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Blunted Response (blunted + response)
Selected AbstractsRelationship of prolactin response to meta-chlorophenylpiperazine with severity of drug use in cocaine dependenceHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2006Ashwin A. Patkar Abstract Rationale Serotonergic (5-HT) mechanisms appear to mediate central effects of cocaine. Therefore 5-HT disturbances could be associated with drug severity. Objectives We investigated whether prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a mixed 5-HT agonist/antagonist were associated with severity of cocaine use. Methods Thirty-six cocaine-dependent subjects and 33 controls underwent a challenge with 0.5,mg/kg of oral m-CPP. Severity of drug use was assessed using the Addiction Severity Index (ASI). Results The PRL response to m-CPP was significantly blunted in cocaine patients compared to controls (F,=,21.86, p,<,0.001). ,PRL (peak PRL,baseline PRL) was negatively correlated with ASI-drug (r,=,,0.45, p,<,0.01), ASI-alcohol (r,=,,0.32, p,<,0.05), and ASI-psychological (r,=,,0.41, p,<,0.01) composite scores, and with the quantity, frequency and duration of drug use (r ranged from ,,0.41 to ,,0.32, p ranged from <,0.01 to 0.05). Hierarchical regressions showed that ASI-drug composite scores significantly predicted the variance in ,PRL after controlling for behavioral and demographic variables (F,=,4.27, p,<,0.05). Conclusions The results indicate that disturbances in 5-HT function as reflected by a blunted response to m-CPP seem to be primarily associated with severity of drug use and to a lesser, although significant extent with behavioral traits in cocaine-dependent patients. Copyright © 2006 John Wiley & Sons, Ltd. [source] Craniosynostosis-Associated Gene Nell-1 Is Regulated by Runx2,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007Thien Truong Abstract We studied the transcriptional regulation of NELL-1, a craniosynostosis-related gene. We identitifed three OSE2 elements in the NELL-1 promoter that are directly bound and transactivated by Runx2. Forced expression of Runx2 induces NELL-1 expression in rat calvarial cells. Introduction: We previously reported the upregulation of NELL-1 in human craniosynostosis and the overexpression of Nell-1 in transgenic animals that induced premature suture closure associated with increased osteoblast differentiation. To study the transcriptional regulation of NELL-1, we analyzed the 5, flanking region of the human NELL-1 gene. We identified three osteoblast specific binding elements 2 (OSE2) sites (A, B, and C) within 2.2 kb upstream of the transcription start site and further studied the functionality of these sites. Materials and Methods: An area of 2.2 kb and a truncated 325 bp, which lacked the three OSE sites, were cloned into a luciferase reporter gene, and co-transfected with Runx2 expression plasmid. The three OSE2 sites were individually mutated and co-transfected with Runx2 expression plasmid into Saos2 cells. Gel shifts and supershifts with Runx2 antibodies were used to determine specific binding to OSE2 sites. CHIP assays were used to study in vivo binding of Runx2 to the Nell-1 promoter. Runx2 expression plasmid was transfected into wildtype and Runx2,/, calvarial cells. Nell-1, osteocalcin, and Runx2 expression levels were measured using RT-PCR. Results: Addition of Runx2 dose-dependently increased the luciferase activity in the human NELL-1 promoter-luciferase p2213. The p325 truncated NELL-1 construct showed significantly lower basal level of activity. Nuclear extract from Saos2 cells formed complexes with site A, B, and C probes and were supershifted with Runx2 antibody. Mutation of sites A, B, and C significantly decreased basal promoter activity. Furthermore, mutation of sites B and C had a blunted response to Runx2, whereas mutation of site A had a lesser effect. Runx2 bound to NELL-1 promoter in vivo. Transfection of Runx2 in rat osteoblasts upregulated Nell-1 and Ocn expression, and in Runx2 null calvarial cells, both Nell-1 and Ocn expression were rescued. Conclusions: Runx2 directly binds to the OSE2 elements and transactivates the human NELL-1 promoter. These results suggest that Nell-1 is likely a downstream target of Runx2. These findings may also extend our understanding of the molecular mechanisms governing the pathogenesis of craniosynostosis. [source] Prenatal Alcohol Exposure Alters Biobehavioral Reactivity to Pain in NewbornsALCOHOLISM, Issue 4 2010Tim F. Oberlander Objectives:, To examine biobehavioral responses to an acute pain event in a Cape Town, South Africa, cohort consisting of 28 Cape Colored (mixed ancestry) newborns (n = 14) heavily exposed to alcohol during pregnancy (exposed), and born to abstainers (n = 14) or light (,0.5 oz absolute alcohol/d) drinkers (controls). Methods:, Mothers were recruited during the third trimester of pregnancy. Newborn data were collected on postpartum day 3 in the maternity obstetrical unit where the infant had been delivered. Heavy prenatal alcohol exposure was defined as maternal consumption of at least 14 drinks/wk or at least 1 incident of binge drinking/mo. Acute stress-related biobehavioral markers [salivary cortisol, heart rate (HR), respiratory sinus arrhythmia (RSA), spectral measures of heart rate variability (HRV), and videotaped facial actions] were collected thrice during a heel lance blood collection (baseline, lance, and recovery). After a feeding and nap, newborns were administered an abbreviated Brazelton Neonatal Behavioral Assessment Scale. Results:, There were no between-group differences in maternal age, marital status, parity, gravidity, depression, anxiety, pregnancy smoking, maternal education, or infant gestational age at birth (all ps > 0.15). In both groups, HR increased with the heel lance and decreased during the postlance period. The alcohol-exposed group had lower mean HR than controls throughout, and showed no change in RSA over time. Cortisol levels showed no change over time in controls but decreased over time in exposed infants. Although facial action analyses revealed no group differences in response to the heel lance, behavioral responses assessed on the Brazelton Neonatal Scale showed less arousal in the exposed group. Conclusions:, Both cardiac autonomic and hypothalamic,pituitary,adrenal stress reactivity measures suggest a blunted response to an acute noxious event in alcohol-exposed newborns. This is supported by results on the Brazelton Neonatal Scale indicating reduced behavioral arousal in the exposed group. To our knowledge, these data provide the first biobehavioral examination of early pain reactivity in alcohol-exposed newborns and have important implications for understanding neuro-/biobehavioral effects of prenatal alcohol exposure in the newborn period. [source] Comparison of 2 Doses of Recombinant Human Thyrotropin for Thyroid Function Testing in Healthy and Suspected Hypothyroid DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2009F.S. Boretti Background: Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs. Objective: To evaluate the effectiveness of 2 doses of rhTSH. Animals: Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 ,g rhTSH and 18 clinically healthy dogs. Methods: All dogs were stimulated with 75 and 150 ,g rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration. Results: Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow-up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post-TSH T4 concentrations with the higher compared with the lower dose. Post-TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs. Conclusions and Clinical Relevance: TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 ,g rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication. [source] | ||||||||||