Update on Therapeutic Options in Lipodystrophy

Purpose of Review

The purpose of this review is to summarize the therapeutic approach for lipodystrophy syndromes with conventional treatment options and metreleptin therapy in detail and to point out the current investigational treatments in development.

Recent Findings

The observation of leptin deficiency in patients with lipodystrophy and the potential of leptin replacement to rescue metabolic abnormalities in animal models of lipodystrophy were followed by the first clinical study of leptin therapy in patients with severe lipodystrophy. This and several other long-term studies demonstrated important benefits of recombinant human leptin (metreleptin) to treat metabolic abnormalities of lipodystrophy. These studies ultimately led to the recent FDA approval of metreleptin for the treatment of generalized lipodystrophy and EMA approval for both generalized and partial lipodystrophy. Additional research efforts in progress focus on novel treatment options, predominantly for patients with partial lipodystrophy.

Summary

Current treatment of generalized lipodystrophy includes metreleptin replacement as an adjunct to diet and standard treatment approach for metabolic consequences of lipodystrophy. Beyond metreleptin, a number of different compounds and treatment modalities are being studied for the treatment of partial lipodystrophy.

     

Fatigue toughness of irradiated vitamin E/UHMWPE blends

Radiation cross‐linked ultrahigh molecular weight polyethylenes (UHMWPEs) have become the standard‐of‐care in total joint replacements (TJR) in the last decade because of their superior wear resistance in comparison with previously used “conventional” gamma sterilized UHMWPE. Some first generation radiation cross‐linked UHMWPEs were stabilized against oxidation by post‐irradiation melting, which significantly reduced their fatigue crack propagation resistance or fatigue toughness. Second generation cross‐linked UHMWPEs incorporated instead an antioxidant such as vitamin E, eliminating the need for melting. In this study, we investigated the fatigue crack propagation resistance and the impact toughness of vitamin E‐blended and radiation cross‐linked UHMWPEs as a function of vitamin E concentration and radiation dose. Both properties were strongly dependent on the cross‐link density and they showed a good correlation with each other (R² = 0.89). © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1514–1520, 2016.     

Increased Pleural Soluble Fas Ligand (sFasL) Levels in Tuberculosis Pleurisy and Its Relation with T-helper Type 1 Cytokines

Tuberculosis (TB) pleurisy is accepted to be the best model for evaluating the local protective cellular immune response to Mycobacterium tuberculosis (MTB) since it can be spontaneously self-cured. Therefore, we aimed to evaluate the involvement of cytokines and the soluble apoptosis-modulating factors sFas and sFasL in local protective cellular immunity to MTB. Pleural fluid samples were collected from 35 patients with TB pleurisy, 39 patients with malignant pleurisy, and 14 patients with non-TB nonmalignant (n-TB n-M) pleurisy and were evaluated for the levels of several cytokines, soluble Fas (sFas), and sFas ligand (sFasL) by using ELISA. The levels of IFN-γ, IL-12p40, IL-18, IL-8, and sFasL in TB pleurisy were significantly higher in comparison to those in the malignant pleurisy and n-TB n-M pleurisy groups. In addition, pleural sFasL levels were increased and positively correlated with IFN-γ and IL-18 levels in TB patients. In conclusion, this study demonstrates that Th1-type-specific cellular immunity is responsible for protective immunity in TB and suggests that Fas-mediated apoptosis may be at least a part of protective immunity to tuberculosis and could be regulated by type 1 T-cell response. IFN-γ and sFasL levels can be used as diagnostic markers for differing TB pleurisy from other pleurisies.     

PTFE膜植入牙周病损创面后的细菌污染

用人工膜覆盖根面,避免牙周创面愈合早期龈结缔组织及上皮接触根面,从而形成牙周创面的新附着,即牙周膜诱导性再生术.本实验以扫描电镜为检查手段,观察了人类牙周膜诱导再生术后取出的PTFE膜内面有形成份的分布,并对照临床表现,发现无论膜的边缘是否暴露于口腔,膜内面均存在细菌的污染,但这种污染并不影响新附着的形成.     

乳牙感染根管的菌丛分析

目的分析乳牙根尖周炎感染根管菌丛，为进一步防治提供依据。方法用直接酶法对８例乳牙急性根尖周炎、１４例乳牙慢性根尖周炎感染根管菌丛成分进行分析。结果共检出２４０株细菌，厌氧菌２００株，主要分布于消化链球菌、类杆菌、韦永氏菌、真细菌、丙酸杆菌、放线菌和梭杆菌。急性炎症组类杆菌、梭杆菌的检出率明显高于慢性组（Ｐ＜００５），主要差异在牙龈类杆菌和具核梭杆菌；慢性炎症组小韦永氏菌的检出率明显高于急性组（Ｐ＜０．０５）。结论乳牙急、慢性根尖周炎感染根管内是以厌氧菌为优势菌的混合感染。牙龈类杆菌、具核梭杆菌可能与乳牙根尖周炎的急性症状有关。小韦永氏菌在乳牙慢性根尖周炎中的作用不容忽视