Multivariate study of the Open Field Drink Test using undernourished rats and desipramine as an antipanic drug

Approach-avoidance animal models are useful as initial screens for drugs affecting anxiety, but the components of anxiety assessed by these models remain poorly defined. Complex models of evaluation allow more complete inferences than those which are obtained when only one behavior is evaluated. Previous studies demonstrate that the tricyclic-antidepressant desipramine exerts a selective anticonflict effect on adult rats submitted to a protein deprivation schedule at perinatal age, in parameters of spontaneous behavior (elevated plus-maze) and conditioned intake (Geller Seifter). These deprived rats show alterations in noradrenergic neurotransmission that resembled the generalized activation of noradrenergic system displayed by patients suffering from panic attacks. The desipramine anticonflict activity was evaluated by a test of ethological conflict: the Open Field Drink Test, without discarding any behavior a priori under a multivaried approach. This approach has not been considered in previous studies with the open field and antipanic drugs. Considering the four variables selected by factorial analysis, desipramine (10 mg/kg/day) administered IP during just 7 days produced a significant diet x drug interaction which was consistent with previous studies. That interaction was independent of the effects of both treatments on weight or intake and was expressed, on deprived rats, as a decrease in all the behaviors, except for the time of drinking, with respect to the control rats, which displayed, in general, a decrease in all the behaviors except for the frequency of grooming.     

Effect of Beetroot Juice Supplementation on Aerobic Response during Swimming

The beneficial effects of beetroot juice supplementation (BJS) have been tested during cycling, walking, and running. The purpose of the present study was to investigate whether BJS can also improve performance in swimmers. Fourteen moderately trained male master swimmers were recruited and underwent two incremental swimming tests randomly assigned in a pool during which workload, oxygen uptake (VO₂), carbon dioxide production (VCO₂), pulmonary ventilation (VE), and aerobic energy cost (AEC) of swimming were measured. One was a control swimming test (CSW) and the other a swimming test after six days of BJS (0.5l/day organic beetroot juice containing about 5.5 mmol of NO₃⁻). Results show that workload at anaerobic threshold was significantly increased by BJS as compared to the CSW test (6.3 ± 1 and 6.7 ± 1.1 kg during the CSW and the BJS test respectively). Moreover, AEC was significantly reduced during the BJS test (1.9 ± 0.5 during the SW test vs. 1.7 ± 0.3 kcal·kg⁻¹·h⁻¹ during the BJS test). The other variables lacked a statistically significant effect with BJS. The present investigation provides evidence that BJS positively affects performance of swimmers as it reduces the AEC and increases the workload at anaerobic threshold.     

A novel type of familial transthyretin amyloidosis, ATTR Asn124Ser, with co-localization of kappa light chains.

A 68-year-old Italian woman who had a clinical history of thyroidectomy in 2002 presented with slowly progressing renal insufficiency and non-nephrotic proteinurea in 2004. A renal biopsy showed the occurrence of amyloid; the thyroid biopsy previously taken also revealed amyloid infiltration. Other amyloid-containing tissues included bone marrow and heart. The plasma cell level in the bone marrow was found to be less than 5% and both serum and urine samples were positive for a monoclonal kappa light chain band. DNA analysis unexpectedly revealed the presence of a novel transthyretin (TTR) mutation, ATTR Asn124Ser. Histologically, amyloid deposits in the thyroid had a homogeneous appearance with moderate Congophilia. In immunohistochemistry, a kappa light chain antiserum showed positive immunoreactivity with amyloid deposits in the thyroid. Furthermore, a TTR antiserum, anti-TTR50-127, also recognized a number of amyloid deposits stained positive with the kappa light chain antiserum. Overall, the kappa light chain antiserum reacted with most of the amyloid deposits in the thyroid, whereas TTR immunoreactivity was scarcer, with a scattered appearance. In contrast, only the anti-TTR50-127 antiserum labeled amyloid in the kidney, albeit not all deposits. In this study, we report a patient having a novel TTR variant, ATTR Asn124Ser, with co-localization of kappa light chains in the amyloid deposits in the thyroid tissue.     

The acid-labile subunit of human ternary insulin-like growth factor-binding protein complex in girls with central precocious puberty before and during gonadotropin-releasing hormone analog therapy

The aim of the study was to evaluate serum acid-labile subunit (ALS) concentrations and their relationship with other parameters of the human ternary IGF-I-binding protein (IGFBP) complex in girls with central precocious puberty (CPP) before and after pharmacological arrest of puberty. We studied serum ALS, free IGF-I, total IGF-I, IGFBP-3 levels and IGFBP-3 protease activity in 13 girls, aged 1.6-7.8 yr (mean, 5.9 +/- 2.2), diagnosed as having CPP before and after 6 and 12 months of GnRH analog (GnRHa) therapy. The ALS SD score before treatment was high (1.4 +/- 0.72) and decreased significantly after 6 and 12 months of GnRHa therapy [0.4 +/- 0.54 (P < 0.01) and -0.4 +/- 0.61 (P < 0.01), respectively]. Serum IGF-I and IGFBP-3 were also increased before treatment, but both of these factors remained elevated after 6 and 12 months of GnRH-A therapy [IGF-I SD score, 3.20 +/- 1.64, 2.92 +/- 1.82, and 3.68 +/- 1.94 (P = NS), respectively; IGFBP-3 SD score, 1.02 +/- 0.53, 0.94 +/- 0.68, and 1.22 +/- 0.87 (P = NS), respectively]. Serum free IGF-I levels and IGFBP-3 proteolytic activity did not vary significantly from their pretreatment values during GnRHa therapy. In conclusion, serum ALS levels were elevated in girls with CPP and decreased significantly during the first year of GnRHa therapy. Serum IGF-I and IGFBP-3 levels were also increased before therapy, but their levels were not influenced by treatment. The ALS decrease seems to be the sole GH-dependent factor that parallels the decreases in steroid levels and growth velocity during GnRHa therapy.     

Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells

Hydroxyurea, a drug widely used for treating myeloproliferative diseases, has also been approved for the treatment of sickle cell disease by raising fetal hemoglobin (HbF). We have shown that nitric oxide (NO) and the soluble guanylyl cyclase (sGC) pathways are involved in hydroxyurea induction of HbF levels in erythroid progenitor cells (EPCs). We demonstrate now that during erythroid differentiation, endothelial NO synthase mRNA and protein levels decline steadily, as does the production of NO derivatives and cyclic adenosine monophosphate (cAMP) levels, but guanosine 3',5'-cyclic monophosphate (cGMP) levels are stable. Hydroxyurea increased intracellular cGMP levels and cAMP levels in EPCs. The NO donor, DEANONOate, induced much higher cGMP levels, but reduced cAMP levels. Hydroxyurea (1 mM) induced production of approximately 45 pM cGMP/minute/ng of purified sGC, similar to induction by 1 muM DEANONOate. We found that hydroxyurea and ProliNONOate produced iron-nitrosyl derivatives of sGC. Thus, we confirm that hydroxyurea can directly interact with the deoxy-heme of sGC, presumably by a free-radical nitroxide pathway, and activate cGMP production. These data add to an expanding appreciation of the role of hydroxyurea as an inducer of the NO/cGMP pathway in EPCs. These mechanisms may also be involved in the cytostatic effects of hydroxyurea, as well as the induction of HbF.     

Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum and Hippocampus of Nondemented Older Adults: An [18F]FDG-PET Study

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