387 research outputs found
INSULIN BINDING AND BIOLOGICAL-ACTIVITIES IN THE FRTL-5 RAT-THYROID CELL-LINE
No full textA cloned rat thyroid cell line (FRTL-5) was examined for both insulin binding and responsiveness. The characteristics of insulin binding to thyroid cells were similar to those observed in typical insulin target cells. The 125I-insulin binding was time and temperature dependent and Scatchard analysis suggested the presence of two major binding sites with high and low affinity constant (Kd = 1.4 x 10-10 mol/L and 1.5 x 10-9 mol/L, respectively). 125I-insulin was also internalized and degraded in a temperature-dependent manner. IGF1 was weakly effective in completing 125I-insulin binding to FRTL-5 cells (57% inhibition at 333 nmol/L), whereas noninsulin-related peptide hormones were ineffective. Exposure of FRTL-5 cells to insulin stimulated both methyl-aminoisobutyric acid (M-AIB) and 2-deoxy-D-glucose (2DG) transport. These effects were evident at 10-9 mol/L and maximal at 10-7 mol/L insulin. Maximal stimulation was three- to four-fold over basal value for both M-AIB and 2DG transport. These data suggest that insulin specifically binds to FRTL-5 cells and regulates different biological functions of this thyroid cell line
DESENSITIZATION OF THE THYROID CYCLIC-AMP RESPONSE TO THYROID STIMULATING IMMUNOGLOBULIN - COMPARISON WITH TSH
No full textStudies were conducted to examine the characteristics of thyroid cell cAMP stimulation by thyroid stimulating immunoglobulins (TSI) and to compare the cAMP response to TSI and TSH in desensitized human thyroid cells. In terms of cAMP production, preexposure (eight hours) of the cells to TSI induced a desensitization very similar to TSH-induced desensitization: both TSH- and TSI-desensitized cells showed a normal response to cholera toxin and forskolin stimulation; TSH and TSI desensitization was interchangeable in that desensitization by either stimulator affected the action of the other; the time of recovery from either TSH and TSH desensitization was identical; the cycloheximide (10(-4) mol/L) prevented both TSI- and TSH-induced desensitization; preexposure of the cells to iodine, which affects mainly the adenylate cyclase catalytic unit, or to epinephrine, which activate the inhibitory regulatory protein Ni by the alpha 2-adrenergic stimulation, induced a similar inhibition of the subsequent stimulation by both TSH or TSI. The remarkable similarities between TSH and TSI in stimulating and desensitizing thyroid cells strongly support the concept that TSI activates thyroid adenylate cyclase by interacting with the TSH receptor and not through an allosteric mechanism
Cystatin C, a Controversial Biomarker in Hypothyroid Patients under Levothyroxine Therapy: THYRenal, a Pilot Cohort Observational Study
No full textCystatin C (Cys-C) is recognized as one of the most reliable renal function parameters in the general population, although it might be biased by thyroid status. Herein, we tested Cys-C and conventional renal parameters in a cohort of hypothyroid patients treated with Levothyroxine
Features of sequential learning in hemicerebellectomized rats
No full textBecause the sequencing property is one of the functions in which cerebellar circuits are involved, it is important to analyze the features of sequential learning in the presence of cerebellar damage. Hemicerebellectomized and control rats were tested in a four-choice visuomotor learning task that required both the detection of a specific sequence of correct choices and the acquisition of procedural rules about how to perform the task. The findings indicate that the presence of the hemicerebellectomy did not affect the first phases of detection and acquisition of the sequential visuomotor task, delayed but did not prevent the learning of the sequential task, slowed down speed-up and proceduralization phases, and loosened the reward-response associative structure. The performances of hemicerebellectomized animals in the serial learning task as well as in the open field task demonstrated that the delayed sequential learning task could not be ascribed to impairment of motor functions or discriminative abilities or to low levels of motivation. The delay in sequential learning observed in the presence of a cerebellar lesion appeared to be related mainly to a delay of the automatization of the response. In conclusion, it may be advanced that, through cortical and subcortical connections, the cerebellum provides the acquisition of rapid and accurate sensory-guided sequence of responses. (C) 2009 Wiley-Liss, Inc
Leukocyte filtration improves pulmonary function and reduces the need for postoperative non-invasive ventilation
No full textOBJECTIVES: Leukocyte depletion (LD) has been reported to reduce inflammatory damage during cardiopulmonary bypass (CPB). We evaluated the role of LD in pulmonary function and inflammatory response.
METHODS: Seventy consecutive CABG patients were randomized (1:1) to receive LD on both arterial and cardioplegia lines (Filters) or standard arterial filters (Controls) during CPB. Estimates of pulmonary function, inflammatory and anti-inflammatory cytokines were collected pre-, intra- and postoperatively.
RESULTS: Hospital mortality, intensive care and in-hospital lengths of stay were similar. Although duration of ventilation and incidence of pneumonia were comparable, leukodepleted patients showed higher PaO2/FiO2 (p-between groups = 0.005; ICU arrival p = 0.023; 24 hours p = 0.039; 48 hours p<0.001) and lower need for postoperative non-invasive ventilation (NIV), (p = 0.029). Moreover, Filters showed lower inflammatory burst at 24 hours (IL-6 p<0.001; IL-8 p = 0.002) and 48 hours (IL-6 p = 0.015). This was associated with a lower release of the anti-inflammatory IL-10 (p-between groups = 0.030; ICU admission p = 0.002; 24 hours p = 0.003). Furthermore, IL-2 concentration proved higher in Filters (p-between groups = 0.013; ICU arrival p = 0.029; 24 hours p = 0.040; 48 hours p = 0.021) in association with lower leukocyte and platelet counts at ICU admission.
CONCLUSIONS: LD resulted in lower inflammatory burst and less need for release of anti-inflammatory cytokines. Although hospital outcomes were similar in terms of mortality and length of stay, improvements in pulmonary function and reduced need for postoperative NIV support the use of LD
Cerebellar Damage Loosens the Strategic Use of the Spatial Structure of the Search Space
No full textThe influence of a hemicerebellar lesion on the exploration of environments with different spatial distributions of multiple rewards was analyzed. Hemicerebellectomized (HCbed) and intact rats were submitted to a search task in which they had to explore nine food trays in an open field, avoiding repeated visits. Trays were spatially arranged in four configurations: cross, 3 x 3 matrix, circle, and three clusters of three trays each. Lesioned and intact rats' performances improved in all configurations used. However, the explorative activity of the HCbed animals differed from that of intact rats. Lesioned animals spent more time, made more errors, displayed lower search efficiency, exhibited shorter final spans, and traveled longer distances. They tended to perseverate and to neglect some trays. The cerebellar damage differentially influenced performances as a specific effect of the susceptibility of the configurations to being explored in a principled way. In the cross configuration that had strong spatial constraints, both groups made their lowest number of errors. In the circle configuration, the altered explorative strategies of lesioned animals made extremely demanding the acquisition of the task of searching multiple rewards, in spite of the attempt of favoring their altered procedures through an appropriate spatial arrangement. Since the procedural impairment elicited by cerebellar damage affected the central exploration, the matrix configuration was the most difficult configuration to be explored by the HCbed rats. The poor performances in the cluster configuration indicated that chunking was a strategy of relative strength in rats in general and in HCbed rats in particular
Exposure to an Enriched Environment Accelerates Recovery from Cerebellar Lesion
No full textThe exposure to enriched environments allows the maintenance of normal cognitive functioning even in the presence of brain pathology. Up until now, clinical and experimental studies have investigated environmental effects mainly on the symptoms linked to the presence of neuro-degenerative diseases, and no study has yet analyzed whether prolonged exposure to complex environments allows modifying the clinical expression and compensation of deficits of cerebellar origin. In animals previously exposed to complex stimulations, the effects of cerebellar lesions have been analyzed to verify whether a prolonged and intense exposure to complex stimulations affected the compensation of motor and cognitive functions following a cerebellar lesion. Hemicerebellectomized or intact animals housed in enriched or standard conditions were administered spatial tests. Postural asymmetries and motor behavior were also assessed. Exposure to the enriched environment almost completely compensated the effects of the hemicerebellectomy. In fact, the motor and cognitive performances of the enriched hemicerebellectomized animals were similar to those of the intact animals. The plastic changes induced by enhanced mental and physical activity seem to provide the development of compensatory responses against the disrupting motor and cognitive consequences of the cerebellar damage
Intra-aortic balloon pump induced pulsatile perfusion reduces endothelial activation and inflammatory response following cardiopulmonary bypass
No full textOBJECTIVE: Intra-aortic balloon pump (IABP)-induced pulsatile perfusion has demonstrated that it can preserve organ function during cardiopulmonary bypass (CPB). We evaluated the role of IABP pulsatile perfusion on endothelial response.
METHODS: Forty consecutive isolated CABG undergoing preoperative IABP were randomized to receive IABP pulsatile CPB during aortic cross-clamping (group A, 20 patients) or standard linear CPB (group B, 20 patients) during cross-clamp time. Hemodynamic results were analyzed by Swan-Ganz catheter [mean arterial pressure (MAP), cardiac index (CI), indexed systemic vascular resistances (ISVR), indexed pulmonary vascular resistances (IPVR), wedge pressure (PCWP)]. Inflammatory/endothelial response was analyzed by pro-inflammatory (IL-2, IL-6, IL-8), anti-inflammatory cytokines (IL-10), and endothelial markers [vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1)]. All measurements were recorded preoperatively (T0), before aortic declamping (T1), at the end of surgery (T2), 12h (T3) and 24h (T4) postoperatively. ANOVA for repeated measures was used to evaluate the differences of means.
RESULTS: Hemodynamic response was comparable except for higher MAP (p=0.01 at T1) and lower ISVR (p=0.001 at T1, p=0.003 at T2) in group A. No differences were found in perioperative leakage of IL-2, IL-6, and IL-8 between the two groups (within-group p=0.0001 either in group A and group B; between-groups p=NS at 2-ANOVA). Group A showed significantly lower VEGF (between-groups p=0.001 at 2-ANOVA, p=0.001 at T1, T2) and MCP-1 (between-groups p=0.001 at 2-ANOVA, p=0.001 at T1, T2) with higher IL-10 secretion (between-groups p=0.001 at 2-ANOVA, p=0.01 at T1, T2, T3).
CONCLUSIONS: IABP-induced pulsatile perfusion allows lower endothelial activation during CPB and higher anti-inflammatory cytokines secretion
Interaction does count: A cross-fostering study on transgenerational effects of pre-reproductive maternal enrichment
No full textPre-reproductive environmental enrichment of female rats influences sensorimotor development and spatial behavior of the offspring, possibly through the changed maternal nurturing. Nevertheless, maternal care could be not the solely responsible for changing offspring developmental trajectories. To disentangle the specific contribution to the transgenerational inheritance of pre- and post-natal factors, a cross-fostering study was performed. Female rats were reared in an enriched environment from weaning to sexual maturity, while control female rats were reared under standard conditions. Following mating with standard-reared males, all females were housed individually. Immediately after delivery, in- or cross-fostering manipulations were performed so that any foster dams received pups born to another dam of the same (in-fostering) or the opposite (cross-fostering) pre-reproductive rearing condition. In lactating dams maternal care and nesting activities were assessed, while in their male pups spatial abilities were assessed through Morris Water Maze (MWM) test at post-natal day 45. Moreover, the expression of Brain-Derived-Neurotrophic-Factor (BDNF) was evaluated in the hippocampus and frontal cortex of dams and pups at weaning. Pre-reproductive maternal environmental enrichment, followed by adoption procedures, loosened its potential in modifying maternal care and offspring developmental trajectories, as indicated by the lack of differences between in-fostered groups of dams and pups. In addition, enriched dams rearing standard pups showed the least complex maternal repertoire (the highest sniffing duration and the lowest nest quality), and their pups showed a reduced spatial learning in the MWM. Nevertheless, pre-reproductive maternal enrichment kept influencing neurotrophic pattern, with enriched dams expressing increased frontal BDNF levels (regardless of the kind of fostered pups), and their offspring expressing increased hippocampal BDNF levels. The present findings enlighten the crucial importance of the early mother-pups interactions in influencing maternal care and offspring phenotype, with the enriched dam-standard pups couple resulting in the most maladaptive encounter. Our study thus sustains that the bidirectional interactions between mother and pups are able to deeply shape offspring phenoty
Pre-reproductive maternal enrichment influences offspring developmental trajectories: motor behavior and neurotrophin expression
No full textEnvironmental enrichment is usually applied immediately after weaning or in adulthood, with strong effects on CNS anatomy and behavior. To examine the hypothesis that a pre-reproductive environmental enrichment of females could affect the motor development of their offspring, female rats were reared in an enriched environment from weaning to sexual maturity, while other female rats used as controls were reared under standard conditions. Following mating with standard-reared males, all females were housed individually. To evaluate the eventual transgenerational influence of positive pre-reproductive maternal experiences, postural and motor development of male pups was analyzed from birth to weaning. Moreover, expression of Brain Derived Neurotrophic Factor and Nerve Growth Factor in different brain regions was evaluated at birth and weaning. Pre-reproductive environmental enrichment of females affected the offspring motor development, as indicated by the earlier acquisition of complex motor abilities displayed by the pups of enriched females. The earlier acquisition of motor abilities was associated with enhanced neurotrophin levels in striatum and cerebellum. In conclusion, maternal positive experiences were transgenerationally transmitted, and influenced offspring phenotype at both behavioral and biochemical levels.Environmental enrichment is usually applied immediately after weaning or in adulthood, with strong effects on CNS anatomy and behavior. To examine the hypothesis that a pre-reproductive environmental enrichment of females could affect the motor development of their offspring, female rats were reared in an enriched environment from weaning to sexual maturity, while other female rats used as controls were reared under standard conditions. Following mating with standard-reared males, all females were housed individually. To evaluate the eventual transgenerational influence of positive pre-reproductive maternal experiences, postural and motor development of male pups was analyzed from birth to weaning. Moreover, expression of Brain Derived Neurotrophic Factor and Nerve Growth Factor in different brain regions was evaluated at birth and weaning. Pre-reproductive environmental enrichment of females affected the offspring motor development, as indicated by the earlier acquisition of complex
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