Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction in children with asthma.

In the present study, we evaluated the effect of roxithromycin, a semisynthetic macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten hospitalized asthmatic children (8 boys and 2 girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. All the patients underwent AA inhalation challenge before and 2, 4, and 8 weeks after the administration of roxithromycin. Seven of the 10 patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent UNDW inhalation challege at the same time. The cough threshold values, the lowest concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20% fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05). No significant change was observed in baseline FEV1 or serum theophylline concentrations throughout the study. These results support the notion that administration of roxithromycin may have favorable results in the treatment of childhood asthma.

Gene expression of insulin signal-transduction pathway intermediates is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet.

To elucidate the effects of dietary fatty acid composition on the insulin signaling pathway, we measured the gene expression of the earliest steps in the insulin action pathway in skeletal muscle of rats fed a safflower oil diet or a beef tallow diet. Rats were meal-fed an isoenergetic diet based on either safflower oil or beef tallow for 8 weeks. Both diets provided 45%, 35%, and 20% of energy as fat, carbohydrate, and protein, respectively. Insulin resistance, assessed from the diurnal rhythm of plasma glucose and insulin and the oral glucose tolerance test (OGTT), developed in rats fed a beef tallow diet. Body fat content was greater in rats fed a beef tallow diet versus a safflower oil diet. The level of insulin receptor mRNA, relative expression of the insulin receptor mRNA isoforms, and receptor protein were not affected by the composition of dietary fatty acids. The abundance of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol (PI) 3-kinase mRNA and protein was significantly lower in rats fed a beef tallow diet versus a safflower oil diet. We conclude that long-term feeding of a high-fat diet with saturated fatty acids induces decrease in IRS-1 and PI 3-kinase mRNA and protein levels, causing insulin resistance in skeletal muscle.

Effect of dietary fat type on beta-oxidation of brown adipose tissue and Na+ channel density of brain nerve membrane in rats.

Effect of dietary fat type on beta-oxidation of brown adipose tissue and Na+ channel density of brain nerve membrane was studied in rats. Rats were fed an experimental diet containing lard, high oleic safflower oil, safflower oil or linseed oil for 12 weeks. The activities of carnitine palmitoyltransferase and cytochrome oxidase in brown adipose tissue were significantly lower in rats fed the lard diet than in those fed the high-oleic safflower oil diet, safflower oil diet or linseed oil diet. However, the peroxisomal beta-oxidation activity in brown adipose tissue was significantly higher in rats fed the lard diet than in those fed the other diet. The Na+ channel density in brain nerve membrane was not significantly different among the diet groups. These results suggest that intake of the lard diet rich in saturated fatty acids, compared with the vegetable oil diets rich in unsaturated fatty acids decrease mitochondrial beta-oxidation in brown adipose tissue, and that the dietary fat type has a differential effect on mitochondrial and peroxisomal beta-oxidation in brown adipose tissue.

Serum triiodothyronine concentration and Na+,K(+)-ATPase activity in liver and skeletal muscle are influenced by dietary fat type in rats.

It has been shown previously that dietary fat type influences body fat accumulation in rats. The effects of dietary fat type on serum thyroid hormone, activity of Na+,K(+)-ATPase and lipoprotein lipase were studied. Rats were fed an experimental diet containing lard, high oleic safflower oil, safflower oil or linseed oil for 12 wk. Carcass fat content was significantly higher in rats fed the lard diet than in those fed the other diets. However, intra-abdominal adipose tissue weights were not affected by type of dietary fat. The serum triiodothyronine concentration and the activity of Na+,K(+)-ATPase in the liver and skeletal muscle were significantly lower in the lard diet group than in the other diet groups. The lipoprotein lipase activity of abdominal subcutaneous fat was significantly higher in rats fed the lard diet than in rats fed the other diets, but the activity of lipoprotein lipase in intra-abdominal fat was not significantly different. These results suggest that the intake of lard, compared with the intake of the vegetable oils, may decrease Na+,K(+)-ATPase activity in the liver and skeletal muscle by lowering serum triiodothyronine concentration, resulting in the promotion of body fat accumulation.

Sympathetic activity is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet.

Effects of dietary fats consisting of different fatty acids on sympathetic activity and body fat accumulation were studied in rats. Rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for 8 weeks. Carcass fat content was greater (P < .05) in rats fed the beef tallow diet than in rats fed the safflower oil diet. Norepinephrine (NE) turnover rate was significantly lower (P < .05) in interscapular brown adipose tissue (IBAT) and pancreas in rats fed the beef tallow diet than in rats fed the safflower oil diet, resulting in a decreased (P < .05) diet-induced thermogenesis (DIT) and an increased (P < .05) serum insulin concentration in the former. To confirm the effects of dietary fats on sympathetic activity in relation to body fat accumulation, rats were chemically sympathectomized. Sympathectomy abolished the differences in body fat accumulation, DIT, and serum insulin concentration between the two dietary groups. These results suggest that the beef tallow diet promotes body fat accumulation by reducing sympathetic activity as compared with intake of the safflower oil diet.

Diet-induced thermogenesis is lower in rats fed a lard diet than in those fed a high oleic acid safflower oil diet, a safflower oil diet or a linseed oil diet.

The objectives of the present study were to examine the effects of dietary fats differing in fatty acid composition on diet-induced thermogenesis, sympathetic activity in brown adipose tissue and body fat accumulation in rats. Rats were meal-fed for 12 wk an isoenergetic diet based on lard, high oleic acid safflower oil, safflower oil or linseed oil, and norepinephrine turnover rates in brown adipose tissue were then estimated. Whole-body oxygen consumption after the meal indicated that diet-induced thermogenesis was significantly lower in rats fed the lard diet than in those fed the other diets. The norepinephrine turnover rate in the interscapular brown adipose tissue was also significantly lower in the lard diet group than in the other diet groups. The carcass fat content was significantly higher in the lard diet group than in the other diet groups, whereas the abdominal adipose tissue weights were the same in all diet groups. These results suggest that the intake of animal fats rich in saturated fatty acids, compared with the intake of vegetable oils rich in monounsaturated or polyunsaturated fatty acids, decreases diet-induced thermogenesis by a decline of sympathetic activity in brown adipose tissue, resulting in the promotion of body fat accumulation.

Trans-catheter hepatic arterial injection of lipiodol soluble anti-cancer agent SMANCS and ADR suspension in lipiodol combined with arterial embolization and local hyperthermia for treatment of hepatocellular carcinoma.

The clinical effect and safety of Lp-TAE alone and combined with radiofrequency (RF) capacitive hyperthermia (HT) were evaluated in 20 patients with hepatocellular carcinoma (HCC) associated with cirrhosis of the liver. After the oily carcinostatic agents were administered by Lp-TAE, HT, at a temperature of greater than 42.5 degrees C, was induced for 40 min, twice a week by an RF of 8 MHz for a total of 10 to 38 times. The response rate was 40% in the 10 cases that were treated with Lp-TAE combined with HT and 20% in the 10 cases that were treated with Lp-TAE. The patients who were treated with Lp-TAE combined with HT had a tendency to have better survival rates than those of the Lp-TAE group (p less than 0.099). The main side-effects of Lp-TAE combined with HT were low-grade fever, localized pain, myelo-suppression and liver dysfunction, but these were transient and eventually disappeared.

Hepatocellular carcinoma detected by iodized oil.

This study assesses the diagnostic value of Lipiodol (iodized oil) and computed tomography (CT) in detecting hepatocellular carcinoma (HCC). Twenty-four patients who were suspected of having HCC received injections of a small amount of Lipiodol, along with an antitumor agent, in the hepatic artery following routine celiac angiography. CT scans obtained 7-10 days after Lipiodol administration demonstrated HCC in distinct contrast to the surrounding noncancerous parenchyma. In particular, the CT-Lipiodol procedure disclosed many small HCC lesions that were not shown by celiac angiography, scintigraphy, CT with and without contrast medium enhancement, and ultrasonography. Although this procedure may miss very small or highly fibrotic lesions, it is recommended for patients suspected of having HCC and for patients for whom hepatic resection is being considered.

[Combined treatment with intra-arterial administration of oily anti-cancer agents and transcatheter arterial embolization--clinical and pathological study on 2 cases with resected small hepatoma].

Combined treatment with intraarterial administration of oily anti-cancer agent (SMANCS-Lipiodol; copolymer of styrene maleic acid conjugate of Neocarcinostatin disolved in Ethiodol) and transcatheter arterial embolization (TAE) was employed in 2 patients with small hepatoma. At 3-4 weeks after treatment, hepatic resection was performed. Histopathological examination of the 2 resected specimens showed total cell necrosis; CT and Softex revealed the distribution of lipiodol in the tumor and adjacent regions. This combination treatment showed combined effects, i.e. embolization by TAE, the anti-cancer effect of SMANCS and the selective delivery of lipidol to the hepatoma, especially the area of capsula invasion, the daughter nodule and tumor thrombus.

Carnitine metabolism in thyroid hormone treated rats and mice.

This study was undertaken to investigate the changes in carnitine metabolism in rats and mice injected with T4 for 3 days and 10 days, respectively, and in rats fed a T3 and T4-supplemented diet for 6 weeks. Thyroid hormone administration brought about a significant increase in urinary excretion of total carnitine. In T3 + T4-treated rats urinary esterified-carnitine to free-carnitine ratio increased significantly in the later phase of administration. Carnitine pool size in the body was significantly decreased in both T4-injected mice and T3 + T4-fed rats. In the latter animals, this decrease was due to the reduced carnitine contents in organs other than the liver, especially in skeletal muscle. The amount of carnitine synthesized by control and T3 + T4-treated rats was calculated from the data on carnitine intake, urinary carnitine excretion and carnitine pool size in the body over the 6-week period. Values obtained were 66.2 +/- 3.2 (mean +/- SEM) mumol/rat and 28.5 +/- 4.9 mumol/rat, respectively, and the difference was significant (p less than 0.05). These results indicate that carnitine synthesis is depressed by thyroid hormone, however, some possibilities that thyroid hormone may increase carnitine synthesis were also discussed.