scholarly journals Complement Activation Products in the Urine from Proteinuric Patients

2000 ◽  
Vol 11 (4) ◽  
pp. 700-707 ◽  
Author(s):  
YOSHIKI MORITA ◽  
HIROSHI IKEGUCHI ◽  
JIRO NAKAMURA ◽  
NIGISHI HOTTA ◽  
YUKIO YUZAWA ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Complement Activation ◽  
Plasma Proteins ◽  
Excretion Rate ◽  
Membrane Attack Complex ◽  
Glomerular Sclerosis ◽  
Focal Glomerular Sclerosis ◽  
Activation Products

Abstract. The presence of plasma proteins in the tubular lumen has variety of adverse effects on the tubular cells. Among various plasma proteins filtered through glomerular barrier, complement has been proven as the possible candidate inducing tubulointerstitial injury. To study the role of intratubular complement activation in proteinuric patients, complement activation products (CAP) at C3 level (iC3b and Bb) and C9 level (membrane attack complex) were measured in both plasma and urine of patients with minimal change nephrotic syndrome (MCNS), focal glomerular sclerosis, IgA nephropathy, membranous nephropathy, and diabetic nephropathy. For evaluation of the effect of metabolic acidosis on the intratubular complement activation, urinary CAP were measured before and after sodium bicarbonate administration in patients with renal insufficiency. The following results were obtained: (1) Patients with focal glomerular sclerosis and diabetic nephropathy showed the highest level of urinary CAP excretion rate (unit/creatinine), while MCNS revealed no increase. (2) Patients with membranous nephropathy showed a unique finding,i.e., isolated increase of membrane attack complex excretion. (3) There was no significant correlation between urine and plasma levels of CAP. (4) Except for MCNS patients, the urinary excretion rate of CAP significantly increased when the level of proteinuria exceeded the nephrotic range, and it was significantly correlated with the serum creatinine level. (5) Urinary CAP excretion rate significantly decreased 2 wk after sodium bicarbonate administration without affecting the level of proteinuria or plasma CAP. These results suggest that the degree of intratubular complement activation correlates with the level of proteinuria, type of glomerular disease, impairment of renal function, and metabolic acidosis.

scholarly journals Systemic and lung physiological changes in rats after intravascular activation of complement

2001 ◽  
Vol 90 (6) ◽  
pp. 2289-2295 ◽  
Author(s):  
John G. Younger ◽  
Nobuyoshi Sasaki ◽  
Joao Delgado ◽  
Angela C. Ko ◽  
Trac X. Nghiem ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Acidosis ◽  
Mean Arterial Pressure ◽  
Complement Activation ◽  
Physiological Changes ◽  
Circulatory Collapse ◽  
Gut Permeability ◽  
Activation Products ◽  
Neutrophil Depletion ◽  
High Doses

Systemic complement activation has been noted in a variety of shock states, and there is growing evidence that, in addition to being proinflammatory effectors, products of complement activation contribute directly to generalized manifestations of shock, such as hypotension and acidosis. To study the effects of complement activation, we examined responses in rats to systemic activation of complement with cobra venom factor (CVF), including blood pressure, metabolic acidosis, changes in vascular permeability, and lung function. High doses of CVF produced circulatory collapse (mean arterial pressure = 110 ± 16 and 35 ± 9 mmHg in control and with CVF, respectively, P < 0.05), metabolic acidosis (HCO[Formula: see text] concentration = 27.8 ± 1.7 and 9.6 ± 3.4 meq/l in control and with CVF, respectively, P < 0.05), extravasation of albumin into the lung and gut, and modest arterial hypoxemia (Po 2 = 486 ± 51 and 201 ± 36 Torr in control and during 100% O2 breathing, respectively, P < 0.05). Prior depletion of complement protected against these abnormalities. Other interventions, including neutrophil depletion and cyclooxygenase inhibition, prevented lung injury but had much less effect on systemic hemodynamics or gut permeability, suggesting that complement activation products induce injury by neutrophil- and cyclooxygenase-dependent pathways in the lung but not in the gut. These studies underscore the significant systemic abnormalities developing after systemic activation of complement.

scholarly journals Complement Activation in Chromosome 13 Dementias

2002 ◽  
Vol 277 (51) ◽  
pp. 49782-49790 ◽  
Author(s):  
Agueda Rostagno ◽  
Tamas Revesz ◽  
Tammaryn Lashley ◽  
Yasushi Tomidokoro ◽  
Laura Magnotti ◽  
...  
Keyword(s):  
Complement Activation ◽  
Alternative Pathway ◽  
Membrane Attack Complex ◽  
Classical Pathway ◽  
Chromosome 13 ◽  
Chronic Inflammatory Response ◽  
General Terms ◽  
Familial Danish Dementia ◽  
Activation Products

Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits (ABri in FBD, ADan in FDD, and Aβ in AD), these disorders are all characterized by the presence of neurofibrillary tangles and parenchymal and vascular amyloid deposits co-localizing with markers of glial activation, suggestive of local inflammation. Proteins of the complement system and their pro-inflammatory activation products are among the inflammation markers associated with AD lesions. Immunohistochemistry of FBD and FDD brain sections demonstrated the presence of complement activation components of the classical and alternative pathways as well as the neo-epitope of the membrane attack complex. Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by Aβ1–42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds ∼70–75% through the classical pathway while only ∼25–30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptidesin vivomight be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions.

scholarly journals Protective Effects of Ethanolic Extract from Rhizome of Polygoni avicularis against Renal Fibrosis and Inflammation in a Diabetic Nephropathy Model

2021 ◽  
Vol 22 (13) ◽  
pp. 7230
Author(s):  
Jung-Joo Yoon ◽  
Ji-Hun Park ◽  
Yun-Jung Lee ◽  
Hye-Yoom Kim ◽  
Byung-Hyuk Han ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Diabetic Nephropathy ◽  
Renal Dysfunction ◽  
Renal Fibrosis ◽  
Mesangial Cells ◽  
Resistance Index ◽  
Ethanolic Extract ◽  
Glomerular Sclerosis ◽  
Oral Glucose ◽  
Inflammatory Factor

Progressive diabetic nephropathy (DN) in diabetes leads to major morbidity and mortality. The major pathological alterations of DN include mesangial expansion, extracellular matrix alterations, tubulointerstitial fibrosis, and glomerular sclerosis. Polygoni avicularis is widely used in traditional oriental medicine and has long been used as a diuretic, astringent, insecticide and antihypertensive. However, to the best of the authors’ knowledge, the effects of the ethanolic extract from rhizome of Polygoni avicularis (ER-PA) on DN have not yet been assessed. The present study aimed to identify the effect of ER-PA on renal dysfunction, which has been implicated in DN in human renal mesangial cells and db/db mice and investigate its mechanism of action. The in vivo experiment was performed using Polygoni avicularis-ethanol soluble fraction (ER-PA) and was administrated to db/db mice at 10 and 50 mg/kg dose. For the in vitro experiments, the human renal mesangial cells were induced by high glucose (HG, 25 mM). The ER-PA group showed significant amelioration in oral glucose tolerance, and insulin resistance index. ER-PA significantly improved the albumin excretion and markedly reduced plasma creatinine, kidney injury molecule-1 and C-reactive protein. In addition, ER-PA significantly suppressed inflammatory cytokines. Histopathologically, ER-PA attenuated glomerular expansion and tubular fibrosis in db/db mice. Furthermore, ER-PA suppressed the expression of renal fibrosis biomarkers (TGF and Collagen IV). ER-PA also reduced the NLR family pyrin domain containing 3 inflammatory factor level. These results suggest that ER-PA has a protective effect against renal dysfunction through improved insulin resistance as well as the inhibition of nephritis and fibrosis in DN.

scholarly journals A Multianalyte Assay Panel With Cell‐Bound Complement Activation Products Predicts Transition of Probable Lupus to American College of Rheumatology–Classified Lupus

2021 ◽  
Vol 3 (2) ◽  
pp. 116-123
Author(s):  
Rosalind Ramsey‐Goldman ◽  
Roberta Vezza Alexander ◽  
John Conklin ◽  
Cristina Arriens ◽  
Sonali Narain ◽  
...  
Keyword(s):  
Complement Activation ◽  
American College Of Rheumatology ◽  
Activation Products

Tris-hydroxymethyl aminomethane and sodium bicarbonate to buffer metabolic acidosis in an isolated heart model.

1997 ◽  
Vol 155 (3) ◽  
pp. 957-963 ◽  
Author(s):  
D Sirieix ◽  
S Delayance ◽  
M Paris ◽  
S Massonnet-Castel ◽  
A Carpentier ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Isolated Heart ◽  
Heart Model

scholarly journals Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment

2021 ◽  
pp. 1-16
Author(s):  
Marcin Adamczak ◽  
Stanisław Surma
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Current Knowledge ◽  
Venous Blood ◽  
The Body ◽  
Hydrogen Ions ◽  
Ckd Progression ◽  
New Drug ◽  
Treatment And Prevention

<b><i>Background:</i></b> Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients. <b><i>Summary:</i></b> Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. <b><i>Key Message:</i></b> The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.

Messenger RNA Expression for Growth Factors in Glomeruli from Focal Glomerular Sclerosis

1993 ◽  
Vol 66 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Tsukasa Nakamura ◽  
Isao Ebihara ◽  
Mitsumine Fukui ◽  
Shiori Osada ◽  
Isao Nagaoka ◽  
...  
Keyword(s):  
Growth Factors ◽  
Messenger Rna ◽  
Glomerular Sclerosis ◽  
Rna Expression ◽  
Focal Glomerular Sclerosis

Mitochondrial calcium overload triggers complement-dependent superoxide-mediated programmed cell death in Trypanosoma cruzi

2009 ◽  
Vol 418 (3) ◽  
pp. 595-604 ◽  
Author(s):  
Florencia Irigoín ◽  
Natalia M. Inada ◽  
Mariana P. Fernandes ◽  
Lucía Piacenza ◽  
Fernanda R. Gadelha ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Trypanosoma Cruzi ◽  
Complement Activation ◽  
Superoxide Radical ◽  
Membrane Attack Complex ◽  
Cell Respiration ◽  
Mitochondrial Uncoupling ◽  
O2 Production ◽  
Complement Deposition

The epimastigote stage of Trypanosoma cruzi undergoes PCD (programmed cell death) when exposed to FHS (fresh human serum). Although it has been known for over 30 years that complement is responsible for FHS-induced death, the link between complement activation and triggering of PCD has not been established. We have previously shown that the mitochondrion participates in the orchestration of PCD in this model. Several changes in mitochondrial function were described, and in particular it was shown that mitochondrion-derived O2•− (superoxide radical) is necessary for PCD. In the present study, we establish mitochondrial Ca2+ overload as the link between complement deposition and the observed changes in mitochondrial physiology and the triggering of PCD. We show that complement activation ends with the assembly of the MAC (membrane attack complex), which allows influx of Ca2+ and release of respiratory substrates to the medium. Direct consequences of these events are accumulation of Ca2+ in the mitochondrion and decrease in cell respiration. Mitochondrial Ca2+ causes partial dissipation of the inner membrane potential and consequent mitochondrial uncoupling. Moreover, we provide evidence that mitochondrial Ca2+ overload is responsible for the increased O2•− production, and that if cytosolic Ca2+ rise is not accompanied by the accumulation of the cation in the mitochondrion and consequent production of O2•−, epimastigotes die by necrosis instead of PCD. Thus our results suggest a model in which MAC assembly on the parasite surface allows Ca2+ entry and its accumulation in the mitochondrion, leading to O2•− production, which in turn constitutes a PCD signal.

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