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Areas covered: The paper reports the most recent advances in pharmacotherapy for women taking into account the biopsychosocial model. Hormone therapy, including estrogens, testosterone, tibolone and dehydroepiandrosterone, are discussed in term of efficacy and safety in postmenopausal women both for female sexual interest/arousal disorder (FSIAD) and genito-pelvic pain/penetration disorder. Ospemifene, a selective estrogen receptor modulator, approved to treat dyspareunia at menopause, is also discussed. Data on psychoactive agents for treatment of FSIAD in premenopausal women are discussed, including the potential use of on-demand combined hormonal (testosterone) and non-hormonal (buspirone or sildenafil) treatments to address possible neurophysiological profiles of women.
Expert opinion: We are still waiting for an approved pharmacotherapy for FSD. This is not the result of gender inequality in sexual medicine, but it reflects the need of balancing benefits and risks in order to provide effective and safe treatments to women of any age. 相似文献
Objective: To review the evidence that HCA is a classifiable skin sensitizer against the standards set by the Globally Harmonized Scheme (GHS), and determine whether it represents an appropriate choice for a positive control substance for predictive testing.
Methods: Using the GHS criteria, mechanistic data, and in vitro, in vivo and human evidence relating to HCA and skin sensitization have been reviewed.
Results: The chemistry of HCA is consistent with potential for skin sensitization and predictive in vivo test data support this conclusion. However, the human data are relatively sparse, consistent with HCA possessing a low capacity to induce skin sensitization under conditions of consumer exposures.
Conclusions: Using GHS criteria (and applying a precautionary approach) HCA would classify as a weaker skin sensitizer than predicted by the local lymph node assay (LLNA). However, given the human experience, it is necessary to consider whether HCA is the most appropriate choice for use as a positive regulatory control. 相似文献
Aim:
Methyl eugenol is a major active component extracted from the Chinese herb Asari Radix et Rhizoma, which has been used to treat toothache and other pain. Previous in vivo studies have shown that methyl eugenol has anesthetic and antinociceptive effects. The aim of this study was to determine the possible mechanism underlying its effect on nervous system disorders.Methods:
The direct interaction of methyl eugenol with Na+ channels was explored and characterized using electrophysiological recordings from Nav1.7-transfected CHO cells.Results:
In whole-cell patch clamp mode, methyl eugenol tonically inhibited peripheral nerve Nav1.7 currents in a concentration- and voltage-dependent manner, with an IC50 of 295 μmol/L at a −100 mV holding potential. Functionally, methyl eugenol preferentially bound to Nav1.7 channels in the inactivated and/or open state, with weaker binding to channels in the resting state. Thus, in the presence of methyl eugenol, Nav1.7 channels exhibited reduced availability for activation in a steady-state inactivation protocol, strong use-dependent inhibition, enhanced binding kinetics, and slow recovery from inactivation compared to untreated channels. An estimation of the affinity of methyl eugenol for the resting and inactivated states of the channel also demonstrated that methyl eugenol preferentially binds to inactivated channels, with a 6.4 times greater affinity compared to channels in the resting state. The failure of inactivated channels to completely recover to control levels at higher concentrations of methyl eugenol implies that the drug may drive more drug-bound, fast-inactivated channels into drug-bound, slow-inactivated channels.Conclusion:
Methyl eugenol is a potential candidate as an effective local anesthetic and analgesic. The antinociceptive and anesthetic effects of methyl eugenol result from the inhibitory action of methyl eugenol on peripheral Na+ channels. 相似文献Design—Retrospective review. Patient acceptability in the second half of the study was routinely assessed within 24 hours.
Setting—Regional cardiac centre.
Patients—45 consecutive patients with either aborted sudden death or haemodynamically unstable ventricular tachycardia were referred for ICD im- plantation.
Interventions—A subpectoral implantation technique was employed. Twelve procedures were performed under general anaesthesia. Thirty three patients were sedated with midazolam and diamorphine, and local anaesthesia was achieved with bupivicaine. Ventricular fibrillation for defibrillation threshold testing was induced by alternating current, T wave shock, or ultrarapid burst pacing. Patients were contacted after the procedure to assess acceptability.
Results—32 patients having implantation under local anaesthesia did not recall the surgical procedure. One patient described an awareness of "pushing" as the generator was positioned in the pocket. Seven patients said that the procedure was painless but recalled a test shock, four describing it as mildly uncomfortable. All 33 patients stated that they would be willing to have a second implant under local anaesthesia. Twelve patients who had the implant performed under general anaesthesia had no recollection of the procedure. Mean (SD) total procedure duration was significantly longer in those who had general anaesthesia (93 (16) v 67 (17) minutes; p = 0.0009).
Conclusions—Subpectoral implantation of ICDs may be performed safely with patient acceptability under local anaesthesia with conscious sedation.
Keywords: cardioverter defibrillator; subpectoral implantation; local anaesthesia; pacing 相似文献