Biomedical subjects

Yasuhiro Ueno

Publications and source records attributed to Yasuhiro Ueno.

30 records · Page 2Linked to original sources

PubMed2003

Alcoholic muscle disease and biomembrane perturbations (review).

Excessive alcohol ingestion is damaging and gives rise to a number of pathologies that influence nutritional status. Most organs of the body are affected such as the liver and gastrointestinal tract. However, skeletal muscle appears to be particularly susceptible, giving rise to the disease entity alcoholic myopathy. Alcoholic myopathy is far more common than overt liver disease such as cirrhosis or gastrointestinal tract pathologies. Alcohol myopathy is characterised by selective atrophy of Type II (anaerobic, white glycolic) muscle fibres: Type I (aerobic, red oxidative) muscle fibres are relatively protected. Affected patients have marked reductions in muscle mass and impaired muscle strength with subjective symptoms of cramps, myalgia and difficulty in gait. This affects 40-60% of chronic alcoholics (in contrast to cirrhosis, which only affects 15-20% of chronic alcohol misuers).Many, if not all, of these features of alcoholic myopathy can be reproduced in experimental animals, which are used to elucidate the pathological mechanisms responsible for the disease. However, membrane changes within these muscles are difficult to discern even under the normal light and electron microscope. Instead attention has focused on biochemical and other functional studies. In this review, we provide evidence from these models to show that alcohol-induced defects in the membrane occur, including the formation of acetaldehyde protein adducts and increases in sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (protein and enzyme activity). Concomitant increases in cholesterol hydroperoxides and oxysterol also arise, possibly reflecting free radical-mediated damage to the membrane. Overall, changes within muscle membranes may reflect, contribute to, or initiate the disturbances in muscle function or reductions in muscle mass seen in alcoholic myopathy. Present evidence suggest that the changes in alcoholic muscle disease are not due to dietary deficiencies but rather the direct effect of ethanol or its ensuing metabolites.

Acetaldehyde↗

PubMed2003

7-hydroperoxycholesterol and oxysterols as indices of oxidative stress: chronic ethanol feeding and rat skeletal muscle.

The present study is undertaken to determine if ethanol affects 7-hydroperoxycholesterol or oxysterols in rat skeletal muscle after chronic ethanol feeding. Wistar rats were fed a liquid diet containing ethanol as 35% of total calories. After 6 weeks, soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) skeletal muscles were dissected out. We measured 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH) and 3beta-hydroxycholest-5-en-7-one (7-keto). We found that in response to chronic alcohol feeding, there were significant increases in soleus 7alpha-OH (P=0.0005), 7beta-OH (P=0.0005) and 7-keto (P=0.0007), but in the plantaris, 7beta-OH increased (P=0.0418). Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.

Animals↗

PubMed2003

Sexual asphyxia by hanging--a case report and a review of the literature.

A case of sexual asphyxial death by hanging is presented. A 35-year-old male, found dead lying on his face in a bed of a truck cab, had hanged himself from a window frame using a leather belt. He was completely naked. There were pornographic and sadomasochistic magazines beneath his face, opened to pages depicted nude photographs of a woman. Autopsy findings revealed a ligature mark on the neck and petechial hemorrhages in the conjunctivae, but there were no hemorrhages in the neck muscles or fractures of the hyoid bone or the thyroid cartilage. The alcohol levels in the blood and urine were 0.78 and 0.45 mg/ml, respectively. The circumstances suggested that his death was accidental, and due to asphyxia by hanging performed to enhance sexual gratification during masturbation. Sexual asphyxia is reviewed and discussed.

Accidents↗

PubMed2003

Fatty acid profile in skeletal muscle of the rat in response to acute (2.5 hours) and prolonged (6 weeks) ethanol-dosage.

We tested the hypothesis that phospholipids are altered in skeletal muscles of rats exposed to ethanol for either acute (2.5 hours) or prolonged (6 weeks) periods. In acute studies, rats were dosed with saline (0.15 mmol/l; controls) or ethanol (75 mmol/kg body weight; treated). There were four groups: (A) saline (control); (B) cyanamide (an aldehyde dehydrogenase inhibitor); (C) ethanol; and (D) cyanamide + ethanol. In prolonged studies, two groups of rats were fed liquid diets containing 35% of total dietary energy as either glucose [group (E)] or ethanol [group (F)]. At the end of the treatments, membrane phospholipids were measured in soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) muscle. In acute studies, ethanol alone [(A) vs. (C)] and cyanamide + ethanol [(A) vs. (D)] significantly increased 18 : 2 in plantaris (p < 0.05), whereas in soleus none of the treatments had any effect on the phospholipids. In prolonged studies [(E) vs. (F)], there were decreases in 16 : 0 (p < 0.05) and 18 : 1 (p < 0.01) and increases in 18 : 2 (p < 0.001) in plantaris. In soleus, decreases in 18 : 1 (p < 0.05) and increases in 18 : 2 (p < 0.01) occurred. In conclusion, alterations in the proportions of 16 : 0, 18 : 1 and 18 : 2 provide evidence of an altered membrane domain which may contribute to the pathogenesis of alcohol-induced muscle disease. Changes due to prolonged exposure are more profound than those in acute exposure and the preferential effects in Type II plantaris may reflect the greater susceptibility of this muscle to alcohol.

Aldehyde Dehydrogenase↗

PubMed2002

Lack of an association between 5-HT1A receptor gene structural polymorphisms and suicide victims.

A serotonergic dysfunction in the brain has been reported to be involved in suicidal behavior independently of the presence of a specific psychiatric disorder. Serotonin 1A (5-HT1A) receptors are known to be located on serotonergic nerve terminals and to be involved in the presynaptic regulation of serotonin release. Genetic factors partly explain the risks for suicide, and a suicide completion group is thought to be more uniform than a suicide attempt group. To explore the hypothesis that the 5-HT1A receptor-induced serotonergic dysfunction is implicated genetically in suicide, we focused on the structural polymorphisms, Pro16Leu and Gly272Asp, of the 5-HT1A receptor gene, and examined the association between suicide victims who completed suicide and these two polymorphisms. In both polymorphisms, we found no significant difference in genotype distribution or allele frequencies between suicide victims and controls. These findings suggest that neither of these two polymorphisms is associated with suicide victims and it is unlikely that the 5-HT1A receptor gene is implicated in the susceptibility to suicide.

Female↗

PubMed2002

Free radicals in alcoholic myopathy: indices of damage and preventive studies.

Chronic alcoholic myopathy affects up to two-thirds of all alcohol misusers and is characterized by selective atrophy of Type II (glycolytic, fast-twitch, anaerobic) fibers. In contrast, the Type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. Alcohol increases the concentration of cholesterol hydroperoxides and malondialdehyde-protein adducts, though protein-carbonyl concentration levels do not appear to be overtly increased and may actually decrease in some studies. In alcoholics, plasma concentrations of alpha-tocopherol may be reduced in myopathic patients. However, alpha-tocopherol supplementation has failed to prevent either the loss of skeletal muscle protein or the reductions in protein synthesis in alcohol-dosed animals. The evidence for increased oxidative stress in alcohol-exposed skeletal muscle is thus inconsistent. Further work into the role of ROS in alcoholic myopathy is clearly warranted.

Alcoholism↗

PubMed2002

No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides.

Monoamine oxidase A (MAOA) has been implicated in the control of aggression and/or impulsivity in humans and been involved in suicide. This gene has a functional polymorphism in which there is a variable number tandem repeat (VNTR) in the upstream region (MAOA-uVNTR). We hypothesized that MAOA dysfunction due to this polymorphism was associated with suicide genetically through the disinhibition of aggression and/or impulsivity. We performed an association study between completed suicides and the MAOA-uVNTR polymorphism. No significant difference in genotype distribution or allele frequencies was found between completed suicides and comparison groups either in males or females. These results show no evidence of an association between the MAOA-uVNTR polymorphism and completed suicides and suggest that MAOA is not involved in the susceptibility to suicide.

Adult↗

PubMed2002

Chronic ethanol feeding increases 7-hydroperoxycholesterol and oxysterols in rat skeletal muscle.

It was our hypothesis that, as a consequence of increased oxidative stress, cholesterol-derived hydroperoxides and oxysterols are increased in skeletal muscles chronically exposed to ethanol. To test this we fed male Wistar rats (0.1 kg initial body weight) a nutritionally complete liquid diet containing ethanol as 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 1(1/2) months, soleus (type I fiber-predominant) and plantaris (type II fiber-predominant) skeletal muscles were dissected out. We measured 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH), as well as 7 alpha- and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH), and 3 beta-hydroxycholest-5-en-7-one (also termed 7-ketocholesterol; 7-keto). We identified and confirmed by LC-MS the presence of 7 alpha-OOH, 7 beta-OOH and 7 alpha-OH, 7 beta-OH and 7-keto in skeletal muscle of rats. We also showed that in response to chronic alcohol feeding, there were significant increases in soleus 7 alpha-OH (P =.0005), 7 beta-OH (P =.0005), and 7-keto (P =.0007). In the plantaris, mean 7 alpha-OH and 7-keto were not significantly altered (P >.05), but 7 beta-OH increased (P =.0418). This is the first report of 7 alpha-OH, 7 beta-OH, and 7-keto oxysterols being identified in skeletal muscle of rats. Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.

Administration, Oral↗

PubMed2002

Oxysterols as indices of oxidative stress in man after paraquat ingestion.

The aim of this study is to evaluate oxidative stress in man after paraquat ingestion by analyzing 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha- and 7beta-OOH) as well as oxysterols, cholesterol oxidation products, as indices of lipid peroxidation. Lung, kidney, and liver were collected at autopsy from seven patients with paraquat poisoning and seven controls matched for age and sex. We identified for the first time 7-ketocholesterol (7-keto) and 7-hydroxycholesterol (7alpha-OH and 7beta-OH) in human kidney by LC-MS. Next, we quantified 7alpha-OOH and 7beta-OOH by HPLC with postcolumn chemiluminescence as well as oxysterols by HPLC-UV. Both 7alpha-OOH and 7beta-OOH detected in lung and kidney from the controls were as low as the paraquat group. In contrast, we found both 7-keto and 7beta-OH in lung and 7-keto in kidney from the paraquat group were significantly higher than from the controls. This is the first report on accumulated oxysterols in lung and kidney from human paraquat poisoning. It seems to reflect greater oxidative stress in the pathology of paraquat intoxication.

Adult↗

PubMed2002

Effect of chronic ethanol feeding on oxysterols in rat liver.

It was our hypothesis that, as a consequence of increased oxidative stress, cholesterol-derived hydroperoxides and oxysterols are increased in livers of rats exposed to ethanol. To test this we dosed Wistar rats (approximately 0.1 kg initial body weight) with ethanol chronically (rats fed a nutritionally complete liquid diet containing ethanol as 35% of total calories; sampled liver at approximately 6-7 weeks). We measured concentrations of 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH) as well as 7 alpha- and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH), and 3 beta-hydroxycholest-5-en-7-one (also termed 7-ketocholesterol; 7-keto). In response to chronic alcohol feeding, there were significant elevations in the concentrations of 7 alpha-OOH (+169%, P = 0.005) and 7 beta-OOH (+199%, P = 0.011). Increases in the concentrations of hepatic 7-keto (+74%, P = 0.01) and decreases in cholesterol (-43%; P = 0.03) also occurred. In contrast, the concentrations of both 7 alpha-OH and 7 beta-OH were not significant (NS). However, when oxysterols in chronic ethanol-fed rats were expressed relative to cholesterol there were significant increases in 7-keto/cholesterol (P = 0.0006), 7 alpha-OH/cholesterol (P = 0.0018) and 7 beta-OH/cholesterol (P = 0.0047). In conclusion, this is the first report of increased 7 alpha-OOH, 7 beta-OOH, and 7-keto in liver of rats and their elevation in chronic experimental alcoholism represent evidence of increased oxidative stress.

Alcoholism↗

PubMed2002

Accidental hanging by a sweater: an unusual case.

An accidental atypical hanging with the collar of a sweater is reported. A 67-year-old man was found dead in the sitting position with the collar of his sweater hanging off the brake handle of a motorcycle. Autopsy findings revealed a ligature mark on the surface of the neck; hemorrhages in the sternohyoid muscles; submucosal hemorrhages in the left greater horn of the hyoid bone; a large degree of submucosal petechial hemorrhages in the larynx, oral mucosa, and palpebral conjunctivae; and dark-red liquid blood with little clotting in the heart cavities. The alcohol levels in the blood and urine were 2.84 mg/ml and 3.52 mg/ml, respectively. It was concluded that the man had died from hanging by the sweater, and it was speculated that when he became inebriated, he might have lost consciousness and then fell with the collar of his sweater hanging from the brake handle of the motorcycle.

Accidents↗

PubMed2002

Decreased arterial responses in WHHL rabbits, an animal model of spontaneous hypercholesterolemia and atherosclerosis.

We examined changes in blood pressure and blood flow of the arteries of WHHL and Japanese white rabbits after intravenous bolus injections of acetylcholine (3.0 micrograms/kg), bradykinin (0.5 microgram/kg), and sodium nitroprusside (3.0 micrograms/kg) under a condition of anesthesia. These vasodilators lowered the blood pressure and increased the blood flow in WHHL and Japanese white rabbits. The changes in the hemodynamic parameters of WHHL rabbits after injection of sodium nitroprusside were similar to those of Japanese white rabbits. This suggests that the relaxation response of the tunica media was not diminished in WHHL rabbits. In contrast, the changes in the hemodynamic parameters of WHHL rabbits after injection of acetylcholine or bradykinin were significantly lower than those in Japanese white rabbits. In the histopathological and immunohistological examination, atherosclerotic lesions were observed in the ascending aortas of WHHL rabbits. In the surface of the atheromatous plaques, CD31-positive endothelial cells disappeared partly and the accumulation of RAM-11-positive macrophages was observed in these regions. In addition, plasma NO2- and NO3- levels of WHHL rabbits were significantly lower than those of Japanese white rabbits. These findings suggest that relaxation responses derived from arterial endothelial cells were probably depressed in WHHL rabbits due to dysfunction or denudation of the arterial endothelial cells.

Animals↗