Inhibition of nitric oxide synthase increases synaptophysin mRNA expression in the hippocampal formation of rats

Synaptophysin is a protein involved in the biogenesis of synaptic vesicles and budding. It has been used as an important tool to investigate plastic effects on synaptic transmission. Nitric oxide (NO) can influence plastic changes in specific brain regions related to cognition and emotion. Experimental evidence suggests that NO and synaptophysin are co-localized in several brain regions and that NO may change synaptophysin expression. Therefore, the aim of the present work was to investigate if inhibition of NO formation would change synaptophysin mRNA expression in the hippocampal formation. Male Wistar rats received single or repeated (once a day for 4 days) i.p. injections of saline or l-nitro-arginine (l-NOARG, 40 mg/kg), a non-selective inhibitor of nitric oxide synthase (NOS). Twenty-four hours after the last injection the animals were sacrificed and their brains removed for ‘in situ’ hybridization study using ³⁵S-labeled oligonucleotide probe complementary to synaptophysin mRNA. The results were analyzed by computerized densitometry. Acute administration of l-NOARG induced a significant (p < 0.05, ANOVA) increase in synaptophysin mRNA expression in the dentate gyrus, CA1 and CA3. The effect disappeared after repeated drug administration. No change was found in the striatum, cingulated cortex, substantia nigra or nucleus accumbens. These results reinforce the proposal that nitric oxide is involved in plastic events in the hippocampus.     

Effect of pharmacological purging on natural killer cell number and activity in human bone marrow.

We assayed natural killer (NK) cell activity and phenotype from human bone marrow (BM) following "purge" with 4-hydroperoxycyclophosphamide (4HC) at 60 micrograms/ml for 30 min in vitro. In all cases studied, lytic activity against the K562 cell line was either significantly decreased or abolished following 4HC purge. Although NK activity was significantly affected by 4HC treatment, no major differences in the phenotype between the purged and unpurged population were seen. Further, while in vitro culture of BM with IL2 resulted in a significant increment of NK activity, no IL-2 responsive cells were found in the 4HC purged BM after 14 days of culture. This study demonstrates that pharmacological purging of bone marrow results in a persistent functional decline of NK cell activity and may serve as a useful model for the study of the ontogeny of NK cells.     

Yolk sac tumors with pure and mixed polyvesicular vitelline patterns

Four cases of polyvesicular vitelline tumor are presented; two were of a previously unreported pure type, and the other two were mixed with endodermal sinus tumor.The morphologic features of the vesicles favor an endodermal origin, as originally proposed by Teilum. Marked specialization of the vesicular lining cells, seen ultrastructurally, suggests a differentiation toward gut structures and mature yolk sac. One case of pure polyvesicular vitelline tumor showed massive erythropoiesis. We propose that the pure tumor reflects an intermediate degree of differentiation within the selectively endodermal yolk sac tumor group, that is, a further stage of organization than the endodermal sinus tumor.In our cases of pure polyvesicular vitelline tumor, the marked degree of differentiation was correlated with an improved prognosis, as in the case of the possible homologue of this tumor, the yolk sac tumor of the infant testis. In contrast, the two cases of the tumor admixed with endodermal sinus tumor illustrated the low survival rate expected in the pure endodermal sinus tumor; in these cases the metastases had no polyvesicular component. Because of the significance of such a difference in prognosis we emphasize the importance of an accurate diagnosis, suggesting that a large number of sections be taken in order to demonstrate any endodermal sinus tumor component that may be present, and that the possibility of pure polyvesicular vitelline tumor always be considered in the differential diagnosis of multicystic ovarian tumors.     

Post-traumatic diffuse brain swelling: isolated or associated with cerebral axonal injury

Eighteen children with severe head injuries and diffuse brain swelling were studied. They were separated into two groups based on the computed tomography (CT) findings. Seven patients had small ventricles in the normal location and small or absent cisterns. Eleven had these signs plus small deep-seated intraparenchymal hemorrhagic foci and/or intraventricular hemorrhage. Patients in the first group were in relatively good neurological condition; their intracranial pressure was easily controlled and all had a favourable outcome. On contrast, children in the second group had a more severe clinical presentation, frequently had uncontrollable intracranial hypertension, and more than 50% died.     

Amphetamine-clonidine interaction on neurotransmission in the vas deferens of the rat

The interaction between amphetamine and clonidine on neurotransmission in the rat vas deferens was studied. In the whole vas deferens, clonidine 0.037 mumol/l displaced to the right the frequency-response curve evoked by either hypogastric or field stimulation. The frequency of stimulation that produced 50% of the maximal response (EF 50) was: control 4.0 Hz, clonidine 18.3 Hz (P less than 0.001 n = 4), for hypogastric nerve stimulation; and 2.1 Hz in controls and 17.1 Hz in clonidine-treated preparations, for field stimulation (P less than 0.001 n = 5). Preincubation with 5.4 mumol/l amphetamine antagonized the effect of clonidine (EF 50 amphetamine alone 6.2 Hz, amphetamine + clonidine 7.3 Hz; P greater than 0.5). After 12 min of incubation with clonidine 0.037 mumol/l the responses to 6.4 Hz (3 s, 0.5 ms) were decreased by 77 +/- 2.2%. Both yohimbine and amphetamine, in a concentration-dependent manner, attenuated the inhibition. Washout of clonidine produced a slow recovery of the responses. Inhibition of the motor response to nerve stimulation (6.4 Hz, 3 s) by 30 mumol/l 2',3'-cAMP was increased by 10 mumol/l dipyridamole and impaired by 100 mumol/l theophylline. Amphetamine, in a concentration that markedly reduced clonidine inhibition of neurotransmission failed to antagonize 2',3'-cAMP. In the bisected vas deferens clonidine inhibited the peak motor response to short trains of field stimuli in the prostatic portion ("non-adrenergic") and the sustained response in the epididymal portion ("adrenergic"). Yohimbine potentiated both types of responses and fully prevented the effect of clonidine. In the prostatic portion amphetamine slightly inhibited the peak motor response and attenuated the inhibitory effect of clonidine in both portions of the vas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Doctor,please make me freer: Capabilities enhancement as a goal of medicine

Medicine, Health Care and Philosophy - Biomedical innovations are making possible the enhancement of human capabilities. There are two philosophical stances on the role that medicine should play in...     

Catastrophic household expenditure associated with out-of-pocket payments for dental healthcare in Spain

The European Journal of Health Economics - To estimate the prevalence of catastrophic health expenditure due to dental healthcare (CHED) in Spain, quantify its intensity and examine the related...     

Short-term multiorgan metabolic benefits of rapid weight loss after sleeve gastrectomy in severely obese patients

BackgroundSleeve gastrectomy (SG) has become the most prevalent bariatric-metabolic surgical approach in the United States. Its popularity among surgeons and patients is mainly due to a better safety profile and less overall morbidity, with broad benefits from a systemic and metabolic perspective.ObjectiveComprehensively describe the short-term multiorgan metabolic effects of rapid weight loss after SG.SettingAcademic hospital, United States.MethodsWe retrospectively reviewed the charts of patients that underwent SG at our institution between 2012 and 2016. We analyzed the required variables to calculate multiple risk scores, such as cardiovascular, hypertension, and diabetes risk scores. Furthermore, the renal and hepatic functions and the metabolic and hematologic profiles were assessed at 12 months of follow-up.ResultsA total of 1002 patients were included in the analysis. The percentage of excess body mass index loss was, on average, 65% at 12 months of follow-up. We observed a positive cardio-renal-hepatic improvement, demonstrated by a substantial reduction of the 10-year cardiovascular risk. We noticed an improvement of renal function, which was more significant in chronic kidney disease (stage ≥2), and a significant improvement on liver function tests (measured by decreased aspartate aminotransferase and alanine transaminase) at 12 months of follow-up. Our data also show a positive impact on decreasing the risk of developing hypertension and type 2 diabetes. There was a positive impact on the lipid profile, with the exception of low-density lipoprotein.ConclusionThere are significant short-term benefits on multiorgan metabolic parameters after rapid weight loss in severely obese patients undergoing sleeve gastrectomy.