Confronting the opioid crisis: Practical pain management and strategies: AOA 2018 critical issues symposium

The United States is in the midst of an opioid crisis. Clinicians have been part of the problem because of overprescribing of narcotics for perioperative pain management. Clinicians need to understand the pathophysiology and science of addiction to improve perioperative management of pain for their patients. Multiple modalities for pain management exist that decrease the use of narcotics. Physical strategies, cognitive strategies, and multimodal medication can all provide improved pain relief and decrease the use of narcotics. National medical societies are developing clinical practice guidelines for pain management that incorporate multimodal strategies and multimodal medication. Changes to policy that improve provider education, access to naloxone, and treatment for addiction can decrease narcotic misuse and the risk of addiction

Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets

Recognition of pancreatic beta cell antigens by autoreactive T lymphocytes plays a central role in the pathogenesis of insulin-dependent type 1 diabetes. Recent results suggest that non-conventional antigenic epitope processing and presentation may contribute to triggering and maintaining autoreactive responses. Moreover, promising results raise hope that autoantigens may become safe and specific therapeutics for type 1 diabetes in the future

Dietary soy and green tea in the prevention of prostate cancer

Prostate cancer risk is significantly lower in Asian countries compared to the US, which has prompted interest in the chemo-preventative action of dietary components such as soy and green tea commonly found in Asian diets, such as soy and green tea. Studies have suggested that soy isoflavones and green tea catechins exert anticarcinogenic effects; however, the effects of dietary soy and green tea on prostate cancer development in vivo are understudied. We proposed that soy and green tea, containing a mixture of bioactive components, would be more potent chemopreventative agents than individual supplements. Using an in vitro system, we observed that soy extract induced significantly more apoptosis and Bax expression than the individual soy isoflavones genistein or daidzein. Similarly, green tea induced more apoptosis than epigallocatechin gallate (EGCG), by decreasing inhibitors of apoptosis proteins, XIAP, cIAP-1 and cIAP-2. Notably, soy extract and green tea did not induce cell cycle arrest or apoptosis in non-cancerous benign prostate hyperplasia (BPH-1) cells, suggesting that the effects of whole foods were tumor-cell specific. Chronic inflammation and nuclear factor-kappa B (NFkB) have been implicated in prostate cancer development, suggesting that factors that inhibit NFkB may serve as effective chemo-preventative agents. We therefore examined the effects of dietary soy, green tea, and the combination of soy and green tea in vivo on inflammation, NFkB activation and cancer development using a hormone-induced prostate cancer model. The combination of both soy and green tea decreased prostate inflammatory infiltration and cytokine (TNFa, IL-6 and IL-1b) levels, increased Bax expression, and decreased prostate hyperplasia. Interestingly, these effects were not apparent in soy alone or tea alone treated animals. The combination of soy and green tea also suppressed NFkB p50 activity via induction of IkBa. Together these results suggest that the combination of soy and green tea may inhibit hormone-induced proinflammatory NFkB signals that contribute to prostate cancer development. These studies suggest that food products that bear a combination of active compounds may be more efficacious as chemo-preventative agents than individual compounds, and combination of different dietary compounds may offer additional beneficial effects. This “whole food” based approach is significant for the development of dietary recommendations for prostate cancer prevention

miR-29b inhibits TGF-β1-induced cell proliferation in articular chondrocytes

Transforming growth factor β1 (TGF-β1) is a known regulator of chondrocyte proliferation and promotes cartilage repair in osteoarthritis (OA). microRNA-29b-3p (miR-29b-3p) is downregulated by TGF-β1 and overexpressed in OA cartilage. However, the ability of miR-29b-3p to mediate the chondrocyte pro-proliferative effects of TGF-β1 is not yet understood. This current study aimed to investigate the effect of miR-29b-3p on TGF-β1-induced cell proliferation in murine articular chondrocytes. The stimulation of chondrocytes by TGF-β1 for 24 h resulted in the downregulation of miR-29b-3p expression. The ratio of G0/G1 phase cells decreased in response to TGF-β1 whereas the ratio of S phase cells was increased. Consistent with this observation, miR-29b-3p overexpression inhibited TGF-β1’s ability to promote the ratio of S phase cells and downregulate the ratio of G0/G1 phase cells. These findings suggest that the downregulation of miR-29b-3p is a likely requirement for TGF-β1-mediated proliferation of murine articular chondrocytes. Furthermore, implying that miR-29b-3p expression may be involved in reduced chondrocyte proliferation in OA

Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

<p>Abstract</p> <p>Background</p> <p>The lanthanide cation, gadolinium (GdCl₃) protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl₃interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl₃protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl₃treatment for reperfusion injury on 1) circulating monoctye and neutrophil counts, 2) secretion of inflammatory cytokines, and 3) influx of monocytes and neutrophils into the myocardium.</p> <p>Methods</p> <p>Rats (n = 3-6/gp) were treated with saline or GdCl₃(20 μmol/kg) 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO) and α-naphthyl acetate esterase (ANAE).</p> <p>Results</p> <p>GdCl₃did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl₃decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl₃decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl₃decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both control and GdCl₃treated rats. Likewise, IL-8 levels increased throughout the 3 hour time period in the Sham group. There was no difference in IL-8 detected in the myocardium after 120 min reperfusion between groups. In contrast, after 120 min reperfusion GdCl₃decreased the myocardial tissue levels of macrophage secreted cytokines, GM-CSF and IL-1.</p> <p>Conclusion</p> <p>GdCl₃treatment prior to ischemia and reperfusion injury decreased circulating monocytes and neutrophils, macrophage secreted cytokines, and leukocyte infiltration into injured myocardium. These results suggest GdCl₃decreased monoctye and neutrophil migration and activation and may be a novel treatment for inflammation during ischemia and reperfusion.</p

Impact of Heavy Metals in Ambient Air in Insulin Resistance of Shipyard Welders in Northern Taiwan

Exposure to metals poses potential health risks, including insulin resistance (IR), to those exposed to them in excess. Limited studies have examined such risks in occupational workers, including welders, and these have yielded inconsistent results. Thus, we examined the associations between exposure to welding metals and IR in welders. We recruited 78 welders and 75 administrative staff from a shipyard located in northern Taiwan. Personal exposure to heavy metals, including chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), and cadmium (Cd), was monitored through particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) and urine analysis by inductively coupled plasma mass spectrometry (ICP–MS). After each participant fasted overnight, blood samples were collected and analyzed for IR assessment through updated homeostasis model assessment (HOMA2) modeling. Air sampling in the personal breathing zone was performed during a Monday shift prior to the blood and urine sample collection the following morning. The welders’ median personal Cr, Mn, Fe, Ni, Cu, and Zn airborne PM2.5 levels and urinary Cd levels were significantly higher than those of the administrative staff. After adjustment for covariates, logarithmic PM2.5-Mn, PM2.5-Fe, PM2.5-Cu, and PM2.5-Zn levels were positively correlated with logarithmic fasting plasma glucose (P-FGAC) levels (PM2.5-Mn: β = 0.0105, 95% C.I.: 0.0027–0.0183; PM2.5-Fe: β = 0.0127, 95% C.I.: 0.0027–0.0227; PM2.5-Cu: β = 0.0193, 95% C.I.: 0.0032–0.0355; PM2.5-Zn: β = 0.0132, 95% C.I.: 0.0005–0.0260). Logarithmic urinary Zn was positively correlated with logarithmic serum insulin and HOMA2-IR levels and negatively correlated with logarithmic HOMA2-insulin sensitivity (%S; βinsulin = 0.2171, 95% C.I.: 0.0025–0.4318; βIR = 0.2179, 95% C.I.: 0.0027–0.4330; β%S = −0.2180, 95% C.I.: −0.4334 to −0.0026). We observed that glucose homeostasis was disrupted by Mn, Fe, Cu, and Zn exposure through increasing P-FGAC and IR levels in shipyard welders