Disposición plasmática y residuos tisulares de marbofloxacina en truchas arco iris (oncorhynchus mykiss) en condiciones estivales e invernales. Plasmatic disposition and tissue residues of marbofloxacin in rainbow trouts (oncorhynchus mykiss) in summer and winter conditions

Los sistemas intensivos de producción, predisponen en los peces a la presentación de diversas enfermedades, lo que demanda el empleo de antimicrobianos para mantener la salud de los lotes de cultivo. En tal sentido es importante contar con información local en cuanto al comportamiento cinético a los efectos de determinar una adecuada dosificación de los antimicrobianos empleados y con esta información, establecer los periodos de resguardo necesarios para evitar la presencia violativa de estos fármacos en el animal destinado a consumo humano. En el presente proyecto se propone efectuar un estudio farmacocinético de concentraciones plasmáticas y tisulares alcanzadas y establecer los periodos de resguardo para marbofloxacina, antimicrobiano del cual no se tienen antecedentes regionales en cuanto a su disposición a diferentes temperaturas como las que condicionan las estaciones de verano e invierno, de marcada variación en la provincia, modificando la actividad metabólica de los peces. La concreción de este proyecto permitirá entregar conocimientos concretos y de aplicación directa en la cría intensiva de la trucha arco iris (Oncorhynchus mykiss) en diferentes condiciones ambientales, al contarse con la información necesaria para una adecuada dosificación y periodos de resguardo necesarios para evitar el residuo de este fármaco. Además, permitirá consolidar una línea de investigación dentro de la acuicultura muy poco desarrollada actualmente en el país. Intensive production systems predispose fishes to diverse diseases, which demands antimicrobial use for health maintenance in the lots of culture. In such sense it is important to have local information of the kinetic behavior to determine a suitable dosing of the antimicrobials employed, and on this information, to establish withdrawal periods to avoid the violative presence of these drugs in animals for human consumption. The present project will carry out a pharmacokinetic study of plasmatic and tissue concentrations to establish the withdrawal period for marbofloxacin, being known that temperature, modify the metabolic activity of the fish, and there are no local antecedents of disposition at different temperatures in summer and winter for this antimicrobial. The concretion of this project will allow to give concrete knowledge of direct application in intensive production of rainbow trout (Oncorhynchus mykiss), in different environmental conditions, counting with the necessary information for a suitable dosification and withdrawal periods to avoid residues of this drug. In addition, it will allow to consolidate an investigation line in acuiculture, not much developed in our country.

A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents

A method is described which permits to determine in vivo an in a short period of time (4-6 hours) the sensitivity of T. cruzo strains to known active chemotherapeutic agents. By using resistant- and sensitive T. cruzi stains a fairly good correlation was observed between the results obtained with this rapid method (which detects activity against the circulating blood forms) and those obtained with long-term schedules which involve drug adminstration for at least 20 consecutive days and a prolonged period of assessment. This method may be used to characterize susceptibility to active drugs used clinically, provide infomation on the specific action against circulating trypomastigotes and screen active compounds. Differences in the natural susceptibility of Trypanosoma cruzi strains to active drugs have been already reported using different criteria, mostly demanding long-term study of the animal (Hauschka, 1949; Bock, Gonnert & Haberkorn, 1969; Brener, Costa & Chiari, 1976; Andrade & Figueira, 1977; Schlemper, 1982). In this paper we report a method which detects in 4-6 hours the effect of drugs on bloodstream forms in mice with established T. cruzi infections. The results obtained with this method show a fairly good correlation with those obtained by prolonged treatment schedules used to assess the action of drugs in experimental Chagas' disease and may be used to study the sensitivity of T. cruzi strains to active drugs.

La representació de cançons en gèneres audiovisuals musicals: Anàlisi de dos documentals musicals subtitulats i d'onze videoclips de Madonna

La subtitulació de cançons és un camp força inexplorat en el món de la traducció audiovisual. En aquest treball de recerca proposo un estudi més exhaustiu sobre la traducció de cançons, especialment pel que fa a la subtitulació, tot posant com a exemple una part de la producció discogràfica i cinematogràfica d’una de les icones internacionals de la música pop actual: Madonna. El treball està dividit en un primer capítol teòric sobre l’estat de la qüestió en relació a la subtitulació de cançons, un segon capítol amb els resultats d’una enquesta sobre la recepció de Madonna, un tercer capítol d’anàlisi del corpus escollit (els documentals musicals subtitulats In bed with Madonna i I’m going to tell you a secret i onze videoclips musicals de Madonna), i un quart i últim capítol de conclusions finals. L’objectiu principal del treball de recerca és determinar la importància de subtitular les cançons incloses als documentals musicals i, també, als videoclips musicals, gèneres audiovisuals en auge en l’actualitat. Song subtitling is a largely unexplored field in audiovisual translation. In this research paper I carry out a more exhaustive analysis on song translation, specially on subtitling, taking as an example a part of the music and film production of one of the most international icons of pop music nowadays: Madonna. The paper is divided into: a first chapter on the state of the art on song subtitling, a second chapter including the results of a survey about the reception of Madonna, a third chapter analysing the corpus (music documentaries In Bed With Madonna and I’m Going to Tell You a Secret and eleven Madonna music videos), and a fourth chapter with concluding remarks. The main object of this research is to determine the importance of subtitling the songs included in music documentaries and music videos, both currently flourishing genres.

Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test.

BACKGROUND: The availability of a rapid diagnostic test for malaria (RDTm) allows accurate diagnosis at all levels of health facilities. The objective of the present study was to evaluate the safety of withholding antimalarials in febrile children who have a negative test result. METHODS: We conducted a prospective 2-arm longitudinal study in areas of Tanzania that are moderately and highly endemic for malaria. Children with a history of fever were managed routinely by resident clinicians of 2 health facilities, except that no antimalarials were prescribed if the RDTm result was negative. Children were followed up at home on day 7. The main outcome was the occurrence of complications in children with negative RDTm results; children with positive RDTm results were followed up for the same outcomes for indirect comparison. RESULTS: One thousand children (median age, 24 months) were recruited. Six hundred three children (60%) had a negative RDTm result. Five hundred seventy-three (97%) of these children were cured on day 7. Forty-nine (8%) of the children with negative RDTm results spontaneously visited the dispensary before day 7, compared with 10 (3%) of the children with positive RDTm results. All children who had negative initial results had negative results again when they were tested either at spontaneous attendance or on day 7 because they were not cured clinically, except for 3 who gave positive results on days 2, 4, and 7 respectively but who did not experience any complication. Four children who had negative initial results were admitted to the hospital subsequently, all with negative results for malaria tests upon admission. Two of them died, of causes other than malaria. CONCLUSIONS: Not giving antimalarial drugs in febrile children who had a negative RDTm result was safe, even in an area highly endemic for malaria. Our study provides evidence for treatment recommendations based on parasitological diagnosis in children <5 years old.

Involvement of amphetamines in sudden and unexpected death.

In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.

New Strategic Direction for Alcohol and Drugs (2006-2011) (Online Publication)

Executive Summary and Strategy Document (May 2006) The New Strategic Direction has a set of overarching long-term aims to: • Provide accessible and effective treatment and support for people who are consuming alcohol and/or using drugs in a potentially hazardous, harmful or dependent way. • Reduce the level, breadth and depth of alcohol and drug-related harm to users, their families and/or their carers and the wider community. • Increase awareness on all aspects of alcohol and drug-related harm in all settings and for all age groups. • Integrate those policies which contribute to the reduction of alcohol and drug-related harm into all Government Department strategies. • Develop a competent skilled workforce across all sectors that can respond to the complexities of alcohol and drug use and misuse. • Promote opportunities for those under the age of 18 years to develop appropriate skills, attitudes and behaviours to enable them to resist societal pressures to drink alcohol and/or use illicit drugs, with a particular emphasis on those identified as potentially vulnerable. • Reduce the availability of illicit drugs in Northern Ireland åÊ

New Strategic Direction for Alcohol and Drugs (2006-2011) Executive Summary

Executive Summary and Strategy Document (May 2006) The New Strategic Direction has a set of overarching long-term aims to: • Provide accessible and effective treatment and support for people who are consuming alcohol and/or using drugs in a potentially hazardous, harmful or dependent way. • Reduce the level, breadth and depth of alcohol and drug-related harm to users, their families and/or their carers and the wider community. • Increase awareness on all aspects of alcohol and drug-related harm in all settings and for all age groups. • Integrate those policies which contribute to the reduction of alcohol and drug-related harm into all Government Department strategies. • Develop a competent skilled workforce across all sectors that can respond to the complexities of alcohol and drug use and misuse. • Promote opportunities for those under the age of 18 years to develop appropriate skills, attitudes and behaviours to enable them to resist societal pressures to drink alcohol and/or use illicit drugs, with a particular emphasis on those identified as potentially vulnerable. • Reduce the availability of illicit drugs in Northern Ireland

Photodynamic drug delivery enhancement in tumours does not depend on leukocyte-endothelial interaction in a human mesothelioma xenograft model.

OBJECTIVES: The pre-treatment of tumour neovessels by low-level photodynamic therapy (PDT) improves the distribution of concomitantly administered systemic chemotherapy. The mechanism by which PDT permeabilizes the tumour vessel wall is only partially known. We have recently shown that leukocyte-endothelial cell interaction is essential for photodynamic drug delivery to normal tissue. The present study investigates whether PDT enhances drug delivery in malignant mesothelioma and whether it involves comparable mechanisms of actions. METHODS: Human mesothelioma xenografts (H-meso-1) were grown in the dorsal skinfold chambers of 28 nude mice. By intravital microscopy, the rolling and recruitment of leukocytes were assessed in tumour vessels following PDT (Visudyne(®) 400 μg/kg, fluence rate 200 mW/cm(2) and fluence 60 J/cm(2)) using intravital microscopy. Likewise, the distribution of fluorescently labelled macromolecular dextran (FITC-dextran, MW 2000 kDa) was determined after PDT. Study groups included no PDT, PDT, PDT plus a functionally blocking anti-pan-selectin antibody cocktail and PDT plus isotype control antibody. RESULTS: PDT significantly enhanced the extravascular accumulation of FITC-dextran in mesothelioma xenografts, but not in normal tissue. PDT significantly increased leukocyte-endothelial cell interaction in tumour. While PDT-induced leukocyte recruitment was significantly blunted by the anti-pan-selectin antibodies in the tumour xenograft, this manipulation did not affect the PDT-induced extravasation of FITC-dextran. CONCLUSIONS: Low-level PDT pre-treatment selectively enhances the uptake of systemically circulating macromolecular drugs in malignant mesothelioma, but not in normal tissue. Leukocyte-endothelial cell interaction is not required for PDT-induced drug delivery to malignant mesothelioma.

Guidelines for the safe administration of cytotoxic medical preparations in the treatment of patients with cancer

The Minister for Health’s Strategy for effective health care in the 1990s has emphasised quality of service as one of its key principles.  Within the medical sphere, almost no other field has developed and continues to expand as rapidly as that of cancer biology and treatment.  Cytotoxic therapies are a major part of these developments. The Cancer Strategy has highlighted the importance of these drugs in the treatment of cancers. Download the Report here

Funding: North Dublin City & County Regional Drugs Task Force

The North Dublin City and County Regional Drugs Task Force invites applications for this once-off funding which will be provided through four pillars by way of a grant up to €3,000 for innovative initiatives: • Prevention, Education & Awareness – to develop programmes and supports in the community which offer information and education in order to generate awareness. • Treatment & Rehabilitation – to develop additional short-term supports for those undertaking treatment for drug misuse or innovative rehabilitative supports. • Research – to undertake local research into drug misuse in North Dublin within the RDTF area. • Supply Reduction – to reduce access to all drugs, in particular those that cause most harm, among young people in neighbourhoods where misuse is most prevalent. Terms and conditions apply. To request an application pack or for more information contact 01 813 1786 orThis resource was contributed by The National Documentation Centre on Drug Use.

Mental health and growing up factsheet. Cannabis and mental health: information for young people.

About this leaflet This is one in a series of leaflets for parents, teachers and young people entitled Mental Health and Growing Up. These leaflets aim to provide practical, up-to-date information about mental health problems (emotional, behavioural and psychiatric disorders) that can affect children and young people. This leaflet gives you some basic facts about cannabis and also how it might affect your mental health. Introduction Lots of young people want to know about drugs. Often, people around you are taking them, and you may wonder how it will make you feel. You may even feel under pressure to use drugs in order to fit in, or be â?~coolâ?T. You may have heard that cannabis is no worse than cigarettes, or that it is harmless. What is cannabis? The cannabis plant is a member of the nettle family that has grown wild throughout the world for centuries. People have used it for lots of reasons, other than the popular relaxing effect. It comes in two main forms: ï,§ resin, which is a brown black lump also known as bhang, ganja or hashish ï,§ herbal cannabis, which is made up of the dried leaves and flowering tops, and is known as grass, marijuana, spliff, weed, etc. Skunk cannabis is made from a cannabis plant that has more active chemicals in it (THC), and the effect on your brain is stronger. Because â?~streetâ?T cannabis varies so much in strength, you will not be able to tell exactly how it will make you feel at any particular time. What does it do to you? When you smoke cannabis, the active compounds reach your brain quickly through your bloodstream. It then binds/sticks to a special receptor in your brain. This causes your nerve cells to release different chemicals, and causes the effects that you feel. These effects can be enjoyable or unpleasant. Often the bad effects take longer to appear than the pleasant ones. ï,§ Good/pleasant effects: You may feel relaxed and talkative, and colours or music may seem more intense. ï,§ Unpleasant effects: Feeling sick/panicky, feeling paranoid or hearing voices, feeling depressed and unmotivated. Unfortunately, some people can find cannabis addictive and so have trouble stopping use even when they are not enjoying it. The effects on your mental health Using cannabis triggers mental health problems in people who seemed to be well before, or it can worsen any mental health problems you already have. Research has shown that people who are already at risk of developing mental health problems are more likely to start showing symptoms of mental illness if they use cannabis regularly. For example if someone in your family has depression or schizophrenia, you are at higher risk of getting these illness when you use cannabis. The younger you are when you start using it, the more you may be at risk. This is because your brain is still developing and can be more easily damaged by the active chemicals in cannabis. If you stop using cannabis once you have started to show symptoms of mental illness, such as depression, paranoia or hearing voices, these symptoms may go away. However, not everyone will get better just by stopping smoking. If you go on using cannabis, the symptoms can get worse. It can also make any treatment that your doctor might prescribe for you, work less well. Your illness may come back more quickly, and more often if you continue to use cannabis once you get well again. Some people with mental health problems find that using cannabis makes them feel a bit better for a while. Unfortunately this does not last, and it does nothing to treat the illness. In fact, it may delay you from getting help you need and the illness may get worse in the longer term. [For the full factsheet, click on the link above]This resource was contributed by The National Documentation Centre on Drug Use.

Antibiotic-dependent correlation between drug-induced killing and loss of luminescence in Streptococcus gordonii expressing luciferase.

Measuring antibiotic-induced killing relies on time-consuming biological tests. The firefly luciferase gene (luc) was successfully used as a reporter gene to assess antibiotic efficacy rapidly in slow-growing Mycobacterium tuberculosis. We tested whether luc expression could also provide a rapid evaluation of bactericidal drugs in Streptococcus gordonii. The suicide vectors pFW5luc and a modified version of pJDC9 carrying a promoterless luc gene were used to construct transcriptional-fusion mutants. One mutant susceptible to penicillin-induced killing (LMI2) and three penicillin-tolerant derivatives (LMI103, LMI104, and LMI105) producing luciferase under independent streptococcal promoters were tested. The correlation between antibiotic-induced killing and luminescence was determined with mechanistically unrelated drugs. Chloramphenicol (20 times the MIC) inhibited bacterial growth. In parallel, luciferase stopped increasing and remained stable, as determined by luminescence and Western blots. Ciprofloxacin (200 times the MIC) rapidly killed 1.5 log10 CFU/ml in 2-4 hr. Luminescence decreased simultaneously by 10-fold. In contrast, penicillin (200 times the MIC) gave discordant results. Although killing was slow (&lt; or = 0.5 log10 CFU/ml in 2 hr), luminescence dropped abruptly by 50-100-times in the same time. Inactivating penicillin with penicillinase restored luminescence, irrespective of viable counts. This was not due to altered luciferase expression or stability, suggesting some kind of post-translational modification. Luciferase shares homology with aminoacyl-tRNA synthetase and acyl-CoA ligase, which might be regulated by macromolecule synthesis and hence affected in penicillin-inhibited cells. Because of resemblance, luciferase might be down-regulated simultaneously. Luminescence cannot be universally used to predict antibiotic-induced killing. Thus, introducing reporter enzymes sharing mechanistic similarities with normal metabolic reactions might reveal other effects than those expected.

Binding of d-methadone, l-methadone, and dl-methadone to proteins in plasma of healthy volunteers: role of the variants of alpha 1-acid glycoprotein.

The plasma concentrations of alpha 1-acid glycoprotein (AAG), albumin, triglycerides, cholesterol, and total proteins, as well as the plasma binding of racemic, d-methadone, and l-methadone were measured in 45 healthy subjects. The AAG phenotypes and the concentrations of AAG variants were also determined. The measured free fractions for racemic, d-methadone, and l-methadone were, respectively, 12.7% +/- 3.3%, 10.0% +/- 2.9%, and 14.2% +/- 3.2% (mean +/- SD). A significant correlation was obtained between the binding ratio (B/F) for dl-methadone and the total AAG concentration (r = 0.724; p less than 0.001). A multiple stepwise regression analysis showed that AAG was the main explanatory variable for the binding of the racemate. When concentrations of AAG variants were considered, a significant correlation was obtained between the binding ratio of dl-methadone and orosomucoid2 A concentration (r = 0.715; p less than 0.001), a weak correlation between dl-methadone and orosomucoid1 S concentration (r = 0.494; p less than 0.001), and no correlation between dl-methadone and orosomucoid1 F1 concentration (r = 0.049; not significant). Similar findings were obtained with the enantiomers. This study shows the importance of considering not only total AAG but also concentrations of AAG variants when measuring the binding of methadone and possibly of other drugs in plasma.

Therapeutic Blockade of LIGHT Interaction With Herpesvirus Entry Mediator and Lymphotoxin β Receptor Attenuates In Vivo Cytotoxic Allogeneic Responses.

BACKGROUND: Tumor necrosis factor/tumor necrosis factor receptor superfamily members conform a group of molecular interaction pathways of essential relevance during the process of T-cell activation and differentiation toward effector cells and particularly for the maintenance phase of the immune response. Specific blockade of these interacting pathways, such as CD40-CD40L, contributes to modulate the deleterious outcome of allogeneic immune responses. We postulated that antagonizing the interaction of LIGHT expression on activated T cells with its receptors, herpesvirus entry mediator and lymphotoxin β receptor, may decrease T cell-mediated allogeneic responses. METHODS: A flow cytometry competition assay was designed to identify anti-LIGHT monoclonal antibodies capable to prevent the interaction of mouse LIGHT with its receptors expressed on transfected cells. An antibody with the desired specificity was evaluated in a short-term in vivo allogeneic cytotoxic assay and tested for its ability to detect endogenous mouse LIGHT. RESULTS: We provide evidence for the first time that in mice, as previously described in humans, LIGHT protein is rapidly and transiently expressed after T-cell activation, and this expression was stronger on CD8 T cells than on CD4 T cells. Two anti-LIGHT antibodies prevented interactions of mouse LIGHT with its two known receptors, herpesvirus entry mediator and lymphotoxin β receptor. In vivo administration of anti-LIGHT antibody (clone 10F12) ameliorated host antidonor short-term cytotoxic response in wild type B6 mice, although to a lesser extent than that observed in LIGHT-deficient mice. CONCLUSION: The therapeutic targeting of LIGHT may contribute to achieve a better control of cytotoxic responses refractory to current immunosuppressive drugs in transplantation.

Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

Chloroquine (CQ) resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1%) of the patients were cured and 44 (37.9%) failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP) and 20 received chlorpheniramine + chloroquine (CH+CQ) combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05). There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92% while those of CH+CQ was 85%. There was a significant difference in parasite clearance time (p = 0.01) between the two groups. The 38% treatment failure for CQ reported in this study is higher than the 10% recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.