PGC-1α is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle

The aim of the present study was to test the hypothesis that exercise training prevents an age-associated decline in skeletal muscle mitochondrial enzymes through a PGC-1α dependent mechanism. Whole body PGC-1α knock-out (KO) and littermate wildtype (WT) mice were submitted to long term running wheel exercise training or a sedentary lifestyle from 2 to 13 month of age. Furthermore, a group of approximately 4-month-old mice was used as young untrained controls. There was in both genotypes an age-associated ∼30% decrease in citrate synthase (CS) activity and superoxide dismutase (SOD)2 protein content in 13-month-old untrained mice compared with young untrained mice. However, training prevented the age-associated decrease in CS activity and SOD2 protein content only in WT mice, but long term exercise training did increase HKII protein content in both genotypes. In addition, while CS activity and protein expression of cytc and SOD2 were 50–150% lower in skeletal muscle of PGC-1α mice than WT mice, the expression of the pro-apoptotic protein Bax and the anti-apoptotic Bcl2 was ∼30% elevated in PGC-1α KO mice. In conclusion, the present findings indicate that PGC-1α is required for training-induced prevention of an age-associated decline in CS activity and SOD2 protein expression in skeletal muscle.     

Fetal circulation in left-sided congenital heart disease measured by cardiovascular magnetic resonance: a case–control study

Background

The distribution of blood flow in fetuses with congenital heart disease (CHD) is likely to influence fetal growth, organ development, and postnatal outcome, but has previously been difficult to study. We present the first measurements of the distribution of the fetal circulation in left-sided CHD made using phase contrast cardiac magnetic resonance (CMR).

Methods

Twenty-two fetuses with suspected left-sided CHD and twelve normal controls underwent fetal CMR and echocardiography at a mean of 35 weeks gestation (range 30–39 weeks).

Results

Fetuses with left-sided CHD had a mean combined ventricular output 19% lower than normal controls (p < 0.01). In fetuses with left-sided CHD with pulmonary venous obstruction, pulmonary blood flow was significantly lower than in those with left-sided CHD without pulmonary venous obstruction (p < 0.01). All three fetuses with pulmonary venous obstruction had pulmonary lymphangectasia by fetal CMR and postnatal histology. Fetuses with small but apex forming left ventricles with left ventricular outflow tract or aortic arch obstruction had reduced ascending aortic and foramen ovale flow compared with normals (p < 0.01). Fetuses with left-sided CHD had more variable superior vena caval flows than normal controls (p < 0.05). Six fetuses with CHD had brain weights at or below the 5^th centile for gestational age, while none of the fetuses in the normal control group had brain weights below the 25^th centile.

Conclusions

Measurement of the distribution of the fetal circulation in late gestation left-sided CHD is feasible with CMR. We demonstrated links between fetal blood flow distribution and postnatal course, and examined the relationship between fetal hemodynamics and lung and brain development. CMR enhances our understanding of pathophysiology of the fetal circulation and, with more experience, may help with the planning of perinatal management and fetal counselling.     

创伤病人输注浓缩红细胞导致的高钾血症

研究表明病人输注细胞类制品,特别是浓缩红细胞(PRBC)和新鲜全血,将导致钾离子稳态的紊乱.在成人和儿童中,报道的低钾血症比高钾血症常见.我们所知的最大的回顾性研究是肝移植儿童,低钾血症的发生率为72%,高钾血症低于5%.     

Functional status decline as a measure of adverse events in home health care: an observational study

Background  

Research that examines the quality of home health care is complex because no gold standard exists for measuring adverse outcomes, and because the patient and clinician populations are highly heterogeneous. The objectives in this study are to develop models to predict functional decline for three indices of functional status as measures of adverse events in home health care and determine which index is most appropriate for risk-adjusting for future quality research.     

Lipoxin A4 attenuates zymosan-induced arthritis by modulating endothelin-1 and its effects

BACKGROUND AND PURPOSE

Lipoxin A₄ (LXA₄) is a lipid mediator involved in the resolution of inflammation. Increased levels of LXA₄ in synovial fluid and enhanced expression of the formyl peptide receptor 2/lipoxin A₄ receptor (FPR2/ALX) in the synovial tissues of rheumatoid arthritis patients have been reported. Endothelins (ETs) play a pivotal pro-inflammatory role in acute articular inflammatory responses. Here, we evaluated the anti-inflammatory role of LXA₄, during the acute phase of zymosan-induced arthritis, focusing on the modulation of ET-1 expression and its effects.

EXPERIMENTAL APPROACH

The anti-inflammatory effects of LXA₄, BML-111 (agonist of FPR2/ALX receptors) and acetylsalicylic acid (ASA) pre- and post-treatments were investigated in a murine model of zymosan-induced arthritis. Articular inflammation was assessed by examining knee joint oedema; neutrophil accumulation in synovial cavities; and levels of prepro-ET-1 mRNA, leukotriene (LT)B₄, tumour necrosis factor (TNF)-α and the chemokine KC/CXCL1, after stimulation. The direct effect of LXA₄ on ET-1-induced neutrophil activation and chemotaxis was evaluated by shape change and Boyden chamber assays respectively.

KEY RESULTS

LXA₄, BML-111 and ASA administered as pre- or post-treatment inhibited oedema and neutrophil influx induced by zymosan stimulation. Zymosan-induced preproET-1 mRNA, KC/CXCL1, LTB₄ and TNF-α levels were also decreased after LXA₄ pretreatment. In vitro, ET-1-induced neutrophil chemotaxis was inhibited by LXA₄ pretreatment. LXA₄ treatment also inhibited ET-1-induced oedema formation and neutrophil influx into mouse knee joints.

CONCLUSION AND IMPLICATION

LXA₄ exerted anti-inflammatory effects on articular inflammation through a mechanism that involved the inhibition of ET-1 expression and its effects.     

Familial florid cemento-osseous dysplasia: a report of three cases and review of the literature

Familial cases of benign fibro-osseous lesions of the jaws are rare and have been described under numerous terms including familial gigantiform cementoma, multiple cemento-ossifying fibromas, sclerotic cemental masses and familial florid cemento-osseous dysplasia. The synonymous and interchangeable use of these terms to describe distinct entities with overlapping features has resulted in confusion and inaccurate categorisation of these lesions. This study highlights three family members with diffuse fibro-osseous jaw lesions with areas of significant expansion. In the pursuit of finding the best clinicopathological categorisation for the reported cases, familial florid cemento-osseous dysplasia and familial gigantiform cementoma were investigated. The final consensus of these three cases was that of familial florid cemento-osseous dysplasia, and one patient presented with a concurrent “ossifying fibromatoid lesion”. A literature review on the above entities was performed in an attempt to provide clarification and delineate distinguishing features of the individual diseases.     

Studies of a familial platelet disorder

At least 22 members of a large kindred have a bleeding tendency resulting from an autosomal dominant disorder of platelet production and function. Phenotypic manifestations include mild to moderate thrombocytopenia, bleeding time prolongation, and abnormal platelet aggregation. Platelet survival time is normal. The platelet disorder in this family appears to differ from known hereditary thrombocytopenic or thrombocytopathic syndromes and may represent a new genetic disease. Six family members reportedly developed hematologic neoplasms: acute monocytic leukemia nine years after treatment for congenital neuroblastoma; lymphosarcoma at age 10 years; myeloid leukemia at age 23 years; acute myelocytic leukemia at age 62 years; leukemia of unknown type at age 48 years; and lymphocytic lymphoma at age 52 years.