Hypertension medication from guidelines to practice: A cohort study in western Iran.

PURPOSE: Hypertension (HTN) is one of the most common risk factors for non-communicable chronic diseases. The aim of the current study is to evaluate the prescribing patterns of antihypertensive medications in Kermanshah Province, west of Iran. METHODS: The Ravansar Non-Communicable Diseases (RaNCD) cohort study is the first Kurdish community-based study; subjects' age ranged from 35 to 65 years. In order to examine the use of medications to control blood pressure, participants were asked to bring all prescribed medications to the study center. Treatments were compared with 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of arterial HTN. RESULTS: From a total of 10 040 participants in RaNCD cohort, 1575 (15.7%) individuals were hypertensive, of whom, 1271 (80.7%) people were aware of their condition. From 1153 (73.20%) people under treatment, 840 (72.8%) had their HTN properly controlled. The most common medications used to treat HTN were losartan (27.5%), metoprolol (14.3%), and captopril (11.9%). Regardless of type of treatment, 49.3% of all patients have received the medication for l 6 ≥ years. The most commonly used drugs were ß-blockers and angiotension receptor blockers as 620 (31.0%) and 612 (30.6%), respectively. Multivariable analysis showed that female gender, those receive ≥3 antihypertensive agents, and using preferred combinations were associated with a better blood pressure control. In addition, the probability of hypertension control was less likely with increasing duration of treatment (i.e >6 years) and in obese patients with ≥35 kg/m2 . CONCLUSIONS: Even though adherence to the international guidelines was acceptable, improvements can be made for better control of HTN. Therefore, it is imperative to educate healthcare professionals on improving their selection of antihypertensive medications and combination therapy for hypertensive patients.

Inhibition of Methamphetamine-Induced Cytotoxicity in the U87-Cell Line by Atorvastatin-Conjugated Carbon Nanotubes.

In biological systems, carbon nanotubes can enhance the biological effects of drugs and reduce their side effects. Methamphetamine (METH) is a stimulant drug that induces cell death in various cell types, primarily neural cells. On the other hand, specific doses of atorvastatin (ATO) can stimulate cell growth and inhibit cell death in different cell lines. This study aimed to investigate the improvement effect of ATO@single-walled carbon nanotube (SWCNT) on METH-induced cell cytotoxicity in the U87 glioblastoma cell line. In this study, cells were cultured in 10 mM of METH during the cell treatment with 0-10 nM of ATO and ATO@SWCNT. The conjugated drugs to SWCNT as Van der Waals were detected using field emission scanning electron microscopy, Fourier transform-infrared spectroscopy, and other analyses. Then, the in vitro proliferating of ATO@SWCNT was explored against glioblastoma cells compared to pure ATO. This examine was performed using methyl thiazole tetrazolium approach, terminal deoxynucleotidyl transferase deoxy uridine-triphosphate nick end labeling assay, caspase-3 method, lactate dehydrogenase assay, and RH-123 assay with 10 mM METH. The results obtained from transmission electron microscopy analysis showed the average size of 50 nm for ATO@SWCNT. This study indicated that U87 cells, which were exposed to METH and suffered cell death, were severely reduced in the presence of ATO, especially ATO@SWCNT (for its anti-apoptotic effect), but they survived. This study suggests that ATO, which was primarily used to reduce blood lipids, can significantly reduce brain cell death. The findings of this study indicate that by using SWCNT, more drugs can reach the target cells. This method reduces the total amount of required medication and shows a more beneficial therapeutic effect.

Dual loading of Nigella sativa oil-atorvastatin in chitosan-carboxymethyl cellulose nanogel as a transdermal delivery system.

Both Nigella sativa oil and atorvastatin possess anti-inflammatory, immunomodulatory, antioxidant, and antibacterial properties that benefit wound healing. In this work, chitosan-carboxymethyl cellulose was loaded on N. sativa oil to synthesize oil nanogel (ONG) which was later used to load with atorvastatin to obtain atorvastatin-oil nanogel (ATONG). Evaluation of the particle size of ONG and ATONG proved the average of 172 and 193 nm, and their surface charges were found to be 32.2 and 34.7 mV, respectively. Transmission electron microscopy of the sample showed that the particles had homogeneous size distributions with spherical structures. Moreover, drug loading efficiency, drug release, and stability of ATONG were investigated, and their results confirmed the appropriate loading and release of atorvastatin. Cytotoxicity evaluation demonstrated that ATONG can safely release atorvastatin intracellularly in fibroblasts. Results from in vitro skin permeation of ONG and ATONG also revealed that the nanogels (NGs) has proper flux through the skin layers. The in vitro wound closure assay for ATONG verified the proliferation and migration capabilities of fibroblasts, confirming the positive effect on wound-healing applications. In scratch model of fibroblasts, the treatment with ATONG resulted in an increase in the expression of the FGF2, TGF-ß1, and VEGF genes involved in fibroblast proliferation and migration aimed at wound healing (p < .001). ATONG, also demonstrated bactericidal effects against Staphylococcus, S. aureus, and S. epidermidis species. Based on the results, ONG and ATONG exhibited great potential to be used as a transdermal drug carrier and skin wound healing NG, respectively.

Signal Transduction of Improving Effects of Ibudilast on Methamphetamine Induced Cell Death.

Objective: Interaction of methamphetamine and sigma (σ) receptors lead to up-regulation and activation of these receptors. The σ receptors induced apoptosis in some parts of the brain by increasing calcium, dopamine, ROS, mitochondrial pores and caspase activity. Ibudilast is a phosphodiesterase inhibitor and anti-inflammatory drug, which can decrease the inflammatory cytokines. Also, it has a neuroprotective effect. It seems that ibudilast can reduce the methamphetamine-induced cell death due to inhibition of σ receptors. Materials and Methods: There were seven treatments including; control: culture medium, Treatment 1: 1mM methamphetamine, Treatment 2: 1mM methamphetamine and 1nM ibudilast, Treatment 3: 1mM methamphetamine and 10nM ibudilast, Treatment 4: 1mM methamphetamine and 100nM ibudilast, Treatment 5: 1mM methamphetamine and 1uM ibudilast, Treatment 6: 1mM methamphetamine and 10uM ibudilast, and Treatment 7: 1mM methamphetamine and 100uM ibudilast. Finally, for inhibition of PKA, CREB, IP3 receptor, NMDA receptor, Sigma receptor antagonist, sigma receptor agonist, cells were preincubated with adding H89 dihydrochloride, 666-15, Heparin, Ketamine, BMY 14802, and Pentazocine. MTT and LDH tests were performed for cell viability and cytotoxicity measurement, respectively. In continuing, the caspase activity colorimetric assay kit used for caspase 3 activity diagnosis. Rhodamine-123 performed to detection of mitochondrial membrane potential. TUNEL test used to DNA fragmentation and apoptosis, Fura-2 used to Measurement of (Ca2+) ic and (Ca2+) m, and fluorescence microscope used to Measurement of antioxidant enzyme activities. Results: Ibudilast increased the cell viability and the rhodamine-123 absorbance in methamphetamin-treated PC12 cells. It reduced cell cytotoxicity, caspase 3 activity, ic and m Ca2+ concentration, (OH) generation and DNA fragmentation in all concentrations of 1 nM t0 100 µM (p<0.05) by the optimal concentration of 100 µM, between our tested treatments. Conclusion: Ibudilast as a phosphodiesterase inhibitor can reduce the methamphetamine-induced cell death due to inhibition of σ receptors through cAMP production.

Shikonin Production by Callus Culture of Onosma bulbotrichom as Active Pharmaceutical Ingredient.

The objective of this research was in-vitro germination and callus induction of Onosma bulbotrichum (O.bulbotrichum) as a medicinal herb which belongs to Boraginaceae family. For germination, the seeds were cultured on growth regulator-free MS medium and for callus induction, seeds were sown on modified MS medium containing different concentrations of kinetin (kn)- Indole-3-acetic acid (IAA) and kn- 2,4-D (2,4-dichlorophenoxyacetic acid), respectively. The plates were maintained in the dark at growth chamber. After 7 days seed germination on hormone-free medium and after 10 days callus initiation on modified medium in the presence of hormones was occurred. The maximum pigmented callus (100%) was observed on modified MS medium with a combination of 0.2 mg.L-1 IAA + 2.10 mg.L-1 kn. Shikonin determination was performed by HPLC method. In addition, total hydroxynaphtoquinons as polyphenols in sum of callus and culture medium were measured by spectrophotometric method and revealed that total naphtoquinones content at IAA was more than 2, 4-D.

Preparation and characterization of pH-sensitive camptothecin-cis-aconityl grafted chitosan oligosaccharide nanomicelles.

Camptothecin (CPT) was introduced to water-soluble chitosan oligosaccharide (CHO) using cis-aconityl (CA), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. CPTCACHO. The triple conjugates were synthesized in three ratios (5%, 7.5%, and 10%) and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1HNMR). Thermo gravimetric analysis and critical micelle concentration (CMC) assessments were performed. Prepared nano-micelles were analyzed for particle size, polydispersity index (PDI), drug release and in vitro cytotoxicity. CPTCACHO 7.5% micelles as optimum micelles had a mean diameter of 50nm (observed by transmission electron microscopy), a zeta potential of +45.9mV, and a CMC of about 9.97×10-5g/L. The release results showed that CPTCACHO 7.5% has the burst release at acidic pH, and cytotoxicity study indicated that IC50 of CPTCACHO 7.5% for MCF-7 cell line was 0.8µg/mL. These properties altogether make CPTCACHO micelles, as a pH sensitive cargo with inherent cytotoxicity, a potential candidate for hydrophobic anticancer drugs.

Preparation and clinical evaluation of Finastride gel in the treatment of idiopathic Hirsutism.

OBJECTIVE: Hirsutism is the presence of excess terminal hairs in females in a male-like pattern. The most accepted hypothesis for the development of hirsutism is increased 5α-reductase activity in hair follicles of hirsute women. Finasteride partially blocks the conversion of testosterone to dihydrotestosterone through inhibition of 5α-reductase in hair follicles. This study was designed to determine the efficacy of finasteride gel 0.25% in management of idiopathic hirsutism and treatment of hirsutism with topical finasteride to lessen the side-effects. METHODS: Women after puberty that have idiopathic hirsutism criteria are divided randomly in two groups; treatment and control. The number of patients in each group is 15 and received finasteride and placebo gel once a day on their skins. The patients were visited every month by a dermatologist and the amount of response to the treatment and the patient satisfaction was recorded. Ferriman-Gallwey score of the treated area was determined. RESULTS: After 6-months, mean thickness hairs in treating group were decreased from 102.00 ± 9.58 µm to 86.4 ± 11.4 µm (p < 0.05), this difference was statistically significant. Gel application did not indicate any type of side-effects. LIMITATIONS: Inclusion and exclusion criteria. CONCLUSION: Finasteride partially blocks 5α-reductase. Because of the good absorption through the skin and good solubility of this medicine, the prepared gel formulation applied on the hirsutism area showed a significant decrease in hair growth locally, so finasteride gel is an efficient and harmless therapy in patients with idiopathic hirsutism.

Hydroxylation index of omeprazole in relation to CYP2C19 polymorphism and sex in a healthy Iranian population.

BACKGROUND: Polymorphism of CYP2C19 gene is one of the important factors in pharmacokinetics of CYP2C19 substrates. Omeprazole is a proton pump inhibitor which is mainly metabolized by cytochrome P450 2C19 (CYP2C19). The aim of present study was to assess omeprazole hydroxylation index as a measure of CYP2C19 activity considering new variant allele (CYP2C19*17) in Iranian population and also to see if this activity is sex dependent. METHODS: One hundred and eighty healthy unrelated Iranian individuals attended in this study. Blood samples for genotyping and phenotyping were collected 3 hours after administration of 20 mg omeprazole orally. Genotyping of 2C19 variant alleles *2, *3 and *17 was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and semi-nested PCR methods. Plasma concentrations of omeprazole and hydroxyomeprazole were determined by high performance liquid chromatography (HPLC) technique and hydxroxylation index (HI) (omeprazole/ hydroxyomeprazole) was calculated. RESULTS: The CYP2C19*17 was the most common variant allele in the studied population (21.6%). Genotype frequencies of CYP2C19*17*17, *1*17, and *2*17 were 5.5%, 28.8% and 3.3% respectively. The lowest and the highest median omeprazole HI was observed in *17*17 and *2*2 genotypes respectively (0.36 vs. 13.09). The median HI of omeprazole in subjects homozygous for CYP2C19*1 was 2.16-fold higher than individuals homozygous for CYP2C19*17 (P < 0.001) and the median HI of CYP2C19*1*17 genotype was 1.98-fold higher than CYP2C19 *17*17 subjects (P < 0.001). However, subjects with CYP2C19*2*17 (median HI: 1.74) and CYP2C19*1*2 (median HI: 1.98) genotypes and also CYP2C19*1*17 (median HI: 0.71) and CYP2C19*1*1 (mean HI: 0.78) did not show any significantly different enzyme activity. In addition, no statistically significant difference was found between women and men in distribution of CYP2C19 genotypes. Furthermore, the hydroxylation index of Omeprazole was not different between women and men in the studied population. CONCLUSION: Our data point out the importance of CYP2C19*2 and CYP2C19*17 variant alleles in metabolism of omeprazole and therefore CYP2C19 activity. Regarding the high frequency of CYP2C19*17 in Iranian population, the importance of this new variant allele in metabolism of CYP2C19 substrates shall be considered.

Ethno-pharmaceutical Formulations in Kurdish Ethno-medicine.

Kermanshah is a city in west of Iran with a specific customs and cultures between the people who are living here. According to historical documents these cultures are very ancient and belong to more than one thousand years. The climate condition in this place forces people to find the solution of their problems using the plants and natural facilities. Therefore traditional healers were so active in Kermanshah. From 8000 of plant species in Iran more than 1200 species has grown in Kermanshah. The ancient customs, cultures, traditional medicine and formulations generally used by rural populations was transfer from ancient to modern people. Documentation of these traditional methods was studied in this research in order to compare and certified the traditional medicine with modern methods and find new dosage forms of drug with botanical source. It was established that about 50 plant species and 8 types of diseases were distinguished and cured by these people. It is also concluding that utilization of these plants approximately the same as application of plants in recent publications.

A Simple Sample Preparation with HPLC-UV Method for Estimation of Clomipramine from Plasma.

Clomipramine is a tricyclic antidepressant. Different methods for determination of clomipramine hydrochloride in plasma have been described. Most of these procedures favor the use of acidic back-extraction in extraction procedure and HPLC as the analytical technique. In this study, the clomipramine extraction procedure was modified and a direct injection to the column was performed to shorten the time of sample preparation considerably. Furthermore, the method was applied in bioequivalence study of new formulations of clomipramine in comparison with reference tablets. THE DRUG AND INTERNAL STANDARD WERE EXTRACTED FROM PLASMA WITH HEPTAN : isoamyl alcohol (95:5) and re-extracted with 200 µL of orthophosphoric acid (0.3% v/v). The organic layer was discharged and analysis was performed on C8 reverse phase ODS2 HPLC column with a mobile phase, acetonitrile : water (75:25) and UV detection set at 215 nm. Additionally, a single dose study was carried out with a two-sequence, crossover block-randomized design for bioequivalence study. Clomipramine tablets (3 × 25 mg) of either formulations (reference or test products) were administered separately in two occasions to 12 fasting healthy male volunteers. Blood samples were taken prior to and at 9 points within 48 h after dose administration. The retention time of internal standard (cisapride), clomipramine, and desmethyl clomipramine were 5.6 ± 0.2, 10.3 ± 0.3, and 9.5 ± 0.3 min, respectively. The standard curve covering the concentration ranges of 2.5-120 ng/mL was linear (r(2) = 0.9950 and 0.9979) for clomipramine and desmethyl clomipramine. The co-efficient of variation for intra-day and inter-day accuracy and precision was less than 18.3%. The pharmacokinetic parameters Cmax and Tmax were obtained directly from plasma clomipramine concentrations. Kel was estimated by log-linear regression and AUC was calculated by the linear trapezoidal rule. The pharmacokinetic parameters AUC and Cmax were tested for equivalence after log-transformation of data. The 90% standard confidence intervals of the mean values for the test/reference ratios, AUC, and Cmax were within the acceptable bioequivalence limits of 0.80-1.20. These results indicated that the analytical method was linear and accurate. Test and reference formulations were found to be bioequivalent and therefore interchangeable.