P0305DIAGNOSTIC VALUE OF TGF-B-1 AND ANG II EXCRERION IN URINE IN CHILDREN WITH VESICOURETERAL REFLUX DEPENDING ON THE THERAPEUTIC APPROACH

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Natalia Zaicova ◽  
Tatiana Sudareva ◽  
Vladimir Dlin ◽  
Lilia Sinitsina ◽  
Anatolii Korsunskiy

Abstract Background and Aims to determine the diagnostic value of profibrogenic cytokines of transforming growth factor (TGF-β1) and angiotensin II (AngII) in urine to detect the severity of tubulointerstitial fibrosis in children with vesicoureteral reflux (VUR) depending on the therapeutic approach. Method 117 patients aged 3 to 16 years (mean age 10.2 ± 4.5, 70.1% of girls) with VUR were examined. The control group consisted of 20 healthy children. All children underwent a complete nephrological examination. The levels of TGF-β1 and AngII were determined in morning urine using the ELISA method and counted for urine creatinine. To identify the severity of the lesion of the renal parenchyma, a static DMSA scintigraphy was performed. Results depending on the therapeutic approach, the children were divided into 2 groups: 1 gr. - children on conservative treatment (63.2%), 2 gr. - children, after surgical correction of VUR (36.8%). In each group, 3 subgroups were identified depending on the development of tubulo-interstitial fibrosis according to DMSA: A subgr. - without signs of sclerosis (15.4%), B subgr. - 1-2 foci (44.74%) and C subgr - > 3-4 foci of sclerosis (40.1%). All patients with VUR had a high urinary excretion of TGF-β1/Cr and AngII/Cr when compared with the control group (p<0.05). Regardless of the therapeutic approach, in subgroups A (without foci of sclerosis) and B (1-2 foci of sclerosis), patients had a statistically significantly lower level of excretion of these cytokines when compared with patients from subgroup C (p <0.05). No significant difference was found in the urinary excretion of TGF-β1/Cr and AngII/Cr depending on the therapeutic approach. Conclusion we established a reliable dependence of the excretion of TGF-β1/Cr and AngII /Cr in the urine on the severity of tubulo-interstitial fibrosis according to DMSA scintigraphy in children with VUR. At the same time, we did not note the dependence of the excretion of TGF-β1/Cr and AngII/Cr in the urine on the method of the therapeutic approach. Therefore, the study of the excretion of TGF-β1/Cr and AngII/Cr in the urine as non-invasive markers can be used as a criterion for the progression of nephropathy in VUR, regardless of treatment methods.

2021 ◽  
Vol 100 (3) ◽  
pp. 88-96
Author(s):  
A.V. Eremeeva ◽  
◽  
V.V. Dlin ◽  
D.A. Kudlay ◽  
A.A. Korsunskiy ◽  
...  

Objective of the study: to study the clinical significance of the determination of angiotensin 2 (Ang II) and transforming growth factor β1 (TGF-β1) in urine of children with acute and chronic secondary pyelonephritis (PN) for increasing the efficiency of diagnosis of the disease. Materials and methods of research: a prospective open non-randomized controlled longitudinal single-center study was carried out in the Speransky City Children’s Hospital № 9 from January 10, 2015 to June 2020 to study the sensitivity and specificity of the tests under study. 60 children from 1 to 15 years old with acute and chronic secondary PN were examined. Children were divided into 2 groups: 1st – 30 patients with the onset of acute PN, 2nd – 30 patients with recurrent chronic secondary PN. The control group consisted of 20 apparently healthy children. In the 1st group of patients, girls predominated (24 children, 80%), the median age was 7 [3; 9] years, the median duration of followup is 41 [8; 45] months from the onset of the disease. In the 2nd group girls also predominated – 23 (77%), the median age – 8 [5; 11] years, the median duration of the disease at the time of inclusion in the study was 5 [3; 9] years. Most children were diagnosed with vesicoureteral reflux (VUR): grade I–II – in 18 (60%) and grade II–III – in 7 (23%). Incomplete renal doubling was detected in 4 (14%) patients, complete – in one (3%). The control group mainly consisted of girls – 16 (80%), the median age – 5,5 [3,25; 8,75] years. All patients underwent a study of general clinical and biochemical blood test, general analysis of urine, determination in a single morning portion of urine by enzyme immunoassay method according to ELISA TGF-β1 and Ang II. To standardize the level of TGF-β1 and Ang II in the urine, the level of creatinine in each portion of urine was determined and the results were converted to 1 mg of creatinine. Instrumental examination included ultrasound of the kidneys and bladder before and after micturition. Static nephroscintigraphy was performed 6 months after the onset of the disease or recurrence of chronic secondary PN. Results: it was found that at the onset of acute PN and with relapses of chronic secondary PN, there was an increased urinary excretion of TGF-β1 (p=0,002) and Ang II (p=0,002) when compared with the control group. It was shown that the level of increase in these markers depended on the form of PN. There were statistically significant differences in the urinary excretion of TGF-β1 and Ang II in children with acute PN and exacerbation of chronic secondary PN prior to the initiation of antibiotic therapy (p=0,001 and p=0,001, respectively). Urinary levels of Ang II and TGF-β1 in patients with exacerbation of chronic secondary PN in the first days of the microbial-inflammatory process in the renal parenchyma were by an order of magnitude higher than those in children with the onset of acute PN. A high degree of correlation was revealed between the level of uAng II/Cr and uTGF-β1/Cr (r=0,75, p=0,0001 and r=0,89, p=0,0001, respectively) in the 1st and 2nd groups of children (r=0,86, p=0,0001 and r=0,75, p=0,001, respectively) in the acute phase of the disease before antibiotic therapy with the data obtained during static nephroscintigraphy in the period of remission of the disease. Conclusion: the results indicate the importance of studying the urinary excretion of Ang II/Cr and TGF-β1/Cr as additional diagnostic markers for the identification of patients with a relapse current of PN, as well as to predict the degree of development of sclerotic processes in the renal tissue in children with different forms of PN.


2004 ◽  
Vol 287 (6) ◽  
pp. L1160-L1164 ◽  
Author(s):  
Reza Aghanouri ◽  
Mostafa Ghanei ◽  
Jafar Aslani ◽  
Hossein Keivani-Amine ◽  
Ferdos Rastegar ◽  
...  

Over 100,000 Iranian war veterans suffer from chronic effects of mustard gas exposure. Sulfur mustard was used by Iraq during the Iraqi-imposed war on Iran (between 1980 and 1988). The major complaints of these patients are mild interstitial fibrosis and bronchiolitis. We aimed to determine the state of fibrosis progression and assessed transforming growth factor (TGF)-β1 levels in pulmonary samples and in bronchoalveolar lavage (BAL) aspirates. A total of 126 war veterans confirmed for lung disease were assessed and compared with three control groups: 1) 64 veterans not exposed to chemical agents, 2) 12 idiopathic pulmonary fibrosis civilian patients, and 3) 33 normal persons. BAL was performed via a flexible fiber-optic bronchoscope and the standard manual method. Total protein was measured by Bradford assay, and samples were corrected with regard to coefficients. Samples were concentrated 15-fold by lyophilization and resolubilization. Samples were double-checked using an ELISA test kit. The Mann-Whitney test was used for the data analysis using commercial software. We detected that significant differences between TGF-β1 levels between the case group and control group 1 ( P = 0.001) and control group 3 ( P = 0.003). No significant differences were found between the case group and control group 2 ( P = 0.57). Inflammation and fibrotic processes in lung tissue of patients exposed to sulfur mustard may be progressive so IFN-γ may be a useful drug to these patients' treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Shahram Bamdad ◽  
Fatemeh Sanie-Jahromi ◽  
Marzieh Alamolhoda ◽  
Nasrin Masihpour ◽  
Mohammad-Hossein Karimi

Background. To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-β1 (TGF-β1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. Methods. A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-β1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. Results. At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80–2.98; 95% CI2: 1.00–4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06–4.92). The analysis of TGF-β1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-β1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-β1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18–0.96). Conclusion. The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-β1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.


2021 ◽  
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  

Abstract BackgroundDendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. MethodsTwenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed using a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect mRNA expression of TGF-β1 and alpha-smooth muscle actin (α-SMA) genes and proteins, respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. ResultsDMix significantly reduced FBG level, BW, KW, and blood lipid level, and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced protein and mRNA expression of TGF-β1 and α-SMA, and inhibited Smad2 and Smad3 phosphorylation. ConclusionsThe findings suggest that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway. Key words: Diabetic nephropathy, Dendrobium mixture, TGF-β1/Smads signaling pathway


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-β1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-β1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Melek Pehlivan ◽  
Tülay K. Ayna ◽  
Maşallah Baran ◽  
Mustafa Soyöz ◽  
Aslı Ö. Koçyiğit ◽  
...  

Abstract Objectives There are several hypotheses on the effects of the rs1738074 T/C single nucleotide polymorphism in the TAGAP gene; however, there has been no study on Turkish pediatric patients. We aimed to investigate the association of celiac disease (CD) and type 1 diabetes mellitus (T1DM) comorbidity with the polymorphism in the TAGAP gene of Turkish pediatric patients. Methods Totally, 127 pediatric CD patients and 100 healthy children were included. We determined the polymorphism by the allele-specific polymerase chain reaction method. We used IBM SPSS Statistics version 25.0 and Arlequin 3.5.2 for the statistical analyses. The authors have no conflict of interest. Results It was determined that 72% (n=154) of only CD patients had C allele, whereas 28% (n=60) had T allele. Of the patients with celiac and T1DM, 42.5% (n=17) and 57.5% (n=23) had T and C alleles, respectively. Of the individuals in control group, 67% (n=134) had C allele, whereas 33% (n=66) had T allele. Conclusions There was no significant difference in the genotype and allele frequencies between the patient and control groups (p>0.05). There was no significant association between the disease risk and the polymorphism in our study group.


Author(s):  
Elif Karatoprak ◽  
Samet Paksoy

AbstractThe aim of this study was to investigate the thyroid functions in children receiving levetiracetam or valproate monotherapy. We retrospectively reviewed the records of children with controlled epilepsy receiving valproic acid (VPA group) or levetiracetam monotherapy (LEV group) for at least 6 months. Free thyroxine 4 levels (fT4) and thyroid stimulating hormone (TSH) levels were compared between VPA group, LEV group, and age- and gender-matched healthy children (control group). A total of 190 children were included in the study: 63 were in the VPA, 60 in the LEV, and 67 in the control group. Although there was no significant difference regarding average fT4 levels, higher TSH levels were found in the VPA group when compared with the LEV and control groups (p < 0.001 and p < 0.001, respectively). There was no significant difference in terms of fT4 and TSH values in the LEV group when compared with the control group (p = 0.56 and p = 0.61, respectively). Subclinical hypothyroidism (defined as a TSH level above 5 uIU/mL with a normal fT4 level was detected in 16% of patients in the VPA group, none in the LEV and control groups. Our study found that VPA therapy is associated with an increased risk of subclinical hypothyroidism while LEV had no effect on thyroid function tests.


Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.


2020 ◽  
Vol 21 (19) ◽  
pp. 7374
Author(s):  
Gilberto Y. Nakama ◽  
Sabrina Gonzalez ◽  
Polina Matre ◽  
Xiaodong Mu ◽  
Kaitlyn E. Whitney ◽  
...  

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).


2014 ◽  
Vol 86 (3) ◽  
pp. 212 ◽  
Author(s):  
Orhan Koca ◽  
Mehmet Akyüz ◽  
Bilal Karaman ◽  
Zeynep Yesim Özcan ◽  
Metin Öztürk ◽  
...  

Objectives: Nocturnal enuresis (NE) is very common and is one of the most common causes for patients to be admitted to urology, pediatrics, child psychiatry and child surgery departments. We aimed to investigate the effect on depression and self-esteem of this disorder that can cause problems on person's social development and human relations. Material and methods: 90 patients who were admitted to our clinic with complaints of nocturnal enuresis were enrolled. Investigations to rule out organic causes were performed in this group of patients. Out of them 38 children and adolescents (age range 8-18 years) with primary monosymptomatic nocturnal enuresis (PMNE) agreed to participate in the study In the same period 46 healthy children and adolescents with a similar age range without bed wetting complaint were included in the study as a control group. The age of the family, educational and socioeconomic level were questioned and Piers-Harris Children's Self-Concept Scale (PHCSCS) and Children's Depression Inventory (CDI) forms were filled out. Results: Mean age of the cases (18 females or 47.4% and 20 males or 52.6%) was 10.76 ± 3.82 years whereas mean age of controls (26 females or 56.5% and 20 males or 43.5%) was 10.89 ± 3.11 years. Depression scale was significantly higher (p = 0.001) in the case group than in the control group (10.42 ± 4.31 vs 7.09 ± 4.35). In both groups there was no statistically significant difference by age and sex in terms of depression scale (p &gt; 0.05). Conclusion: NE is widely seen as in the community and is a source of stresses either for children and for their families. When patients were admitted to physicians for treatment, a multidisciplinary approach should be offered and the necessary psychological support should be provided jointly by child psychiatrists and psychologists.


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