Pathogenetic Concepts Research Articles

Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities.

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, increasingly contributing to the burden of liver transplantation. In search for effective treatments, novel strategies addressing metabolic dysregulation, inflammation, and fibrosis are continuously emerging. Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.

Modern aspects of the treatment of patients with gastroesophageal reflux disease against the background of type 2 diabetes mellitus and obesity

This review presents new pathogenetic concepts of type 2 diabetes mellitus (DM 2) and gastroesophageal reflux disease (GERD) against the background of obesity and methods of therapeutic correction of these nosologies. The important role in the etiology of adipocytokines (ghrelin and leptin) and overweigh has been proved, the latter also may be DM 2 predictor. The interaction between indicators of these adipocytokines is described, which equates to normal and pathological deviations, according to the literature. The formation and progression of metabolic syndrome (MS), onset of insulin resistance (IR) and DM 2, and progression of complications against DM 2 background are stipulated by a violation of ghrelin and leptin biorhythms. This review describes the effects of prolonged hyperglycemia on the nervous system with further diabetic neuropathy (DN) formation, which causes diabetic gastroparesis. Possibilities of these pathogenic factors to affect function of the lower esophageal sphincter (LES) against the DM 2 background and the formation of GERD in future have been revealed. The analysis has been performed for the data on comorbid pathology (GERD against the DM 2 background), and possible predictors of the formation or progression of symptoms, specific for gastrointestinal pathology, have been identified. The efficacy of such measures to attenuate manifestation of GERD and DM 2 as lifestyle modification, dosed physical exercises, change in body position, normalization of nutrition etc., have been proved. In accordance with modern concepts and data of meta‑analysis, the possibilities of therapeutic correction of changes in carbohydrate metabolism at DM 2 are highlighted. It has been established that it is not always possible to achieve an adequate glycemic control against the background of metformin monotherapy. The most important medications’ groups have been described, advisable of the treatment of GERD and DM 2 as both separate pathologies and combined course. The information on the use of thioctic acid against the background of the formation of oxidative stress in patients with DM 2 and the positive effects of reducing the manifestations of diabetic neuropathy and GERD was analyzed.

WAYS TO OPTIMIZE REHABILITATION ACTIVITIES IN HEMORRHAGIC AND ISCHEMIC STROKE

The development of acute cerebral ischemia triggers pathobiochemical cascade reactions, the outcome of which is cerebral infarction (MI), which is formed by two mechanisms: necrotic cell death and apoptosis - programmed cell death. These modern pathogenetic concepts have made it possible to propose a sequence of stages »Based on their causal relationships. Each stage of the cascade is a target for the therapeutic effect of drugs, primarily with neuroprotective effects.

Diagnostic Tools, Biomarkers, and Treatments in Diabetic polyneuropathy and Cardiovascular Autonomic Neuropathy.

The various manifestations of diabetic neuropathy, including distal symmetric sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN), are among the most prevalent chronic complications of diabetes. Major clinical complications of diabetic neuropathies, such as neuropathic pain, chronic foot ulcers, and orthostatic hypotension, are associated with considerable morbidity, increased mortality, and diminished quality of life. Despite the substantial individual and socioeconomic burden, the strategies to diagnose and treat diabetic neuropathies remain insufficient. This review provides an overview of the current clinical aspects and recent advances in exploring local and systemic biomarkers of both DSPN and CAN assessed in human studies (such as biomarkers of inflammation and oxidative stress) for better understanding of the underlying pathophysiology and for improving early detection. Current therapeutic options for DSPN are (I) causal treatment, including lifestyle modification, optimal glycemic control, and multifactorial risk intervention, (II) pharmacotherapy derived from pathogenetic concepts, and (III) analgesic treatment against neuropathic pain. Recent advances in each category are discussed, including non-pharmacological approaches, such as electrical stimulation. Finally, the current therapeutic options for cardiovascular autonomic complications are provided. These insights should contribute to a broader understanding of the various manifestations of diabetic neuropathies from both the research and clinical perspectives.

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders.

The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

Current Problems of Diagnostics and Treatment of Purulent-Inflammatory Diseases and Sepsis in Medical Practice

Background: Poor treatment of burns can lead to sepsis and even death. Especially promising is the use of the method of fluorescence spectroscopy for its diagnostics. The aim of the research is to create a pathogenetic concept as the basis of a diagnostic and treatment model of purulent-inflammatory diseases and sepsis. Material and methods: The study lasted from 2001 to 2019 and included 4 stages. The experimental base of luminescent research at all stages was the luminescence laboratory of the Department of Experimental Physics of the Ivan Franko National University of Lviv. The study was performed by using optical monochromators MDR-2 and MDR-12. The excitation of the blood serum was performed with light with a wavelength of 280 nm, which corresponds to the glow region of human serum albumin. Results: The main indicators, used for the analysis, were the fluorescence intensity (IF) and the position of the maximum fluorescence band (λmax). The object of the study was samples of the blood serum of patients of the main and control groups. In the case of the presence of endogenous intoxication in the body, albumin binding centers are blocked by the products of bacterial metabolism and therefore such “pathological” albumin is unable to perform its functions, including transport and detoxification. Conclusions: The pathogenetic concept as the basis of the diagnostic and treating model of purulent-inflammatory diseases and sepsis was devised. In particular, the important role of albumin solution infusion in the treatment of the above-mentioned diseases was established.

Features of antitussive therapy in whooping cough in pediatric practice

Whooping cough is an acute highly contagious infectious disease, the main manifestation of which is a prolonged paroxysmal cough. Despite the availability of the vaccine, over the past 10 years there has been an increase in the incidence of pertussis in both Russia and the world, which is associated both with the refusal of the parents to vaccinate and with the use of the acellular vaccine that induces a time-limited immune response. In the phase of spasmodic cough, the severity of the condition is determined by the frequency and intensity of cough paroxysms. Against the background of coughing, young children may develop apnea and hypoxic encephalopathy, and older children and adolescents may develop neurosis-like reactions, sleep disturbance, enuresis. Virulence factors for bacteria of the genus Bordetella are known, but the pathogenesis of coughing with whooping cough has not been adequately studied. Antibacterial therapy accelerates the eradication of the pathogen, but practically does not affect the duration of symptoms. Due to the severe course of whooping cough, children in the first year of life often require hospitalization in the intensive care unit. Many common methods of treating cough (inhalation therapy, the use of acetylcysteine, carbocysteine, codeine-containing drugs) worsen the course of disease. In this regard, the main place in therapy is the correct treatment of cough. The article provides an overview of the main pathogenetic concepts of coughing and approaches to therapy: during the period of an obsessive spasmodic cough, to reduce the frequency and intensity of coughing, it is recommended to use an antitussive drug with a central effect of butamirate, oxygen therapy, refuse to perform invasive ventilation methods when child has apnea, and rapid rehabilitation of the children.

D-манноза в профилактике и лечении инфекций нижних мочевыводящих путей: патогенетические основы и клинические результаты

Non-antibacterial methods of prevention and treatment of lower urinary tract infection are described in the article. The current view on the mechanism of treatment effect of D-mannose is presented, which contributes to the prevention of bacterial invasion. Pathogenetic concepts for using D-mannose as specific antiadhesin or a competitive blocker of bacterial invasion is provided. In addition, we discussed the results of basic and clinical studies, proving the efficiency of D-mannose for prevention and treatment of lower urinary tract infection.

A half-century of participant observation in psychiatry. Part I. Schizophrenia.

In three articles, I discuss the 50 years of my work in psychiatry, in the formula of so called participant observation. The first one is about schizophrenia. I present important events of the pathogenesis and diagnostics in a recent half-century and my attempts to contribute to the research. Significant for clinical description was distinguishing the positive and negative symptoms of schizophrenia. The evidence for subcortical dopaminergic hyperactivity associated with positive (psychotic) symptoms, and prefrontal dopaminergic hypoactivity, responsible for mental deficits and cognitive impairment, has been obtained. Inhibition of the dopaminergic system (blocking of dopaminergic receptors D2) isthe main therapeutic mechanism of antipsychotic drugs. Neurobiological and genetic data also pointed to the role of the glutamatergic system in schizophrenia, which prompted trials of pharmacotherapy. For more than 30 years, the neurodevelopmental hypothesis of schizophrenia, assuming the interaction of genetic and environmental factors, leading to the first psychotic episode, has been the most important pathogenetic concept. In the 1990s, under my direction, neurobiological studies on schizophrenia were performed in the context of positive and negative symptoms and differences vs. mood disorders. Verification of the niacin test, apossible diagnostic aid in schizophrenia, was also made. In the recent two decades, molecular-genetic studies in schizophrenia, also using cognitive endophenotypes and eye movements, have been performed. The association of the polymorphism of various genes with schizophrenia or its endophenotype has been demonstrated, frequently, the first time in the world. In recent years, I directed a team implementing the Polish versions of new scales for the assessment of negative symptoms of schizophrenia.

Efficacy and safety of Mildronate in treatment of postinfectious asthenic syndrome (clinical examples)

Asthenic syndrome is a non‑specific syndrome that is often found in general medical practice in patients with various somatic pathologies both during an exacerbation of a chronic disease, and after an acute process. The leading symptoms in the clinic of asthenia are pathological weakness and fatigue. According to various researchers, they are found in 15–45 % of people. To date, there is no universally accepted definition and clear classification of this syndrome. The main pathogenetic concepts are the psychosocial, infectious‑immune theory of asthenia. The development of asthenic syndrome in patients with somatic pathology may be associated with the depletion of the functional capabilities of the nervous system due to disturbances in the blood supply to the brain, auto‑toxicity or exposure to exogenous toxic factors in bacterial, viral infections. There is no specific treatment for this condition. This article presents two clinical cases of the development of post‑infection asthenic syndrome in a 47‑year‑old patient against community‑acquired pneumonia and in a 36‑year‑old patient after an acute respiratory‑viral infection of moderate severity. In both cases, drug treatment with Mildronate was carried out with a positive trend in the form of regression of asthenia symptoms, side effects during treatment. Mildronate belongs to the class of cytoprotectors – antihypoxants, activates glycolysis and prevents impaired transport of adenosine triphosphate, providing a sufficient level of energy synthesis, which allows cells to maintain homeostasis and morphological integrity. The immunoadjuvant properties of Mildronate are very important in post‑infectious asthenic syndrome, since a violation of the immune response plays a central role in its pathogenesis. The immunoadjuvant properties of Mildronate have been discovered in a number of studies.

Calcium phosphate bions: towards a pathogenetic concept

Supersaturation of blood with calcium and phosphate is associated with higher risk of major adverse cardiovascular events; however, pathophysiological basis of such association remains unclear. Upon an excess of serum calcium and phosphate, mineral chaperone fetuin-A aggregates mineral ions into calcium phosphate bions (CPB, alternatively termed calciprotein particles), which are irreversibly internalised by endothelial cells causing lysosome membrane permeabilisation, non-specific inflammatory response and cell death. Altogether, these processes contribute to pathological microenvironment potentiating endothelial dysfunction, osteochondrogenic differentiation of vascular smooth muscle cells, and adventitial inflammation which in turn culminate into intimal hyperplasia and medial arterial calcification. Albeit the correlation between increased CPB count in the blood and higher risk of cardiovascular events/cardiovascular death has initially been found in patients with chronic kidney disease, recent investigations suggest similar scenario in patients with arterial hypertension and coronary artery disease without renal dysfunction testifying to the general pathophysiological mechanism. Here we discuss the existing data on how CPB do form and how they affect the development of cardiovascular disease. We further consider advantages and shortcomings of the relevant experimental models as well as diagnostic significance of measuring CPB in the serum and clinical potential of anti-CPP therapies for the patients with chronic kidney disease, coronary artery disease, and cerebrovascular disease.

The battle with uneven opponent – Sudden Infant Death Syndrome

Abstract SIDS is one of the biggest problems of modern medicine. In the diagnosis of SIDS, we take into account all possible diseases that may be the cause of death, as well as factors indicating an accident or murder. The etiology of SIDS is not yet known. There are several pathogenetic concepts, most of which refer to pathophysiological changes associated with nervous system hypoplasia. The most important risk factors include the effects of tobacco smoke, obstetric history, and incorrect sleep position. The role of risk factors in the pathogenesis of SIDS and their interdependence is still the subject of many studies. There are many theories developed on this subject, but none have been supported by scientific research and which is extremely difficult to carry out in this group of newborns. In most cases, medical help finds a newborn already dead, so it is difficult to say what is the main cause or marker of cot death. A considerable success in preventing the onset of sudden infant death syndrome turned out to be educational campaigns for parents - in order to follow up, an information leaflet was prepared with the basic recommendations in the prevention of SIDS. Among the parents of newborn children there are still many controversial opinions about risk factors in the onset of sudden infant death syndrome, the article contains and explains the meaning of individual activities that are considered to predispose to SIDS.

Contribution of Fractalkine to Incorrect Angiogenesis in Preeclamptic Placentas

Disregarding the multiple research in the field of preeclampsia, the exact pathology remains unclear. The shallow invasion of extravillous trophoblast (EVT) in spiral arteries leads to the development of pregnancy‐induced hypertension, nevertheless the etiological factor is unknown. Disturbed differentiation of EVT and incorrect placental angiogenesis seem to be one of the most important starting points for pathogenetic and etiological concepts in preeclampsia. As fractalkine (chemokine CX3CL1) by the activation of its only receptor CX3CR1 stimulates angiogenesis and integrin‐dependent cell migration, the authors ask the question about the possible role of CX3CL1 in placental angiogenesis in preeclampsia. A total number of 58 pregnant patients were included into the study, preeclampsia was diagnosed in 29 patients, and 29 patients were healthy, normotensive term pregnancies. In all women between 30 and 32 week of pregnancy CX3CL1 level was assessed in plasma using ELISA and the expression of CX3CR1 and angiogenesis score (V/EVTI: vascular/extravascular tissular index) were assessed in placental tissues obtained after delivery. Quantitative immunohistochemistry was applied for assessment of both CX3CR1 expression and V/EVTI in placental sections. For this second purpose, morphometric measurements of the placental microvasculature were performed after immunohistochemistry of endothelial cells with CD‐34 antibody. The average duration of pregnancy in preeclamptic group was shorter by 5,3 weeks than in normotensive pregnancies. CXC3CL1 plasma concentration was significantly lower in preeclamptic patients (mean 279 pg/ml ± 243 vs mean 846 pg/ml ± 418), whereas CX3CR1 expression was significantly (p < 0.05) higher in preeclamptic group. A negative correlation between CX3CL1 level and CX3CR1 expression was observed. Moreover, the V/EVTI value was lowered in preeclampsia (p < 0.05). In conclusion, disturbed placental angiogenesis in preeclampsia may be associated with low plasma fractalkine level.Support or Funding InformationWUM grant: 2M2‐W1‐18This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis.

In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has disease-specific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation ('go') and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest ('stop') under oxidative stress conditions. This model underscores a subtype-dependent 'go or stop' dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.

Клинико-патогенетическая концепция диагностики и комплексного лечения пациентов с сочетанной патологией венозной и опорно-двигательной систем нижних конечностей

Клинико-патогенетическая концепция диагностики и комплексного лечения пациентов с сочетанной патологией венозной и опорно-двигательной систем нижних конечностей

THE REAEARCH OF TREATMENT ACTIVITY OF COMBINED COMPOSITION OF RECTAL CREAM ON THE MODEL OF THE CHRONIC ANAL FISSURE

Relevance. The development of a new pharmaceutical composition, in the form of a rectal cream containing diltiazem, lidocaine and methyluracil, for the conservative treatment of a chronic anal fissure (KAT) is scientifically substantiated. But by this time in Ukraine none of the above local medicines has been produced, which would be in line with the current pathogenetic concept of HAT therapy. Thus, the introduction of a new domestic medicinal product for the purpose of import substitution in this pharmaco-therapeutic group is an urgent task of the pharmacological science.
 Objective of the trial is to research the therapeutic effect of the rectal cream of the combined composition (RCCC) on the model of chronic anal fissure.
 Materials and methods. Chronic anal fissures were reproduced using the method of Adieva R.F. with co-authors. The research was performed on 48 white nonlinear rats. Evaluation of the therapeutic effect of the rectal cream and the comparator was carried out daily during the experiment based on criteria of severity of the pathological process and data macroscopic observations, hematological and morphological examination, as well as the integral index, considered the death rate of the animals.
 Results. The research allowed to determine that use of pharmaceutical composition which contains diltiazem, lidocaine and methyluracil in the experiment of chronic anal fissure leads to decreasing the severity of inflammation on 31 %, decreasing of the purulonecrotic complications on 57,1 % as well as improving the reparative processes of marginal epithelialization on 42,9 %.
 Conclusion. The therapeutic effect of the investigated cream is most likely caused its ability to decrease the tone of the muscle fibers of the internal anal sphincter, normalize the microcirculation and stimulate cell proliferation. It was also concluded that the comparator product "Proctosan" is inferior to the investigated cream on the effectiveness and practically does not show a therapeutic effect on the model of chronic anal fissure.

Emerging Biomarkers, Tools, and Treatments for Diabetic Polyneuropathy.

Diabetic neuropathy, with its major clinical sequels, notably neuropathic pain, foot ulcers, and autonomic dysfunction, is associated with substantial morbidity, increased risk of mortality, and reduced quality of life. Despite its major clinical impact, diabetic neuropathy remains underdiagnosed and undertreated. Moreover, the evidence supporting a benefit for causal treatment is weak at least in patients with type 2 diabetes, and current pharmacotherapy is largely limited to symptomatic treatment options. Thus, a better understanding of the underlying pathophysiology is mandatory for translation into new diagnostic and treatment approaches. Improved knowledge about pathogenic pathways implicated in the development of diabetic neuropathy could lead to novel diagnostic techniques that have the potential of improving the early detection of neuropathy in diabetes and prediabetes to eventually embark on new treatment strategies. In this review, we first provide an overview on the current clinical aspects and illustrate the pathogenetic concepts of (pre)diabetic neuropathy. We then describe the biomarkers emerging from these concepts and novel diagnostic tools and appraise their utility in the early detection and prediction of predominantly distal sensorimotor polyneuropathy. Finally, we discuss the evidence for and limitations of the current and novel therapy options with particular emphasis on lifestyle modification and pathogenesis-derived treatment approaches. Altogether, recent years have brought forth a multitude of emerging biomarkers reflecting different pathogenic pathways such as oxidative stress and inflammation and diagnostic tools for an early detection and prediction of (pre)diabetic neuropathy. Ultimately, these insights should culminate in improving our therapeutic armamentarium against this common and debilitating or even life-threatening condition.

Complement depletion and Coombs positivity in pneumococcal hemolytic uremic syndrome (pnHUS). Case series and plea to revisit an old pathogenetic concept

Hemolytic uremic syndrome is a rare complication of invasive pneumococcal infection (pnHUS). Its pathogenesis is poorly understood, and treatment remains controversial. The emerging role of complement in various forms of HUS warrants a new look at this “old” disease.We performed a retrospective analysis of clinical and laboratory features of three sequential cases of pnHUS since 2008 associated with pneumonia/pleural empyema, two due to Streptococcus pneumoniae serotype 19 A. Profound depletion of complement C3 (and less of C4) was observed in two patients. One patient was Coombs test positive. Her red blood cells (RBCs) strongly agglutinated with blood group compatible donor serum at 0 °C, but not at 37 °C. All three patients were treated with hemodialysis, concentrated RBCs, and platelets. Patient 2 received frozen plasma for hepatic failure with coagulation factor depletion. Intravenous immunoglobulin infusion, intended to neutralize pneumococcal neuraminidase in patient 3, was associated with rapid normalization of platelets and cessation of hemolysis. Two patients recovered without sequelae or disease recurrence. Patient 2 died within 2½ days of admission due to complicating Pseudomonas aeruginosa sepsis and multiorgan failure.Our observations suggest that pnHUS can be associated with dramatic, transient complement consumption early in the course of the disease, probably via the alternative pathway. A critical review of the literature and the reported cases argue against the postulated pathological role of preformed antibodies against the neuraminidase-exposed Thomsen-Friedenreich neoantigen (T antigen) in pnHUS. The improved understanding of complement regulation and bacterial strategies of complement evasion allows to propose a testable, new pathogenetic model of pnHUS. This model shifts emphasis from the action of natural anti-T antibodies toward impaired Complement Factor H (CFH) binding and function on desialylated membranes. Removal of neuraminic acid residues converts (protected) self to non-self surfaces that supports membrane attack complex (MAC) assembly. Complement activation is potentially exacerbated by decreased CFH availability following tight CFH binding to pneumococcal evasion proteins and/or by the presence of genetic variants of complement regulator proteins. Detailed clinical and experimental investigations are warranted to better understand the role of unregulated complement activation in pnHUS. Instead of avoidance of plasma, a new, integrated model is evolving, which may include short-term therapeutic complement blockade, particularly where genetic or functional APC dysregulation is suspected, in addition to bacterial elimination and, potentially, neuraminidase neutralization.

Peculiar aspects of endometriosis in adolescents

Although documented rates of endometriosis in adolescent patients undergoing laparoscopy for chronic pelvic pain range from about 25% to 45%, adolescent endometriosis has received limited attention in terms of research activity and follow-up studies. In this manuscript, distinctive characteristics of adolescent and young endometriosis have been considered in order to define pathogenetic and scientific concepts that might be useful in clarifying some aspects of the adult disease as well. Some highlights relative to the cellular origin of the disease can be derived from reported cases before menarche, from the appearance of endometriotic lesions in teenagers (mostly stage I-II endometriosis), and from the relative infrequency of ovarian endometriotic cysts in this population. Adolescents and young patients might be also particularly useful for studying the natural course of the disease. To this end, clinical manifestations and recurrence patterns of the disease in adolescent patients need to be elucidated. ...

Disorders of the gallbladder and sphincter of Oddi in the Rome criteria IV: diagnostic capabilities, or searching for a “gold standard”

The aim of the work is to study and describe modern ideas on the functional gallbladder and sphincter of Oddi disorders (FGSOD). The main methods of FGSOD diagnosis are described, their diagnostic capabilities and possible adverse consequences are indicated. The changes of indications for the use of invasive methods of FGSOD diagnosis and treatment are reflected through the historical context. A comparative analysis of FGSOD classifications in the Rome criteria for functional gastrointestinal disorders in 2006 and 2016 was conducted. The main results of the most significant studies, devoted to the different variants of FGSOD, carried out in various countries during the last decade, are given. The new pathogenetic concepts about the mechanism of biliary pain and the methods of treatment of FGSOD are described. The refined diagnostic criteria of FGSOD can be of significant interest to practicing gastroenterologists and therapists.