Congenital disorder of glycosylation (PMM2‐CDG) in a patient with antithrombin deficiency and severe thrombophilia

de la Morena‐Barrio ME, Sevivas TS, Martínez‐Martínez I, Miñano A, Vicente V, Jaeken J, Corral J. Congenital disorder of glycosylation (PMM2‐CDG) in a patient with antithrombin deficiency and severe thrombophilia. J Thromb Haemost 2012; 10 : 2625–7.     

Aktuelle Therapieoptionen bei Larynx- und Hypopharynxkarzinomen

The prognosis of squamous epithelial cell carcinoma of the upper aerodigestive tract has improved considerably in the last 30 years. Patients presenting with stage I or II disease are treated with surgery or radiation therapy with curative intent. Although the efficacy is comparable between the two methods, surgery is usually preferred so that the side effects and late toxic effects of radiation can be avoided. For the treatment of advanced stages of disease, surgery, radiotherapy, chemotherapy and immunotherapy are usually combined. The introduction of concurrent administration of chemotherapy and radiotherapy (chemoradiotherapy) has been a major advancement. This has resulted in local control and survival rates comparable to those seen following radical surgery and postoperative radiotherapy, but with preservation of the larynx in most patients. However, recent epidemiological observations have shown declining survival rates in laryngeal cancer patients, raising concern about uncritical and too frequent use of this approach. The rationale for choosing treatment options for patients with laryngeal and hypopharyngeal carcinoma is discussed.     

Treatment of hypertriglyceridemia

Hypertriglyceridemia is a disorder commonly encountered in clinical practice. Treatment of this condition aims to prevent the major complications of hypertriglyceridemia, which differ depending on whether triglyceride elevations are moderate or severe. This review discusses the pathophysiology and clinical consequences of hypertriglyceridemia and outlines treatment approaches based on the degree of triglyceride elevation. Special consideration is given to clinical trials using medications that primarily target triglycerides.     

Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes

Recent studies reveal a strong relationship between reduced mitochondrial content and insulin resistance in human skeletal muscle, although the underlying factors responsible for this association remain unknown. To address this question, we analyzed muscle biopsy samples from young, lean, insulin resistant (IR) offspring of parents with type 2 diabetes and control subjects by microarray analyses and found significant differences in expression of ~512 probe pairs. We then screened these genes for their potential involvement in the regulation of mitochondrial biogenesis using RNA interference and found that mRNA and protein expression of lipoprotein lipase (LPL) in skeletal muscle was significantly decreased in the IR offspring and was associated with decreased mitochondrial density. Furthermore, we show that LPL knockdown in muscle cells decreased mitochondrial content by effectively decreasing fatty acid delivery and subsequent activation of peroxisome proliferator-activated receptor (PPAR)-δ. Taken together, these data suggest that decreased mitochondrial content in muscle of IR offspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased PPAR-δ activation.