Seminal Tract Amyloidosis: Synchronous Amyloidosis of the Seminal Vesicles, Deferent Ducts and Ejaculatory Ducts.

Senile Seminal Vesicle Amyloidosis (SSVA) increases with age. Involvement of the whole seminal tract, i.e. the seminal vesicles, ejaculatory and deferent ducts was first reported by us in the International Symposium on Amyloidosis 1998. Since then we encountered four more cases of SSVA. In all these cases the ejaculatory and deferent ducts were also involved by amyloid. The amyloid was located mostly sub-epithelially, stained positively with Congo red, gave green birefringence under polarized light and was permanganate sensitive, slightly positive for lactoferrin immunostaining and negative for all known amyloid types. In recent years the amyloid was found to be derived from Semenogelin I, a major constituent of the seminal fluid which is present in the epithelial cells of the seminal vesicle and vas deference. This would explain the deposition of amyloid not only in the seminal vesicles but also in the deferent an ejaculatory ducts which transport the seminal fluid. In a review of the literature we found three more articles on SSVA in which the amyloid was not limited to the seminal vesicles alone. We propose to designate this type of amyloid as "Senile seminal Tract Amyloidosis" (SSTA) instead of "Senile Seminal Vesicle Amyloidosis (SSVA)".

Attempts at suppression of amyloidogenesis in a mouse model by a variety of anti-inflammatory agents.

OBJECTIVE: The mainstay of AA amyloidosis prevention and treatment is suppression of inflammation. In the present study we have tried to determine the efficacy of a variety of anti-inflammatory agents at suppressing AA amyloidosis in a mouse model of the disease. METHODS: AA amyloidosis was induced in Swiss male mice using amyloid enhancing factor and AgNO(3). Suppression of amyloid formation was studied in comparison to saline, using i.p. injections of several non-steroidal anti-inflammatory agents, TNF-α inhibitors, interferon-α, leflunomide and a variety of chemotherapeutic agents, commonly used in the treatment of inflammatory illnesses such as methotrexate, azathioprine, chlorambucil and cyclophosphamide. The degree of splenic amyloid deposition was determined using Congo red staining of smears and a 5 grade scale. RESULTS: The alkylating agents, chlorambucil and cyclophosphamide, each resulted in a significant 88% reduction in amyloid deposition, yielded the most striking effect on amyloidogenesis suppression in the enhanced mouse model (p<0.0002). The non-steroidal anti-inflammatory agents tested varied widely in their ability to suppress amyloid formation in our mouse model, but only diflunisal was significantly effective, inducing a suppression of 57% (p=0.04). Other chemotherapeutic agents tested, methotrexate and azathioprine, yielded 32% and 27% suppression, which fell short of statistical significance. Surprisingly, the immunomodulatory agents etanercept, infliximab, leflunomide and interferon-α had insignificant effects on amyloid formation in this model. CONCLUSION: Our findings suggest that alkylating agents may have a role in the prevention of amyloidogenesis. Further testing of these agents in animal models and in the clinical setting is needed.

Suppression of amyloidogenesis in a mouse model by corticosteroid intervention.

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 inhibition. 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. These 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.

Evaluation of disease severity in familial Mediterranean fever.

OBJECTIVE: To establish a new, objective, statistically based severity score for familial Mediterranean fever (FMF). METHODS: One hundred consecutive FMF patients were evaluated independently by 2 FMF experts for severity of their disease and were assigned to 1 of 3 severity levels: mild, intermediate, or severe. Nine candidate criteria, reflecting objective suffering and disability, were analyzed to determine their weight for patient placement in the 3 predefined severity groups. RESULTS: Candidate criteria best differentiating between the 3 patient categories were the frequency of attacks, the number of sites affected during an attack and during the course of the disease, and the duration of the attacks. These criteria were applied in a classification-tree model to establish a new FMF-severity score (F-SS). The first set of F-SS (F-SS-1) was highly sensitive and specific. Integrating F-SS-1 with clinical parameters strongly associated with disease severity resulted in a simplified score, the second set of F-SS (F-SS-2). CONCLUSIONS: New, useful, objective, and valid severity scores were established and found to distinguish between patients with mild, intermediate, and severe diseases with high sensitivity and specificity. RELEVANCE: The F-SS established may be important for treatment decisions, prognosis evaluation, and comparative analysis of patient populations.

Urine leukotriene B4 in familial Mediterranean fever and other forms of right lower abdominal pain.

BACKGROUND: Acute right lower abdominal pain may present a diagnostic dilemma. Leukotrienes have been found to be elevated in familial Mediterranean fever (FMF), a disease manifesting with recurrent episodes of "acute abdomen." OBJECTIVES: To determine whether urine leukotriene B4 (LTB4) may differentiate between an FMF attack and some other forms of acute right lower abdominal pain. METHODS: The LTB4 level was determined, using a commercial enzyme-linked immunosorbent assay (ELISA), in urine samples obtained from 36 patients with acute (< 24 hours) right lower abdominal pain presenting to the emergency department, and from 18 healthy volunteers. RESULTS: Compared with the healthy control subjects, LTB4 was significantly higher in those who had FMF (12 patients, p < 0.03). In other forms of acute right lower abdominal pain, including appendicitis (eight patients), urologic disorders (eight patients), and nonspecific abdominal pain (eight patients), intermediate levels of LTB4 were observed, not significantly different from those of either FMF patients or healthy control subjects. CONCLUSIONS: In the samples tested, urine LTB4 levels were not instrumental in differentiating FMF from other acute right lower abdominal pain.

Raft lipids as common components of human extracellular amyloid fibrils.

Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis of amyloid fibrils derived from various human diseases (AA, ATTR, Abeta2M, ALlambda, and ALkappa amyloidosis) shows that these are associated with a common lipid component that has a conserved chemical composition and that is specifically rich in cholesterol and sphingolipids, the major components of cellular lipid rafts. This pattern is not notably affected by the purification procedure, and no tight lipid interactions can be detected when preformed fibrils are mixed with lipids. By contrast, the early and prefibrillar aggregates formed in an AA amyloid-producing cell system interact with the raft marker ganglioside-1, and amyloid formation is impaired by addition of cholesterol-reducing agents. These data suggest the existence of common cellular mechanisms in the generation of different types of clinical amyloid deposits.