Iranian Journal of Pharmaceutical Research
Volume:10 Issue: 3, Summer 2011

Many classes of antibacterial drugs are currently available for physicians to use, however the plan of antibiotic development has slowed during the last decade. The World Health Organization (WHO) has identified antimicrobial resistance as one of the 3 most important problems for human health. Antimicrobial resistance is a growing problem worldwide, especially in hospitals, where resistant organisms are often first detected in ICU (Intensive Care Unit). It is demonstrated that resistant bacteria are more isolated from ICUs compared with other hospital wards and outpatient clinics, and ICU stay may be an independent risk factor for acquiring multidrug-resistant strains infection. Moreover, it must be considered that ICUs patients are often colonized with multidrug- resistant strains, which often spread to other wards.

The dried fruit of Terminalia chebula is widely used for its laxative properties. The objective of the present study was to examine the flowability and compressibility of Terminalia chebula fruit powder, subsequently developing its tablet formulations by utilizing wet granulation and direct compression technology. Initial studies on flowability and compressibility revealed that the fruit powder flows poorly, is poorly compressible and mucilaginous in nature. The consolidation behaviors of the fruit powder and of its tablet formulations were studied using the Kawakita, Heckel and Leuenberger equations. Kawakita analysis revealed reduced cohesiveness hence improved flowability was achieved in formulations prepared by direct compression and the wet granulation technique. The Heckel plot showed that the Terminalia chebula fruit powder when formulated using direct compression showed initial fragmentation followed by plastic deformation and that the granules exhibited plastic deformation without initial fragmentation. The compression susceptibility parameter obtained from the Leuenberger equation for compacts formed by using the direct compression and wet granulation techniques indicated that the maximum crushing strength is reached faster and at lower compression pressures. The Tannin content (with reference to standard tannin) in fruit powder and tablet formulations was determined by UV spectrophotometry at 273 nm. The in-vitro dissolution study in simulated SGF (without enzymes) showed more than a 90% release of tannin from the tablets with in 1 h. The brittle fracture index value revealed that tablets prepared from granules showed less fracture tendency in comparison to those formed by direct compression formulation. From this study, it was concluded that the desired flowability, compressibility and compactibility of Terminalia chebula fruit powder can be obtained by using the direct compression and wet granulation techniques.

The extracts of Piper sarmentosum, a medicinal plant, are being used to prepare phytopharmaceuticals while the information about chemical kinetics of constituents of the extract is unavailable to assign precise shelf life (t90) and find optimum storage conditions of the product for patient safety, and to avoid economic repercussions of launching an unstable product. The extract was exposed to three different conditions of high temperature and relative humidity (RH) for six months. The samples were then analyzed at 0, 1, 2, 4 and 6 months by high performance liquid chromatography (HPLC) using pellitorine, sarmentine and sarmentosine as markers. Different chemical kinetic parameters of the markers were evaluated by Arrhenius equation to predict shelf life (t90) at different storage conditions and at room temperature. The markers in the extract followed the zero order degradation, and the activation energy, pre exponential factor and rate constant of the reaction of the markers were found to be varying in samples stored at different conditions. The contents of the markers were found to be decreasing at high temperature and humidity with the passage of time. The predicted shelf life (t90) of the markers at room temperature was found to be 16 months approximately. Results of this study indicate that extracts of the plant are stable at room temperature for 16 months. Moreover, the chemical kinetic data of the markers and the analytical method used to quantify the markers may be useful for phytopharmaceutical industry to produce efficacious and stable products from extracts of the plant.

The present study is aimed at the overall improvement in the efficacy, reduced toxicity and enhancement of therapeutic index of cisplatin. Nanocapsules of cisplatin containing ethylcellulose have been prepared using solvent evaporation technique under ambient conditions. The prepared nanocapsules were used for controlled drug release of anticancer agents with gold and iron oxide nanoparticles. The drug-entrapped nanocapsules were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier transform infrared (FTIR) studies indicated the absence of chemical interactions between the drug, polymer and metal nanoparticles. The drug loaded nanoparticles are spherical in shape and had average diameter in the range of 100-300 nm. Drug release study showed that the acidic media provided a faster release than the phosphate buffer media. These findings were also compared statistically through calculating mean, standard deviation and coefficient of variation for various polymer nanocapsules. However, the drug release for gold nanoparticles/anticancer drug (Au@cis) incorporated ethylcellulose nanocapsules was controlled and slow compared to iron oxide nanoparticles@cisplatin incorporated ethylcellulose nanocapsules. Hence, gold nanoparticles act as good trapping agents which slow down the rate of drug release from nanocapsules.

The uptake and transport of 9-nitrocamptothecin (9-NC), a potent anticancer agent, across Caco-2 cell monolayers was studied as a free and PLGA nanoparticle loaded drug. Different sizes (110 to 950 nm) of 9-nitrocamptothecin nanoparticles using poly (lactic-glycolic acid) were prepared by via the nanoprecipitation method. The transport of nanoparticles across the Caco-2 cell monolayer as a function of incubation time and concentration was evaluated for each different nanoparticle formulation. The amount of 9-NC transported from the apical to the basolateral side and the uptake of the drug into the cells was determined by HPLC. The uptake of intact nanoparticles into Caco-2 cells was visualized by confocal laser scanning microscopy using 6-coumarin as a fluorescent marker. The study demonstrated that Caco-2 cell uptake and transport of encapsulated 9-nitrocamptothecin is significantly affected by the diameter of the carrier and incubation time. In addition it was shown to be independent of concentration. The results indicated a significant accumulation of the drug in the cell membrane and an enhanced diffusion across the cell membrane. There was also a sustained release of characteristics pertaining to polymeric carriers that provided prolonged drug availability for absorptive cells.

The objective of this work was to develop bioadhesive topical gel of Aceclofenac with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Poloxamer 407 (PL-407 = X1) and hydroxypropylmethyl cellulose K100 M (HPMC = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. Quadratic model was found to be the best for all the responses. Both independent variable (X1 and X2) were found to have synergistic effect on bioadhesion (Y1) but the effect of HPMC was more pronounced than PL-407. Consistency index was enhanced by increasing the level of both independent variables. An antagonistic effect of both independent variables was found on cumulative percentage release of drug in 2 (Y3) and 8 h (Y4). Both independent variables approximately equally contributed the antagonistic effect on Y3 whereas antagonistic effect of HPMC was more pronounced than PL-407. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial experimental design and generated quadratic mathematical equations.

The purpose of this research was to prepare a floating matrix tablet containing domperidone as a model drug. Polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) were evaluated for matrix-forming properties. A simplex lattice design was applied to systemically optimize the drug release profile. The amounts of PEO WSR 303, HPMC K15M and sodium bicarbonate were selected as independent variables and floating lag time, time required to release 50% of drug (t50) and 80% of drug (t80), diffusion coefficient (n) and release rate (k) as dependent variables. The amount of PEO and HPMC both had significant influence on the dependent variables. It was found that the content of PEO had dominating role as drug release controlling factor, but using suitable concentration of sodium bicarbonate, one can tailor the desired drug release from hydrophilic matrixes. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). The tablets of promising formulation were found to be stable for 3 months under accelerated (40°C / 75% RH) stability testing.

The objective of this study was to formulate and evaluate the drug-polymer interaction of mefenamic acid (MA) using two polymers with different characteristics as ethylcellulose (EC) and/or cellulose acetate phthalate (CAP). Microspheres were prepared by the modified emulsion solvent evaporation (MESE). The effect of drug-polymer interaction was studied for each of microspheres. Important parameters in the evaluation of a microencapsulation technique are encapsulation efficiency, yield production, particle size, surface characteristics of microspheres, scanning electronic microscopy (SEM), powder X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). The in-vitro release studies are performed in Tris buffer (pH 9) with Sodium lauryl sulfate (SLS). Microspheres containing CAP and EC showed 68-97% and 63-76% of entrapment efficiency, respectively. The thermogram X-ray and DSC showed stable character of MA in the microspheres and revealed an absence of drug polymer interaction. The prepared microspheres were spherical in shape and had a size range of 235-436 μm for CAP-microspheres and 358-442 μm for EC-microspheres. The results suggest that MA was successfully and efficiently encapsulated; the release rates of matrix microspheres are related to the type of polymer, only when polymers (EC and CAP combine with 1: 1 ratio) were used to get prolonged drug release with reducing the polymers content in the microspheres. Data obtained from in-vitro release for microspheres and commercial capsule were fitted to various kinetic models and the high correlation was obtained in the peppas model.

Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.

Silver nanoparticles have proved to possess significant antibacterial properties. Nanosilver produced by electrochemical reduction stabilized by cellulose derivatives, has been evaluated by European standards (CEN TC 216) in order to find out whether they could be applied in food, industrial, domestic and institutional areas as a suitable disinfectant. Moreover, bactericidal activity of nanosilver has been compared to Deconex 53 Instrument, which is a potent disinfectant. Silver nanoparticles not only passed the standards, but also showed a competitive bactericidal activity against Deconex 53.

DNA intercalators belong to aromatic heterocyclic compounds interacting reversibly with DNA. These compounds have been used extremely as cytotoxic agents against cancer. In this study, the synthesis and biological activity of some novel derivatives of cyclopenta [b] quinoline-1, 8-dione as new intercalating agent were investigated. Twenty novel derivatives of cyclopenta [b] quinoline-1, 8-dione were synthesized by molecular condensation of equivalent amount of 3-imino cyclopentanone, corresponding aldehyde and cyclohexane-1, 3-dione. Then, their cytotoxic activity was evaluated against HeLa, LS180, MCF-7 and Raji cancer cell lines by MTT assay. The results of cytotoxic activity evaluation indicate that the most of synthesized compounds show weak cytotoxic effect on the different cell lines (IC50 of these compounds is higher than 50 or 100 m). According to previous studies, in the case of compounds with the weak biological activity, it is more suitable to use IC15 and IC30 instead of IC50 as the indicator of biological activity. Since most of compounds have weak cytotoxic effect, we also calculated IC15 and IC30 for evaluating the cytotoxic activity of synthesized compounds. The most potent compound, 6 h (9-(3-Bromo-phenyl)-4-pheny l-2, 3, 5, 6, 7, 9-hexahydro-4H-cyclopenta [b] quinoline-1, 8-dione), containing bromophenyl moiety and phenyl substitute on nitrogen of central quinoline ring, show significant cytotoxic activity especially in Raji and HeLa cell lines (IC30: 82 and 24.4 m M respectively) comparing to other compounds. Although the results of cytotoxic activity evaluation demonstrated that the in-vitro anti-cancer effect of synthesized compounds are mainly low, it seems that this structure can be used as a novel cytotoxic scaffold for further modification and design of novel potent compounds.

The 1,4-dihydropyridine (DHP) derivatives are a known class of calcium channel blockers. Some derivatives of DHP showed significant cytotoxicity. It was shown that this effect may not be the result of interaction with Ca2+ channels. In this study, we performed an investigation about the intrinsic cytotoxicity of some derivatives of DHP containing nitroimidazole moiety on their C4 position on four different cancer cell lines (Raji, K562, Fen and HeLa). The result showed that these compounds had moderate-good cytotoxic activity. In addition, QSAR model show the importance of N atom in cytotoxicity; Ca2+ channels.

The antitumor activity of ethanol extract of Prosopis glandulosa Torr. (EPG) was evaluated against Ehrlich ascites carcinoma (EAC) tumor model in Swiss albino mice on dose dependent manner. The activity was assessed using survival time, average increase in body weight, hematological parameters and solid tumor volume. Oral administration of EPG at the dose of 100, 200 and 400 mg/Kg, significantly (p < 0.001) increased the survival time and decreased the average body weight of the tumor bearing mice. After 14 days of inoculation, EPG was able to reverse the changes in the hematological parameters, protein and PCV consequent to tumor inoculation. Oral administration of EPG was effective in reducing solid tumor mass development induced by EAC cells. The results indicate that EPG possess significant antitumor activity on dose dependent manner.

Clinical data showed consumption of buckwheat played a very positive role in the relief of diabetes and its complications. The purpose of this study was to explore the effects and mechanisms of the overall flavonoids from buckwheat flowers and leaves (TFBFL) on renal damage in type 2 diabetes mellitus (T2DM) rats. Seventy male Wistar rats were selected. Ten rats were randomly allocated into a normal group and the other sixty were intragastrically injected with a lipid emulsion and small doses of alloxan to induce the T2DM model. T2DM inducement was judged by the fasting blood glucose (FBG) and oral glucose tolerance test (OGTT). Those whose FBG was ≥ 16.7 mmol/L and less tolerant to glucose were considered as being T2DM rats. These rats were then randomly divided into a groups termed: model (purified water, 5 mL•kg-1•d-1), BNPL (positive control) (Benazepril, 4 mg•kg-1•d-1), L-TFBFL (TFBFL 100 mg•kg-1•d-1), M-TFBFL (TBFL 200 mg•kg-1•d-1) and H-TFBFL (TFBFL 400 mg•kg-1•d-1). Each group then received medication for a period of 4 weeks. The normal rats were treated with purified water in a synchronous manner. Subsequently, FBG, plasma insulin (INS), OGTT, 24 h urinary protein output, blood and urinary creatinine content were assayed. Then the insulin sensitive index (ISI), bilateral kidney index, and creatinine clearance rate (Ccr) were calculated. Renal morphological changes and expression of protein tyrosine phosphatase 1B (PTP1B) in the kidneys were observed. TFBFL lowered FBG, improved insulin resistance, caused Ccr, and renal morphological changes, down-regulated the expression of PTP1B in T2DM rats and showed dose-dependence. TFBFL had a significant protective effect on renal damage in T2DM rats. This effect may be due to lowering blood glucose and diminishing renal damage by inhibiting PTP1B expression.

Pomegranate (Punica granatum L.), Lythraceae, is mainly grown in Mediterranean region. It is one of the major cultivated productions of Iran, which have been used in folk medicine for many centuries. It has been proved that pomegranate has a high antioxidant activity and is effective in the prevention of atherosclerosis. This study compares the antioxidant activity, total phenolic and flavonoid contents of eight different pomegranate cultivars grown in Iran. Aqueous solutions of known Fe+2 concentration, vitamin E, vitamin C, gallic acid and catechin were used for calibration. The results showed that Sour summer pulp cultivar had the most antioxidant effect with significant difference with the other cultivar (p < 0.05) which can be introduced as a potent source of natural antioxidants, and the peel of three cultivars (Sweet saveh malas, Sour summer and Black peel) as a suitable source for extraction and purification of phenolic and flavonoid compound. The antioxidant capacity of pomegranate peel extract is 10 times higher than the pulp extract.

In the present study, anti-anaphylactic, anti-inflammatory and membrane stabilizing properties of a lupine alkaloid plumerianine (compound 1), isolated from the root bark of Plumeria acutifolia Poir were investigated in animal models. The anti-anaphylactic activity of compound 1 (10, 25 and 50 mg/Kg) was studied by using models such as passive cutaneous anaphylaxis, passive paw anaphylaxis and also investigated for its anti-inflammatory activity against the carrageenin induced paw edema and cotton pellet granuloma in albino rats. A dose-dependent beneficial effect was observed on the leakage of Evans Blue dye in skin challenged with antigen and on paw anaphylaxis induced by antiserum. The compound 1 also exhibited a significant (p < 0.01) inhibition of rat paw edema and granuloma tissue formation, including significant protection of RBC against the hemolytic effect of hypotonic solution, an indication of membrane-stabilizing activity. Anti-anaphylactic activity of compound 1 may be possibly due to the inhibition of releasing various inflammatory mediators. Anti-inflammatory activity of compound 1 may be related to the inhibition of the early phase and late phase of inflammatory events.

Salvia verticillata is one of the salvia species which possesses remarkable antioxidant activity. In the present study, we investigated the possible effects of hydro-alcoholic extract from Salvia verticillata plant (SVE) in various models of anxiety, depression and seizure in mice. Mice were randomly divided into control (saline), SVE-treated and standard treatment groups. The SVE-treated groups received oral administration of various doses of SVE. As a standard treatment, diazepam and imipramine were used orally for anxiety/seizure and depression tests, respectively. The results of the study revealed that the plant extract produced significant anticonvulsant activity in maximal electroshock and pentylenetetrazol induced seizure models. Moreover, in forced swim test and tail suspension test of depression, SVE produced significant antidepressant effect in mice compared to control group. However, SVE did not show any effects on anxiety-like behavior of mice in elevated plus maze and light-dark tests. These results suggest potential therapeutic effects of the plant extract in seizure and depression.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common pharmacological group that has three primary therapeutic effects including anti-inflammatory, anti-pyrexia, and analgesia. In this study, seven of NSAIDs were tested against two species of skin pathogenic fungi (dermatophytes). Percentage inhibition was determined for effective agents. Diclofenac, Aspirin and Naproxen showed much more ability to inhibit dermatophytes growth. Epidermophyton floccosum revealed susceptibility to more tested agents than those of Trichophyton mentagrophytes. In conclusion, many of NSAIDs may have the ability to inhibit pathogenic fungi. Others may also have potential activity toward fungal growth.

Three different Aspergillus Niger MTCC strains (872, 1785 and 2208) were used for the production of chitosan. Multivariate growth mediums in varying incubation periods were analyzed for the production. The produced chitosan was characterized by its physical appearance, moisture content (by means of gravimetric method), percentage of ash and solubility (through the Association of Official Agricultural Chemists (AOAC) methods) and also the degree of deacetylation (with Infra red spectroscopy). The infrared (IR) spectrum of produced fungal chitosan shows strong similarity with the IR spectrum of commercial chitosan. Our experimental results concluded that the maximum yield of chitosan (26.1%) was obtained from Aspergillus niger MTCC 2208 grown in supplemented Potato Dextrose Broth (PDB) medium, incubated at 30°C for 120 h in 180 rpm. The antimicrobial activity of produced chitosan was tested against five bacteria by Disc diffusion technique, which confirmed that chitosan have minimal antimicrobial activity.

Hepcidin is an innate immune element which decreases the iron absorption from diet and iron releasing from macrophage cell. In contrast to the chemical iron chelators, there has been limited effort applied to the specific use of hepcidin as a new drug for decreasing the iron overload. Hepcidin is produced in different biological systems. For instance, E-coli is used for human hepcidin expression, however, post-translational modification is impaired. We have used a simple baculovirus expression system (BES) to improve the hepcidin folding and activity. Hepcidin Messenger Ribonucleic acid (mRNA) was isolated from mouse liver cells and its complementary Deoxyribonucleic acid (cDNA) was produced and amplified. PFastBac HTB vector was used for recombinant bacmid production. Recombinant baculovirus was produced using SF-9 cell line. The mouse hepcidin-1 protein was expressed in a large quantity and functional tests were performed for this recombinant peptide. The yield of hepcidin in BES was 20 μg/mL and anti-histidine (anti-His) tag antibody was used for the confirmation of hepcidin on western blot nitrocellulose paper. Functional tests showed that mouse hepcidin accumulates iron in the macrophage cell line J774A.1 up to 63%. In addition, our data showed that the mouse hepcidin-1 has less toxicity compared to the synthetic human hepcidin-25 (p = 0.000).

Diabetes mellitus is accompanied with disturbances in learning, memory, and cognitive skills in the humans and experimental animals. Due to the anti-diabetic and antioxidant activity of pelargonidin (PG), this research study was conducted to evaluate the efficacy of chronic oral PG on alleviating learning and memory disturbance in streptozotocin-diabetic rats. Male Wistar rats were divided into control, diabetic, PG-treated control and PG (single- and/or multiple-dose)-treated diabetic groups. PG was administered p.o. once at a dose of 10 mg/kg and/or multiple doses on alternate days for 8 weeks. For induction of diabetes, streptozotocin (STZ) was injected IP in a single dose of 60 mg/kg. For the evaluation of learning and memory, initial latency (IL) and step-through latency (STL) were determined at the end of study using a passive avoidance test. Meanwhile, spatial memory was assessed in a Y-maze task. It was found that the alternation score of the diabetic rats was lower than the control (p < 0.05) and that single dose PG-treated diabetic rats (p < 0.05) showed a higher alternation score in comparison with the diabetic group. Regarding initial latency, there was no significant difference among the groups. In addition, diabetic and single-dose PG-treated diabetic rats developed a significant impairment in retention and recall in the passive avoidance test (p < 0.01), as was evident by a lower STL. Furthermore, the retention and recall of multiple-dose PG-treated diabetic rats was significantly higher in comparison with diabetic rats (p < 0.05). Therefore, it can be concluded that single-dose oral PG may attenuate spatial memory in the Y maze paradigm and multiple-dose chronic PG could improve retention and recall capability in the passive avoidance test in STZ-diabetic rats.

This research was designed to study sexual differences in place conditioning induced by morphine in offspring born of female Wistar rats mated with drug-naïve males. Mothers were exposed to morphine during the 14th-16th days of gestational. Control dams were simply saline-injected. Female and male virgin offspring born of morphine-treated or saline-treated mothers were separately housed until become fully matured. A 3-day schedule of an unbiased conditioning procedure was used to the induce conditioning to morphine (2.5-7.5 mg/Kg, SC) in the offspring. According to the results, female offspring born of saline-administered mothers were morphine place-conditioned at lower doses of opioid (2.5 mg/Kg) in comparison to the males. An increase in locomotor activity in the females at 7.5 mg/Kg of opioid was also revealed. In contrast, administration of morphine (2.5-7.5 mg/Kg, SC), induced a significant aversion in either sexes of offspring born of morphine-exposed mothers. Moreover, female offspring of this category acquired more pronounced aversion at higher doses of morphine than males. In addition, a significant morphine-dose effect (7.5 mg/Kg, SC) on locomotor activity of these females’ offspring was observed. This study may highlight sex differences in conditioning effects induced by morphine between offspring derived of morphine-treated mothers and those of saline-treated.

Oxidative stress is one of the important causes of the type 1 diabetes induced changes in the sperm quality. Bioflavonoids, Rutin 10 mg/Kg and Naringin 10 mg/Kg were evaluated for their protective effects on sperm parameters, oxidative stress, and histopathology of type 1 diabetic rats. Results demonstrated the reduction in sperm count, sperm motility and vitality in diabetic rats. Mass drug administration (MDA) levels were increased and superoxide dismutase (SOD) catalase levels were decreased. Histopathological changes were evident and in accordance with the above results. In the treatment groups, both Rutin and Naringin in combination with insulin treatment in diabetic rats produced protection from diabetes and improved all the sperm parameters, decreased the MDA levels and increased the SOD and catalase levels. Protection was evident in histological examination. Our data suggests that the possible protection of testicular tissue and reproduction from oxidative stress have been induced by type 1 diabetes mellitus.

This study examines the controlled release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs derived from Caesalpinia pulcherrima seed Gum isolated from Caesalpinia pulcherrima kernel powder. It further investigates the effect of incorporating diluents such as microcrystalline cellulose and lactose on caffeine release. In addition the effect the gum’s (polysaccharide) partial cross-linking had on release of acetaminophen was examined. Applying the exponential equation, the soluble drugs mechanism of release was found to be anomalous. The insoluble drugs showed a near case II or zero order release mechanism. The rate of release in descending order was caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in the release kinetics of the drug was observed on blending with diluents. However, the rate of release varied with the type and amount of blend within the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of drug release decreased upon partial cross-linking and the mechanism of release was found to be of super case II.

Downward phase of dose-response morphine converted U shape curve was chosen as a base for investigating the effects of different doses of naloxone (0.05-0.4 mg/Kg) on morphine reward/aversion properties using place preference method. First, male Wistar rats (200-220 g) were received morphine (1-7.5 mg/Kg) for place conditioning and marginal dose of morphine (5 mg/Kg) calculated by GraphPad software. In the next part, the animals received different naloxone challenge doses (0.05-0.4 mg/Kg; IP) on the test day. Animals’ behavior was monitored using a video camera during the test session. Time spent in each compartment was calculated as the main sign of drug seeking behavior. In addition, numbers of rearing and sniffing as well as locomotion activity for each animal were counted as important dopamine-dependent behavioral signs. More over, the total compartment crossing by each animal as the sign of decision making was also counted. Our results indicated that naloxone showed biphasic effects on the appearance of morphine-induced place preference. The antagonist potentiates the expression of morphine-induced place preference on the dose of 0.05 and 0.4 mg/Kg while inhibits the morphine effect on the dose of 0.1 mg/Kg. On the other hand, the total animal sniffing, rearing, locomotion, and compartment entering were not significantly changed among the groups. It could be concluded that the inhibition of opioid receptors may enhance or inhibit the expression of morphine reward according to the naloxone dose, which in turn indicate the influence of several opioid receptor in this regard. In addition, opioid receptor blocking did not enhance the signs of drug seeking behavior linked to the activity of mesolimbic dopamine system.

The present study was designed to explore the anti-inflammatory effect of fluvoxamine, as a selective serotonin reuptake inhibitor (SSRI) anti-depressant, on carrageenan-induced paw edema in more details. At first, fluvoxamine was administered intra-peritoneally (2.5, 12.5, 25 and 50 mg Kg-1) 30 min before the subplantar injection of carrageenan. Fluvoxamine was also injected intra-peritoneally at a dose of 50 mg Kg-1 30 or 90 min after carrageenan injection. Then, fluvoxamine was given intra-cerebroventricularly (25, 50 and 100 μg/rat) and intra-thecally (25, 50 and 100 μg/rat) 30 min before the carrageenan challenge. Finally, the effect of mifepristone (5 mg Kg-1), an antagonist of the glucocorticoid receptor, on the anti-edema effect of fluvoxamine (50 mg Kg-1) was investigated. Results showed that intra-peritoneal (IP) administration of fluvoxamine before or after carrageenan injection considerably inhibited paw edema response at 4 h post-carrageenan (p < 0.001), but intra-cerebroventricular (i.c.v.) and intra-thecal (i.t.) injection of fluvoxamine did not alter the degree of paw swelling. The inhibitory effect of fluvoxamine was reduced by the pretreatment of mifepristone (p < 0.01). Our results suggest that IP administration of fluvoxamine produces a noticeable anti-inflammatory effect in the carrageenan-induced paw edema in rats and at least, a part of this effect is mediated through glucocorticoid receptor. Moreover, it seems unlikely that central sites have an important role in this inhibitory effect of fluvoxamine.

The effect of hypericin on the expression of morphine-induced conditioned place preference (CPP) was investigated and compared with the effect of the synthetic antidepressants. The CPP paradigms took place over six days using an unbiased procedure. The results demonstrate that intra-peritoneal (IP) injection of morphine sulfate (2.5, 5 and 10 mg/Kg) significantly induce the CPP in rat. Intra-peritoneal and intracerebroventricular (ICV) injection of hypericin and/or synthetic antidepressants augmented morphine-induced CPP. It has been suggested that the adrenergic, serotonergic and dopaminergic neurotransmissions play an important role in mediating the antidepressant effect of hypericin and this effect may be due to its inhibitory effect on the reuptake of neurotransmitters. Morphine produces a reinforcement (reward) effect by activating. The μ-receptors that facilitate dopaminergic transmission. Serotonin is also a potent stimulator of dopamine release in such a way that an increase in brain serotonin could possibly stimulate the dopaminergic system. In conclusion, it may suggest that the augmentation of morphine-induced CPP by hypericin and synthetic antidepressants may be related to the increasing dopamine and serotonin concentrations in synaptic clefts.

Ghrelin increases food intakes and body weight. Bombesin decreases food intakes and inhibits the stimulatory effect of Ghrelin on food intakes. Thyroid hormones have a crucial role in the regulation of body weight and yet the effect of bombesin on thyroid axis activity is not fully clear. Therefore, the goal of this study was to determine the effect of different doses of Ghrelin or bombesin on mean plasma thyroid-stimulating hormone (TSH), Triiodothyronine (T3) and Thyroxin (T4) concentration and also, the effect of interaction between Ghrelin and bombesin on thyroid axis activity. Forty-nine rats in seven groups received saline or different doses of Ghrelin (4, 10 or 15 nmol) and bombesin (2.5, 5 or 10 nmol) and forty-two rats in six groups received simultaneous injection of Ghrelin (10 or 15 nmol) and different doses of bombesin (2.5, 5 or 10 nmol) via lateral cerebral ventricle. Blood samples were collected via decapitation 20 min after the injection and plasma was assayed for plasma TSH, T3 and T4 concentration by Radioimmunoassay (RIA). Ghrelin significantly decreased the concentration of mean plasma thyroid hormones compared to saline. Bombesin did not significantly increase thyroid hormones concentration compared to saline but bombesin blocked the inhibitory effect of Ghrelin on thyroid axis activity. Bombesin may be the antagonist of Ghrelin action.

The aim of this study was to determine the association of n-acetyltransferase-2 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Iranian pulmonary tuberculosis patients. Acetylating phenotypes was studied in 50 Iranian pulmonary tuberculosis patients using metabolic ratio of plasma acetyl-Isoniazid to Isoniazid. The association between hepatotoxicity and the n-acetyltransferase-2 phenotype was evaluated by using the chi-square (x2) test. The metabolic ratio had a bimodal distribution with an antimode value of 1.0. Based on the metabolic ratio of the mentioned patients, 20 (40%) were slow acetylators and 30 (60%) were fast ones. Hepatotoxicity was manifested in 9 of 20 slow acetylators (45%) and only in 5 of 30 rapid acetylators (16.7%). There was a significant difference in the frequency of hepatotoxicity between the slow and fast acetylators (x2 = 4.778, and p = 0.03). Sex and age were not found to be risk factors for hepatotoxicity. Our findings show that slow acetylation profile is significantly associated with a higher risk of developing hepatotoxicity due to the anti-TB drugs in Iranian pulmonary tuberculosis patients.

Topical solutions containing aluminum chloride are known to be the first line of therapy for hyperhidrosis. Palmar hyperhidrosis however, is less responsive to aluminum chloride therapy and successful treatment may require 6-8 h application of high concentrations up to 30% that commonly leads to skin irritation. The purpose of this study is to investigate the effect of 30 min iontophoretic application of low concentration (1%) aluminum chloride solution in patients with palmar hyperhidrosis. Iontophoresis of 1% aluminum chloride was applied to one hand of twelve patients with palmar hyperhidrosis for four successive days. The subjects’ other hand ‎was treated topically with the same solution at the same time. Gravimetric and iodine-‎starch tests were performed at baseline, 3 days, 1, 2, 3 and 4 ‎weeks after the last treatment. ‎Experimental hand showed significant hypohidrosis from the 3rd day until the 4th week post-treatment (p < 0.04) which was lower than the control hand throughout the follow-up period. Iontophoresis of low concentration aluminum chloride hexahydrate can induce hypohidrosis that is more persistent than its topical ‎application and with no side effects.

Drug and poison information centers have a critical role in fulfillment of rational drug use programs. The Loghman-Hakim Drug and Poison Information Center (LHDPIC) has been established in 2006. The main mission of this center is to provide accurate, unbiased and upto- date information on medications and poisons for the health care team and the public. This center has received more than 9000 telephone calls since its establishment. The aim of this study was to evaluate the recorded queries in the LHDPIC in the past 3 years. A descriptive analysis was conducted on all recorded inquiries to the center from March 2006 to March 2008. Data such as patient age and sex, identity of the callers, question categories and information resources were obtained from the recorded calls and were analyzed. During the period of evaluation, a total of 9694 telephone calls were recorded. The patients’ age ranged between 18-40 years old (49.42%) containing 61% female and 39% male. Most of the recorded calls were from patients’ relatives (49%) and then the patients (45.2%) themselves. The most frequent questions were about drug indications (24%), adverse drug reactions (20.14%) and drug evaluation (17.64%). Antidepressants (12.42%), antimicrobials (12%) and analgesics (11.17%) were the most frequent drug classes that were inquired. The LHDPIC has an important role for providing of drug information for the lay public, but more efforts are still needed to encourage health care professionals to utilize services provided by this center.