Dietary fish oil does not prevent doxorubicin-induced cardiomyopathy in rats

BACKGROUND: Dietary fish oil potentiates the susceptibility of cellular membranes to lipid peroxidation, although it is also known to have beneficial effects on the development of cardiovascular diseases. OBJECTIVE: The effects of dietary fish oil against doxorubicin-induced cardiomyopathy, in which free radicals and lipid peroxidation are involved, were investigated in rats. ANIMALS AND METHODS: Sprague-Dawley rats (100 g) were fed a standard diet or a high fish oil diet (containing 10% fish oil) throughout the experimental period. Four weeks after starting each diet, experimental rats were treated with doxorubicin (cumulative dose 15 mg/kg) or vehicle (0.28 M dextrose solution). After three weeks of doxorubicin treatment, the cardiac performance, myocardial lipid peroxidation and myocardial vitamin E level were assessed. RESULTS: Compared with control rats, doxorubicin-treated rats showed a significantly increased mortality rate (P<0.05), and significantly decreased systolic blood pressure and left ventricular fractional shortening (P<0.01). The myocardial thiobarbituric acid-reactive substance level was significantly higher in doxorubicin-treated rats than in control rats (P<0.01), while the myocardial vitamin E level was significantly lower (P<0.05). Dietary fish oil enhanced the myocardial lipid peroxidation caused by doxorubicin, which was associated with a further decrease in myocardial vitamin E level. As a result, the rats treated with both doxorubicin and the high fish oil diet showed the highest mortality rate and the lowest cardiac performance of all the experimental groups. CONCLUSIONS: Dietary fish oil may reduce antioxidant defences and accelerate susceptibility of the myocardium to lipid peroxidation in rats under doxorubicin treatment. This may partly explain why dietary fish oil does not prevent doxorubicin-induced cardiomyopathy.     

Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK

Evaluation of potential health effects from high energy charged particle radiation exposure during long duration space travel is important for the future of manned missions. Cognitive health of an organism is considered to be maintained by the capacity of hippocampal precursors to proliferate and differentiate. Environmental stressors including irradiation have been shown to inhibit neurogenesis and are associated with the onset of cognitive impairments. The present study reports on the protective effects of N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a melatonin metabolite, against high energy charged particle radiation-induced oxidative damage to the brain. We observed that radiation exposure (2.0 Gy of 500 MeV/nucleon (56)Fe beams, a ground-based model of space radiation) impaired the spatial memory of mice at later intervals without affecting the motor activities. AFMK pretreatment significantly ameliorated these neurobehavioral ailments. Radiation-induced changes in the population of immature and proliferating neurons in the dentate gyrus were localized using anti-doublecortin (Dcx) and anti-Ki-67 expression. AFMK pretreatment significantly inhibited the loss of Dcx and Ki-67 positive cells. Moreover, AFMK pretreatment ameliorated the radiation-induced augmentation of protein carbonyls and 4-hydroxyalkenal + malondialdehyde (MDA + HAE) in the brain and maintained the total antioxidant capacity of plasma and nonprotein sulfhydryl contents in brain.     

Usefulness of preheparin lipoprotein lipase mass as a parameter for predicting the efficacy of colestimide

This study was conducted to clarify the characteristics of colestimide responders. Forty-seven non-diabetic patients with high levels of low-density lipoprotein cholesterol (LDL-C) received colestimide at 3,000 mg/day and were followed up for 4 months. After 4 months, body weight was reduced but the change was not statistically significant. Total serum cholesterol (TC) and LDL-C levels significantly decreased from 280 to 232 mg/dl and from 195 to 150 mg/dl, respectively (p<0.01 versus before colestimide was administered). Serum triglyceride (TG) levels increased, but the change was not significant. Preheparin lipoprotein lipase mass (preheparin LPL mass) at baseline was significantly higher in colestimide responders (greater than a 20% decrease of LDL-C: n=28) than non-responders (76.2 ng/ml versus 50.3 ng/ml, p<0.05: n=19). Next, the subjects were divided into those with a high (n=33) and low (n=14) preheparin LPL mass at baseline. LDL-C levels were significantly decreased in patients with a high preheparin LPL mass while TG levels were significantly increased in patients with a low preheparin LPL mass. These results suggest that baseline preheparin LPL mass may be a marker of the response to colestimide.     

Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy

Sustained hyperleptinemia of 8 ng/ml was induced for 28 days in normal Wistar rats by infusing a recombinant adenovirus containing the rat leptin cDNA (AdCMV-leptin). Hyperleptinemic rats exhibited a 30–50% reduction in food intake and gained only 22 g over the experimental period versus 115–132 g in control animals that received saline infusions or a recombinant virus containing the β-galactosidase gene (AdCMV-βGal). Body fat was absent in hyperleptinemic rats, whereas control rats pair-fed to the hyperleptinemic rats retained ≈50% body fat. Further, plasma triglycerides and insulin levels were significantly lower in hyperleptinemic versus pair-fed controls, while fatty acid and glucose levels were similar in the two groups, suggestive of enhanced insulin sensitivity in the hyperleptinemic animals. Thus, despite equivalent reductions in food intake and weight gain in hyperleptinemic and pair-fed animals, identifiable fat tissue was completely ablated only in the former group, raising the possibility of a specific lipoatrophic activity for leptin.     

A case of micronodular pneumocyte hyperplasia diagnosed through lung biopsy using thoracoscopy

We present a case of a 39-year-old woman with sporadic tuberous sclerosis (TSC), whose chest radiograph demonstrated bilateral diffuse nodular shadowing. A transbronchial lung biopsy specimen revealed the possibility of multiple atypical adenomatous hyperplasia (AAH), which had not been reported in TSC. Thoracoscopic lung biopsy was, therefore, performed. The specimens revealed the characteristic histological and immunohistochemical features of micronodular pneumocyte hyperplasia, which has been reported as an extremely rare pulmonary manifestation of TSC. In addition, no evidence of AAH or any other pulmonary involvements of TSC including lymphangioleiomyomatosis were detected in biopsy specimens obtained at thoracoscopy.     

Cushing's syndrome associated with adenocarcinoma of the lung

Paraneoplastic Cushing's syndrome caused by ectopic adrenocorticotropin production has been reported in association with a variety of malignant tumors. However, most cases of this syndrome are associated with neuroendocrine tumors such as small-cell lung cancer (SCLC), carcinoid tumors, and medullary carcinoma of the thyroid. We present a 49-year-old man who developed Cushing's syndrome associated with adenocarcinoma of the lung. He had a wide variety of clinical symptoms and comorbidity related to this syndrome during the course, and died 4 months after the diagnosis. This is a very rare case report of Cushing's syndrome associated with adenocarcinoma of the lung.     

Genetic Analysis of Non-Hydrogen Sulfide-Producing Salmonella enterica Serovar Typhimurium and S. enterica Serovar Infantis Isolates in Japan

Whole-genome sequencing of non-H₂S-producing Salmonella enterica serovar Typhimurium and S. enterica serovar Infantis isolates from poultry meat revealed a nonsense mutation in the phsA thiosulfate reductase gene and carriage of a CMY-2 β-lactamase. The lack of production of H₂S might lead to the incorrect identification of S. enterica isolates carrying antimicrobial resistance genes.