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Biomedical subjects

A Yu

Publications and source records attributed to A Yu.

126 records · Page 7Linked to original sources

Effects of phenobarbital upon triacylglycerol metabolism in the guinea pig.

The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male guinea pigs injected intraperitoneally with 50 mg phenobarbital x kg-1 for 7 days. Enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity, cytochrome P450 content, and hepatic gamma-glutamyl-transferase activity. Increased activity of gamma-glutamyltransferase was also observed in the blood serum of treated animals. The phenobarbital-treated guinea pigs manifested increased hepatic triacylglycerol content and serum triacylglycerol concentration, accompanied by enhanced ability of cell-free fractions of liver to synthesize glycerolipids in vitro from sn-[14C]glycerol 3-phosphate and fatty acids. Microsomal phosphatidate phosphohydrolase accounted for 97% of the total liver activity of this enzyme, and its specific activity was 50-fold higher than that of the cytosolic enzyme when each was measured under optimal conditions. Activity of the cytosolic phosphohydrolase per liver doubled and that of the microsomal phosphohydrolase increased by 40% in the phenobarbital-treated guinea pigs. The microsomal, but not the cytosolic enzyme, showed a significant correlation with hepatic triacylglycerol content. Significant correlation was observed between the various parameters of hepatic microsomal enzyme induction and hepatic triacylglycerol content, suggesting that enzyme induction may promote triacylglycerol synthesis and consequent hypertriglyceridaemia in the guinea pig.

Aminopyrine N-Demethylase↗

Enzyme induction and hepatic glycerolipid synthesis in rats treated with 3-methylcholanthrene.

Fasting male rats fed 3-methylcholanthrene in a daily dose of 40 mg . kg body weight-1 gave evidence of hepatic microsomal enzyme induction after 3 days through significantly increased hepatic aryl hydrocarbon hydroxylase activity, cytochrome P448 content, and characteristic changes in microsomal proteins analysed by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Concomitantly, activities of aminopyrine N-demethylase and microsomal gamma-glutamyltransferase, which are increased in phenobarbital-treated rats, significantly declined. In contrast to phenobarbital, which has been previously shown to increase hepatic triacylglycerol content and in vitro glycerolipid synthesis, 3-methylcholanthrene did not affect hepatic triacylglycerol content, but did inhibit glycerolipid synthesis by cell-free preparations of rat liver and significantly reduced serum triacylglycerol concentration. Thus, the two prototypical drugs inducing characteristically different changes in microsomal enzyme and hemoprotein response also seem to differ in their effect upon another important microsomal function, hepatic glycerolipid synthesis.

Animals↗

Effects of phenobarbital upon triacylglycerol metabolism in the rabbit.

1. The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male rabbits (2kg body wt.) injected intra-peritoneally with 50 mg of phenobarbital per kg for 10 days. 2. Occurrence of enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity and cytochrome P-450 content, as well as a doubling of microsomal protein per g of liver and a 54% increase in liver weight. Parallel increments in hepatic gamma-glutamyltransferase (EC 2.3.2.2) activity occurred; these were more pronounced in the whole homogenate than in the microsomes, which only accounted for 12.5% of the total enzyme activity in the controls and 17.0% in the animals given phenobarbital. Increased activity of gamma-glutamyltransferase activity was also observed in the blood serum of the test animals. 3. The rabbits given phenobarbital manifested increased hepatic triacylglycerol content and the triacylglycerol concentration of blood serum was also elevated. These changes were accompanied by a significantly enhanced ability of cell-free fractions of liver from the test animals (postmitochondrial supernatant and microsomal fractions) to synthesize glycerolipids in vitro from sn-[14C] glycerol 3-phosphate and fatty acids, when expressed per whole liver. Relative to the protein content of the fraction, glycerolipid synthesis in vitro was significantly decreased in the microsomes, presumably consequent upon the dramatic increase in their total protein content, whereas no change occurred in the postmitochondrial supernatant, possibly due to the protective effect of cytosolic factors present in this fraction and known to enhance glycerolipid synthesis. 4. Microsomal phosphatidate phosphohydrolase accounted for 85% of the total liver activity of this enzyme and its specific activity was 20-fold higher than that of the cytosolic phosphatidate phosphohydrolase (EC 3.1.3.4), when each was measured under optimal conditions. A significant increase in the activity of both enzymes per whole liver occurred in the rabbits given phenobarbital. A closer correlation between hepatic triacylglycerol content and and microsomal phosphatidate phosphohydrolase, as well as the above observation, suggest that this, rather than the cytosolic enzyme, may be rate-limiting for triacylglycerol synthesis in rabbit liver. 5. Significant correlations were observed between the various factors of hepatic microsomal-enzyme induction (aminopyrine N-demethylase and gamma-glutamyltransferase activity as well as cytochrome P-450 content) and hepatic triacylglycerol content, suggesting that that microsomal enzyme induction may promote hepatic triacylglycerol synthesis and consequently hypertriglyceridaemia in the rabbit.

Animals↗

Absence of preferential glutamine uptake into neurons--an indication of a net transfer of TCA constituents from nerve endings to astrocytes?

Uptake kinetics for glutamine were studied in several different neuronal preparations (perikarya prepared by gradient centrifugation, cultured cortical neurons, cultured, presumably glutamatergic cerebellar neurons, and brain prisms). In no case were any indications found of a high affinity uptake but a rather efficient low affinity uptake did occur. A similar, equally efficient low affinity uptake is, however, found in astrocytes. Thus, no preferential glutamine uptake occurs into neurons. It is, therefore, not likely that a net flow of glutamine takes place from astrocytes to neurons, compensating for the loss of TCA constituents when glutamate and GABA are released.

Animals↗

Concomitant presence of tumor-specific cytotoxic and inhibitor lymphocytes in patients with osteogenic sarcoma.

The lack of detectable tumor-specific cytotoxicity by the peripheral blood lymphocytes of patients with cancer may be due to a lack of cytotoxic lymphocytes or the presence of suppressor lymphocytes that inhibit cytotoxic cells. Unfractionated peripheral blood lymphocytes from 12 of 28 patients with osteogenic sarcoma were cytotoxic to osteogenic sarcoma cells in vitro (P less than 0,001). When the peripheral blood lymphocytes from patients whose lymphocytes were not cytotoxic underwent fractionation, a tumor-specific cytotoxic subpopulation was isolated from 11 of 13 patients (P less than 0.0001). Lymphocytes that inhibited cytotoxic activity of autologous tumor-specific cytotoxic lymphocytes were found in four of 10 patients with osteogenic sarcoma but not in six normal controls. Inhibitor lymphocytes form rosettes with sheep erythrocytes and adhere to nylon, whereas cytotoxic lymphocytes have a receptor for C3 but no surface immunoglobulin. The lack of tumor-specific lymphocytotoxicity in some patients can be due to inhibitor lymphocytes.

Cell Fractionation↗

Detection of a TL(+) murine leukemia cell line that resists the cytotoxic effects of guinea pig complement and specific antiserum.

RADA-1 cells [H-2a thy-1b; thymus-leukemia (TL) 1, 2, 3], a radiation-induced murine leukemia cell line maintained by serial transfer in histocompatible recipients, resisted lysis by guinea pig complement (GPC) and TL 1, 3; TL 2; or TL 1, 2, 3 antiserum. The cells expressed TL antigenic specificities as determined by indirect fluorescent antibody methods, the direct isolation of TL antigens from the cells, and the capacity of the cells to reduce known titers of TL antisera. GPC was consumed to the same extent during the reaction of resistant cells and TL antisera as occurred in the reaction of sensitive cells (killed under similar conditions) and TL antisera. RADA-1 cells were not nonspecifically resistant to complement (C)-mediated lysis; they were killed in the presence of H-2a antiserum and GPC. The TL antisera contained antibodies for TL determinants. They stimulated the C-mediated lysis of ASL-1 cells (TL 1, 2, 3) and thymocytes from strain A mice (TL 1, 2, 3). The TL antigens of resistant RADA-1 cells underwent antigenic modulation, the reversible disappearance of TL antigens from the cells stimulated by specific antiserum. After the cells were treated with neuraminidase, they became susceptible to the cytotoxic effects of aliquots of the same TL antisera and GPC used previously.

Animals↗

Hepatic abscess following transhepatic drainage of subphrenic abscess.

A case of an hepatic abscess that developed after percutaneous transhepatic drainage of a subphrenic abscess is presented. The location of the abscess immediately along the tract of the drainage catheter and the similar organisms recovered from bacteriologic culture suggest that the abscess was related to direct contamination along the tract of the drainage catheter. The potential for abscess formation within the liver should be considered in the choice of access route for percutaneous drainage of retroabdominal abscesses. It may be preferable to avoid transhepatic drainage in patients in whom it is anticipated that the catheter drainage will require considerable length of time.

Catheterization↗

A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia.

The potential mechanisms underlying back pain and/or myalgia experienced by men taking tadalafil were investigated. An integrated analysis of 10 placebo-controlled tadalafil clinical trials (N=1846) showed that the incidence of back pain and/or myalgia was 9.4% in patients receiving tadalafil 10 mg (N=394), 8.3% in patients receiving tadalafil 20 mg (N=883) and 3.7% in placebo-treated patients (N=569). One (0.3%) patient receiving tadalafil 10 mg, six (0.7%) patients receiving tadalafil 20 mg, and no patients receiving placebo discontinued treatment due to back pain and/or myalgia. In a prospective study in healthy volunteers, no substantial changes were observed in laboratory markers indicative of inflammation or muscle damage, and tadalafil did not affect renal plasma flow nor produce lumbar or gluteal myositis by positron emission tomography scan or magnetic resonance imaging. Although the mechanism of back pain and/or myalgia remains unknown, these events appear to be self-limiting and a general effect of phosphodiesterase 5 inhibition.

Adolescent↗

Portal film quality: a multiple institutional study.

The variation in quality of the several thousand portal films submitted to the Quality Assurance Review Center (QARC) has been substantial. To ascertain the nature and severity of this problem, a detailed study of "whole brain" portal films which were taken at 23 different radiotherapy departments for patients entered on three national leukemia studies was performed. Each film was analyzed in two ways: (a) independent subjective evaluation by four experienced radiotherapists and (b) measurement of objective parameters. Scores from 416 evaluations together with measured parameters were stored in a data base system for easy statistical manipulation. The dependence of perceived film quality on these objective parameters has been correlated and is the subject of this report.

Humans↗

Imidazoline receptor agonist drugs for treatment of systemic hypertension and congestive heart failure.

The imidazoline receptors recently have been discovered to be involved in the central nervous system control of sympathetic outflow. A new class of centrally acting antihypertensive agents, the imidazoline receptor agonists (rilmenidine and moxonidine), have been developed to control blood pressure effectively without the adverse effects of sedation and mental depression that usually are associated with centrally acting antihypertensive agents. This new generation of centrally acting antihypertensive agents is highly selective for the imidazoline receptor but has a low affinity for alpha(2)-adrenergic receptors. The usefulness of these agents in the treatment of congestive heart failure has not been demonstrated.

Animals↗

Persantine improves acute pancreatitis in vitro.

Persantine combined with TNF-a enhances antiproliferative activity in human tumor cells. We hypothesized that the vasodilator persantine would ameliorate acute pancreatitis (AP) in vitro. Rat pancreatic ductal cells were cultured using standard techniques. Acute pancreatitis was induced by adding cerulein (10(-9) M) or TNF-a (200 ng/ml). AP was verified by increased amylase production. Persantine was added at concentrations from 0.1 uM to 100 uM post cerulein or TNF-a treatment. Statistical analysis was achieved by ANOVA. Amylase production was significantly increased (p < 0.05) compared with control upon stimulation with either cerulein or TNF-a. When persantine was added in graded concentrations from 0.1 uM to 100 uM to cerulein treated cells, it decreased amylase production significantly (p < 0.05) at 100 uM. However, when persantine was added to TNF-a treated cells, it decreased amylase production (p < 0.05) at the lower concentrations of 0.1 uM and 1 uM. We have shown for the first time that AP, resulting from either mild (cerulein) or severe (TNF-a) stimulation, is significantly improved by treatment with persantine.

Acute Disease↗

Contact dermatitis by sensitization to amine-type antioxidants.

Numerous reports had been published implicating IPPD and other amine-type antioxidants as the causative agents in patients with allergic sensitization following the use of industrial and household products that have black rubber in their composition. The amine-type antioxidants, used to stabilize the polymer chains and to prevent rubber from cracking, are the agents more frequently implicated in this type of contact allergic dermatitis. Based on a case of a patient who had erythematous edematous and vesiculous processes in the periocular region that appeared a few hours after the use of a video camera with a black rubber eyepiece, we reviewed the clinical features, and the etiological agents of this infrequent form of contact dermatitis. This patient represents the first described case in the literature of allergic sensitivity after the use of a video camera eyepiece.

Adult↗