scholarly journals Treatment of experimental amyloidosis with antirheumatic drugs

2010 ◽  
Vol 17 (1-2) ◽  
pp. 17-29
Author(s):  
Laima LEONAVIČIENĖ ◽  
Danutė POVILĖNAITĖ ◽  
Rūta BRADŪNAITĖ ◽  
Dalia VAITKIENĖ ◽  
Algirdas VENALIS
Keyword(s):  
Prophylactic Treatment ◽  
Combined Treatment ◽  
Amyloid Deposition ◽  
Secondary Amyloidosis ◽  
Amyloid Formation ◽  
Aa Amyloidosis ◽  
Therapeutic Treatment ◽  
Antirheumatic Drugs ◽  
Experimental Amyloidosis ◽  
Amyloid Deposits

Background. Because at present there is no known specific effective therapy for secondary amyloidosis, the aim of this study was to determine whether antirheumatic drugs inhibit the development of experimental AA amyloidosis induced in C57BL/6 mice by casein and fibrin injections. Materials and methods. Monotherapy with sulfasalazine (SSL) and diclofenac (D) and a combined treatment with diclofenac and prednisolone (D/P) according to prophylactic and therapeutic treatment protocols were investigated. The drugs were administered through intragastric gavage 5 times a week for 5 or 4 weeks in the following doses: D – 1 mg/kg, P – 10 mg/kg, and SSL – 100 mg/kg. A histopathological examination of splenic, kidney and hepatic tissues of mice was performed. The amount of amyloid was assessed semi-quantitatively by polarizing microscopy after Congo red staining. Results. Our study indicated that no positive effect of the prophylactic treatment with D could be seen on amyloid deposition in the target organs. Prophylactic combined treatment with D/P resulted in a significant improvement of disease symptoms and markedly reduced amyloid deposits in the spleen, kidneys and liver (p < 0.02–0.001). SSL therapy alone was more successful in the prophylactic treatment of experimental amyloidosis: the decrease of amyloid deposits was statistically significant in all examined organs (p < 0.04–0.001), and the suppression of amyloid formation was most significant in the kidneys and liver (p < 0.004–0.001). In the therapeutic treatment of experimental amyloidosis, combined treatment with D/P showed the most pronounced inhibition of amyloid formation in the internal organs (p < 0.006–0.001). The suppression (by 86.7%; p < 0.001) of amyloid deposits was most notable in the liver. Treatment of mice with D alone produced a significant reduction in amyloid deposition only in the liver (p < 0.03) and with SSL only in the spleen (p < 0.03). Conclusions. These findings suggest that D/P and SSL at relevant doses suppress amyloidogenesis, and this suppression is possibly related to the anti-inflammatory effect of antirheumatic drugs. Although these drugs cannot completely inhibit the disease in this model, a possibility remains that they may be clinically useful in rheumatic diseases associated with the formation of amyloidogenic derivatives. Keywords: mice, experimental AA amyloidosis, antirheumatic drugs

scholarly journals Amyloid deposition in granuloma of tuberculosis patients: A pilot study

2021 ◽  
Author(s):  
Shreya Ghosh ◽  
Akansha Garg ◽  
Chayanika Kala ◽  
Ashwani Kumar Thakur
Keyword(s):  
Serum Amyloid A ◽  
Amyloid Deposition ◽  
Serum Amyloid ◽  
Secondary Amyloidosis ◽  
Amyloid Formation ◽  
Tuberculosis Patients ◽  
Amyloid A ◽  
Inflammatory Conditions ◽  
Amyloid Deposits ◽  
Serum Amyloid A Protein

AbstractThe formation of granuloma is one of the characteristic feature of tuberculosis. Besides, rise in the concentration of acute phase response proteins mainly serum amyloid A is the indicator for chronic inflammation associated with tuberculosis. Serum amyloid A drives secondary amyloidosis in tuberculosis and other chronic inflammatory conditions. The linkage between serum amyloid A (SAA) protein and amyloid deposition site is not well understood in tuberculosis and other chronic inflammatory conditions. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of serum amyloid A protein and proteases that cleave SAA and trigger amyloid formation. Based on this hypothesis, for the first time we have shown the presence of amyloid deposits in the granuloma of tuberculosis patients using the gold standard, Congo red dye staining.

scholarly journals A temporal and ultrastructural relationship between heparan sulfate proteoglycans and AA amyloid in experimental amyloidosis.

1991 ◽  
Vol 39 (10) ◽  
pp. 1321-1330 ◽  
Author(s):  
A D Snow ◽  
R Bramson ◽  
H Mar ◽  
T N Wight ◽  
R Kisilevsky
Keyword(s):  
Heparan Sulfate ◽  
Amyloid Fibrils ◽  
Dermatan Sulfate ◽  
Polyclonal Antibodies ◽  
Amyloid Deposition ◽  
Sulfate Proteoglycan ◽  
Aa Amyloidosis ◽  
Experimental Amyloidosis ◽  
Protein Core ◽  
Dermatan Sulfate Proteoglycan

Previous histochemical studies have suggested a close temporal relationship between the deposition of highly sulfated glycosaminoglycans (GAGs) and amyloid during experimental AA amyloidosis. In the present investigation, we extended these initial observations by using specific immunocytochemical probes to analyze the temporal and ultrastructural relationship between heparan sulfate proteoglycan (HSPG) accumulation and amyloid deposition in a mouse model of AA amyloidosis. Antibodies against the basement membrane-derived HSPG (either protein core or GAG chains) demonstrated a virtually concurrent deposition of HSPGs and amyloid in specific tissue sites regardless of the organ involved (spleen or liver) or the induction protocol used (amyloid enhancing factor + silver nitrate, or daily azocasein injections). Polyclonal antibodies to AA amyloid protein and amyloid P component also demonstrated co-localization to sites of HSPG deposition in amyloid sites, whereas no positive immunostaining was observed in these locales with a polyclonal antibody to the protein core of a dermatan sulfate proteoglycan (known as "decorin"). Immunogold labeling of HSPGs (either protein core or GAG chains) in amyloidotic mouse spleen or liver revealed specific localization of HSPGs to amyloid fibrils. In the liver, heparan sulfate GAGs were also immunolocalized to the lysosomal compartment of hepatocytes and/or Kupffer cells adjacent to sites of amyloid deposition, suggesting that these cells are involved in HSPG production and/or degradation. The close temporal and ultrastructural relationship between HSPGs and AA amyloid further implies an important role for HSPGs during the initial stages of AA amyloidosis.

scholarly journals Deposition, Clearance, and Reinduction of Amyloid A Amyloid in Interleukin 1 Receptor Antagonist Knockout Mice

2016 ◽  
Vol 54 (1) ◽  
pp. 99-110 ◽  
Author(s):  
K. Watanabe ◽  
K. Uchida ◽  
J. K. Chambers ◽  
N. Ushio ◽  
H. Nakayama
Keyword(s):  
Receptor Antagonist ◽  
Knockout Mice ◽  
Interleukin 1 ◽  
Recovery Process ◽  
Amyloid Deposition ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Enhancing Factor ◽  
Amyloid Deposits ◽  
Amyloid Enhancing Factor

Amyloid A (AA) amyloidosis is characterized by the extracellular deposition of AA amyloid and results in the irreversible dysfunction of parenchymal organs. In experimental models, AA amyloid deposits are cleared following a decrease in circulating serum amyloid A (SAA) concentrations. Additional inflammatory stimuli during this recovery process may induce more severe amyloid redeposition. In the present study, we confirmed the deposition, clearance, and reinduction of AA amyloid deposits in interleukin 1 receptor antagonist knockout mice (IL-1raKO) and studied the SAA levels and amyloid-enhancing factor activity based on the time-dependent changes of amyloid deposition. Histopathologically, following initial (day 0) injection of amyloid-enhancing factor in combination with an inflammatory stimulus (silver nitrate [AgNO3]), amyloid deposition peaked by day 20, and its deposition gradually decreased after day 35. SAA concentrations in serum were precipitously elevated on day 1 but returned to normal levels by day 10, whereas the SAA dimer was detected in serum after day 45. An additional AgNO3 injection was administered to mice with amyloidosis on day 5, 10, 35, or 50, and all mice developed large amyloid deposits. Amyloid deposition was most severe in mice treated with AgNO3 on day 35. The inoculation of sera from mice with AA amyloidosis, combined with AgNO3, induced AA amyloidosis. Serum samples collected on days 35 and 50, which contained high concentrations of the SAA dimer, induced amyloidosis in a high proportion (83%) of mice. Therefore, increased SAA and/or its dimer in serum during the recovery process may markedly exacerbate the development of AA amyloidosis.

scholarly journals Spontaneous, Experimentally Induced, and Transmissible AA Amyloidosis in Japanese Quail (Coturnix japonica)

2017 ◽  
Vol 54 (6) ◽  
pp. 912-921 ◽  
Author(s):  
Yumi Nakayama ◽  
Junichi Kamiie ◽  
Gen Watanabe ◽  
Kazuhiko Suzuki ◽  
Tomoaki Murakami
Keyword(s):  
Japanese Quail ◽  
Intestinal Tract ◽  
Amyloid Fibrils ◽  
Amyloid Deposition ◽  
Coturnix Japonica ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Amyloid Deposits ◽  
Amyloid Enhancing Factor ◽  
Apparently Healthy

The authors describe a spontaneous case of amyloid A (AA) amyloidosis in an adult female Japanese quail ( Coturnix japonica). The bird developed AA amyloidosis secondary to chronic peritonitis caused by a Gram-negative bacillus infection. Mild amyloid deposition was also identified in the intestinal tract of apparently healthy adult individuals, suggesting that quail may develop intestinal amyloidosis with age. Based on these observations, it was hypothesized that quail can develop AA amyloidosis following inflammatory stimulation with lipopolysaccharide (LPS). Therefore, adult quail were repeatedly injected with LPS and the development of AA amyloidosis was confirmed. The amyloid deposition in this model increased when quail amyloid was intravenously injected as an amyloid-enhancing factor. The experiments were repeated with young quail, but amyloid deposits were not observed following LPS injections. However, AA amyloidosis did develop when quail amyloid was injected in addition to LPS. These results indicated that adult quail develop AA amyloidosis after inflammatory stimulation with LPS. Furthermore, quail AA amyloidosis was shown to have transmissibility regardless of age. Interestingly, the authors found that administration of chicken amyloid fibrils also induced AA amyloidosis in young quail. This is the first report of cross-species transmission of avian AA amyloidosis.

scholarly journals Secondary Amyloidosis Presenting as Ischemic Proctitis

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Saad Hashmi ◽  
Assad Munis ◽  
Ryan T. Hoff ◽  
Hymie Kavin ◽  
Eli D. Ehrenpreis
Keyword(s):  
Low Voltage ◽  
Rectal Wall ◽  
Amyloid Deposition ◽  
Wall Thickening ◽  
Secondary Amyloidosis ◽  
Gastrointestinal Involvement ◽  
Aa Amyloidosis ◽  
Mediterranean Fever ◽  
Electrocardiogram Ecg ◽  
Ischemic Proctitis

A 49-year-old man presented with abdominal pain and rectal bleeding for two days associated with a 50-pound unintentional weight loss. History was notable for hypertension, chronic kidney disease, obesity, gout, and acute cholecystitis status post cholecystectomy. Computed tomography (CT) of the abdomen and pelvis showed rectal wall thickening. Colonoscopy showed proctitis with superficial ulcerations. In the setting of renal insufficiency, malabsorption, and low-voltage QRS complexes on electrocardiogram (ECG), amyloidosis was considered in the differential diagnosis. Rectal and renal biopsies with subsequent retrospective staining of gallbladder tissue confirmed amyloid deposition. Gastrointestinal involvement of amyloidosis is relatively uncommon. Particularly, amyloid deposition in the gallbladder and rectum is very rare. The development of AA amyloidosis in our patient may have been related to gout, obesity, and the presence of a heterozygous complex variant for the MEFV (familial Mediterranean fever) gene. Awareness of this atypical presentation of amyloidosis is important, as additional staining of biopsy samples is necessary, and diagnosis allows for directed treatment.

Generalized AA-amyloidosis in Siberian Tigers (Panthera tigris altaica) with Predominant Renal Medullary Amyloid Deposition

1998 ◽  
Vol 35 (1) ◽  
pp. 70-74 ◽  
Author(s):  
C. Schulze ◽  
M. Brügmann ◽  
M. Böer ◽  
H.-P. Brandt ◽  
J. Pohlenz ◽  
...  
Keyword(s):  
Congo Red ◽  
Kidney Diseases ◽  
Amyloid Deposition ◽  
Panthera Tigris ◽  
Aa Amyloidosis ◽  
Familial Predisposition ◽  
Amyloid A ◽  
Panthera Tigris Altaica ◽  
Amyloid Deposits ◽  
Congo Red Staining

Generalized amyloidosis with predominant renal medullary amyloid deposition was found in four closely related Siberian tigers ( Panthera tigris altaica) suffering from end stage kidney diseases. Only minimal to mild amounts of amyloid were deposited in various organs outside the kidneys with individually variable organ involvement. The Congo red staining affinity of amyloid deposits was sensitive to potassium permanganate oxidation. The deposits were further characterized as being of the amyloid-A (AA) type by immunohistochemistry using the mouse monoclonal antibody mc4 directed against a conserved region of the human AA-protein. A combination of immunohistochemistry and Congo red staining was much more sensitive for the diagnosis of amyloid deposits than Congo red staining alone. With this combination, even minimal amyloid deposits were detected that had been missed in the first reading using Congo-red-stained slides alone. Since no common primary cause was identified, the amyloidosis was classified as idiopathic generalized AA-amyloidosis with a potential familial predisposition.

scholarly journals Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ivana Slamova ◽  
Rozita Adib ◽  
Stephan Ellmerich ◽  
Michal R. Golos ◽  
Janet A. Gilbertson ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Deposition ◽  
Amyloid Formation ◽  
Plasmin Activity ◽  
Transthyretin Amyloidosis ◽  
In Vivo Models ◽  
Transgenic Expression ◽  
Attr Amyloidosis ◽  
Amyloid Deposits

AbstractCardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments.

scholarly journals Isolated AA Amyloidosis of the Radial Nerve

Hand ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. NP136-NP139 ◽  
Author(s):  
Teresa Pérez-de la Fuente ◽  
Javier Fernández-Jara ◽  
Pilar Rodríguez-Urcelay ◽  
Jose Jiménez-Heffernan ◽  
Ángel Juárez
Keyword(s):  
Radial Nerve ◽  
Nerve Palsy ◽  
Distal Part ◽  
Radial Nerve Palsy ◽  
Primary Amyloidosis ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Nerve Paralysis ◽  
Amyloid Deposits ◽  
History Of

Background: Amyloidosis affecting peripheral nerve is usually seen in primary amyloidosis. Methods: We are reporting on the case of a 74-year-old man with a 16-month history of progressive left radial nerve paralysis. Perioperative imaging detected an enlarged radial nerve in the middle-distal part of the arm. The patient had an antecedent of amyloid deposits in the lung. Results: A radial nerve amyloidosis was suspected and confirmed with a biopsy assisted by ultrasonography, resulting in a secondary amyloidosis form. Conclusions: Isolated radial nerve palsy due to nerve damage by amyloidosis has been reported before, but not in AA or secondary amyloidosis.

scholarly journals Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 136 ◽  
Author(s):  
Levent Kilic ◽  
Abdulsamet Erden ◽  
Yusuf Sener ◽  
Berkan Armagan ◽  
Alper Sari ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Improvement ◽  
Inflammatory Diseases ◽  
Case Series ◽  
New Drugs ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Significant Clinical Improvement

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.

scholarly journals Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature

2021 ◽  
Vol 8 ◽  
Author(s):  
Per Eriksson ◽  
Johan Mölne ◽  
Lina Wirestam ◽  
Christopher Sjöwall
Keyword(s):  
Ankylosing Spondylitis ◽  
Therapeutic Option ◽  
Relevant Literature ◽  
Acute Phase Reactant ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Beneficial Effects ◽  
Amyloid A ◽  
Inflammatory Conditions

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.

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