products were characterized with X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-Gravimetric Analysis (TGA), Dynamic light scattering (DLS) analysis, Contact Angle Measurement (CAM) and nitrogen adsorption [i.e. Brunauer-Emmett-Teller (BET) Surface Area Analysis] techniques. The porosimetric measurements of the nanofibers structures showed that high porosity diameter, adsorption cross-section area, pore volumes and dead volume were obtained as 0.162 nm2, 0.1005 cm3g-1 and 15.693 cm3, respectively. TGA curve of the core/shell nanofibrous structures shows thermal stability between 240 °C and 260 °C.

A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica.

There is no effective treatment modality available against different forms of leishmaniasis. Therefore, the aim of this study was to improve the penetration and efficacy of selenium and glucantime coupled with niosomes and compared them with their simple forms alone on in vitro susceptibility assays. In this study, the niosomal formulations of selenium and in combination with glucantime were prepared. The size and morphology of the niosomal formulations were characterized and the effectivity of the new formulation was also evaluated using in vitro MTT assay, intra-macrophage model, and gene expression profile. From the results obtained, no cytotoxicity effect was observed for niosomal and simple forms of drugs, as alone or in combination. Niosomal formulations of the drugs significantly showed more inhibitory effects (P ≤ 0.001) than the simple drugs when the selectivity index was considered. The gene expression levels of Interleukin (IL-10) significantly decreased, while the level of IL-12 and metacaspase significantly increased (P ≤ 0.001). The results of the present study showed that selenium plus glucantime niosome possess a potent anti-leishmanial effect and enhanced their lethal activity as evidenced by the in vitro experiments.

A road to bring Brij52 back to attention: Shear stress sensitive Brij52 niosomal carriers for targeted drug delivery to obstructed blood vessels.

Thrombosis is a shared perpetrating event in the pathophysiology of several cardiovascular disorders such as ischemic stroke, venous thromboembolism, atherosclerosis, and myocardial infarction. Despite holding a wide range of ammunition in our arsenal to ameliorate such conditions, we are still facing with many stumbling blocks in the satisfactory pharmacotherapy of cardiovascular diseases among which the risk of hemorrhage and life threatening drug interactions can be highlighted. Our hypothesis focuses on mimicking the nature of platelet activation, to design a novel targeted delivery system based on the alterations of a physical parameter, the hemodynamic shear stress, to aim at the offending thrombi in an attempt to offer a noninvasive, rapid, and monitoring-free method that not only can prolong the circulation time of the cargo, but also deliver it locally and reduce both the undesirable adverse effects and drug interactions. Brij52 is our chosen candidate due to its unique non-spherical morphology after forming a niosomal vesicle. We surmised that thanks to its non-spherical shape, diverse shear rates may generate different shear stresses to its equators and axes which might result in the breakdown or at least distortion of niosomal structure under elevated shear stress. The vesicles have to be synthesized in the size of platelets or in the nano-sized scale. In order to prolong the time vesicles are circulating in the blood, PEGylation may help and to make such carriers highly selective to be only activated during pathophysiological clot formation, attachment of domain A1 von Willebrand factor can be of benefit to lead this proposed delivery system to the site of thrombus formation where shear rate exceeds those of 1000 s-1. There is now an emerging fast growing universal research on shear activated carriers, and the present theory is an endeavor to reach a successful treatment strategy to combat cardiovascular diseases based on the hypothesis that a non-spherical nano-carrier such as Brij 52 niosomal vesicle can be of paramount benefit to deliver current antithrombotic agents in a targeted and controlled manner in the presence of elevated shear stress of the obstructed blood vessels. With more radical advanced drug delivery systems being developed and new strategies being pursued, there will be more options in our arsenal to represent a promising avenue for achieving preventive, well-tolerated, and intelligent drug carriers to circumvent the drawbacks of antithrombotic pharmacotherapy.

Prevalence of Aflatoxin Contamination in Herbs and Spices in Different Regions of Iran.

BACKGROUND: Mycotoxins are natural toxins, produced by several fungal species and are associated with morbidity or even mortality in animals, plants, and humans. In this study, 120 samples of herbs and spices in both bulk and packaged forms were prepared in order to measure aflatoxin level in different regions of Iran. METHODS: The aflatoxin was extracted during Mar to May 2015, using 80% methanol and then purified via immunoaffinity column. Measurements were performed, using high-performance liquid chromatography, equipped with a fluorescence detection system at excitation and emission wavelengths of 365 and 435 nm, respectively. RESULTS: The highest prevalence of aflatoxin contamination in food products was attributed to aflatoxin B1 (30.8%). In addition, the highest prevalence of aflatoxin contamination was reported in red pepper (100%). Examination of effective factors indicated the substantial impact of moisture on aflatoxin level (P=0.046). CONCLUSION: Even at low levels of aflatoxin, contamination could be a serious threat, given the prevalent use of spices (either raw or not) as ingredients in food preparation. Therefore, regular monitoring of spices, especially chili pepper, is highly recommended.

The effect of tobramycin incorporated with bismuth-ethanedithiol loaded on niosomes on the quorum sensing and biofilm formation of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen, enable of causing infections especially in immunocompromised patients. Recently many isolates developed multiple drug resistance, resulting in treatment failure in serious infections. In this study, the effect of tobramycin incorporated with bismuth-ethanedithiol loaded on niosomes on the quorum sensing and biofilm production by P. aeruginosa was evaluated. Thin layer hydration method with cholesterol (30%), Span 40 and Tween 40 were used to make niosomes. The physical properties and particle size of the niosomes were investigated. Micro dilution method was used to determine the Minimum Inhibitory Concentration (MIC) for tobramycin, niosomal tobramycin, bismuth ethanedithiol, niosomal bismuth ethanedithiol, tobramycin incorporated with bismuth-ethanedithiol and niosomal tobramycin incorporated with bismuth-ethanedithiol. Biofilm formation was evaluated using microtiter plate. The effect of different combination on N-acyl homoserine lactone (AHL) production was evaluated in presence of Agrobacterium tumefaciens strain (GV3101). The best combination inhibiting the growth of various strains of P. aeruginosa were niosomal tobramycin and niosomal tobramycin incorporated with bismuth-ethanedithiol which reduced the MIC of tobramycin significantly. Sub-MIC concentration of these compounds reduced the rate of biofilm formation 80% lower than the untreated bacteria, and effectively inhibited the production of AHL molecule. The prepared formulations containing non-ionic surfactants, can kept the drug and gradually release it. Encapsulation of tobramycin in combination with bismuth-ethanedithiol in niosome had the ability to reduce the MIC of tobramycin and effectively inhibiting the biofilm formation. These combinations can be used as an excellent combination for further evaluation for treatment of infections caused by MDR isolates of P. aeruginosa.

What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients?

To permit appropriate targeted therapy, the present clinical study was aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty-eight male DAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1mg/kg per 12h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independence measure (FIM). The markers of inflammation [interleukin-1ß (IL-1ß), IL-6, transforming growth factor-ß1 (TGF-ß1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIM scores were observed in progesterone group at the six-month follow-up (P<0.05 and P<0.01, respectively). Meanwhile, a reduction in the serum levels of IL-1ß, MDA and S-100B was noticed in progesterone group 24h after injury (P<0.05, P<0.001 and P<0.05, respectively), and there was an increase in serum levels of IL-6 and TGF-ß1 (P<0.01 and P<0.05, respectively). Also, lower levels of MDA and S-100B, and higher levels of TGF-ß1 were observed in progesterone group six days after injury (P<0.05). According to these findings, progesterone may improve the outcome in DAI patients probably through modulation in the levels of cytokines, and reduction in the injury and oxidant activity.

Preparation and characterization of physicochemical properties of N, N-diethyl-meta-toluamide niosomes.

INTRODUCTION: The insect repellent compounds are used to protect humans, animals and plants against insect bites. Aromatic amides have insect repellent effects. N,N-diethyl-meta-toluamide (DEET) (C12 H17 NO) is one of the best insect repellents has been used for many years. DEET is a colorless, odorless liquid that is approximately insoluble in water and soluble in glycerin, ethanol, and isopropyl alcohol. Due to the solubility problem of DEET, its topical formulations usually have alcoholic bases, but these kind of formulations increase skin permeation and also systemic absorption of DEET, which leads to some toxic effects. The main goal of this study was to prepare the formulation of DEET niosomes in a topical dosage form with suitable stability properties. MATERIALS AND METHODS: Three different methods were used to prepare niosome formulations: Dehydration rehydration vesicle method, direct mixing method, homogenizer method. Sorbitan surfactants, cholesterol, polyoxyethylenecetyl, phosphate buffer (pH 7.4), and charge inductive compounds like cetyltrimethylammonium bromide were used to provide a net negative charge to the final membrane structure. A high-performance liquid chromatography method was then used for the determination of the loaded DEET. RESULTS: A large number of niosomes were multi-layered and have a spherical shape. In comparison, syringe method against direct mixing is more appropriate because of creation MLV and uniform niosomes but the best method is homogenizer method. Drug entrapment was between 14% and 21% in selected formulation. CONCLUSION: According to this study, homogenizing method can be used for formulation of DEET in niosome form in topical formulations.

Determination of Vitamin D Serum Levels and Status of the C3435T Polymorphism of Multidrug Resistance 1 Gene in Southeastern Iranian Patients with Ulcerative Colitis.

BACKGROUND Ulcerative colitis (UC) is a multi-factorial autoimmune disease. P-glycoprotein is encoded by the multidrug resistance 1 (MDR1) gene. The C3435T polymorphism in the MDR1 gene is correlated with low P-glycoprotein expression. Additionally, vitamin D has regulatory effects on the immune system. The aim of our study was to determine the association between the C3435T MDR1 polymorphism and UC and to detect the vitamin D serum levels in patients with UC. METHODS One hundred healthy controls and 85 patients with UC were evaluated. Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) was used to detect the C3435T MDR1 polymorphisms. Serum levels of vitamin D were measured by Enzyme-linked immunosorbent assay (ELISA). The research was performed in Kerman, Iran, from 2011 to 2013. RESULTS We could not find any association between the C3435T MDR1 polymorphism and susceptibility to UC. There was a significant decrease in serum levels of vitamin D in patients with UC compared with healthy controls (p<0.001). CONCLUSION Controversies regarding the association between the C3435T MDR1 polymorphism with UC have been reported in different populations. The difference between our results and others may be attributed to the heterogeneity of the Iranian population and the sample size. Additionally, our data indicated that UC might be correlated with vitamin D insufficiency. Therefore, the administration of vitamin D might be suggested as a valuable treatment for patients with UC.

Anti-leishmanial effect of itraconazole niosome on in vitro susceptibility of Leishmania tropica.

The novel niosomal system aimed to deliver the active drug entity to the target site. The objective of this study was to prepare and evaluate the effect of itraconazole niosome on the in vitro susceptibility of Leishmania tropica as compared to itraconazole alone or tartar emetic. The overall growth rate of promastigotes treated with various concentrations of itraconazole niosome was significantly lower than that of itraconazole alone (IC50=0.24 µg/ml vs. IC50=0.43 µg/ml, P<0.01). In contrast, the mean multiplication rate of amastigotes inside the macrophages and also the mean number of amastigotes in each macrophage treated with itraconazole niosome (34.9 and 3.0) were significantly lower (P<0.01) than those treated with itraconazole alone (62.0 and 3.8) or tartar emetic (63.9 and 4.2), respectively. These findings indicated that niosomes could be developed as a novel drug delivery for itraconazole in the in vitro model. Further studies are required to evaluate the effect of itraconazole niosome on volunteer human subjects.