Marker For Pathological Changes Research Articles

CLINICAL DIAGNOSTIC ALGORITHMS OF ACTION IN THE PRACTICE OF A DOCTOR OF GENERAL PRACTICE – FAMILY MEDICINE DISEASES OF THE URINARY SYSTEM IN CHILDREN

Chronic kidney disease (CKD) is the presence of markers of pathological changes in the urinary system lasting more than 12 weeks, regardless of their cause. The number of cases in children with diseases of the urinary system has documented confi rmed chronic kidney disease according to the implemented regional registry of patients with CKD, but its signifi cant spread is observed. Early manifestations of CKD are often underestimated and not treated in time. CKD and chronic renal failure are not a narrowly defi ned nephrological problem. Nowadays, military aggression and the consequences of the 2019 coronavirus pandemic (COVID-19), which led to the destruction of standard ways (patient clinical routes) in the provision of medical care, the issue of providing medical care to children on the basis of evidence- based and personalized medicine is of particular relevance in Ukraine, which, according to the WHO strategy, should meet the needs and be safe,eff ective, timely and of appropriate quality. The introduction of innovations in pediatric practice in terms of standardization of medical care helps the physician to act eff ectively in specifi c clinical situations, avoiding ineff ective actions. Involvement of specialists of other specialties (general practitioners- family medicine, endocrinologists, urologists, cardiologists, pediatricians, ophthalmologists) in the management of CKD without coordination of cooperation to ensure the principle of continuity complicates the diagnostic and/or therapeutic support of the patient. Early diagnosis, proper management tactics of pediatric patients with diseases of the urinary system at the outpatient stage is an important component in the provision of integrated, patient- oriented medical care in the practice of a general practitioner- family medicine. The article highlights the clinical and diagnostic algorithms of action of a general practitioner- family medicine regarding the tactics ofmanagement of pediatric patients with the most common nephrological symptoms: leukocyturia (bacteriuria), proteinuria and erythrocyturia. The scientifi c research was carried out within the framework of the Department of Pediatrics, Neonatology and Perinatal Medicine of the Bukovinian State Medical University. The research topics included: Research project on «Chronobiological and adaptive aspects and features of autonomic regulation in pathological conditions in children of diff erent age groups» (State registration number: 0122U002245, duration: 01.01.2022-31.12.2026).

Tear lactoferrin concentration in patients with recurrent herpetic stromal keratitis and therapeutic effect of Lacto eyedrops in the multicomponent treatment for this disorder

Background: Herpetic stromal keratitis (HSK) is an immunomodulatory disease that develops as a result of herpes simplex virus (HSV)1 or HSV2 reactivation. HSK is the most common form (20-50%) of recurrent herpetic keratitis (HK) that most commonly results in significantly reduced vision. It is well known that changes in biological compound levels in tear fluid can be indicative of the state of the ocular surface and determine whether ocular surface pathology is present, and, therefore, can be used as diagnostic markers of pathological changes in the ocular surface. Lactoferrin (LF) is one of these compounds and has been proven to have innate antibacterial, antifungal, antiviral, antiparasite, anti-inflammatory, immunomodulatory, antioxidative and other properties. Purpose: To determine tear Lf concentration in patients with recurrent acute HSK, its effect on functional characteristics of the ocular surface, and the therapeutic effect of Lacto eyedrops in the comprehensive treatment for this disorder. Material and Methods: The study was conducted at the site of Corneal Pathology Department and Immunology Laboratory of the Institute in January to December 2021. Seventeen patients (17 affected eyes and 17 fellow eyes) with recurrent acute HSK were included in the study. Mean patient age plus or minus standard deviation (SD) was 48.7 ± 16.0 years. The ophthalmological examination included biomicroscopy of the bulbar conjunctiva and cornea, fluorescein test, determination of corneal sensation and basal tear production (Schirmer’s II test), and microbiological examination of the conjunctiva. Tear Lf concentration was determined by a human Lf enzyme-linked immunosorbent assay (ELISA) kit (Elabscience Biotechnology, Inc., Wuhan, China). The results were photometrically measured at 450 nm with an ELISA reader (Stat Fax 2100, Awareness Technology Inc, Palm City, FL). Lacto eyedrops were administered two times a day for 30 days. Tear Lf concentrations were determined at baseline and at day 30. Results: Mean tear LF concentration plus or minus SD in eyes of patients with recurrent HSK was 1.21 ± 0.52 g/l, with no significant difference between the affected eye and fellow eye. However, a subnormal tear LF concentration was more common in the affected eye than in the fellow eye (2 = 4.24, р = 0.04). After a 30-day anti-inflammatory treatment with Lacto eyedrops, mean tear LF concentration plus or minus SD increased by 47% to 1.78 ± 0.7 g/l in the affected eyes. A corneal sensation score of 1 to 9 was 12.4 times more common in HSK eyes than in fellow eyes (OR = 12.4; 95% CI, 2.0–76.8), which reflects neurosensory abnormalities in the affected eye. Corneal sensation loss, was, however, more common in HSK eyes with a low tear Lf concentration than in fellow eyes with a low tear Lf concentration. Median basal tear production (as assessed by Schirmer’s II test) was as low as 7-8 mm in eyes with a low tear Lf concentration and as high as 13-16 mm in eyes with a high tear Lf concentration (p less 0.05). There was a direct correlation between the basal tear production and the tear Lf concentration (r=0.45; p less 0.05). Among study patients with recurrent HSK, 24.9% showed baseline microbiological evidence of potentially pathogenic or fungal organisms in the conjunctiva. A course of multicomponent anti-inflammatory treatment with Lacto eyedrops contributed to complete removal of these organisms. Conclusion: We determined mean tear Lf concentrations in affected and fellow eyes of patients with recurrent HSK, and established certain relationships between functional characteristics of the ocular surface and tear Lf concentrations in these eyes. A disinfecting effect of Lacto eyedrops against any microorganisms present in the conjunctival sac of patients with recurrent HSK was confirmed by the absence of culture growth on completion of the multicomponent anti-inflammatory treatment.

The features of autoimmunity in complicated atherosclerosis: A pilot study

Background: There is increasing evidence that autoimmunity plays an essential role in atherogenesis. At the same time, changes in the profile of natural autoantibodies (AAb) are characteristic not only of autoimmune, but also of all somatic diseases in general, since AAb can, without being the cause of the disease, respond to illness-related changes being a kind of bioregulators of homeostasis and/or immunological clearance factors. Methods: The enzyme immunoassays ELI-Cardio-Test was used to determine changes in serum content of a 12 natural AAb towards the autoantigens, which are the markers of pathological changes in myocardium and blood vessel walls, in 5 patients with diagnosis of severe complicated atherosclerosis and 5 healthy individuals. Results: patients with atherosclerosis were characterized by significantly more frequent and pronounced deviations in the autoimmunoreactivity against platelet membrane antigen (TrM) than healthy controls. The level of other natural AAb did not differ between study groups. Conclusions: It is not possible to distinguish between individuals without atherosclerosis and those with severe atherosclerosis, based on the overall picture of the autoimmune profile for manufacturer-selected antigens. However, the obvious discordance of groups in terms of autoimmunoreactivity to TrM merits further study. Perhaps, it is worth for a manufacturer to modify the set of autoantigens in this panel and focus more on the autoimmunity against platelet antigens as well as add the appropriate information about anti-TrM autoimmunity to the kit leaflet.

Impact of food load test on microcirculation parameters in the liver of rats of different gender and age

Introduction. One of the promising directions of studying liver microcirculation is searching for age-related features of its hemodynamics and early markers of pathological changes. Objective – to study the parameters of microcirculation in the liver of animals of different sex and age during a load test. Materials and methods. The study was conducted on 60 mongrel rats of both sexes weighing 120–270 g, divided into three age groups. The first group included 20 rats aged 1 month, the second – 20 rats aged 6–12 months and the third – 20 rats aged more than 18–24 months. The study of microcirculation was performed using a laser Doppler flowmeter LAKK-02 (Russia) under zoletil-xylazine anesthesia. Then, the rats were injected per os with mixture for enteral nutrition Nutridrink (Nutricia) in a ratio of 5 mg/kg of body weight. After 15 minutes the microcirculation parameters were determined again. Digital data were processed by methods of variation statistics. Results. In the liver of rats, the basic parameters of microcirculation were slightly higher in females compared to males: by 8.22 % (R=0.31) in the I, by 8.66 % (R= 0.05) in the II and by 1.19 % (R=0.48) in the III age group. With an increase in the age of the animals, the microcirculation indicators decreased. After the load test, an increase in microcirculation indexes was noted in the liver of rats in all age groups: by 45.13 % (R=0.82) in the I, by 27.99 % (R=0.64) in the II and by 15.88 % (R=0.91) in the III age group. Conclusion. There was no statistically significant dependence of the parameters of microcirculation in the liver of rats on the sex of the animals. With an increase in the rat’s age, the microcirculation rates decreased. After a food load test in the liver of rats, a statistically significant increase of the parameters of microcirculation was noted in all age groups. With an increase in the age of animals, the increase in microcirculation rates after a food load test significantly decreased.

Are High Frequency Oscillations in Scalp EEG Related to Age?

BackgroundHigh-frequency oscillations (HFOs) have received much attention in recent years, particularly in the clinical context. In addition to their application as a marker for pathological changes in patients with epilepsy, HFOs have also been brought into context with several physiological mechanisms. Furthermore, recent studies reported a relation between an increase of HFO rate and age in invasive EEG recordings. The present study aimed to investigate whether this relation can be replicated in scalp-EEG.MethodsWe recorded high-density EEG from 11 epilepsy patients at rest as well as during motor performance. Manual detection of HFOs was performed by two independent raters following a standardized protocol. Patients were grouped by age into younger (<25 years) and older (>50 years) participants.ResultsNo significant difference of HFO-rates was found between groups [U = 10.5, p = 0.429, r = 0.3].ConclusionsLack of replicability of the age effect of HFOs may be due to the local propagation patterns of age-related HFOs occurring in deep structures. However, limitations such as small sample size, decreased signal-to-noise ratio as compared to invasive recordings, as well as HFO-mimicking artifacts must be considered.

Association of serum brain-specific protein fragments and brain metastases in patients with metastatic breast cancer.

e14007 Background: Brain metastases (BrMs) occur frequently in patients with breast cancer (BC) and represent one of the most difficult-to-treat events. Novel clinical tools are needed to identify BC patients at high risk of developing BrMs. Blood-based liquid biopsies represent a minimally invasive procedure that may detect surrogate markers of pathological changes occuring in the brain as a result of BrMs. Here we evaluated serum levels of a panel of brain-specific protein fragments in metastatic BC patients with BrMs, with no-BrMs and controls. Methods: Our cohort includes stage IV BC patients with BrMs (n= 27; median age 51 y.o.) and no-BrMs (n=50; median age 53.5 y.o.), and healthy controls (H) (n=23, median age 50 y.o.). Serum levels of 5 brain-specific protein fragments were measured by immunoassays and compared between groups. No-BrMs samples were collected at the time of metastatic disease diagnosis; BrMs samples were collected at BrMs diagnosis and before local treatment. Association with overall survival (OS) was evaluated by univariate Cox regression analysis. Results: All markers were significantly higher in patients with no-BrMs compared to H. Only Neurocan, Tenascin-R and GFAP were significantly higher in patients with BrMs compared to H. When comparing metastatic BC patients, significantly higher levels of Tau-A, Tau-C, Neurocan and GFAP were found in no-BrMs patients versus BrMs (Table). Association with OS was not found in BrMs patients, although a trend for high Tau-A levels to predict poor OS was detected in the no-BrMs group (HR 4.4, 95%CI 0.9-21.3, p=0.068). Conclusions: Protein fragments expected to be derived from brain remodeling consequent to BrMs were elevated in BC patients both with BrMs and no-BrMs at the time of sampling, with an overall trend for the highest levels to be found in patients with no-BrMs. This may suggest that brain remodeling processes are associated with BC and could partly explain the relatively high incidence of BrMs relapse in BC. Further studies requiring samples collected pre- and post-treatment are needed to further validate the diagnostic and prognostic value of these non-invasive biomarkers in BC BrMs setting. [Table: see text]

The first case of autochthonous Echinococcus multilocularis in human in the Republic of Kalmykia

Purpose: Two recognized species of Echinococcus, have special medical importance - E. granulosus and E. multilocularis - causing cystic echinococcosis (CE) and alveolar echinococcosis (AE) in humans. Due to the developed pasture livestock farming, the prevalence of the rural population in the territory of the Republic of Kalmykia, cases of CE are recorded annually. However, no cases of AE have been observed in this area. Purpose to describe the first case of AE in the territory of the south of Russua. Methods & Materials: Case of AE was described in 46-year-old patient, who contracted disease in non-endemic area. Results: In September 2016, a 46-year-old patient, a resident of the rural area of Kalmykia, applied to the surgical clinic of Rostov Medical University. The patient complained of the appearance of large tumor in the right side of the abdomen. With tomography, a lumpy tumor of the right lobe of the liver was found, 18 × 20 cm in size, with sharp uneven contours, and an inhomogeneous density. Condition of health in patient was relatively satisfactory. Markers of pathological changes in the blood tests were absent. The level of AlAt exceeded the normal values by 3 times. Patient was examined with an enzyme-linked immunosorbent assay (ELISA) and antibodies G against E. Granulosus were discovered (coefficient of positivity 1.5). A Western Blot IgG reaction detected antigen fractions 26–28 kDa specific for E. multilocularis. The tumor was removed in the surgical clinic of Rostov Medical University. The patient underwent liver resection. Alveolar echinococcosis was verified by histological examination of the tumor. The patient was under medical supervision in clinic of infectious and parasitic diseases of Rostov-on-Don Research Institute of Microbiology and Parasitology. The patient received chemotherapy with albendazole 800 mg per day per day in 2 doses with an interval of 12 hours continuous course during 9 months. The patient was examined in March 2018, signs of recurrence of alveococcosis were not revealed. Conclusion: The appearance of alveolar echinococcosis in areas where it was not previously recorded in human is also noted by some European scientists. Thus, it is necessary to improve the serological methods for diagnosis AE.

Evaluation of Noncystic Fibrosis Bronchiectasis Using Clinical and Radiological Scorings in Children.

The aim of this study was to evaluate radiological, clinical, and demographic data of patients with noncystic fibrosis bronchiectasis and to compare high-resolution computed tomography (HRCT) scores based on the demographic and clinical characteristics. A total of 34 patients (18 male, 16 female) were assessed in terms of age at symptom onset, age at diagnosis, annual attack frequency, cough severity score, physical examination findings, and pulmonary function test results. Modified Bhalla scoring system (B total) and anatomical prevalence degree score (D total) were used for HRCT examination. There was a strong negative correlation between forced expiratory volume at first second (FEV1) and bronchial dilatation degree (SBRDIL). There was a moderate negative correlation of FEV1, forced vital capacity (FVC), and maximum mid-expiratory flow rate (MEF; 25-75) with bronchiectasis degree (EXBRNC), bronchial wall thickness degree (SBWTHICK), and mucus accumulation in the major airways (PMPLA). The B total, D total, EXBRNC, and SBRDIL scores were significantly higher in patients with hemoptysis and sputum. In comparing B and D total scoring systems, B total provided better results in terms of rale, annual exacerbation frequency (AEF), cough severity score (CSS), and FEV1 values. As it is proved using HRCT, pulmonary function impairment, sputum production, hemoptysis, and increase in AEF strongly correlating with objective HRCT scoring can be accepted as markers for pathological changes due to bronchiectasis.

Investigation of metabolic changes in STZ-induced diabetic rats with hyperpolarized [1-13C]acetate.

In the metabolism of acetate several enzymes are involved, which play an important role in free fatty acid oxidation. Fatty acid metabolism is altered in diabetes patients and therefore acetate might serve as a marker for pathological changes in the fuel selection of cells, as these changes occur in diabetes patients. Acetylcarnitine is a metabolic product of acetate, which enables its transport into the mitochondria for energy production. This study investigates whether the ratio of acetylcarnitine to acetate, measured by noninvasive hyperpolarized [1-13C]acetate magnetic resonance spectroscopy, could serve as a marker for myocardial, hepatic, and renal metabolic changes in rats with Streptozotocin (STZ)-induced diabetes in vivo. We demonstrate that the conversion of acetate to acetylcarnitine could be detected and quantified in all three organs of interest. More interestingly, we found that the hyperpolarized acetylcarnitine to acetate ratio was independent of blood glucose levels and prolonged hyperglycemia following diabetes induction in a type-1 diabetes model.

Multicenter measurements of myelin water fraction and geometric mean T2: Intra‐ and intersite reproducibility

To assess the reproducibility of myelin water fraction (MWF) and geometric mean T2 (GMT2 ), which are in vivo markers of pathological changes underlying disability and progression in diseases such as multiple sclerosis. Five healthy volunteers were scanned twice within 24 hours at six different sites using the same manufacturer's 3T magnetic resonance (MR) system. T2 distributions were produced by fitting multiecho 3D T2 data using non-negative least squares, with stimulated echo correction. MWF, the fraction of signal with T2 between 15 and 40 msec to the entire signal, and GMT2 , the mean T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white matter. Intrasite coefficients of variation (COVs) were low (mean 3.99% for MWF and 0.51% for GMT2 ), as were intersite COVs (mean 4.68% for MWF, 0.31% for GMT2 ). Scan-rescan intraclass correlation coefficients (ICCs) (0.76 for MWF and 0.93 for GMT2 ) and Bland-Altman plots indicated good agreement between single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for GMT2 ), revealing good intersite reliability. MWF and GMT2 measures are reproducible between scans and across sites with an equivalent MR scanner and sequence protocol. Multicenter clinical trials using quantitative T2 relaxation are feasible.

Cofilin-1 in the podocyte: a molecular switch for actin dynamics

Studies by Garg et al. and Ashworth et al. investigated the functional relevance of a key regulatory protein, cofilin-1, for podocyte actin dynamics (Ashworth et al. in PLos One 5:e12626, 2010; Garg et al. in J Biol Chem 285:22676-22688, 2010). Using different model organisms (zebrafish or transgenic mice), both groups observed a collapse of the glomerular filtration barrier upon inactivation of cofilin-1. In elegant biochemical studies, Garg et al. established that cofilin-1 activity is regulated by nephrin, which is part of the slit diaphragm complex. Two feedback loops stabilize cofilin-1 in the phosphorylated versus dephosphorylated state. The novel findings render cofilin-1 activity as potential diagnostic marker for pathological changes in the podocyte cytoarchitecture.

Ultrasound detection of endometrial fluid in postmenopausal women

The aim, of this prospective study was to estimate whether the presence of endometrial fluid detected by transvaginal ultrasound investigation was a marker for the pathological changes of the endometrium in postmenopausal women. 128 postmenopausal women with uterine bleeding and 29 asymptomatic postmenopausal women underwent transvaginal ultrasound investigation, curettage and histopathological investigation of the curettage specimens. There were significantly more asymptomatic women with endometrial fluid collection was found (41,4%) than those with uterine bleeding (7,8%) (p<0,001). We found 4 cases of carcinoma of the endometrium, 4 with hyperplasia and 1 with polyp of the endometrium in women with uterine bleeding and endometrial fluid collection. In the asymptomatic group of women we found 1 case with polyp and 1 with carcinoma of the endometrium. In the presence of endometrial fluid collection the least thickness of the endometrium measured by transvaginal ultrasound was 12 mm in postmenopausal women with carcinoma of the endometrium, 7 mm in women with hyperplasia and 5 mm with polyp. No pathological changes were found below the above values. The presence of endometrial fluid detected by transvaginal ultrasonography is a good marker for pathological changes of the endometrium in postmenopausal women if the endometrial thickness is greater than 4 mm. If the endometrial thickness is 4 mm or less, the presence of endometrial fluid is not an indication for further invasive investigation of endometrial cavity, but we must eliminate possible presence of ednexal or cervical malignant disease in some patients.

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome

Burning mouth syndrome is a common disorder that frequently affects women in the 5th–7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two-thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the pathogenesis of the disease. We examined 12 patients with clinically definite burning mouth syndrome for at least 6 months. We obtained superficial biopsies of the lateral aspect of the anterior two-thirds of the tongue from all patients and nine healthy controls. Immunohistochemical and confocal microscope co-localization studies were performed with cytoplasmatic, cytoskeletric, Schwann cell, and myelin markers for pathological changes. The density of epithelial nerve fibers was quantified. Patients showed a significantly lower density of epithelial nerve fibers than controls, with a trend toward correlation with the duration of symptoms. Epithelial and sub-papillary nerve fibers showed diffuse morphological changes reflecting axonal degeneration. Our study demonstrates that burning mouth syndrome is caused by a trigeminal small-fiber sensory neuropathy and that superficial biopsy of the tongue can be helpful in assessing the diagnosis. These findings shed light into the pathogenesis of this common disorder and could contribute to evaluate targeted therapies in patients.

Studies on Trace Elements in Progressive Pathology of DMBA-Induced Hamster Buccal Pouch Carcinogenesis.

Alterations in the levels of copper, zinc, and cadmium were investigated in both serum and buccal mucosa of hamsters in progressive pathology, namely, hyperplasia, papilloma, early invasive carcinoma, and well-differentiated squamous cell carcinoma. Hamster buccal pouch carcinogenesis was induced by tri-weekly topical application of a 0.5% solution of 7, 12-dimethylbenz(a)anthracene (DMBA) in liquid paraffin applied with a brush on the right buccal mucosa for 16 weeks. Serum copper levels and the copper/zinc ratio were generally elevated, and serum zinc levels were generally depressed, during carcinogenesis; and these alterations were related to the advancing stages of carcinogenesis. In transformed buccal mucosa, a significant decrease in the level of copper and a significant increase in the level of zinc were seen with papillomatous tissues onwards, and the alterations were progressive with the development of carcinomas. The changes in the levels of cadmium were moderate and occurred only in carcinomas. These data suggest that the alterations in the levels of copper, zinc, and copper/zinc ratio may be used as markers for pathological changes in the malignant transformation of oral mucosa.

Basement membrane proteoglycans and development

Basement membranes contain distinct collagen, glycoprotein and proteoglycan species, and these exhibit considerable heterogeneity in isoform or type when different tissue types are compared. Additionally, many components are differentially expressed in organogenesis. We have considered the distributions in glomerulogenesis of two distinct basement membrane proteoglycans, a small heparan sulfate proteoglycan and a chondroitin sulfate proteoglycan (BM-CSPG). While the former was present in all kidney basement membranes through development, the latter was apparently regulated in distribution. BM-CSPG was only strongly expressed in the vasculature invading late comma stage glomeruli, and later in presumptive and mature Bowman's capsule. Over the first six to eight weeks, the capillary basement membranes contained BM-CSPG, but in gradually decreasing amounts until it became completely undetectable. The basement membrane of the adult rat glomerulus is unique in its lack of BM-CSPG. However, in diabetic rats, BM-CSPG is apparently re-expressed in the glomerular basement membrane, a potential marker for pathological changes in glomerular structure. While its function awaits elucidation, BM-CSPG may be essential for basement membrane integrity or stability and have important roles in kidney development.