scholarly journals Molecular Evolution of Podocyte Slit-diaphragm Proteins

2020 ◽  
Author(s):  
NSK Mulukala ◽  
V Kambhampati ◽  
SAH Qadri ◽  
AK Pasupulati
Keyword(s):  
Protein Complexes ◽  
Slit Diaphragm ◽  
Ankyrin Repeats ◽  
Protein Loss ◽  
Acid Base Balance ◽  
Src Homology 3 ◽  
Base Balance ◽  
Src Homology ◽  
Spfh Domain ◽  
First Time

AbstractVertebrates kidneys contribute to the homeostasis by regulating electrolyte, acid-base balance, and prevent protein loss into the urine. Glomerular podocytes constitute blood-urine barrier and podocyte slit-diaphragm, a modified tight junction contributes to the glomerular permselectivity. Nephrin, podocin, CD2AP, and TRPC6 are considered to be crucial members, which largely interact with each other and contribute to the structural and functional integrity of the slit-diaphragm. In this study, we analyzed the distribution of these four-key slit-diaphragm proteins across the organisms for which the genome sequence is available. We found that nephrin has a diverse distribution ranging from nematodes to higher vertebrates whereas podocin, CD2AP, and TRPC6 are predominantly restricted to the vertebrates. In the invertebrates nephrin and its orthologs consist of more immunoglobulin-3 and immunoglobulin-5 domains when compared to the vertebrates wherein, CD80-like C2-set Ig2 domains were predominant. Src Homology-3 (SH3) domain of CD2AP and SPFH domain of podocin are highly conserved among vertebrates. Although the majority of the TRPC6 and its orthologs had conserved ankyrin repeats, TRP, and ion transport domains, the orthologs of TRPC6 present in Rhincodon typus and Acanthaster planci do not possess the ankyrin repeats. Intrinsically unstructured regions (IURs), which are considered to contribute to the interactions among these proteins are largely conserved among orthologs of these proteins, suggesting the importance of IURs in the protein complexes that constitute slit-diaphragm. This study for the first time reports the evolutionary insights of vertebrate slit-diaphragm proteins and its invertebrate orthologs.

scholarly journals Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254917
Author(s):  
Sandeep K. N. Mulukala ◽  
Vaishnavi Kambhampati ◽  
Abrar H. Qadri ◽  
Anil K. Pasupulati
Keyword(s):  
Protein Complexes ◽  
Slit Diaphragm ◽  
Ankyrin Repeats ◽  
Protein Loss ◽  
Acid Base Balance ◽  
Src Homology 3 ◽  
Base Balance ◽  
Src Homology ◽  
Spfh Domain ◽  
Unstructured Regions

Vertebrate kidneys contribute to homeostasis by regulating electrolyte, acid-base balance, removing toxic metabolites from blood, and preventing protein loss into the urine. Glomerular podocytes constitute the blood-urine barrier, and podocyte slit-diaphragm (SD), a modified tight junction, contributes to the glomerular permselectivity. Nephrin, KIRREL1, podocin, CD2AP, and TRPC6 are crucial members of the SD that interact with each other and contribute to the SD’s structural and functional integrity. This study analyzed the distribution of these five essential SD proteins across the organisms for which the genome sequence is available. We found a diverse distribution of nephrin and KIRREL1 ranging from nematodes to higher vertebrates, whereas podocin, CD2AP, and TRPC6 are restricted to the vertebrates. Among invertebrates, nephrin and its orthologs consist of more immunoglobulin-3 domains, whereas in the vertebrates, CD80-like C2-set domains are predominant. In the case of KIRREL1 and its orthologs, more Ig domains were observed in invertebrates than vertebrates. Src Homology-3 (SH3) domain of CD2AP and SPFH domain of podocin are highly conserved among vertebrates. TRPC6 and its orthologs had conserved ankyrin repeats, TRP, and ion transport domains, except Chondrichthyes and Echinodermata, which do not possess the ankyrin repeats. Intrinsically unstructured regions (IURs) are conserved across the SD orthologs, suggesting IURs importance in the protein complexes that constitute the slit-diaphragm. For the first time, a study reports the evolutionary insights of vertebrate SD proteins and their invertebrate orthologs.

scholarly journals P1803EFFICACY, SAFETY AND IMPACT ON RENAL FUNCTIONALITY OF ACETAZOLAMIDE TREATMENT IN PATIENTS WITH PMM2-CDG (AZATAX CLINICAL TRIAL)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mercedes Serano Guimaré ◽  
Pedro Arango Sancho ◽  
Víctor López Baez ◽  
Elena Codina Sampera ◽  
Yolanda Calzada Baños ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Ultrasound ◽  
Second Phase ◽  
Protein Loss ◽  
Acid Base Balance ◽  
Base Balance ◽  
Renal Prognosis ◽  
Intellectual Deficit ◽  
Glycosylation Defect

Abstract Background and Aims Deficit of phosphomanomutase-(PMM2-CDG) is the most frequent congenital N-glycosylation defect, producing cerebellar syndrome with intellectual deficit and “stroke-like” episodes. It has been associated with renal alterations such as proteinuria, diffuse cortical hyperechogenicity and malformations. We evaluated efficacy, safety and renal repercussion of acetazolamide as a new therapeutic tool. Method First clinical trial in phase II including PMM2-CDG patients (5-21-years). First phase: 6 months treatment group with acetazolamide. Second phase: 5 weeks randomized withdrawal in responders (acetazolamide vs placebo), assessing renal functionality and effects of this medication. Dosing acetazolamide by 8 to 30mg/kg/day in 2-3 doses. Controls were performed at 3, 6, 14, 25 and 30 weeks determining acid-base balance, ionogram, renal function (creatinine) and Pr/Cr, Ca/Cr index and B2-microglobulin in first morning urine. All patients underwent in a bone densitometry study and renal ultrasound. Results 24 patients were included (mean age 12.3 ± 4.5 years). Bicarbonate levels and plasma pH were significantly lower at week 25(p <0.001). 13 patient needs to reduce acetazolamide dose due to excessive metabolic acidosis or asthenia. They showed a decrease in sodium (p=0.06), potassium (p<0.001) and serum calcium(p=0.030), although maintained in low normality limit with a decrease in protein loss(p=0.019) and increase in calcium/creatinine index(p=0.025) without B2-microglobulin alterations. The previously ultrasound renal described findings; the cortical hyperechogenicity was observed in 8.4% without renal dysfunction or associated nephrocalcinosis. One patient presented microlithiasis and another, symptomatic renal lithiasis. Densitometric study 69% of patients presented values in the range of osteopenia at the end of trial (-0.9 to -4.9SD, average of -2.36SD). Conclusion The efficacy of acetazolamide in the neurological symptoms of PMM2-CDG, due to an enzymatic stimulation mechanism mediated by acidosis, generates the possibility of chronic treatment with the drug in this group of patients, with possible renal adverse effects associated with long-term, overshadowing the skeletal and renal prognosis.

scholarly journals Of Bars and Rings: Hof1-Dependent Cytokinesis in Multiseptated Hyphae of Ashbya gossypii

2008 ◽  
Vol 29 (3) ◽  
pp. 771-783 ◽  
Author(s):  
Andreas Kaufmann ◽  
Peter Philippsen
Keyword(s):  
Ashbya Gossypii ◽  
Actin Ring ◽  
Src Homology 3 ◽  
Filamentous Ascomycete ◽  
Multinucleated Cells ◽  
Ring Assembly ◽  
Src Homology ◽  
Type Ii Myosin ◽  
First Time

ABSTRACT We analyzed the development of multiple septa in elongated multinucleated cells (hyphae) of the filamentous ascomycete Ashbya gossypii in which septation is apparently uncoupled from nuclear cycles. A key player for this compartmentalization is the PCH protein Hof1. Hyphae that are lacking this protein form neither actin rings nor septa but still elongate at wild-type speed. Using in vivo fluorescence microscopy, we present for the first time the coordination of cytokinesis and septation in multiseptated and multinucleated cells. Hof1, the type II myosin Myo1, the landmark protein Bud3, and the IQGAP Cyk1 form collars of cortical bars already adjacent to hyphal tips, thereby marking the sites of septation. While hyphae continue to elongate, these proteins gradually form cortical rings. This bar-to-ring transition depends on Hof1 and Cyk1 but not Myo1 and is required for actin ring assembly. The Fes/CIP4 homology (FCH) domain of Hof1 ensures efficient localization of Hof1, whereas ring integrity is conferred by the Src homology 3 (SH3) domain. Up to several hours after site selection, actin ring contraction leads to membrane invagination and subsequent cytokinesis. Simultaneously, a septum forms between the adjacent hyphal compartments, which do not separate. During evolution, A. gossypii lost the homologs of two enzymes essential for cell separation in Saccharomyces cerevisiae.

scholarly journals P1830HEMODIALYSIS IN CHILDREN:NINE YEARS OF EXPERIENCE OF ALBANIAN CHILDREN HEMODIALYSIS CENTER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ornela Xhango ◽  
Rezar Xhepa ◽  
Diamant Shtiza
Keyword(s):  
Statistical Data ◽  
Fatal Outcome ◽  
Kidney Injury ◽  
Acid Base Balance ◽  
Acid Base ◽  
Chronic Injury ◽  
Renal Replacement Therapies ◽  
Limited Experience ◽  
Base Balance ◽  
First Time

Abstract Background and Aims Hemodialysis is one of the modalities of renal replacement therapies, which is required for patients with serious acute or chronic renal dysfunction, in consequence, with uremic toxicity and derangement of electrolytes and acid-base balance. We started provided an hemodyalisis treatment for children in Albania, for the first time about nine years ago. We want to show you our modest experience and some statistical data about the only centre of the hemodialysis for children in Albania. Method All patients who received hemodyalisis treatment between September 2010 and September 2019, were enrolled in the study. Results 55 children with acute or chronic injury received hemodyalisis treatment over 9 years; 28 females and 27 males, aged from 6 months to 17 years old. 29 cases had acute kidney injury (14 of them due to HUS). 23 of AKI cases are completely recovered. 5 cases had fatal outcome, one left with renal sequelae. Of 26 children with chronic kidney disease, 13 of them underwent live-related renal transplantation, 3 children are left to continue their treatments abroad, one child actually is in CAPD, 2children died, the others continue the dialysis treatments. 14 children came from Kosovo. Conclusion Despite the limited experience, our hemodialysis center has successfully handled cases not only from Albania, but also from Kosovo.

scholarly journals THE INDICATORS OF BASAL METABOLISM IN INFLAMMATORY SYNDROME BACTERIAL ORIGIN: PREDICTORS OF PROGNOSIS OR THE NEED FOR TIMELY CORRECTION?

2019 ◽  
Vol 64 (2) ◽  
pp. 122-127
Author(s):  
Yu. L. Ketsko ◽  
A. V. Lunina ◽  
O. A. Gusyakova ◽  
E. V. Petrovskaya ◽  
A. V. Lyamin ◽  
...  
Keyword(s):  
Antibacterial Therapy ◽  
Nutritional Therapy ◽  
Basal Metabolism ◽  
Protein Loss ◽  
Acid Base Balance ◽  
Logistic Analysis ◽  
Therapy Strategy ◽  
Base Balance ◽  
Inflammatory Syndrome

The aim of the study was to determine the comparative significance of basal metabolism indicators and inflammatory process markers for the closest prognosis of patients in ICUs with systemic inflammation syndrome caused with infectious genesis. The paper presents the results of a retrospective analysis of the plan of treatment of 198 patients with confirmed clinical and laboratory signs of bacterial infection. The number of leukocytes, platelets, the percentage of lymphocytes, the concentration of procalcitonin, creatinine, bilirubin, C-reactive protein, acid-base balance values were determined in patients. Patients were assessed on a SOFA scale. The type of biomaterial for microbiological research was determined depending on the intended source of infectious inflammation. Identification of the isolated microorganisms was carried out using the MALDI ToF mass spectrometry method, followed by determination of antibiotic resistance. Empirical antibiotic therapy was prescribed upon admission of the patient to the ICU. Patients were switched to etiotropic antibacterial therapy after 48 hours, taking into account the results of a microbiological study. Determination of basal metabolic rate was carried out using the method of indirect calorimetry (CCM Express, Medical Graphics) with the calculation of basal metabolism, respiratory coefficient, absolute and relative amount of macronutrients. The calculation of the protein was made on the basis of the nitrogen level of the daily urine urea. Logistic analysis (ROC analysis) revealed that the antibacterial therapy strategy used, age, gender of patients, tinctorial properties of microorganisms isolated from patients, do not affect the nearest prognosis of the disease. On the contrary, SOFA score, the concentration of procalcitonin in the blood, and such parameters of the metabolic status as the need for kilocalories per kilogram of actual body weight and the percentage of protein calories significantly affect the nearest prognosis of the disease. The percentage of calories derived from protein metabolism, in the main exchange has a high reliable predictive value. The results of the study confirm the importance of adequate nutritional therapy in the treatment of patients with infectious inflammatory syndrome, including the calculation and correction of protein loss and total daily calorie.

scholarly journals Ammonia and Acid-Base Balance During High Ammonia Exposure in a Marine Teleost (Myoxocephalus Octodecimspinosus)

1988 ◽  
Vol 140 (1) ◽  
pp. 89-105 ◽  
Author(s):  
JAMES B. CLAIBORNE ◽  
DAVID H. EVANS
Keyword(s):  
Marine Teleost ◽  
Acid Base Balance ◽  
Acid Base ◽  
External Application ◽  
Blood Ph ◽  
High Ammonia ◽  
Total Ammonia ◽  
Base Balance ◽  
First Time ◽  
Ammonia Exposure

For the first time in a marine teleost (the long-horned sculpin; Myoxocephalus octodecimspinosus), the maintenance of blood pH, PCoCo2, [HCO3− and the net movements of NH4+ HCO3− and H+ between the fish and the water have been studied during exposure to ammonia stress induced either by infusion (NH4Cl or NH4HCO3; 5 mmol kg−1) or by external application (NH4Cl; approx. 1 mmoll−1). Following NH4Cl infusion, a rapid decrease in blood pH (0.36 units) and [HCO3−] (2.38 mmoll−1) was observed, and within 1 h about 40% of the ammonia load had been excreted to the water. Analysis of NH4+ and HCO3− transfers revealed that the total ammonia (TAmm) efflux was due to a loss of NH3 and NH4+ in approximately equal proportions when an outwardly directed NH3 diffusion gradient was established. Infusion of NH4HCO3 induced only small changes in plasma pH, and the rate of net HCO3− excretion was some 90% higher than that of NH4+ over 20 h. These data indicate a predominance of NH3 as the form of ammonia lost. In both infusion experiments, a presumed intracellular buffering of a majority of the ammonia load was noted. High external TAmm induced an initial uptake of NH4+, but after 4 h of exposure ammonia efflux resumed even though NH3 diffusion gradients were negligible. Thus, in this seawater teleost, a role for the excretion of ammonia in the form of NH4+ is also likely.

Laboratory diagnostics in the urine of young and pregnant ewes

2011 ◽  
Vol 39 (02) ◽  
pp. 82-87 ◽  
Author(s):  
Y. Cetin ◽  
K. Failing ◽  
A. Wehrend ◽  
S. Sendag
Keyword(s):  
Dairy Cows ◽  
Ph Value ◽  
Urine Samples ◽  
Laboratory Diagnostics ◽  
Weak Correlation ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance ◽  
Weak Negative Correlation ◽  
First Time

Summary Objective: The purpose of this study was to identify values for net acid base excretion (NABE) which are significant indicators of the acidbase equilibrium in pregnant and young ewes and to show its relationship with other parameters (base, acid, ammonium [NH4], base-acid quotient, sodium [Na], potassium [K], calcium [Ca]) in ovine urine. In contrast to dairy cows, data are rare on these parameters in ewes. Material and methods: A total of 99 animals were used in the study, consisting of 56 young (average of 5.6 ± 1.1 months) and 43 pregnant ewes (average of 35.2 ± 18.8 months). Measurement of fractional NABE in urine samples was carried out according to the method reported by Kutas. The pH value of the urine was measured with a laboratory pH meter. Na, K and total Ca were measured with a flame photometer. Results: For all values except Na significant differences occurred between urine samples of pregnant ewes and young ewes (p < 0.001). Base, acid, NH4, NABE, K and Ca values were significantly higher in the urine of the youngs than in pregnant ewes. In young ewes, a strong correlation was found between NABE and base values while a weak correlation could be observed between pH and base values. In pregnant ewes, strong NABE-base, NABE-K, K-acid and K-base correlations were found as well as weak NH4-base, NH4-NABE and NH4-K correlations. There was a strongly positive correlation between NABE and NH4 in pregnant ewes, while a weak negative correlation between those values was observed in young ewes. Conclusion: For the first time, we established values for NABE and certain other parameters in urine of pregnant ewes and young ewes. It was shown that the acid-base balance in pregnant ewes and young ewes can be evaluated by measuring NABE and certain trace elements in urine like in cattle.

External quality assessment programs of laboratory test results conducted by the Central Center for Quality Research in Laboratory Diagnostics in 2018

2019 ◽  
Vol 55 (3) ◽  
pp. 209-228 ◽  
Author(s):  
Barbara Przybył-Hac ◽  
Jadwiga Ciechowicz ◽  
Dorota Waszczuk-Łysiuk
Keyword(s):  
Quality Assessment ◽  
Glycated Hemoglobin ◽  
External Quality Assessment ◽  
Laboratory Diagnostics ◽  
Acid Base Balance ◽  
External Quality ◽  
Quality Research ◽  
Laboratory Test Results ◽  
Base Balance ◽  
First Time

In 2018, the Center for Quality Research in Laboratory Diagnostics conducted 22 editions under eight external quality assessment programs. In two programs (in the field of hematology and parameters of acid-base balance and electrolytes of ISE) the frequency of editing from two to four has been increased, gradually adapting the programs to the requirements of the Regulation of the Minister of Health of December 15, 2017 (Journal of Laws). As part of the extension of the program offer, the Central Center introduced 12 new analytes in the coagulology program and implemented a new external quality assessment program for HbA1c glycated hemoglobin controls. The Central Center also implemented in 2018 a new procedure for transporting samples of control materials to laboratories. For the first time, the parcels were delivered by courier. In all programs implemented in 2018, higher percentages of correct results were obtained according to the adopted criteria and annual regularity assessments comparable to 2017. Very satisfactory results were also obtained for glycated hemoglobin, HbA1c – a pilot program implemented in 2018.

Interlaboratory EQA programmes realized in 2017 by Centre for Quality Assessment in Laboratory Medicine

2019 ◽  
Vol 54 (4) ◽  
pp. 245-266
Author(s):  
Barbara Przybył-Hac ◽  
Andrzej M. Brzeziński ◽  
Jadwiga Ciechowicz ◽  
Dorota Waszczuk-Łysiuk
Keyword(s):  
Quality Assessment ◽  
Clinical Chemistry ◽  
Laboratory Medicine ◽  
Acid Base Balance ◽  
Acid Base ◽  
Central Program ◽  
Medical Diagnostic ◽  
Base Balance ◽  
General Program ◽  
First Time

In 2017, the Center for Quality Assessment in Laboratory Medicine conducted, in accordance with the adopted annual schedule, 28 editions of interlaboratory tests as part of the general program and the central program. The general program included tests in the field of clinical chemistry, acid-base balance parameters and ISE electrolytes, hematology, coagulology and immunochemistry (basic, extended and cardiac markers). In the common chemical program, four editions of tests were carried out, evaluating 8 different control materials. The remaining programs were carried out with the frequency of 2 editions a year and evaluated only 4 different control materials, with the exception of the acid-base balance program and ISE electrolytes (6 control materials per year). General program tests were available to all MLD who performed routine testing of analytes within the scope of individual testing programs (over 1,500 medical diagnostic laboratories), and chemical tests under the central program, implemented for over 40 years, concerned about 250 selected laboratories. In all completed editions of the tests, a slight increase in the odometer of results assessed as correct according to the adopted assessment criteria was observed. In 2017, participants of the programs were provided with a new certificate format with annual regularity assessments and for the first time in a general program in the field of clinical chemistry, quality certificates were issued in accordance with the Regulation of the Minister of Health of 15 December 2017.

First successful hemoadsorption using CytoSorb® in a septic pediatric patient in Kazakhstan: A case report

2019 ◽  
Vol 42 (6) ◽  
pp. 315-317 ◽  
Author(s):  
Askhat Saparov ◽  
Vitaliy Sazonov ◽  
Zaure Tobylbaeva ◽  
Samat Isakov ◽  
Almat Bekpan ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Pediatric Patient ◽  
Inflammation Markers ◽  
C Reactive Protein ◽  
Acid Base Balance ◽  
Acid Base ◽  
Reactive Protein ◽  
Base Balance ◽  
First Time ◽  
Extracorporeal Support

Purpose: For the first time in Kazakhstan, we have used a combined extracorporeal support, by including the CytoSorb system in a continuous veno-venous hemofiltration system in an 8-month-old patient with a body weight of 5600 g. Results: The CytoSorb therapy session resulted in a reduction of inflammation markers IL-6, S100, procalcitonin, and C-reactive protein. Simultaneously, the level of transaminases, creatine kinase, and troponin were normalized, by the end of the session patient hemodynamics were stable and there was no need for vasopressors, acid–base balance was maintained, and the patient was weaned from mechanical ventilation to spontaneous breathing. Conclusion: Treatment using the CytoSorb device was safe and well-tolerated in a pediatric patient and has proven its practical value as an adjuvant therapy for sepsis in pediatric patient populations.

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