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April 20, 2009

Micronization processes with supercritical fluids: Fundamentals and mechanisms

Filed under: Pharmacology, Toxicology and Pharmaceutical Science — Tags: , — medical insurance @ 10:55 am

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Supercritical fluid techniques for materials precipitation have been proposed as an alternative to conventional precipitation processes as they allow to improve the performance of these processes in terms of reduction of particle size and control of morphology and particle size distribution, without degradation or contamination of the product. These techniques have received much attention during the last years, and their feasibility and performance have been experimentally demonstrated for many substances. One of the main pending tasks is the development of a systematic procedure for the design and scale-up of these processes. This requires not only empirical knowledge, but also information about the fundamentals of the process. This work aims to review the published literature dealing with a fundamental investigation or modeling of supercritical fluid precipitation processes.

A. Martína M.J. CoceroaEmail:mjcocero@iq.uva.es
[a]Departamento de Ingeniería Química y Tecnología del Medio Ambiente, Facultad de Ciencias, Universidad de Valladolid, 47011 Valladolid, Spain

April 10, 2009

Proline-rich, amphipathic cell-penetrating peptides

Filed under: Pharmacology, Toxicology and Pharmaceutical Science — Tags: , — medical insurance @ 9:34 am

Proline-rich peptides are a chemically and structurally diverse family of cell-penetrating vectors characterised by the presence of pyrrolidine rings from prolines. Amphipathic Pro-rich peptides are particularly effective, demonstrating efficient cellular uptake and non-cytotoxicity. Derivatives with hydrophobic moieties, such as fatty acids or silaproline, have shown highly improved internalisation efficiency; an all D-amino acid version of the CPP SAP was shown to be completely protease resistant and was evaluated in a preliminary in vivo study. CD and TEM studies regarding the self-assembly properties of this family of peptides highlight the possible role of aggregated species in the internalisation process. Finally, these CPPs were shown to be internalised via caveolae or lipid-rafts mediated endocytosis, which circumvents the lysosomal route of degradation.

Sílvia Pujalsa Ernest GiraltaEmail:egiralt@pcb.ub.es
[a]Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, Spain;[b]Department of Organic Chemistry, University of Barcelona, Spain

April 6, 2009

The joint association of average volume of alcohol and binge drinking with hazardous driving behaviour and traffic crashes

Filed under: Nursing and Health Professions — Tags: , — medical insurance @ 12:22 pm

Background Previous studies on alcohol-related road safety have not assessed the joint impact of average volume of alcohol and binge drinking. Aim To examine the joint and separate association of average volume of alcohol and binge drinking with hazardous driving behaviour and traffic crashes. Methods Data were drawn from telephone interviews conducted in the period 2000-2005, with 12 037 individuals representative of the population aged 18-64 years in the Madrid region, Spain. The threshold between average moderate and heavy volumes was 40 g of alcohol/day in men and 24 g/day in women. Binge drinking was defined as intake of >/= 80 g of alcohol in men and >/= 60 g in women, during any drinking occasion in the preceding 30 days. Individuals were classified into the following categories: (i) non-drinkers; (ii) moderate drinkers with no binge drinking (MDNB); (iii) moderate drinkers with binge drinking (MDB); (iv) heavy drinkers with no binge drinking (HDNB); and (v) heavy drinkers with binge drinking (HDB). Analyses were performed using logistic regression, with adjustment for sex, age and educational level. Findings Frequency of inadequate seat-belt use increased progressively across categories of alcohol consumption, with odds ratio (OR) 1 in non-drinkers, 1.19 [95% confidence interval (CI) 1.06-1.33] in MDNB, 1.69 (1.41-2.03) in MDB, 1.68 (1.24-2.29) in HDNB and 2.41 (1.83-3.18) in HDB (P for trend < 0.001). Compared with MDNB, alcohol-impaired driving was also more frequent in MDB (OR 7.43; 95% CI: 5.52-10.00), HDNB (OR 7.31; 95% CI: 4.37-12.25) and in HDB (OR 15.50; 95% CI: 10.62-22.61). Lastly, compared with non-drinkers, frequency of traffic crashes increased progressively across categories of alcohol consumption (P for trend = 0.028), although it only reached statistical significance in HDB (OR 2.01; 95% CI: 1.00-4.09). Conclusions Self-reported average volume of alcohol and binge drinking are both associated with self-reported hazardous driving behaviour and traffic crashes. The strength of the association is greater when average heavy consumption and binge drinking occur jointly.

Valencia-Martin,JL Galan,I Rodriguez-Artalejo,F
CIBER de Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.

March 22, 2009

The shifting pattern of cause-specific mortality in a cohort of human immunodeficiency virus-infected and non-infected injecting drug users.

Filed under: Nursing and Health Professions — Tags: , — medical insurance @ 12:37 pm

AIMS: To monitor changes in cause-specific mortality before and after 1997 according to human immunodeficiency virus (HIV) serological status in a cohort of injecting drug users (IDUs) observed for a 17-year period (1987–2004). DESIGN: Community-based prospective cohort study of IDUs recruited in three acquired immunodeficiency virus (AIDS) prevention centres (1987–96) and followed-up until to 2004. METHODS: We obtained annual overall mortality rates and mortality rates by specific causes according to HIV status. Poisson regression models were adjusted to compare mortality rates between calendar periods. Significant changes in slope trends were evaluated by join-point regression. Disease-specific mortality rates were estimated using competing risk models. FINDINGS: From 7186 IDUs recruited (80677.218 person-years), 1589 deaths were observed with an overall mortality rate of 19.7 per 1000 person-years (95% CI, 18.8-20.7). This rate decreased from 22.9 per 1000 (95% CI, 21.4-24.7) before 1997 to 17.4 per 1000 (95% CI, 16.3-18.6) after 1997 [relative risk (RR) 0.83; 95% confidence interval (CI), 0.75-0.92]. Risk of death for HIV-positive was four times higher than for HIV-negative (RR 4.08; 95% CI, 3.63-4.58). Among HIV-positive individuals a significantly decreased change point in trend was found in 1997 for both total and AIDS mortality. HIV-negative individuals showed a similar pattern for drug overdose, suicide and accident mortality. Both groups showed an increase in proportional mortality by liver-related causes, cardiovascular diseases and cancer. Furthermore, a progressively increasing trend was observed for the three causes. However, there were no significant differences according to serological groups. CONCLUSIONS: Cardiovascular and cancer mortality are increasing among IDUs, but the increases are not related to HIV infection. We have not found a link between highly active antiretroviral therapy (HAART) introduction and increases in mortality for specific causes.

Ferreros,I Lumbreras,B Hurtado,I Perez-Hoyos,S Hernandez-Aguado,I
Unitat d’Epidemiologia i Estadistica, Escola Valenciana d’Estudis en Salut (EVES),Valencia, Spain. ferreros_inm@gva.es

March 16, 2009

Importance of house dust and storage mites in canine atopic dermatitis in the geographic region of Galicia, Spain.

Filed under: Veterinary Science and Veterinary Medicine — Tags: , — medical insurance @ 7:05 pm

Sensitisation to mites is frequent in atopic dogs. The main mite genus involved in canine atopic dermatitis is Dermatophagoides. The importance of storage mite allergens in dogs has been controversial. The aim of this study was to evaluate the sensitisation rates against storage mites (Lepidoglyphus destructor and Tyrophagus putrescentiae) and house dust mites (Dermatophagoides farinae and D. pteronyssinus) in atopic dogs from Galicia, a highly humid and temperate region of Spain, using a Fc epsilon RI alpha -based immunoglobulin E (IgE) in vitro test. The study was performed on 95 dogs suffering from atopic dermatitis and presenting detectable specific serum IgE levels: 91.6% of the dogs tested positive for storage mites, whereas sensitisation to house dust mites was detected in 87.4%. These results indicate the importance of storage mites in this specific geographic area.

Goicoa, A. Espino, L. Rodriguez, I. Puigdemont, A. Brazis, P. Rejas, J.
Department of Veterinary Clinical Sciences, Rof Codina Veterinary Teaching Hospital, Faculty of Veterinary Medicine, University of Santiago de Compostela, 22741 Lugo, Spain.

March 15, 2009

Psychiatric comorbidity in young cocaine users: induced versus independent disorders

Filed under: Nursing and Health Professions — Tags: , — medical insurance @ 11:44 am

AIMS: To examine the psychiatric status of young cocaine users using a validated instrument for the evaluation of psychiatric comorbidity, emphasizing the distinction between independent and induced psychiatric conditions. DESIGN: Cross-sectional study. SETTING: Barcelona, Spain. PARTICIPANTS: A cohort of 139 young (18-30 years) adult current regular cocaine users. MEASUREMENTS: The Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV, which produces diagnoses according to DSM-IV criteria, including Axis II antisocial and borderline personality disorders). FINDINGS: Nearly 42.5% of the subjects presented psychiatric comorbidity. The most common Axis I diagnoses were mood disorders (26.6%) and anxiety disorders (13%). Increasing age, having ever received treatment for drug use and freebase cocaine use were associated with substance-induced disorders diagnoses relative to primary Axis I disorders. CONCLUSIONS: This study has shown a relatively high prevalence of psychiatric comorbidity in cocaine users recruited in non-clinical settings. Future studies examining potential differential factors associated with primary versus substance-induced disorders are necessary to optimize the implementation of more suitable approaching programmes for young regular cocaine users.

Herrero,MJ Domingo-Salvany,A Torrens,M Brugal,MT
Health Services Research Unit (IMIM-Hospital del Mar), Barcelona, Spain.

March 2, 2009

Association between heroin dependence and 5-HT2A receptor gene polymorphisms.

Filed under: Nursing and Health Professions — Tags: , — medical insurance @ 9:28 pm

OBJECTIVE: To investigate the association between four polymorphisms of the 5-HT(2A) receptor and 5-HT transporter genes and heroin dependence. METHODS: 113 heroin- dependent patients (DSM-IV criteria) and 420 unrelated healthy controls from Asturias (Northern Spain) were genotyped using standard methods. RESULTS: There was an apparent difference in the distribution of genotypes for A-1438G polymorphisms (p = 0.024, not significant after Bonferroni correction). The 5-HT(2A) -1438A allele was significantly more common in patients than controls [0.55 and 0.45, respectively; corrected p = 0.042, OR = 1.51 (95% CI = 1.13-2.03)]. An interaction was observed between A-1438G of 5-HT(2A) and 5-HTT polymorphisms. The association between the -1438AA vs. AG/GG genotypes and heroin dependence was enhanced in the presence of 12-repeat 5-HTT VNTR and short 5-HTTLPR alleles [24.8% in heroin-dependent patients vs. 12.6% in controls; corrected p = 0.045, OR = 2.28 (95% CI = 1.36-3.82)]. CONCLUSIONS: Our findings support a contribution of the 5-HT(2A) gene to susceptibility to heroin dependence, as well as a possible synergistic effect of 5-HT(2A) and 5-HTT genes on susceptibility to heroin dependence.

Saiz,PA Garcia-Portilla,MP Arango,C Morales,B Martinez-Barrondo,S Alvarez,C San-Narciso,G Carreno,E Alvarez,V Coto,E Bobes,J
Department of Psychiatry, School of Medicine, University of Oviedo, Oviedo, Spain. frank@uniovi.es

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