Bioavailability of mefenamic acid: influence of food and water intake

The influence of food and water intake on mefenamic acid (N-2,3-xylylanthranilic acid) bioavailability from commercial capsules of high bioavailability was studied in four healthy male volunteers. The drug was administered as a single oral dose of 250 mg, under fasting or nonfasting conditions, and a 4 X 4 Latin-square design was used. Eight blood samples were collected over a 24-h period following drug administration, and the drug plasma concentrations were determined by HPLC. The bioavailability of mefenamic acid from capsules was markedly influenced in the fasting subjects by the water but not by the food intake. A good correlation was found between the bioavailability and amount of water ingested with the drug in the fasting subjects. The area under the plasma concentration-time curve (AUC0-infinity) of mefenamic acid was highest when the capsule was taken with 50 mL of water or immediately after a meal. Increasing the amount of water from 50 to 500 mL in the fasting subjects caused a significant reduction in AUC0-infinity.     

Prediction of remission in Graves' disease after thionamide therapy by technetium-99m early uptake]

In the clinical management of Graves' thyrotoxicosis, one of the most important subject is when to stop antithyroid drugs after achieving an euthyroid state. T3 suppression test and other methods have been used to forecast the outcome after drug cessation, but the results were not always satisfactory. We have attempted to predict remission of Graves' disease by single measurement of early technetium uptake without administration of triiodothyronine. Drugs were discontinued in the seventy-five patients with Graves' disease on maintenance doses of either methimazole or propylthiouracil who showed normalized uptake (4.0% or less). Of 64 patients evaluable after twelve months, 55 (86%) remained euthyroid, 8 relapsed, and 1 became hypothyroid. With its accuracy in prediction of short-term remission comparable or superior to T3 suppression test, this rapid and simple method seemed suitable for routine use in clinical practice.     

Bending and torsion fractures in long bones (a mechanical and radiologic assessment of clinical cases).

Long bone injuries in clinical cases are studied by comparison of roentgenograms with a rational mechanical analysis of the injuries. Fractures produced by torsional loads have a spiral shape with a smooth and even surface. Fractures induced by bending loads have uneven and rugged fracture surfaces perpendicular to the bone axis. Long bones are weak in torsion but strong in tensile stress produced by bending. This result corresponds to the clinical fact that a large direct external force is needed to produce a transverse fracture while a spiral fracture is produced by a relatively small torque.     

Noradrenergic activation of immediate early genes in rat cerebral cortex.

Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.     

Total-body protein turnover in parenterally fed neonates: effects of energy source studied by using [15N]glycine and [1-13C]leucine

The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.     

Cardiocirculatory disturbances after surgery of carcinoma of the thoracic esophagus

From 1976 to 1985, 277 cases of carcinoma of the esophagus were resected in the Second Department of Surgery, Tohoku University School of Medicine. Postoperative cardiocirculatory disturbances occurred in 114 cases (41.2%), arrhythmia being the disturbance most frequently observed (86.8%). Low cardiac output syndrome occurred in 8 cases and myocardial infarction occurred in 3 cases. The majority of the cases were treated successfully, but 5 patients died within one month after operation. Causes of death were as follows: myocardial infarction, constrictive pericarditis, cardiac tamponade, non-occlusive mesenteric ischemia and acute cardiac failure. Postoperative arrhythmia occurred mainly up to the third postoperative day. Low cardiac output syndrome occurred just after operation or on the first postoperative day. All cases of myocardial infarction occurred on the first postoperative day. The rate of occurrence of cardiocirculatory disturbances in aged patients (greater than or equal to 70) was significantly higher than other group (less than or equal to 69), (56.7%:38.1%, p less than 0.05). The rate of occurrence of cardiocirculatory disturbances in patients who had a history of hypertension or in patients with abnormal preoperative electrocardiographic findings were relatively higher than those in patients who had no history of hypertension or in patients with no abnormal preoperative electrocardiographic findings. The rate of occurrence of cardiocirculatory disturbances in patients who had undergone total resection of the thoracic esophagus was significantly higher than that in patients who had undergone partial resection of the thoracic esophagus (42.8%:23.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal antinociceptive effects of adenosine compounds in mice

The effects of injecting ATP, ADP, AMP, adenosine and adenine intrathecally on the pain response induced by the injection of substance P (10 ng/mouse) intrathecally were studied. All the compounds except adenine inhibited the pain response in a dose-related manner. The ED50 values of ATP, ADP, AMP and adenosine were 2.10, 0.93, 0.88 and 0.48 micrograms/mouse, respectively. Pretreatment with theophylline at a dose of 100 mg/kg p.o. markedly diminished all the antinociceptive effects. The effect of adenosine was not affected by s.c. injection of naloxone. These results suggest the existence of adenosine receptors which modulate spinal nociceptive sensory processing, independently of the endogenous opiate system.