Disease relevance of ANCA

• Frogs and toads treated with high doses of anthracene-9-carboxylic acid (A-9-C) develop prolonged muscular contractions and 'divebomber' electromyograms characteristic of myotonia [1].
• Consensus therapeutic regimens for ANCA-associated systemic vasculitis. The European Community Systemic Vasculitis Study Group [2].
• Is vasculitis in subacute bacterial endocarditis associated with ANCA [3]?
• The effect of 9-AC and radiation on normal tissue toxicity was assessed in two normal tissues, jejunum and skin, in separate groups of mice [4].
• 9-Amino-20(S)-camptothecin (9-AC) has demonstrated efficacy against several human cancer xenografts, including cancers of the colon, breast, lung, ovary, and stomach and malignant melanoma, and is currently undergoing Phase I clinical trials [4].

Psychiatry related information on ANCA

• METHODS: We analyzed the incidence of 5/7 Id in patients with ANCA-associated vasculitides (WG, microscopic polyangiitis, Churg-Strauss syndrome), in disease controls (systemic lupus erythematosus patients), and in healthy donors [5].
• Residents tested for HCV in persons with: increased transaminases (83%), history of blood transfusion (46%), multiple tattoos (57%), +ANCA (16%), and alcohol abuse (31%) [6].
• Sheep, relatively more sensitive to chemicals that affect food intake, were injected IV with the d-and l-isomers of tetrahydrocannabinol and with a 9-aza-cannabinol) 9-AC) (8-(1,2-dimethylheptyl)-5,5-dimethyl-5H-[1]benzopyranol[3,4]pyridin-10-01, HCL) and feeding behavior was monitored [7].

High impact information on ANCA

• The target antigen of anti-neutrophil cytoplasm antibodies (ACPA; also known as ANCA) was isolated by affinity chromatography from supernatants of human neutrophils, stimulated with phorbol ester to induce degranulation [8].
• IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11 [9].
• RESULTS: SN-38 and CPT were more cytotoxic than 9-AC and TPT, and CPT-11 was almost inactive toward HT-29 cells [9].
• In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C1000), values were 0.037 microM for SN-38, 0.051 microM for CPT, 0.085 microM for 9-AC, 0.28 microM for TPT, and greater than 1 microM for CPT-11 [9].
• Furthermore, the ANCA-negative UC patients had an increase in the DR4 allele compared with ANCA-positive UC (P = 0.004) [10].

Chemical compound and disease context of ANCA

• 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy [11].
• This study aimed to identify clinical and histologic prognostic indicators of renal outcome in patients with ANCA-associated vasculitis and severe renal involvement (serum creatinine >500 micromol/L) [12].
• Epithelial cells were isolated from human nasal polyps, cultured for 5-7 days, and used to test the effect of anthracene 9-carboxylate (9-AC), known to inhibit Cl- conductance across the epithelial membrane, on the incorporation and desaturation of [1-14C]linoleic acid (C18:2,n-6) in experiments of up to 4 h duration [13].
• METHODS: We describe the clinical presentation, course, and outcome of 4 patients and review the medical literature registered in the Medline PubMed database from 1966 to 2004 by using the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis, arthritis, rash, ANA, and ANCA [14].
• The treatment of ANCA-small vessel vasculitis and glomerulonephritis rests primarily on the use of induction high-dose corticosteroids and cyclophosphamide [15].

Biological context of ANCA

• Thus, with the combination of a subclinical marker (ANCAs) and molecular genetic markers, genetic heterogeneity has been demonstrated within UC: ANCA-positive UC associated with DR2, and ANCA-negative UC likely associated with DR4 [10].
• Pharmacokinetics showed a substantial interpatient variation of the area under the plasma concentration-time curve (AUC) of 9-AC [16].
• A significant correlation was observed between the percentage decrease in WBC count and the AUC of 9-AC lactone (r(2) = 0.86) [16].
• We conducted a phase I and pharmacokinetic study of the oral PEG-1000 formulation of 9-AC to define the maximum-tolerated dose, toxicity profiles, pharmacokinetic-dynamic relationships, and preliminary antitumor activity in patients with solid tumors [16].
• Jejunal crypt cell survival was decreased in those mice given single doses of 9-AC ranging from 0.5-4.0 mg/kg and 12.5 Gy of total body radiation compared with those given 12.5 Gy of total body irradiation alone [4].

Anatomical context of ANCA

• Short-chain glucose polymer and anthracene-9-carboxylic acid inhibit water and electrolyte secretion induced by dibutyryl cyclic AMP in the small intestine [17].
• Moreover, PR-3 was also translocated into the cell membrane, becoming accessible to ANCA [18].
• In addition, the gastrointestinal tract but not skin could be a critical target tissue for the use of 9-AC combined with radiation [4].
• Elimination of B cells by rituximab therapy may prove to be an effective and safe new treatment modality for ANCA-associated vasculitis and possibly other autoimmune diseases [19].
• Herein is reported a new model for anti-MPO-mediated glomerulonephritis and vasculitis that further documents the pathogenic potential of ANCA and demonstrates that bone marrow (BM)-derived cells are sufficient targets to cause anti-MPO disease in the absence of MPO in other cell type [20].

Associations of ANCA with other chemical compounds

• Based on Erev measurements, the permeability sequence for this PKC-activated Cl- channel was determined to be SCN- > I- > Br- congruent to Cl-. The PKC-activated Cl- current was not inhibited by the Cl- channel blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (100 mumol/L) but could be blocked by anthracene-9-carboxylic acid (1 mmol/L) [21].
• The effect of 8-pCPT-cGMP was also assessed in the presence of the anion channel inhibitors niflumic acid (100 microM), diisothiocyanatostilbene-2,2' disulfonic acid (DIDS; 1 mM), anthracene-9-carboxylic acid (9-AC; 1 mM), or the K+ channel blocker tetraethylammonium chloride (TEA; 10 mM). cGMP production was measured by immunoassay [22].
• Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG [23].
• 1. The conventional whole-cell recording technique was used to study the effects of the chloride channel inhibitors ethacrynic acid, anthracene-9-carboxylic acid (A-9-C) and indanyloxyacetic acid (IAA) on membrane currents in rabbit portal vein smooth muscle cells at a holding potential of 0 mV [24].
• 2. In intact epithelium, quercetin induced an increase in short-circuit current (I(sc)), which was diminished by the Cl(-) channel blockers NPPB and DPC, but not by glibenclamide, DIDS or anthracene-9-carboxylic acid [25].

Gene context of ANCA

• ANCA antigen increase was prevented by p38 MAPK inhibition and by heat exposure [26].
• Both IL8 (class I)- and TNF (class II)-stimulated Cl- efflux exhibited similar sensitivity to inhibition by different types of ion transport inhibitors [ethacrynic acid (EA), amiloride, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, anthracene-9-carboxylic acid, and 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid] [27].
• While more than two thirds of the patients with PSC were positive for ANCA, there was no correlation between the presence of ANCA or ANCA titre and serum levels of either IL8, IL10 and sCD23 [28].
• Mean TGF beta 1 plasma levels in the ANCA associated vasculitis (AAV) patients ranged from 8.9 (Wegeners granulomatosis, WG) to 13.3 ng/ml (Churg-Strauss syndrome, CSS)(control: 4.2 ng/ml, p < 0.01) while TGF beta 2 levels were not elevated [29].
• Expression of somatostatin receptors in inflammatory lesions and diagnostic value of somatostatin receptor scintigraphy in patients with ANCA-associated small vessel vasculitis [30].

Analytical, diagnostic and therapeutic context of ANCA

• Immunoglobulin A enzyme-linked immunosorbent assays to ASCA, outer-membrane porin C, or I2 and immunoglobulin G enzyme-linked immunosorbent assay to ASCA and ANCA determined the presence and level of antibodies [31].
• This study is an investigation of single-dose concentration-time profiles of 1 g off MMF in 16 patients with AID, including 10 patients with ANCA-associated vasculitis and 6 patients with systemic lupus erythematosus, and compares them with profiles of 16 renal transplant recipients (RTX) [32].
• This novel animal model further documents ANCA IgG interactions with neutrophils as a cause of ANCA-associated glomerulonephritis and vasculitis [20].
• Both chronic and acute tubulointerstitial lesions predicted GFR12 in severe ANCA-associated glomerulonephritis, whereas plasma exchange was a positive predictor of dialysis independence after 12 mo for the entire patient group [12].
• Many patients with systemic vasculitis have antibodies to neutrophil cytoplasm antigens (ANCA) detectable by indirect immunofluorescence [33].

References