Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes

Interleukin 6 (IL6) is a pleiotropic cytokine that not only affects the immune system, but also plays an active role in many physiological events in various organs. Notably, 35% of systemic IL6 originates from adipose tissues under noninflammatory conditions. Here, we describe a previously unknown function of melanocortins in regulating Il6 gene expression and production in 3T3-L1 adipocytes through membrane receptors which are called melanocortin receptors (MCRs). Of the five MCRs that have been cloned, MC2R and MC5R are expressed during adipocyte differentiation. α-Melanocyte-stimulating hormone (α-MSH) or ACTH treatment of 3T3-L1 adipocytes induces Il6 gene expression and production in a time- and concentration-dependent manner via various signaling pathways including the protein kinase A, p38 mitogen-activated protein kinase, cJun N-terminal kinase, and IκB kinase pathways. Specific inhibition of MC2R and MC5R expression with short interfering Mc2r and Mc5r RNAs significantly attenuated the α-MSH-induced increase of intracellular cAMP and both the level of Il6 mRNA and secretion of IL6 in 3T3-L1 adipocytes. Finally, when injected into mouse tail vein, α-MSH dramatically increased the Il6 transcript levels in epididymal fat pads. These results suggest that α-MSH in addition to ACTH may function as a regulator of inflammation by regulating cytokine production

Heterosporis anguillarum infections in farm cultured eels (Anguilla japonica) in Korea

Ten eels (Anguilla japonica) from a fish farm in Korea were examined and diagnosed with a Heterosporis infection. The gross lesions on the trunk were uneven and the concave parts were pasty. Histopathologically, lyses of the trunk muscles, degenerative muscle fibers and the scattered spores were observed. The sporophorocyst (SPC) contained several spores with a variety of shapes. Some SPC were disrupted and the spores in the SPC were scattered in the muscle tissues. Macrophages existed near the scattered spores. Electron microscopy revealed special structures such as sporophorocyst containing various developmental parasitic stages such as meronts, sporonts, sporophorous vesicles and spores

Differential wedging of vertebral body and intervertebral disc in thoracic and lumbar spine in adolescent idiopathic scoliosis – A cross sectional study in 150 patients

<p>Abstract</p> <p>Background</p> <p>Hueter-Volkmann's law regarding growth modulation suggests that increased pressure on the end plate of bone retards the growth (Hueter) and conversely, reduced pressure accelerates the growth (Volkmann). Literature described the same principle in Rat-tail model. Human spine and its deformity i.e. scoliosis has also same kind of pattern during the growth period which causes wedging in disc or vertebral body.</p> <p>Methods</p> <p>This cross sectional study in 150 patients of adolescent idiopathic scoliosis was done to evaluate vertebral body and disc wedging in scoliosis and to compare the extent of differential wedging of body and disc, in thoracic and lumbar area. We measured wedging of vertebral bodies and discs, along with two adjacent vertebrae and disc, above and below the apex and evaluated them according to severity of curve (curve < 30° and curve > 30°) to find the relationship of vertebral body or disc wedging with scoliosis in thoracic and lumbar spine. We also compared the wedging and rotations of vertebrae.</p> <p>Results</p> <p>In both thoracic and lumbar curves, we found that greater the degree of scoliosis, greater the wedging in both disc and body and the degree of wedging was more at apex supporting the theory of growth retardation in stress concentration area. However, the degree of wedging in vertebral body is more than the disc in thoracic spine while the wedging was more in disc than body in lumbar spine. On comparing the wedging with the rotation, we did not find any significant relationship suggesting that it has no relation with rotation.</p> <p>Conclusion</p> <p>From our study, we can conclude that wedging in disc and body are increasing with progression on scoliosis and maximum at apex; however there is differential wedging of body and disc, in thoracic and lumbar area, that is vertebral body wedging is more profound in thoracic area while disc wedging is more profound in lumbar area which possibly form 'vicious cycle' by asymmetric loading to spine for the progression of curve.</p

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial

BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803)

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Modeling Dye Assisted Photocoagulation of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is major cause of blindness in Americans aged 50 years and up. In 2010, there were more than 2 million cases of AMD in the United States and the National Eye Institute projects that there will be nearly 5.5 million cases per year by 2050. The more detrimental form of AMD, the “wet” form, is caused by the development of new blood vessels within the macular region of the eye, a condition known as choroidal neovascularization (CNV). Several treatment modalities are available for AMD, however the most common is laser photocoagulation in which the abnormal blood vessels are coagulated using a high intensity laser as a heating source. While this treatment modality is effective, high temperatures within the deep eye tissue can cause unwanted collateral damage. Optimizing this thermal treatment thus amounts to minimizing the duration of treatment such that the abnormal blood vessels are destroyed but damage to other tissues is minimized. One possible extension was also explored in this study which is the injection of highly absorbent dye into the abnormal feeder vessel to improve the laser absorbance. The model used in this study employs a 3D Cartesian geometry over which Pennes bioheat equation is solved for the temperature profile over a time scale of 1 second. The thermal damage is then analyzed by observing the temperature history in abnormal and healthy tissue with the goal of achieving a cumulative effective number of minutes at 43oC greater than 80 minutes within the target tissue, the feeder vessel, while minimizing the thermal damage elsewhere. Results from the model suggest that after 1 second of laser application, temperatures in the feeder vessel rapidly rise to a maximum of 67oC and temperatures in the retinal pigment epithelium (RPE) rise to 86oC. In the hottest section of the feeder vessel, that section which is directly exposed to the center of the laser spot, the desired thermal damage is achieved within 0.55 s. The model was assessed for sensitivity to thermal properties as well as the absorbance coefficient, μa, in the feeder vessel and RPE sections. Results from this analysis suggested a change in temperature of less than 0.5% when these parameters were varied within the reasonable limits found in the literature. This suggests good applicability of the results to individual patients. The use of dye to target and improve heat transfer is a novel improvement to the existing photocoagulation process. To assess the efficacy of such a modification, the absorbance coefficient was increased from 4610 m-1 to 9000 m-1 to simulate the effect of the dye. The results show very little variation in feeder vessel temperatures suggesting that dye assisted photocoagulation is not a large improvement from the current process. The effect of blood flow velocity was also assessed in this study. As expected, it was found that increasing blood flow velocity shifted the maximum temperature in the feeder vessel along the direction of flow and resulted in slightly lower maximum feeder vessel temperatures as the blood cools the feeder vessel by convection. The results of this study suggest that shorter treatment times may be useful in reducing collateral tissue damage, however a treatment time of 1 second is justified as a margin of safety to ensure complete destruction of the desired tissue

Channel Scaling Dependent Photoresponse of Copper-Based Flexible Photodetectors Fabricated Using Laser-Induced Oxidation

Copper (Cu) oxide compounds (CuxO), which include cupric (CuO) and cuprous (Cu2O) oxide, have been recognized as a promising p-channel material with useful photovoltaic properties and superior thermal conductivity. Typically, deposition methods or thermal oxidation can be used to obtain CuxO. However, these processes are difficult to apply to flexible substrates because plastics have a comparatively low glass transition temperature. Also, additional patterning steps are needed to fabricate applications. In this work, we fabricated a metal- semiconductor-metal photodetector using laser-induced oxidation of thin Cu films under ambient conditions. Raman spectroscopy, scanning electron microscopy-energy-dispersive X-ray spectroscopy, and atomic force microscopy were used to study the composition and morphology of our devices. Moreover, the photoresponse of this device is reported herein. We performed an in-depth analysis of the relationship between the channel size and number of carriers using scanning photocurrent microscopy. The carrier transport behaviors were identified; the photocurrent decreased as the length and width of the channel increased. Furthermore, we verified the suitability of the device as a flexible photodetector using a variety of bending tests. Our in-depth analysis of this Cu-based flexible photodetector could play an important role in understanding the mechanisms of other flexible photovoltaic applications