Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.

No abstract

PMPs can become a useful public health surveillance tool to monitor the medical and non-medical use of prescription opioids and to inform public health and safety policy.

No abstract

Capillaries were isolated from epididymal fat, and a catecholamine-sensitive adenylate cyclase found in these capillaries was characterized. The effect of various hormones on the accumulation of adenosine 3': 5'-cyclic monophosphate in capillary endothelial cells was determined and the cyclase was found to exhibit mixed alpha and beta characteristics. Cyclase was cytochemically localized in these endothelial cells with 5'-adenylyl-imidodiphosphate as a specific cyclase substrate and alloxan as a specific cyclase inhibitor. Lead imidodiphosphate was precipitated at or near the site of cyclase activity upon hydrolysis of 5'-adenylyl-imidodiphosphate by cyclase. This reaction product was observed primarily on the luminal surface of intact capillaries, in micropinocytic invaginations, in free vesicles within the cytoplasm, and in the intracellular junctions.Digestion of epididymal fat with collagenase has been used by several investigators to obtain pure fractions of fat cells (1, 2). Upon centrifugation of the dissociated adipose tissue, adipocytes collect at the top and the vascular and stromal cells are pelleted. This study describes a method for partial purification of the vascular-stromal pellet to obtain a relatively homogeneous preparation of intact capillaries and reports the biochemical characterization and cytochemical localization of a catecholamine-sensitive adenylate cyclase (cyclase) associated with capillary endothelial cells.A modification of the method of Reik et al. (3) was used in the cytochemical localization of capillary cyclase activity. The substrate, 5'-adenylyl-imidodiphosphate, which is specifically hydrolyzed by cyclase but not by other ATPases (4, 5), was used in comparison with ATP; the specificity of localization was enhanced by a reaction in which lead imidodiphosphate is precipitated at or near the site of cyclase activity. Further specificity was achieved by the use of alloxan, which has been shown to selectively inhibit cyclase while sparing other membrane ATPase (6), and thus would be expected to inhibit product formation when 5'-adenylyl-imidodiphosphate is used as substrate. METHODS AND MATERIALSIsolation of Capillaries. The distal portion of epididymal fat pads from Sprague-Dawley rats (250-300 g) were removed and placed in Tyrode's basal salt solution (pH 7.2) at 00, thoroughly minced, and placed in siliconized vials (three fat pads per vial) each containing 40 mg of crude collagenase (Worthington Biochemicals), 6 mg of bovine-serum albumin, and 6 ml of Tyrode's balanced salt solution. The mixture was incubated at 370 for 45 min on a wrist action shaker and centrifuged in siliconized conical tubes (30 X g for 2 min). The resulting pellet contained larger blood vessels, stromal cells, and attached fat cells, and was discarded. The supernatant containing the fat cake was decanted and centrifuged (800 X g for 2 min). The vascular pellets from the second centrifugation were twice pooled and washed in Tyrode's solution, and collected by centrifugation at 800 X g for 2 min. T...