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The Western Journal of Medicine Jul 1981Platelets may be useful as markers of thromboembolic disease. When labeled with indium 111 they allow external imaging of localized clots. Indium 111 is much superior to... (Review)
Review
Platelets may be useful as markers of thromboembolic disease. When labeled with indium 111 they allow external imaging of localized clots. Indium 111 is much superior to chromium 51 for this procedure. Detection of circulating platelet aggregates also appears to be a simple means of determining the presence of thromboembolic disorders. In response to injury or involvement in clotting, platelets release several unique proteins not normally found in the plasma. Therefore, elevated levels of these proteins suggest the presence of such damage. Platelet factor 4 and beta-thromboglobulin are the most widely studied of these proteins, and both can be quantitated by radioimmunoassay. Such assays are now commercially available. Elevated levels have been demonstrated in such diverse disorders as deep venous thrombosis, atherosclerosis and diabetes. However, blood must be drawn with great care to avoid in vitro damage to platelets and false elevation of these markers. All of these procedures are promising at present, but their precise role and value await further study.
Topics: Beta-Globulins; Blood Coagulation Factors; Humans; Platelet Aggregation; Platelet Factor 4; Radioimmunoassay; Thromboembolism; beta-Thromboglobulin
PubMed: 6167074
DOI: No ID Found -
Experimental Biology and Medicine... May 2023Intravascular hemolysis results in the release of cell-free hemoglobin and heme in plasma. In sickle cell disease, the fragility of the sickle red blood cell leads to...
Intravascular hemolysis results in the release of cell-free hemoglobin and heme in plasma. In sickle cell disease, the fragility of the sickle red blood cell leads to chronic hemolysis, which can contribute to oxidative damage and activation of inflammatory pathways. The scavenger proteins haptoglobin and hemopexin provide pathways to remove hemoglobin and heme, respectively, from the circulation. Heme also intercalates in membranes of blood cells and endothelial cells in the vasculature and associates with other plasma components such as albumin and lipoproteins. Hemopexin has a much higher affinity and can strip heme from the other pools and detoxify plasma from cell-free circulatory heme. However, due to chronic hemolysis, hemopexin is depleted in individuals with sickle cell disease. Thus, cell-free unbound heme is expected to accumulate in plasma. We developed a methodology for the accurate quantification of the fraction of heme, which is pathologically relevant in sickle cell disease, that does not appear to be sequestered to a plasma compartment. Our data show significant variation in the concentration of unbound heme, and rather unexpectedly, the size of the unbound fraction does not correlate to the degree of hemolysis, as measured by the concentration of bound heme. Very high heme concentrations (>150 µM) were obtained in some plasma with unbound concentrations that were several fold lower than in plasma with much lower hemolysis (<50 µM). These findings underscore the long-term effects of chronic hemolysis on the blood components and of the disruption of the essential equilibrium between release of hemoproteins/heme in the circulation and adaptative response of the scavenging/removal mechanisms. Understanding the clinical implications of this loss of response may provide insights into diagnostic and therapeutic targets in patients with sickle cell disease.
Topics: Humans; Heme; Hemolysis; Hemopexin; Endothelial Cells; Anemia, Sickle Cell; Hemoglobins
PubMed: 36941786
DOI: 10.1177/15353702231157920 -
Frontiers in Public Health 2022It is still unknown whether the dietary inflammatory index (DII) is associated with sex hormones and sex hormone binding globulin (SHBG) in adult women.
CONTEXT
It is still unknown whether the dietary inflammatory index (DII) is associated with sex hormones and sex hormone binding globulin (SHBG) in adult women.
OBJECTIVE
This study examined the association between DII and sex hormones and SHBG in U.S. adult women.
DESIGN AND PARTICIPANTS
This was a cross-sectional study. A total of 2,092 female participants (age ≥ 20) from the 2013-2016 National Health and Nutrition Examination Survey were enrolled. Dietary inflammatory potential was assessed by DII based on 24-h dietary recall. SHBG was assessed using immuno-antibodies and chemo-luminescence, whereas sex hormones were measured by ID-LC-MS/MS.
RESULTS
The average DII was 0.21 ± 1.68, ranging from -4.54 (most anti-inflammatory) to 4.28 (most pro-inflammatory). After adjusting all covariates, a per-unit DII increase in DII tertile 3 was related to an 8.05 nmol/L SHBG decrease compared to DII tertile 1 ( = 0.0366). Subgroup analysis stratified by perimenopausal period found that this negative association remained strong but only existed in women before (β = -3.71, 95% CI: -7.43, -0.12, = 0.0423) the perimenopausal period. Interaction terms were added to both subgroup analyses and found no significant heterogeneity among different body mass index (BMI) or perimenopausal groups ( > 0.05). Treshold analyses showed that the association of age with SHBG was an inverted -shaped curve (inflection point: age = 50 yrs).
CONCLUSION
A proinflammatory diet caused decreased SHBG. However, more well-designed studies are still needed to validate and verify the causal relationship between DII and sex hormones and SHBG.
Topics: Adult; Chromatography, Liquid; Cross-Sectional Studies; Diet; Female; Gonadal Steroid Hormones; Humans; Middle Aged; Nutrition Surveys; Sex Hormone-Binding Globulin; Tandem Mass Spectrometry
PubMed: 35493382
DOI: 10.3389/fpubh.2022.802945 -
Chinese Medical Journal Sep 2022The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a...
BACKGROUND
The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population.
METHODS
A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR <60 mL·min -1 ·1.73 m -2 .
RESULTS
After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, β -2.53, 95% confidence interval -3.89, -1.17, Ptrend < 0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference <90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no).
CONCLUSIONS
Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.
Topics: Humans; Male; Middle Aged; China; Kidney; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Tomography, Emission-Computed, Single-Photon; Glomerular Filtration Rate
PubMed: 35170516
DOI: 10.1097/CM9.0000000000002046 -
Blood Feb 1981Measurement of plasma levels of two secreted platelet proteins (beta-thromboglobulin and platelet factor 4) has been suggested as a means for detecting increased... (Review)
Review
Measurement of plasma levels of two secreted platelet proteins (beta-thromboglobulin and platelet factor 4) has been suggested as a means for detecting increased platelet activation in vivo. A crucial question in the measurement is the distinction between in vivo and in vitro secretion of the proteins. One approach to this distinction is the measurement of both proteins in each sample. These proteins are present in platelets in similar amounts and are released in similar quantities, but the plasma levels of beta-thromboglobulin exceed the plasma levels of platelet factor 4. This difference in plasma level is presumably due to more rapid removal of platelet factor 4 from the plasma level, and there is suggestive evidence that the rapid removal of released platelet factor 4 is due to its binding to endothelial cells. It appears that when there is increased release of beta-thromboglobulin and platelet factor 4 in vivo, there is an increase in the ratio of plasma beta-thromboglobulin to plasma platelet factor 4 compared to that found in normal individuals, whereas when in vitro release is responsible for elevated levels, the ratio decreases. Thus measurements of both proteins in each blood sample will allow distinction between in vivo release and artefactual in vitro release.
Topics: Arteriosclerosis; Beta-Globulins; Blood Coagulation Factors; Blood Platelets; Evaluation Studies as Topic; Humans; Platelet Aggregation; Platelet Factor 4; Radioimmunoassay; Reference Values; Thrombosis; beta-Thromboglobulin
PubMed: 6160890
DOI: No ID Found -
Molecular Autism Aug 2023Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk....
BACKGROUND
Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism.
OBJECTIVE
This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure.
STUDY DESIGN
Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure.
RESULTS
Increased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01-1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04-1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55-0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure.
LIMITATIONS
The relative racial and ethnic homogeneity of Utah's population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power.
CONCLUSION
Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.
Topics: Male; Female; Pregnancy; Humans; Pregnancy Trimester, Second; Sex Hormone-Binding Globulin; Autistic Disorder; Estradiol; Testosterone; Biomarkers
PubMed: 37573326
DOI: 10.1186/s13229-023-00562-5 -
Clinical and Experimental Immunology Feb 1971Rabbit antisera to human tracheal mucosa, liver and gastric mucosa, after complete absorption with human serum, reacted with extracts of all human tissues tested. Monkey...
Rabbit antisera to human tracheal mucosa, liver and gastric mucosa, after complete absorption with human serum, reacted with extracts of all human tissues tested. Monkey tissue extracts also reacted, but tissues of other species did not. The reactions were attributed to `species-specific tissue antigens'. Two of the most prominent antigens were partially isolated and characterized by chromatography, gel filtration, and electrophoresis. Antigen I migrated as β-globulin, Antigen E as a β-globulin. The antigens persisted in malignant and in long-term cultured cells.
Topics: Absorption; Animals; Antigens; Ascitic Fluid; Beta-Globulins; Cattle; Chromatography; Chromatography, DEAE-Cellulose; Chromatography, Gel; Cross Reactions; Culture Techniques; Epitopes; Gastric Mucosa; Haplorhini; Hemagglutination Inhibition Tests; Horses; Humans; Immunodiffusion; Immunoelectrophoresis; Liver; Neoplasms; Plasma; Rabbits; Sheep; Species Specificity; Swine; Trachea
PubMed: 4102258
DOI: No ID Found -
Journal of Endocrinological... Jun 2022De novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained...
Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a.
PURPOSE
De novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained uncertain. We, therefore, studied individuals with glycogen storage disease type 1a (GSD1a), who are characterized by a genetic defect in glucose-6-phosphatase resulting in increased rates of de novo lipogenesis, to assess the downstream effect on serum SHBG levels.
METHODS
A case-control study comparing serum SHBG levels in patients with GSD1a (n = 10) and controls matched for age, sex, and BMI (n = 10). Intrahepatic lipid content and saturated fatty acid fraction were quantified by proton magnetic resonance spectroscopy.
RESULTS
Serum SHBG levels were statistically significantly lower in patients with GSD1a compared to the controls (p = 0.041), while intrahepatic lipid content and intrahepatic saturated fatty acid fraction-a marker of de novo lipogenesis-were significantly higher in patients with GSD1a (p = 0.001 and p = 0.019, respectively). In addition, there was a statistically significant, inverse association of intrahepatic lipid content and saturated fatty acid fraction with serum SHBG levels in patients and controls combined (β: - 0.28, 95% CI: - 0.47;- 0.09 and β: - 0.02, 95% CI: - 0.04;- 0.01, respectively).
CONCLUSION
Patients with GSD1a, who are characterized by genetically determined higher rates of de novo lipogenesis, have lower serum SHBG levels than controls.
Topics: Adult; Case-Control Studies; Fatty Acids; Glycogen Storage Disease Type I; Humans; Sex Hormone-Binding Globulin
PubMed: 35132570
DOI: 10.1007/s40618-022-01753-2 -
Frontiers in Endocrinology 2023Type 2 diabetes mellitus (T2DM) is an endocrine-related disease with an increasing incidence worldwide. Male sexual dysfunction is common in diabetic patients....
OBJECTIVE
Type 2 diabetes mellitus (T2DM) is an endocrine-related disease with an increasing incidence worldwide. Male sexual dysfunction is common in diabetic patients. Therefore, we designed a Mendelian randomization (MR) study to investigate the association of type 2 diabetes and 3 glycemic traits with testosterone levels.
METHODS
Uncorrelated single nucleotide polymorphisms (SNPs) associated with T2DM (N = 228), fasting insulin (N = 38), fasting glucose (N = 71), and HbA1c (N = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with testosterone levels (total testosterone, TT, bioavailable testosterone, BT, and sex hormone-binding globulin, SHBG) were obtained from the UK Biobank studies and other large consortia. Two-sample MR analysis was used to minimize the bias caused by confounding factors and response causality. Multivariable MR analysis was performed using Body mass index (BMI), Triglycerides (TG), LDL cholesterol (LDL), and adiponectin to adjust for the effects of potential confounders.
RESULTS
Type 2 diabetes mellitus was associated with the decrease of total testosterone (β: -0.021,95%CI: -0.032, -0.010, p<0.001) and sex hormone binding globulin (β: -0.048,95%CI: -0.065, -0.031, p<0.001). In males, total testosterone (β: 0.058, 95% CI: 0.088, 0.028, p < 0.001) decreased. In females, it was associated with an increase in bioavailable testosterone (β: 0.077,95%CI: 0.058,0.096, p<0.001). Each unit (pmol/L) increase in fasting insulin was associated with 0.283nmol/L decrease in sex hormone-binding globulin (95%CI: -0.464, -0.102, p=0.002) and 0.260nmol/L increase in bioavailable testosterone (95%CI: -0.464, -0.102, p= 0.002). In males, sex hormone binding globulin decreased by 0.507nmol/L (95%CI: -0.960, -0.054, p= 0.028) and bioavailable testosterone increased by 0.216nmol/L (95%CI: 0.087,0.344, p= 0.001). In females, sex hormone binding globulin decreased by 0.714 nmol/L (95%CI: -1.093, -0.335, p<0.001) and bioavailable testosterone increased by 0.467nmol/L (95%CI: 0.286,0.648, p<0.001). Each unit (%) increase in HbA1c was associated with 0.060nmol/L decrease in sex hormone-binding globulin (95%CI: -0.113, -0.007, p= 0.026). In males, total testosterone decreased by 0.171nmol/L (95%CI: -0.288, -0.053, p=0.005) and sex hormone binding globulin decreased by 0.206nmol/L (95%CI: -0.340, -0.072, p=0.003). Total testosterone increased by 0.122nmol/L (95%CI: 0.012,0.233, p=0.029) and bioavailable testosterone increased by 0.163nmol/L (95%CI: 0.042,0.285, p=0.008) in females.
CONCLUSIONS
Using MR Analysis, we found independent effects of type 2 diabetes, fasting insulin, and HbA1c on total testosterone and sex hormone-binding globulin after maximum exclusion of the effects of obesity, BMI, TG, LDL and Adiponectin.
Topics: Female; Humans; Male; Diabetes Mellitus, Type 2; Sex Hormone-Binding Globulin; Glycated Hemoglobin; Adiponectin; Mendelian Randomization Analysis; Testosterone; Insulin; Triglycerides
PubMed: 37900148
DOI: 10.3389/fendo.2023.1238090 -
Clinical Endocrinology Nov 2022The role of the anti-Müllerian hormone (AMH) as an indicator of physical and reproductive health in men is unclear. We assessed the relationships between AMH and...
OBJECTIVE
The role of the anti-Müllerian hormone (AMH) as an indicator of physical and reproductive health in men is unclear. We assessed the relationships between AMH and follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and metabolic parameters, in a cohort of expectant fathers.
DESIGN
ORIGINS Project prospective cohort study.
SETTING
Community-dwelling men.
PARTICIPANTS
Partners of pregnant women attending antenatal appointments.
MAIN OUTCOME MEASURES
Serum AMH, FSH, LH, testosterone, and metabolic parameters.
RESULTS
In 485 expectant fathers, median age 33 years, median AMH was 40 pmol/L (quartiles 29, 56). AMH was inversely correlated with FSH, age, and body mass index (BMI) (correlation coefficients: -.32, -.24, and -.17 respectively). The age association was nonlinear, with peak AMH between 20 and 30 years, a decline thereafter, and somewhat steady levels after 45 years. The inverse association of AMH with FSH was log-linear and independent of age and BMI (β: -.07, SE: 0.01, p < .001). AMH was inversely correlated with waist circumference and directly associated with sex hormone-binding globulin. Testosterone was moderately correlated with AMH (correlation coefficient: .09, β: .011, SE: 0.004, p = .014): this association was mediated by an inverse relationship with BMI (mediated proportion 0.49, p < .001).
CONCLUSIONS
In reproductively active men, lower AMH is a biomarker for advancing age, and for poorer metabolic and reproductive health. The inverse association between AMH and FSH is independent of age and BMI, whereas the association of AMH and testosterone is mediated via BMI. The utility of AMH to predict reproductive and cardiometabolic outcomes in men warrants further investigation.
Topics: Adiposity; Adult; Anti-Mullerian Hormone; Biomarkers; Fathers; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Obesity; Obesity, Abdominal; Pregnancy; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Young Adult
PubMed: 35319116
DOI: 10.1111/cen.14725