The pharmacological stimulation of NMDA receptors via co-agonist site: an fMRI study in the rat brain

d-Serine has been proposed as an endogenous modulator at the co-agonist glycine-binding site of N-methyl-d-aspartate (NMDA) receptors. There is still some debate as to whether this site is saturated in vivo, but it seems likely that this depends on regional differences in local glycine or d-serine concentrations. In order to identify areas where the co-agonist site was not fully activated in vivo, we studied the effect of intraperitoneal d-serine administration in the rat brain using functional magnetic resonance imaging (fMRI). Using contrast agent injection, the variations in the relative cerebral blood volume (CBVrel) in several regions of interest were evaluated. d-Serine (50 mg/kg) elicited a significant statistical increase in the CBVrel in the hippocampus. This effect was inhibited by the specific full antagonist of the co-agonist glycine site L-701,324 indicating that the hippocampal activation occurred through the binding of the agonist d-serine to the glycine-binding site of NMDA receptors. This result demonstrates that in the hippocampus, the co-agonist sites of NMDA receptors are not endogenously saturated under our experimental conditions, suggesting an important role of d-serine in the modulation of receptor function in the hippocampus.     

Relating cistrons and functions in bacteriophage PM2

An approach to correlate functions with cistrons in bacteriophage PM2 is presented. Two of the temperature-sensitive mutants obtained differed from the wild type in heat sensitivity and four differed in host range. Comparison of the electrophoretic patterns of DNA from cells infected at the restrictive temperature with those obtained in wildtype infection revealed that viral DNA bands were absent with three additional mutants. Complementation analysis assigned the four host range mutants to cistron I and the three mutants defective in DNA synthesis to cistron IV. Recombination frequencies were used to locate cistrons III and IV on the partial genetic map of PM2.     

Orofacial evaluation of individuals with temporomandibular disorder after LED therapy associated or not of occlusal splint: a randomized double-blind controlled clinical study

Lasers in Medical Science - This study compared the effects of LED therapy associated with occlusal splint (OS) on the signs and symptoms of temporomandibular disorder (TMD). In this randomized,...     

Synaptosomal glutamate release induced by the fraction Bc2 from the venom of the sea anemone Bunodosoma caissarum

The effect of a fraction (Bc2) from the venom of the sea anemone Bunodosoma caissarum on [3H]glutamate release from rat cortical synaptosomes was investigated. Bc2 (2-20 microg/ml) provoked massive glutamate release without causing synaptosome disruption. Glutamate release stimulated by Bc2 was independent of extracellular Ca2+ and of voltage-sensitive Na+ channels, and it was completely abolished by the addition of sphingomyelin. No definitive evidence about the mechanism underlying the stimulatory effect of Bc2 is available as yet. However, a direct interaction with the exocytotic machinery cannot be ruled out.     

Influence of ticlopidine on the development of experimental Staphylococcus aureus endocarditis

Previously, we have shown that aspirin administration reduces the bacterial density and weight of aortic vegetations in a rabbit model of Staphylococcus aureus endocarditis. In the present paper, we sought to determine if ticlopidine, another potent inhibitor of platelet aggregation, also influences the development of endocarditis. Animals received either no ticlopidine (control), or oral doses of 10, 50, and 100 mg/kg daily. The 10 and 100 mg/kg treated groups had a statistically significant reduction of the vegetative weight as compared with the untreated controls. Although the 50 mg/kg dose did not result in a statistically significant difference (P = 0.058) in weight when compared with control, this dose also produced a substantial reduction in aortic value vegetation weights. None of the ticlopidine doses tested significantly altered the bacterial density relative to untreated controls. These findings suggest that ticlopidine alters the development of cardiac vegetations and may be useful agent for the prevention and/or treatment of infective endocarditis.     

Sialic acid concentration in the attached gingival tissue of rates realted to age and sex

Determination of N-acetylneuraminic acid concentration in the attached gingival tissue of rats related to the age and sex of the animals was carried out. The concentration of the sialic acid decreased with increasing age. Differences between male and female animals were noted.     

In Vitro Activity of Novel Gyrase Inhibitors against a Highly Resistant Population of Pseudomonas aeruginosa

The activity of five novel gyrase inhibitors was evaluated against 303 nonduplicate Pseudomonas aeruginosa strains collected from 53 North American institutions. The most active compound, GP-2, displayed MIC₅₀ and MIC₉₀ values of 1 and 2 μg/ml, respectively. Cross-resistance to other commercially available antipseudomonal compounds was not evident, as no major change was observed in the gyrase inhibitor MIC distribution when stratified by nonsusceptible phenotypes, including the fluoroquinolones and those isolates classified as multidrug resistant (MDR).     

Performance of the PIRO score for predicting mortality in patients with ventilator-associated pneumonia

The ventilator-associated pneumonia (VAP) PIRO score is a new scoring system based on the PIRO concept. The aim of this study was to validate the PIRO score against the Acute Physiology and Chronic Health Evaluation (APACHE) II and VAP APACHE II in an independent group of VAP patients. Areas under the receiver operating characteristic curves were compared to determine the tests' abilities to predict intensive care unit and 28-day mortality. Variables associated with intensive care unit mortality were evaluated. One hundred and forty-eight intensive care unit patients who met radiographic and clinical criteria for VAP were included. The area under the receiver operating characteristic curves for predicting intensive care unit mortality with the PIRO, APACHE II and VAP APACHE II scores were 0.605 (P=0.03), 0.631 (P=0.01) and 0.724 (P <0.0001), respectively. Areas under the receiver operating characteristic curve for predicting 28-day mortality were 0.614 (P=0.01) for PIRO, 0.633 (P=0.01) for APACHE II and 0.697 (P=0.002) for VAP APACHE II. No differences in area under the receiver operating characteristic curve between scores were found at either endpoint. Variables independently associated with intensive care unit mortality were bacteraemia (adjusted odds ratio 7.16, 95% confidence interval 1.19 to 42.98, P=0.03) and APACHE II (1.06, 1.01 to 1.11, P=0.006). VAP PIRO score was not a good predictor of intensive care unit and 28-day mortality. The low sensitivity and specificity of VAP PIRO score preclude its use clinically.     

Simultaneous pancreas-kidney transplantation: is the failure of the grafts also simultaneous?

INTRODUCTION: It is well known that after a simultaneous pancreas and kidney transplantation (SPKT) there is a higher incidence of pancreatic graft loss in the acute period, due to technical problems. However, there is little information about the survival of pancreatic and kidney grafts 1 year after transplantation. AIMS: To analyze the causes of long-term graft loss of SPKT in our hospital and to determine if this loss occurs simultaneously or is isolated. PATIENTS AND METHODS: We analyzed the data of 63 SPKTs performed between February 1983 and October 2005, including the cases with normal renal and pancreatic function after 1 year of transplantation, and with a loss of one or two organs during the follow-up period (8 +/- 4 years). We defined simultaneous SPKT failure as failure that occurs at the same time or when the period between pancreatic and renal graft failure is shorter than 9 months. RESULTS: In 28 patients (44%), there was a simultaneous graft failure, whereas in 35 (56%) the loss of function occurred in only one organ or in both, but separately. Death was responsible for 75% (21/28) of simultaneous graft losses, representing 25% (9/35) of isolated graft failures. Cardiovascular disease was the leading cause of death. In 14 of 35 isolated graft failures, there was loss of renal and pancreatic function (11/14 kidney failed first) with a 2.9 +/- 2.3 years of interval. In 12 cases there was only loss of pancreatic function, whereas in nine cases the affected organ was the kidney. Graft chronic nephropathy and chronic rejection in the pancreas were the main causes of graft failure. CONCLUSIONS: The main cause of simultaneous SPKT failure is patient death; however, among isolated or separated SPKT failures, the kidney failed first, more frequently.