Protective effect of aloe extract against the cytotoxicity of 1,4-naphthoquinone in isolated rat hepatocytes involves modulations in cellular thiol levels

Aloe is a familiar ingredient in a wide range of health care and cosmetic products and has been reported to possess various physiological effects, antioxidative, anticarcinogenic, antiinflammatory and laxative. Aloe has also been reported to have an effect on liver function. The cytoprotective effect of aloe extract against 1,4-naphthoquinone-induced hepatotoxicity was evaluated in primary cultured rat hepatocytes. After exposure to 1,4-naphthoquinone (100 microM), a decrease in cell viability measured as >60% lactate dehydrogenase depletion was induced. Cellular glutathione (GSH) and protein-SH levels were also significantly decreased in a time-dependent manner. However addition of aloe extract resulted in a dose-dependent improvement of these effects. This cytoprotective effect of aloe could be attributed to its inhibition of GSH and protein-SH depletions. The effect of the aloe extracts were also dose-dependent. Addition of diethyl maleate (1 mM), a cellular glutathione-depleting agent, to hepatocytes treated with both 1,4-naphthoquinone and aloe extract, induced depletion of GSH, but did not affect protein-SH or lactate dehydrogenase. These results suggest that the 1,4-naphthoquinone-induced toxicity in rat hepatocytes was inhibited by aloe extract, and that this protective effect was due to the maintenance of cellular thiols, especially protein-SH.     

Peripheral-type benzodiazepine receptors on platelets are correlated with the degrees of anxiety in normal human subjects

RATIONALE: Anxiety is the one of the main symptoms of psychiatric disorders. Psychosocial stressors have been shown to be related to the onset of anxious episodes. Peripheral-type benzodiazepine receptors (PBR) are involved in regulating stress responses. The sensitivity of PBR to acute or chronic stress has been demonstrated in various situations. The State-Trait Anxiety Inventory (STAI) is one of the longest standing and most frequently used measures of anxiety. The development, evaluation, and use of biological markers with anxious conditions in psychiatry are extremely important. OBJECTIVES: The aims of this survey are to see whether PBR can be used in screening the degrees of anxiety which occur when normal persons are placed in the stressful conditions. METHODS: Twenty-four healthy volunteers (14 men, 10 women; mean age 46 years) participated in this study. We administered the STAI to all the volunteers. The binding of the radioactive PBR antagonist [(3)H]PK 11195 to platelet membranes was determined for these volunteers. RESULTS: The mean STAI scores were 40.3+/-8.0 for trait anxiety and 39.0+/-8.9 for state anxiety. B(max) of the platelet PBR binding was 2845+/-2109 fmol/mg protein. Pearson correlational analyses revealed that B(max) values were significantly and positively correlated with scores for trait anxiety but not significantly correlated with scores for state anxiety. CONCLUSIONS: PBR on platelets are correlated with trait anxiety scales of the STAI in healthy normal subjects. It is therefore suggested that the density of platelet PBR is highly associated with these personality traits for anxiety tolerance. PBR density in platelet could also be used as a promising biological marker of stressful conditions.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).     

Significant increase of colonic mutated crypts in ulcerative colitis correlatively with duration of illness

Mild periodic acid-Schiff (mPAS) staining can discriminate non-O-acetylated(mPAS positive) from O-acetylated (mPAS negative) epithelial sialoglycoproteins in human colonic mucosa, giving three haplotypes of expression of a single polymorphic autosomal gene (oat). Increase in mPAS-positive crypts in heterozygotes is an indication of mutations, and wholly mPAS-positive (stem cell mutated) crypts and clusters of two or more mPAS-positive crypts in heterozygotes of ulcerative colitis (P < 0.0001) were found to be increased significantly, compared with controls. The observed correlation with ulcerative colitis duration (r = 0.892 and 0.853, respectively) supports a chronic inflammation-carcinoma sequence.     

A case of ventricular tachycardia immediately after electroconvulsive therapy in a schinzophrenic patient

A 33 year-old man weighting, 93 kg with schizophrenia underwent repeated electroconvulsive therapy (ECT) under general anesthesia with thiamylal 200 mg and suxamethonium 80 mg. On his fourth ECT, he developed ventricular tachycardia (VT) immediately after the treatment under general anesthesia with the same agents. The duration of VT was approximately 30 s. The VT returned to sinus rhythm without any special treatment. We speculate that light anesthesia with a small amount of thiopental associated with release of serum potassium caused by suxamethonium induced increased release of catecholamine by ECT to cause VT. After that incident, the patient underwent ECT six times under general anesthesia with thiamylal 250 mg and vecuronium 8 mg, in combination with preventive injection of magnesium sulfate 20 g without any cardiovascular complications. We conclude that the anesthetic management of patients undergoing ECT under general anesthesia should be paid a careful attention for cardiovascular instability, even if they do not have any heart diseases.     

Chronic graft-versus-host autoimmune disease in Fc receptor gamma chain-deficient mice results in lipoprotein glomerulopathy

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by intraglomerular lipoprotein thrombi associated with severe proteinuria and frequent progression to renal failure. The histologic hallmark of LPG is the presence of laminated thrombi, consisting of lipid droplet, within the lumina of dilated glomerular capillaries. The findings of thrombi consisting of lipoproteins raised the possibilities that LPG might be related to a primary abnormality in lipid metabolism. However, the precise pathogenic basis of LPG remains unresolved. It was herein found that chronic graft-versus-host disease (GVHD) induced by the transfer of Ia-incompatible spleen cells from B6.C-H2(bm12) into coisogenic C57BL/6 mice with deficiency of Fc receptor gamma chain (FcRgamma) resulted in glomerulopathy that resembled LPG. The uptake of acetylated LDL was partially decreased in peritoneal macrophages isolated from FcRgamma-deficient mice compared with wild-type mice, suggesting that partial impairment of modified LDL uptake might contribute to the development of LPG associated with chronic GVHD in FcRgamma-deficient mice. LPG has been suggested to be a disorder of primary abnormality in lipid metabolism; these findings would therefore provide novel insight into the disease process.     

Analysis of Breathing Pattern in Children with Asthma

The breathing pattern in children with asthma was studied, using respiratory inductive plethysmography. The subjects were 31 children with mild to moderate asthma (15 males, 16 females; aged 6∼15 years, average 11 years). The respiratory rate was 25.5±10.7/min. (mean ± S.D.) during asthma attacks and 18.4 ± 5.0/min. between attacks with a significant increase during attacks (P < 0.001). The expiratory time was 1.774 ± 0.833 second during attacks, and 2.125 ± 0.602 seconds between attacks. The expiratory time to total respiratory time ratio (T_E/T_TOT) was 0.631 ± 0.056 during attacks and 0.608 ± 0.035 between attacks. Thus there was a slight prolongation at the time of attack, but the difference was not significant. The tidal volume was increased slightly during mild and moderate attacks. V_T/T_I (mean inspiratory flow) was increased during attacks. The respiratory pattern was thoracic during attacks and changed to the abdominal pattern with improvement.     

Case report of dysgerminoma in a patient with 46,XX pure gonadal dysgenesis

A clinicopathological study of a 42-year-old female with pure gonadal dysgenesis and dysgerminoma was made. At the age of 29, the patient with primary amenorrhea had been evaluated clinically and cytogenetically. (1) The results of cytogenetic studies were X-chromatin positive and revealed a karyotype in peripheral blood leukocytes of 46,XX. (2) Laboratory studies indicated hypergonadotropic hypogonadism and no response of the gonads to the human menopausal gonadotropin stumulation test. (3) At laparotomy, the gonads were streak-like. Pathological examinations of biopsy specimens from both gonads revealed dense, fibrous connective tissue resembling ovarian stroma and no primary follicles. Eleven years after the laparotomy, the patient complained of lower abdominal distention and severe pain, and laparotomy then revealed a 15 × 17-cm right solid adnexal mass occupying the pelvic cavity. The histological diagnosis of tissues from the partially removed tumor was pure dysgerminoma. Second-look operation after Linac X-ray irradiation showed complete remission of the residual tumor. Insofar as we are aware, the present patient represents the first case of dysgerminoma which occurred in the dysgenetic gonads of a phenotypic female with normal 46,XX sex-chromosomal constitutions in peripheral blood leukocytes and the skin fibroblasts although a possibility exists that mosaicism was possibly present but undetected, particularly since the streak gonads were not analyzed chromosomally.     

Impact of Prol2Ala variant in the peroxisome proliferator-activated receptor (PPAR) gamma2 on obesity and insulin resistance in Japanese Type 2 diabetic and healthy subjects

The peroxisome proliferator-activated receptor (PPAR) gamma is an important regulator of adipocyte differentiation and a modulator of intracellular insulin-signaling events. We examined the roles of the Pro12Ala variant of PPAR gamma2 in obesity and insulin resistance in 402 Japanese patients with type 2 diabetes and 116 control subjects. Among the diabetes subjects, the Pro12Pro homozygotes showed significantly higher body mass index (BMI) than those with the Pro12Ala variant (p = 0.020), while there was no association between genotype and BMI in the controls. Furthermore, diabetic subjects with Pro12Pro showed significantly higher fat body mass index (FBMI) than those with Pro12Ala (p = 0.016), while no association between genotype and lean body mass index (LBMI) was observed. Regarding insulin resistance, there was no difference in the HOMA index or in clamp index between Pro12Ala and Pro12Pro variants. These data suggest that the Pro12Ala polymorphism of PPAR gamma2 does not influence insulin resistance but body composition in Japanese diabetic subjects.