1 The in¯uence of a chronic treatment with the d-selective opioid antagonist naltrindole (1 mg kg 71 ) during the preweanling period (daily injections from birth to postnatal day 19), on the antinociceptive and sympatholytic e ects of the a 2 -adrenergic agonist clonidine in male and female rats of 20 and 25 days of age was investigated. 2 Nociception was assessed using the tail immersion test (water at 508C) and plasma levels of adrenaline were measured by high-performance liquid chromatography. 3 The dose of clonidine (1.5 mg kg 71 ) and the time point at which nociceptive responses were recorded (30 min after the administration of the drug) were chosen on the basis of dose-response (0.5, 1, 1.5 and 2 mg kg 71 ) and time-response (5, 10, 15, 30 and 60 min) curves which were previously carried out in naive control neonatal rats. 4 In females, the functional blockade of the d-receptor by neonatal naltrindole treatment did not modify the sympatholytic e ect of clonidine but prevented clonidine induced antinociception. Conversely, in males naltrindole treatment allowed the appearance of clonidine antinociception and the sympatholytic e ect of clonidine. 5 The results indicate that the d-receptor is involved in the modulation of antinociceptive and sympatholytic responses to clonidine in neonatal rats and suggest the existence of sex di erences in the interactions between d-opioid and a 2 -adrenergic receptors.
Patients with prostate cancer (PCa) on androgen-deprivation therapy (ADT) are at high risk of osteoporosis and fragility fractures. We aimed to provide some practical insights into the delivery of optimal bone health care for PCa patients, particularly those on ADT. An interdisciplinary group of experts, including urologists and rheumatologists developed recommendations based on their expertise, current evidence and guidelines. The multidisciplinary group's main recommendations are: fragility fracture risk should be assessed in all PCa patient, especially, in those under ADT. FRAX® tool may be incorporated into clinical practice to identify patients at high risk of fracture. Bone mineral density (BMD) should be measured routinely by dual energy X-ray absorptiometry in all patients scheduled for or on ADT. Thoracic and lumbar spine X-ray may be performed at the initial evaluation of patients with the diagnosis of osteoporosis and in case of suspected clinical vertebral fracture. Basic laboratory tests are recommended to exclude secondary osteoporosis. Treatment with bisphosphonates or denosumab should be considered in patients on ADT with fragility fracture, osteoporosis (BMD T-score ≤−2.5), or high risk of fracture according to FRAX®. Referral to a bone metabolism specialist should be contemplated in some cases. The recommendations provided in this document, tailored for clinicians treating PCa patients, may be of help to identify and treat patients at high risk of fracture.
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