Absence of correlation between glycated hemoglobin and lipid composition of erythrocyte membrane in type 2 diabetic patients

Correlation of glycated hemoglobin (HbA(1c)) level with degrees of certain peroxidative changes in erythrocyte membrane lipids in diabetic patients have been reported. In the present study, peroxidation of erythrocyte lipids was assessed by changes in tocopherols (Toc), phospholipids (PL), and malondialdehyde (MDA). Membrane cholesterol, Toc, and PL were determined from the same lipid extract. Toc and cholesterol were measured simultaneously by high-performance liquid chromatography (HPLC), and each PL class was determined by a single HPLC elution with ultraviolet light (UV) detection. The detection of PL with UV depends primarily on double bonds in fatty acids and shows a decrease in fatty acids by peroxidation. Changes in Toc and each PL were calculated on the basis of cholesterol and SM, respectively, since cholesterol and sphingomyelin (SM) in the cell membrane are not prone to peroxidation. MDA was measured by an HPLC method with fluorescence detection. These methods for assessment for peroxidation of membrane lipids in intact erythrocytes were validated by experiments with 2, 2-azobis(2-amidinopropane)dihydrochloride (AAPH) and tert-butylhydroperoxide (tBHP); nevertheless, significant differences in the levels of Toc, each PL class, and MDA between a high-HbA(1c) group and a low-HbA(1c) group were not detected.     

Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus

Yorifuji T, Fujimaru R, Hosokawa Y, Tamagawa N, Shiozaki M, Aizu K, Jinno K, Maruo Y, Nagasaka H, Tajima T, Kobayashi K, Urakami T. Comprehensive molecular analysis of Japanese patients with pediatric‐onset MODY‐type diabetes mellitus. Background: In Asians, mutations in the known maturity‐onset diabetes of the young (MODY) genes have been identified in only <15% of patients. These results were obtained mostly through studies on adult patients. Objective: To investigate the molecular basis of Japanese patients with pediatric‐onset MODY‐type diabetes. Subjects: Eighty Japanese patients with pediatric‐onset MODY‐type diabetes. Methods: Mitochondrial 3243A>G mutation was first tested by the polymerase chain reaction restriction fragment length polymorphism analysis for maternally inherited families. Then, all coding exons and exon–intron boundaries of the HNF1A, HNF1B, GCK, and HNF4A genes were amplified from genomic DNA and directly sequenced. Multiplex ligation‐dependent probe amplification analysis was also performed to detect whole‐exon deletions. Results: After excluding one patient with a mitochondrial 3243A>G, mutations were identified in 38 (48.1%) patients; 18 had GCK mutations, 11 had HNF1A mutations, 3 had HNF4A mutations, and 6 had HNF1B mutations. In patients aged <8 yr, mutations were detected mostly in GCK at a higher frequency (63.6%). In patients >9 yr of age, mutations were identified less frequently (45.1%), with HNF1A mutations being the most frequent. A large fraction of mutation‐negative patients showed elevated homeostasis model assessment (HOMA) insulin‐resistance and normal HOMA‐β indices. Most of the HNF1B mutations were large deletions, and, interestingly, renal cysts were undetectable in two patients with whole‐gene deletion of HNF1B. Conclusion: In Japanese patients with pediatric‐onset MODY‐type diabetes, mutations in known genes were identified at a much higher frequency than previously reported for adult Asians. A fraction of mutation‐negative patients presented with insulin‐resistance and normal insulin‐secretory capacities resembling early‐onset type 2 diabetes.     

Local regulation of neutrophil elastase activity by endogenous α1-antitrypsin in lipopolysaccharide-primed hematological cells

Neutrophil elastase released from activated neutrophils contributes in combating bacterial infection. While chronic inflammation results in anemia and decreased bone marrow activities, little is known about the effect of neutrophil elastase on hematological cell growth in severe inflammatory states. Here, we demonstrated that α1-antitrypsin, a physiological inhibitor of neutrophil elastase, functions as a regulator for cell growth by neutralizing neutrophil elastase activity in lipopolysaccharide-primed hematological cells. HL-60 cells were resistant to neutrophil elastase, as they also expressed α1-antitrypsin. The growth of HL-60 cells transduced with a LentiLox-short hairpin α1-antitrypsin vector was significantly suppressed by neutrophil elastase or lipopolysaccharide. When CD34⁺ progenitor cells were differentiated towards a granulocytic lineage, they concomitantly expressed neutrophil elastase and α1-antitrypsin and prevented neutrophil elastase-induced growth inhibition. These results suggest that granulocytes might protect themselves from neutrophil elastase-induced cellular damage by efficiently neutralizing its activity through the simultaneous secretion of endogenous α1-antitrypsin.     

Effect of intra-articular lesions on the outcome of periacetabular osteotomy in patients with symptomatic hip dysplasia

In order to clarify how intra-articular lesions influence the survival of a periacetabular osteotomy in patients with dysplasia of the hip, we performed an observational study of 121 patients (121 hips) who underwent a transposition osteotomy of the acetabulum combined with an arthroscopy. Their mean age was 40.2 years (13 to 64) and the mean follow-up was 9.9 years (2 to 18). Labral and cartilage degeneration tended to originate from the anterosuperior part of the acetabulum, followed by the femoral side. In all, eight hips (6.6%) had post-operative progression to Kellgren-Lawrence grade 4 changes, and these hips were associated with the following factors: moderate osteoarthritis, decreased width of the joint space, joint incongruity, and advanced intra-articular lesions (subchondral bone exposure in the cartilage and a full-thickness labral tear). Multivariate analysis indicated subchondral bone exposure on the femoral head as an independent risk factor for progression of osteoarthritis (p = 0.003). In hips with early stage osteoarthritis, femoral subchondral bone exposure was a risk factor for progression of the grade of osteoarthritis. Although the outcome of transposition osteotomy of the acetabulum was satisfactory, post-operative progression of osteoarthritis occurred at a high rate in hips with advanced intra-articular lesions, particularly in those where the degenerative process had reached the point of femoral subchondral bone exposure.     

A patient with early syphilis complicated by fatty liver who showed an alleviation of hepatopathy accompanied by jaundice after receiving anti-syphilitic therapy

A 42-year-old male with visceral obesity and a fatty liver presented with hepatopathy accompanied by jaundice and was diagnosed to have early syphilis based on the results of standard serologic tests and clinical findings. Both the subjective and objective findings including hepatopathy were rapidly alleviated by anti-syphilitic therapy. Severe hepatopathy accompanied by jaundice used to be considered a rare complication. However, due to contemporary unhealthy lifestyle patterns characterized by hypernutrition and a lack of exercise the occurrence of fatty liver is now dramatically increasing. Our findings suggest that the occurrence of fatty liver can exacerbate the damage to the hepatic parenchyma due to a Treponema pallidum infection.