scholarly journals Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

2021 ◽  
Vol 10 (14) ◽  
pp. 3160
Author(s):  
Agnieszka Pukajło-Marczyk ◽  
Danuta Zwolińska

Hemopexin (Hpx) is considered a factor in the pathogenesis of idiopathic nephrotic syndrome (INS). The aim of the study was to evaluate the serum and urine values of Hpx (sHpx and uHpx) in children with INS, analyze the role of Hpx, and assess its usefulness as a marker of the disease course. 51 children with INS and 18 age-matched controls were examined. Patients were divided into subgroups depending on the number of relapses (group IA—the first episode of INS, group IB—with relapses) and according to method of treatment (group IIA treated with gluco-corticosteroids (GCS), group IIB treated with GCS and other immunosuppressants). Hpx concentrations were determined by enzyme-linked immunosorbent assay (ELISA). sHpx and uHpx values in relapse were elevated in the whole INS group versus controls (p < 0.000). In remission their levels decreased, but still remained higher than in the control group (p < 0.000). In group IB uHpx levels were increased during remission as compared to group IA (p < 0.006). No significant impact of immuno-suppressants on sHpx was observed, but uHpx excretion in group IIA was higher in relapse (p < 0.026) and lower in remission (p < 0.0017) as compared to group IIB. The results suggest the role of Hpx in the pathogenesis of INS. Hpx may be a useful indicator for continuation of treatment, but it requires confirmation by further controlled studies.

2019 ◽  
Author(s):  
Natalia Maria Serwin ◽  
Magda Wiśniewska ◽  
Elżbieta Cecerska-Heryć ◽  
Krzysztof Safranow ◽  
Edyta Skwirczyńska ◽  
...  

Abstract Background Renalase is a flavoprotein involved in pathomechanisms of chronic kidney disease and heart and circulatory system disorders. Secretion and way of action of this protein are still discussed. Aim of our study was to initially estimate the balance between serum and urine renalase in healthy adults and to compare obtained ratio to chronic kidney disease patients. Methods Our study involved 28 healthy volunteers and 62 patients with diagnosed chronic kidney disease in stages I to IV. Concentration of renalase in blood serum and urine was measured using enzyme-linked immunosorbent assay (ELISA) kit (Uscn Life Science, Wuhan, China). We analyzed serum-to-urine renalase proportion in both groups and evaluated the differences using Mann Whitney U-test. Results Renalase serum-to-urine ratio was significantly higher in chronic kidney disease patients in comparison with control group (1.146 and 0.177, respectively; p<0.05). Also renalase serum-to-urine/mg creatinine ratio was higher in CKD patients than in healthy subjects (0.863 and 0.176, respectively; p<0.05). In both groups, no correlation between renalase concentration or serum-to-urine ratio, and eGFR, was found. Conclusions Renalase is involved in chronic kidney disease pathomechanism and is highly secreted and cumulated in blood of subjects with chronic kidney disease, what is accompanied by reduction of urinary renalase excretion. This may occur due to the potential role of renalase as a cytokine, preventing further kidney, and probably heart, dysfunction or injury. Chronic kidney disease causes higher expression of renalase, but its balance between serum and urine depends on more factors and conditions, involved in CKD pathomechanism.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None


1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Roberta da Silva Filha ◽  
Sérgio Veloso Brant Pinheiro ◽  
Thiago Macedo e Cordeiro ◽  
Victor Feracin ◽  
Érica Leandro Marciano Vieira ◽  
...  

AbstractIntroduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Saif Bushnaq ◽  
Atif Zafar ◽  
Kempuraj Duraisamy ◽  
Nudrat Tasneem ◽  
Mohammad M Khan ◽  
...  

Background: Interleukin-37 (IL-37) is a new member of IL-1 cytokine family with a defined role as a negative feedback inhibitor of pro-inflammatory responses. IL-37 has yet to be evaluated in non-immune neurological diseases like ischemic or hemorrhagic stroke. This study aimed to measure the urine and serum IL-37 levels in patients with acute ischemic stroke. Method: Twelve patients consented for the study. Two sets of serum and urine samples were obtained and analyzed; one upon admission to the hospital, and the second the next morning after overnight fasting. The trends in serum level of IL-37 in 5 stroke patients, while trends in urine level of 6 patients were available, measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Prior studies with healthy volunteers as control group have consistently showed IL-37 plasma level around or less than 65 pg/ml with maximum normal levels on ELISA approximated at 130 pg/ml. Results: IL-37 level in urine in stroke patients ranged from 297 - 4467. IL-37 levels were in the range of 300s to 1000s in patients with ischemic stroke compared with reported healthy controls in literature where the level was always less than 90. Three of these 10 patients presented within 3 hours of stroke onset with IL-37 serum levels being 2655 pg/ml, 3517 pg/ml and 5235 pg/ml. In all others, it ranged much less than that, with the trend of delayed presentation giving less IL-37 levels, both in urine and serum. There were no clear differences found in patients with or without tPA, diabetes, hyperlipidemia and high blood pressure in our small study. Conclusion: The study shows a rather stable elevation of IL-37 levels post-ischemic stroke, which if compared to available data from other studies, is 3-10 times elevated after acute ischemic stroke with an uptrend in the first few days. IL-37 plays some role in mediating post-stroke inflammation with significant rise in serum and urine IL-37 levels suggesting a key role of this novel cytokine in post-stroke pathology. This is the first ever reported study measuring and trending IL-37 levels in human plasma after an acute ischemic stroke.


2020 ◽  
Vol 45 (8) ◽  
pp. 2508-2517
Author(s):  
Xue Yang ◽  
Fang-Lin Hou ◽  
Cheng Zhao ◽  
Cai-Yun Jiang ◽  
Xiu-Mei Li ◽  
...  

2020 ◽  
Vol 34 ◽  
pp. 205873842092391 ◽  
Author(s):  
Min-na Dong ◽  
Yun Xiao ◽  
Yun-fei Li ◽  
Dong-mei Wang ◽  
Ya-ping Qu ◽  
...  

Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice.


2019 ◽  
Vol 20 (1) ◽  
pp. 159 ◽  
Author(s):  
Radzisław Mierzyński ◽  
Elżbieta Poniedziałek-Czajkowska ◽  
Dominik Dłuski ◽  
Jolanta Patro-Małysza ◽  
Żaneta Kimber-Trojnar ◽  
...  

Gestational diabetes mellitus (GDM) is considered to be one of the most frequent medical complication observed among pregnant women. The role of adipokines in the pathogenesis of GDM remains strictly unknown. Different adipokines have been studied throughout gestation, and they have been proposed as biomarkers of GDM and other pregnancy-related complications; however, there is no biomarker reported for GDM screening at present. The aim of this study was to evaluate serum nesfatin-1 and vaspin levels in GDM and non-GDM women, to characterize the correlation between these adipokines, and to assess the potential role of circulating adipokines in the prediction of risk of gestational diabetes mellitus. Serum concentrations of nesfatin-1 and vaspin were measured in 153 women with GDM, and in 84 patients with uncomplicated pregnancy by enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer’s instructions. Circulating levels of nesfatin-1 and vaspin were significantly lower in the GDM group than in the control group. Nesfatin-1 levels were negatively correlated with vaspin levels. The results of this study point out the possible role of nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of GDM. Further studies are necessary to evaluate the influence of nesfatin-1 and vaspin on glucose metabolism in the early stages of GDM.


1995 ◽  
Vol 13 (11) ◽  
pp. 2776-2783 ◽  
Author(s):  
E T Creagan ◽  
R J Dalton ◽  
D L Ahmann ◽  
S H Jung ◽  
R F Morton ◽  
...  

PURPOSE We conducted a randomized prospective trial in selected patients with fully resected high-risk stage I and II malignant melanoma. PATIENTS AND METHODS Interferon alfa-2a (IFN-alpha 2a) 20 x 10(6) U/m2 was administered three times each week for 12 weeks by the intramuscular route. Both the treatment group (n = 131) and the control group (n = 131) were evenly balanced with regard to relevant prognostic discriminants. RESULTS The median disease-free survival (DFS) time was 2.4 years for the IFN-alpha 2a group and 2.0 years for the observation group (log-rank P = 0.19). The median survival times were 6.6 years for IFN-alpha 2a and 5.0 years for observation (log-rank P = .40). For stage I patients (n = 102), there was no apparent therapeutic advantage from IFN-alpha 2a therapy. The DFS for stage II patients was a median of 10.8 months in the control group versus 17 months in the treatment group. The overall survival time was 4.1 years for the treatment group versus 2.7 years for the control group. The differences in DFS for stage II patient were significant in a Cox model. These results must be interpreted cautiously because of subset analysis. A severe flu-like toxicity occurred in 44% of patients, 13% lost at least 10% of their baseline weight, and 45% experienced a worsening of Eastern Cooperative Oncology Group (ECOG) performance score. CONCLUSION Our findings indicate trends that suggest a possible benefit for selected patients with high-risk malignant melanoma. The results will require further study in a larger patient population for confirmation.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3944-3944
Author(s):  
Fernanda A Silva ◽  
Gisele M Vasconcelos ◽  
Synara NS Cordeiro ◽  
Mariana Sant’Ana ◽  
Silvia Maia Farias de Carvalho ◽  
...  

Abstract Background. Indirect epidemiologic evidences have suggested that viral infections may represent an important risk factor in the etiological mechanisms of B cell precursor lymphoblastic leukemia (BpALL), specially common-ALL. Parvovirus B19 (PvB19) is associated with aplastic crisis, thrombocytopenia, and congenital anemia. Five studies have reported the concurrent PvB19 infection in pediatric ALL. In a view of the increasing contest about the direct or indirect role of viral infection in ALL, we evaluated the possible associations of PvB19 and herpes virus 6 (HHV-6) in samples from children suffering from hematological disorders in order to estimate the magnitude of risk of association with common-BpALL. Material and Methods. A total of 659 blood samples were randomly selected to perform the serological tests. They were part of diagnostic samples referred to CPq-INCA-Rio de Janeiro, Brazil, from 2002–2006, for diagnostic purpose. Blood samples were exclusively selected from patients in whom samples were taken at the time of the onset of sickness. The diagnosis of BpALL was based on immunophenotyping methods according to EGIL criteria. The presence of serum antibodies for PvB19 and HHV-6 were determinate by enzyme-linked immunosorbent assay. Statistical analyses were conducted using SPSS for Windows 11.0. All p values were two sided; p&lt;0.05 was considered statistically significant. Results. Common-ALL (n=176) and non-leukemic samples (n=107) considered as control group were stratified according to age-groups at diagnosis. Age distribution was: less than 2 years (15.5%); 2–6 years-old (46.0%), and 7–12 years-old (17.7%). The estimation of associated risk PvB19 IgG+ antibodies with common-BpALL was OR 0.53 95% CI (0.52–0.54); whereas HHV-6 IgG was OR 2.36, 95% CI (1.08–5.17). Conclusions. We find out a higher prevalence of HHV-6 antibodies in patients with common-BpALL, suggesting an association between HHV-6 infection e common-BpALL in Brazilian children. There is a long history in developed countries regarding the role of infections in leukemogenesis process. Further tests are necessary to confirm these results.


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