Insulin receptor (IR) expression in human trophoblasts of recurrent pregnancy loss (RPL)

Purpose: Insulin and glucose pathways play a key role to fetal viability and growth. The focus of the study is to investigate the potential differences of immunohistochemical expression of IR in trophoblastic and decidual cells between women who had recurrent pregnancy loss and women that underwent an abortion. Materials and methods: Trophoblastic and decidual tissues from fifty (50) women with elective abortion used as control group and from fifty (50) women with recurrent miscarriages were collected during gestational weeks 6 to 12. IR antibodies were used as immunohistochemical staining markers. Nuclear and cytoplasmic expression was evaluated. Results: No IR immunohistochemical expression was detected in both trophoblastic cells of the implantation site and deciduas basalis of the two study groups. Conclusion: The effort made to enhance our knowledge on the physiology and histology of IR expression in connection with pregnancy was halted because the results were inconclusive. While studying, though, the correlation of recurrent miscarriage with IR expression, it became evident that a lot of hormones and pathways form the weave of gestational pathology and its delicate harmony. Every piece of knowledge may clarify this still obscure field

Multiple Sclerosis and MEN2 Neoplasia in a Female Patient: A Unique Co-Existence with Expanded Immunological Interest and Therapeutical Challenges, before and after Patient’s COVID-19 Infection

Multiple sclerosis (MS) and its various comorbidities that may be observed are of great interest due to the complexity of MS pathophysiology and all of the immunological changes that follow. The incidence of cancer in MS has been investigated for several years, as not only does it affect ongoing therapeutical decisions, but also, certain disease-modifying treatments (DMTs) may increase the risk of tumorigenesis. For the first time, we present a case of a female patient with pediatric-onset MS (POMS) and multiple endocrine neoplasia 2B (MEN2B) and analyze the immunological impact of these diseases on the therapeutical choice, under the umbrella of her COVID-19 infection and the SARS-CoV-2 pandemic as a whole. We also review the existing literature regarding the immunogenetic and immunological correlations between these two extremely rare diseases and discuss the most suitable treatment for our case, which seems to be an anti-CD20 agent due to a better outcome in putative MS worsening and tumor progression, when killer immunoglobulin-like receptors’ (KIR) expression is reduced in natural killer (NK) cells. We also broaden our concerns on this comorbidity issue, at the same time focusing on the future research needed in this unexplored field of the comorbidity of MS and cancers

Immunohistochemical study of immunological markers: HLAG, CD16, CD25, CD56 and CD68 in placenta tissues in recurrent pregnancy loss

Introduction: Recurrent pregnancy loss (RPL) of unknown etiology is correlated with immunological alterations during pregnancy. Normally, changes in leukocyte subpopulations and HLA expression take place in pregnant uterus in order to tolerate the semi-allogenic embryo. Objective: Our research tries to enlighten the immunological changes that take place in the uterus of women with recurrent abortions of unknown etiology during first trimester of pregnancy. Materials and methods: The miscarriage group was obtained from 25 women who miscarried between the ages of 35 to 42 years and controls consisted of 25 healthy women between the ages of 27 to 39 years, who had electively terminated their pregnancies during the first trimester of pregnancy. The abortion was processed and specimens taken were studied using immunohistochemical methods. Specimens were taken from decidua basalis and decidua parietalis. Monoclonal antibodies were used against HLAG (Human Leukocyte Antigen G), CD68( Cluster of Differentiation 68), CD56, CD16 and CD25. The results were statistically analysed with Mann-Whitney test. Results: HLA-G expression in decidua basalis from miscarriage group was found to be decreased. CD25+ cell expression was found to be invariable in deciduas from both groups. CD16+ cell and CD68 + cell expression was found to be increased in deciduas from the miscarriage group. CD56+ cell expression was found to be increased in decidua parietalis from miscarriage group. Conclusion : Several differences in the immunological profile of deciduas from RPL group were observed. Changes in feto-protective HLA-G expression and a possible implication of macrophages and NK cells were found

Low expression of Progesterone Receptor A in intermediate trophoblast of miscarriages

Summary. Objective: To examine the potential differences in the expression of Progesterone Receptor A and Estrogen Receptor A in intermediate trophoblastic cells at the implantation site in elective abortions and miscarriages by immunohistochemistry. Study Design: Twenty two (22) samples of miscarriages and eighteen (18) samples of elective abortions were obtained during gestational weeks 6 to 12. Monoclonal antibodies against Cytokeratin 7 and prolactin were used to help discriminate between trophoblastic and decidual cells at the feto-maternal interface on formalin-fixed paraffin-embedded sections. Samples were then stained with ERA and PRA antibodies. Nuclear expression was considered positive. Staining intensity was measured according to a 4 grade scale. Statistical analysis of the results was performed using the Mann-Whitney test and the Wilcoxon signed rank test. Results: PRA expression in intermediate trophoblastic cells was significantly higher in elective abortions (control group) compared to miscarriages. ERA expression was uniformly negative in both groups. Conclusion: PRA expression is significantly lower in intermediate trophoblastic cells of miscarriages compared to elective abortion pregnancies. Although this could be solely a result of a secondary event, it is still an important finding in the effort to unravel the complex molecular pathobiology of spontaneous abortions

The antihypertensive treatment effect on left ventricular diastolic function is reflected in exercise electrocardiogram

Background/Purpose: Exercise electrocardiographic hump sign is associated with uncontrolled arterial hypertension (AH), left ventricular (LV) diastolic dysfunction, and false-positive exercise testing (ET). The aim of this prospective study was to evaluate the antihypertensive treatment effect on hump and on pseudoischemic ST-segment depression and potential correlations to LV diastolic function and mass changes. Methods: The study comprised 59 non coronary artery disease patients (45.9 years; 67.8% men) with never-treated arterial hypertension (143.2/95.1 mm Hg). Treadmill ET and echocardiography were performed at baseline and 6 months after pharmaceutical blood pressure normalization. Prevalence of hump and ST depression, transmitral (E/A) and tissue Doppler imaging (E’/A’) early/late velocities ratios, E/E’ ratio, and LV mass index (LVMI) were all defined. Results: Prevalence of hump was reduced from 69.5% to 23.7% and false-positive ETs from 35.6% to 18.6% (P < .05). Significant improvement (P < .05) was found in E’/A’ ratio (0.68 vs 0.84), E/E’ ratio (9.3 vs 7.9), and LVMI (109.2 vs 99.8 g/m(2)). Changes in hump were related to ST-depression changes (r = 0.632, P < .001) and to LV diastolic indices changes; patients with hump only at first ET (54.2%) improved E/A and E’/A’ ratios, whereas patients with hump only at second ET (8.5%) worsened diastolic indices with similar changes in blood pressure and LVMI. Conclusions: Antihypertensive treatment reduces the prevalence of hump and exercise ischemic-appearing ST depression probably through LV diastolic function improvement. (C) 2012 Elsevier Inc. All rights reserved

The Interplay of Exercise Heart Rate and Blood Pressure as a Predictor of Coronary Artery Disease and Arterial Hypertension

J Clin Hypertens (Greenwich). 2012;00:0000. (c) 2012 Wiley Periodicals, Inc. Delayed blood pressure (BP) and heart rate (HR) decline at recovery post-exercise are independent predictors of incident coronary artery disease (CAD). Delayed BP recovery and exaggerated BP response to exercise are independent predictors of future arterial hypertension (AH). This study sought to examine whether the combination of two exercise parameters provides additional prognostic value than each variable alone. A total of 830 non-CAD patients (374 normotensive) were followed for new-onset CAD and/or AH for 5years after diagnostic exercise testing (ET). At the end of follow-up, patients without overt CAD underwent a second ET. Stress imaging modalities and coronary angiography, where appropriate, ruled out CAD. New-onset CAD was detected in 110 participants (13.3%) whereas AH was detected in 41 former normotensives (11.0%). The adjusted (for confounders) relative risk (RR) of CAD in abnormal BP and HR recovery patients was 1.95 (95% confidence interval [CI], 1.282.98; P=.011) compared with delayed BP and normal HR recovery patients and 1.71 (95% CI, 1.082.75; P=.014) compared with normal BP and delayed HR recovery patients. The adjusted RR of AH in normotensives with abnormal BP recovery and response was 2.18 (95% CI, 1.034.72; P=.047) compared with delayed BP recovery and normal BP response patients and 2.48 (95% CI, 1.144.97; P=.038) compared with normal BP recovery and exaggerated BP response individuals. In conclusion, the combination of two independent exercise predictors is an even stronger CAD/AH predictor than its components. J Clin Hypertens (Greenwich). 2013;15:162-170. (C) 2012 Wiley Periodicals, Inc