IMMUNOLOGICAL AND PATHOMORPHOLOGICAL ASPECTS OF EARLY AND LATE PREECLAMPSIA

Preeclampsia (PE) is one of the most common complications of pregnancy, and it can be after 20 weeks of gestation. It ends only with a complete dissection of afterbirth. Traditionally, PE is subdivided into the early one, taking place through 34 weeks of pregnancy (EOPE) and the late one, which is after 34 weeks of gestation (LOPE). Clinical manifestations are similar in both cases however, risk factors and the severity of PE are different . It has been established that EOPE is determined by impaired trophoblast invasion and transformation of the spiral arteries of the uterus in early pregnancy, and late onset of PE is associated with oxidative stress of syncytiotrophoblast, which occurs secondarily, with limited gas exchange and insufficient intake of nutrients. Numerous studies have noted a significant contribution of immune responses to the pathogenesis of preeclampsia, however, the state of B-lymphocytes in EOPE and LOPE has not been studied. A comprehensive assessment of the condition of women with early (up to 34 weeks of pregnancy inclusive) and late (after 34 weeks) development of preeclampsia was carried out, taking into account clinical and anamnestic characteristics, the peculiarities of the formation of the structural components of the placenta, as well as determining the nature of differentiation and functional activity of B-lymphocytes. In peripheral venous blood, the content of CD19+, CD20+, CD19+CD27+IgD±, CD19+CD20- CD38+, CD20+CD5+-cells and serum levels of IL-5, IL-9, IL-13 were examined. Morphological examination included gross description, organometry, survey histology, and transmission electron microscopy. In the group of women with early preeclampsia in history, there were more often perinatal losses, premature births and medical abortions, and in the current pregnancy, intrauterine infection, oligohydramnios, placental insufficiency and fetal growth retardation. With late preeclampsia, metabolic syndrome, anemia, and a history of arterial hypertension were more often observed. In the peripheral blood of all women with preeclampsia, there was an increase in the content of CD20+CD5+-cells in comparison with those in uncomplicated pregnancy, more pronounced in the late onset of preeclampsia. Only in women with early preeclampsia blood levels of CD19+CD20- CD38+ and CD19+CD27+IgD±-cells, IL-5, IL-9 and IL-13 increased. Studies of the placenta in early preeclampsia indicated impaired implantation and pathological placentation with the development of primary placental insufficiency, which becomes chronic. In late preeclampsia, the development of placental insufficiency was determined by chronic disorders of maternal and fetal hemocirculation with increased deposition of fibrin and fibrinoid in the basal lamina and in the zones of villous epithelium necrosis. The study showed that the timing of the manifestation of preeclampsia is determined by the action of factors of the clinical history, structural rearrangements in the placenta and immune responses of B-lymphocytes are closely interrelated.

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Incomplete androgen insensitivity: asymmetry in morphology and steroid profile and metabolism of the gonads. An analysis of a case

Acta Endocrinologica ◽

10.1530/acta.0.1100564 ◽

1985 ◽

Vol 110 (4) ◽

pp. 564-571 ◽

Cited By ~ 3

Author(s):

Bengt Fredricsson ◽

Kjell Carlström ◽

Berndt Kjessler ◽

Jan Lindstedt ◽

Leif Plöen ◽

...

Keyword(s):

Venous Blood ◽

Clinical Manifestations ◽

Androgen Insensitivity Syndrome ◽

Seminiferous Tubules ◽

Blood Levels ◽

Androgen Insensitivity ◽

Gonadal Tissue ◽

Oestrone Sulphate ◽

The Right

Abstract. A patient with clinical manifestations of the incomplete androgen insensitivity syndrome was studied with respect to peripheral blood levels of steroids and steroid sulphates before, during and after gonadectomy. Steroid and steroid sulphate concentrations were also analyzed in spermatic venous blood and gonadal tissue collected during surgery. The metabolic capacity of gonadal tissue was also studied in vitro using progesterone, dehydroepiandrosterone sulphate and oestrone sulphate as substrates. Profound differences between the two gonads were noted with respect to both steroid content and release into pampiniform veins and to in vitro conversion of progesterone and oestrone sulphate. Histological examination revealed the presence of seminiferous tubules with carcinoma in situ in both gonads. It is suggested that the differences between the gonads may be due to an autonomous steroid production in the right gonad in spite of adequate or even elevated gonadotrophic stimulation resulting in a steroidogenic situation resembling the complete androgen insenstitivity syndrome, while the conditions found in the left gonad more resembles the incomplete form of the disease.

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Arterio-Venous Differences in the Components of the Fibrinolytic Enzyme System

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655624 ◽

1966 ◽

Vol 16 (01/02) ◽

pp. 032-037 ◽

Cited By ~ 5

Author(s):

D Ogston ◽

C. M Ogston ◽

N. B Bennett

Keyword(s):

Plasminogen Activator ◽

Enzyme System ◽

Venous Blood ◽

Fibrinolytic Enzyme ◽

Blood Levels ◽

Activator Concentration ◽

Blood Samples ◽

Arterial Blood ◽

Male Subjects

Summary1. The concentration of the major components of the fibrinolytic enzyme system was compared in venous and arterial blood samples from male subjects.2. The plasminogen activator concentration was higher in venous blood and the arterio-venous difference increased as its concentration rose, but the ratio of the arterial to venous level remained constant.3. No arterio-venous difference was found for anti-urokinase activity, antiplasmin, plasminogen and fibrinogen.4. It is concluded that venous blood determinations of the components of the fibrinolytic enzyme system reflect satisfactorily arterial blood levels.

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Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities

International Journal of Molecular Sciences ◽

10.3390/ijms22010165 ◽

2020 ◽

Vol 22 (1) ◽

pp. 165

Author(s):

Lucía Pérez-Roque ◽

Elena Núñez-Gómez ◽

Alicia Rodríguez-Barbero ◽

Carmelo Bernabéu ◽

José M. López-Novoa ◽

...

Keyword(s):

Plasma Levels ◽

Ex Vivo ◽

Clinical Manifestations ◽

High Plasma ◽

Trophoblast Invasion ◽

Future Research ◽

Soluble Factors ◽

Human Trophoblast ◽

Soluble Endoglin ◽

Pregnant Mice

Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.

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Neuralgic amyotrophy: an underrecognized entity

Journal of International Medical Research ◽

10.1177/03000605211006542 ◽

2021 ◽

Vol 49 (4) ◽

pp. 030006052110065

Author(s):

Tae Uk Kim ◽

Min Cheol Chang

Keyword(s):

Clinical Practice ◽

Magnetic Resonance ◽

Clinical Manifestations ◽

Clinical History ◽

Cervical Radiculopathy ◽

Sudden Onset ◽

Clinical Findings ◽

Magnetic Resonance Neurography ◽

Essential Information ◽

Neuralgic Amyotrophy

Neuralgic amyotrophy (NA) is markedly underdiagnosed in clinical practice, and its actual incidence rate is about 1 per 1000 per year. In the current article, we provide an overview of essential information about NA, including the etiology, clinical manifestations, diagnostic investigations, differential diagnosis, treatment, and prognosis. The causes of NA are multifactorial and include immunological, mechanical, or genetic factors. Typical clinical findings are a sudden onset of pain in the shoulder region, followed by patchy flaccid paralysis of muscles in the shoulder and/or arm. A diagnosis of NA is based on a patient’s clinical history and physical examination. Gadolinium-enhanced magnetic resonance imaging and high-resolution magnetic resonance neurography are useful for confirming the diagnosis and choosing the appropriate treatment. However, before a diagnosis of NA is confirmed, other disorders with similar symptoms, such as cervical radiculopathy or rotator cuff tear, need to be ruled out. The prognosis of NA depends on the degree of axonal damage. In conclusion, many patients with motor weakness and pain are encountered in clinical practice, and some of these patients will exhibit NA. It is important that clinicians understand the key features of this disorder to avoid misdiagnosis.

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Age-Related Association of Calcitonin with Parameters of Anthropometry, Bone and Calcium Metabolism during Childhood

Hormone Research in Paediatrics ◽

10.1159/000512107 ◽

2020 ◽

pp. 1-10

Author(s):

Juliane Sonntag ◽

Mandy Vogel ◽

Mandy Geserick ◽

Felix Eckelt ◽

Antje Körner ◽

...

Keyword(s):

Bone Formation ◽

Bone Growth ◽

Venous Blood ◽

Physiological Role ◽

Blood Levels ◽

Childhood And Adolescence ◽

Procollagen Type ◽

Child Study ◽

Age Related ◽

High Bone

Introduction: The thyroid parafollicular hormone calcitonin (CT) shows particularly high blood levels in early childhood, a period of high bone turnover, which decrease with increasing age. Data about the physiological role of CT during infancy, childhood, and adolescence are contradictory or lacking. Objective: We hypothesize that CT demonstrates age-related correlations with parameters of bone growth and turnover as well as with parameters of calcium homeostasis. Methods: 5,410 measurements of anthropometric data and venous blood samples were collected from 2,636 participants of the LIFE Child study, aged 2 months–18 years. Univariate correlations and multiple regression analysis were performed between serum CT and anthropometric indicators (height standard deviation scores [SDS] and BMI-SDS), markers of calcium (Ca) homeostasis (Ca, parathyroid hormone, 25-OH vitamin D, and phosphate [P]), bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin), and bone resorption (β-CrossLaps). Results: CT was significantly associated with Ca (β = 0.26, p < 0.05) and P1NP/100 (β = 0.005, p < 0.05) in children aged 2 months–1.1 years. These relations were independent of age and sex and could not be confirmed in children aged 1.1–8 years. Independent of age, sex, puberty, P, and height SDS CT showed a significant positive relation to Ca (β = 0.26; p < 0.001) in children aged 8–18 years. Conclusions: Our findings suggest a unique association between CT and Ca in periods of rapid bone growth and point to a possible involvement of CT in promoting bone formation during the first year of life.

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Diffuse Bullous Eruptions in an Elderly Woman: Late-Onset Bullous Systemic Lupus Erythematosus

Case Reports in Dermatology ◽

10.1159/000448392 ◽

2016 ◽

Vol 8 (3) ◽

pp. 278-282 ◽

Cited By ~ 3

Author(s):

Prajwal Boddu ◽

Mojtaba Nadiri ◽

Owais Malik

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Late Onset ◽

Clinical History ◽

The Elderly ◽

Direct Immunofluorescence ◽

Systemic Lupus ◽

Diverse Range ◽

American College Of Rheumatology ◽

Type Vii Collagen

Vesiculobullous eruptions in the elderly represent a diverse range of varying pathophysiologies and can present a significant clinical dilemma to the diagnostician. Diagnosis requires a careful review of clinical history, attention to detail on physical and histomorphological examination, and appropriate immunofluorescence testing. We describe the case of a 73-year-old female who presented to our hospital with a painful blistering skin rash developed over 2 days. Examination of the skin was remarkable for numerous flaccid hemorrhagic bullae on a normal-appearing nonerythematous skin involving both the upper and lower extremities. Histopathology of the biopsy lesion showed interface change at the epidermo-dermal region with subepidermal blister formation, mild dermal fibrosis, and sparse interstitial neutrophilic infiltrate. Immunohistological analysis was significant for positive IgG basement membrane zone antibodies with a dermal pattern of localization on direct immunofluorescence and positive IgG antinuclear antibodies on indirect immunofluorescence. Evidence of antibodies to type VII collagen suggested the diagnosis of epidermolysis bullosa acquisita versus bullous systemic lupus erythematosus (BSLE). A diagnosis of BSLE was made based on positive American College of Rheumatology criteria, acquired vesiculo-bullous eruptions with compatible histopathological and immunofluorescence findings. This case illustrates one of many difficulties a physician encounters while arriving at a diagnosis from a myriad of immunobullous dermatoses. Also, it is important for internists and dermatologists alike to be aware of and differentiate this uncommon and nonspecific cutaneous SLE manifestation from a myriad of disorders presenting with vesiculobullous skin eruptions in the elderly.

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FURTHER OBSERVATIONS OF A PATIENT WITH HYPERGLYCINEMIA

PEDIATRICS ◽

10.1542/peds.33.3.403 ◽

1964 ◽

Vol 33 (3) ◽

pp. 403-412 ◽

Cited By ~ 1

Author(s):

Barton Childs ◽

William L. Nyhan

Keyword(s):

Amino Acids ◽

Clinical Manifestations ◽

Protein Diet ◽

Low Protein Diet ◽

Blood Levels ◽

Low Protein

Observations of a patient with hyperglycinemia have been extended. The patient, who has been subsisting on a low protein diet, has shown some improvement in the clinical manifestations though he has failed to grow. Loading experiments have increased the list of amino acids capable of inducing ketosis and symptoms in the patient to five: leucine, isoleucine, valine, threonine, and methionine. Eleven other amino acids have been similarly tested and were found to be beneficial, reducing the toxicity of the five ketogenic amino acids. Blood levels of the amino acids have been measured under a variety of circumstances. When given alone, the toxic amino acids were found to accumulate in the blood. Such accumulations were less striking when the nonketogenic amino acids were given together with the ketogenic ones. The patient has been benefitted by a diet low in protein which has been supplemented by the innocuous amino acids.

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Emerging evidence for associations between periodontitis and the development of Alzheimer’s disease

Faculty Dental Journal ◽

10.1308/204268514x13859766312719 ◽

2014 ◽

Vol 5 (1) ◽

pp. 38-42 ◽

Cited By ~ 5

Author(s):

Sophie Poole ◽

Sim K Singhrao ◽

St John Crean

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Immune Responses ◽

Periodontal Disease ◽

Potential Risk ◽

Inflammatory Disease ◽

Pathogenic Bacteria ◽

Late Onset ◽

Systemic Circulation

Periodontal disease (PD) is an inflammatory disease affecting tooth-supporting tissues in which interaction of specific bacteria and the host’s immune responses play a pivotal role. The pathogenic bacteria associated with PD are a source of systemic inflammation as they have the ability to enter systemic circulation during everyday tasks such as brushing teeth and chewing food. Alzheimer’s disease (AD) is a form of dementia whereby inflammation is thought to play a key role in its pathogenesis and the risk of developing the disease increasing with age. The exact aetiology of the late-onset AD is unknown but peripheral infections are being considered as a potential risk factor.

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Great Obstetrical Syndromes In G20210a Mutation Carriers Associated With High Prothrombin Activity

10.21203/rs.3.rs-67776/v1 ◽

2020 ◽

Author(s):

Mariya Nikolaeva ◽

Andrey Pavlovich Momot ◽

Marina Sabirovna Zainulina ◽

Natalia Nikolaevna Yasafova ◽

Irina Alekseevna Taranenko

Keyword(s):

Blood Plasma ◽

Venous Blood ◽

Threshold Value ◽

Main Group ◽

Trophoblast Invasion ◽

Control Group ◽

G20210a Mutation ◽

Factor Ii ◽

Invasion Waves ◽

In Blood Plasma

Abstract Objective: to study the association between high activity of Factor II (prothrombin) in blood plasma with G20210A mutation and the development of great obstetrical syndromes.Material and methods: A prospective clinical cohort study was conducted on 290 pregnant women (average age 31.7±4.7 years old). The main group was made up of 140 G20210A patients, while the control group comprised 150 women with the wild G20210G type. The aim was to evaluate the activity of Factor II in the venous blood plasma during the stages of pregnancy with regard to trophoblast invasion waves. As per results, association analysis of Factor II activity value and gestational complications was carried out.Results: In the control group, the median (Me) of Factor II activity ranged from 108% (preconception period) to 144% (pregnancy) [95% CI 130-150]. In patients with the GA type, the value was significantly higher in related periods, ranging from 149% to 181% [95% CI 142-195], p<0.0001. With Factor II activity ranging from 148.5% to 180.6%, pregnancies in the main group had no complications. Higher levels of Factor II activity were associated with the development of early and/or severe preeclampsia (PE) and fetal growth retardation (FGR).Conclusion: The data obtained regarding Factor II activity in blood plasma, juxtaposed with the development of great obstetrical syndromes, allow to assume that manifestation of G20210A in early and/or severe PE and FGR is associated with this coagulation factor's level of activity. Threshold value of the Factor II activity with G20210A mutation, allowing to predict the development of PE, comprised 171.0% at the preconception stage (AUC – 0.86; p<0.0001) and within 7-8 weeks of gestation it was 181.3% (AUC – 0.84; p<0.0001).

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A systematic review of immune pathogenesis of SARS-COV-2 infection

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20212411 ◽

2021 ◽

Vol 8 (7) ◽

pp. 978

Author(s):

Shabarini Srikumar ◽

Shridharan Perumal

Keyword(s):

Immune Responses ◽

Critical Role ◽

Clinical Manifestations ◽

Multiple Organ ◽

World Health ◽

Multiple Organ Dysfunction ◽

Viral Immunity ◽

Secondary Infections ◽

Rational Management ◽

Health Organization

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by the world health organization on March 11, 2020. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 causes direct activation of anti-viral immune responses and leads to the release of uncontrolled inflammatory mediators. These SARS-CoV-2-induced immune responses may lead to various other abnormalities like lymphopenia, thrombocytopenia and granulocyte and monocyte dysfunction, making the patient more prone to secondary infections by microorganisms, which may result in further further serious complications like septic shock, severe multiple organ dysfunction and eventually death. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 disease must be elucidated to guide clinical management of the disease. Rational management in combating the disease includes enhancing anti-viral immunity and inhibiting systemic inflammation, which is key to successful treatment.

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