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חקר עמילואידוזס בחיות מעבדה

 

עבודות מחקר בנושא מודל חיות לעמילואידוזס ראקטיבית ניתן למצוא ברשימת המאמרים המלאה, במאמרים הבאים: 84, 99, 117, 166, 209, 220, 232, 287, 295, 361, 465. (לרשימת המאמרים המלאה). להלן, מובאים תקצירים של 5 מאמרים נבחרים:

 

1.  Scand J Immunol. 1994 Dec;40(6):653-8.
Direct evidence for SAA deposition in tissues during murine amyloidogenesis.
Yakar S, Kaplan B, Livneh A, Martin B, Miura K, Ali-Khan Z, Shtrasburg S, Pras  M.

 

Abstract
To study the mechanism of amyloid deposition, the nature of amyloid proteins formed in experimental murine amyloidosis, was examined. Spleen specimens, 15-60 mg, were homogenized and extracted using aqueous acidic acetonitrile, in a recently developed procedure, making it possible to obtain amyloid proteins from minute amounts of tissue. The extracted material, 1.5-4 mg, was analysed by Western blotting and ELISA using antibodies recognizing differentially proteins AA and SAA. Two immunoreactive proteins of 8 and 12 KDa were isolated and subjected to amino acid analysis and N-terminal sequence determination. The results of immunochemical and chemical examination showed that the 8 and 12 KDa proteins represented proteins AA and SAA, respectively. The data obtained provide new direct evidence for SAA in tissues during murine amyloidogenesis.

 

2. J Lab Clin Med. 2000 Oct;136(4):314-9.
Pregnancy and amyloidosis: II. Suppression of amyloidogenesis during pregnancy.
Shtrasburg S, Pras M, Dolitzky M, Pariente C, Gal R, Livneh A.

 

Abstract
The observation of a deleterious effect of pregnancy on kidney function in amyloidosis of familial Mediterranean fever suggests that pregnancy may enhance amyloidogenesis. To determine whether pregnancy may indeed affect amyloidogenesis, pregnant mice were made amyloidotic by administration ofamyloid-enhancing factor (AEF) and AgNO3 at different points in time from conception, and amyloid- deposition was studied with the crush-and-smear technique. A possible effect of exogenous female sex hormones (beta-estradiol and progesterone) on amyloidogenesis was studied by administration of these hormones during amyloid induction in nonpregnant female mice. Amyloidogenesis was found to be significantly suppressed in mice during pregnancy. The reduction was possibly 
related to the effect of pregnancy on the inflammatory stimulus (AgNO3) and not on the administered AEF. Exogenous estrogen and progesterone failed to inhibit amyloidogenesis in nonpregnant mice. These findings suggest that pregnancy may suppress amyloidogenesis in mice. The suppression is caused by an anti-inflammatory effect of pregnancy. Estrogen and progesterone are probably unrelated to this finding.

 

3. J Lab Clin Med. 2001 Aug;138(2):107-11.
Inhibition of the second phase of amyloidogenesis in a mouse model by a single-dose colchicine regimen.
Shtrasburg S, Pras M, Gal R, Salai M, Livneh A.

 

Abstract
Amyloidogenesis consists of two stages. In the first, amyloid enhancing factor (AEF) is generated, and in the second, deposition of amyloid fibrils occurs. Colchicine is a known inhibitor of amyloidosis of familial Mediterranean fever (FMF) and of mouse experimental amyloidosis, but the timing and mechanism of its effect are still unclear. The aim of this study is to determine whether colchicine inhibits the second phase of amyloidogenesis and to study the time correlate of such an effect. To that end, amyloid was induced in Swiss male mice with AEF and AgNO(3) (an inflammatory stimulus), a method that skips the first phase of amyloidogenesis. Two amyloid induction protocols were used: a standard protocol, in which AEF and AgNO(3) were administered concurrently, and a prolonged protocol, in which the administration of AgNO(3) was delayed by 24 hours or 7 days. To study the inhibitory effect of colchicine on the second phase of amyloidogenesis, a single dose of colchicine (30 microg) was injected intravenously before, during, or after administration of AgNO(3) in both the standard and prolonged amyloid induction protocols. The amount of amyloid deposition in the spleens was determined with the crush-and-smear technique and a 5-grade scale. Colchicine was found to inhibit the second phase of amyloidogenesis. Its best effect was achieved when administered 48 hours after initiation of AgNO(3) injections. The pattern of colchicine-inhibition-in-time in the standard and the prolonged amyloid induction protocols was similar, indicating that colchicine exerts inhibition through its effect on the
inflammatory stimulus (AgNO(3)). These findings suggest that (1) colchicine suppresses amyloidogenesis in the late (second) stage and that (2) this suppression is possibly related to the anti-inflammatory effect of colchicine. 

 

4. Clin Exp Rheumatol. 2004 Jul-Aug;22(4):421-6.
Increased propensity for amyloidogenesis in male mice.
Shtrasburg S, Pras M, Dulitzky M, Pariente C, Gal R, Mor A, Livneh A.

 

Abstract
BACKGROUND: The male sex is a risk factor for reactive amyloidogenesis in several disease entities. Environmental, socioeconomic or genetic factors may underlie this male preponderance. This study was aimed at discovering whether male sex predisposes to reactive amyloidosis also in mice and to elucidate some of the hormonal associations of this risk.
METHODS: Male and female Swiss mice were subjected to an established amyloid induction protocol and the amount of their splenic amyloid was determined and compared. The effect of estrogen, progesterone, testosterone and adrenalin on amyloidogenesis was studied in both sexes by administering these hormnones during amyloid induction and comparing the amount of splenic amyloid of the study mice with the control mice which received the amyloid induction protocol alone. 
RESULTS: Amyloid deposition appeared to be more abundant in male mice. This gender difference was not associated with any of the 3 sex hormones tested. Despite an expected increment, adrenalin caused an attenuation of amyloid deposition.
CONCLUSIONS: The preferential expression of reactive amyloidosis in male mice seems to be unrelated to the common sex hormones. Increased production of other hormones such as adrenalin, or perhaps an augmented susceptibility to their effect, may cause gender differences by suppressing female amyloidogenesis. Our study favors the hypothesis of genetic predisposition as the mechanism leading to sex differences in amyloidogenesis. Further validation of our findings in gonadal ablated models and other amyloid induction protocols is warranted.

 

5. Transl Res. 2007 Jul;150(1):66-72. Epub 2007 May 25.
Suppression of amyloidogenesis in a mouse model by corticosteroid intervention.
Shtrasburg S, Lidar M, Pras M, Pariente C, Gal R, Livneh A.

 

Abstract
Steroid treatment of amyloidosis was studied previously in human and murine models of reactive amyloidosis but with limited success and with conflicting results. To determine whether steroids may inhibit amyloidogenesis, and to study factors that may play a role in this effect, the authors induced amyloidosis in Swiss male mice, using the enhanced protocol with a single intravenous injection of amyloid-enhancing factor (AEF) and 3 successive daily subcutaneous AgNO(3) injections. Suppression of amyloid formation by various commonly used steroid preparations was evaluated from the amount of splenic amyloid, using the crush-and-smear technique. All steroid preparations examined were found to suppress amyloidogenesis but with differences between them in the degree and duration of nhibition. In general, hydrocortisone and dexamethasone had the highest suppressive effect, whereas methylprednisolone displayed lower activity for shorter duration. Single-dose experiments revealed that steroid effect is limited to the onset of amyloidogenesis. hese experiments show that corticosteroids may significantly suppress amyloidogenesis but only briefly and, therefore, discourage a long-term and late use of steroid supplement in different anti-amyloid treatment protocols.

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