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11.
Sam R.J Hoare 《Current Neuropharmacology》2007,5(3):168-179
Class B GPCR’s are activated by peptide ligands, typically 30-40 amino acid residues, that are involved in major physiological functions such as glucose homeostasis (glucagon and glucagon-like peptide 1), calcium homeostasis and bone turnover (parathyroid hormone and calcitonin), and control of the stress axis (corticotropin-releasing factor). Peptide therapeutics have been developed targeting these receptors but development of nonpeptide ligands, enabling oral administration, has proved challenging. Allosteric modulation of these receptors provides a potential route to developing nonpeptide ligands that inhibit, activate, or potentiate activation of these receptors. Here the known mechanisms of allosteric modulators targeting Class B GPCR’s are reviewed, particularly nonpeptide antagonists of the corticotropin-releasing factor 1 receptor and allosteric enhancers of the glucagon-like peptide-1 receptor. Also discussed is the potential for antagonist ligands to operate by competitive inhibition of one of the peptide binding sites, analogous to the Charniere mechanism. These mechanisms are then used to discuss potential strategies and management of pharmacological complexity in the future development of allosteric modulators for Class B GPCR’s. 相似文献
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Although information regarding attitudes and characteristics of human blood donors has been researched, little is known about the motivations and demographic and personality characteristics of women who choose to donate their breast milk. Eight milk banks in France participated in a study examining donor characteristics, providing data on 103 women. The results showed that the donors were women of average childbearing age with strong support at home. Almost half did not work outside of the home, compared to the national average of 80% of women in this age group; similarly, a large number (currently working or not) were from the health and social services fields. Reasons for donation were largely altruistic, and a general optimistic attitude prevailed within the participants. The results of this study provide useful information for the recruitment of potential donors as well as information on how to facilitate and provide optimal service through milk donation. 相似文献
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15.
The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing. 相似文献
16.
The bedside assessment of dysphagia may be difficult, due to the inability to witness the act of swallowing directly. The milk test described in this paper gives a good assessment of swallowing, is cheap and easily portable and allows an instant decision to be made without recourse to special investigations. 相似文献
17.
Matthew Hoare Tracy Woodall Graeme J M Alexander 《Journal of interferon & cytokine research》2005,25(3):174-176
First-line therapy for hepatitis C virus (HCV) infection comprises interferon-alpha (IFN-alpha) and ribavirin for 6 or 12 months. Mild complications of therapy are common, but more serious complications are rare. Three patients with chronic HCV infection, acquired through injecting drug use, developed idiopathic facial paralysis (Bell's palsy) during therapy, with spontaneous resolution after withdrawal of treatment. Large-scale cohort studies reveal that IFNs are associated rarely with neurologic complications, and only one previous report has linked IFN-alpha therapy and Bell's palsy. We postulate that IFN-alpha therapy led to a breakdown of peripheral tolerance to myelin sheath antigens, leading to neuropathy, just as IFN-alpha therapy can cause autoimmune thyroiditis through breakdown of tolerance to native thyroid antigens. 相似文献
18.
Dawn Stacey RN MScN CON Annette M. O'Connor RN PhD † Cathy DeGrasse RN MScN ‡ Shailendra Verma MD FRCP § 《Health expectations》2003,6(1):3-18
Objective To develop and evaluate the effectiveness of a breast cancer prevention decision aid for women aged 50 and older at higher risk of breast cancer. Design Pre‐test–post‐test study using decision aid alone and in combination with counselling. Setting Breast Cancer Risk Assessment Clinic. Participants Twenty‐seven women aged 50–69 with 1.66% or higher 5‐year risk of breast cancer. Intervention Self‐administered breast cancer prevention decision aid. Main outcome measures Acceptability; decisional conflict; knowledge; realistic expectations; choice predisposition; intention to improve life‐style practices; psychological distress; and satisfaction with preparation for consultation. Results The decision aid alone, or in combination with counselling, decreased some dimensions of decisional conflict, increased knowledge (P < 0.01), and created more realistic expectations (P < 0.01). The aid in combination with counselling, significantly reduced decisional conflict (P < 0.01) and psychological distress (P < 0.02), helped the uncertain become certain (P < 0.02), and increased intentions to adopt healthier life‐style practices (P < 0.03). Women rated the aid as acceptable, and both women and practitioners were satisfied with the effect it had on the counselling session. Conclusion The decision aid shows promise as a useful decision support tool. Further research should compare the effect of the decision aid in combination with counselling to counselling alone. 相似文献
19.
Stacey M Pollock-Barziv Anne I Dipchand Brian W McCrindle Nadya Nalli Lori J West 《The Journal of heart and lung transplantation》2005,24(2):190-194
BACKGROUND: While Tacrolimus (Tac) and Cyclosporine (Cya) immunosuppression are used after cardiac transplantation (tx), few studies have evaluated their use in pediatric patients. METHODS: We randomized 26 heart transplant recipients (pts) in a prospective, open-label trial to Tac (n = 14) or Cya (n = 12) to compare their efficacy and side-effects. Mean age at tx was 4.2 years for Tac and 5.8 years for Cya. Mean follow-up was 26 months (range: 11-39 months) for Tac and 24 months for Cya (range: 33-13 months). RESULTS: Our data suggest that both regimens are efficacious in the pediatric population. Conversion from Cya to Tac was useful for dealing with persistent rejection, although this sample did not suggest lower incidence of acute cellular rejection in the Tac group. CONCLUSIONS: Further studies are required to establish pharmacokinetic parameters to enhance therapeutic monitoring of these patients to minimize side effects and enhance outcomes. 相似文献
20.
The Stiles-Crawford effect of the first kind (SCE-I) was measured on both emmetropic and myopic subjects at six different retinal locations. The results revealed a number of significant discrepancies in receptor alignment between the groups of different refractive errors. In myopic subjects, the receptors in the nasal retina (i.e. between the fovea and the optic nerve head) were found to be aligned nasally towards the optic nerve head, whereas the receptors in the temporal retina were aligned towards the centre of the exit pupil. In emmetropic subjects, the receptors across the retina were finely tuned towards the centre of the exit pupil. The magnitude of the receptor displacement in myopic subjects was found to be directly associated with the length of the eyeball. 相似文献