Suppression of elevated alanine aminotransferase activity in liver disease by vigabatrin

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for many conditions including arthritis. A rare complication of their use is diaphragm-like strictures of the small and large intestines. A 65-year-old woman with a 12-year history of arthritis came to us with a 35-pound weight loss and anorexia. She had been taking piroxicam for 3 years. Evaluation including enteroclysis revealed multiple mid-ileal diaphragm-like strictures and proximal small bowel dilatation. The symptoms persisted despite discontinuance of the drug. Abdominal exploration with intraoperative enteroscopy revealed five ileal strictures within a short segment of bowel. Resection was done and completion enteroscopy showed no other strictures. The patient recovered uneventfully and had full resolution of the symptoms. We discuss the difficulties in diagnosis and management of this drug complication and briefly review the literature.     

Distribution and characterization of anandamide amidohydrolase in mouse brain and liver

Anandamide (N-Arachidonoylethanolamine) amidohydrolase catalyzing hydrolysis of anandamide was characterized in mice. The enzymatic activity was highest in the liver, followed by the brain and testis. Negligible activity was found in heart, lung and spleen. The activity in brain and liver was mainly localized in the microsomal fractions. Kinetic experiments demonstrated that Km (microM) and Vmax (nmol/min/mg protein) for the brain microsomes were 9.3 and 2.58, respectively, while those for the hepatic microsomes were 180 and 18.9, respectively. The activity in the microsomes from the liver and brain was markedly inhibited by Cu2+, Hg2+, Se4+, phenylmethylsulfonylfluoride and sodium dodecylsulfate. Brain but not hepatic microsomal enzyme activity was inhibited by delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Kinetic parameters demonstrated that the inhibition by the cannabinoids was competitive in nature. Relatively high distribution of the enzyme activity in brain suggests an importance of the enzyme in the central nervous system to regulate the neuromodulatory fatty-acid amides.     

Ovarian dysfunction in mice following chromium (VI) exposure

The verbal autopsy (VA) questionnaire is a widely used method for collecting information on cause-specific mortality where the medical certification of deaths in childhood is incomplete. This paper discusses review by physicians and expert algorithms as approaches to ascribing cause of deaths from the VA questionnaire and proposes an alternative, data-derived approach. In this validation study, the relatives of 295 children who had died in hospital were interviewed using a VA questionnaire. The children were assigned causes of death using data-derived algorithms obtained under logistic regression and using expert algorithms. For most causes of death, the data-derived algorithms and expert algorithms yielded similar levels of diagnostic accuracy. However, a data-derived algorithm for malaria gave a sensitivity of 71% (95% Cl: 58-84%), which was significantly higher than the sensitivity of 47% obtained under an expert algorithm. The need for exploring this and other ways in which the VA technique can be improved are discussed. The implications of less-than-perfect sensitivity and specificity are explored using numerical examples. Misclassification bias should be taken into consideration when planning and evaluating epidemiological studies.     

Analysis of glutaminase activity and RNA expression in preimplantation mouse embryos

The efficiency of the American Optical Company (Hardy, Rand and Rittler) (HRR) plates for screening, grading and classifying red-green colour deficiency was examined for 401 male colour deficient subjects previously identified and diagnosed with Nagel anomaloscope. There were 83 protanopes, 30 protanomalous trichromats, 96 deuteranopes and 192 deuteranomalous trichromats. Screening sensitivity was found to be 100% for dichromats and 96.4% for anomalous trichromats based on one screening error (35 subjects, including 7 dichromats, where identified by a single error). Thirty subjects (13.5%) made errors on screening plates only and were identified as having minimal colour deficiency. The HRR grading system did not distinguish dichromats and anomalous trichromats; 54% of dichromats were graded as having moderate rather than severe colour deficiency. Protan/deutan classification was correct for 95% of subjects who failed grading plates. HRR grades for anomalous trichromats were compared with the anomaloscope matching range and with pass or fail of the D15 test. The results show that only two rather than four grading categories can be distinguished by the HRR plates and that both the D15 and the HRR plates are needed in a vocational test battery to establish the severity of colour deficiency.     

Chronic imipramine treatment-induced changes in acetylcholinesterase (EC 3.1.1.7) activity in discrete rat brain regions

Cholinergic as well as monoaminergic neurotransmission seems to be involved in the etiology of affective disorders. Chronic treatment with imipramine, a classical antidepressant drug, induces adaptive changes in monoaminergic neurotransmission. In order to identify possible changes in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brain regions after chronic imipramine treatment. Changes in Achase activity would indicate alterations in acetylcholine (Ach) availability to bind to its receptors in the synaptic cleft. Male rats were treated with imipramine (20 mg/kg, i.p.) for 21 days, once a day. Twenty-four hours after the last dose the rats were sacrificed and homogenates from several brain regions were prepared. Membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) after chronic imipramine treatment was significantly decreased in the hippocampus (control = 188.8 +/- 19.4, imipramine = 154.4 +/- 7.5, P < 0.005) and striatum (control = 850.9 +/- 59.6, imipramine = 742.5 +/- 34.7, P < 0.005). A small increase in total Achase activity was observed in the medulla oblongata and pons. No changes in enzyme activity were detected in the thalamus or total cerebral cortex. Since the levels of Achase seem to be enhanced through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endings. Therefore, our data indicate that cholinergic neurotransmission is decreased after chronic imipramine treatment which is consistent with the idea of an interaction between monoaminergic and cholinergic neurotransmission in the antidepressant effect of imipramine.     

Glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities in riboflavin-deficient rats infected with Plasmodium berghei malaria

Our understanding of animal development has been revolutionized by genetic approaches to the identification and isolation of pattern-regulating genes. In the past several years, fundamental embryological concepts such as morphogenetic fields, compartments, and organizers have been defined at a molecular level and visualized in developing animals. Here, I will discuss how the focus on the regulation and function of genes with dramatic effects on pattern formation, primarily by through the analysis of gene expression patterns as surrogates of physical pattern elements, has elucidated gene hierarchies that control developmental pathways.     

苯并(a)芘和滴滴涕联合暴露对小鼠肝脏细胞凋亡的影响

目的:探讨不同剂量苯并(a)芘[benzo(a)pyrene,B(a)P]、滴滴涕(chlomphenothane,DDT)单独及联合暴露对小鼠肝脏细胞的毒性效应.方法:成年雌性昆明种小鼠66只,随机分为11组:分别为0.5、5、50 mg/(kg·d)B(a)P染毒组,0.025、0.25、2.5mg/(kg·d)DDT染毒组,0.5 mg/(kg·d)B(a)P+0.025 mg/(kg·d)DDT联合染毒组,5 mg/(kg·d)B(a)P+0.25 mg/(kg·d)DDT联合染毒组,50 mg/(kg·d)B(a)P+2.5 mg/(kg·d)DDT联合染毒组,空白对照组(正常饲养)和溶剂对照组(植物油处理).染毒组用含B(a)P、DDT的食用油进行腹腔注射,每天1次,连续21 d,于末次给药24 h后处死小鼠.取肝脏制作冰冻切片,利用原位缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法检测肝细胞凋亡情况.结果:5和50 mg/(kg·d)B(a)P染毒组小鼠肝脏细胞凋亡率显著高于对照组(P<0.05),且50 mg/(kg·d)剂量组显著高于0.5和5 mg/(ks·d)剂量组(P<0.05);各DDT染毒组与对照组比较,差异无统计学意义(P>0.05);各浓度联合染毒组小鼠肝脏细胞凋亡率均高于对照组(P<0.01),各联合染毒组细胞凋亡率间的差异无统计学意义(P>0.05),联合染毒组细胞凋亡率和相应的B(a)P染毒组比较,差异无统计学意义(P>0.05).结论:B(a)P的单独暴露以及与DDT的联合暴露均可导致小鼠肝脏细胞凋亡的发生,并可能引发其他毒性效应.     

Metabolic role of glutamine and its importance in nutritional therapy

The advances in the field of nutritional support have made certain nutrients very relevant, which, although they have been known for a long time, at present represent an important chapter in nutrition, entering into what is known as "nutritional pharmacology". Among these nutrients is glutamine, an amino acid classified as non-essential, but which in certain circumstances may become to be considered as an "essential nutrient". In the present review, a review is made of its metabolic role, synthesis and degradation, metabolic routes and functions under normal conditions as well as under critical conditions. It is known that glutamine stimulates the synthesis and inhibits the degradation of proteins, it is an important vehicle for the transport of nitrogen and carbon within the tissues, it stimulates the synthesis of hepatic glycogen, it is an energy source for cell division, for the growth of different cells of rapid replication, such as enterocytes, colonocytes, and fibroblasts, as well as for other cells of the immune system, such as lymphocytes and macrophages. Thus its role in the maintenance of structure, in metabolism and function of the intestinal mucosa, and in dysfunctions of the immune system. In parenteral nutrition, at present there are no preparations which include it, given the stability problems which it presents, although attempts have been made to resolve this, using different possibilities, such as di-peptides. However, in enteral nutrition, the diets tend to include it, although in a small proportion. Nevertheless, having recognized its beneficial role in a certain type of patients, at present there are diets which contain glutamine in higher doses, with the object of attempting to cover the increased demands of glutamine which shall arise in these situations. The inclusion of glutamine in nutritional therapy is supported by multiple studies which reflect the beneficial effect of this nutrient, both in enteral nutrition as in parenteral nutrition.     

Ubiquitin-mediated degradation of tyrosine aminotransferase (TAT) in vitro and in vivo

Cells coexpressing lymphoid and myeloid cell surface markers have been described for various leukemias and non-Hodgkin's lymphomas. It is unclear whether these mixed lineage characteristics are due to malignancies of early progenitor cells or alternatively to malignant cells with lineage infidelity. Recently, it has been shown that cells coexpressing lymphoid and myeloid markers can be generated from peripheral blood lymphocytes from normal individuals as well. In this review, consequences of this surprising fact are discussed.     

Changes in urinary enzyme activity following silicon therapy of vesico-ureteral reflux

The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS) and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children's. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but that of GGT, ALP and DDP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzymes' activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprofilactic drug at the time of both urine sampling, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.     

Surgical therapy of metabolic liver diseases (glycogenosis, hypercholesterolemia)

Up-to-date, most patients with serious chronic hepatic disease are best treated by liver transplantation. It has been confirmed the striking benefit of liver transplantation also for patients with glycogen storage disease or homozygous familial hypercholesterolemia who were refractory to medical treatment. Nevertheless, the advantage of achieving palliation without transplantation, thereby avoiding the need for chronic immunosuppression, is obvious. With reference to the mentioned above diseases, end-to-side portacaval shunt was used. A favourable effect was noted on body growth and a number of metabolic abnormalities. Hepatic failure did not occur, although in a few patients blood ammonia concentrations and serum alkaline phosphatase levels increased relative to preoperative values. To avoid an incomplete palliation provided by portacaval shunt, appropriate case selection is a problem. The Authors report their personal experience with portacaval shunt for the treatment of glycogenosis and familial hypercholesterolemia.     

Efficacy of microwave coagulation therapy (MCT) in patients with liver tumors

We evaluated the efficacy of microwave coagulation therapy (MCT) in 84 patients with hepatocellular carcinomas (HCC) and 40 with metastatic liver tumors (MLT). The response rates calculated with diagnostic imaging were 92% in HCC and 80% in MLT. The regional recurrence rates were relatively higher in patients with MLT (33%) than in HCC (14%). The average surgical margin in operative MCT group was 11 mm. The cumulative survival rates at three and five years were 63% and 38% in HCC and 43% and 33% in MLT, respectively. The complications were similarly encountered in HCC and MLT (12% versus 13%). When these observations are taken together, MCT is a radical and safe locoregional therapy which can keep an adequate surgical margin and assure long survival.     

Correlation between sexual steroid effect and activity changes and isoenzyme distribution of lactate dehydrogenase (EC 1.1.1.27) in rat anterior pituitary

Sexual steroid feed-back is a fundamental regulating factor oification of pituitary metabolism in rat. Oestrogen synthesis and/or activity of M subunif testosterone, in males testosterone treatment as well as lack of oestrogen result in characteristic pituitary LDH activity and isoenzyme distribution. Physiological doses of sexual steroids affect, directly or indirectly, pituitary LDH activity, oxydative metabolism, and imply different biochemical bases for the polypeptide hormone production in the anterior pituitary gland.     

In situ detection of myocardial infarction in pig by measurements of aspartate aminotransferase (ASAT) activity in the interstitial fluid

Recent studies have suggested that the fetal dysmorphogenesis in diabetic pregnancies is associated with an increase in embryonic oxygen-free radicals. This excess of oxygen-free radicals may result from either overproduction or decreased clearance by the enzymatic scavenging mechanism. However, there are no in vivo data on the activity of embryonic oxygen-free radical scavenging enzymes. The purpose of the current study is to investigate whether this increase in embryonic oxygen-free radicals is the result of a change in the activity of the fetal oxygen-free radical scavenging/antioxidant enzymes during pregnancy complicated by maternal diabetes in an in vivo rat model. Thirty-six Sprague-Dawley rats were randomly assigned to one of two study groups: nondiabetic control and an untreated diabetic group. On day 12, fetuses were examined for crown-rump lengths, somite numbers, and external anomalies. The activity of fetal oxygen-free radical scavenging enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), were determined. The untreated diabetic group of rats had a significantly higher mean blood glucose level than that of the nondiabetic controls and also a significantly lower weight gain, higher resorption rate, smaller embryonic size with lower total protein content, and a approximately 6-fold increase in the rate of fetal neural tube defects compared to the nondiabetic controls. Superoxide dismutase activity was significantly reduced in the embryos with neural tube defects regardless of maternal diabetic status (2.25 +/- 0.83 vs. 1.17 +/- 0.04 u/mg protein; P < 0.05). Glutathione peroxidase and catalase activity were significantly reduced in malformed versus normal-formed embryos of nondiabetic mothers (GPX-2.68 +/- 1.15 vs. 4.46 +/- 1.12 mu/mg protein, CAT -1.67 +/- 0.53 vs 2.49 +/- 0.61 u/mg protein respectively; P < 0.01). However, overall catalase activity was increased in embryos of diabetic mothers as compared to controls. Two-way analysis of variance identified fetal malformations as the variance associated with reduced fetal SOD activity, whereas maternal diabetes was associated with the increase in fetal catalase activity. Neither neural tube defect nor maternal diabetes was found to be the variable affecting fetal GPX activity, Fetal oxygen-free radical scavenging enzymes respond differently to the adverse environment created by maternal diabetes during pregnancy. Defects in embryonic SOD and catalase activity, regardless of maternal diabetic status, may reduce the ability of the fetus to clear free oxygen radicals, thereby exposing it to an increased oxidative load that may cause fetal dysmorphogenesis. The diabetic state of the mothers did not decrease embryonic activity of any of the scavenging enzymes. Therefore, although excess oxidative load, as observed in diabetes, may cause tissue injury and embryopathy, the mechanism does not appear to be a diabetes-induced reduction in the action of the scavenging enzymes.     

Decrease in high density lipoprotein cholesterol (HDL-C) levels following gemfibrozil therapy

A matter of debate is whether the use of a video-endoscope impairs visual orientation and manual precision in endonasal surgery. We investigated the influence of video-endoscopy compared to endoscopy on stereoacuity in a model of the nasal cavity. Twenty medical staff members were asked to touch defined points in a spatial model of the nasal cavity as quickly as possible and in correct order using 0 degree and 30 degrees endoscopes, looking directly through the endoscope or looking at a video monitor connected to a CCD camera on the endoscope. Time, number of omissions of points and faults in point sequence were recorded. Manipulations were significantly quicker when the "operative field" was seen directly through the endoscope compared to orientation from the monitor for both 0 degree endoscope 96 +/- 4.7 s. vs. 108 +/- 5.6 s. and 30 degrees endoscope 84 +/- 3.9 s. vs. 96 +/- 5.5 s. (+/- SEM). There was no difference in number of omissions and faults in sequence between "endoscope" and "video-endoscope." The fact that the use of a video-endoscope did not increase the number of faults in our experiment does not support the notion that performing endoscopic sinus surgery using a monitor is unsafe. In the hands of the participants who were experienced with the endoscope, however, the use of a video-endoscope slowed down manipulations to a significant degree. To which extent this may be due to the effect of training or to superiority of the endoscope per se will remain a matter of discussion until a group of experienced video-endoscopists will have repeated the study.     

Decrease of disaccharidase activity following application of bencyclan-hydrogenfumarate (author's transl)

The disaccharidase activity of the small bowel mucosa of the rat is decreased by intraperitoneal application of Bencyclan-hydrogenfumarate. The doses applied were 10, 50 and 100 mg/kg body weight. The decrease rate after 100 mg/kg attained up to 50% of the control values. Furthermore, a reduction of villous height and an increase of the crypt depth has been observed in correlation with the enzyme activity decrease. Though functional and morphological alterations show a correlation, they cannot be explained by an antimetabolic-like effect because of the fact that the enzyme function recovers 72 h after application of the drug. Whilst our results do not sustain a cytostatic effect of Bencyclan-hydrogenfumarate, there is no doubt that the intraperitoneally applied drug influences the disaccharidase activity. These facts have to be considered in clinical therapy.