Iranian Journal of Pharmaceutical Research
Volume:4 Issue: 4, Autumn 2005

Ethanolic crude extract of I. imbricata Lindl. (Iridaceae) was subjected to column chromatography on silica gel with varying portions of MeOH: CHCl3. Nigicin (irisolone) was isolated and its identification carried out by IR, UV, MS, 1-D and 2-D NMR spectroscopy

Original ArticleMortazavi SA and Tabandeh H The Influence of Various Silicones on the Rheological Parameters of AZG Containing Silicone-Based GelsIranian J Pharm Res (2005) 4: 205-211Moghimi H and Momajjad AAn In-Vitro Iontophoretic Permeation Study of Nicotine through Rat SkinIranian J Pharm Res (2005) 4: 213-219Yazdanpanah H, Eskandari Gheidari P, Zarghi A and Mirkarimi SKSurvey of fumonisin B1 contamination of cornin Northern Iran during 2000Iranian J Pharm Res (2005) 4: 221-225Abdi K, Mandgary K, Amini M, Bagheri M and Gerami-Panah MDetermination of Residual Methylmethacrylate Monomerin Denture Base Resins by Gas ChromatographyIranian J Pharm Res (2005) 4: 227-232Ghaffari MA, Kadkhodaei-Elyaderani M, Saffari MR and Pedram MMonitoring of Serum Nitric oxide in Patients with Acute LeukemiaIranian J Pharm Res (2005) 4: 233-237Rzaei-Tavirani M, Moghaddamnia SH, Ranjbar B, Namaki S and Zolfaghari PThe Effects of Acetaminophen on Human Serum Albumin (HSA)Iranian J Pharm Res (2005) 4: 239-244Rasekh HR, Yazdanpanah H, Hosseinzadeh L, Bazmohammadi N and Kamalinejad MAcute and Subchronic Toxicity of Teucrium polium Total Extract in RatsIranian J Pharm Res (2005) 4: 245-249Ayatollahi SAM, Moein MR, Kobarfard F, Nasim S and Choudhary MI1-D and 2D-NMR assignments of nigricin from Iris imbricataIranian J Pharm Res (2005) 4: 123-136Abstract HTML PDF

While drug toxicity (especially hepatotoxicity) is the most frequent reason cited for withdrawal of an approved drug, no simple solution exists to adequately predict such adverse events. Simple cytotoxicity assays in HepG2 cells are relatively insensitive to human hepatotoxic drugs in a retrospective analysis of marketed pharmaceuticals. In comparison, a panel of pre-lethal mechanistic cellular assays hold the promise to deliver a more sensitive approach to detect endpoint-specific drug toxicities. The panel of assays covered by this review includes steatosis, cholestasis, phospholipidosis, reactive intermediates, mitochondria membrane function, oxidative stress, and drug interactions. In addition, the use of metabolically competent cells or the introduction of major human hepatocytes in these in-vitro studies allow a more complete picture of potential drug side effect. Since inter-individual therapeutic index (TI) may differ from patient to patient, the rational use of one or more of these cellular assay and targeted in-vivo exposure data may allow pharmaceutical scientists to select drug candidates with a higher TI potential in the drug discovery phase.

Aluminium zirconium tetrachlorohydrex glycine (AZG) is a popular antiperspirant/deodorant agent, formulated in various forms including the clear gels. Silicones are used for the preparation of these gels, giving them desirable characteristics. The aim of this study was to investigate the influence of various silicones, when used in combination, on the rheological properties of the resulting AZG gels prepared. Based on preliminary studies, various AZG containing silicone-based gel formulations were prepared. Silicones used (as ternary mixtures) included ABIL® EM 97, ABIL® 8839 and ABIL® 8852. Formulations prepared were then examined rheologically and their plastic viscosity and yield values determined. Results showed that the amount of ABIL® EM 97 (used as an emulsifier) present within the gel formulation is critical. An increase in the amount of this silicone, corresponding to a small decrease in the amount of the hydrophobic structure building (gelling agent) ABIL® B8839, increased the plastic viscosity and yield values of the gel. On the other hand, an excess amount of ABIL® B8852, as a hydrophilic co-surfactant, reduced the viscosity and yield values of the resulting gel. Eventually, among the formulations prepared, formulation F5 with suitable aesthetic and skin feel properties, spreadability and rheological behaviors, was selected for further studies. By constructing the up-curve and down-curve of this formulation, presence of a plastic thixotropic behavior was confirmed. Inclusion of various amounts of the hydrophobic silicone-based agent, dimethicone, within formulation F5 showed that by increasing the amount of dimethicone present, the plastic viscosity and yield values of the gel would be reduced. This reduction was significant at dimethicone concentrations above 0.5%. Furthermore, by increasing the amount of dimethicone present, the calculated "percentage of reduction in plastic viscosity" also increased. This means that the extent of thixotropicity of the gel formulation increases by the addition of dimethicone. This finding was also backed up by the resulting rheograms constructed. Overall, addition of 0.75% dimethicone produced the most acceptable product in terms of an appropriate viscosity, yield value and extent of thixotropicity. In conclusion, this study shows that in-depth rheological assessment of AZG gels prepared from silicones could be used as an important tool during their formulation and characterization in order to obtain an effective formulation with desirable properties.

Nicotine transdermal systems are being used as an aid to smoking cessation programs. As the kinetics of nicotine delivery is important in success of a smoking cessation program, rapid and high input of nicotine is required, which is not possible by passive methods and requires enhancement strategies such as iontophoresis. Iontophoretic permeation, of nicotine looks promising, based on published data on human skin. However, to optimize this method, permeation pathways should be known and further parameters have to studied, which are the subject of the present investigation. In this study iontophoretic permeation of nicotine through rat skin was performed and the effects of different variables on this phenomenon were studied. Anodic iontophoresis of nicotine from a solution at pH 2.8, using a 0.5 mA/cm2 current density resulted in a considerable enhancement (about 3-fold) of nicotine absorption through rat skin. Nicotine concentration and current density showed a directly increasing effect on permeation of the drug, but the effect of concentration was not linear. Pulsatile current delivery was more effective in permeation of nicotine than the continuous method. Anodic iontophoresis was around 2-fold more effective than the cathodic method in increasing the flux. Post iontophoretic permeation studies showed good reversibility of the membrane barrier properties. Results were in good agreement with the reported human data and might be considered as an evidence of the ability of rat skin to model human skin and also the importance of intercellular pathway of the stratum corneum in iontophoretic delivery of nicotine and possibly other drugs. Donor''s pH showed no effect on permeation of nicotine under the studied conditions, pH values of <3. Results also showed that the electr-osmotic flow could occur at pH values lower than 4. Finally, this study show that by controlling the effective parameters of iontophoretic delivery, a more effective nicotine transdermal delivery method would achievable.

Fumonisin B1 (FB1) is the most abundant of the fumonisin mycotoxins, mainly produced in corn by fungi of the genus Fusarium. FB1 has been shown to be hepatocarcinogenic and nephrocarcinogenic in animals. Contamination of corn with FB1 was assayed in samples collected from Mazandaran Province, situated on the Caspian littoral of Iran, in September 2000. In this survey, 38 corn samples were analyzed using HPLC, and all except one showed high levels of FB1 contamination ranged between 1.19 and 12.95 mg/kg. These results confirm the relatively high levels of FB1 contamination in corn of Mazandaran Province.

Acrylic base resins are widely used in orthopedics and dental surgery. It is generally accepted that due to the incomplete conversion of methyl methacrylate (MMA) monomer to the polymer form during polymerization of the resin, some MMA monomers remain in the hardened material. MMA monomer has been reported to cause abnormalities or lesions in several organs of animals. Study of the literatures showed that there are no perfect and valid methods for analysis of MMA. The aim of this study was to develop a simple and valid method for determination of MMA residual monomer in the denture base resins.We have developed and validated an analytical procedure employing gas chromatography with flame ionization detector (GC-FID), with temperature programming, and a close analogue internal standard for fast and repeatable analysis of MMA residual monomer contents in denture base polymers. For quantification of monomer, two calibration curves were used by two different methods of solution preparation and they were compared to each other. The assay was linear over the range of 0.03-0.6 mg/ml MMA with correlation coefficients (r2) of greater than 0.99. Accuracy, intra-day (Error<9.1%) and inter-day (Error<6.6%), precision (RSD<5.5% and RSD<6.5%, respectively) were in acceptable values over the examined concentration range. Limit of detection (LOD) and limit of Quantification (LOQ) for MMA were 0.01 and 0.02 mg/ml, respectively. In conclusion, the proposed method was a simple and fast assay for MMA residual monomer in denture base resins.

Nitric oxide (NO) is a molecule required for many physiological functions, produced from L-arginine by NO synthases (NOS). It is a free radical, producing many reactive intermediates that account for its bioactivity. Sustained induction of the inducible form of NOS (iNOS) in chronic inflammation may be mutagenic, through NO-mediated DNA damage or hindrance to DNA repair, and thus potentially carcinogenic. Due to the short half-life of NO, usually its end products (nitrate or nitrite) are measured as an index of NO production. There is evidence that expression of iNOS in tumor cells, including acute myeloid leukemia and chronic lymphocytic leukemia increased. In this study, the levels of nitrate and nitrite (nitric oxide products) in the serum of patients with acute leukemia were determined.The serum levels of these compounds were measured in 40 acute leukemia patients. The results of serum nitrite and nitrate of patients were compared with corresponding values obtained in 40 healthy volunteers. These results indicate that patients with acute leukemia had a significant increase in the serum level of nitrite and nitrate.

Thermal conformational changes in human serum albumin (HSA) in present with a 10 mM phosphate buffer, at pH=7 have been investigated via circular dichroism (CD) and UV spectroscopic methods. The results indicate that temperature in a range of 25oC to 55oC could induce a reversible conformational change in the structure of HSA. The HSA phase transition corresponds to the physiological and pathological conditions of the body, especially fever. The conformational change observed in HSA is accompanied by a mild conversion of its secondary structures. Acetaminophen is a papular pain killer, and HSA is used as a drug carrier. Hence, acetaminophen could it interact with HSA. The study of HSA – acetaminophen interaction reveals the effects of acetaminophen on HSA structure, preventing it’s phase transition. HSA – acetaminophen interaction leads to the stabilization of HAS. This interaction is accompanied with 8 kJ/mol of free energy change. The structural changes within HSA due to it’s interaction with acetaminophen could be considered as a drug side effect and it may affect the protein functions.

Teucrium Polium L. (TP) is widely used in traditional medicine of many countries including Iran. There are various reports about pharmacological properties of TP such as calcium antagonist, anti- ulcer, anti – diabetic. There are a few reports about possible toxicological effects of this plant. In the present study we designed to evaluate the subchronic toxicity of Teucrium Polium total extract in rats.Sprague Dawley rats (40 males, 40 females) were divided into four dose groups(10 animals/dose/sex) and were gavaged daily with either 100, 300 or 600 mg/kg of the total extract for 44 days. Control group was received normal saline. Body weight and food consumption was monitored daily. After 45 days animal was sacrificed and hematological and biochemical parameters, as well as weight of left kidney and liver were measured.There was no significant difference in hematological parameters in both sexes as compared to their respective Controls. In biochemical parameters, a significant increase (p<0.05) was seen in both ALT and AST enzyme activities in female rats receiving 300 mg/kg TP. There was also a significant increase in liver weight of male rats receiving 600 mg/kg. No other significant changes in any other parameter were observed.Present data suggests that female rats are more sensitive to higher doses of TP and that liver could serve as a target organ toxicity of this extract.