Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma.

Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues and hepatocellular carcinomas were determined for comparison with normal liver tissues. In hepatocellular carcinoma, glutamine synthetase activity was approximately one-third of that in normal liver, whereas no detectable change in the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and phosphate-independent glutaminase activities were increased approximately 20-fold and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with those from normal liver, Oxypolarographic tests showed that the rate of glutamine oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher than that in the liver mitochondria. The rate of glutamate oxidation in the liver mitochondria was comparable to that in the cirrhotic liver and tumor mitochondria. Glutamine oxidation was inhibited by prior incubation of the mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial glutaminase. These results indicate that the product of glutamine hydrolysis, glutamate, is catabolized in the tumor and cirrhotic liver mitochondria to supply ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via a transamination pathway in the tumor mitochondria.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

Is preserving the entire aganglionic colon reasonable in the surgical treatment of total colonic aganglionosis?

Clinical reports describe an increased incidence of severe enterocolitis in infants with total colonic aganglionosis (TCA) following the Martin extended Duhamel procedure using the entire aganglionic colon. This study evaluates the efficacy of this procedure in an experimental model of TCA in comparison with an antimesenteric aganglionic colon patch in rats. TCA was produced by serosal application of 0.1% benzalkonium chloride in 18 Sprague-Dawley rats (250 g). Five additional rats served as operated controls. Ileoanal pull-through was performed in 18 TCA rats, in conjunction with the Martin extended Duhamel procedure using the entire colon in six rats, with an aganglionic colon patch in nine (using the right [3 rats], transverse [3 rats] and left [3 rats] colon), and without other procedures in three rats. Animals were evaluated for survival, weight change, food intake, stool consistency and volume, barium enema, complete blood cell count (CBC), total protein, and serum electrolytes at 4 and 12 weeks. Survival was 83% (5/6) rats with the Martin procedure, 100% in the nine rats with various colon patches, zero in three rats with ileoanal pull-through alone, and 100% in controls. Rats with the Martin procedure gained 2.2 +/- 3.27% of preoperative weight, while controls gained 11.2 +/- 0.52% at 4 weeks. All other rats showed an early weight loss. At 12 weeks, right and transverse colon patched rats had weight gain. Blood count and laboratory studies were similar in each group. Barium enema showed rapid transit in rats with ileoanal pull-through, and slower transit in rats with colon patches or the Martin procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of postapoplectic hemichorea/ballism to GPi pallidotomy: progressive improvement resulting in complete relief.

We report on a 66-year-old woman in whom GPi pallidotomy produced progressive and eventually complete relief of hemichorea/ballism (HCB) after a subthalamic hemorrhage. Although choreoballistic movements were unchanged during and immediately after the surgery, the symptoms were gradually improved and consequently abolished by 5 days postoperatively. HCB has never recurred up to the present (9 months follow-up period). This note is the first report describing detailed postsurgical process in HCB relief after pallidotomy.     

Epidural midazolam with saline--optimal dose for postoperative pain]

Optimal dose of epidural midazolam with saline for postoperative pain relief was investigated. Forty three patients for upper abdominal surgery were divided into 5 groups. Each group had either 10 ml saline only (saline group), 10 ml saline + midazolam 0.025 mg.kg-1 (0.025 group), 10 ml saline + midazolam 0.05 mg.kg-1 (0.05 group), 10 ml saline + midazolam 0.075 mg.kg-1 (0.075 group), or 10 ml saline + midazolam 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP was unchanged compared with preinjection level. HR changes were less in 0.05 and 0.1 group than in others. RR changes were less in 0.025 and 0.05 group than in others. Optimal SSs were obtained in 0.025 and 0.05 groups. In 0.075 and 0.1 groups, many patients fell into complete sleep (not responded to verbal command). TNA was about 2 hours in 0.025 and 0.05 groups, over 6 hours in 0.075 and 0.1 groups. Complete sleep was the cause of long TNA in 0.075 and 0.1 groups. It was concluded that optimal dose of epidural midazolam with saline 10 ml was 0.05 mg.kg-1 for postoperative pain relief after upper abdominal surgery.     

Effects of bifemelane on the free fatty acid levels during ischemia

Using the four-vessel extracranial one staged occlusion model of adult Wistar rats, we analyzed quantitatively released free fatty acids during ischemia. Also have we analyzed the effect of bifemelane to reduce free fatty acid accumulation after the onset of ischemia. Bifemelane (15 mg/kg, 30 mg/kg) and saline as control were intraperitoneally administered to adult Wistar rat prior to 30 minutes of experimentally induced ischemia. The results obtained were analyzed by one or two way analysis of variance (ANOVA). Physiological variables (systemic arterial pressure, PaO2, PaCO2, pH) did not change significantly in all four experimental groups. Total free fatty acid levels (sum of 5 fatty acid) increased significantly after ischemia (30 minutes). Higher dose (30 mg/kg) of bifemelane administration significantly reduced total free fatty acid accumulation, though lower dose (15 mg/kg) did have no effect. Bifemelane (30 mg/kg) reduced significant accumulation in the amount of saturated and monounsaturated fatty acid (palmitic acid [16:0], stearic acid [18:0] and oleic acid [18:1]). Arachidonic (20:4) and docosahexaenoic (22:6) acid failed to show any effective reduction by bifemelane pre-treatment of lower nor higher dose. Bifemelane is supposed to have many pharmacological effects such as increase in cerebral blood flow, augmentation of glucose uptake, monoamine metabolism, cerebral vasodilatation and platelet antiaggregation. Free fatty acid accumulation is effectively suppressed by the higher dose of bifemelane administration. Although the exact mechanism are not clearly identified by the result obtained in this experiment, selective inhibition of accumulation in saturated and monounsaturated fatty acids by bifemelane pretreatment may be obtained by the improvement of energy metabolism, which may help to reacylation of fatty acid into phospholipid.     

Surgical Treatment of Intractable Seizures Due to Hypothalamic Hamartoma

Summary: A 6.5-year-old boy developed seizures at age 2.8 years consisting of episodes of unconsciousness and laughing attacks. By age 6 years, multiple seizure types, including generalized tonic-clonic (GTC), complex partial (CPS) and akinetic seizures, and drop attacks were occurring several times daily. EEG showed multifocal epileptic discharges. Antiepileptic drugs (AEDs) did not control the seizures. With progression of the epilepsy, cognitive deterioration developed. There were no manifestations of precocious puberty. Neuroimaging disclosed a suprasellar mass in continuity with the hypothalamus, and a diagnosis of hypothalamic hamartoma was made. After surgical resection of the hamartoma, the seizures were completely alleviated, and the epileptic EEG discharges disappeared. Improvement of mental function was also noted.