Anticonvulsant drug concentrations in epileptic patients

Using Wistar stain male rats, it has been shown that 2 atmospheric pressures associated with oxygen saturation, together or singly for 90 minutes daily for successive 46 days, resulted in no significant change on the ratio of testes to body weight. No significant change was observed in the incorporation of 3H-thymidine into testes and pituitary glands between the pressure-treated groups and the control group.     

Renaturation of formyltetrahydrofolate synthetase from urea and guanidinium chloride solutions

Formyltetrahydrofolate synthetase from Clostridium cylindrosporum and Clostridium acidi-urici was denatured in 6 M urea and 4 M guanidinium chloride. Viscometric, fluorimetric and ultracentrifugal measurements were used to determine that the protein is completely unfolded under these conditions. The polypeptide chains refold upon dilution of the denaturant-protein solutions to give final concentrations of 0.5 M urea or 0.1 M guanidinium chloride. In the presence of NH4+, but not in its absence, the refolded proteins associate to produce the catalytically active tetramer. Refolding and reassociation were followed by measuring changes in protein fluorescence and by determination of sedimentation constants. Under most conditions 80% of the enzymic activity is recovered.     

Inactivation of pyridoxal phosphate dependent enzymes by mono- and polyhaloalanines

beta,beta-Dichloro- and beta,beta,beta-trifluoroalanine irreversibly inactivate a number of pyridoxal phosphate dependent enzymes which catalyze beta- or gamma-elimination reactions. The inactivation is time dependent and the rate of inactivation is first order in enzyme concentration. This suggests that inactivation is due to covalent modification of the enzyme by a species generated at the active site from the polyhaloalanine (i.e., suicide inactivation). Monohaloalanines are substrates and do not inactivate. For gamma-cystathionase, covalent and stoichiometric attachment of [1-14C]beta,beta,beta-trifluoroalanine was shown. It is proposed that the mechanism of inactivation involves Schiff base formation between inactivator and enzyme-bound pyridoxal and subsequent elimination of HC1 from dichloroalanine or HF from trifluoroalanine. This results in the formation of a beta-halo-alpha,beta unsaturated imine, an activated Michael acceptor. Michael addition of a nucleophile at the active site leads to covalent labeling of the enzyme and inactivation. Alanine racemase is also inactivated by the two polyhaloalanines. Glutamate-pyruvate and gultamate-oxaloacetate transaminase are inactivated by monohaloalanines but not by polyhaloalanines.     

Bilateral pulmonary hilar lymphadenopathy. An unusual manifestation of metastatic renal cell carcinoma

The significance of glucagon for the alterations in carbohydrate and fat metabolism during swimming has been evaluated. Fed, male rats were used. Blood was drawn by cardiac puncture for glucose analysis and either rabbit-antiglucagonserum (A-rats) or normal rabbitserum (N-rats) injected. Twenty-nine rats were then forced to swim (S-rats) with a tail weight for 60 min, while 16 rats were resting controls (C-rats). Subsequently blood was drawn and samples of liver and muscle tissue collected. In SN-rats glucagon concentrations increased from 152 +/- 18 (S.E.) pg/ml (CN-rats) to 332 +/- 61 (P less than 0.05), while liver glycogen decreased (P less than 0.001) and blood glucose increased (P less than 0.05). In SA-rats, however, the changes in liver glycogen and blood glucose were halved indicating that increased glucagon secretion enhances hepatic glycogen depletion during prolonged exercise. NEFA rose in SA-rats (P less than 0.005) as well as in SN-rats (P less than 0.05). Glycerol concentrations, however, only increased in SA-rats (P less than 0.05) indicating a shift towards lipid combustion in antibody treated rats. Muscle glycogen and plasma insulin diminished and blood lactate increased uniformly in exercised rats.     

Immunoreactive growth hormone levels in pigs fed protein or energy restricted diets during the postweaning period

Developmental changes in growth hormone levels during protein or energy malnutrition was studied in weaned pigs. Three or 4 weeks old pigs from control dams were fed a control diet (18% protein), an energy-restricted diet (18% protein) or a low protein diet (6% protein) for 8 weeks. Energy restriction was achieved by feeding the control diet in amounts that allowed very little growth. After the restriction period, all pigs were fed the control diet ad libitum for another 8 weeks. Blood samples were collected at intervals throughout the experiment and the plasma was analyzed for growth hormone by radioimmunoassay. Post weaning protein deprivation resulted in higher growth hormone levels during the restriction period as compared to control pigs or pigs with a restricted energy intake.     

Electrophysiologic effects of propranolol on sinus node function in patients with sinus node dysfunction

The electrophysiologic effects of intravenously administered propranolol (0.1 mg/kg) on three parameters of sinus node function were examined in ten symptomatic patients with sinus node dysfunction. The patients ranged in age from 26 to 79 years. Symptoms ranged from fatigue to frank syncope. Sinoatrial (SA) block and sinus pauses were observed in one patient; sinus pauses alone were observed in three patients. Five (5/10) patients had intraatrial block; three (3/10) patients had atrioventricular block; four (4/10) patients had an intraventricular conduction disturbance. At the time of electrophysiologic study, two patients had a control spontaneous sinus cycle length that exceeded 1000 msec. Following propranolol, the mean spontaneous cycle length increased by 17.4% (924 to 1085 msec, P less than 0.005) and spontaneous second degree SA block reappeared in the one patient. The maximum escape cycle ranged from 116% to 229% of the prepacing spontaneous cycle length and was considered to be prolonged in two of ten patients. Propranolol had no significant effect on the maximum escape cycle/prepacing cycle length X 100 (%). The estimated sinoatrial conduction time (SACT) was determined in seven patients and ranged in value from 120 to 238 mes. Propranolol increased the mean value of the estimated SACT from 179 to 213 msec, P less than 0.025. Propranolol may cause marked bradyarrhythmias in some patients with sinus node dysfunction, and should be used with caution in these patients.     

Persistent obstructive jaundice, cholangitis, and biliary cirrhosis due to common bile duct stenosis in chronic pancreatitis

Long strictures of the intrapancreatic portion of the common bile duct were found in 6 patients with chronic pancreatitis. These strictures were responsible for painless obstructive jaundice, recurrent cholangitis, secondary biliary cirrhosis, and chronic abdominal pain difficult to distinguish from that caused by pancreatitis. Endoscopic retrograde cholangiopancreatography and intraoperative cholangiography were invaluable in making the diagnosis and in planning surgical correction. Decompression of the biliary tree by anastomosis of the gallbladder or common duct to the small intestine completely relieved symptoms and allowed liver function to improve significantly. Common duct stricture as a complication of chronic pancreatitis should be considered in the differential diagnosis of extrahepatic biliary obstruction and whenever surgical treatment of chronic pancreatitis is contemplated.