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.     

Er:YAG激光桩道预处理的研究进展

本文回顾了Er:YAG激光活化根管冲洗技术的最新研究进展,包括光子诱导光声流(photon initiated photoacoustic streaming,PIPS)技术和冲击波增强发射光声流(shock wave enhanced emission photoacoustic streaming,SWEEPS)技术,探讨Er:YAG激光预处理桩道的原理、优点以及对纤维桩粘接强度的影响,以期为临床选择适宜的桩道处理方法提供新思路。     

Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.     

Spread of an Enterococcus faecalis sequence type 6 (CC2) clone in patients undergoing selective decontamination of the digestive tract

Enterococcus faecalis (E. faecalis) is a common cause of nosocomial infection in immunocompromised patients. The presence and dissemination of high‐risk clonal complexes, such as CC2, is an ongoing problem in hospitals. The aim of this work was to characterize 24 E. faecalis isolates from ICU patients undergoing selective decontamination of the digestive tract (SDD) by phenotypical (antimicrobial susceptibility) and genotypical (presence of virulence genes, RAPD‐PCR and MLST) methods. Our results showed high prevalence of the ST6 E. faecalis clone (91.6%), especially adapted to the hospital environment, with a multidrug resistance pattern and a multitude of putative virulence genes. In addition, ST179 (4.2%) and ST191 (4.2%) were detected. By RAPD–PCR analysis, the 22 isolates identified as ST6 showed six different DNA patterns, while the two remaining isolates, ST179 and ST191, showed two additional profiles. CC2 is a known clonal complex with high adaptability to hospital environment and worldwide distribution. The high prevalence of the ST6 clone in the studied population could be related to the presence of gentamicin in the SDD mixture since most strains were gentamicin resistant. Consequently, strict surveillance should be applied for rapid detection and control of this clone to prevent future spread outside the ICU.     

Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres

Purpose

To evaluate the feasibility of a same-day yttrium-90 (⁹⁰Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

The detection and management of complications following the treatment of liver metastases

While once considered as incurable systemic disease, treatment options for liver metastases have increased over the last 30 years and safety has improved dramatically, such that for a selected group of patients the hope of cure can now be offered with radical treatment, and low morbidity interventions can be offered which prolong survival, even in patients with more widely disseminated disease. Advances have been made in selection and surgical technique for liver resection and several adjuncts to resection now exist in the form of portal vein embolization, thermal ablation and targeted drug or radiotherapy delivery options. A natural consequence of these developments has been the delivery of services within fewer specialist units, with the result that later complications of therapy may present to local hospitals, rather than directly to the specialist centres. This article will describe the current common liver-directed therapies and outline the presentation and management of their complications.     

Implantable Transvenous Pacing Leads:

With the dawn of a new millennium, physicians' demands for very thin transvenous leads able to be positioned in nontraditional sites like the Bachmann's bundle, the high and mid-right ventricular septum, and the His bundle have created new and exciting challenges for lead engineers. Bipolar leads can now be as thin and reliable as unipolar leads. Cathode electrodes are very small, porous, and demonstrate high impedance. To optimize stimulation thresholds, steroid-eluting passive- and active-fixation electrodes have become popular for use in the atrium and ventricle. To create thin lead body diameters, new insulation and conductor materials and lead body designs are necessary. Hybrid medical materials having the best features of silicone rubber and polyurethane will allow for reliable insulation. Conductor cables instead of helical coils permit strong thin diameter leads to be designed. Transvenous lead implantation using the traditional stylet may not be possible with thin diameter leads, necessitating the use of sophisticated workstations using steerable catheters to guide these new active-fixation leads to selective sites in the right heart. The pacing lead of the future may be very different from the one used today. Ironically, it will have features and implantation techniques similar to the transvenous leads designed prior to the use of the stylet. We are now approaching full circle in lead development, retracing the footprints of the early implanters of three and a half decades ago. (PACE 2004; 27[Pt. II]:887–893)     

Toxic epidermal necrolysis; 15 years'' experience in a Dutch burns centre

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially fatal drug reaction characterized by an extensive skin rash with blisters and exfoliation, frequently accompanied by mucositis. The wounds caused by TEN are similar to second-degree burns and severe cases may involve large areas of skin loss. OBJECTIVES: Analysis of our results in patients with TEN and evaluation of the variety of therapeutic interventions that has been studied and suggested in TEN. PATIENTS/METHODS: Retrospective analysis of 19 consecutive patients with TEN treated in our burns centre between 1989 and 2004. RESULTS: Immediate withdrawal of any potentially fatal drug, maximum supportive care, and a restricted and tailored antibiotic, medical and surgical treatment regimen confined mortality to 21%, whereas prognosis scores like APACHE II and SCORTEN predicted mortality of 22 and 30%, respectively. A positive contribution of selective digestive decontamination is suggested but has yet to be established. CONCLUSIONS: Because of a potentially fatal outcome, fast referral of a patient suspected of TEN to a specialized centre (mostly a burns unit or specialized dermatology centre) for expert wound management and tailored comprehensive care is strongly advised and contributes to survival.