Iranian Journal of Pharmaceutical Research
Volume:12 Issue: 1, Winter 2013

Antimicrobial therapy remains to be the most important method of wound infection treatment. Systemically administered antimicrobials may not achieve therapeutic level in wound. On the other hand, in the absence of surgical debridement (due to any reason), most topically applied antimicrobials cannot penetrate the wound in therapeutic amount due to the presence of eschar. Burn eschar is a proteinous structure with some lipid components in which proteins seems to play an important role in the barrier effects of eschar. Therefore, in this study the effect of protein-acting enhancer (trypsin) on permeation of hydrophilic model drug (clindamycin phosphate) was investigated.To perform this investigation, permeation of saturated clindamycin phosphate was studied at 32°C through trypsin-treated and untreated eschar samples for 12 h using home-made static diffusion cells. Third-degree burn eschar samples were separated at the time of surgical debridement (7-14 days post burn) from burned patients. Before each experiment, eschar was hydrated for 12 h and samples were then treated with trypsin solution (1%, w/v) for 4 and 24 h. Clindamycin was measured by a HPLC method developed here.Results showed that after trypsin-treatment for 4 and 24 h, clindamycin phosphate permeation flux was increased significantly by about 1.5 and 2 times and permeation lag-time was decreased by about 2 and 1.3 times respectively.The present results show that permeation of drugs through burn eschar can be increased considerably by trypsin.

Recently, 6-(2-naphthyl)-2, 3-dihydro-as-triazine-3-thione (NDTT) was synthesized in laboratory and used successfully for the spectrophotometric determination of nanogram levels of Cu2+ in aqueous solution. This reagent forms a specific red complex with Cu2+ ions after the extraction by chloroform at alkaline pH. The absorption of the complex in the UV region (313 nm) is about 8 times as strong as in the visible one (510 nm). Mercury and nickel ions form yellow complexes with NDTT under the same conditions which interfere in the UV region and without effect on Cu (II) absorbance in the visible region. The studied vegetables include Mentha pipereta L., Anethum graveolens L., Beta vulgaris L., Coriandrum sativum, Petroselinum hortense H., Ocimum basilicum L., Spinacia oleracea L., Lactuca sativa L., and Brassica oleracea L.

Weichang’an (WCA) pill, a traditional Chinese patent medicine consisting of ten Chinese medicinal herbs, has been used to treat irritable bowel syndrome and functional dyspepsia for several decades. In this study, twelve bioactive constituents in the methanol extract of WCA were accurately identified since MS/MS fragmentation behavior of the references and the standards by using HPLC-DAD-ESI-MS/MS analysis and a reliable and accurate method for the simultaneous determination was developed. Twelve active components including costunolide and dehydrodehydrocostus lactone from the principal herb Radix Aucklandiae; naringin, hesperidin and neohesperidin from Fructus Aurantii; magnolol and honokiol from the ministerial herbs Cortex Magnoliae officinalis; aloe-emodin, rhein, emodin, chrysophanol and physcion from adjunctive and messenger herb Radix et Rhizoma Rhei were analyzed in the samples. The chromatographic separation was performed on a Kromasil C18 column with gradient elution of acetonitrile-methanol and 1.0% acetic acid water. In this condition, linearity, inter- and intra-day precision and accuracy were within acceptable ranges. The developed method showed satisfactory precision and accuracy with overall intra- and inter-day variations of 0.68-1.33% and 0.67-2.05% respectively, and the overall recoveries of 97.54-102.69% for twelve compounds. The proposed approach was successfully applied as a powerful tool for the quality control of WCA pill.

Detection of genetically modified organisms (GMOs) in food is an important issue for all the subjects involved in food control and customer’s right. Due to the increasing number of GMOs imported to Iran during the past few years, it has become necessary to screen the products in order to determine the identity of the consumed daily foodstuffs. In this study, following the extraction of genomic DNA from processed foods sold commercially in Iran, qualitative PCR was performed to detect genetically modified maize. The recombinant DNA target sequences were detected with primers highly specific for each investigated transgene such as CaMV35s gene, Bt-11, MON810 and Bt-176 separately. Based on the gel electrophoresis results, Bt-11 and MON810 events were detected in some maize samples, while, in none of them Bt-176 modified gene was detected. For the first time, the results demonstrate the presence of genetically modified maize in Iranian food products, reinforcing the need for the development of labeling system and valid quantitative methods in routine analyses.

More than 30 mineral elements have been found with different key functions in helping plants and animals to survive and live healthy. As a direct result, they have always attracted the attention of scientists. The quest is to find some efficient analytical and quantitative procedures in this study to determine some mineral and trace elements of Iranian Crocus sativus L. corms. Several studies have been made using distinct methods and eventually, to achieve this purpose, three analytical methods were used as follows: Neutron Activation Analysis (NAA), Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) and Atomic Absorption Spectrophotometry (AAS). Seventeen mineral and trace elements (Mg, Na, Ca, K, Mn, Zn, Cu, Pb, Hg, Ni, Fe, Co, Cd, Sr, Rb, Sc, and Br) were determined in Crocus sativus L. corms in two different physiological stages.The mineral elements content in saffron corms showed a wide variability and their concentrations in dormancy stage were higher than waking. Despite of the fact that K concentration was the highest among all mineral elements studied in both samples, it was nil for Sc, Co, Hg, Pb and Cd.

The in vitro antioxidant and antimicrobial activities of the essential oil and methanolic extract of Achillea sieheana Staf. (Asteraceae) were investigated in this study. The chemical composition of the essential oil isolated by hydro-distillation from the aerial parts of A. sieheana was analyzed by GC–MS. Camphor (43.36%), Artemisia ketone (25.95%), 1.8-cineole (6.29%) and camphene (4.77%) were the main components in the essential oil. Their antioxidant activities were also evaluated using phosphomolybdenum, β-carotene bleaching and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. A. sieheana methanolic extract showed an effective DPPH scavenging activity (IC50 = 87.04 μg/mL). The extract had also a high reducing effect (71.08%) on the oxidation of β-carotene. In addition to evaluating the antioxidant activity of this plant, the total phenolic and flavonoid contents were measured in the extract. The antimicrobial activities of the methanolic extract and the oil were also tested against 13 bacteria and two yeasts. The results showed that both had strong antimicrobial activity against the tested microorganisms.

A series of curcumin derivatives containing heterocyclic moiety have been synthesized and evaluated for their antibacterial activities. The chemical structures of the synthesized compounds were verified on the basis of spectral data and elemental analyses. Investigation of antimicrobial activity of the derivatives demonstrated the ability to inhibit Gram-positive microorganisms with zone of inhibition ranging from 14-18 mm, MIC ranging between 0.0625 and 0.25 mg/mL. Among all tested derivatives, diazepine 4 exhibited remarkable potency against Gram-positive bacteria S. aureus. An extensive study is underway to optimize the effectiveness of diazepine type of compounds and to determine their mode of action.

It is now believed that the inhibition of carbohydrate hydrolyzing enzymes (CHEs) in the digestive tract can significantly prolong the overall carbohydrate digestion time and decrease the postprandial hyperglycemia after a meal. Therefore, inhibitors of CHEs can be useful therapeutic approaches in the management of diabetes mellitus, especially in the type 2, and complications associated with the disease. In our previous study, the ethanol extract of the aerial parts of Salvia virgata showed an inhibitory effect on pancreatic α-amylase in-vitro. Bioassay-guided fractionation of the extract using the α-amylase inhibitory assay led to the isolation and identification of an active flavone compound, chrysoeriol. The compound concentration dependently inhibited the α-amylase activity with an IC50 value of 1.27 (1.21-1.33) mM.

Male and female leaves and fruits of eleven different taxons of Iranian conifers (Cupressus sempervirens var. horizontalis, C. sempervirens var. sempervirens, C. sempervirens cv. Cereifeormis, Juniperus communis subsp. hemisphaerica, J. excelsa subsp. excelsa, J. excelsa subsp. polycarpos, J. foetidissima, J. oblonga, J. sabina, Platycladus orientalis and Taxus baccata) were collected from different localities of Iran, dried and extracted with methanol. The extracts were tested for their antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Candida albicans. The extracts were screened qualitatively using four different methods, the disc diffusion, hole plate, cylinder agar diffusion and agar dilution methods, whereas the minimum inhibitory concentrations (MIC) of each extract were determined by the agar dilution method. The best result was obtained by means of hole plate method in qualitative determination of antimicrobial activities of extracts and the greatest activity was found against S. aureus in all tested methods.

Salvia chorassanica Bunge is one of the Iranian endemic species of Salvia. There is not any reported literature on S. chorassanica. This study was designed to examine the in-vitro anti-proliferative and proapoptotic effects of the methanol extract of S. chorassanica and its fractions on HeLa cell line. Cells were cultured in EX-CELL®, an animal free medium specially designed for HeLa cell line and incubated with different concentrations of plant extracts. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide (PI) staining of DNA fragmentation by flow cytometry (sub-G1 peak). Activity of caspase -3, -8 and -9 was measured by the caspase colorimetric kit assay. S. chorassanica inhibited the growth of malignant cells and the CH2Cl2 fraction was determined as the most cytotoxic fraction in comparison with other fractions. The calculated IC50 values for methanol extract, n-hexane, CH2Cl2 and EtOAc fractions were 8.841, 5.45, 2.38, and 58.03 µg/mL, respectively. S. chorassanica induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that the cytotoxic mechanism is characterized by apoptosis induction. The activity of caspase-3 and 8 proteins in treated HeLa cells was significantly higher than that of the control while caspase-9 activity did not change significantly. Based on the result obtained from our study, the apoptosis pathway involved in S. chorassanica-induced cell death may be through the extrinsic pathway and it can be a novel promising candidate in the treatment of cancer.

liver injury induced by viruses, chemicals and drugs can be protected by different medicinal plants. Feijoa sellowiana (Myrtaceae) is an evergreen bush native to southern areas of South America, as well as Iran where the fruits are very popular. Feijoa has shown a potent antimicrobial effect. Morever, the antioxidant activity of total Feijoa extract has also been reported. MDMA or ecstasy is a ring-substituted amphetamine derivative which has been abused as a widespread recreational drug by the young generation. Liver is a target organ for MDMA toxicity. In fact, this sense MDMA is metabolized by cytochromes P4502D, 2B and 3Aand reactive metabolites are readily oxidized to the corresponding o-qiuinones and reactive oxygen species (ROS).This study investigated whether methanilic Feijoa sellowiana fruits can produce biochemical changes using the Isolated Rat Liver Perfusion (IRLP) system. The, the liver was perfused with different concentrations of the extract (10, 20, 40, 50,100 mg/kg), added to the buffer and perfused within 2 h. During the perfusion we tried to find out the antioxidant activity or liver protective effect of Feijoa, by determinining amino-transferases activities (SGOT and SGPT) and glutathione reductase (GSH) level in comparison with the positive and negative controls. Subsequently, sections of liver tissue were examined for any histopathological changes. The results revealed that the activities of SGOT and SGPT were seriously decreased and GSH level was significantly increased by the Feijoa extract. Overall, necrosis in the liver parenchyma was decreased. These findings revealed that Feijoa sellowiana is an effective hepatoprotective plant.

The acute and sub-acute toxicity of safranal were studied in rat and mice within 2 and 21 days after exposure, respectively. For subacute toxicity, changes in weight as well as biochemical, hematological and pathological parameters were studied. The intraperitoneal LD50 values of safranal were 1.48 mL/kg in male mice, 1.88 mL/kg in female mice and 1.50 mL/kg in male rats. Oral LD50 values were 21.42 mL/kg in male mice, 11.42 mL/kg in female mice and 5.53 mL/kg in male rats. For subacute toxicity, safranal was administered orally to male rats once daily for 21 days. In hematological tests, a significant decrease in RBC counts, hematocrit, hemoglobin and platelets were observed. Safranal decreased cholesterol, triglyceride and alkalin phosphatase. Lactate dehydrogenase and serum urea nitrogen were increased by safranal. Histological studies indicated that safranal did not have any toxic effect on the heart, liver and spleen. However, pathological changes were seen in the kidney and lung. According to LD50 values, safranal was low-toxic in acute intraperitoneal route and practically non-toxic in acute oral administration in both mice and rats. In subacute toxicity, safranal changed some hematological and biochemical parameters.

In this study, we investigate the immunostimulatory effects of alcoholic extract of the coffee seed on cell-mediated immune response andcyclophosphamide-induced (CP) immunosuppressed mice. The assessment of cellular immune function was carried out by the measurement of delayed-type hypersensitivity (DTH) response. According to the literature survey, cyclophosphamide has only suppressing effect on the lymphoid organ, white blood cell (WBC) and other parts of humoral immunity. Humoral immunity was assessed by the hemagglutination antibody titre. Mice were treated with three doses of extract (50, 150 and 250 mg/Kg body weight per os). Relative organ weight and WBC counts were also studied in these animals. At doses of 50 and 150, a significant increase (p < 0.05) in relative organ weight of spleen and thymus was observed but there was no effect on kidney and liver weights. WBC counts was also increased significantly (p < 0.001) in all doses of the plant extract. Coffea arabica extract elicited a significant (p < 0.001) increase in the DTH response at doses of 50 and 150 mg/Kg, but the change at higher dose of 250 mg/Kg was not statistically significant. In the HT test, plant extract also showed modulatory effect at all doses groups. Over all, coffee seed showed the stimulatory effect on cellular immune function and cyclophosphamide induced immunosuppression in mice.

Diabetes is one of the most common metabolic disorders and is interrelated to oxidative stress-induced diseases. According to the role of dietary antioxidants in control and prevention of diabetes, this study was aimed to evaluate the effect of green tea extract on serum glucose levels and serum and hepatic total antioxidant capacity (TAC) and lipid (MDA) in diabetic rats. Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (55 mg/Kg). Alcoholic extract of green tea (100, 200 mg/Kg) was given by oral gavage to normal and diabetic rats for 4 weeks. Finally, serum glucose and serum and hepatic levels of MDA and TAC were measured and analyzed statistically. Data showed that green tea extract at dose of 200 mg/Kg significantly decreased the serum glucose levels, serum and hepatic MDA concentration and increased the total antioxidant capacity in diabetic rats (p < 0.05). Green tea supplementation also increased hepatic TAC in normal rats (p < 0.05). The antihyperglycemic and antioxidative features of green tea make it an attractive candidate for the prophylactic treatment of diabetes, although further investigation is needed to determine exact dose and duration of supplementation.

In this study, the effects of Siraitia grosvenorii fruits extracts (SGFE) on physical fatigue were investigated. One hundred and forty-four mice were randomly divided into four groups: control group, low-dose SGE-treated group, middle-dose SGE-treated group and high-dose SGFE-treated group. The animals of control group received an oral administration of physiological saline in a volume of 2.5 mL, and the animals of treated group received the same volume of SGFE (100, 200 and 400 mg/Kg bodyweight, once a day) for 28 days. After 28 days, anti-fatigue effects of SGFE were assessed 10 h after the last treatment by forced swimming test and some biochemical parameters related to fatigue, including blood lactic acid, serum urea nitrogen, liver glycogen and muscle glycogen were measured. The data showed that SGFE can extend the swimming time of the mice, as well as increasing the liver and muscle glycogen contents, but decrease the blood lactic acid and serum urea nitrogen levels. These results indicated that Siraitia grosvenorii fruitsextracts had significant anti-fatigue effects on mice and these effects were dose-dependent.

In the present study, protective effect of Teucrium polium L. (Labiatae) extract on acetaminophen-induced hepatotoxicity was investigated in mice. Animals were divided into six groups, each group consist of 8 mice. Group one as the negative control group received normal saline, while group two received only crude extract of T. polium L. (500 mg/Kg) for five days and group three as the positive group received acetaminophen (500 mg/Kg). Groups four, five and six received crude extract in doses of 125, 250 and 500 mg/Kg, respectively, and on the fifth day, one hour after the last administration, acetaminophen was given orally (500 mg/Kg). Then on the 6th day, animals were sacrificed, their blood was collected to determine serum enzyme activities of ALT, AST and ALP to measure the serum levels of directed and total bilirubin. The livers were removed for histological examination. The results of this study showed the protective effect in all doses but the most significant protection was observed in doses of 250 and 500 mg/Kg (p < 0.05). Also these findings were supported and confirmed by histological examination.

Considerable evidence suggests that mitochondrial dysfunction contributes to the toxicity of uranyl acetate (UA), a soluble salt of depleted uranium (DU). We examined the ability of the two antioxidants, beta-glucan and butylated hydroxyl toluene (BHT), to prevent UA-induced mitochondrial dysfunction using rat-isolated kidney mitochondria. Beta-glucan (150 nM) and BHT (20 nM) attenuated UA-induced mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and glutathione oxidation. Beta-glucan and BHT also prevented the loss of mitochondrial membrane potential (MMP) and mitochondrial swelling following the UA treatment in isolated mitochondria. Our results show that beta-glucan and BHT prevented UA-induced mitochondrial outer membrane damage as well as release of cytochrome c from mitochondria. UA also decreased the ATP production in isolated mitochondria significantly inhibited with beta-glucan and BHT pre-treatment. Our results showed that beta-glucan may be mitochondria-targeted antioxidant and suggested this compound as a possible drug candidate for prophylaxis and treatment against DU-induced nephrotoxicity.

Rifampin, an antibiotic widely used for the treatment of mycobacterial infections, produces hepatic, renal and bone marrow toxicity in human and animals. In this study, the protective effects of vitamin C and n-acetylcysteine (NAC) on the toxicity of rifampin on HepG2 cells were investigated. Human hepatoma cells (HepG2) were cultured in 96-well M of rifampin in the presence of microplate and exposed to 10, 20, 50 and 100 vitamin C (0.1 mg/mL) and NAC (0.2 mg/mL). Protective effect of the two drugs against rifampin toxicity was assessed by MTT assay. Results show that both vitamin C and NAC significantly inhibited HepG2 cellular damage due to rifampin, and vitamin C was relatively more potent than NAC. Rifampin is metabolized by the liver and its toxic metabolites are responsible for the drug›s hepatic toxicity. Based on our results, it seems that reactive metabolites are the main agents responsible for rifampin hepatotoxicity. The importance of this finding is that if vitamin C or NAC do not affect the antibacterial activity of rifampin, they could be used as preventive agents in rifampin users.

The aim of this study was to characterize the effect of typhoid fever on pharmacokinetic parameters of levofloxacin (LF) and compare the pharmacokinetic parameters of the said antibiotic in healthy human volunteers and patients with typhoid fever. Total of 12 subjects were divided into two groups “A” (healthy volunteers) and “B” (typhoid patients). Single oral dose of LF 500 mg was given and 5 mL of blood was collected from each subject at 0, 0.25, 0.5, 1, 2, 3, 6, 12, 24, 36 and 72 h. Plasma concentrations of LF were measured by HPLC. Pharmacokinetic parameters were calculated from plasma concentration-time data by using MW/PHARM pharmacological analysis. In healthy volunteers, the average pharmacokinetic parameters were as Cmax (6.79 μg/mL), Tmax (1.84 h), T½ (10.03 h), Ka (2.23 h-1), AUC (110.09 µgh/mL), Vd (85.84 L), Cl (4.57 L/h) and in typhoid patients were Cmax (6.90 μg/mL), Tmax (1.82 h), T½ (9.42 h), Ka (2.21 h-1), AUC (105.55 µgh/mL), Vd (64.31 L), Cl (4.75 L/h). The difference between pharmacokinetic parameters of LF in healthy human volunteers and typhoid patients was calculated by using unpaired t-test. As the p-value in case of all pharmacokinetic parameters was more than 0.05, the difference between pharmacokinetic parameters in both healthy human volunteers and typhoid patients was insignificant. It is concluded that there is no need to adjust the dose of LF in typhoid patients.

The biological application of nanoparticles (NPs) is a rapidly developing area of nanotechnology that raises new possibilities in the treatment of human cancers. The cytotoxicity was evaluated by MTT and LDH assays. The apoptotic effect of free ICD-85 and ICD-85 NPs on HeLa cells was assessed using caspase-8 colorimetric assay. The MTT assay showed that ICD-85 NPs could enhance the in-vitro cytotoxicity against HeLa cellscompared to the free ICD-85. The IC50 value at 72 h was reduced from 25 ± 2.9 μg/mL for free ICD-85 to 15.5 ± 2.4 μg/mL for ICD-85 NPs. However, LDH assay demonstrated that ICD-85 has dose-dependent cytotoxicity on HeLa cells while ICD-85 NPs exhibited weaker cytotoxicity on same cells. The results also indicate that ICD-85-induced apoptosis on HeLa cells is associated with the activation of caspase-8. Moreover, caspase-8 assay analysis demonstrated that the ICD-85 NPs induced a higher apoptotic rate in HeLa cells compared to free ICD-85. Our results demonstrated that the encapsulation of ICD-85 enhances its anti-proliferative effects. Taken together, these results suggest that the delivery of ICD-85 in nanoparticles may be a promising approach for the treatment of the cancer.

Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.). possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor–kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)-dependent inflammatory responses in lipopolysaccharide (LPS)-activated microglia. In this paper, BV2 microglia were pretreated with different concentrations of oxymatrine (1, 10 and 20 μg/mL) for 30 min as followed by stimulation with LPS (1 µg/mL) for different times (30 min, 1 h, 3 h, and 6 h). Concentrations of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) in supernatant, mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), cytosolic inhibitor of kappa B-alpha (I-κBα) and phospho-I-κBα and nuclear p65 protein levels, and the phosphorylations of MAPK molecules such as extracellular-signal-regulated kinase (ERK) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK) were determined. It was shown that oxymatrine inhibited the productions of NO, PGE2, TNF-α, IL-1β and IL-6, attenuated the mRNA levels of iNOS and COX-2, suppressed the phosphorylation of I-κBα in cytosol, decreased the nuclear levels of p65, and also blocked ERK, p38 and JNK pathway in LPS-stimulated BV2 microglial cells in a dose-dependent manner. According to the results; It is suggested that oxymatrine may attenuate inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in the brain disorders.

This study investigates the effectiveness of the antinociceptive effects of diclofenac, an NSAID, on the nociceptive behavior of morphine-treated rats on formalin test.Rats were treated with morphine-containing drinking water for twenty one days, which induced morphine dependence. The antinociceptive effects of 8, 16, and 32 mg/kg doses of diclofenac were then evaluated and compared with distilled water in a formalin-based model of pain.Diclofenac potentiated pain suppression in morphine-dependent rats during the interphase of the formalin test and reduced the pain score during phase II. The post-test analysis revealed that both 16 mg/kg (p < 0.0001) and 32 mg/kg (p < 0.0001) doses of diclofenac had a significant effect on the interphase, while 8 mg/kg (p < 0.05), 16 mg/kg (p < 0.05), and 32 mg/kg (p < 0.01) doses of diclofenac significantly affected phase II. In contrast, the antinociceptive effects of diclofenac on morphine-naïve rats were observed during phase II only with the a 32 mg/kg dose (p < 0.05).In general, these results suggest that the long-term use of morphine in rats increases their sensitivity to the antinociceptive effects of diclofenac. Furthermore, the results support the existence of a non-opioid-dependent mechanism of pain suppression during the interphase of formalin test.

Human serum albumin has been used as a model protein for protein folding and ligand binding studies over many decades. Due to its long life period and high concentration in plasma, HSA is highly sensitive to glycation. It is reported that 175 mg/dL glucose concentration is a threshold of kidney activity for the beginning of excretion of glucose. pH denaturation of HSA in absence and presence of different concentrations of glucose is studied and based on the Pace two-state model, the findings are analyzed. In addition, florescence emission data of albumin range in the period of 300-500 nm was depicted. The amounts of free energy change and [D]1/2 parameters of unfolding in correspond to florescence date indicate that glucose induces fine structural change in human serum albumin. Results showed that 175 mg/dL glucose concentration is a critical point for albumin structural and functional alteration.

Pain in ICU patients should be managed effectively and safely. Fentanyl and Paracetamol are used frequently in ICU. However experience using IV Paracetamol in the setting of critically ill patients is limited. We evaluated the analgesic effect and adverse reactions of intravenous Paracetamol compared to Fentanyl in ICU patients with mild to moderate pain. Forty patients in a general ICU were randomized into two groups of IV Paracetamol and IV Fentanyl in a single blinded fashion. Pain was assessed by Visual Analogue Scale (VAS) before drug administration and six hourly for 48 h of 1 g IV Paracetamol every 6 h for 48 h in the first group and 25 µg Fentanyl intravenously every three hours for 48 h in the second group. Patients were monitored for significant adverse reactions particularly of CNS and hepatic nature. Results showed the age, sex and pain score before analgesia was matched in both groups. Pain scores were similar in both groups at 24 h 2.60 (± 1.2) and 2.40 (± 1.5) and at 48 h 2.25 (± 0.96) and 2.05 (± 1.1) in Paracetamol and Fentanyl groups respectively. Clinical and laboratory adverse reactions were also similar in both groups. The analgesic properties of Paracetamol and Fentanyl were similar in this study. We did not observe any significant adverse effects in the two groups. Clinical and laboratory findings including liver functions remained without any statistically significant difference in two groups. This study demonstrates intravenous Paracetamol may be as safe and effective as Fentanyl in ICU patients with mild to moderate pain.

Glycine allele at codon 16 has previously been associated with the increase in asthma severity, bronchial hyperresponsiveness and also the increase in inhaled corticosteroid dependence. This study was designed to evaluate the genetic alleles in mild asthma.Thirty-four patients with diagnosis of mild asthma (FEV1 ≥ 80%, positive methacholine test) and body mass index (BMI ≤ 30 Kg/m2) were included in the study. They could only use short acting beta-2 agonists for asthma control. Smoking, infection, occupational sensitizers’ exposure, gastroesophageal reflux, diabetes mellitus and heart failure were also considered as exclusion criteria. All patients were genotyped at 16th and 27th codons.Among all, 20 (58.8%) Arg/Gly, 14 (41.2%) Arg/Arg and no Gly/Gly genotype were detected at codon 16. Genotyping at codon 27 revealed 2 (5.9%) Glu/Glu, 13 (38.2%) Glu/Gln and 18 Gln/Gln (52.9%).Based on the obtained results, Arg/Gly mutation had a higher rate among the studied subjects compared to Arg/Arg polymorphism. This is a pilot study which shows a probable usefulness of genotyping for predicting of asthma severity.

There is possibility of microbial contamination of any single-dose vials (SDVs), multiple-dose vials (MDVs) and admixtures (ADXs) during the preparation and injection to the patients that could be resulted in bloodstream infection. The goal of this study was to investigate the microbial contamination of MDVs and SDVs after multiple use and ADXs prepared by nursing staff in the treatment room versus those prepared by the hospital pharmacist in the clean room. The sterility of 43 opened MDVs and SDVs, 92 prepared ADXs in treatment room and 17 prepared ADXs in clean room were studied by membrane filtration method. Only one of 92 ADXs prepared in treatment room was contaminated with Bacillus subtilis (%1.1) and none of the ADXs prepared in clean room, MDVs and SDVs had microbial contamination. Although good sanitization practices and training of nurses could reduce the risk of microbial contamination in traditional units, using clean room for preparation of parenteral products could be the best strategy.

Nearly 15% to 25% of patients in general hospitals have a catheter at some time during their stay. Up to 97% of nosocomial urinary tract infections (UTIs) are related to catheter. The type of bacteremia is usually polymicrobial which makes the treatment more difficult. Previous studies showed an increase in mortality from bacteremia in these patients. The aim of the present study was to compare the prevalence of UTIs among patients with and without catheter, and to detect the type of bacteriuria and antibacterial resistance pattern. In this cross sectional study, samples were taken between Jan 2011 and July 2011. 678 hospitalized patients in different wards of Afzalipour hospital, Kerman- Iran, were enrolled in the study. E-test was applied to detect the pattern of resistance to gentamicin, nitrofurantoin, ciprofloxacin, ceftriaxon and co-trimoxazole. Results showed positive culture samples in 86% of female patients. Escherichia coli, Candida and Staphylococcus aureus were detected in 72, 20 and 7 percent of the positive cultures, respectively. 52.3% of detected E.coli was sensitive to gentamicin, 62% to ceftriaxone, 71.4% to ciprofloxacin, and 91.9% were sensitive to nitrofurantoin. Therefore, the most sensitive antibiotics in UTIs were ciprofloxacin and ceftriaxone. Unfortunately, the rate of antibacterial drug resistance was high in comparison with developed countries. Wise selection of antibiotics at hospitals and increasing the knowledge of patients to prevent self use of antibiotics can reduce antimicrobial resistance.

Hot flash is among the most common complaints of menopausal women, affecting their career, social activities and quality of life. This study aimed to investigate the effects of Valerian on hot flashes in menopausal women. In this double blind clinical trial, 68 menopausal women with the chief complaint of hot flash were enrolled using sampling at hand and were randomly divided into drug and placebo groups. The women in the drug group were prescribed 255 mg Valerian capsules 3 times a day for 8 weeks. The women in the placebo group were prescribed identical capsules filled with starch. Then, severity and frequency of hot flashes were measured and recorded through questionnaires and information forms in three levels (2 weeks before, four and eight weeks after the treatment). The Severity of hot flashes revealed a meaningful statistical difference pre- and post- Valerian treatment (p <0.001) while this difference was not meaningful in the placebo group. Further, the comparison of the two groups regarding the severity of hot flash after the treatment showed a meaningful statistical difference (p <0.001). Valerian has also led to a reduction of hot flash frequencies 4 and 8 weeks after the treatment (p <0.001) but this difference was not meaningful in drug like group. Valerian can be effective in treatment of menopausal hot flash and that it can be considered as a treatment of choice for reduction of hot flashes among the women who are reluctant to receive hormone therapy due to fear or any other reason.

The multiple etiologic factors involved in acne make the use of various medications necessary to treat the condition. This study aimed to determine the efficacy of mupirocin and rifampin used with standard treatment in the management of acne vulgaris. In a multicentre, randomized controlled, triple-blinded study, a total of 105 acne patients, with a clinical diagnosis of moderate to severe acne,were randomizedly divided into three groups (35 per group), for treatment of acne. The first group was treated with standard treatment alone, the second group received mupirocin plus standard treatment and the third group received rifampin plus standard treatment.There were three study visits according to Global Acne Grading System (GAGS): at baseline and weeks 6 and 12. The absolute changes of GAGS score from baseline to week 6 and 12 demonstrated a reduction in the mean score of GAGS in the three treatment groups (p < 0.001). Due to the difference between GAGS score at the baseline of study, the data were adjusted using the general linear model. The findings showed that all of the treatments significantly improved acne lesions. Nevertheless, none of the treatments was shown to be more effective than the others (p = 0.9). The three treatments were well tolerated, and no serious adverse events were reported. These findings provide evidence on the efficacy of combining mupirocin and rifampin with standard treatment in the management of acne vulgaris, although none of the treatments had superior efficacy compared with the others.

The aim of this study was to determine the frequency of medication errors happened during the preparation and administration of intravenous (IV) drugs. This study was designed as prospective cross-sectional evaluations by direct unconcealed observation in a setting consisted of orthopedic, general surgery and gastroenterology wards of a teaching hospital. Participants were those patients hospitalized in these wards along with nurses responsible for preparation and administration of IV medications. Medication errors occurred in the process of preparation and administration of IV drugs, were recorded by a pharmacist. The frequency of medication errors with suggesting a solution to overcome was the main outcome of this study. Details of the preparation and administration stages of the observed drugs were compared to an instructed checklist prepared by an expert clinical pharmacist. From a total of 357 preparation and administration episodes, the most common type of error (%20.6) was the injection of bolus doses and infusion faster than the recommended rate. Metronidazole had the highest rate of error (%24.3). IV rounds conducted at 12 p.m. had the most rate of error (%26.3). Errors happened in the administration process were more prevalent than those in the preparation. No significant correlation was found between the frequency of errors and nurses’ demographic data. This study revealed that the errors happened in the preparation and administration of IV drugs is prevalent. Improving the medication safety by the implementation of clinical pharmacists’ prepared protocols at the point of care is an important concern.

Rational prescribing increases the quality of health care and patient outcomes. In this study, the quality of drug prescription in specialist physicians in Isfahan province of Iran was assessed for evaluating the rational use of drugs and improving the therapeutic outcomes.This retrospective survey was conducted on a total of 7999530 prescriptions from all general and specialist physicians. The most frequently prescribed drugs and World Health Organization (WHO) prescribing indicators were evaluated in prescriptions of all medical specialties.Assessment of prescribing indicators revealed poor-quality prescribing performance by general practitioners including high number of medicines prescribed per clients, wide range of prescribed medicines in each prescription, over-prescribing of antibiotics, corticosteroids and injectable drugs. There were also wide differences in the pattern of drug prescribing depending on the medical specialties. The average number of drugs prescribed per encounter by specialists was less than generalists except for the cardiologists. General practitioners, otorhinolaryngologists and general surgeons prescribed more antibiotics. Orthopedic surgeons and general practitioners were the top prescribers of injectable and corticosteroid drugs. The most frequently prescribed medicine groups varied according to the prescribers’ medical specialty. Analgesics and antipyretics were the most prescribed preparations in general medicine, pediatrics, orthopedics, general surgery and cardiology.Because of the wide variability in the pattern of drug prescribing depending on the medical specialties, specific performance indicators should be developed for each specific medical specialty for better assessing of prescribing quality in specialist physicians.

Drug-drug interactions (DDIs) can lead to increased toxicity or reduction in therapeutic efficacy. This study was designed to assess the incidence of potential drug interactions (PDI) and rank their clinical value in post coronary care unit (Post-CCU) of a teaching hospital in Tehran, Iran.In this prospective study, three pharmacists with supervision of a clinical pharmacist actively gathered necessary information for detection of DDIs. Data were tabulated according to the combinations of drugs in treatment chart. Verification of potential drug interactions was carried out using the online Lexi-Interact™ 2011.A total of 203 patients (113 males and 90 females) were enrolled in the study. The mean age of patients was 61 ± 12.55 years (range = 26-93). A total of 90 drugs were prescribed to 203 patients and most prescribed drugs were atorvastatin, clopidogrel and metoprolol. Mean of drugs was 11.22 per patient. A total of 3166 potential drug interactions have been identified by Lexi-Interact™, 149 (4.71%) and 55 (1.73%) of which were categorized as D and X, respectively. The most serious interactions were clopidogrel+omeprazole and metoprolol+salbutamol.Drug interactions leading to serious adverse effects are to be cautiously watched for when multiple drugs are used simultaneously. In settings with multiple drug use attendance of a pharmacist or clinical pharmacist, taking the responsibility for monitoring drug interactions and notifying the physician about potential problems could decrease the harm in patient and increase the patient safety.

Internationalization is a matter of committed decision-making that starts with export marketing, in which an organization tries to diagnose and use opportunities in target markets based on realistic evaluation of internal strengths and weaknesses with analysis of macro and microenvironments in order to gain presence in other countries. A developed model for export and international marketing of pharmaceutical companies is introduced. The paper reviews common theories of the internationalization process, followed by examining different methods and models for assessing preparation for export activities and examining conceptual model based on a single case study method on a basket of seven leading domestic firms by using mainly questionares as the data gathering tool along with interviews for bias reduction.Finally, in keeping with the study objectives, the special aspects of the pharmaceutical marketing environment have been covered, revealing special dimensions of pharmaceutical marketing that have been embedded within the appropriate base model. The new model for international activities of pharmaceutical companies was refined by expert opinions extracted from result of questionnaires.