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Endocrine Reviews Aug 2017In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution,... (Review)
Review
In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.
Topics: Humans; Serum Albumin, Human; Sex Hormone-Binding Globulin; Testosterone; Transcortin
PubMed: 28673039
DOI: 10.1210/er.2017-00025 -
Human Vaccines & Immunotherapeutics Dec 2022Rabies is a highly fatal zoonotic disease caused by the rabies virus invading the central nervous system. When suspected of exposure to the rabies virus, post-exposure... (Review)
Review
Rabies is a highly fatal zoonotic disease caused by the rabies virus invading the central nervous system. When suspected of exposure to the rabies virus, post-exposure prophylaxis should be administered as soon as possible. Monoclonal antibodies (mAbs) neutralizing the rabies virus could be better in human rabies post-exposure prophylaxis than equine or human rabies immune globulin in terms of supply, cost, and efficacy. This article reviews anti-rabies mAbs produced by multiple techniques, and the results of clinical trials for anti-rabies mAbs cocktails recognizing non-overlapping epitopes are also discussed.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antineoplastic Agents, Immunological; Horses; Neutralization Tests; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Rabies virus
PubMed: 35172707
DOI: 10.1080/21645515.2022.2026713 -
Frontiers in Endocrinology 2022With the development of economy, the living standard of people all over the world has been greatly improved, and the incidence of diabetes is also increasing. Many...
BACKGROUND
With the development of economy, the living standard of people all over the world has been greatly improved, and the incidence of diabetes is also increasing. Many people with diabetes also develop other complications that reduce their quality of life. Diabetic nephropathy is a common complication of type2 diabetes. Understanding the related factors of diabetic nephropathy is greatly significant to control the occurrence of diabetic nephropathy and improve patient's life quality.
DATA AND METHODS
Data were collected from 2009 to 2018 in NHANES. Curve fitting graph was performed to investigate the association between globulin (GLB) and diabetic nephropathy(DN). Four logistic regression models were conducted to control the potential confounding factors. Subgroup analysis was carried out to assess the stability of results.
RESULTS
GLB was positively correlated with the occurrence of DN after controlling for potential confounders. Higher GLB was associated with an increased risk of diabetic nephropathy [odds ratio(OR), 1.10; 95% confidence interval (CI), 1.07-1.13, < 0.001].
CONCLUSIONS
In this cross-sectional study, GLB was significant positively correlated with the occurrence of DN in patients with type2 diabetes mellitus.
Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Globulins; Humans; Nutrition Surveys; Quality of Life
PubMed: 35898464
DOI: 10.3389/fendo.2022.890273 -
Cleveland Clinic Journal of Medicine Dec 2021The current American Society of Hematology (ASH) guidelines for the management of patients with immune thrombocytopenic purpura (ITP) are an update to the 2011...
The current American Society of Hematology (ASH) guidelines for the management of patients with immune thrombocytopenic purpura (ITP) are an update to the 2011 guidelines. The updates focus on treating patients with ITP without bleeding in both outpatient and inpatient settings, including those with newly diagnosed, persistent, and chronic ITP refractory to first-line therapy. Recommendations for therapy include corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin-receptor agonists, as well as observation.
Topics: Humans; Immunoglobulins, Intravenous; Purpura, Thrombocytopenic, Idiopathic; Rho(D) Immune Globulin; Rituximab; Splenectomy
PubMed: 34857604
DOI: 10.3949/ccjm.88a.20201 -
Haematologica Jul 2017
Topics: Anemia, Aplastic; Antilymphocyte Serum; Humans; Immunosuppressive Agents
PubMed: 28655810
DOI: 10.3324/haematol.2017.171538 -
Hematology. American Society of... Dec 2016Immune thrombocytopenia (ITP) is a rare, acquired autoimmune condition characterized by a low platelet count and an increased risk of bleeding. Although many children... (Review)
Review
Immune thrombocytopenia (ITP) is a rare, acquired autoimmune condition characterized by a low platelet count and an increased risk of bleeding. Although many children and adults with ITP will not need therapy beyond historic first-line treatments of observation, steroids, intravenous immunoglobulin (IVIG), and anti-D globulin, others will have an indication for second-line treatment. Selecting a second-line therapy depends on the reason for treatment, which can vary from bleeding to implications for health-related quality of life (HRQoL) to likelihood of remission and patient preference with regard to adverse effects, route of administration, and cost. Published studies of these treatments are limited by lack of comparative trials, in addition to inconsistent outcome measures, definitions, and efficacy endpoints. This article provides an up-to-date comparison of the second-line treatments, highlighting important outcome measures including bleeding, HRQoL, fatigue, and platelet counts, which influence treatment selection in a shared decision-making model.
Topics: Adult; Costs and Cost Analysis; Hemorrhage; Humans; Immunoglobulins, Intravenous; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Rho(D) Immune Globulin; Risk Factors
PubMed: 27913549
DOI: 10.1182/asheducation-2016.1.698 -
Plant Biotechnology Journal Apr 2020Gluten-free foods cannot substitute for products made from wheat flour. When wheat products are digested, the remaining peptides can trigger an autoimmune disease in 1%...
Gluten-free foods cannot substitute for products made from wheat flour. When wheat products are digested, the remaining peptides can trigger an autoimmune disease in 1% of the North American and European population, called coeliac disease. Because wheat proteins are encoded by a large gene family, it has been impossible to use conventional breeding to select wheat varieties that are coeliac-safe. However, one can test the properties of protein variants by expressing single genes in coeliac-safe cereals like maize. One source of protein that can be considered as coeliac-safe and has bread-making properties is teff (Eragrostis tef), a grain consumed in Ethiopia. Here, we show that teff α-globulin3 (Etglo3) forms storage vacuoles in maize that are morphologically similar to those of wheat. Using transmission electron microscopy, immunogold labelling shows that Etglo3 is almost exclusively deposited in the storage vacuole as electron-dense aggregates. Of maize seed storage proteins, 27-kDa γ-zein is co-deposited with Etglo3. Etglo3 polymerizes via intermolecular disulphide bonds in maize, similar to wheat HMW glutenins under non-reducing conditions. Crossing maize Etglo3 transgenic lines with α-, β- and γ-zein RNA interference (RNAi) lines reveals that Etglo3 accumulation is only dramatically reduced in γ-zein RNAi background. This suggests that Etglo3 and 27-kDa γ-zein together cause storage vacuole formation and behave similar to the interactions of glutenins and gliadins in wheat. Therefore, expression of teff α-globulins in maize presents a major step in the development of a coeliac-safe grain with bread-making properties.
Topics: Alpha-Globulins; Bread; Eragrostis; Flour; Glutens; Plants, Genetically Modified; Seed Storage Proteins; Triticum; Zea mays
PubMed: 31585498
DOI: 10.1111/pbi.13273 -
Frontiers in Public Health 2023Cognitive impairment is on the rise around the world, with profound economic and social consequences. Serum globulin, a marker of liver function, may also play a role in...
BACKGROUND AND AIMS
Cognitive impairment is on the rise around the world, with profound economic and social consequences. Serum globulin, a marker of liver function, may also play a role in cognitive function. Unfortunately, no consistent conclusion exists regarding the association between serum globulin and cognitive function.
METHODS
Data from the 2011 to 2014 National Health and Nutrition Examination Survey were used to assess the association between serum globulin and cognitive impairment. Cognitive function was assessed by three tests: Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency (AF), and Digit Symbol Substitution Test (DSST). Furthermore, the breakthrough point of cognitive impairment correlated with CERAD < 5, AF < 14, and DSST < 34. A weighted multiple logistics regression model was used to verify the association between serum globulin and cognitive impairment. Generalized additive models (GAMs) and a smooth curve fit (penalty spline method) were used to determine a non-linear relationship between serum globulin and cognitive impairment. Finally, subgroup analysis and interaction tests were conducted to further verify the association between serum globulin and cognitive impairment.
RESULTS
Data from 2,768 participants aged ≥60 (in accordance with the study design) were collected for the final analysis. Data suggested that serum globulin levels were associated with an elevated cognitive impairment based on the AF [full adjustment, OR = 1.05, 95% 1.01-1.08] and DSST [full adjustment, OR = 1.06, 95% 1.02-1.10] tests. Eventually, the GAM and smooth curve fit model was conducted to confirm that the association between serum globulin and cognitive impairment was non-linear. Moreover, the inflection point was 27 g/L serum globulin based on the CERAD test and 35 g/L serum globulin based on the AF test. Finally, the interaction term between serum globulin and cognitive impairment based on the AF test indicated no significant interactions among all variables (all for interaction >0.05).
CONCLUSION
The association between serum globulin levels and cognitive impairment is non-linear. A threshold effect exists between serum globulin and cognitive impairment. Large-scale prospective clinical trials are needed to validate our findings.
Topics: Animals; Nutrition Surveys; Prospective Studies; Serum Globulins; Cognitive Dysfunction; Cognition; Alzheimer Disease
PubMed: 37670828
DOI: 10.3389/fpubh.2023.1193993 -
Journal of Orthopaedic Surgery and... Jan 2022Periprosthetic joint infection (PJI) is one of the most challenging complications of total joint arthroplasty (TJI). An early and accurate diagnosis of PJI is associated...
BACKGROUND
Periprosthetic joint infection (PJI) is one of the most challenging complications of total joint arthroplasty (TJI). An early and accurate diagnosis of PJI is associated with better treatment outcomes. However, whether the platelet-related markers and globulin-related markers can be used to assist the diagnosis of PJI remains elusive.
METHODS
A total of 206 patients who underwent revision hip or knee arthroplasty in our institution were divided into two groups: 79 patients in PJI group and 127 patients in aseptic failure group. The levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet-related markers including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT) and PLT to MPV ratio (PMR) and globulin-related markers such as globulin (GLB), albumin to globulin ratio (AGR) and PLT to AGR ratio were compared. The diagnostic value was measured using area under the curve (AUC) after constructing receiver operating characteristic (ROC) curves. The potential of each marker for determining the timing of second-staged reimplantation was also evaluated.
RESULTS
Significantly increased levels of ESR, CRP, PLT, PCT, PMR, GLB and PLT to AGR ratio were identified in PJI group, while decreased levels of MPV and AGR were also found. The diagnostic values of all platelet-related markers and GLB were considered as fair, and good diagnostic values of AGR and PLT to AGR ratio were found, which were comparable to those of ESR and CRP. The levels of GLB and AGR can also be used to predict negative culture result and the timing of second-stage reimplantation.
CONCLUSIONS
Globulin and albumin to globulin ratio were found to have good diagnostic values for PJI, and they can precisely predict the culture results and persistent infection.
Topics: Aged; Aged, 80 and over; Albumins; Arthritis, Infectious; Arthroplasty, Replacement, Hip; Biomarkers; Blood Sedimentation; C-Reactive Protein; Female; Globulins; Humans; Male; Middle Aged; Persistent Infection; Prosthesis-Related Infections; Replantation; Retrospective Studies; Sensitivity and Specificity; Serum Albumin; Serum Globulins
PubMed: 34991649
DOI: 10.1186/s13018-021-02899-0 -
Drug Design, Development and Therapy 2016Aplastic anemia (AA) is a potential life-threatening hematopoietic stem cell (HSC) disorder resulting in cytopenia. The mainstays of treatment for AA are definitive... (Review)
Review
Aplastic anemia (AA) is a potential life-threatening hematopoietic stem cell (HSC) disorder resulting in cytopenia. The mainstays of treatment for AA are definitive therapy to restore HSCs and supportive measures to ameliorate cytopenia-related complications. The standard definitive therapy is HSC transplantation for young and medically fit patients with suitable donors and immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine for the remaining patients. A significant proportion of patients are refractory to IST or relapse after IST. Various strategies have been explored in these patients, including second course of antithymocyte globulin, high-dose cyclophosphamide, and alemtuzumab. Eltrombopag, a thrombopoietin mimetic, has recently emerged as an encouraging and promising agent for patients with refractory AA. It has demonstrated efficacy in restoring trilineage hematopoiesis, and this positive effect continues after discontinuation of the drug. There are ongoing clinical trials exploring the role of eltrombopag as a first-line therapy in moderate to severe AA and a combination of eltrombopag with IST in severe AA.
Topics: Alemtuzumab; Anemia, Aplastic; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Benzoates; Cyclophosphamide; Cyclosporine; Hematopoietic Stem Cells; Humans; Hydrazines; Immunosuppressive Agents; Pyrazoles
PubMed: 27695288
DOI: 10.2147/DDDT.S95715