PHARMACEUTICAL SCIENCES
Year:2007 | Volume:- | Issue:1|Papers Count:7

Objectives: The goal of this study was to evaluate the effects of ACTH and Quercetin on preventing the development of morphine tolerance and dependence in mice.Methods: In this study different groups of mice (20-30 g) received morphine (40 mg/kg, ip), morphine (40 mg/kg, ip) + ACTH (1,2.5,5 IU/mice, ip), morphine (40 mg/kg, ip) + Quercetin (5,10,25 mg/kg, ip), morphine (40 mg/kg, ip) + Quercetin (5mg/kg, ip)+ ACTH (1 IU/mice, ip)] once a day for four days. Tolerance was assessed by administration of morphine (9 mg/kg, ip) and using hot plate test on fifth day. Withdrawal symptoms were assessed by administration of naloxone (4 mg/kg, ip) two hours after co-administration of morphine with either Quercetin or ACTH. Results: It was found that pretreatment with Quercetin or ACTH decreased the degree of tolerance and dependence significantly. Additionally, coadministration of Quercetin and ACTH before morphine administration decreased significantly the tolerance and dependency. From these results it may be concluded that administration of Quercetin or ACTH injection alone or in together could affect the decrease withdrawal signs and tolerance of morphine. These effects may be related to as nitric oxide inhibitor (NOI) behavior of Quercetin and the ability of Morphine and their receptors in the control of the secretion of CRH. Conclusion: ACTH, quercetin and co-administration of both drugs significantly inhibited the development of morphine induced tolerance and dependence in mice.

Objectives: Various systems such as microparticulate systems are utilized for intracellular chemotherapy. One type of these systems is niosomes which are categorized as vesicular systems and essentially composed of non-ionic surfactants and cholesterol. Methods: In this study non-ionic surfactant vesicles (niosomes) from three polyoxyethylene alkyl ethers, i.e. C16EO2 (Brij 52), C18EO2 (Brij 72), C9=9EO2 (Brij 92) and cholesterol encapsulating chloramphenicol sodium succinate (CMP) were prepared by film hydration method. In vitro characterization of niosomes including microscopical observation, size distribution measurement by laser light scattering method, release of CMP in phosphate buffered saline (PBS), pH 7.4 and Minimum Inhibitory Concentration (MIC) determination of free and entrapped antibiotic against E.coli were evaluated. Chloramphenicol concentration was determined by UV spectrophotometry at 276 nm. Results: Log-normal size distribution was observed for all prepared niosome formulations. In the presence of 40 molar percent of cholesterol the release of CMP was best fitted by Baker & Lonsdale model indicating a diffusion based release of antibiotic. In formulation containing 30 molar percent of cholesterol the erosion and dissolution based model (Hixson-Crowell) was best applicable. MIC of encapsulated CMP was less in vesicular systems in comparison with free drug. Morphological study of vesicles revealed different shape and size niosomes which were more as MLVs (Multi Lamellar Vesicles). Brij 92 containing niosomes had less stability, possibly due to liquid nature of this surfactant.Conclusion: Niosomes can be used for controlled release of chloramphenicol. However, although MIC of entrapped antibiotic is less than free one, more studies on in vivo and cell cultures such as mouse macrophages (J774) will be required in future studies.

Objectives: In this study, effects of ischemic postconditioning (IPC) and pharmacologic postconditioning (PPC) by using L-Carnitine (L- Car) on infarct size in the ischemic-reperfused isolated rat heart were investigated and compared. Methods: Male rats were divided in five groups (control, IPC, and three PPC groups treated by L- Car) and were anesthetized by sodium pentobarbital (50 mg/kg-ip). Heart was removed and quickly mounted on a Langendorff apparatus and perfused by a modified Krebs- Henseleit (K/H) solution that was previously equilibrated with 95% O2–5% CO2. The hearts were subjected to 30 min regional ischemia followed by 120 min reperfusion. In the control and IPC groups, the hearts were perfused by normal K/H solution at stabilization, 30 min regional ischemia and 120 min reperfusion, while PPC groups were perfused by 0.5, 2.5 and 5mM of L-Car enriched K/H solution 10 min before and after reperfusion. At the end of reperfusion, infarct size was determined by triphenyltetrazolium chloride method and computerized planimetry. Results: Infarct size was decreased significantly in both IPC and PPC groups versus control. In control group, infarct size was 46.3±2.9 %, however, IPC reduced it to 22.6±1.5 % (p<0.001). Application of 0.5, 2, 5 and 5mM of Car-enriched K/H solution 10 min before and after reperfusion in the PPC groups, reduced the infarct size from control group value to 41.8±4.0 (not significant), 28.1±2.0 (p<0.001) and 25.4±3.9 % (p<0.001), respectively. Except the effects of 0.5 mM L- Car, there was no significant difference between IPC and PPC groups on infarct size reduction. Conclusion: Considering the results, it may be concluded that IPC and PPC (by L- Car) have protective effects against cardiac I/R injuries by reduction of infarct size.

Objective: Salvia and Phlomis species are traditionally used in different infectious conditions. In the present study the antibacterial activities of Salvia sahendica and Phlomis caucasica (Iran endemic taxa) were evaluated against a range of gram positive and negative bacterial strains.Methods: n-Hexane, dichloromethane and methanol extracts of aerial parts of Salvia sahendica and Phlomis caucasica were prepared and their antibacterial activity against gram negative bacterial strains including Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphi and Serratia marcescens as well as gram positive bacterial strains namely Staphylococcus aureus, Micrococcus luteus, Staphylococcus epidermidis, Streptococcus pneumonia and Bacillus cereus were investigated using paper-disk agar diffusion method. SPE method was used for fractionation of methanol extract and activity of the fraction was monitored. Results: n-Hexane and dichloromethane extracts of both plants had no antibacterial effect against none of the examined strains but methanol extracts had a moderate activity on some bacteria especially within the gram positive group. Fractions of methanol extracts showed a remarkable antibacterial activity. Among the tested bacteria, Staphylococcus epidermidis was the most sensitive strain to fraction 40% of Salvia methanolic extract. The sensitivity of the tested bacteria against Phlomis caucasica were lower in comparison with Salvia sahendica, and the most significant effect related to 60% fraction when examined against Bacillus cereus. Conclusion: The results indicate that polar fractions of methanol extract of both plants have significant antibacterial activity on the examined gram positive bacterial strains and the effect of Salvia sahendica is more potent.

Objectives: Sexual hormones affect most of the cerebral functions as well as learning and memory. More investigations are required to clarify the effects of local administration of estradiol in the central nervous system. In this research we aimed at the effects of different doses of estradiol on memory consolidation in female gonadectomized rats. Methods: Female Wistar rats (weighing 200-250 g, aged 3-4 months) were divided into 6 groups randomly (n=9). Five groups of animals were ovariectomized and implanted by cannulae in the CA1 region of hippocampus. Except sham group the other groups treated respectively with saline, sesame oil 0.5 mL and estradiol at the doses of 0.5, 1 and 2 mg / 0.5 mL sesame oil bilaterally in the CA1 region immediately after the passive avoidance training session. They were tested 10 min and 24 h after training.Results: Our results demonstrated that 0.5 mg estradiol had no significant effect on retention latency compared to sham group,1 μg estradiol treated group showed a significant increase (p<0.001) in retention latency compared to sham group while it decreased in the group treated with 2 μg dose of estradiol (p<0.05). Conclusion: According to our findings, it seems that effects of estradiol in local administration are dose dependent and high doses of estradiol caused impairment of passive avoidance learning.

Objectives: Ibuprofen, is one of the non-steroidal anti-inflammatory drugs (NSAIDs) that due to its higher efficiency and less side effects (as compared with other NSAIDs), is widely used specially for children, but its short half life (1.8-2 hours) and requiring to multiple dosing makes it a good candidate drug for sustained release dosage forms. Methods: In this study, Ion-exchange resin system was used to achieve this aim. Ibuprofen was loaded on cholestyramine (an anionic exchanger resin), using a batch method. The resin-drug complex was encapsulated with different amounts of either ethyl cellulose 10cps or 100cps (as a wall –forming agent), by using a solvent evaporation technique. Fractional coat, drug content and drug release rate were determined. Different amounts of polyethylene glycol 4000 (PEG 4000), by using pretreatment method were added to the microencapsulation formula which had the lowest release rate and the later tests were done. Results: The mean amount of drug loaded on resin was 44.8%±0.81% The In vitro release data showed that ethyl cellulose 100cps (EC 100) could not slow release rate of drug and release from these microcapsules, similar to uncoated complex, occurred via particle-diffusion (Bt) model. But ethyl cellulose 10cps (EC10) had a significant inhibitory effect on drug release rate. The lowest release rate was obtained from microcapsules with 30% EC10 (C30). PEG4000 caused an increase in the rate of drug release from EC10 coated complexes. All EC10 coated Formulations (with or without PEG4000) except for (C30) followed a square root of time model, the excepted kinetics for homogeneous and granular matrix systems. The most desirable release profile was obtained from C30 formulation which showed zero order kinetics. Conclusion: Based on the mentioned results EC10 can produce more uniform film than EC100 which has stronger cohesion force. Because of hydrophilicity of PEG 4000, it acts as a channeling agent. In dissolution medium it dissolves out of the microcapsules and leaves channels in EC10 film, from which drug can be released more rapidly.

Objectives: Morphine 6–glucuronide (M6G), a metabolite of morphine, is considerably more potent analgesic than morphine itself. M6G in serum is particularly difficult to measure, due to low lipophilicity of the molecule and low serum concentrations after usual parenteral doses of morphine. Methods: A competitive ELISA assay was developed to measure the concentration of M6G in serum and buffer samples. This competitive ELISA method effectively measured the degree to which samples containing an unknown amount of antigen (M6G) compete with a fixed concentration of an anti-body (R29). Results: The method was shown to be sensitive and reproducible with low intra-assay and inter-assay variation, low matrix effect and low cross reactivity. The method was simple and easy to use, and several samples (10 to 35 samples on each plate) could be analyzed simultaneously.Conclusion: The major advantage of the ELISA method over HPLC was the use of a very small volume (as little as 20 ml) for the assay. This advantage is important in the case of measuring M6G when it is not feasible to obtain a large volume of sample, for example in samples from newborn babies and children.