Chronic ethanol administration is able to induce an oxidative stress in the central nervous system. N-Acetylcysteine (NAC) has antioxidant properties; as a sulphydryl donor, it contributes to the regeneration of glutathione and it acts through a direct reaction with hydroxyl radicals. In this study we investigated a possible beneficial effect of NAC on some of the free radical related parameters. Twenty four male Wistar rats were divided in to three groups and were given ethanol (Group 1), ethanol and NAC (Group 2) and isocaloric dextrose (Group 3). Ethanol and NAC were given intragastrically at doses of 6 g/kg/day and 1 g/kg/day, respectively. Our results show that chronic ethanol intake elicits statistically significant increase in MDA and NO levels and decrease in SOD and GSH levels in both plasma and brain (p<0.001). GPx levels decreased in erythrocytes (p<0.001). CAT activity showed significant decrease only in brain samples (p<0.001). NAC administration effectively restores the above results to nearly normal levels. Therefore we suggest that reactive free radicals are, at least partly, involved in the ethanol-induced injury of brain cells and NAC mitigate the toxic effects of ethanol on the oxidant-antioxidant system of rat plasma and brain.
Some patients with hypertrophic nonobstructive cardiomyopathy (HNCM) suffer symptoms resembling those in obstructive type despite no left ventricular outflow tract (LVOT) gradient could be detected on resting echocardiography. To investigate the value of dobutamine stress echocardiography (DSE) in determining the dynamic left ventricular (LV) obstruction of patients with HNCM. The study was conducted on 31 patients who were diagnosed HNCM on resting echocardiography and 9 healthy person as a control group. Intraventricular flow acceleration of >3 m/sec on DSE was accepted as dynamic LVOT obstruction. Group 1 and 2 included patients without and with dynamic LVOT obstruction, respectively. The occurrence of chest pain and dyspnea seen during DSE was more frequent in group 2 than group 1 and control group. The frequency of SAM was significantly higher (p<0.05) and the septal angle was significantly lower (p<0.001) in Group 2. The presence of SAM significantly correlated with the peak gradient (r=0.61, p<0.001). The septal angle had significant negative correlations with the peak gradient (r=−0.77, p<0.001) reached at DSE. The relative risk for peak gradient was highest when septal angle was ≤100°, with a sensitivity of 93%, specificity of 80%, positive predictive value of 82%, negative predictive value of 92%, and predictive accuracy of 87%. DSE is a reliable tool for the diagnosis of dynamic LV obstruction in patients with HNCM. The presence of SAM together with a low septal angle is highly predictive for the presence of a dynamic LVOT obstruction detected by DSE.
Type II citrullinemia (CTLN2) is characterized by a deficiency of argininosuccinate synthetase (ASS) in the liver. Mutation analysis of the SLC25A13 gene, which is responsible for CTLN2, provides a rapid and accurate diagnosis. We describe clinical, biochemical and histologic features of two patients, whose diagnosis was finally made by mutation analysis. They initially presented with symptoms related to hyperammonemia at 16 to 22 years of age. A patient had shown mental retardation and growth failure from early childhood. Laboratory findings including amino acids, were characteristic, such as elevated citrulline, arginine, and lysine concentrations, but definitive diagnosis had not been made. The patients died of liver cirrhosis and hepatoma at 31 and 34 years old, respectively. Fatty change in the hepatocytes was commonly observed in the autopsied specimens. ASS activity was decreased in the liver of both patients, and a concomitant decrease of arginase activity was found in one case. Investigation for the SLC25A13 mutation revealed that one patient was homozygous for IVS11+1G>A, and the other was compound heterozygote (851del4/S225X). Comparison of genetic, enzymatic and biochemical data among various cases of CTLN2 will be essential to understand the real nature of the disease.
Atherosclerosis is an important cause of cardiovascular morbidity and mortality in recent years. Hyperhomocysteinemia is recognized as an independent risk factor for premature atherosclerosis and venous thrombosis. It is suggested that administration of folic acid, vitamin B6 and vitamin B12 may decrease homocysteine levels. In our study, we induced hyperhomocysteinemia in rabbits by giving methionine and studied the effects of folic acid, vitamin B6 and vitamin B12 on homocysteine levels. A total of 40 (20 female, 20 male New Zealand rabbits) were divided into four groups, each consisting of 10 rabbits. Methionine (100 mg/kg/day), methionine (100 mg/kg/day) plus vitamin B6 (30 mg/kg/day), methionine (100 mg/kg/day) plus vitamin B12 (80 mg/kg/day) and methionine (100 mg/kg/day) plus folic acid (20 mg/kg/day) were given to the first, second, third and forth groups respectively. These rabbits were followed up for two months. We studied homocysteine levels on the 0, 20th, 40th and 60th days in all groups. In rabbits we induced hyperhomocysteinemia by giving methionine for 2 months. The decreases of homocysteine levels in the forth group were significant with respect to the second and third groups. Folic acid supplementation clearly resulted in a reduction of plasma homocysteine levels, whereas vitamin B12 was little effective and vitamin B6 failed to show an effect. We conclude that even folic acid treatment alone may be sufficient for decreasing negative effects of homocysteine.
To investigate the relation between the impairment of isovolumic relaxation and the regional wall motion in acute ischemia, the left ventricular pressure fall and regional myocardial motion were examined in the relaxation phase in dogs during both acute coronary artery occlusion (n=12) and a regional coronary flow reduction (n=6). Fifteen to 40 seconds after complete coronary artery occlusion or in the stable state after a regional coronary flow reduction by 70 to 90% of the control state, a shortening of the non-ischemic region at the early isovolumic relaxation phase (the post-endsystolic shortening) appeared, combined with lengthening of the ischemic region. In these situations, the logarithmic plots of the left ventricular pressure fall was composed of two components (time constant of early part [Ta] and at latter part [Tb]). Ta was greater than Tb (64.3±13.8 milliseconds vs. 36.6±10.4 milliseconds at 15 seconds after coronary occlusion, p<0.01; 67.6±22.9 milliseconds vs. 45.1±17.5 milliseconds at flow reduction, p<0.01) and the time constant at control (p<0.01). These findings suggested that post-endsystolic shortening in the non-ischemic region played a role in a the non-uniformity of the left ventricular contraction and contributed to the impairment of the left ventricular pressure fall in acute regional ischemia, especially in early isovolumic relaxation.
Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is a rare autosomal recessive disorder affecting the urea cycle. The cardinal symptom in the neonatal form is progressive hyperammonemia, which is often life-threatening. However, clinical symptoms in the late onset form are quite heterogeneous. As well as measurement of ASL activity, analysis of the ASL gene is necessary to clarify the genetic basis of various phenotypes. We report a patient with late onset argininosuccinate lyase deficiency (ASLD) who had hepatomegaly and mildly increased level of ammonia. By mutation analysis of the mRNA and genomic DNA from the patient’s leukocytes, we identified a novel missense mutation 1395G>C in the homozygous state, which results in the exchange of a stop codon to tyrosine at amino acid position 465 (X465Y). This unique mutation causes an elongation of fifty amino acids in the C-terminal region of the ASL protein, and is likely related to a milder phenotype compared with previously reported mutations. In addition, this is the first report on mutation analysis in a Japanese ASLD patient.
We previously reported that neutrophils produce sulfite in response to stimulation with lipopolysaccharide, and sulfite production is dependent on inorganic sulfate contained in culture media. Microorganisms such as yeast assimilate sulfate, during which process sulfite is generated by reduction of 3′-phosphoadenosine 5′-phosphosulfate (PAPS), an activated sulfate donor. However, little is known about how sulfite is produced in mammalian cells. In the current study, we demonstrated that chlorate, a specific inhibitor for PAPS synthesis, significantly suppressed production of sulfite by activated neutrophils obtained from rat peritoneal cavity that had been injected with glycogen to induce inflammation. Addition of excess amounts of PAPS could partially overcome the inhibitory effect of chlorate. Moreover, sulfite production from PAPS was clearly demonstrated in the cytosolic fraction of activated neutrophils. These findings strongly suggest that sulfite is generated, at least in part, from PAPS by activated neutrophils.
Lymphoepithelioma is the designation that has been given to describe undifferentiated squamous cell carcinoma variants of nasopharyngeal neoplasms (World Health Organization type 3), and a strong association with Epstein-Barr virus (EBV) infection has been established. Outside the nasopharynx, lymphoepithelioma-like carcinomas (LEC) are exceedingly rare in other head and neck lesions. This report features a rare case of LEC of the palatine tonsil occurring in a 60-year-old Japanese man who presented with a three-month history of a neck mass. The surface of tonsils were smooth, not ulcerated macroscopically, and the ipsilateral tonsil showed only slight enlargement on radiological findings. Diagnosis of lymphoepithelioma was finally made based on the pathological review of the tonsillectomy specimens, preceded by a cervical lymph node biopsy. The patient was treated with irradiation and adjuvant chemotherapy. RNA in situ hybridization as well as polymerase chain reaction (PCR) techniques, and serological testing did not demonstrate an association with EBV infection. The clinical presentation, pathological features and association with EBV are described with a review of the literature.