PPARα is Required for PPARδ action in regulation of body weight and hepatic steatosis in mice.

NlmCategory="UNASSIGNED">Peroxisome proliferator activated receptors alpha (PPARα) and delta (PPARδ) belong to the nuclear receptor superfamily. PPARα is a target of well established lipid-lowering drugs. PPARδ (also known as PPARβ/δ) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδ or deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARα also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARα endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδ in wild type mice. Our results show that both PPARδ and PPARα receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARα working downstream of PPARδ.

Eficacia analgésica del diclofenaco sódico vs. ibuprofeno después de la extracción quirúrgica de un tercer molar inferior incluido

Objetivo: En este estudio evaluamos la eficacia analgésica del diclofenaco sódico en comparación con el ibuprofeno, después de la extracción quirúrgica de un tercer molar inferior incluido. Diseño de estudio: Los pacientes que participaron en el estudio fueron distribuidos de forma aleatoria en dos grupos. Uno fue el grupo ibuprofeno y el otro el grupo diclofenaco. La intervención practicada fue la extracción quirúrgica de un tercer molar inferior cuya dificultad fue determinada en función del grado de inclusión en todos los pacientes. Las variables registradas fueron la intensidad del dolor y la necesidad de medicación de rescate durante un periodo de una semana. Los registros se realizaron una vez al día a la misma hora y registrados en un cuaderno por parte del paciente. Resultados: Un total de 81 pacientes (87.1%) fueron incluidos en el estudio. Los valores fueron similares en las primeras 48 horas postoperatorias, pero a partir del tercer día existió una tendencia del grupo diclofenaco a mostrar valores de dolor superiores, aunque sin llegar a existir diferencias estadísticamente significativas (p>0.05). Esta tendencia a presentar mayor dolor durante el periodo postoperatorio en el grupo diclofenaco también se vio reflejada en el requerimiento del analgésico de rescate y en el número de comprimidos empleados. Conclusiones: No se evidenciaron diferencias estadísticamente significativas en cuanto a la eficacia analgésica del diclofenaco sódico respecto al ibuprofeno, aunque sí pudo observarse una mayor tendencia hacia la necesidad de más medicación suplementaria durante los 2 primeros días del postoperatorio en el grupo diclofenaco pero sin adquirir significación estadística (p>0.05).

Anomalous sub aortic left brachiocephalic vein: a case report

The left brachiocephalic vein occasionally follows an aberrant course. It is usually associated with congenital cardiac anomaly. We present a case of anomalous left brachiocephalic vein which followed a sub aortic course, with no cardiac abnormality. Multi detector computed tomography is very useful in accurate diagnosis of this condition and prevents any further investigation in cases of isolated abnormalities.

Right heart ischemia in cases of sepsis.

Data from the literature suggest that cases of sepsis complicated by right ventricular (RV) dysfunction have poorer prognosis. In these cases progressive hypoperfusion associated to increasing, injury-related, pulmonary vascular resistance account for RV ischemia. In the present analysis, we wanted to evaluate whether prevalent RV cardiac ischemic damage could be detected in a series of fatal sepsis cases. We retrospectively investigated 20 cases of sepsis that underwent forensic autopsy (study group-11♀, 9♂, mean age 57 years) and compared them to a group of 20 cases of hanging (hanging group-4 ♀, 16 ♂, mean age 44 years) as well as to a group of 20 cases of myocardial infarction (MI group-9 ♀, 11 ♂, mean age 65 years), as examples of cardiac damage due to global hypoxia during agony and ischemic damage, respectively. We performed immunohistochemistry with the antibodies anti-fibronectin and C5b-9. The reactions were semiquantitively classified and the groups were compared. In 30% of the cases of sepsis prevalent RV ischemic damage could be detected with the antibody anti-fibronectin. This expression was significantly different from that observed in cases of MI (p=0.028) and hanging (p<0.001). Our study showed that, in cases of fatal sepsis, prevalent RV ischemic damage occurred in a substantial minority of cases.

Schwannoma of the inferior turbinate: case report and review of literature

Schwannomas of the sinonasal tract are rare entities that are amenable to local resection. We present a 69 year old woman with a schwannoma of the inferior turbinate that was successfully resected. Schwannomas arising from the inferior turbinate are very infrequent.

Cell fusion reprogramming leads to a specific hepatic expression pattern during mouse bone marrow derived hepatocyte formation In Vivo

The fusion of bone marrow (BM) hematopoietic cells with hepatocytes to generate BM derived hepatocytes (BMDH) is a natural process, which is enhanced in damaged tissues. However, the reprogramming needed to generate BMDH and the identity of the resultant cells is essentially unknown. In a mouse model of chronic liver damage, here we identify a modification in the chromatin structure of the hematopoietic nucleus during BMDH formation, accompanied by the loss of the key hematopoietic transcription factor PU.1/Sfpi1 (SFFV proviral integration 1) and gain of the key hepatic transcriptional regulator HNF-1A homeobox A (HNF-1A/Hnf1a). Through genome-wide expression analysis of laser captured BMDH, a differential gene expression pattern was detected and the chromatin changes observed were confirmed at the level of chromatin regulator genes. Similarly, Tranforming Growth Factor-β1 (TGF-β1) and neurotransmitter (e.g. Prostaglandin E Receptor 4 [Ptger4]) pathway genes were over-expressed. In summary, in vivo BMDH generation is a process in which the hematopoietic cell nucleus changes its identity and acquires hepatic features. These BMDHs have their own cell identity characterized by an expression pattern different from hematopoietic cells or hepatocytes. The role of these BMDHs in the liver requires further investigation.

Right ventricular rupture due to recurrent mediastinal infection with a closed chest.

Right ventricular (RV) rupture in cases of mediastinitis following cardiac surgery is a rare and dangerous complication. Bleeding from the right ventricle occurs mainly after sternal reopening, due to either iatrogenic manipulation (wire removal, lesions due to wiring maneuvers) or mechanical shearing forces, producing direct injury. We present a case of RV wall perforation due to infection in a recurrent postoperative mediastinitis with a closed chest. The current literature on treatment of postoperative mediastinitis is also reviewed.

Posterior Sub-Tenon Triamcinolone Injection for Chronic Macular Oedema Associated With Non-Ischemic Branch or Central Retinal Vein Occlusion

Aims: To evaluate the effectiveness and safety of Posterior Sub-Tenon (PST) Triamcinolone Acetonide (TA) injection for persistent macular oedema associated with non-ischemic Central Retinal Vein Occlusion (CRVO) or Branch Retinal Vein Occlusion (BRVO) in non-vitrectomized eye. Methods: Fourteen consecutive eyes of 14 patients characterized by macular oedema lasting more than 3 months and with a visual acuity of less than 20/40 were enrolled. Six eyes presented with BRVO, 8 eyes with CRVO. PST injection of 40 mg TA was performed in topical anaesthesia. All patients were phakic, and followed for at least 6 months. Snellen visual acuity converted to LogMAR units and anatomic responses were evaluated before, and at 1, 3, 6, and 12 (if required) months after injections and re-injection considered. Results: In the BRVO group, mean foveal thickness was 548.2±49.50 μm preoperatively, and 452.8±56.2 μm and 280.8±62.5 μm at 1 and 12 month follow-up, respectively. Statistical analysis showed significant differences between preoperative and postoperative measurements (P<.05, paired t test) 3 months after injections. Improvement of visual acuity by at least 0.2 LogMAR was seen in 3(50%) of the 6 eyes. No re-injection was needed. In the CRVO group, mean foveal thickness was 543.7±34.4 μm preoperatively, and 283.0±29.0 μm and 234.8±23.6 μm at 1 and 12 month follow-up, respectively. Statistical analysis showed significant differences between preoperative and postoperative measurements (P<.05, paired t test). Improvement of visual acuity by at least 0.2 LogMAR was seen in 7 eyes (88%). Mean number of re-injection was of 2.1±0.3. Intraocular pressure elevation of 22 mm Hg or higher was found in 2/14 eyes (14%). Cataract progression was noted in 5/14 eyes (36%). Conclusions: PST injection of TA appears to be as safe and effective treatment for chronic macular oedema associated due to both non-ischemic BRVO or CRVO, with a better efficacy in BRVO.

Quelle prise en charge pour une suspicion de thrombose veineuse profonde des membres inférieurs [Suspicion of lower limb deep vein thrombosis: update on diagnosis and treatment].

Si l'examen clinique revêt une importance essentielle en lymphologie et exige des praticiens expérimentés, la lymphoscintigraphie et plus récemment la lympho-fluoroscopie au vert d'indocyanine constituent des moyens d'investigation précieux dans la prévention, le diagnostic et le traitement des pathologies vasculaires lymphatiques. L'intérêt de la lymphoscintigraphie réside dans l'analyse qualitative et quantitative de la migration des macromolécules par les vaisseaux lymphatiques et l'évaluation du secteur lymphatique profond. La lympho-fluoroscopie se distingue de la lymphoscintigraphie par l'obtention d'une cartographie détaillée des vaisseaux lymphatiques superficiels et d'images dynamiques en temps réel. Elle apporte à l'angiologue et au physiothérapeute des informations irremplaçables sur leur contractilité et la présence de dérivations compensatoires à privilégier lors du drainage lymphatique manuel. Venous thromboembolism is a frequent disease with an annual incidence of 0.75-2.69/1000 reaching 2-7/1000 > 70 years. Deep vein thrombosis (DVT) and pulmonary embolism are two manifestations of the same underlying disease. Most frequent localization of DVT is at lower limbs. The diagnostic workup begins with an estimation of DVT risk, a judicious use of D-Dimers, and compression venous ultrasound depending on DVT probability. The development of direct oral anticoagulants and recent data on interventional DVT treatment, in selected cases, have widened the therapeutic spectrum of DVT. The present article aims at informing the primary care physician of the optimized workup of patients with lower limb suspicion of DVT.

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.

E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis, and differentiation. Here, we reveal that E2F1 plays an essential role in liver physiopathology through the regulation of glycolysis and lipogenesis. We demonstrate that E2F1 deficiency leads to a decrease in glycolysis and de novo synthesis of fatty acids in hepatocytes. We further demonstrate that E2F1 directly binds to the promoters of key lipogenic genes, including Fasn, but does not bind directly to genes encoding glycolysis pathway components, suggesting an indirect effect. In murine models, E2F1 expression and activity increased in response to feeding and upon insulin stimulation through canonical activation of the CDK4/pRB pathway. Moreover, E2F1 expression was increased in liver biopsies from obese, glucose-intolerant humans compared with biopsies from lean subjects. Finally, E2f1 deletion completely abrogated hepatic steatosis in different murine models of nonalcoholic fatty liver disease (NAFLD). In conclusion, our data demonstrate that E2F1 regulates lipid synthesis and glycolysis and thus contributes to the development of liver pathology.

A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the upper extremity.

BACKGROUND: No studies have identified which patients with upper-extremity deep vein thrombosis (DVT) are at low risk for adverse events within the first week of therapy. METHODS: We used data from Registro Informatizado de la Enfermedad TromboEmbólica to explore in patients with upper-extremity DVT a prognostic score that correctly identified patients with lower limb DVT at low risk for pulmonary embolism, major bleeding, or death within the first week. RESULTS: As of December 2014, 1135 outpatients with upper-extremity DVT were recruited. Of these, 515 (45%) were treated at home. During the first week, three patients (0.26%) experienced pulmonary embolism, two (0.18%) had major bleeding, and four (0.35%) died. We assigned 1 point to patients with chronic heart failure, creatinine clearance levels 30-60 mL min(-1) , recent bleeding, abnormal platelet count, recent immobility, or cancer without metastases; 2 points to those with metastatic cancer; and 3 points to those with creatinine clearance levels < 30 mL min(-1) . Overall, 759 (67%) patients scored ≤ 1 point and were considered to be at low risk. The rate of the composite outcome within the first week was 0.26% (95% confidence interval [CI] 0.004-0.87) in patients at low risk and 1.86% (95% CI 0.81-3.68) in the remaining patients. C-statistics was 0.73 (95% CI 0.57-0.88). Net reclassification improvement was 22%, and integrated discrimination improvement was 0.0055. CONCLUSIONS: Using six easily available variables, we identified outpatients with upper-extremity DVT at low risk for adverse events within the first week. These data may help to safely treat more patients at home.