PHARMACEUTICAL SCIENCES
Year:2004 | Volume:- | Issue:2|Papers Count:10

The cardiac glycosides have been used in treatment of cardiac disease over two centuries. Digoxin is the most commonly prescribed cardiac glycoside due to its convenient pharmacokinetics, intravenous and oral preparations. Unfortunately the margin between therapeutic and toxic dose of digoxin is very small and toxicity occurs frequently. In the present study toxicity of digoxin was studied in dogs using electrocardiography and clinical signs in monitoring the progress of intoxication. Thirteen healthy, mature, native dogs weighing between 14 and 33 kg were used. The dogs were randomly divided into three groups. Dogs in group one (n=5) were given digoxin (oral + i.v.) and electrocardiographic manifestations of poisoning have been studied. Electrocardiography studies revealed bradycardia initially (while in some, sinus tachycardia was observed first), accompanied by T-wave changes and Premature ventricular beats, which progressed, to multifocal Premature ventricular beats, AV dissociation, ventricular tachycardia and ventricular fibrillation. Dogs in group two (n=3) were administrated hydrochloric acid (0.1 N) intravenously. In this group electrocardiographic disturbances have not been observed. Dogs in group three (n=5) were given digoxin (as same as group one) and when cardiac dysrhythmias were initiated, hydrochloric acid was administered (as same as group two). It is concluded that digoxin toxicity in the dog increases automaticity and delays conduction of the heart and hydrochloric acid h- not significant effects on digoxin induced cardiac dyarhythmias.

Among the proposed theories of mucoadhesion is the theory of mucus dehydration by the mucoadhesive polymer and the theory of polymer chain interpenetration into the mucus gel network, followed by the formation of weak bonds between them. These theories look at the process of mucoadhesion from their own point of view. In this study, it was decided to consider the two theories alongside each other, and to investigate the effect of mucus dehydration by mucoadhesive polymers on the viscoelastic structure of mucus gel. For this purpose polymeric discs (each containing only one polymer) containing carbomer 934 (C934), sodium carboxymethyl cellulose, hydroxypropyl cellulose (HPC), sodium alginate and tragacanth were prepared and placed in contact with the mucus gel for a period of 480 min within sealed containers at 37°C. At set intervals mucus gel was carefully separated from polymeric discs, re-weighed, and their G' (storage modulus) and G" (loss modulus) determined using dynamic oscillatory rheology at a frequency of oscillation between 0.1-10 Hz. Data obtained showed that the dehydration of mucus resulted in the strengthening of the viscoelastic structure of the mucus gel. Furthermore, beside mucus dehydration, polymer chains should be able to desirably penetrate into the glycoprotein chains of the mucus gel and as a result increase elasticity or in another word G", much more than G". In here the non-ionic polymer HPC performed much weaker than the anionic polymers investigated. On the other hand C934, which has dehydrated the mucus gel less than the other three anionic polymers, resulted in the greatest strengthening of the mucus gel structure. Hence, it appears that the collateral consideration of the two mentioned theories could explain the - process of mucoadhesion more appropriately.

Uarnium is considered as one of the natural radioelement for water pollution, therefore its removal from water resources for supplying healthy water for food and pharmaceutical industries is of great importance. This research is carried out to remove uranium from water by ion exchange process. It has been on the basis of the uranium solution preparation (synthetic), the anionic resins (Dowex and Amberlite) selection, determination of void fraction (%), optimum pH, capacity of resins, optimum contact time and absorption curve. Besides Laser Fluorimetry (LF) and Flow Injection Analysis (FIA) were used for measurement of uranium concentration. Maximum uranium absorption by the resins Dowex & Amberlite were respectively in 3 and 2.5 pH, absorption capacity of Dowex & Amberlite resins were respectively 22.50 and 16.90 (mgU/ml.R). Contact time between resins and solution for Dowex & Amberlite were about 25 and 15 minutes, meanwhile, absorption velocity of uranium for Amberlite is more than Dowex. Both Dowex and Amberlite resins have appropriate ability for uranium removal from Water.

Introduction of polymer gel as a dosimeter and its unique advantages in measuring dose distributions opens up some important applications in radiotherapy. This paper will discuss the performance of the gel dosimeter in measurements associated with external beam treatment, which is the most common form of radiotherapy. The central axis depth dose was measured in a cylindrical Perspex of 150mm in diameter. Irradiation was made using radiation field of 5x5 and 8x8 cm and the results compared with data obtained using a small ionization chamber. The investigation was also made to measure dose distribution resulting from a three, four field irradiation, oblique incidence and an inhomogeneous gel. Comparison was made with the plan produced by Helax planning system simulating the experimental condition using "Pips". The percentage depth dose on the central axis in both 5x5 and 8 x 8 radiation fields have shown good agreement with ion chamber within ±4%. For 50% isodose a comparison of dose arease in the gel and Helax in three- field radiation resulted in agreement within ±4% using Pips. Dose distribution produced in the gel for four fields agreed within ±2.7% to 5% up to isodose level of 70% and ±8% at 60% compared to Helax. The measurements of isodose levels for different radiation field in the case of an air gap indicated reasonably good agreement between gel and plan from Helax at the 90% dose level. The produced dose distributions from the 30° obique beam have shown large differences of about 10 mm in 90 to 70% in the Perspex phantom but agree well in the glass phantom. The results have indicated the depth dose and dose distributions from standard radiotherapy techniques produced in the gel agree with ion chamber and also basic dose distributions produced by Helax. The gel performance for measurements using an air gap in the phantom was quite encouraging.

The objective of this study was to formulate liposome preparations loaded with recombinant major surface metalloproteinase glycoprotein of Leishmania (rGP63) to selectively induce cell mediated immunity (CMI) in susceptible BALB/c mice and protect the mice against challenge with virulent L. Major. Liposomes containing rGP63 was prepared as dehydration-rehydration vesicles and composed of DPPC (Dipalmitoylphosphatidylcholin) and cholesterol (Chol) (DRV-DPPC/Chol-rGP63 7:2 molar ratio). To this fonnulation, DOPE (Dioleoylphosphatidylethanolamine) (DRV-DPPC/DOPE/Chol-rGP63 7:1:2 molar ratio) and stearylamine (SA) (DRYDPPC/ SA/Chol-rGP63 7:2:2 molar ratio) were added to produce fusogenic and positively charged liposomes, respectively. Another formulation had all the lipid ingredients (DRV-DPPC/DOPE/SAlChol-rGP63, 7:1:2:2 molar ratio). All the liposome formulations were heterogeneous in size, ranging from 0.1 to 1.5 µm, but their encapsulation (ate was high (46-52%). Liposome preparations containing rGP63 (2µg), rGP63 (2µg) by itself (PBS-rGP63), PBS (Phosphate buffer saline), and a control liposome (DRV-DPPC/Cho 17:2 molar ratio) were injected subcutaneously (Se) three times in groups of 10 female BALB/c mice with three weeks intervals. Three weeks later the mice were tested for delayed type hypersensitivity (DTH) by injecting 2 µg of rGP63 SC to the left footpads; and for comparison the right footpads were injected with PBS. After 24, 48 and 72 hours the footpad thickness was measured on both foot pads. One weak after the DTH test, the mice were challenged with virulent L. major promastigotes (1 x 106/50 µL) SC to the left footpads and the footpad thickness was measured for 10 weeks. The results of DTH test indicated that among different groups, the DRV-DPPC/DOPE/Chol-rGP63 had the greatest positive DTH response compare d to the control groups (p <0.01). The DTH response of the other liposomal formulations containing rGP63 and PB S-rGP63 were also positive (p<0.05); however, it was less. In the challenge test, the DRV-DPPC/DOPE/Chol-rGP63 had a complete protective effect (p<0.001). The DRY-DPPC/Chol-rGP63 had also a good protective effect (p<0.001) but it was less than the DRV-DPPC/DOPE/Chol-rGP63. The DRV-DPPC/SAlChol-rGP63 had a little protective effect that was not statistically significant (p>0.05), DRV-DPPC/DOPE/SAlChol-rGP63 and PBS-rGP63 showed only partial protection (p<0.05). These results indicate that DRV-DPPC/DOPE/Chol-rGP63 could be a suitable immunoadjuvant for rGP63 to induce selective CMI in susceptible BALB/c mice and protect the mice against cutaneous leishmaniasis.

DNA Polymerase enzyme undertake the DNA replication and in molecular research DNA polymerase enzymes especially thermostable enzymes have great importance. In this research, thermostable DNA polymerase was extracted and purified from Bacillus stearothermophilus isolated from Gavmish Goly hot spring in Saraeyn city. Bacteria were cultured in Luria-Bertani broth at 55°C and harvested in logarithm phase. Twenty grams of cell paste obtained and resuspended in related buffer. Crude cell extracts were prepared by using of lysozyme and sonication. Purification were performed by ammonium sulfate precipitation and three steps of chromatography with DEAE-sephadex, phosphocellulose and Heparin-sepharose. DNA polymerase enzyme was purified 127-fold and specific activity of the purified enzyme was 223 (U/mg). DNA polymerase had the most activity at 55°C. Three protein bands were obtained by using of SDS-P AGE. The major band had a molecular weight of approximately 76000 daltons. Bacillus stearothermophlius DNA polymerase can use in DNA replication, site directed mutagenesis and probably in DNA sequencing at high temperature.

Hemolysinhas various diagnostic as well as academic applications. Apart from the regular teaching of this test to postgraduate students of different fields like medicine, pharmacy, immunology and biochemistry, the assessment of complement components' function by performing CH50 test is one of its applicability. The goal of this project was to take a step towards self-efficiency with a minimum expense. Hemolysin was produced in a rabbit by using sheep red blood cells (SRBC) as immunogenic. Heparinized blood from several sheeps were mixed together (pooled) and then washed with serum physiology. The number of red blood cells was counted with a cell counter, and 1-5x109 numbers of red cells were injected intravenously into the rabbit. The production of polyclonal antibodies of IgM class reached its maximumlevel after seven to ten days of injection. The blood was withdrawn from the rabbit and its serum, rich in hemolysin, was separated. Hemolysin was titrated for assessment of the hemolysin function and its standardization. To do this and determining in which titer of hemolysin red blood cells only become sensitive and not agglutinated, different dilutions of hemolysin were made, and added to certain volumes of SRBC. The results showed that 2560 dilution of hemolysin was still capable of sensitizing SRBC for surveying function of total complement components. To be sure of hemolysin function at a standard level, CH50 test was performed using test and standard hemolysin at the same time. The results showed that 2560 dilution of test hemolysin, the same as standard hemolysin was capable of making sheep red blood cells sensitive. High titer of test hemolysin in comparison with titer of standard hemolysinclearly indicates that hemolysin produced in our laboratory is equal in potential to the standard. Thus it is a beneficial production and has importance for diagnostic purposes.

In this study, we tried to formulate nifedipine once a day formulation by using of osmotic pump system. Several formulations was prepared and drug release from each of them was measured by dissolution tester apparatus (No. II) in 3TC and 100rpm. Nifedipine was protected from light during all of the steps. The various polymers with different viscosities and different molecular weights were used in the core formulation such as HPMCE50LV, HPMCK100M, HPMCE5LV, PVPK30MN, NaCMC (200 and 1500 cps) and Carbapols (934 and 940). Among these polymers, HPMCE50LV was chosen as selected gelling agent for the system. KCI also selected as osmotic agent of system. The use of SLS in the core formulation markedly increased the release of the drug from osmotic pump. The drug release enhancement by SLS probably arises from the ability of SLS to suspending the drug particles in the formulation and increasing of solubility. SLS also can increase wetting of drug particles and prevent them from agglomeration after penetrating of water into the system. Cellulose acetate was used in the formulation of semi permeable membrane. Caster oil was used as plasticizers of semi permeable membrane in 1%w/w concentration. The effect of hole diameter on the release of formulations also investigated. These studies showed that the hole diameter is very effective on the release of the drug from osmotic pump and hence, the hole size of system should be optimized.

Several studies indicate that testosterone has a role in pain nociception. Recently, we have shown that castration and flutamide induced analgesia in the male rats using formalin test. This analgesic effect correlated with increase of serotonin in dorsal horn of the spinal cord. The aim of this study is to investigate the effect of chronic administration of fluoxetine on castration and flutamide induced analgesia. Four weeks after castration, we observed analgesia in the second phase of formalin test. Also, Flutamide (10 mg/kg, i.p.), as a testosterone receptor antagonist, induced analgesic effect. Fluoxetine (0.16 mg/kg, i.p. for 5 days) potentiated the analgesic effect of castration and flutamide. The results indicat that castration and flutamide produce analgesia which can be potentiated by co-administraion with chronic adminstration of fluoxetine. This study substantiates our previous report showing a correlation between testosterone and serotoninergic system. However, the exact mechanism of testosterone interaction with serotoninergic system is not clear and remains to be elucidated.

The polymerization and chemistry of activated acrylates have been elaborated in recent years to provide a uniquely versatile method of polymer synythesis. This article discusses the copolymerization of activated acrylates by free radical solution techniques. The use of copolymer for the synthesis of amphiphilic gels containing drug pendent groups was studied.Amphiphilic copolymers containing S-aminosalycilicacid (S-ASA) substitutions were prepared by copolymerization of styrene with trichlorophenyl methacrylate in DMSO solution followed by aminonolysis of the precursor polymer with S-ASA, ethanolamine, and polyethylene glycol. The polymers obtained were characterized by 13C NMR, FT-IR and elemental analysis. The hydrolysis behavior of the copolymers were studied at simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). More highly functionalized gels are obtained via complete displacement of the activating groups by the functionalizing reagent (S-ASA). The hydrolysis profiles of copolymers were indicated that the drug can be released from the polymeric prodrugs. The extend and rate of drug released were influenced by the nature of the copolymers and pH of the hydrolysis medium. The polymeric prodrug of S-ASA described here could be useful in the preparation of colon-specific drug delivery systems.