Analysis of only 0-1 min clip or 1-4 min Clip for focal liver lesions during contrast-enhanced ultrasonography

Purpose: To evaluate the reliability of analysis of only 0-1min clips and 1-4min clips versus the entire clips in performing contrast-enhanced ultrasonography (CEUS) of focal liver lesions (FLLs). Methods: Contrast-enhanced ultrasonography (CEUS) examinations of 43 single FLLs were performed. All clips were analyzed in three ways, the entire clips, 0-1 min clips and 1-4 min clips, benign or malignant diagnosis and pathological diagnosis of each FLL were concluded by the three ways subsequently. Results: The results of correct diagnosis were assessed using Chi-square test. There was no difference with regard to benign or malignant diagnosis, between 0-1min clips and the entire clips, or between 1-4 min clips and the entire clips (p = 0.243 and p = 0.747, respectively). Moreover, no significant differences in pathological diagnosis existed between 0-1min clips and the entire clips, and 1- 4min clips versus entire clips (p=0.808 and p = 0.808, respectively). No significant differences existed among CEUS entire clip, 0-1min clip and 1-4min clip in identifying FLLs, and based on which the diagnosis of two different FLLs during CEUS with only one injection of contrast agent can be available. Conclusion: Only 0-1min clips or 1-4 min clips can be used to instead of the entre clip in performing CEUS of FLLs.

Use of BARD scoring system in non-alcoholic fatty liver disease patients and its correlation with ultrasonographic grading in Gizan, Saudi Arabia

Purpose: To assess the efficacy of the BARD scoring system in Saudi non‐alcoholic fatty liver disease (NAFLD) patients attending Gizan General Hospital and to identify the clinical variables associated with advanced fibrosis. . Methods: The cross-sectional study involved 120 patients aged ≥ 18 years who attended the Ultrasound Department of Gizan General Hospital, Gizan, Saudi Arabia, during January – June 2013. BARD scoring system comprised the following variables: body mass index (BMI) ≥ 28 = 1 point, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio ≥ 0.8 = 2 points, and type 2 diabetes mellitus = 1 point. Results: Patients with advanced fibrosis were older (55.0 years) than patients with no/mild fibrosis (48.6 years), albeit not significantly so. A higher BMI was associated with advanced fibrosis in males, females and all study participants (p = 0.013, 0.016 and 0.001, respectively). Advanced fibrosis was more common in older patients with a higher weight to height ratio. Logistic regression suggested that age ≥ 50 years was associated with a 2.52-fold increase in the risk of advanced fibrosis, but this did not have a significant clinical impact (p = 0.087). BMI > 28 was associated with a 26.73-fold increased risk of advanced fibrosis, while AST/ALT ≥ 0.8 was associated with an 18.46-fold increased risk of advanced liver fibrosis (p = 0.002 and 0.006, respectively). Conclusion: The major risk factors for advanced fibrosis using BARD scoring system in patients with NAFLD were old age, BMI > 28, and AST/ALT ≥ 0.8. In addition, grade 3 ultrasonographic fatty liver significantly correlated with advanced fibrosis.

Community pharmacists’ understanding, attitudes, practice and perceived barriers related to providing pharmaceutical care: a questionnaire-based survey in Macao

Purpose: To explore the knowledge, attitudes, practice and perceived barriers of community pharmacists regarding provision of pharmaceutical care as well as provide recommendations on how to advance the service during the early stage of development in Macao. Methods: A questionnaire comprising 10 items was used to collect respondents’ demographic information and to evaluate their understanding of pharmaceutical care, attitude towards service provision, current practice and perceived barriers. Descriptive and comparative analysis of the results was conducted. Results: While 95 % of the participating pharmacists agreed that patients’ health was their primary responsibility, only 57 % believed that they can provide better pharmaceutical care in the future. The majority spent most of their work time counselling patients (90 %) and checking prescription (70 %). Only a small portion monitored adverse drug reaction and drug compliance (44 %), engaged in health screening or drug safety promotion (20 %) or maintained patient medication records (4 %). Insufficient communication with physicians (90 %), lack of time (79 %) and lack of physical space at the pharmacy (76 %) were considered the most significant barriers. Conclusion: A suboptimal level of pharmaceutical care is provided by pharmacists in Macao. Considering the barriers identified and integrating other country experiences, establishing an enabling atmosphere using policy and regulatory measures is the fundamental element for advancing pharmaceutical care by community pharmacists.

Pharmacists’ knowledge and perception of topical antibacterial drug dispensing in community pharmacy setting in Kedah, Malaysia

Purpose: To assess Pharmacists’ Perceptions and Experiences of Topical Antibacterial Drug Dispensing in Community Pharmacy Setting in Kedah State, Malaysia in order to minimize drug resistance issues. Methods: A cross-sectional study involving a pre-validated questionnaire was conducted in community pharmacies within Kedah State, Malaysia. Descriptive statistics and Spearman’s correlation coefficient were used for data analysis. The collected were analysed using statistical package for social sciences (SPSS) version 18.0. Results: The result shows that, 53.4 % of CPs in Kedah State perceived that topical antibacterial is not necessary for every topical bacterial infection. Fusidic acid was the most frequently dispensed topical antibacterial drug while superficial wound was reported to be the most frequently encountered topical bacterial infection. CPs (12.60 %) encountered antibacterial resistance cases but none reported them. The drug that had resistance issue was neomycin. Conclusion: CPs in Kedah State, Malaysia generally have the right perceptions on the dispensing of topical antibacterial drugs. However, their knowledge on the rational use of topical antibacterial drugs and vigilance on antibacterial resistance issue need improvement.

Comparison of access to medicines between Klang Valley and East Coast of peninsular Malaysia for children living in poor households

Purpose: To compare access to medicines in children living in poor households (income of USD1/person/day) between urbanised Klang Valley and rural East Coast of Peninsular Malaysia. Methods: A semi-structured interview was conducted with caregivers to determine demographics, access to medicines, knowledge, attitude and practice of parents in obtaining medicines for children. Results: There was no significant difference socio-demographically between poor households in Klang Valley (N = 58) and East Coast (N = 40). The study found that access to medicine for children (N = 325) in the households was adequate, where all households that reported illness in the children over the last 1 month and the last 6 month periods, obtained medicines and 99 % of the children were fully immunized. Qualitative analysis showed that poor households face several barriers in accessing medicines for their children such as financial, transportation, physical and attitudinal. Conclusion: Access to medicines for children living in poor households in both areas were similar and adequate. However, barriers to access remain and further studies are required.

Erectile dysfunction: prevalence, risk factors and involvement of antihypertensive drugs intervention

Purpose: To explore the literature regarding prevalance, risk factors and the involvement of antihypertensive drugs in erectile dysfunction (ED). Methods: Original research articles, reviews, editorials and case reports published in English language on the prevalence of sexual/erectile dysfunction in hypertensive men taking antihypertensive drugs and risk factors were identified through a search of four bibliographic databases, namely, PubMed, EMBASE, CINAHL and EBSCO Health. Results: Recent analyses suggest that hypertensive men of almost all age groups suffer from ED but it is more prevalent in elderly male patients. The involvement of β-blockers was found to be controversial. Nevertheless, some evidence had been found regarding the use of propranolol in high doses. Conclusion: The present review indicates the need for research to unravel the role of β-blockers in the manifestation of ED in hypertensive males, whom there are no contributory factors such as sedentary lifestyle, aging, stress and anxiety, etc.

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques. Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure. Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0-∞ , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %). Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.

Autophagy in photodynamic therapy

Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in human diseases. It is a highly conserved intracellular degradation system in eukaryotes for removal and recycling of cytoplasmic components including damaged proteins and organelles to obtain energy. The relationship between cancer and autophagy has been extensively studied in recent years. In cancer and cancer therapy, autophagy acts as a double-edged sword. Photodynamic therapy (PDT) is a kind of tumor therapy applied with a tumor-localizing photosensitizing agent which is followed by activation with the light of a specific wavelength. How much is autophagy involved in photodynamic therapy? The work in this area is still limited.

Development of paclitaxel-loaded liposomal systems with anti-her2 antibody for targeted therapy

Purpose: To develop liposome formulations containing monoclonal antibody anti-HER2 (MabHer2), and Paclitaxel (PTX). Methods: Seven different liposomal systems containing PTX, or MabHer2 or a combination of PTX and MabHer2 were made using lipid film hydration technique and sonication. The effects of liposome preparation conditions and extraction methods on antibody structure were investigated by polyacrylamide gel electrophoresis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The characteristics of the liposomes were determined by a zetasizer, while drug-loading efficiency was evaluated by high-performance liquid chromatography. The cytotoxic effect of the liposome formulations was evaluated on MDA-MB-453 (HER2+) and MCF-7 (HER2-) breast cancer cell lines by MTT assay. Results: The antibody was not significantly affected by the stress conditions and the method of extraction. The particle size of liposomes was < 200 nm while the amount of incorporated PTX was 97.6 % for liposome without cationic agent and 98.2 % for those with cationic agent. Recovery of MabHer2 was 94.38 % after extraction. Combined PTX/MabHer2 liposome was more toxic on HER2 overexpressing positive MDA-MB-453 cell line than PTX-loaded liposomes and MabHer2. MabHer2 and combined PTX/MabHer2 liposomes showed no toxic effects on HER2 overexpressing negative MCF-7 cells relative to cationic PTX-loaded liposomes. Conclusions: This results obtained show that PTX can be encapsulated successfully into liposoma systems and that owing to Her2 specific antibody, these systems can be delivered directly to the target cell.

Affinity purification of recombinant human plasminogen activator from transgenic rabbit milk using a novel polyolresponsive monoclonal antibody

Purpose: To develop processes for effective isolation and purification of recombinant human plasminogen activator (rhPA) from transgenic rabbit milk. Methods: Immunoaffinity chromatography was selected and improved by a special polyol-responsive monoclonal antibody (PR-mAb). Alteplase was used as immunogen because of its similarity to rhPA in terms of structure. The PR-mAb was prepared by hybridoma technology and screened by ELISA-elution assay. Screening antibody was performed using rhPA milk in an ELISA-elution assay. The antibody clone C4-PR-mAb was selected for immunoaffinity chromatography. The rhPA was effectively bound to immobilized C4-PR-mAb on the column and was eluted with Tris buffer comprising 0.75 mol/L ammonium sulfate and 40n% propanediol (pH7.9). The rhPA was further purified by passing through Chromdex75 gel filtration column. Results: There were 12 hybridoma strains selected into the polyol-responsive mAbs screen step and three hybridoma strains were superior for producing PR-mAbs (C1, C4, C8). The rhPA can be purified from transgenic rabbit milk and maintained a higher thrombolytic activity in vitro by FAPA. Conclusion: The results demonstrate the suitability of the alternative approach used in this study. Using immunoaffinity chromatography and gel filtration column is feasible and convenient for extracting rhPA from milk, and should be useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

Molecular detection of Brucella melitensis in sheep and goat milk in Iran

Purpose: To detect Brucella melitensis in the milk of reared sheep and goats from Isfahan and Shahrekord regions, Iran. Methods: A total of 225 milk samples (sheep = 125; goat = 100) were collected from Isfahan and Shahrekord regions, Central Iran. Polymerase chain reaction (PCR) was used to detect the presence of B. melitensis in the milk following standard procedures. Results: From 225 milk samples, 20 (8.9 %) were positive for B. melitensis. Out of 125 sheep milk, 12 (9.6 %) had B. melitensis, and of these, 8 (66.6 %) were milk collected from Shahrekord and 4 (33.3 %) from Isfahan region. On the other hand, out of 100 goat milk samples, 18 (18 %) were positive for B. melitensis, out of which 10 (55.5 %) were from Shahrekord and 8 (44.4 %) from Isfahan. Conclusion: The findings show that B. melitensis is present in a significant proportion of caprine and ovine milk in a section of Iran.

Improved production of chlorogenic acid from cell suspension cultures of Lonicera macranthoids

Purpose: To evaluate the potential of Lonicera macranthoids Hand. -Mazz. Yulei1 suspension culture system for enhanced production of the main secondary metabolite, chlorogenic acid. Methods: The callus of L. macranthoides Hand.-Mazz. “Yulei1” was suspension cultured in B5 liquid medium supplemented with different plant growth regulators. Biomass accumulation was calculated by weight method and chlorogenic acid production was measured using high performance liquid chromatography (HPLC). HPLC was carried out on C18 analytical column at 35 °C and the detection wavelength was set at 324 nm. Results: The results showed that maximum accumulation of biomass and chlorogenic acid were achieved 15 days after culture growth. The optimized conditions for biomass accumulation and chlorogenic acid production were 50 g/L of inoculum on fresh weight basis, B5 medium supplemented with plant growth regulators, 30 - 40 g/L sucrose and initial medium pH of 5.5. Maximum accumulation of chlorogenic acid and biomass were observed when the culture medium was supplemented with 2.0 mg/L6-BA. Optimal accumulation of chlorogenic acid was observed using combination of hormones 2.0 mg/L 6-Benzyladenine (BA) + 0.5 mg/L2, 4-Dichlorophenoxyacetic acid (2,4-D), while optimal accumulation of biomass was observed with 2.0 mg/L 6-BA + 2.0 mg/L2, 4-D. In addition, phenylalanine also contributed to the synthesis of chlorogenic acid at a concentration > 50 mg/L. Conclusion: Cell suspension cultures of L. macranthoides Hand.-Mazz. “Yulei1” have successfully been established. The findings provide a potential basis for large scale production of chlorogenic acid using cell suspension cultures of L. macranthoides.

Ziziphus mauritiana leaf extract emulsion for skin rejuvenation

Purpose: To formulate stable water in oil (W/O) emulsion containing hydroalcoholic crude extract of Ziziphus mauritiana leaves for skin rejuvenation. Methods: Placebo (base) without any plant extract and formulation with 4 % Ziziphus mauritiana extract were prepared by mixing. Samples of the emulsions were subjected to varying storage conditions, i.e., 8, 25, 40 oC and 40 oC + 75 % relative humidity for a period of 4 weeks to predict their stability. During this period, stability parameters, including liquefaction, phase separation, color, electrical conductivity, centrifugation and pH were monitored at specified time intervals. Skin rejuvenation was evaluated using 13 healthy human volunteers over a period of 8 weeks. During this period, various skin parameters such as erythema, melanin level, moisture content, elasticity and sebum content of the skin were evaluated at specified intervals. Results: Both the active formulation and placebo were stable in terms of liquifaction, phase separation and color at all the storage conditions of temperature and humidity. Active formulation showed statistically significant (p < 0.05) improvement in skin melanin as well as in skin moisture and sebum levels, whereas these properties were reduced or even absent in the placebo formulation (p > 0.05). Both active and placebo formulations changed skin elasticity and erythema significantly (p < 0.05). Conclusion: It is evident from the findings that the leaf extract of Ziziphus mauritiana possesses antiaging properties as well as exert skin lightening, moisturizing and viscoelastic effects on human skin.

Antitumor activity of doxorubicine-loaded nanoemulsion against Ehrlich ascites carcinoma-bearing mice

Purpose: To evaluate the antitumor activity of doxorubicine (DOX)-loaded nanoemulsion (NE) on Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. Methods: The mice were divided into five groups (n = 20) according to the administered drug. Groups I - V were labeled as negative control (normal), positive control of the untreated EAC bearing mice (EAC control), blank nanoemulsion (BI-NE), DOX-loaded-NE (DOX/LNE) and free DOX (DOX-Sol), respectively. Cardiotoxicity was assessed by measuring changes in body and organ weight, analyzing serum enzymes and lipids, and examining histological changes in heart tissues by light microscopy. In addition, mean survival time (MST), increase in life span (ILS) and survival (S) of the mice were determined. Results: DOX/LNE group reduced levels of serum enzymes and lowered damage to heart tissues relative to DOX-Sol group. The MST of the DOX/LNE group (80 ± 0.0 days) was significantly greater than that for DOX-Sol group (34.6 ± 8.9 days), while ILS of DOX/LNE (265.30 days) was higher than that of DOX-Sol (57.99 days) by 4.6-fold. Conclusion: Administration of DOX/LNE to EAC-bearing mice improves the efficacy of DOX and reduce its side effects on the heart.

Cardioprotective effects of Dan-Yang-Fu-Xin decoction on chronic heart failure in rats

Purpose: To evaluate the cardioprotective effects and possible mechanisms of Dan-Yang-Fu-Xin decoction (DYFX) in a rat chronic heart failure (CHF). Methods: A CHF rat model induced by ligation of the left anterior descending coronary artery was used to investigate the cardioprotective effects of DYFX. After intragastric administration for 8 weeks, several functional cardiac indices, including fractional shortening (FS), ejection fraction (EF), heart rate (HR) and cardiac output (CO) were assessed by ultrasound examination. Subsequently, inflammatory markers, viz, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), myocardial enzymes, namely, lactate dehydrogenase (LDH) and creatine kinase (CK), were also assessed by enzyme-linked immunosorbent assay (ELISA). Results: Intragastric administration of DYFX (200, 400 and 600 mg/kg) significantly reversed the decrease in body weight and increase in cardiac weight (p < 0.05) induced by CHF. Treatment with DYFX also significantly reversed EF, FS, HR, and CO changes in CHF rats. In addition, DYFX inhibited the two inflammatory cytokines (TNF-α and IL-6) and myocardial enzymes (CK and LDH), suggesting that these effects may include the mechanisms of cardioprotectiion involved in attenuation of CHF. Conclusion: DYFX possesses cardioprotective effects involving CHF. The protective mechanisms may include the suppression of expression of inflammatory mediators and myocardial enzymes.