Abstract 53: Measurement of Peripheral Blood 18-Oxocortisol as the Diagnostic Method of Primary Aldosteronism and Its Subtypes

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Fumitoshi Satoh ◽  
Ryo Morimoto ◽  
Masataka Kudo ◽  
Yoshitsugu Iwakura ◽  
Yoshikiyo Ono ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Peripheral Blood ◽  
Roc Analysis ◽  
Maximum Level ◽  
Immunohistochemical Analysis ◽  
Diagnostic Tools ◽  
Expert Radiologist ◽  
Aldosterone Producing Adenoma ◽  
Higher Sensitivity

Backgrounds: Primary aldosteronism (PA) is diagnosed and treated by the long steps, such as screening, confirmation testing and subtype diagnosis (computed tomography (CT) scan and adrenal venous sampling (AVS)). AVS has been the only reliable subtype classification method between surgically curable unilateral aldosterone producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (BHA). In spite of increased numbers of specialized centers with superior ability of AVS in the world, unfortunately, this test is costly and requires a dedicated and expert radiologist; therefore it is not generally utilizable in most hospitals. It is understandable that easier diagnostic tools to be substitutes for AVS might be hoped by clinicians. Objective: The aim of the study was to determine the role of peripheral plasma levels of 18-oxo-cortisol (p18oxoF) and 18-hydroxycortisol (p18OHF) in differentiate APA from BHA. Patients: The study included 265 PA patients (113 patients with CT-positive macro APA, 31 patients with CT-negative micro APA and 121 patients with BHA) and 79 patients with essential hypertension (EH). Methods: All of 265 PA patients underwent AVS successfully, and any case with APA was surgically proven and pathologically confirmed including immunohistochemical analysis of steroidogenic enzymes. We measured p18oxoF and p18OHF of all PA patients by high sensitive LC ms/ms. Results: APA patients showed significantly higher p18oxoF and p18OHF than those of BHA patients and EH patients. The ROC analysis of p18oxoF in macro APA versus BHA demonstrated clinically useful discrimination with higher sensitivity of 0.83 and higher specificity of 0.99 by cutoff value of 4.7 (ng/dl), compared to the classification by p18OHF. Practically, 86 (76%) of macro APA patients with p18oxoF above 6.1 (ng/dl), which was the maximum level in BHA patients, might have been able to undergo surgery without AVS. Because the maximum p18oxoF in EH patients was 5.6 (ng/dl), the patients with p18oxoF above 6.1 (ng/dl) after screening of PA could also undergo surgery if unilateral adenoma(s) can be found on CT; thus it means omitting confirmation tests. Conclusions: Peripheral blood 18oxoF measurement can be a clinically useful method for the diagnosis of PA and its subtypes.

Study on clinical and endocrine characteristics of dexamethasone-suppressible hyperaldosteronism compared with those in primary aldosteronism owing to aldosterone-producing adenoma

1989 ◽  
Vol 121 (3) ◽  
pp. 334-344 ◽  
Author(s):  
Noriyoshi Yamakita ◽  
Keigo Yasuda ◽  
Nobuyasu Noritake ◽  
Leilani B. Mercado-Asis ◽  
Hiroshi Murase ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Blood Pressure Response ◽  
Laboratory Data ◽  
Japanese Patients ◽  
Pressure Response ◽  
Plasma Aldosterone ◽  
Vascular Damage ◽  
Aldosterone Producing Adenoma

Abstract. The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasonesuppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.

scholarly journals Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism

2020 ◽  
Vol 52 (06) ◽  
pp. 379-385
Author(s):  
Lucie S. Meyer ◽  
Siyuan Gong ◽  
Martin Reincke ◽  
Tracy Ann Williams
Keyword(s):  
Angiotensin Ii ◽  
Primary Aldosteronism ◽  
Functional Role ◽  
Adrenal Hyperplasia ◽  
Endocrine Hypertension ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma ◽  
Agonistic Autoantibodies

AbstractPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.

scholarly journals Clostridium difficile glutamate dehydrogenase is a secreted enzyme that confers resistance to H2O2

Microbiology ◽  
2014 ◽  
Vol 160 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Brintha Prasummanna Girinathan ◽  
Sterling E. Braun ◽  
Revathi Govind
Keyword(s):  
Clostridium Difficile ◽  
Glutamate Dehydrogenase ◽  
Parent Strain ◽  
Diagnostic Tools ◽  
Growth Defect ◽  
Irreversible Reaction ◽  
Yeast Extract Medium ◽  
Stool Samples ◽  
Higher Sensitivity

Clostridium difficile produces an NAD-specific glutamate dehydrogenase (GDH), which converts l-glutamate into α-ketoglutarate through an irreversible reaction. The enzyme GDH is detected in the stool samples of patients with C. difficile‐associated disease and serves as one of the diagnostic tools to detect C. difficile infection (CDI). We demonstrate here that supernatant fluids of C. difficile cultures contain GDH. To understand the role of GDH in the physiology of C. difficile, an isogenic insertional mutant of gluD was created in strain JIR8094. The mutant failed to produce and secrete GDH as shown by Western blot analysis. Various phenotypic assays were performed to understand the importance of GDH in C. difficile physiology. In TY (tryptose yeast extract) medium, the gluD mutant grew slower than the parent strain. Complementation of the gluD mutant with the functional gluD gene reversed the growth defect in TY medium. The presence of extracellular GDH may have a functional role in the pathogenesis of CDI. In support of this assumption we found higher sensitivity to H2O2 in the gluD mutant as compared to the parent strain. Complementation of the gluD mutant with the functional gluD gene reversed the H2O2 sensitivity.

scholarly journals The Role of ICOSL Antibody Intervention in Mouse Model of Neutrophil Asthma

2020 ◽  
Author(s):  
Heting DONG ◽  
Yinying Ren ◽  
Yongdong Yan ◽  
Li Huang ◽  
Meijuan Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Peripheral Blood ◽  
Periodic Acid ◽  
Immunohistochemical Analysis ◽  
Lavage Fluid ◽  
Periodic Acid Schiff ◽  
Pulmonary Tissue ◽  
Inflammatory Infiltration ◽  
Group I

Abstract Background: To investigate the role of ICOSL (Inducible costimulatory molecular ligands) antibody in the mouse model of neutrophilic asthma, and to explore the role of ICOSL in the pathogenesis of Th1/Th2/Th17 imbalance. Methods: 24 Balb/c mice were randomly divided into four groups: C group, N group, my group and G group. The peripheral blood, BALF and lung tissue were collected within 24 hours after the last challenge. Total count and classification of BALF (bronchoalveolar lavage fluid) cells; Detection cytokines of peripheral blood and BALF. Pulmonary tissue section for pathological observation. Results: During seven stimulations,asthma performance in group N was the earliest and obvious and was improved in group I,there was no asthma behavior in group C.The total number of BALF in N group was the highest, in C group was the lowest,(P<0.05).The concentrations of IL-6, IL-13 and IL-17 in peripheral blood and BALF of N group were the highest,(P<0.05).The IFN-γ concentration of C group was higher than that of N and G groups,(P<0.05).HE(hematoxylin-eosin) and PAS(periodic acid-schiff) staining showed that inflammatory infiltration in I group was relative improved than N and G groups.ICOSL immunohistochemical analysis,ICOSL positive cells of alveolar interstitial and airway of N and G groups were more than I group,(P<0.05). Conclusions: After the intervention of ICOSL antibody,the performance of asthma relieved,and airway inflammatory cell infiltration, mucus secretion were reduced.The levels of IL-6, IL-13 and IL-17 in peripheral blood and BALF were partly decreased, and the level of IFN-γwas increased;These results suggest that blocking the ICOS/ICOSL signaling pathway may partially block the development of neutrophilc asthma and provide a new target for the treatment of asthma.

The Local Sanarelli-Shwartzman Phenomenon in Rats Induced by Human Leukaemic Cells

1973 ◽  
Vol 29 (02) ◽  
pp. 353-362
Author(s):  
J Lisiewicz ◽  
A Pituch ◽  
J. A Litwin
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Intravenous Injection ◽  
Peripheral Blood ◽  
Lymphocytic Leukaemia ◽  
Acute Myeloblastic Leukaemia ◽  
Demarcation Line ◽  
E Coli ◽  
Leukaemic Cells ◽  
Shwartzman Phenomenon

SummaryThe local Sanarelli-Shwartzman phenomenon (SSP-L) in the skin of 30 rats was induced by an intr a cutaneous sensitizing injection of leukaemic leucocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL), acute myeloblastic leukaemia (AL) and chronic granulocytic leukaemia (CGL) and challenged by an intravenous injection of 100(μ of E. coli endotoxin. SSP-L was observed in 7 rats after injection of CLL lymphocytes and in 6 and 2 rats after AL myeloblasts and the CGL granulocytes, respectively. The lesions in the skin after AL myeloblasts appeared in a shorter time and were of longer duration compared with those observed after CLL lymphocytes and CGL granulocytes. Histologically, the lesions consisted of areas of destruction in the superficial layers of the skin ; the demarcation line showed the presence of neutrophils, macrophages and erythrocytes. Haemorrhages and fibrin deposits near the demarcation line were larger after injection of CLL lymphocytes and AL myeloblasts than after CGL granulocytes. The possible role of leucocyte procoagulative substances in the differences observed have been discussed.

STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

2020 ◽  
Vol 66 (1) ◽  
pp. 71-78
Author(s):  
Lev Bershteyn ◽  
Aleksandr Ivantsov ◽  
Aglaya Ievleva ◽  
A. Venina ◽  
I. Berlev
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Tumor Tissue ◽  
Immunohistochemical Analysis ◽  
The Body ◽  
Molecular Profile ◽  
Total N ◽  
Number Of Patients ◽  
Her 2

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

Endothelial and Circulating Progenitor Cells in Hematological Diseases and Allogeneic Hematopoietic Stem Cell Transplantation

2018 ◽  
Vol 25 (35) ◽  
pp. 4535-4544 ◽  
Author(s):  
Annalisa Ruggeri ◽  
Annalisa Paviglianiti ◽  
Fernanda Volt ◽  
Chantal Kenzey ◽  
Hanadi Rafii ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Circulating Endothelial Cells ◽  
Hematopoietic Stem ◽  
Hematological Diseases

Background: Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells not associated with vessel walls and detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and other diseases. Objective: This review aims to provide an overview on the characterization of CECs and EPCs, to describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Methods: We performed a detailed search of peer-reviewed literature using keywords related to CECs, EPCs, allogeneic hematopoietic stem cell transplantation, and hematological diseases (hemoglobinopathies, hodgkin and non-hodgkin lymphoma, acute leukemia, myeloproliferative syndromes, chronic lymphocytic leukemia). Results: CECs and EPCs are potential biomarkers for several clinical conditions involving endothelial turnover and remodeling, such as in hematological diseases. These cells may be involved in disease progression and in the neoplastic process. Moreover, CECs and EPCs are probably involved in endothelial damage which is a marker of several complications following allogeneic hematopoietic stem cell transplantation. Conclusion: This review provides information about the role of CECs and EPCs in hematological malignancies and shows their implication in predicting disease activity as well as improving HSCT outcomes.

scholarly journals Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

Reproduction ◽  
2013 ◽  
Vol 146 (2) ◽  
pp. 119-133 ◽  
Author(s):  
Barbara Ambruosi ◽  
Gianluca Accogli ◽  
Cécile Douet ◽  
Sylvie Canepa ◽  
Géraldine Pascal ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Western Blot ◽  
Immunohistochemical Analysis ◽  
Fertilization Rate ◽  
Malignant Brain Tumor ◽  
Estrus Cycle ◽  
Immunofluorescence Analysis ◽  
Oviductal Fluid ◽  
Porcine Spermatozoa

Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and subsequent embryonic development. The aim of this study was to evaluate the effect of oviductal fluid and the possible involvement of deleted in malignant brain tumor 1 (DMBT1) on IVF in porcine and equine species that represent divergent IVF models. We first performed IVF after pre-incubation of oocytes with or without oviductal fluid supplemented or not with antibodies directed against DMBT1. We showed that oviductal fluid induces an increase in the monospermic fertilization rate and that this effect is canceled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase in the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization process. The presence of DMBT1 in the oviduct at different stages of the estrus cycle was shown by western blot and confirmed by immunohistochemical analysis of ampulla and isthmus regions. The presence of DMBT1 in cumulus–oocyte complexes was shown by western blot analysis, and the localization of DMBT1 in the zona pellucida and cytoplasm of equine and porcine oocytes was observed using immunofluorescence analysis and confocal microscopy. Moreover, we showed an interaction between DMBT1 and porcine spermatozoa using surface plasmon resonance studies. Finally, a bioinformatic and phylogenetic analysis allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.

scholarly journals Millimeter (MM) wave and microwave frequency radiation produce deeply penetrating effects: the biology and the physics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall
Keyword(s):  
Magnetic Fields ◽  
Electric Fields ◽  
Cardiac Activity ◽  
Maximum Level ◽  
Voltage Sensor ◽  
The Body ◽  
Time Varying ◽  
The Brain ◽  
Mm Waves

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.

scholarly journals Lower peripheral blood Toll-like receptor 3 expression is associated with an unfavorable outcome in severe COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Clara Saad Menezes ◽  
Alicia Dudy Müller Veiga ◽  
Thais Martins de Lima ◽  
Suely Kunimi Kubo Ariga ◽  
Hermes Vieira Barbeiro ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Peripheral Blood ◽  
World Health ◽  
Control Group ◽  
Pyrin Domain ◽  
Peripheral Blood Gene Expression ◽  
Severe Group ◽  
Health Organization ◽  
The Impact

AbstractThe role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1β (pro-IL-1β), and IL-18 was determined on admission, between 5–9 days, and between 10–15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.

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