Bile acid profile as early indicator of allograft function during orthotopic liver transplantation

Orthotopic liver transplantation was performed in 20 pigs. Serum total bile acids (STBA) were determined and their profile compared with standard early function parameters: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid. In phase I, the STBA level was 32.89 +/- 1.29 mumol/l. In phase II, STBA accumulated to 84.46 +/- 15.25 mumol/l (p less than 0.01), followed by hepatic clearance in phase III (63.61 +/- 9.71 mumol/1; NS). Between phase III and 6- and 12-hour samples, STBA decreased progressively, reaching values of 33.63 +/- 7.05 mumol/l at 24 h. AST was elevated in phases I, II, III, and at 6, 12 and 24 h (p less than 0.001), as was ALT (but with insignificant differences). Thus, STBA and their profile appear to be earlier and more specific indicators of early graft function than conventional parameters.     

Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.

A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.     

MRI of a family with focal abnormalities of gyration

Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. Received: 22 August 1996 Accepted: 7 October 1996     

Low plasma zinc and androgen in insulin-dependent diabetes mellitus

Plasma zinc and pituitary and testicular hormone concentrations were measured in two groups of male adolescents. One group comprised insulin-dependent diabetes mellitus patients, aged 14-19 years; the other, as control, included 12 healthy youngsters aged 13-19 years. Plasma concentration of zinc, prolactin, testosterone, and dihydrotestosterone were lower in diabetics than in controls, whereas the ratios of androstenedione and androstenedione to testosterone + dihydrotestosterone were higher. Plasma FSH and LH were normal. These results suggest a diminished conversion of androstenedione to testosterone and relate zinc with the 17-beta-hydroxysteroid dehydrogenase enzyme activity.     

Effects of neonatal bilateral eye enucleation on postnatal development of the monoamines in posterior thalamus of the rat

Summary Levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (serotonin, 5-HT) and their metabolites, and the activities of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH) and monoamine oxidase A and B (MAO-A and MAO-B) have been determined in the rat posterior thalamus after enucleation during postnatal development. DA and 5-HT turnover rate have been measured as 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) accumulation rates after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015). The major changes were an increase in noradrenergic and serotoninergic metabolism in enucleated animals compared with control animals. A decrease of the MAO-A to MAO-B ratio during postnatal development was found.Abbreviations DA dopamine - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - DOPA 3,4-dihydroxyphenylalanine - NA noradrenaline - MHPG 3-methoxy-4-hydroxyphenylgly-col - NMN normetanephrine - TRP tryptophan - 5-HTP 5-hydroxytryptophan - 5-HT serotonin - 5-HIAA 5-hydroxy-3-indolacetic acid - TH tyrosine hydroxylase - TPH tryptophan hydroxylase - MAO-A monoamine oxidase-A - MAO-B monoamine oxidase-B Recipients of fellowships from I.I.E. del FISS Reincorporación de doctores y tecnólogos del M.E.C., and Perfeccionamiento de doctores y tecnólogos del MEC, Spain     

Efficacy of adjunctive carbamazepine in the treatment of chronic schizophrenia

Six treatment-resistant schizophrenic patients were given a ten-week single-blind trial of carbamazepine. Treatment resistance was determined on the basis of documented failure to respond to treatment with at least three neuroleptic drugs from two different chemical classes. The adjunctive use of carbamazepine resulted in a significant improvement of the negative symptoms of schizophrenia. These symptoms are often poorly responsive to conventional antipsychotic drugs. Therefore, controlled studies should be performed to further assess the possible efficacy of carbamazepine in schizophrenia.     

Effects of genistein, an isoflavone isolated from Genista tridentata, on isolated guinea-pig ileum and guinea-pig ileal myenteric plexus.

The inhibitory action of the major constituent of Genista tridentata L. (Papilionaceae), 4',5,7-trihydroxyisoflavone (genistein), on contractions induced by agonists and electrical field stimulation of smooth muscle was analysed. Genistein inhibited twitches evoked by electrical-stimulation of strips of guinea-pig ileum with an IC50 value of 34 microM. Genistein (34 microM) inhibited contractions of the guinea-pig ileum by several agonists in a non-selective, antispasmodic action and had no effect on inhibition of 3H-ACh release from ileal myenteric plexus. Genistein (34 microM) produces an increase in cAMP levels of guinea-pig ileum which resulted in a smooth muscle relaxation which leads us to think that there must be a blockade of its phosphodiesterase.     

Natural history of experimental pulmonary atelectasis in dogs with closed chest

In order to establish an animal model of pulmonary vasoconstriction we followed the time course of intrapulmonary shunt (Qs/Qt) in a canine model of lobar atelectasis with closed chest. Ten mongrel dogs were studied. Bronchial occlusion of the right lower lobe (RLL) was performed by inflating the balloon of a Foley catheter placed through a rigid bronchoscopy. Analysis of variance was used for statistical analysis. (15 minutes) After occlusion Qs/Qt reached its maximum increasing from 8.2 +/- 3.6 to 29.7 +/- 11.7% (p less than 0.05) and PaO2 decreased from 357 +/- 49 to 100 +/- 43 mm Hg (p less than 0.05). Afterwards, there was a progressive decline of Qs/QT accompanied by an also progressive increase in PaO2. At the end of the experiment (3 hrs post atelectasis) Qs/Qt was 11.2 +/- 4.9 and PaO2 251 +/- 124 mm Hg (p less than 0.05). Pulmonary vascular resistance increased post atelectasis from 439 +/- 168 to 598 +/- 256 d.s.cm-5 (p less than 0.05). Complete atelectasis of the RLL was confirmed postmortem. As the changes in Qs/Qt and PaO2 did not parallel the change in cardiac output we conclude that the mechanism of decrease in Qs/Qt was hypoxic vasoconstriction.