Effects of regular exercise on neutrophil functions, oxidative stress parameters and antibody responses against 4-hydroxy-2-nonenal adducts in middle aged humans.

Regular exercise has recognized health benefits, partly because it reportedly lowers the levels of the oxidation products of proteins and DNA at rest, in contrast with the effect of acute exercise. However, when we compared oxidative response markers in active middle-aged subjects with those in sedentary ones, the level of urinary 8-OHdG was higher in active subjects. Because neutrophils are the first line of defense against a variety of infectious diseases, we then compared the cell density, functions and apoptosis of neutrophils in active subjects with those in sedentary ones. The cell density of neutrophils and phagocytosis of opsonized zymosan by neutrophils were higher in active subjects, being similar with the reported effects of acute exercise. To determine any beneficial effects of oxidative stress in active subjects, we then compared the levels of antibodies against 4-hydroxy-2-nonenal adducts in active subjects with those in sedentary ones, because 4-hydroxy-2-nonenal is one of the most common bioactive aldehyde products of oxidative stress, and because the IgM class of antibodies against oxidized low-density lipoprotein is associated with atheroprotective properties. The level of the IgM but not the IgG class of antibodies against 4-hydroxy-2-nonenal adducts was higher in active subjects. Overall, this study revealed that our active middle-aged subjects showed both oxidative responses and a higher IgM response to reactive carbonyl derivatives, possibly providing a basis for a health benefit by exercise in our active subjects.

Effects of calorie-restricted low-carbohydrate diet on glucose and lipid metabolism in Otsuka Long Evans Tokushima Fatty rats.

AIM: We investigated the effects of a calorie-restricted low-carbohydrate diet on glucose and lipid metabolism, and body fat distribution, especially on the secretion of leptin and lipoprotein lipase from adipose tissue in Otsuka Long Evans Tokushima Fatty (OLETF) rats. METHODS: Forty-three week-old male OLETF rats were randomized into three groups (n=6 per group): the HC group (HC) was fed a diet with 60% carbohydrate; the LC group (LC) with 30% carbohydrate; and the P-HC group (P-HC) with 60% carbohydrate and pioglitazone (0.1%). The total calorie intake was restricted to 70% of the average intake from each diet (60 kcal/day). The diets were continued for 8 weeks. RESULTS: Similar decreases in body weight and serum glucose were observed in the three groups. Serum insulin concentration was significantly decreased in LC and P-HC compared to HC. Serum total cholesterol and triglycerides decreased significantly (p<0.05) in LC and P-HC compared to HC. The decrease of visceral fat area measured by computed tomography was greatest in LC among the three groups. At the end of the diet, leptin secretion from visceral adipose tissue and lipoprotein lipase (LPL) activity in subcutaneous adipose tissue were significantly higher in LC and P-HC compared to HC (p<0.05). CONCLUSION: These results indicate that under calorie-restricted conditions, low carbohydrates are much more effective than high carbohydrates in improving insulin sensitivity.

[Successful chemotherapy with carboplatin and docetaxel for an elderly patient with advanced non-small cell lung cancer].

A 79-year-old man was admitted to our hospital with right hypochondrium pain. His chest X-ray and CT scan showed a mass lesion on the left upper lobe, and multiple metastases in the liver. The diagnosis was non-small cell carcinoma of the lung. He received 4 courses of combined chemotherapy of carboplatin and docetaxel every 4 weeks. At the end of 4 courses, a partial response was achieved. Two courses of a in similar regimen were added at the time of a later recurrence, and the effect was a partial response. Carboplatin+docetaxel combined chemotherapy, which can be conducted relatively safely on an outpatient basis, may be an effective treatment for non-small cell lung cancer in the elderly.

A case of hyperlipidemia with homozygous apolipoprotein E5 (Glu3-->Lys).

In this study, we present clinical feature of a novel case with homozygous apolipoprotein (apo) E5. The patient was a 53-year-old Japanese woman. She was from a small island off the coast of Kagoshima Prefecture, Japan. Her parents were first degree cousins. No corneal opacification, xanthomatosis, lymphadenopathy, or hepatosplenomegaly was observed. There have been no signs of clinically overt atherosclerosis to date. Her serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL)-cholesterol levels were 11.6, 6.1 and 1.2 mmol/l, respectively, and apo A-I, A-II, B, C-II, C-III and E levels were 121, 34.8, 269, 10.4, 25.7 and 10.3 mg/dl, respectively. Serum lipoprotein profile analyzed by agarose gel electrophoresis and differential staining revealed markedly increased cholesterol and TG in both beta and prebeta-migrated lipoproteins, whereas alpha-migrated lipoprotein showed decreased cholesterol. Her apo E isoform analyzed by isoelectric focusing (IEF) was found to be homozygous apo E5. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis of her apo E and lipoprotein lipase (LPL) genes revealed that she had a homozygous apo E (Glu3-->Lys) and heterozygous LPL variant Ser447 to Ter. Her son and daughter, both of whom had hyperlipidemia, were found to have apo E3/5 phenotype. Direct sequencing analysis of her apo E gene confirmed a homozygous one nucleotide change: G to A at nucleotide position of 2836 in the exon 3, resulting in Glu3-->Lys mutation. This is the first report of lipids and lipoprotein profiles in patients with homozygous apo E5 (Glu3-->Lys).