No abstract

ABSTRACT. Hyperglycemia-induced reactive oxygen species production can cause diabetes and its complications, including atherosclerosis. The role of mitochondrial DNA variants and mitochondrial copy number in the pathogenesis of diabetic atherogenesis is not well understood. We examined 36 diabetic patients who had undergone amputation for diabetic foot and seven non-diabetic patients who had undergone amputation after traumatic injury. Mitochondrial DNA was extracted and used for sequencing. Single nucleotide polymorphisms (SNPs) relative to the Cambridge reference sequence were analyzed. Mitochondrial DNA copy number was quantified by real-time PCR. Twenty-one novel variants were detected in 29 diabetic patients with arterial stenosis; six of the variants were heteroplasmic, and most occurred in highly evolutionarily conserved residues. These variants were more prevalent in patients with arterial stenosis than in those without stenosis. The novel ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3339-3348 (2012) M.C. Chien et al. 3340

Hypokalemic paralysis is a rare presentation of Fanconi syndrome (FS) caused by Sjögren Syndrome (SS). We describe a 39-year-old man who manifested flaccid paralysis of 4 limbs. Laboratory investigations showed profound hypokalemia (1.6 mmol/L) with renal K wasting, hyperchloremic metabolic acidosis with positive urine anion gap, hypophosphatemia with hyperphosphaturia, hypouricemia with hyperuricosuria, normoglycemic glycosuria, and abnormal serum creatinine concentration 2.2 mg/dL. A thorough survey for the cause of FS revealed that he had xerophthalmia and xerostomia accompanied by high anti-Ro antibody, positive Schirmer test, and delayed saliva excretion on sialoscintigraphy, confirming the diagnosis of SS. Potassium citrate, active vitamin D3, and high phosphate diet for his FS coupled with mycophenolate mofetil for SS resolved clinical symptoms and ameliorated renal function. Early recognition of HP due to the underlying SS-related FS with prompt therapy not only could terminate potentially life-threatening hypokalemia, but also improve renal outcome.

ABSTRACT. The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factorkB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.