Showing papers by "Farzad Kobarfard published in 2009"

Development and optimization of solid lipid nanoparticles of amikacin by central composite design.

Abstract: Solid lipid nanoparticles (SLNs) have been studied as a drug-delivery system for the controlling of drug release. These colloidal systems have many important advantages, such as biocompatibility, good tolerability, and ease of scale-up. In the preparation of SLNs, many factors are involved in the characteristics of the particles, such as particle size, drug loading, and zeta potential. In this study, fractional factorial design was applied to examine which variables affect the physicochemical properties of amikacin SLNs. Study was continued by a statistical central composite design (CCD) to minimize particle size and maximize drug-loading efficiency of particles. The results showed that three quantitative factors, including the amount of lipid phase, ratio of drug to lipid, and volume of aqueous phase, were the most important variables on studied responses. The best predicted model for particle size was the quadratic model, and for drug-loading efficiency, was the linear model without any significant lack of fit. Optimum condition was achieved when the ratio of drug to lipid was set at 0.5, the amount of lipid phase at 314 mg, and the volume of aqueous phase at 229 mL. The optimized particle size was 149 +/- 4 nm and the drug-loading efficiency 88 +/- 5%. Polydispersity index was less than 0.3. The prepared particles had spherical shape, and the drug release from nanoparticles continued for 144 hours (6 days) without significant burst effect.

Ion release and pH of a new endodontic cement, MTA and Portland cement.

Abstract: Introduction: This in vitro study measured and compared pH and phosphate and calcium ions release of a new endodontic material (CEM cement), mineral trioxide aggregate (MTA), and Portland cement (PC) using UV-visible technique, atomic absorption spectrophotometry methods, and pH meter, respectively. Materials and Methods: Each material was placed in a plastic tube (n=10) and immersed in a glass flask containing deionized water. Half of the samples were tested for determining pH and released ions after 1h, 3h, 24h, 48h, 7d and 28d. Remaining samples (n=5), were evaluated after 28d. Data was analyzed using one way ANOVA and Tukey tests. Results: Results indicated that all materials were highly alkaline and released calcium and low concentration of phosphate ions in all the time intervals. CEM cement released considerably higher concentration of phosphate during the first hour (P<0.05). Conclusion: This novel endodontic cement promoted alkaline pH in a similar manner to MTA and released calcium and phosphate. These conditions can stimulate the calcification process and explain the basic physico-chemical mechanisms of hard tissue regeneration of CEM cement. [Iranian Endodontic Journal 2009;4(2):74-8]

Biological reactive intermediates that mediate dacarbazine cytotoxicity.

Abstract: Purpose In the following, the cellular and molecular mechanism of cytotoxicity induced by prodrug dacarbazine toward the isolated rat hepatocytes was studied.

Two flavones from Salvia leriaefolia.

Abstract: The methanolic extract of the aerial parts of Salvia leriaefolia (labiatae) afforded 5-hydroxy4´, 6, 7-trimethoxy flavone (Salvigenin) and (5,4´-dihydroxy-7-methoxy flavone (Genkwanin). The structures of the isolated compounds were elucidated using 1 and 2 D-NMR, IR, UV and MS.

Terpens from aerial parts of Euphorbia splendida.

Abstract: Euphorbia splendida Mobayen (Euphorbiaceae) is one of the Euphorbia species that has not been studied so far. The aerial parts of this plant was collected from Arak, Iran and extracted with methanol (by maceration). The dried extract was subjected to exhaustive separation by column chromatography and preparative TLC. Two terpens, a lupane-type triterpenoid and a diterpene with a tricylic lathyrane skeletone, were isolated and purified and identified as 3i¢-28-dihydroxylup-20(29)-ene (betulin) and decipinone respectively for the first time from this plant. The structures of the isolated compounds were elucidated on the basis of spectroscopic methods including 1 and 2 D-NMR, IR, UV and MS. Key words: Chromatography, diterpene, triterpen, betulin, decipinone.

Diterpenoids of Otostegia persica (Burm.) Boiss

Abstract: Background and propose of the study: As there is no significant work on O. persica, a phytochemical investigation of this species was carried out in this study. Methods: The structures of the compounds 1-4 were established by their spectral data and their relative configuration was determined by 2D NMR. Results and major conclusion: Four known diterpenoids belonging to the clerodane and tetracyclic diterpene types were isolated for the first time from Otostegia persica (Burm.) Boiss. These compounds are known to occur only in genus Otostegia.

Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spectrometry.

Abstract: Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.

Serum copper (Cu) alterations in pulmonary tuberculosis patients under treatment with ethambutol.

Abstract: Ethambutol is an oral anti-tuberculosis agent with chelating effects owing to its chemical structure which is similar to that of penicillamine. Copper (Cu) is an essential trace element that has important roles in physiological function of the body organs. The aim of present study was to determine (1) whether ethambutol usage can alter serum Cu concentration in patients with tuberculosis and (2) whether there is any relationship between age, sex, and smoking habit of patients with changes in serum Cu levels. Sixty patients with diagnosis of pulmonary tuberculosis were enrolled the study. Blood samples were obtained before treatment (baseline) and 10 days after starting anti-tuberculosis therapy. The amounts of serum Cu were determined in all samples by atomic absorption. Mean ± SD levels of Cu at baseline and on the 10th day of ethambutol use were 0.94 ± 0.24 and 0.64 ± 0.24 μg/mL, respectively. Statistical analysis confirmed a significant difference (p < 0.0001). Also, there was not any relationship between changes in Cu concentration and study variables of age, sex, and smoking habit. Our findings endorse the chelating effect of ethambutol leading to a decrease in serum levels of cationic trace elements, e.g., Cu.

Effect of Antituberculosis Regimen Containing Ethambutol on Serum Magnesium Level in Pulmonary Tuberculosis Patients

Abstract: Magnesium is an essential metal that has important roles in physiological function of the body organs. Ethambutol is an oral antitubercular agent with chelating effects owing to its chemical structure. The aim of present study is to determine whether ethambutol usage can alter serum magnesium concentration in patients with pulmonary tuberculosis. Sixty patients with diagnosis of pulmonary tuberculosis were enrolled in the study. Blood samples were obtained before treatment from patients. Ten days after starting anti tuberculosis therapy, second blood samples were obtained. The amounts of serum magnesium were determined in all samples by spectrophotometric method. Statistical analysis showed that serum magnesium concentrations at baseline (0.61± 0.08 mmol/l) and at day 10 (0.62± 0.11 mmol/l) were not different. It is possible that ethambotol does not affect magnesium concentration in tuberculosis patients, however further studies about the other cationic trace elements are recommended.

Simultaneous determination of a new antituberculosis agent KBF-611 and its de-acetylated metabolite in mouse and rabbit plasma by HPLC

Abstract: KBF-611 is a new thiosemicarbazone derivative which has demonstrated significant antituberculosis effect. A sensitive and specific HPLC method was established and validated for the determination of KBF-611 and its deacetylated metabolite (KM) in mouse and rabbit plasma. Chromatographic separation was achieved on a Eurospher-100 C8 column using acetonitrile, methanol, phosphate buffer (pH 7) and TEA (25:5:70:0.1, v/v), as mobile phase at a flow rate of 1 mL/min. KBF-611, KM and internal standard (4-acetamido-3-chlorobenzaldehyde thiosemicarbazone) were detected at the wavelength of 323 nm. The calibration curves were linear within the concentration range from 0.02–5 µg/mL and 0.02–1 µg/mL for KBF-611 and KM respectively. The limit of detection and the limit of quantitation were 6 ng/mL and 20 ng/mL respectively for both KBF-611 and KM. The relative standard deviation for intra- and inter-day precision was less than 7.5%. Average recoveries were 70.8% and 75.0% for KBF-611 and KM respectively. The established HPLC method was validated to be a simple, rapid and reliable procedure and successfully applied to study the preclinical pharmacokinetics of KBF-611 and KM in mice and rabbits.

Synthesis of a quaternary bis derivative of imipramine as a novel compound with potential anti-enuretic effect.

Abstract: Objectives Imipramine has been used for over four decades (early reports in 1960s) for the treatment of nocturnal enuresis, although the reason for its effect is not clear. Imipramine is a tertiary amine, which may act both in the periphery and/or pass through the blood-brain barrier (BBB) in unionized form and exhibit a central effect. Since imipramine has anti-cholinergic properties, some believe it may exert its anti-enuretic effect by affecting peripheral cholinergic receptors, i.e. its anti-enuretic effect may be due to peripheral anti-cholinergic properties, whereas others think it can pass through the BBB and interact with central nervous system (CNS) receptors. If the anti-enuretic effect of imipramine is due to its peripheral anti-cholinergic effects, its entrance into the CNS is unnecessary. Therefore, the synthesis of a form of imipramine that can exhibit peripheral anti-cholinergic effects but does not have CNS adverse effects would have a safer drug profile in this case. On the other hand, if the anti-enuretic effect of imipramine is primarily due to its action on the CNS, a form of imipramine that cannot pass through the BBB has no effect on nocturnal enuresis treatment and thus may help to clarify the mechanism of action of imipramine in nocturnal enuresis treatment. Methods This article describes the synthesis and evaluation of the anti-cholinergic effect of a new bis derivative of imipramine, which contains two imipramine units in its structure. Key findings The compound exhibited anti-cholinergic activity comparable with that of imipramine on isolated guinea pig ileum. Conclusions Being a quaternary ammonium, this compound is not expected to be able to cross the BBB and thus would cause fewer CNS side effects.