Endothelial Dysfunction in Children With Nephrotic Syndrome: A Cross-Sectional Study.

Background Children with nephrotic syndrome (NS) have a higher risk of cardiovascular morbidity. Studies on the evaluation of arterial stiffness and endothelial function and its predictive risk factors in these children are limited. Objective The primary objective of the study was to determine arterial stiffness by measuring carotid intimal medial thickness, flow-mediated dilatation, and physiological parameters in children with nephrotic syndrome to predict the risk of premature atherosclerosis as compared to controls. Participants A total number of 33 children with NS in the age group of 2-14 years in remission and 39 healthy controls were enrolled in the study. Out of 33 children with nephrotic syndrome, five were infrequently relapsing NS, eight were frequently relapsing, 16 were steroid dependent, and four were steroid-resistant NS. Intervention Relevant history, physical examination, anthropometric measurements, and laboratory investigations were done. Carotid intimal medial thickness (cIMT), flow-mediated dilatation (FMD), and other physiological parameters were measured in both children with NS and control groups. Outcome Carotid intimal medial thickness (cIMT), flow-mediated dilatation (FMD), and other physiological parameters were compared between children with NS and healthy controls for detecting arterial stiffness and endothelial dysfunction. Results Dyslipidaemia was seen in more than 50% of children during remission. There was neither significant difference in mean cIMT in the common carotid artery nor FMD between the control and study groups. There was a trend of lower Reactive Hyperemia Index (RHI) in children with NS. Conclusion Dyslipidemia persists even during the remission phase in NS. No statistically significant difference is observed in cIMT and percentage proportionate change in FMD in both the study and control groups. Nevertheless, RHI is notably lower in children with NS. These findings need further validation in future studies.

Assessment of the relationship of systemic vascular dysfunction and cardiac autonomic neuropathy (CAN) with diabetic retinopathy.

Context: Diabetic retinopathy, a form of microvasculopathy, is the leading cause of the visual abnormality. However, there is no conclusive evidence of the relationship of systemic vascular dysfunction with retinal microvasculopathy. In addition, diabetes-associated cardiac autonomic neuropathy may also compromise vascular function. Aims: The present study intends to correlate arterial stiffness, endothelial function, and heart rate variability (HRV) as a standardized measure of cardiac autonomic neuropathy with diabetic retinopathy. Settings and Design: The present cross-sectional, observational study was conducted in the Department of Physiology. Materials and Methods: Twenty subjects were recruited in group 1 (T2DM, type 2 diabetes mellitus patients, without retinopathy) and group 2 (T2DM with retinopathy). The vascular parameters such as heart rate, peripheral and central blood pressure, augmentation index [AIx (%)], brachial -ankle pulse wave velocity (baPWV), and reactive hyperaemia index (RHI) were recorded. Statistical Analysis Used: Independent sample t-test (for parametric data) and Mann-Whitney U test (for non-parametric data) were employed to compare the variables of two groups. Spearman correlation was used to examine the relationship among the parameters. Linear regression analysis was performed to examine the important vascular predictor for diabetic retinopathy. Results: baPWV was significantly higher in group 2 than in group 1 and positively associated with group 2. RHI was significantly less in group 2 than group 1 and negatively associated with group 2. Among HRV metrics, standard deviation of successive differences (SDSD), root mean square of successive differences between normal heartbeats (RMSSD), and high frequency (HF) power were significantly decreased in group 2 than in group 1. SDSD, RMSSD, and HF power were negatively associated with group 2. RHI emerged as a significant predictor of diabetic retinopathy following linear regression. Conclusions: Overall, the result of the present study indicates that metabolic dysregulation of glucose may affect the normal functioning of the autonomic nervous system and vascular function. Therefore, screening of vascular function and cardiac autonomic tone may be advocated in diabetic patients in routine clinics to examine the existence of any comorbid condition, such as diabetic retinopathy, as systemic vascular changes may also affect ophthalmic vasculature.

Impact of Cardiac Autonomic Dysfunction on Cognitive Event-Related Potential in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition that is responsible for various long-term complications. Cognitive impairment is one of the most common complications, but the underlying mechanisms are still undetermined. The autonomic imbalance is a major cause for CVS morbidity in T2DM which could also potentially affect cognition. But there is sparse data available in the literature to prove the association between autonomic dysfunction and cognitive impairment. Methodology: We recruited 40 T2DM patients and 40 healthy controls. The assessment of cognitive functions was done by cognitive P300 event-related potential (ERP) and MoCA. Heart rate variability (HRV) was done to assess autonomic function. Results: The P300 ERP latency in Fz, Cz and Pz sites was significantly prolonged in T2DM patients (P < 0.001). We found moderate correlation is present between P300 latency and total power (r = -0.466, P < 0.01) and LFnu (r = -0.423, P < 0.01) in T2DM patients. The total power and HbA1C show independent association with P300 latency after adjustment for confounding factors like age and duration of diabetes (P < 0.05). Conclusion: As the incidence of Alzheimer's disease is rising among T2DM patients increasing their dependency, making necessary lifestyle measures at earliest to improve autonomic balance may prevent or delay the onset of cognitive decline and alleviate its consequences and improve the quality of life in T2DM patients.

Vascular Dysfunction and Its Cardiovascular Consequences During and After COVID-19 Infection: A Narrative Review.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV2) has brought out changes in our daily life and has caused severe morbidity and mortality across the globe. Especially, post covid complications may remain a threat to the patient's life. It may also increase the burden on existing health infrastructure and the country's economy. This disease affects the respiratory system and other organ systems of the body, such as the cardiovascular system. The aim of the present narrative review is to understand how COVID-19 infection deranges vascular homeostasis, leading to endothelial dysfunction and arterial stiffness in the acute phase and following infection. To this effect, definite keywords were employed to obtain relevant information using PubMed database and Google Scholar search engines. It was documented that preexisting cardiovascular disease enhances morbidity in COVID-19 patients. Moreover, an elevated risk of development of new onset cardiovascular events has also been reported. Even a small amount of myocardial injury was significantly associated with death. The presence of virus in myocardial cells has also been documented. Furthermore, endothelial dysfunction and arterial stiffness were documented in the acute phase and 3-4 weeks to 4 months after COVID infection. The virus enters endothelial cells by binding with ACE2 "receptor" on its surface and deranges cellular machinery. It results in reduced conversion of Ang II to Ang (1-7). Accumulated Ang II then activates PI3K-Akt signaling pathway and regulates endothelial activation and production of IL-6 and reactive oxygen species (ROS). An imbalance between renin angiotensin aldosterone system (RAAS) and kallikrein kinin system (KKS) also occurs, which may cause endothelial dysfunction. It is understandable that the underlying pathophysiology of this altered arterial stiffness is multifactorial, involving various cellular and immunological biomolecules.

Effect of Laboratory Mental Stressors on Cardiovascular Reactivity in Young Women During Different Phases of Menstrual Cycle: An Observational Study.

Introduction: Excessive cardiovascular reactivity to mental stress may be a risk factor for cardiovascular disease. However, there is inconsistent report in the literature regarding change in cardiac autonomic tone with the phase of the menstrual cycle and how it is affected by mental stress. Therefore, the present study was aimed at determining the cardiovascular reactivity to different laboratory mental stressors during follicular and luteal phase of menstrual cycle using heart rate variability (HRV). Methods: Thirty-three regularly cycling young females (19-35 years of age) were exposed to four cognitive tasks (Stroop test, Mental Rotation test, n-back test, and Mental Arithmetic Stress Test [MAST]) employed as laboratory mental stressors. HRV of the study participants were recorded before, during, and after each cognitive task and the recording was done in both phases of menstrual cycle for each individual. Results: A significant difference was observed in time domain parameters and nonlinear parameters of HRV in pretest versus during-test condition and during-test versus post-test conditions, but not in frequency domain parameters. No phase difference was found in time domain or frequency domain analysis of HRV in baseline or during performance of task. MAST performance (score out of 50) was significantly higher in luteal than follicular phase, while other tests showed no such difference. Conclusion: All four mental stress tasks used in the present study were able to elicit significant decrease in parasympathetic tone during performance of task as compared with baseline values of HRV. The present study did not elicit any phase difference in cardiovascular reactivity.

Molecular correlates of syncytialization in muscle and placenta.

Syncytialization is one of the most fundamental processes in life. It is observed during development of muscle and osteoclast, and syncytiotrophoblast formation in placental villi. Syncytialization involves recognition, migration, adhesion and finally cell fusion between two interacting cells. It is an energy-dependent process which is essentially restricted to a small portion of interacting cellular membranes. Such regions of membranes may differ from other regions of cell surface in terms of physico-chemistry and expression of specific protein biomolecules resulting in restriction of this process to cells of specific competence. Despite the fact that membrane biologists have given significant quanta of efforts to understand the basic principle underlying this fundamental process of life, further large scale initiatives have to be undertaken to dissect the underlying molecular correlates central to this event.

Effect of (Ala8,13,18)-magainin II amide on human trophoblast cells in vitro.

Magainins are cationic peptides with anti-bacterial and anti-tumor properties. The anti-nidatory function of a synthetic analogue of magainin, (Ala8,13,18)-magainin II amide, has earlier been reported, and it has been indicated that placental trophoblast cells could be a target of magainin resulting in its contragestational action. The aim of the present study was to examine the effect of (Ala8,13,18)-magainin II amide (100 ng/ml and 1000 ng/ml) on attachment efficiency, viability, differentiation in terms of hCG secretion and invasive function of isolated first trimester, human placental trophoblast cells grown on rat-tail collagen type-I matrix in primary cell culture. In the present experimental model, magainin was not found to affect human trophoblast cell functions in vitro.

Immunohistochemical localization of macrophage CD68+, HLA-DR+, L1+ and CD44+ subsets in uterine endometrium during different phases of menstrual cycle.

Different tissue macrophage subsets were immunohistochemically examined in normal endometrial samples collected from proliferative (n=4), peri-ovulatory (n=6) and secretory (n=8) phases of menstrual cycles in women. The different macrophage subsets, namely CD68 (pan macrophage marker), CD44 (transmembrane adhesion molecule), HLA-DR (transmembrane heterodimeric protein involved in antigen presentation) and L1 (calprotectin)-positive cells, as well as, CD45 (common leucocytic antigen)-positive cells were examined on the basis of immunohistochemical staining, and areas of immunoprecipitation were analyzed morphometrically using computer-assisted video imaging system. The stage-specific distribution of receptors for estrogen (ER) and progesterone (PR) in endometrial cells were examined and morphometrically analyzed. There was an increase in the number of CD45+ cells (P < 0.01) and CD68+ cells (P < 0.05) in secretory phase endometrium compared with proliferative and peri-ovulatory phases. There was no remarkable cycle dependent pattern in HLA-DR+ and L1+ cells. However, there was an increase in CD44 immunopositive area in peri-ovulatory (P < 0.05) and in secretory (P < 0.01) phases of endometrium compared with proliferative phase endometrium. A higher (P < 0.01) degree of immunopositivity for ER was observed during peri-ovulatory phase, and for PR, during peri-ovulatory (P < 0.05) and secretory (P < 0.01) phases compared with proliferative phase of cycle. Positive correlations between areas occupied by (i) CD68+ cells and PR (P < 0.01), (ii) HLA-DR+ and L1+ cells (P < 0.05), (iii) CD45+ and CD68+ cells (P < 0.01), (iv) CD45+ and L1+ cells (P < 0.05), and (v) PR and L1+ cells (P < 0.05) were obtained. It appears that the recruitment of different macrophage subsets in human endometrium involves a complex set of endocrine and paracrine factors.

Effect of vaginally administered fumagillin on immunohistochemical distribution of leukemia inhibitory factor, interleukin 6, transforming growth factor beta and vascular endothelial growth factor in implantation stage endometrium of the rhesus monkey.

Intravaginal administration of an anti-angiogenic agent, fumagillin, during blastocyst implantation inhibits pregnancy establishment in a dose-related manner in the rhesus monkey. In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial tissue samples were collected on cycle day 24 from all monkeys and processed for histological examination and immunohistochemical localization for LIF, IL-6, TGF-beta and VEGF. Concentrations of estradiol-17 beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From the serum profiles of the hormones, 2 monkeys in group 1, and 1 monkey in group 2 appeared pregnant. However, endometrial morphology revealed histological evidence of pregnancy in 3 out of 6 fumagillin-treated animals. Histometric analysis of immunohistochemical staining in epithelial, stromal and vascular compartments revealed that per cent areas occupied by immunoprecipitate for the cytokines studies did not change in epithelial and stromal compartments, except that for TGF-beta which was higher (P < 0.05) in epithelial compartment in group 2. No change was observed in immunoprecipitation areas for IL-6 in epithelial, stromal and vascular compartments. On the other hand, changes (P < 0.05) for LIF, TGF-beta and VEGF were evident in the vascular compartment. It is possible that disparate responses observed in glandular, stromal and vascular compartments in implantation stage endometrium following fumagillin treatment actually caused from associated decline in progesterone concentration in peripheral circulation. It is also possible that fumagillin, an angiostatic agent, affects the synthesis and secretion of cytokines primarily in the vascular compartment of implantation stage endometrium, and thereby manifests differential responses in epithelial, stromal and vascular compartments.

Role of biomarkers in early detection of preeclampsia.

Preeclampsia (PE) is a pregnancy-related, potentially life threatening condition. The incidence of PE has increased in the past decade, which has been attributed to various predisposing factors. Abnormal placentation is central to the evolution of this disease process. However, the triggering factor for this is still unknown. Interestingly, intense research done in this arena has unveiled the names of some important biomolecules which play important role in the vasculognesis of the early placenta, namely, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and their antagonists, namely, soluble fms-like tyrosine kinase 1 (sFlt-1, also known as sVEGFR1), and soluble endoglin (sEng). Besides these, Renin Angiotensin System (RAS) was also implicated in this disease process. The roles of immune factors, genetic factors have been stressed from time to time. More novel approaches made, have shed light on the upcoming biomolecules. All these endeavours are directed to diagnose PE as early as possible, which is a real challenge. Question remains whether a single set parameters could diagnose a disease entity which is as complex as PE. Therefore, it is imperative to design feasible, predictive test-set utilizing multiple biomarkers.

Evaluation of Examination Stress and Its Effect on Cognitive Function among First Year Medical Students.

BACKGROUND: Medical students experience stress at every phase of curriculum more so before examination. This stress may affect physiological, psychological and cognitive functions of the students. AIM: The present study aimed to evaluate stress status among first year MBBS students by recording pulse rate (PR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and using stress questionnaire; its effect on cognitive function by recording auditory reaction time (ART) and visual reaction time (VRT). SETTING AND DESIGN: It is a cross-sectional study. MATERIALS AND METHODS: A total of 100 (49 males and 51 females) first year healthy MBBS students participated. Stress questionnaire was given and assessed. Cardiovascular parameters were also assessed. The ART and VRT were recorded before (pre examination setting) and after 3 month of examination (post-examination setting). STATISTICAL ANALYSIS: The data were analysed by using SPSS 21.0 version. RESULTS: All parameters namely PR, SBP, DBP, ART, VRT and stress scores were increased in preexamination setting irrespective of gender. Increased PR was observed in female learners where as stress score and SBP were increased in males in pre-examination setting. ART and VRT were more in females as compared to males in both setting. CONCLUSION: It is concluded that examination in the form of stressor hampers cognitive function of first year medical students. The cognitive functions of the female learners were more affected as compared to males. Therefore, proper counselling of the students should be initiated at the earliest to decrease their stress level.

Histochemical and morphological examination of proliferation and apoptosis in human first trimester villous trophoblast.

BACKGROUND: Our present knowledge about trophoblast turnover in human first trimester placental villi based on multiparametric examination of proliferation and apoptosis is limited. METHODS: Human villous placentae collected during 6, 7 and 8 weeks (n = 10/each group) of gestation were examined for trophoblast proliferation and apoptosis based on quantitative analyses of immunopositive Fas, tumor necrosis factor receptor 1 (TNFR1), cytokeratin 18 fragment (18f), number of proliferating cell nuclear antigen (PCNA), Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive nuclei, scores of mitotic and apoptotic indices and ultrastructural characteristics. RESULTS: Mitotic index in cytotrophoblast higher (P < 0.05) at 6 week compared with 7 and 8 weeks of gestation showed significant (P < 0.05) negative correlation between its prevalence and gestational age. Syncytiotrophoblast exhibited higher number of TUNEL positive nuclei (P < 0.01), TUNEL positive apoptotic nuclei (P < 0.05) and apoptotic index (P < 0.05) compared with cytotrophoblast at same gestational age. Positive correlations found between cytokeratin 18f and apoptotic index (P < 0.01), Fas and apoptotic index (P < 0.01), TUNEL positive nuclei and apoptotic index (P < 0.05), cytokeratin 18f and Fas (P < 0.01), whereas cytokeratin 18f (P < 0.05) and Fas (P < 0.05) showed positive correlation only with TUNEL positive apoptotic nuclear data. Phalangeal intrusions of syncytiotrophoblast between transitional cytotrophoblasts showed apposed plasma membranes bearing thickened membrane leaflets, inter-membranous gaps enclosing membranous invaginations, liposome-like particles; patches of membrane seen to be dissolved resulting in cytoplasmic continuity typical of syncytial formation. CONCLUSION: Cellular remodeling of first trimester villous placenta requires a complex homeodynamics involving proliferation in cytotrophoblast, development-associated syncytialization and apoptosis in syncytiotrophoblast.