Pharmaceutical Sciences
Volume:12 Issue: 1, 2006

The objective of this study was preparation and evaluation of recombinant 26 antigen of Leishmania infantum (L. infantum) for serodiagnosis of visceral leishmaniasis (VL) in endemic regions of Iran. Genomic DNA was extracted from L. infantum promastigotes by phenol-chloroform method and used for PCR amplification of k26 gene. The PCR product was purified, cloned into the Bluescript vector and subjected to DNA sequencing. For production of recombinant 26 protein, the insert was removed by restriction digestion, subcloned into the pQE-80L vector and expressed in E. coli. The recombinant protein was purified by Ni-NTA column and used for evaluation of response of VL patients by immunoblotting. PCR amplification of K26 gene using L. infantum genomic DNA as a template was resulted in amplification of a 756 bp fragment. Cloning and sequencing of amplified fragment showed that there is a 98 % homology to L. chagasi and 95 % to L. donovani 26 gene sequence. Recombinant expression and purification of L. infantum K26 gene produced a highly pure protein appeared as a 45 kDa band in SDS-PAGE analysis. Western blot analysis showed that the sera from visceral leishmaniasis patients contain a high titer of antibody against K26 antigen. Western blot analysis using purified recombinant antigen showed that K26 antigens are recognized by sera from VL patient due to L. infantum and that this antigen can be exploited for serodiagnosis of VL. EMRO/tdr Grant SGS 05/95.

The endogenous estrogens are important female gonad hormones that havemany diverse physiological and pathophysiological actions. Some of clinical trials showed that lower incidence of cardiovascular diseases in premenopausal women is related to the cardio protective effect of estrogens. But, estrogens have been suspected of having carcinogen properties. In order to investigation role of functional groups in specialty of steroid drugs and decreasing (or increasing) estrogenic effects by these groups, we considered in developing new ethynyl estradiols in which simple groups such as carboxylic (CO2H), ester (-CO2Et), amide (-CONH2) and nitrile (-CN) substituted at ethynyl moiety. Two synthesis pathways were suggested to providing the main compounds: In the first path, treatment of Ethynyl estradiol with n-BuLi in THF at -15 C°followed by bubbling anhydrous CO2 (g) through the solution gave the carboxylic compound (-COOH) in 40% yield. Then, ethyl ester compound (-COOEt) was prepared from the carboxylic acid derivative by reaction with absolute ethanol in the presence of acidic catalyst in 70% yield. The amide derivative (-CONH2) was synthesized by passing ammonia (g) from ethanolic solution of ester in reflux state. Its yield was 65%. Treatment of 3, 17 dibenzoyl ethynyl estradiol (was prepared from the reaction of ethynyl estradiol with benzoyl chloride) with n-Buli at -78 °C followed by the addition of cyanogens bromide gave related nitrile compound in 40% yield. The second pathway which was suggested for synthesis of functionalized estradiol derivatives was based on reaction of Ethyl propiolate with 3O-protected estrone in the presence of metal alkalis. All efforts which are accomplished on this reaction along with changing reaction conditions such as alkali reagent (LiNH2, NaNH2, BuLi), different solvents (THF and Ether), reaction temperature (-60 °C to reflux), Amounts of reactants and time of reaction (1 hour to 48 hours) gave no yields higher than 10%. In these efforts, a reaction with quantitative yield was developed for preparing 3- methoxyestrone. All reactions were monitored by TLC (Silicagel 60F 254) in Hexane – EtOAc or Toluene- Acetone. Elucidation of chemical structures of the compounds was made by FT- IR and H NMR.

Oral Mucositis (OM) or Stomatitis is a significant medical and nursing problem and a common side effect of chemotherapy. OM is associated with pain, reduced oral intake, higher incidence of infections and prolonged hospitalization and treatment. In this study, the efficacy of two protocols for oral care using either allopurinol or as normal saline oral rinses was compared in view point of preventing mucositis in patients undergoing chemotherapy. 69 patients were randomized to receive either alloporinol (n=28), normal saline (n=27) or water (14) for prevention of Oral Mucositis. With starting of chemotherapy, alloporinol and normal saline groups used their mouthwashes for 16 days and control group was advised to use water for washing their mouth. The results showed that intensity of stomatitis and related pain were decreased significantly as well as their maintenance in allopurinol group in comparison with other groups (P< 0.05). Also it was showed that the differences between normal saline and control groups was significant (P<0.05). It can be concluded that using allopurinol mouthwash could decrease the occurrence and intensity of stomatitis. Then using allopurinol mouthwash for the prevention of stomatitis during chemotherapy was advised.

Anemia is one of the most prevalent illnesses in Iran especially among children, the youth and women. Iron, copper and zinc, important elements in prevention of anemia, enter the body through food and cereals play a main role in providing them. Wheat malt extract (samanoo) is one of the Iranian traditional foods which is made from cereals. The purpose of this study was determination of phytic acid, iron, copper and zinc in the wheat malt extract (samanoo) of normal wheat and the enriched wheat and studying the probable usefulness of wheat malt extract in overcoming the deficiency of these elements. 31 samples including 5 enriched wheat malt, 23 normal ones and 3 samples from commercially available wheat germ powders were studied. Phytate was determined by spectrophotometry and iron, zinc and copper were determined by atomic absorption. The results of analysis of iron, zinc, copper and phytic acid in enriched wheat malt extracts were as 0.13±0.08mg/100g, 0.57± 0.15mg/100g, 0.21±0.14 mg/100g and 17.2 ± 0.16 mg/100g, respectively. These results for normal wheat malt extracts were 0.07±0.06mg/100g, 0.35±0.16mg/100g, 0.06±0.05mg/100g and 12.8 ± 0.06mg/100g respectively. In addition, the results of the study about the wheat germ powders were obtained as following: 0.15±0.02mg/100g, 0.30±0.05mg/100g, 0.22±0.05mg/100g and 18.7 ± 0.42mg /100g. The differences of Ash, Copper, Zinc and phytate contents of normal and enriched samanoos were statistically significant (P<0.05). The results of wheat germ powders were also significantly different from the results of normal samanoos. The higher rate of iron, zinc and copper in the enriched wheat malt extract (samanoo) indicates that providing the malt extract from enriched wheat, could prepare these useful elements in higher amounts.

The present study was performed to investigate the role of 5-HT2 receptors in dorsal and median raphe nuclei on the withdrawal syndrome of morphine and accelerated the restraint of opioides. Experiments were performed on adult male wistar rats weighing between 225 and 275 g. The control group (n=8) had 9 days s.c. injections of morphine (5, 10, 10, 15, 15, 20, 20, 25, 25mg/kg/12h) and the last day, 60 minutes after first injection of morphine, mg/kg naloxone was injected (i.p.) and signs of withdrawal syndrome were recorded for 60 minutes. In the sham and test groups a guide cannula was implanted into the DRN and MRN in the separated groups (n=8). After five days recovery of animals, injections of morphine began and the 9th day, 55 minutes after first s.c. injection of morphine, 1μl/2min of α-Me-5HT vehicle was injected into the nuclei in the sham group. But in the test groups, 2.5, 5.0 and 10.0 μg/μl/2min of α-Me-5HT (agonist of 5-HT2 receptors) was injected into the nuclei, and then naloxone was injected (i.p.). Data signs were analyzed by one way ANOVA and Tukey post test. The results of this study showed a significant decrease in some of the recorded morphine withdrawal signs (for example for highest dose of α-Me- 5HT in DRN: jumping p<0.05, teeth chattering p<0.01, wet-dog shakes p<0.001 and genital grooming p<0.05) in test groups in comparisons with the control group. The results confirmed the important role of 5-HT2 receptors in raphe nucleuses on some of the morphine withdrawal signs and may dissolve problems of opioides addiction.

Failure of Glaucoma filtering Bleb is caused mainly by proliferation of subconjunctival Fibroblasts and by their biosynthesis of collagen and other extra cellular Tissues. A number of antimetabolite drugs have been shown to suppress fibroblast activity. Mitomycin C is an antineoplastic antibiotic which is obtained from streptomyces caespitosis and inhibits DNA synthesis. Histological studies have shown that mitomycin stopped fibroblastic growth and proliferation. Therefore, the reason for using mitomycin C is increasing of surgical success and consistency of bleb and fistul in trabeculectomy. Since there is not an established dose of mitomycin C application (used dose is 0.1 – 0.4 mg), the aim of the present study is investigating mitomycin C in higher doses and longer application in high risk patients. This study was an experimental work in 2000-2002, during the study the patients who had glaucoma. IOP, more than 20 mmHg, optic nerve damaged and visual Acuity Reduced was entered the study. Among them, the patients, whom their disease was advancing in spite of using several antiglaucoma drugs, their disease was advancing, were selected for surgery. Thus the patients for Trabeculectomy in addition to having indication for surgery had one or more high risk factors. After surgery, intraocular pressure decreased to 66%, success rate was 100% a thin avascular bleb was 90%, wound leak was 25%, shallow anterior chamber was 20%, choroidal detachment was 20%, and cataract development was 10% of all subjects. we concluded that the application of high dose of mitomycin C for longer period in high risk patients will be useful if it is used properly and the complications are managed carefully.

Both physical mixtures of drug and polymers and their solid dispersion systems (SD) have been used in preparation ofinert insoluble matrices. In some studies it has been shown that SD systems are more effective in controlling drug release rate. This study has been performed in order to evaluate the SD systems of acetaminophen (as a model drug) and ethylcellulose, Eudragit RS or Eudragit RL in preparation of sustained release matrices and to investigate the effect of solvent (ethanol, acetone or isopropanol) used in preparation of SD system on characteristics of matrices. SD systems were prepared by solvent evaporation method. Matrices were prepared from both physical mixtures and SD systems of drug and polymers and were characterized by hardness, friability and dissolution tests. The results showed that matrices prepared from physical mixtures of drug and ethylcellulose were harder than those prepared from SD systems. Opposite results were observed for Eudragit matrices. The results of friability test were in agreement with the results of hardness test. Acetaminophen release rate was the slowest for matrices prepared from physical mixture of drug and ethylcellulose. However the use of SD system of drug and Eudragits resulted in decreasing drug release rate compared to matrices prepared from physical mixtures. Finally the result of this study showed that the type of solvent used in preparation of SD systems did not have any profound effect on compressibility of resulting films and therefore on hardness of matrices. It was also revealed that the type of solvent did not affect the release rate of drug form matrices of SD systems. The use of SD system was efficient in preparation of Eudragit and acetaminophen matrices (especially Eudragit RS) however no benefit was obtained in using SD system in preparation of ethylcellulose and acetaminophen matrices. The solvent used in preparation of SD systems did not affect the matrix characteristics.