Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

How Do Students Source and Supply Drugs? Characteristics of the University Illegal Drug Trade

Background: It is widely known that a proportion of university students use drugs. However, much less is known about how they source and supply their drugs. Objectives: In this article, we investigate student drug trading activity, including how they obtained their drugs, whether they sold drugs, and the extent to which their drug trading might be described as a form of “social supply”. Methods: A survey was conducted of all students across seven of the nine universities of Wales. In total, 7855 students submitted a questionnaire and 1877 of these reported drug use in the current academic year. All students who reported using one or more illegal drugs in the current academic year were asked how they obtained their drugs, how they funded their drug use, whether they had sold, traded or given away illegal drugs, along with their motives for drug trading. Results: The results showed that about half of users obtained drugs solely from friends and associates and one-fifth obtained them solely from external dealers. One-quarter used friends and associates as well as external markets. In many cases, supplying drugs amounted to sharing them or giving them away. However, over one-third of students said that they had sold drugs. Conclusions: Overall, the methods of sourcing and supplying drug among university students shares features of both “social supply” and “traditional” drug markets. We conclude that the student drug market investigated is best described as a “hybrid” combination of both.     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

'Reprofessionalization' or 'occupational imperialism'?: some reflections on pharmacy in Britain

Drawing upon preliminary research findings, this paper considers whether pharmacists in Britain face a crisis in their occupational status and identity as a result of changes in their work and market situations. It further examines some of the ways in which they are responding to the challenges and opportunities presented. The paper also comments on the utility of the concepts of 'reprofessionalization' and 'occupational imperialism' in the study of British pharmacy.     

Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Percutaneous decompression: treatment for respiratory distress secondary to multicystic dysplastic kidney

Multicystic dysplastic kidney is a common renal anomaly in the newborn. Long-term problems, such as pain, infection, hypertension and neoplasm, although infrequent, have been reported. Acute, life-threatening complications resulting from the size of the affected kidney are rare and emergency nephrectomy has been the only reported effective therapy. We present a case of ultrasound-guided percutaneous cyst decompression used as definitive treatment of respiratory failure associated with multicystic dysplastic kidney.     

IUD insertion forces: effects of recent childbirth and lactation

This investigation compared the force required to insert an IUD in women who were breastfeeding and who had recently delivered a child with that required in control women who were not breastfeeding and who had not recently delivered. Twenty-eight women who had recently delivered and who were breastfeeding were compared with twenty-eight controls. The women were matched for age and parity and for the type of IUD used. The mean IUD insertion force in the breastfeeding, recently-delivered women was 1.75 newtons (N) as compared to 2.80 N in the controls. The difference was statistically highly significant (pairedt-test,p<0.01). Recent childbirth and lactation are associated with a reduction in IUD-related insertion pain, probably due to a reduction in the force required for insertion. This reduction in IUD insertion force is not necessarily related to lower uterine perforation rates in IUD insertion in this group. A number of physiological mechanisms may be responsible for this finding.

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Resumen Esta investigacion comparó la fuerza requerida para insertar un DIU en mujeres amamantando y que habían parido recientemente, con mujeres de control que no amamantaban ni habían parido recientemente. Veintiocho mujeres que habían parido recientemente y amamantando fueron comparadas con veintiocho controles. Las mujeres fueron apareadas por edad y paridad y por el tipo de DIU usado. La fuerza media de inserción de un DIU en la mujer que había parido recientemente y estaba amamantando, fué de 1.75 newtons (N) comparada con 2.80 N en los controles. La diferencia fué estadísticamente altamente significativa (t-test apareado,p<0.01). Lactancia y reciente paridad están asociadas con la reducción en el dolor relacionado a la inserción del DIU. Esta reducción en la fuerza de inserción no está necesariamente relacionada con las tasas de perforación uterina baja en la inserción de un DIU en este grupo. Un número de mecanismos fisiológicos podrían ser responsables de este hallazgo.

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Résumé On a cherché à comparer la force nécessaire pour insérer un DIU chez des femmes qui allaitaient et avaient récemment mis au monde un enfant et chez des femmes qui n'allaitaient pas et qui n'avaient pas récemment accouché. La comparaison portait sur vingt-huit femmes dans un cas comme dans l'autre. On a veillé à faire corresponde les deux séries du point de vue de l'âe, du nombre de grossesses antérieures et du type de DIU utilisé. Chez les femmes allaitant et ayant récemment accouché, la force nécessaire pour insérer un stérilet était en moyenne de 1,75 newton (N), au lieu de 2,80 N chez les sujets témoins. Cette différence est très significative du point de vue statistique (t test sur séries appariées, p<0,0.1). Un accouchement récent et l'allaitement sont associés à une réduction des douleurs causées par l'insertion d'un DIU, probablement du fait que la force nécessaire pour pratiquer cette opération est moindre. Cette réduction de la force d'insersion n'est pas forcément liée à des taux inférieurs de perforation utérine lors de l'insersion d'un DIU dans ce groupe. Il est possible qu'un certain nombre de mécanismes physiologiques soient responsables des faits ainsi constatés.

     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.