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Regula E Egli Thomas L Kash Kevin Choo Valentina Savchenko Robert T Matthews Randy D Blakely Danny G Winder 《Neuropsychopharmacology》2005,30(4):657-668
The bed nucleus of the stria terminalis (BNST) and its adrenergic input are key components in stress-induced reinstatement and maintenance of drug use. Intra-BNST injections of either beta-adrenergic receptor (beta-AR) antagonists or alpha2-adrenergic receptor (alpha2-AR) agonists can inhibit footshock-induced reinstatement and maintenance of cocaine- and morphine-seeking. Using electrophysiological recording methods in an in vitro slice preparation from C57/Bl6j adult male mouse BNST, we have examined the effects of adrenergic receptor activation on excitatory synaptic transmission in the lateral dorsal supracommissural BNST (dBNST) and subcommissural BNST (vBNST). Alpha2-AR activation via UK-14,304 (10 microM) results in a decrease in excitatory transmission in both dBNST and vBNST, an effect predominantly dependent upon the alpha2A-AR subtype. Beta-AR activation via isoproterenol (1 microM) results in an increase in excitatory transmission in dBNST, but not in vBNST. Consistent with the work with receptor subtype specific agonists, application of the endogenous ligand norepinephrine (NE, 100 microM) elicits two distinct effects on glutamatergic transmission. In dBNST, NE elicits an increase in transmission (62% of dBNST NE experiments) or a decrease in transmission (38% of dBNST NE experiments). In vBNST, NE elicits a decrease in transmission in 100% of the experiments. In dBNST, the NE-induced increase in synaptic transmission is blocked by beta1/beta2- and beta2-, but not beta1-specific antagonists. In addition, this increase is also reduced by the alpha2-AR antagonist yohimbine and is absent in the alpha2A-AR knockout mouse. In vBNST, the NE-induced decrease in synaptic transmission is markedly reduced in the alpha2A-AR knockout mouse. Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with beta-AR function. 相似文献
3.
Sheryl Brennan 《Nursing inquiry》1998,5(1):11-17
The present paper addresses the relationship between community based child health nursing services and social constructions of motherhood within Australia during the 1920s. Following the First World War, child health nursing services (then generally known as infant welfare or child welfare services) were established in all Australian states. The focus of the paper is mainly upon the development of the Tasmanian child health service, with some reference to similar services in other states. Within two decades of their establishment, most child-bearing women in Tasmania were in contact with child health services and this apparent success meant that, thereafter, women in Tasmania cared for their children under the 'expert' guidance of nurses. As the 1920s progressed, child health nurses increasingly promoted one particular, and ultimately extremely influential, construction of motherhood, 'scientific motherhood', based upon the philosophy of Dr Truby King. I argue that an understanding of how nursing services have historically reinforced and promoted ideological constructions of motherhood enhances the practice of present day nurses working with women. This argument is supported by reference to present day nursing practice in relation to postnatal depression. 相似文献
4.
Hea-Young P. Choo Hea-Ran Yoon Hwha-Soon Park Dong-Hyun Kim Jongsei Park Dong H. Kim 《Archives of pharmacal research》1998,21(2):168-173
The epoxyalkanoyl derivatives were designed and synthesized as ACE inhibitors. Coupling of unsaturated carboxylic acids with amino acids and following epoxidation with dimethyldioxirane gave the epoxyalkanoyls with high yield. The inhibitory activity of synthesized compounds on angiotensin converting enzyme was IC50 values of 0.06≈5.5 μM. 相似文献
5.
Activity at 5-HT1 and 5-HT2 receptor sites influences sexual behavior in male and female rats. 5-HT3 antagonists reportedly have no effect on copulatory activity in rats of either sex although they influence a variety of other behaviors. The effects of 5-HT3 agonists on sexual behavior are unknown. The following experiments were undertaken to assess the influence of the 5-HT3 agonists 1-phenylbiguanide (PBG) and 2-methyl-serotonin (2-Me-5-HT) on sexual behavior, when administered intracerebroventricularly. Consistent with earlier reports indicating that 5-HT1 and 5-HT2 receptor activity influences reproductive activity in a sex-dependent manner, PBG was found to facilitate male, but not female, rat sexual behavior. 2-Me-5-HT, however, failed to modify either female or male rat sexual activity. Evidence that PBG, but not 2-Me-5-HT, induces carrier-mediated dopamine release suggests that the effect of PBG in male rats is due to dopaminergic mediation. Overall, the present data indicate that 5-HT3 receptor activation has only slight effects on rat sexual behavior. 相似文献
6.
Diego A Preciado Louise Lawson Colm Madden David Myer Chris Ngo John K Bradshaw Daniel I Choo John H Greinwald 《Otology & neurotology》2005,26(4):610-615
OBJECTIVES: To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural hearing loss (SNHL). DESIGN: Prospective prevalence study. SETTING: Tertiary referral children's hospital. PATIENTS: Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years. INTERVENTIONS: All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations. MAIN OUTCOME MEASURES: 1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach. RESULTS: Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing. CONCLUSIONS: A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history. 相似文献
7.
The effect of five different irrigating solutions on patency of four different types of microvascular anastomoses was studied. The solutions used were lactated Ringer's without heparin and four lactated Ringer's solutions with varying concentrations of heparin ranging from 10,000 units/liter to 100,000 units/liter. These were tested on four different anastomotic models in the rat: 1) end-to-end femoral arterial anastomosis; 2) end-to-side arterial bypass graft; 3) end-to-end venous anastomosis; and 4) end-to-side venous bypass graft. There were statistically significant differences in patency rates among the solutions only in the end-to-end venous anastomosis group. In these, significantly higher patency was achieved with heparinized lactated Ringer's solution at 20,000 units/liter. The use of higher concentrations of heparin in these solutions resulted in decreasing patency rates and appears to be contraindicated. 相似文献
8.
Perry D. Cohen Linda Herman Sheryl Jedlinski Peggy Willocks Paula Wittekind 《Neurotherapeutics》2007,4(3):537-544
A patient-centered paradigm for clinical research and medical care is presented as a solution to the problem of declining
innovation and increasing costs and development time in the pipeline for new therapies. Fundamental differences in values
and motivations among scientists, clinicians, industry sponsor, and patients in neurotherapeutics provide a framework for
analysis of ethical conflicts and the loss of public confidence in medical research. Parkinson advocates’ views on clinical
trial participation, perceived risks and benefits, placebo controls, and sham surgery are presented. These views reflect the
sense of urgency and the unique perspective that comes from living with this progressive, debilitating condition full time.
A patient-centered paradigm that includes authentic voices of patients as collaborators at every stage of development will
help to resolve conflicts, build trust, recruit trial participants, and accelerate new therapies. Key elements are adaptive
clinical trial methods and the development of information technology for the assessment of outcomes and surveillance of safety
over the life cycle of a medical product. Supported by the Parkinson’s Disease Foundation, the Parkinson Pipeline Project
is a grassroots group of Parkinson’s patients whose goal is to represent an authentic voice for patients in the treatment
development process. This group promotes education and communication between members of the Parkinson’s community and active
stakeholders in medical research, industry, and regulatory agencies. Its members are an example of a new breed of knowledgeable
consumers, armed with first-hand access to research findings and reinforced by on-line connections to like-minded peers throughout
the world. 相似文献
9.
Using the polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis, we have examined the highly conserved regions of the p53 gene in 58 biopsy samples of head and neck tumors. Mutations were found in 13/58 (23%) tumor specimens, but not in 6 normal tissues. Ten of 13 mutations were due to single base changes and the remaining 3 were 1- or 8-base deletion mutants. These mutations were clustered in exons 5 and 7 and resulted in amino acid changes. Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies. The relationship of Epstein-Barr virus or human papillomavirus and p53 gene mutations in this group of cancers was also analyzed and discussed. 相似文献
10.
Sheryl A. Scott Seth Dinowitz Kristen Terhaar Diane Sherlock Maurice A. Campbell Dreania Levine 《The Journal of comparative neurology》1994,350(2):302-310
The goal of the present study was to identify cytochemical markers characteristic of muscle afferents in hatchling chicks. To this end, we stained neurons in the trigeminal mesencephalic nucleus with a variety of markers that label subsets of neurons in avian dorsal root ganglia. We found that trigeminal mesencephalic neurons are surprisingly heterogeneous in their cytochemical make-up, expressing, to varying degrees, substance P, cholecystokinin, carbonic anhydrase, calbindin D-28k, parvalbumin, and S-100β. Calbindin D28k and S-100β appeared to be expressed equally in medial and lateral divisions of the trigeminal mesencephalic nucleus. In contrast, substance P- and cholecystokinin-immunoreactive neurons were more abundant in the medial division, whereas carbonic anhydrase activity and parvalbumin immunoreactivity were stronger in the lateral division. We were unable to detect met-enkephalin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal peptide, somatostatin, γ-aminobutyric acid, or tyrosine hydroxylase in the trigeminal mesencephalic nucleus. Moreover, these neurons did not appear to bind the lectin Dolichos biflorus agglutinin. The heterogeneity of expression of markers among trigeminal mesencephalic nucleus neurons, especially between neurons in the medial and lateral divisions, suggests that these neurons are functionally diverse. 相似文献