Jenningsjohannessen9065

Introduction From 1986, the World Health Organization (WHO) analgesic ladder has been used as the simple and valuable pain-relieving guidance in the pharmaceutical pain management, however, with the development of medical history, notions about pain physiology and pain management have already updated. Is the analgesic ladder still appropriate for chronic non-cancer pain (CNCP) patients? This study aims to analyse the current usage of the analgesic ladder in patients with CNCP by evaluating previously published pertinent studies. Methods Literature published in English from January 1980 to April 2019 and cited on PubMed database was included. Analysis on the analgesic ladder, current status of CNCP management, and a new revised ladder model were developed based on relevant literature. Results The WHO analgesic ladder for cancer pain is not appropriate for current CNCP management. It is revised into a four-step ladder the integrative therapies being adopted at each step for reducing or even stopping the use of opioid analgesics; interventional therapies being considered as step 3 before upgrading to strong opioids if non-opioids and weak opioids failed in CNCP management. Discussion A simple and valuable guideline in past years, the WHO analgesic ladder is inappropriate for the current use of CNCP control. A revised four-step analgesic ladder aligned with integrative medicine principles and minimally invasive interventions is recommended for control of CNCP. © 2020 Yang et al.Aim The present study was conducted to determine the predictive value of Selenium (Se) in the diagnosis of Geatational diabetes Mellitus (GDM). Methods This is a nested case-control study with 636 normal pregnant mothers in their 11th-13th weeks. Gestational diabetes screening was done in weeks 24-28. Twenty-five individuals were detected as GDM, and for every GDM two gestational age-matched normal pregnant women were selected. The blood selenium level was measured in both groups. Results The serum Se level in the case group was lower than that of the control group (50.60 ± 10.88 versus 66.02 ± 10.57) in the first trimester. Also, in the second trimester, Se was lower in the case group (39.87 ± 10.23 versus 63.17 ± 10.22). The best cut-off point for selenium in order to predict the incidence of gestational diabetes in our study was 48.2. Pregnant women with selenium levels below 48.2 were more likely to develop gestational diabetes. Conclusion Serum selenium was lower in the GDM subjects compared with age-matched control group; the clinical concept and mechanism of this finding need to be investigated through further studies. © 2020 Moshfeghy et al.Aim of Study To investigate podocyte density in aging diabetic Ins2± and Ins2±, A1AR-/- mouse models in C57Bl/6 background. Methods Ins2± mice and especially Ins2±, adenosine A1 receptor knockout mice (Ins2±, A1AR-/-) are mouse models with a phenotype of diabetic nephropathy. Aged mice (at ~40 weeks) were assessed for glomerular filtration barrier function by measuring albuminuria, glomerular filtration, glomerular damage by electron microscopy, and podocyte numbers by Wilms Tumor protein (WT-1) staining. Results Compared to healthy wild-type mice, both diabetic mouse models developed diabetic nephropathy, including hyperfiltration (p less then 0.01) and albuminuria (p less then 0.05). Typical diabetic structural glomerular and podocyte damage was visualized by electron microscopy. Podocyte count per glomerular area (podocyte density) was significantly decreased in both diabetic mouse models (p less then 0.01). In contrast, no significant correlation was detected between albuminuria and absolute podocyte count per glomerulus. Conclusion The amount of albuminuria as marker of diabetic nephropathy does not correlate with the podocytes density; however, a relative podocyte deficiency became evident with an increase in glomerular area in the diabetic animals, suggesting a relative podocytopenia. © 2020 Faulhaber-Walter et al.Background Sepsis is one of the most dangerous syndromes, has extremely high mortality, and is caused by the body's extreme responses to an infection. The pathogenesis of sepsis is very complex and remains largely unknown and thus the treatments for sepsis are limited. Here, we evaluated the treatment results of two potential drugs, glutamine and ulinastatin, on sepsis. Methods CLP rat model was used to study sepsis. Gastrostomy was performed to deliver the drugs. Flow cytometry was employed to measure CD4 and CD8 levels. May-Grünwald-Giemsa staining was used to count the numbers of monocytes and neutrophils in the blood. Selleckchem BIIB129 ELISA assay was performed to assess the levels of PCT, IL-6, TNFα, and IL-1β. Results Sepsis was successfully induced with the standard CLP rat model. Both glutamine and ulinastatin treatments greatly improved the outcomes of sepsis, but the combination of both treatments had the maximum therapeutic effect. Mechanistically, PCT, IL-6, TNFα, and IL-1β levels were significantly diminished following glutamine and ulinastatin treatments, suggesting an inhibition of inflammatory responses. Further, CD4 and CD4/CD8 ratio, and the numbers of monocytes and neutrophils were greatly up-regulated by glutamine and ulinastatin, indicating an enhanced immunity. Conclusion Glutamine and ulinastatin treatments largely mitigate sepsis shock by suppressing the inflammatory responses of the body and strengthening the immune system. Combination of these two drugs could serve as a potential treatment for sepsis. © 2020 Wang et al.Mitochondria are organelles with highly dynamic ultrastructure maintained by flexible fusion and fission rates governed by Guanosine Triphosphatases (GTPases) dependent proteins. Balanced control of mitochondrial quality control is crucial for maintaining cellular energy and metabolic homeostasis; however, dysfunction of the dynamics of fusion and fission causes loss of integrity and functions with the accumulation of damaged mitochondria and mitochondrial deoxyribose nucleic acid (mtDNA) that can halt energy production and induce oxidative stress. Mitochondrial derived reactive oxygen species (ROS) can mediate redox signaling or, in excess, causing activation of inflammatory proteins and further exacerbate mitochondrial deterioration and oxidative stress. ROS have a deleterious effect on many cellular components, including lipids, proteins, both nuclear and mtDNA and cell membrane lipids producing the net result of the accumulation of damage associated molecular pattern (DAMPs) capable of activating pathogen recognition receptors (PRRs) on the surface and in the cytoplasm of immune cells.