运动与原发性骨疏松

目的原发性骨质疏松指绝经期后骨质疏松和老年性骨质疏松.绝经期后骨质疏松的发生与妇女雌激素水平迅速下降有关.老年性骨质疏松的发生与整体功能下降、运动减少、营养代谢功能下降等有关.探述运动与原发性骨质疏松的关系. 方法论述了运动减少对骨的影响、骨的力学特性、骨的压电效应、运动与骨质疏松发生的关系. 结果力学刺激的减少,可增加骨质吸收,减少骨形成,造成骨量减少.运动员荷可以使疏松骨骼骨量增加. 结论原发性骨质疏松的发生与该类患者骨运动减少有关,而适当的运动训练可以预防和治疗骨质疏松.     

复方聚乙二醇电解质散在老年肠道准备的临床观察

目的 比较甘露醇、蓖麻油、复方聚乙二醇电解质散在老年科肠道镜检肠道准备的效果、耐受性及不良反应发生率.方法 选取门诊及同期住院进行肠镜检查的93例老年病人(分为甘露醇组31例,蓖麻油组32例,复方聚乙二醇电解质散组30例),对肠道准备过程中清洁肠道的效果、病人的耐受性和胃肠道反应情况进行比较.结果 甘露醇组、蓖麻油组、复方聚乙二醇电解质散组发生肠胃肠道反应者分别为7例、12例和3例,复方聚乙二醇电解质散组与前两组比较,p＜0.05;不能耐受者甘露醇组、蓖麻油组和复方聚乙二醇电解质散组分别为7例、9例和1例,复方聚乙二醇电解质散组与前两组比较,p＜0.05;肠道清洁度Ⅰ Ⅱ级者甘露醇组、蓖麻油组和复方聚乙二醇电解质散组分别为12例、11例和28例,复方聚乙二醇电解质散组明显优于前2组,p＜0.05.结论 复方聚乙二醇电解质散有明显的泻下作用,病人耐受性好,胃肠道反应少而轻,清洁肠道效果明显优于甘露醇和蓖麻油.     

Induction of Retinol Dehydrogenase 9 Expression in Podocytes Attenuates Kidney Injury

The intracellular concentration of retinoic acid is determined by two sequential oxidation reactions that convert retinol to retinoic acid. We recently demonstrated that retinoic acid synthesis is significantly impaired in glomeruli of HIV-1 transgenic mice (Tg26), a murine model of HIV-associated nephropathy. This impaired retinoic acid synthesis correlates with reduced renal expression of retinol dehydrogenase 9, which catalyzes the rate-limiting step of retinoic acid synthesis by converting retinol to retinal. Because retinoic acid has renal protective effects and can induce podocyte differentiation, we hypothesized that restoration of retinoic acid synthesis could slow the progression of renal disease. Herein, we demonstrate that overexpression of retinol dehydrogenase 9 in cultured podocytes induces the expression of podocyte differentiation markers. Furthermore, we confirm that podocyte-specific overexpression of retinol dehydrogenase 9 in mice with established kidney disease due to either HIV-associated nephropathy or adriamycin-induced nephropathy decreases proteinuria, attenuates kidney injury, and restores podocyte differentiation markers. Our data suggest that restoration of retinoic acid synthesis could be a new approach to treat kidney disease.Retinoic acids (RAs) are derivatives of vitamin A and have multiple cellular functions, including inhibition of proliferation, induction of cell differentiation, and inhibition of inflammation.¹ In addition to their established benefits in the treatment of a variety of cancers, RA has also been shown to protect against renal injury in multiple experimental models of kidney disease,² including HIV-associated nephropathy (HIVAN).³ Both in vitro and in vivo studies suggest that RA restores the expression of podocyte differentiation markers, including nephrin, podocin, and synaptopodin.^3,4 These studies provide strong evidence supporting the therapeutic benefit of RA in kidney diseases with podocyte injury. In fact, a phase II clinical trial examining the efficacy of RA for treatment of podocyte diseases, including minimal change disease, FSGS, or collapsing glomerulopathy, is ongoing (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00098020","term_id":"NCT00098020"}}NCT00098020). However, clinical use of RA is challenging because of its side effects.⁵After cellular uptake, retinol is converted to RA by two sequential oxidation reactions. Retinol dehydrogenases (RHDs) oxidize retinol to retinal,⁶ which is further metabolized to retinoic acid by retinaldehyde dehydrogenases (ALDHs).⁷ The expression of these enzymes varies greatly among different cell types and at different stages of cell differentiation.⁷ Both the synthesis and metabolism of the bioactive metabolites of retinol are impaired in cancer cells.⁸ The kidney is a major organ for retinoid metabolism. However, not much is known regarding how retinoid metabolism is altered in renal disease.Our previous work showed that although the expression of retinoic acid receptor-α–target genes is suppressed in kidneys of a murine model of HIVAN (Tg26) and of patients with HIVAN, the expression of retinoic acid receptor-α is not different between normal and diseased kidneys.⁹ The concentration of RA, however, is significantly reduced in the kidney cortex and isolated glomeruli of Tg26. We also found that the glomerular concentration of RA is >10-fold higher than the concentration in the kidney cortex.⁹ Examination of enzymes involved in RA metabolism reveal that two key enzymes in the RA synthetic pathway, retinol dehydrogenase type 1 and type 9 (RDH1 and RDH9), were significantly downregulated in Tg26 glomeruli.⁹ RDH9 is a rate-limiting enzyme in RA synthesis. Because it is known that RA has renal protective effects and is able to induce podocyte differentiation, we hypothesize that overexpression of RDH9 to restore endogenous RA synthesis could slow the progression of renal disease.Consistent with our findings, recent studies also showed that endogenous RA synthesis is impaired in kidneys of diabetic db/db mice¹⁰ and TGF-β transgenic mice.¹¹ These data together with ours suggest that endogenous RA synthesis is impaired in diseased kidneys. Thus, a better understanding of RA metabolism in kidney disease could help us to identify potential new therapy for kidney diseases.     

Mitogen-Activated Protein Kinase Phosphatase 3 (MKP-3)–Deficient Mice Are Resistant to Diet-Induced Obesity

Mitogen-activated protein kinase phosphatase 3 (MKP-3) is a negative regulator of extracellular signal–related kinase signaling. Our laboratory recently demonstrated that MKP-3 plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output. This study shows that MKP-3 deficiency attenuates body weight gain induced by a high-fat diet (HFD) and protects mice from developing obesity-related hepatosteatosis. Triglyceride (TG) contents are dramatically decreased in the liver of MKP-3^−/− mice fed an HFD compared with wild-type (WT) controls. The absence of MKP-3 also reduces adiposity, possibly by repressing adipocyte differentiation. In addition, MKP-3^−/− mice display increased energy expenditure, enhanced peripheral glucose disposal, and improved systemic insulin sensitivity. We performed global phosphoproteomic studies to search for downstream mediators of MKP-3 action in liver lipid metabolism. Our results revealed that MKP-3 deficiency increases the phosphorylation of histone deacetylase (HDAC) 1 on serine 393 by 3.3-fold and HDAC2 on serine 394 by 2.33-fold. Activities of HDAC1 and 2 are increased in the livers of MKP-3^−/− mice fed an HFD. Reduction of HDAC1/2 activities is sufficient to restore TG content of MKP-3^−/− primary hepatocytes to a level similar to that in WT cells.     

Endoscopic management for pancreatic injuries due to blunt abdominal trauma decreases failure of nonoperative management and incidence of pancreatic-related complications

Introduction

The actual benefit of endoscopic techniques in the non-operative management (NOM) of pancreatic injury is still unclear, with its role and effectiveness in the NOM of pancreatic injury remains defined and doubted. The purpose of this study was to evaluate the feasibility and long-term results of endoscopic techniques in the NOM of blunt pancreatic injury, and to determine whether NOM can be performed safely for selective patients with pancreatic injury.

Patients and methods

The records and follow-up data of all patients with blunt pancreatic injuries over 16-year period from October 1, 1996, to September 30, 2012 at our department were retrospectively reviewed. Failure of NOM (FNOM) occurred if laparotomy was required after attempted NOM.

Results

132 patients (32% of all patients with blunt pancreatic injury) underwent NOM, including 58 who underwent endoscopic management (EM) and 74 who were observed without EM (NO-EM). FNOM of overall NOM was 20%, including 30% of NO-EM and 9% of EM. There was no significant difference in FNOM for NO-EM versus EM for grade I, however, a significant decrease in FNOM was noted with the addition of EM for grade II and III. EM was a statistically significant independent risk factor. Regular follow-up of 1 year showed that, for patients from grade I to III, 53 patients (42%) from operative management (OM) and 34 patients (46%) of the NO-EM developed various pancreatic-related complications, while only 15 patients (26%) of the EM developed such complications, and the difference was significant.

Conclusion

Application of strictly defined selection criteria for NOM and EM in patients with blunt pancreatic injury resulted in one of the lowest FNOM rates (9%) and pancreatic-related complications incidence (25%). Selective application of EM for hemodynamically stable patients with blunt pancreatic injury will extend the indications for, and improve success of NOM.