Injection drug use among street-involved youth in a Canadian setting

Background  

Street-involved youth contend with an array of health and social challenges, including elevated rates of blood-borne infections and mortality. In addition, there has been growing concern regarding high-risk drug use among street-involved youth, in particular injection drug use. We undertook this study to examine the prevalence of injection drug use and associated risks among street-involved youth in Vancouver, Canada.     

Evaluation of the Antioxidant Activity of Sida cordifolia.

Abstract

Sida cordifolia. Linn. (Malvaceae) is commonly known as bala. and widely used in Ayurveda. The comparative antioxidant potential of ethanol extracts of Sida cordifolia. leaf, stem, root, and whole plant was studied. Anti–lipid peroxidation, free-radical scavenging, reducing power, nitric oxide scavenging, superoxide scavenging antioxidant assay, and further estimation of total phenolic content and HPTLC studies were carried out. Various antioxidant activities were compared with standard antioxidants such as BHA, α-tocopherol, and ascorbic acid. Ethanol extracts were found to be a good scavenger of DPPH radical in the order roots > stem > leaves > whole plant with values 76.62%, 63.87%, 58% and 29% at a dose of 1 mg, respectively. All extracts of Sida cordifolia. (SC) have effective reducing power and free-radical scavenging activity. Only the root extract exhibited superoxide-scavenging activity and inhibited lipid peroxidation in rat liver homogenate. All these antioxidant properties were concentration dependent. In addition, total phenolics content of all the extracts of S. cordifolia. were determined as gallic acid equivalents. The highest antioxidant activity was observed in the root extract. The results obtained in the current study indicate that S. cordifolia. is a potential source of natural antioxidants.     

A randomized, crossover study to determine bioequivalence of two brands of dexibuprofen 400 mg tablets in healthy Asian adult male subjects of Indian origin

AIM: To estimate the bioavailability and evaluate bioequivalence of a single dose of a dexibuprofen tablet (test formulation, containing dexibuprofen 400 mg, manufactured by Emcure Pharmaceuticals Ltd., Pune, India) and to compare it with that of a single dose of a Seractil tablet (reference formulation, containing dexibuprofen 400 mg, manufactured by Genus Pharmaceuticals, Bershire, UK) under fasting conditions. SUBJECTS AND METHODS: Using a two-treatment, two-period, two-sequence, randomized crossover design, test and reference formulations were administered as individual single doses to 24 healthy adult Asian male subjects of Indian origin under non-fed conditions, with 4 days washout period between dosing. 17 blood samples were drawn from each subject over a 12-hour period. Pharmacokinetic parameters, Cmax, AUC0-t, AUC0-infinity and Cmax/AUC0-infinity were calculated from the plasma concentration-time data of each individual and during each period by applying non-compartmental analysis. Analysis of variance was carried out using logarithmically transformed and non-transformed values of the stated pharmacokinetic parameters. Data for test and reference formulations were analyzed statistically to test for bioequivalence of the two formulations. RESULTS: All 24 subjects who received the two formulations on two occasions with a washout period of 4 days, completed the study and provided an adequate amount of blood at each sampling point. After oral administration the values of Cmax (microg/ml), tmax (h), AUC0-t (microg/ml x h), AUC0-infinity (microg/ml x h) for reference and test formulations were 23.501 and 22.948, 1.156 and 1.281, 69.795 and 68.455, and 72.454 and 70.208, respectively. ANOVA and CI test showed no significant (p > 0.05) variation in these pharmacokinetic parameters of test and reference formulations. When the AUC0-t values for both formulations for non-transformed and log-transformed data were compared, the test formulation showed a bioavailability of 98.08% and 99.56%, respectively, as compared to reference formulation. These values are within the acceptance limit of 80 - 120%. No adverse events were observed in any of the subjects during the two runs of the study. Both clinical and laboratory parameters of all subjects showed no clinically significant changes. CONCLUSION: The test formulation containing dexibuprofen 400 mg (manufactured by Emcure Pharmaceuticals Ltd., Pune, India) was bioequivalent to reference formulation (Seractil, manufactured by Genus Pharmaceuticals, Berkshire, UK). Both formulations were well tolerated. The test formulation can be considered a pharmaceutically and therapeutically equivalent alternative to Seractil.     

Formulation and evaluation of flurbiprofen microemulsion

The purpose of the present study was to investigate the microemulsion formulations for topical delivery of Flurbiprofen (FP) in order to by pass its gastrointestinal adverse effects. The pseudoternary phase diagrams were developed and various microemulsion formulations were prepared using Isopropyl Myristate (IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant and Sorbitan Monooleate as cosurfactant. The transdermal permeability of flurbiprofen from microemulsions containing IPM and EO as two different oil phases was analyzed using Keshary-Chien diffusion cell through excised rat skin. Flurbiprofen showed higher in vitro permeation from IPM as compared to that of from EO microemulsion. Thus microemulsion containing IPM as oil phase were selected for optimization. The optimization was carried out using 2(3) factorial design. The optimized formula was then subjected to in vivo anti-inflammatory study and the performance of flurbiprofen from optimized formulation was compared with that of gel cream. Flurbiprofen from optimized microemulsion formulation was found to be more effective as compared to gel cream in inhibiting the carrageenan induced rat paw edema at all time intervals. Histopathological investigation of rat skin revealed the safety of microemulsion formulation for topical use. Thus the present study indicates that, microemulsion can be a promising vehicle for the topical delivery of flurbiprofen.     

UV and Three Derivative Spectrophotometric Methods for Determination of Ezetimibe in Tablet Formulation

UV, first, second and third derivative spectrophotometric methods have been developed for the determination of ezetimibe in pharmaceutical formulation. The solutions of standard and sample were prepared in methanol. For the first method, UV spectrophotometry, the quantitative determination of the drug was carried at 233 nm and the linearity range was found to be 6-16 μg/ml. For the first, second and third derivative spectrophotometric methods the drug was determined at 259.5 nm, 269 nm and 248 nm with the linearity ranges 4-14 μg/ml, 4-14 μg/ml and 4-16 μg/ml. The calibration graphs constructed at their wavelength of determination were found to be linear for UV and derivative spectrophotometric methods. All the proposed methods have been extensively validated. The described methods can be readily utilized for the analysis of pharmaceutical formulation. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations.     

Individual,Social, and Environmental Factors Associated with Initiating Methamphetamine Injection: Implications for Drug Use and HIV Prevention Strategies

The purpose of this study was to determine the incidence and predictors of initiating methamphetamine injection among a cohort of injection drug users (IDU). We conducted a longitudinal analysis of IDU participating in a prospective study between June 2001 and May 2008 in Vancouver, Canada. IDU who had never reported injecting methamphetamine at the study’s commencement were eligible. We used Cox proportional hazards models to identify the predictors of initiating methamphetamine injection. The outcome was time to first report of methamphetamine injection. Time-updated independent variables of interest included sociodemographic characteristics, drug use patterns, and social, economic and environmental factors. Of 1317 eligible individuals, the median age was 39.9 and 522 (39.6%) were female. At the study’s conclusion, 200 (15.2%) participants had initiated injecting methamphetamine (incidence density: 4.3 per 100 person-years). In multivariate analysis, age (adjusted hazard ratio [aHR]: 0.96 per year older, 95%CI: 0.95–0.98), female sex (aHR: 0.58, 95%CI: 0.41–0.82), sexual abuse (aHR: 1.63, 95%CI: 1.18–2.23), using drugs in Vancouver’s drug scene epicentre (aHR: 2.15 95%CI: 1.49–3.10), homelessness (aHR: 1.43, 95%CI: 1.01–2.04), non-injection crack cocaine use (aHR: 2.06, 95%CI: 1.36–3.14), and non-injection methamphetamine use (aHR: 3.69, 95%CI: 2.03–6.70) were associated with initiating methamphetamine injection. We observed a high incidence of methamphetamine initiation, particularly among young IDU, stimulant users, homeless individuals, and those involved in the city’s open drug scene. These data should be useful for the development of a broad set of interventions aimed at reducing initiation into methamphetamine injection among IDU.     

石杉碱甲类似物的研究Ⅲ．N－甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲（１）是从中草药石杉属植物千层塔（ＬｙｃｏｐｏｄｉｕｍｓｅｒｒａｔｕｍＴｈｕｎｂ．）中分得的一种高效可逆的乙酰胆碱酯酶抑制剂，临床试验证实它对早老性痴呆症有显著疗效。本文报道Ｎ－甲基吡啶酮石杉碱甲类似物２和３的合成。２－甲氧基－５－甲氧羰基－１１－亚甲基－５，９－甲撑环辛－７－烯并吡啶（９）在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮１０，再用甲醇钠和碘甲烷甲基化得Ｎ－甲基吡啶酮１１，１１经碱性水解，Ｃｕｒｔｉｕｓ重排和氨基的脱保护得Ｎ－甲基吡啶酮石杉碱甲类似物２。通过类似的途径从中间体２－甲氧基－５－甲氧羰基－７－甲基－１１－酮－５，９－甲撑环辛－７－烯并吡啶（１４）合成了类似物３。类似物２和３的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Clinical multimorbidity and physical function in older adults: a record and health status linkage study in general practice

BACKGROUND: Multiple chronic conditions occurring in the same individual are associated with adverse health outcomes. In family practice, individuals are seen who, over time, may experience many different symptoms, illnesses and chronic diseases. Measures for defining multimorbidity, which incorporate the diverse range of health problems seen in population-based family practice, remain to be developed. We have investigated whether routinely collected consultation data could be used as the basis for a simple classification of multimorbidity that reflects an individual's overall health status. METHODS: Morbidity consultation data for 9,439 English patients aged 50 years and over in an 18-month time period were linked to their self-reported physical health status measured by Short-Form 12 at the end point. Associations between physical function and all-cause multimorbidity counts were estimated relative to single morbidity only, and between physical function and morbidity severity (185 morbidities categorized on four ordinal scales of severity) relative to persons who had not consulted about any of the 185. RESULTS: In the 18-month period, 19% had consulted for a single morbidity and 23% for six or more (a high multimorbidity count). An estimated 24% of poor physical function in the family practice consulting population may be attributable to high multimorbidity. There was an increasing strength of association between poor physical function and increasing severity of multimorbidity on all four severity scales. Estimated associations (adjusted odds ratios) of the most severe morbidity categories with poor physical function were, for each of the four scales, respectively, 5.6 for chronicity [95% confidence interval (CI) 4.4-7.1], 7.0 for time course (4.5-10.6) and 3.6 for health care use (2.0-6.6) and for patient impact (6.7; 5.2-8.8). CONCLUSIONS: Multimorbidity defined by using routinely collected family practice consultation data and classified by count and by severity was associated with poorer physical function. This approach offers the potential for systematic use of routine records to classify multimorbidity and to identify groups with high likelihood of poor physical status for needs assessment and targeted intervention.     

Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid for colon-specific drug delivery in inflammatory bowel disease

Mutual azo prodrug of 5-aminosalicylic acid with l-tyrosine was synthesized by coupling l-tyrosine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in rat fecal matter showed 87.18% release of 5-aminosalicylic acid with a half-life of 140.28min, following first order kinetics. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. Myeloperoxidase activity was determined by the method of Krawisz et al. The synthesized prodrug was found to produce comparable mitigating effect as that of sulfasalazine on colitis in rats.