Pharmaceutical Sciences
Volume:13 Issue: 4, 2008

In this study, prophylactic effects of natural honey as a pharmacologic preconditioning agent on ischemia/reperfusion (I/R) induced cardiac arrhythmias and infarct size were investigated in isolated rat heart. Isolated rat hearts were mounted on a Langendorff apparatus then subjected to 30min regional ischemia followed by 120minreperfusion. In control group, the hearts were perfused by a modified Krebs-Henseleit solution throughout the experiment, however, in the test groups they were perfused by enriched Krebs solution with natural honey (0.25, 0.5 and 1%) 10min before to 10min after ischemia. The arrhythmias were analyzed based on the Lambeth conventions. The infarct size was determined by Triphenyltetrazolium chloride and planimetry methods. At the ischemia, the total number of ventricular ectopic beats (VEBs) in the control group was 667±116 while perfusion of natural honey (0.25, 0.5 and 1%) reduced it to 128±35 (p<0.01), 161±35 (p<0.01) and 303±94 (p<0.05), respectively. The number of ischemic ventricular tachycardia (VT) and the time spent in VT were significantly lowered by the same concentrations. Honey (0.25 and 0.5%) decreased the incidence of VT from 100% (control) to 13% (p<0.001) and 25% (p 0.01), respectively. During reperfusion phase, the number of VEBs and VT were significantly reduced by all used concentrations. In addition, honey (0.25%) significantly decreased the incidence and time spent for reversible ventricular fibrillation. Moreover, perfusion of honey (0.25, 0.5 and 1%) reduced infarct size from 46.3±2.9% (control value) to 3.3±1.3, 9.2±1.9 and 11.7±2.2%, respectively (p<0.001 for all). The results of this study showed antiarrhythmic and anti infarct properties of natural honey as a preconditioning agent against I/R injuries in isolated rat heart. Probably, antioxidant activity of honey, scavenging of free radicals and presence of energy sources such as glucose may involve in these cardioprotective effects.

The novel drug delivery systems (NDDSs) have many advantages over traditional dosage forms such as longer duration, lower side effects, more uniformly blood concentrations and more patient compliance. Oral osmotic systems are NDDSs which can release their drug contents in long period of time (24h) with constant release rate. In this study we tried to formulate osmotic pump with two layered core and evaluate the effects of some parameters on the extent and kinetics of indomethacin release from it. Cellulose acetate was used as film former polymer in formulation of semipermeable membrane (SPM). Dip coating method was used for coating of the core tablets and a small orifice was drilled on one side of them by using standard microdrills. The drug release was tested by standard dissolution tester (paddle apparatus) and the drug concentration in the samples was measured by UV spectrophotometer. Various formulations were compared in terms of different parameter such as D10h (percent released within 10 hours), tL (lag time), Devzero (deviation of the drug release from zero order kinetics) and RSQzero. The results showed that SPM thickness has the significant effects on 10h and tL. tL was increased and D10h was decreased by increasing SPM thickness from 90 to 190μm regularly. The best drug release kinetic was observed in 130μm SPM thickness. Increasing orifice diameter from 350 to 80 μm improved D10h and tL but improvement in zero-order release kinetic of the drug was seen only to an optimum orifice diameter (700μm) also this parameter should be optimized in formulation. The results also showed a direct relationship between the amount of caster oil as lipophilic plasticizer and tL. D10h also decreased with increasing of caster oil in SPM formulation. Omitting of glycerine as hydrophilic plasticizer produced great enhancement in tL (46.7 in presence of 1.5% glycerin vs 207.8min for formulation without glycerine). with optimization of the main system parameters such as aperture diameter, SPM thickness, type and amounts of hydrophilic and lipophilic plasticizer, we can obtain suitable drug release (near zero order) from the osmotic system

Nowadays, nondrug treatments (mineral waters and plants) are novel therapeutic approaches for hyperlipidemia. The aim of the present study was the evaluation of the effects of calcic and magnesic sulfate mineral water and total extract of Hypericum perforatum on the serum lipid profile (T-CH, TG, HDL-CH, LDL-CH) in hypercholesterolemic rats. Thirty male rats (SD) weighing 100-150g were randomly divided into 5 experimental groups. The rats in control group were fed a standard diet and the other groups were fed a cholesterolrich diet for 60 days. Then, hypercholesterolemia was observed through analyzing the blood samples (P<0.001). In the second phase(therapeutic phase), control group(group1) was continued with standard laboratory diet, and hyperlipidemic rats were treated with total extract of Hypericum perforatum, tap water or mineral water for the next 60 days, as the following: group2: cholesterol-rich diet and tap water, group3: cholesterol-rich diet, tap water, total extract of Hypericum perforatum (4mg/kg, ip), group4: cholesterol-rich diet, tap water and total extract of Hypericum perforatum (12mg/kg, ip), group5: cholesterol-rich diet and mineral water. All groups received saline normal and DMSO as a solvent for extract through intra peritoneal (ip) injection. At the end of the period, blood samples of each group were drawn from venus plexus of eye and analyzed for the lipid levels of plasma. The results indicated that treatment by mineral water or total extract of Hypericum\ perforatum at the doses of 4 and 12mg/kg could reduce the levels of T-CH, TG, LDL-CH significantly (P<0.001). Total extract of Hypericum perforatum (4mg/kg, ip) and mineral water administration alter a statistically significant difference to the level of TG (P<0.001), but could not reduce T-CH, LDL-CH levels. Calcic and Magnesic Sulfate mineral water and total extract of Hypericum perforatum could reduce lipid profile especially TG. More studies are recommended.

Psoriasis is a chronic, recurrent disease that affects between 1% and 6% of the population. Methotrexate (MTX) is an effective systemic chemotherapeutic agent for the treatment of psoriasis and possibly cutaneous lymphoma (CTCL).However the risk of hepatic fibrosis and other systemic toxicity, such as bone marrow suppression, has precluded its use in all but the most severe cases of these diseases. In considering the potential severe toxicity associated with systemic administration of MTX, a topical formulation might be of greater utility for the treatment of psoriasis and other hyperproliferative skin disorders. One of the presumed reasons for the lack of clinical activity of topical methotrexate in psoriasis is insufficient percutaneous penetration necessary to inhibit epidermal DNA synthesis. The present study was undertaken to prepare a formulation to optimize penetration of MTX in vitro. For this mean, several gel formulations were prepared and investigated in the case of stability and physical characteristics. Among them three formulations were selected for percutaneous absorption studies using rat skin and standard Franz diffusion cells. Assay of drug was done using HPLC method. For enhancing percutaneous absorption, three penetration enhancers were added to the bases formulation with different concentrations. Among the evaluated formulations, the best one from view point of having better penetration profile was selected and the effect of various enhancers on penetration profile investigated. For this mean three surfactants (anionic, cationic and nonionic) were incorporated into formulations with different concentrations. Finally salicylic acid as a keratolytic material was added for more enhancement effect. The results showed that SLS (sodium louryl sulphate) and alkyl benzyl dimethyl chloride had not any significant enhancement property on penetration of MTX.Lower ability of these surfactants on drug penetration through the skin probably aroused from drug enhancer complexation and formation of micells with low penetration ability containing the drug molecules. Transcutol P was able to enhance transdermal absorption of MTX and the higher enhancement ratio was obtained with 2% (w/w) concentration of transcutol P. Adding of salicylic acid increased this ratio. Better penetration profile was shown with increasing of salicylic acid concentration. prepared formulation containing transcutol p 2% (w/w) and salicylic acid 6% (w/w) had higher enhancement property and could be used clinically for local treatment of psoriasis.

Urinary tract infection (UTI) is one of the most common infections that afflicts humans and if not treated properly and timely could cause serious damages to the urinary tract. Nowadays increasing antibiotic resistance is one of the problems in managing UTI. Availability of new information about sensitivity of prevalent bacteria in a given area could help in the selection of proper treatment regimens especially in the empirical therapy which is naturally based on such information. Urine specimens of in-patients and out patients in Shabestar hospital were cultured on blood agar and eosin methylene blue agar (EMB). Isolated bacteria were identified according to standard microbiological tests and then subjected to sensitivity testing according to routine method of disk agar diffusion technique. Out of 9495 urine specimens tested, 1821 cases (19.1%) were identified as having UTI. The most prevalent bacteria belonged to enterobacteriaceae family and the upmost resistance was recorded against ampicillin (95.3%), while the least resistance recorded for amikacin (6.6%) and ciprofloxacin (10.2%). Our findings suggest a growing trend of resistance among bacteria causing UTI, which was more obvious in use of gentamicin, cephalotin, and ampicillin. results of the present study underline the need for sensitivity tests prior to antibiotic therapy in UTI, which could help and guide in proper choosing of antibiotics and effective treatment and therefor prevention of antibiotic resistance.

The vasorelaxant effect of estrogens on blood vessels is one of the important cardiovascular protective mechanisms of estrogen. The present experiments were designed to study the mechanisms of vasorelaxant effect of 17β-estradiol (E2) in human saphenous veins (HSV). HSV were obtained from patients undergoing coronary artery bypass graft surgery in Tabriz Madani Heart Center. The role of K+ channels and endothelium derived hyperpolarizing factor (EDHF) in the effects of E2 were studied by incubating tissues with K+ channels blockers: glibenclamid (3μM), 4-aminopyridin (1mm), tetraethyl ammonium (TEA, at lower and higher concentration: 1mm and 10mM), BaCl2 (30μM) and combination of charybdotoxin and apamin. In order to assess the role of endothelium in the inhibitory effect of TEA (10mM) on the relaxant effect of E2, responses were elicited in endothelium denuded vein rings. TEA at 1mm, (selective inhibitor of large-conductance, BKCa, Ca2+ activated K+ channels), 4- aminopyridin (selective inhibitor of voltage dependent K+ channels) and glibenclamid (selective inhibitor of ATP dependent K+ channels) did not affect the vasorelaxant effects of E2 on PGF2α-induced contractions. TEA at higher concentration, an inhibitor of small-conductance (SKCa) and intermediate-conductance (IKCa) Ca2+ activated K+ channels, significantly inhibited E2-induced vasorelaxation. This inhibitory effect was endothelium-dependent and abolished by endothelium denuding. In intact tissues, pretreatment either with a combination of charybdotoxin and apamin (inhibitors of EDHF), or BaCl2, significantly reduced the relaxation produced by E2. The data suggest that vasorelaxant effect of E2 in HSV maybe mediated by EDHF which involves apamin/charybdotoxin-sensitive K+-channels and K+.

The hippocampus has been implicated in many learning and memory functions including spatial memory. Leptin is a peptide hormone secreted by adipose tissue. Some studies have also suggested that leptin affect learning and memory. The present study is scheduled to investigate the effect of intraperitoneal (IP) injection of different doses of leptin on spatial memory formation. 60 male rats were divided into 6 groups in our experiments: (1) control, (2) sham, and (3), (4), (5), (6) intraperitoneal injection of 0.0, 0.1, 0.25 and 0.5 mg/kg doses of leptin respectively. All groups were trained in Morris water maze for two days. Learning parameters were compared between groups. Our results showed there were significant differences between sham group and test groups in spatial learning. Together our findings suggest that intraperitoneally injection of leptin improved spatial memory in rat. Leptin shows its highest effect with medium doses.