Pathohistological analysis of kidney tissue in obese patients and obesity impact evalution of the chronic renal failure progression

Gojaznost je definisana povećanjem masne mase tela koja dovodi do narušavanja zdravlja. Gojazne osobe imaju veliki rizik za razvoj sleep apnea sindroma, hiperlipidemije, hipertenzije, koronarne vaskularne bolesti, insulinske rezistenzije i dijabetesa. Poslednjih 15 godina ekvivalentan porast prevalence gojaznosti i terminalne bubrežne slabosti uslovio je i povećan interes za ispitivanje uloge gojaznosti u nastanku gojaznošću uslovljene bolesti bubrega. Gojaznost ne samo da ubrzava progresiju već postojećeg bubrežnog oštećenja, već je i sama po sebi nezavistan faktor rizika za nastanak bubrežnog oštećenja. Najpoznatija bubrežna bolest nastala zbog gojaznosti je gojaznošću uslovljena glomerulopatija (GUG), entitet koji se karakteriše proteinurijom, glomerulomegalijom, progresivnom glomerulosklerozom i smanjenjem funkcije bubrega. Ovaj patohistološki entitet je sekundarna forma bolesti glomerula kod gojaznih bolesnika sa morfološkim karakteristikama fokalno segmentne glomeruloskleroze (FSGS) i uvećanjem glomerula ili samo uvećanjem glomerula. Srećom, sve gojazne osobe neće razviti GUG. Cilj: Cilj ove doktorske disertacije je utvrditi parametre morfometrijske i fraktalne analize glomerula, klinički tok i ishod nakon dve godine praćenja gojaznih i negojaznih ispitanika. Metode: Studija je obavljena na Klinici za nefrologiju, Kliničkog centra Srbije u periodu od 2015. do 2017.godine. Patohistološka analiza tkiva bubrega obavljena je na Institutu za patologiju, Medicinskog fakulteta. U studiju je uključeno 125 ispitanika (77 muškaraca, prosečne starosti 46.92±15.10 godina) kod kojih postavljena dijagnoza: fokalno segmentne glomeruloskleroze, IgA nefropatije, membranoznog glomerulonefritisa, membranoproliferativnog glomerulonefritisa, bolest minimalnih promena, dijabetesne nefropatije i nefroangioskleroze. Na osnovu indeksa telesne mase ispitanici su podeljeni u dve grupe: gojazni (BMI ≥ 27 kg/m2- 63 ispitanika, prosečne starosti 50.1±15.1 godina) i negojazni (BMI< 27 kg/m2- 62 ispitanika, prosečne starosti 44.1±14.5 godina). Na dan biopsije, 6, 12 i 24 meseca nakon biopsije praćeni su sledeći parametri: koncentracija hemoglobina, kreatinina, ukupnih proteina, albumina, holesterola, triglicerida, proteinurije u 24h urinu. Jačina glomerulske filtracije (JGF) procenjena je formulama: Cockcroft-Gault# (Cockcroft-Gault -BMI < 27 kg/m2 i Cockcroft- GaultLBW - BMI ≥27 kg/m2) i CKD- EPI...Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health. Obese persons are at a greater risc to develop sleep apnea syndrome, hyperlipidemia, hypertension, coronary vascular disease, insulin resistance and diabetes. During the last 15 years there has been an equivalent dramatic rise in the prevalence of obesity and end stage renal disease, increasing the interest on the role of obesity- related kidney disease. Obesity not only increases the risk preexisting renal disease progression, but is itself also the independent risk factor of renal injury. The best known renal disease secondary to obesity is obesity related glomerulopathy (ORG), a distinct entity featuring proteinuria, glomerulomegalia, progressive glomerulosclerosis and renal functional decline. This pathohistological entity is described as a secondary form of glomerular disease in obese patients with morphological characteristics of focal segmental glomerulosclerosis (FSGS) and enlargement of the glomeruli, or only by enlargement of the glomeruli. Fortunately, not all obese persons develop ORG. Aim: The aim of this dissertation was to evaluate the glomerular morphometry, fractal analysis parameters, clinical features and two years outcome in obese and non-obese patients. Methods: The study was performed at the Clinic of Nephrology, Clinical center of Serbia in the period between 2015 and 2017 year. The pathohistological analysis of kidney tissue was done at the Institute for Pathology, School of Medicine. The study included 125 patients (77 males, mean age 46.92±15.10 years) who were diagnosed with one of the following diseases: focal segmental glomerulosclerosis (FSGS), IgA nephropathy, membranous glomerulonephritis, membranoproliferative glomerulonephritis, minimal change disease, diabetic nephropathy and nephroangiosclerosis. Based on BMI patients were divided into two groups: obese (BMI≥ 27 kg/m2- 63 patients, mean age 50.1±15.1 years) and non-obese (BMI< 27 kg/m2- 62 patients, age 44.1±14.5 years). At the time of the kidney biopsy, 6, 12 and 24 months after the biopsy following parameters were determined: haemoglobine concentration, serum concentration of creatinine, total proteins, albumin, cholesterol, triglyceride and 24-hour urine protein test. The estimated glomerular filtratio rate (eGFR) was calculated according to formulas: Cockcroft- Gault# (Cockcroft-Gault -BMI < 27 kg/m2 and Cockcroft-GaultLBW - BMI ≥27 kg/m2) and CKD- EPI..

Pathohistological analysis of kidney tissue in obese patients and obesity impact evalution of the chronic renal failure progression

Gojaznost je definisana povećanjem masne mase tela koja dovodi do narušavanja zdravlja. Gojazne osobe imaju veliki rizik za razvoj sleep apnea sindroma, hiperlipidemije, hipertenzije, koronarne vaskularne bolesti, insulinske rezistenzije i dijabetesa. Poslednjih 15 godina ekvivalentan porast prevalence gojaznosti i terminalne bubrežne slabosti uslovio je i povećan interes za ispitivanje uloge gojaznosti u nastanku gojaznošću uslovljene bolesti bubrega. Gojaznost ne samo da ubrzava progresiju već postojećeg bubrežnog oštećenja, već je i sama po sebi nezavistan faktor rizika za nastanak bubrežnog oštećenja. Najpoznatija bubrežna bolest nastala zbog gojaznosti je gojaznošću uslovljena glomerulopatija (GUG), entitet koji se karakteriše proteinurijom, glomerulomegalijom, progresivnom glomerulosklerozom i smanjenjem funkcije bubrega. Ovaj patohistološki entitet je sekundarna forma bolesti glomerula kod gojaznih bolesnika sa morfološkim karakteristikama fokalno segmentne glomeruloskleroze (FSGS) i uvećanjem glomerula ili samo uvećanjem glomerula. Srećom, sve gojazne osobe neće razviti GUG. Cilj: Cilj ove doktorske disertacije je utvrditi parametre morfometrijske i fraktalne analize glomerula, klinički tok i ishod nakon dve godine praćenja gojaznih i negojaznih ispitanika. Metode: Studija je obavljena na Klinici za nefrologiju, Kliničkog centra Srbije u periodu od 2015. do 2017.godine. Patohistološka analiza tkiva bubrega obavljena je na Institutu za patologiju, Medicinskog fakulteta. U studiju je uključeno 125 ispitanika (77 muškaraca, prosečne starosti 46.92±15.10 godina) kod kojih postavljena dijagnoza: fokalno segmentne glomeruloskleroze, IgA nefropatije, membranoznog glomerulonefritisa, membranoproliferativnog glomerulonefritisa, bolest minimalnih promena, dijabetesne nefropatije i nefroangioskleroze. Na osnovu indeksa telesne mase ispitanici su podeljeni u dve grupe: gojazni (BMI ≥ 27 kg/m2- 63 ispitanika, prosečne starosti 50.1±15.1 godina) i negojazni (BMI< 27 kg/m2- 62 ispitanika, prosečne starosti 44.1±14.5 godina). Na dan biopsije, 6, 12 i 24 meseca nakon biopsije praćeni su sledeći parametri: koncentracija hemoglobina, kreatinina, ukupnih proteina, albumina, holesterola, triglicerida, proteinurije u 24h urinu. Jačina glomerulske filtracije (JGF) procenjena je formulama: Cockcroft-Gault# (Cockcroft-Gault -BMI < 27 kg/m2 i Cockcroft- GaultLBW - BMI ≥27 kg/m2) i CKD- EPI...Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health. Obese persons are at a greater risc to develop sleep apnea syndrome, hyperlipidemia, hypertension, coronary vascular disease, insulin resistance and diabetes. During the last 15 years there has been an equivalent dramatic rise in the prevalence of obesity and end stage renal disease, increasing the interest on the role of obesity- related kidney disease. Obesity not only increases the risk preexisting renal disease progression, but is itself also the independent risk factor of renal injury. The best known renal disease secondary to obesity is obesity related glomerulopathy (ORG), a distinct entity featuring proteinuria, glomerulomegalia, progressive glomerulosclerosis and renal functional decline. This pathohistological entity is described as a secondary form of glomerular disease in obese patients with morphological characteristics of focal segmental glomerulosclerosis (FSGS) and enlargement of the glomeruli, or only by enlargement of the glomeruli. Fortunately, not all obese persons develop ORG. Aim: The aim of this dissertation was to evaluate the glomerular morphometry, fractal analysis parameters, clinical features and two years outcome in obese and non-obese patients. Methods: The study was performed at the Clinic of Nephrology, Clinical center of Serbia in the period between 2015 and 2017 year. The pathohistological analysis of kidney tissue was done at the Institute for Pathology, School of Medicine. The study included 125 patients (77 males, mean age 46.92±15.10 years) who were diagnosed with one of the following diseases: focal segmental glomerulosclerosis (FSGS), IgA nephropathy, membranous glomerulonephritis, membranoproliferative glomerulonephritis, minimal change disease, diabetic nephropathy and nephroangiosclerosis. Based on BMI patients were divided into two groups: obese (BMI≥ 27 kg/m2- 63 patients, mean age 50.1±15.1 years) and non-obese (BMI< 27 kg/m2- 62 patients, age 44.1±14.5 years). At the time of the kidney biopsy, 6, 12 and 24 months after the biopsy following parameters were determined: haemoglobine concentration, serum concentration of creatinine, total proteins, albumin, cholesterol, triglyceride and 24-hour urine protein test. The estimated glomerular filtratio rate (eGFR) was calculated according to formulas: Cockcroft- Gault# (Cockcroft-Gault -BMI < 27 kg/m2 and Cockcroft-GaultLBW - BMI ≥27 kg/m2) and CKD- EPI..

Visual acuity after trabeculectomy

Background/Aim. In this study we compared the two groups of glaucoma patients who had underwent trabeculectomy, with or without intraoperative application of antimetabolite 5-Fluorouracile (5 FU). Methods. We followed up 50 glaucoma patients (group I) in a four-years period after trabeculectomy alone (antimetabolites were not applied), and 50 patients in whom antimetabolite 5 FU was applied (group II). We followed up intraocular pressure (IOP), visual acuity (VA), lens transparency, optic disc changes, visual fields (VF perimetry).The IOP at the time of the surgery, and the period of the treatment before the surgery were the important data for the follow-up. Results. The results that we got in the first group were: in 8 patients (16%) there was no change of VA, and of optic disc with a mild VF deterioration; in 18 patients (33%) the worsening of VA by 1 Snellen line (3 years after the surgery) with no change of the disc and a mild VF progressing; in 10 patients (20%) VA decreased by 2 Snellen lines with the progressive VF changes and cataract appearance, (cataract and VA worsening appeared mainly 3 years after the surgery); in 6 patients (12%) by 3 Snellen lines, and in 4 patients (8%) by 4 Snellen lines. In 4 patients (8%), the highest worsening of VA - (0.2) and the best (0.9) at the time of the surgery were observed. The VA ranging from 0.4-0.6 at the time of the surgery yielded the longest preservation of vision. In the group II (5 FU applied intraoperatively): in 5 patients (10%) there was no change of VA and of optic disc with a mild VF deterioration; in 20 patients (40%) the worsening of VA by 1 Snellen line, with no change of the disc and a mild VF progressing. In 14 patients (28%) VA decreased by 2 Snellen lines with the progressive VF changes and cataract appearance; in 7 patients (14%) by 3 Snellen lines, and in 4 patients (8%) by 4 Snellen lines. Conclusion. All of the checked parameters were better in the group II of the patients, (5 FU applied intraoperatively). Also, in the group of the patients with the longest treatment before the surgery and with the good VA, and in the patients with the shorter treatment and with the bad VA, the quickest progression of the vision lost was observed. The best preservation of VA was recordered in the patients with a mild IOP, and in those who had not been treated more than 1 or 2 years with the drops before the surgery. The VA ranging from 0.4-0.6 at the time of the surgery allowed the longest preservation of vision

The cornea and methods for measuring intraocular pressure

Introduction: The study aimed to assert the relationship between central corneal thickness (CCT) and intraocular pressure (IOP) measured by: Goldmann applanation tonometry (GAT) and Dynamic contour tonometry (DCT). Materials and Methods: The study included 150 patients with a mean age of 59.39 ± 13.12 years. Patients were divided into three groups: 50 primary open-angle glaucoma (POAG) patients, 50 ocular hypertension (OHT) patients, and 50 normal tension glaucoma (NTG) patients. IOP was determined using GAT and DCT. CCT was measured by ultrasound pachymetry. Results: IOP measured with DCT was higher than IOP measured with GAT (19.80 ± 3.67 mmHg vs 17.71 ± 3.35 mmHg). A significant positive association between IOP measured with GAT and IOP measured with DCT was found in all patients (r = 0.867, p 0.05). Conclusion: CCT-influenced IOP was measured by both methods, GAT and DCT. DCT can not replace GAT, but it is very useful, especially in cases where errors are in the IOP GAT measurement

THE IMPORTANCE OF DETERMINING THE UROMODULIN SERUM CONCENTRATION IN DIABETES MELLITUS TYPE 2 PATIENTS

Introduction: In the kidney, cells in the thick ascending limb of the loop of the Henle synthesized uromodulin (UMOD). This study aims to present the evaluation of the uromodulin serum concentration in diabetes mellitus type 2 (T2DM) patients in the early detection of kidney damage. Materials and methods: The study included 50 T2DM patients with a mean age of 60.75±11.23 years with estimated glomerular filtration rate (eGFR) 114.38±22.12 ml/min and a control group of 20 healthy persons. We measured serum concentration of haemoglobin, urea, creatinine, uromodulin (ELISA method), and cystatin C (nephelometry). We determined formulas: Cockcroft-Gault# (combination Cockcroft- Gault for patients with BMI< 30 kg/m2 and Cockcroft- GaultLBW for patients with BMI≥ 30 kg/m2), CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration equation), and simple Cystatin C. Results: T2DM patients had lower hemoglobin serum concentration as well as eGFR calculated by formulas: Cockcroft- Gault# and CKD-EPI. T2DM patients had significantly higher BMI and cystatin C compared to control group. T2DM patients had significantly lower serum uromodulin concentration (136.51±84.34 vs 220.50±92.39 ng/ml) than in controls. Significant positive correlation between uromodulin and Cockcroft- Gault# (r= 0.432, p= 0.000), CKD- EPI (r = 0.439; p = 0.000) formulas as well as simple cystatin C (r = 0.250, p = 0.02), but negative correlation with age (r = -0.476, p =0.000), BMI (r = -0.313, p = 0.002) and cystatin C serum concentration (r = -0.293, p = 0.015) were found. Conclusion: The role of serum uromodulin concentration is not still fortified. The results of this study showed that reduced uromodulin serum concentration indicated early kidney damage in T2DM patients

Fatty acid- and retinoid-binding proteins have distinct binding pockets for the two types of cargo

Parasitic nematodes cause serious diseases in humans, animals, and plants. They have limited lipid metabolism and are reliant on lipid-binding proteins to acquire these metabolites from their hosts. Several structurally novel families of lipid-binding proteins in nematodes have been described, including the fatty acid- and retinoid-binding protein family (FAR). In Caenorhabditis elegans, used as a model for studying parasitic nematodes, eight C. elegans FAR proteins have been described. The crystal structure of C. elegans FAR-7 is the first structure of a FAR protein, and it exhibits a novel fold. It differs radically from the mammalian fatty acid-binding proteins and has two ligand binding pockets joined by a surface groove. The first can accommodate the aliphatic chain of fatty acids, whereas the second can accommodate the bulkier retinoids. In addition to demonstrating lipid binding by fluorescence spectroscopy, we present evidence that retinol binding is positively regulated by casein kinase II phosphorylation at a conserved site near the bottom of the second pocket. far-7::GFP (green fluorescent protein) expression shows that it is localized in the head hypodermal syncytia and the excretory cell but that this localization changes under starvation conditions. In conclusion, our study provides the basic structural and functional information for investigation of inhibitors of lipid binding by FAR proteins

The fractal and textural analysis of glomeruli in obese and non-obese patients

BackgroundFractal dimension is an indirect indicator of signal complexity. The aim was to evaluate the fractal and textural analysis parameters of glomeruli in obese and non-obese patients with glomerular diseases and association of these parameters with clinical features.MethodsThe study included 125 patients mean age 46 ± 15.2 years: obese (BMI ≥ 27 kg/m2—63 patients) and non-obese (BMI  0.05) compared to non-obese. Mean value of COR (t = 0.108) and IDM (t = 0.185) were almost the same in two patient groups. Obese patients had higher value of lacunarity (t = 0.499) in comparison with non-obese, the mean value of fractal dimension (t = 0.225) was almost the same in two groups. Significantly positive association between variance and creatinine concentration (r = 0.499, P < 0.01), significantly negative association between variance and CKD-EPI (r = -0.448, P < 0.01), variance and sex (r = -0.339, P < 0.05) were found.ConclusionsVariance showed significant correlation with serum creatinine concentration, CKD-EPI and sex. CON and IDM were significantly related to sex. Fractal and textural analysis parameters of glomeruli could become a supplement to histopathologic analysis of kidney tissue

Arthrospira (Spirulina) platensis supplementation affects folliculogenesis, progesterone and ghrelin levels in fattening pre-pubertal gilts

The aim of the present investigation was to study the effect of Arthrospira (Spirulina) platensis supplemented diet on follicular development and related endocrine parameters, such as estradiol and progesterone levels as well as ghrelin levels in pre-pubertal gilts. Twenty-one 60-day-old Danube White gilts, randomly divided in three groups—control and two experimental—were involved in the experiment. The diet of experimental animals was supplemented with 2 and 3 g of dry biomass/capita daily of the micro alga A. platensis (SP), respectively, during 120 days. Pigs weighing between 109.3 and 114.7 kg were slaughtered at the age of 180 days. The visual macroscopic and histological analysis of removed ovaries was done. Progesterone and estradiol levels by radioimmunoassay (RIA) and ghrelin by ELISE methods were measured. The presence of corpora lutea in the ovaries of animals from all three groups as well as the progesterone and estradiol levels indicated that the animals were cycling and puberty had started at the time of slaughtering. In the SP 3-g group, the number of large follicles and corpora lutea was significantly higher compared to the control group and the corpora albicans were found. A positive correlation was observed between ghrelin and progesterone among all groups as well as between estradiol and ghrelin in the experimental groups independent on dosages of SP. Arthrospira platensis-supplemented diet provoked a successful follicular development and an earlier ovulation during sexual maturation of pigs between 60 and 180 days