scholarly journals Elevated Endostatin Expression Is Regulated by the pIgA Immune Complex and Associated with Disease Severity of IgA Nephropathy

2020 ◽  
pp. 1-13
Author(s):  
Yaling Zhai ◽  
Xiaoqing Long ◽  
Jingge Gao ◽  
Xingchen Yao ◽  
Xinnian Wang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Disease Severity ◽  
Immune Complex ◽  
Poor Prognosis ◽  
High Serum ◽  
Endothelial Cell Proliferation ◽  
Renal Interstitium ◽  
Before And After ◽  
Poor Outcomes

<b><i>Background/Aims:</i></b> Renal vascular injury accounts for the poor outcomes of patients with IgA nephropathy (IgAN). In this study, we investigated whether endostatin, a potent inhibitor of angiogenesis, is associated with IgAN. <b><i>Methods:</i></b> Serum endostatin levels were detected in patients with IgAN, disease controls, and healthy controls, and the correlation among endostatin and clinicopathologic manifestations, as well as prognosis in patients with IgAN, was analyzed. In addition, serum endostatin levels were compared in patients “before” and “after” treatment. Data on endostatin expression in the renal interstitium of patients with IgAN were downloaded and analyzed from the GSE35489 array in the GEO database. The poly-IgA1 (pIgA) immune complex is widely recognized as the “trigger” of IgAN initiation. pIgA in the plasma of patients was extracted and used to stimulate human glomerular endothelial cells (GECs). Endostatin, IL-6, and CXCL1 in the cell supernatant were detected by ELISA kits. <b><i>Results:</i></b> We found that serum endostatin levels were significantly increased in patients with IgAN, as was endostatin expression in the renal interstitium. Patients with IgAN were divided into 2 groups according to the median value. The high endostatin expression group had significantly higher levels of serum creatinine and BUN and more severe tubular/interstitial damage. Moreover, patients with arteriolar injury and endothelial cell proliferation had higher serum endostatin levels. Patients with high serum endostatin levels had poor prognosis. According to the in vitro experiment, the GEC apoptosis rate and the supernatant levels of endostatin, IL-6, and CXCL1 were significantly increased following pIgA stimulation. <b><i>Conclusion:</i></b> Our study found that elevated endostatin expression was associated with disease severity and poor prognosis in patients with IgAN and can be upregulated by pIgA, but how it participates in the pathogenesis of IgAN deserves further exploration.

scholarly journals A New Vision of IgA Nephropathy: The Missing Link

2019 ◽  
Vol 21 (1) ◽  
pp. 189 ◽  
Author(s):  
Fabio Sallustio ◽  
Claudia Curci ◽  
Vincenzo Di Leo ◽  
Anna Gallone ◽  
Francesco Pesce ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
High Serum ◽  
In Vitro Production ◽  
Peripheral Blood Mononuclear ◽  
Familial Form ◽  
New Vision ◽  
New Perspective

IgA Nephropathy (IgAN) is a primary glomerulonephritis problem worldwide that develops mainly in the 2nd and 3rd decade of life and reaches end-stage kidney disease after 20 years from the biopsy-proven diagnosis, implying a great socio-economic burden. IgAN may occur in a sporadic or familial form. Studies on familial IgAN have shown that 66% of asymptomatic relatives carry immunological defects such as high IgA serum levels, abnormal spontaneous in vitro production of IgA from peripheral blood mononuclear cells (PBMCs), high serum levels of aberrantly glycosylated IgA1, and an altered PBMC cytokine production profile. Recent findings led us to focus our attention on a new perspective to study the pathogenesis of this disease, and new studies showed the involvement of factors driven by environment, lifestyle or diet that could affect the disease. In this review, we describe the results of studies carried out in IgAN patients derived from genomic and epigenomic studies. Moreover, we discuss the role of the microbiome in the disease. Finally, we suggest a new vision to consider IgA Nephropathy as a disease that is not disconnected from the environment in which we live but influenced, in addition to the genetic background, also by other environmental and behavioral factors that could be useful for developing precision nephrology and personalized therapy.

scholarly journals Vascular Response on a Novel Fibrin-Based Coated Flow Diverter

2021 ◽  
Author(s):  
Ruben Mühl-Benninghaus ◽  
Frederik Fries ◽  
Mara Kießling ◽  
Toshiki Tomori ◽  
Stefanie Krajewski ◽  
...  
Keyword(s):  
Animal Model ◽  
Flow Diverter ◽  
Endothelial Cell Proliferation ◽  
The Novel ◽  
Nano Coating ◽  
Before And After ◽  
Proliferation In Vitro

Abstract Purpose Due to thromboembolic complications and in-stent-stenosis after flow diverter (FD) treatment, the long-term use of dual antiplatelet treatment (DAPT) is mandatory. The tested nano-coating has been shown to reduce material thrombogenicity and promote endothelial cell proliferation in vitro. We compared the biocompatibility of coated (Derivo Heal) and non-coated (Derivo bare) FDs with DAPT in an animal model. Methods Derivo® bare (n = 10) and Derivo® Heal (n = 10) FD were implanted in the common carotid arteries (CCAs) of New Zealand white rabbits. One additional FD, alternately a Derivo bare (n = 5) or Derivo Heal (n = 5), was implanted in the abdominal aorta (AA) for assessment of the patency of branch arteries. Histopathological examinations were performed after 28 days. Angiography was performed before and after FD implantation and at follow-up. Results Statistical analysis of the included specimens showed complete endothelialization of all FDs with no significant differences in neointima thickness between Derivo® bare and Derivo® Heal (CCA: p = 0.91; AA: p = 0.59). A significantly reduced number of macrophages in the vessel wall of the Derivo Heal was observed for the CCA (p = 0.02), and significantly reduced fibrin and platelet deposition on the surface of the Derivo Heal was observed for the AA. All branch arteries of the stented aorta remained patent. Conclusion In this animal model, the novel fibrin-based coated FD showed a similar blood and tissue compatibility as the non-coated FD.

scholarly journals Experimental IgA nephropathy.

1979 ◽  
Vol 150 (5) ◽  
pp. 1161-1173 ◽  
Author(s):  
A Rifai ◽  
P A Small ◽  
P O Teague ◽  
E M Ayoub
Keyword(s):  
Iga Nephropathy ◽  
Immune Complex ◽  
Immune Complexes ◽  
Secretory Iga ◽  
Glomerular Lesions ◽  
Glomerular Deposits ◽  
Focal Glomerulonephritis ◽  
Iga Immune Complexes

An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.

Electron microscopic study of the membrane glycoproteins in the rat kidney after cisplatin treatment

1989 ◽  
Vol 47 ◽  
pp. 912-913
Author(s):  
S.K. Aggarwal
Keyword(s):  
Alkaline Phosphatase ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Kidney Tissue ◽  
Membrane Glycoproteins ◽  
Electron Microscopic ◽  
Before And After ◽  
Interstrand Cross Links ◽  
Cross Links

The proposed primary mechanism of action of the anticancer drug cisplatin (Cis-DDP) is through its interaction with DNA, mostly through DNA intrastrand cross-links or DNA interstrand cross-links. DNA repair mechanisms can circumvent this arrest thus permitting replication and transcription to proceed. Various membrane transport enzymes have also been demonstrated to be effected by cisplatin. Glycoprotein alkaline phosphatase was looked at in the proximal tubule cells before and after cisplatin both in vivo and in vitro for its inactivation or its removal from the membrane using light and electron microscopy.Outbred male Swiss Webster (Crl: (WI) BR) rats weighing 150-250g were given ip injections of cisplatin (7mg/kg). Animals were killed on day 3 and day 5. Thick slices (20-50.um) of kidney tissue from treated and untreated animals were fixed in 1% buffered glutaraldehyde and 1% formaldehyde (0.05 M cacodylate buffer, pH 7.3) for 30 min at 4°C. Alkaline phosphatase activity and carbohydrates were demonstrated according to methods described earlier.

Structural integrity after cold storage of human epidermal model in hypothermosol: A correlative ultrastructural and fluorescent assay

1994 ◽  
Vol 52 ◽  
pp. 270-271
Author(s):  
Henry H. Eichelberger ◽  
John G. Baust ◽  
Robert G. Van Buskirk
Keyword(s):  
Cold Storage ◽  
Structural Integrity ◽  
Culture Media ◽  
Cell Structure ◽  
Natural State ◽  
Sodium Cacodylate ◽  
Ruthenium Tetroxide ◽  
Cacodylate Buffer ◽  
Before And After

For research in cell differentiation and in vitro toxicology it is essential to provide a natural state of cell structure as a benchmark for interpreting results. Hypothermosol (Cryomedical Sciences, Rockville, MD) has proven useful in insuring the viability of synthetic human epidermis during cold-storage and in maintaining the epidermis’ ability to continue to differentiate following warming.Human epidermal equivalent, EpiDerm (MatTek Corporation, Ashland, MA) consisting of fully differentiated stratified human epidermal cells were grown on a microporous membrane. EpiDerm samples were fixed before and after cold-storage (4°C) for 5 days in Hypothermosol or skin culture media (MatTek Corporation) and allowed to recover for 7 days at 37°C. EpiDerm samples were fixed 1 hour in 2.5% glutaraldehyde in sodium cacodylate buffer (pH 7.2). A secondary fixation with 0.2% ruthenium tetroxide (Polysciences, Inc., Warrington, PA) in sodium cacodylate was carried out for 3 hours at 4°C. Other samples were similarly fixed, but with 1% Osmium tetroxide in place of ruthenium tetroxide. Samples were dehydrated through a graded acetone series, infiltrated with Spurrs resin (Polysciences Inc.) and polymerized at 70°C.

Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

2020 ◽  
pp. 1-9
Author(s):  
Pınar Ercan ◽  
Sedef Nehir El
Keyword(s):  
Inhibitory Activity ◽  
Digestive Enzymes ◽  
Positive Control ◽  
Anthocyanin Content ◽  
Inhibitory Effects ◽  
Total Anthocyanin ◽  
Total Anthocyanin Content ◽  
Before And After ◽  
Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo
Keyword(s):  
Thyroid Function Test ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Function Test ◽  
Before And After ◽  
Adrenal Response ◽  
Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

In vitro Behaviour of Alumina-Hydroxiapatite Composites Coatings

2018 ◽  
Vol 69 (6) ◽  
pp. 1416-1418
Author(s):  
Alexandru Szabo ◽  
Ilare Bordeasu ◽  
Ion Dragos Utu ◽  
Ion Mitelea
Keyword(s):  
Pure Titanium ◽  
Titanium Substrate ◽  
High Strength ◽  
Biological Properties ◽  
Commercially Pure Titanium ◽  
Hvof Spraying ◽  
Before And After ◽  
Sbf Solution ◽  
Oxygen Fuel

Hydroxyapatite (HA) is a very common material used for biomedical applications. Usually, in order to improve its poor mechanical properties is combined or coated with other high-strength materials.The present paper reports the manufacturing and the biocompatibility behaviour of two different biocomposite coatings consisting of alumina (Al2O3) and hydroxyapatite (HA) using the high velocity oxygen fuel (HVOF) spraying method which were deposited onto the surface of a commercially pure titanium substrate. The biological properties of the Al2O3-HA materials were evaluated by in vitro studies. The morphology of the coatings before and after their immersing in the simulated body fluid (SBF) solution was characterized by scanning electron microscopy (SEM). The results showed an important germination of the biologic hydroxyapatite crystallite on the surface of both coatings.

scholarly journals TO010A NEW IMMUN-TOXICOLOGICAL TEST TO DETECT POLYSULFONE HYPERSENSITIVITY IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Joachim Beige ◽  
Ralph Wendt ◽  
Despina Rüssmann ◽  
Karl-Peter Ringel
Keyword(s):  
False Negative ◽  
False Negative Rate ◽  
Lymphocyte Transformation ◽  
Clinical Problem ◽  
Lymphocyte Transformation Test ◽  
Laboratory Research ◽  
Humoral Immune ◽  
Before And After ◽  
Positive Results

Abstract Background and Aims Incompatibility of dialysis procedure due to hypersensitivity against dialyzer material which currently is mainly based on polysulfone and derivatives can not be assessed by routine laboratory tests. Although the frequency of such symptoms is suspected to be low (below 2%) such resembles an important clinical problem because dialysis procedures are frequently accompanied by symptoms of non-tolerability with reasons not being entirely clear while circulatory reasons are suspected to play a major role. Method To enlighten the role of polysulfone hypersensitivity, we adapted known standardized material immune-toxicological tests (lymphocyte transformation test, basophil degranulation test) to the specific conditions of dialysis and polysulfone material sensitivity. We developed a method of polysulfone micronisation and measured humoral immune response of isolated patient´s lymphocytes when incubated with polysulfone dispersion. Results 39 samples from 103 patients with suspected polysulfone hypersensitivity showed positive results for type 1 (n=19), type 4 (n=18) or both type (n=2) reactions. There were no significant differences in the level of stimulation measured for DI, SI and lymphogenesis before and after dialysis (average delta -0.4; -0.28; - 1.74, p = 0.71; 0.34; 0.37) and with different dialyzer materials (Tab. 1). Patients with pos. type 4 results (LTT and lymphogenesis) showed highly correlated results in either LTT or lymphogenesis test (Fig. 1, R=0.87, p&lt;0.0001). 8 out of 8 samples from patients with repeated test on different PS showed positive results on either PS. One patient tested positive on PS showed no hypersensitivity with another non-PS (PMMA) material. Conclusion This is the first methodological report showing plausible in-vitro results of patients samples concerning polysulfone intolerance. On the first superficial view, a “false-negative” rate of 60% looks rather disappointing, because all samples derived from patients with suspicion of PS hypersensitivity. However, due to the clinical variability of intolerance symptoms and the high prevalence of any problems after HD initiation, mainly of circulatory origin after initiating extracorporeal circuit, this rate may obviously express the true frequency of isolated PS material hypersensitivity in suspected patients. Alternative pathophysiological pathways of material sensitivity like complement activation, remain to be elucidated and incorporated into a comprehensive future testing panel. Further clinical and laboratory research is needed to define true polysulfone hypersensitivity and to enlighten the field of hypothetic subclinical material incompatibility in patients with impaired dialysis tolerability.

Sign in / Sign up

Export Citation Format

Share Document