Gout: Ben-Chetrit E

Ben-Chetrit E, Ozdogan H. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #19026114 No free full text.

This publication has no abstract.

Ben-Chetrit E, Bergmann S, Sood R. · Department of Biochemistry, School of Medicine, Stanford University, CA, USA. · Rheumatology (Oxford). · Pubmed #16188942 links to  free full text

Abstract: OBJECTIVE: Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. METHODS: HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. RESULTS: Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. CONCLUSIONS: The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF.

Ben-Chetrit E, Berkun Y, Ben-Chetrit E, Ben-Chetrit A. · Department of Medicine, Hadassah University Hospital, POB 12000, Jerusalem, Israel. · Semin Arthritis Rheum. · Pubmed #15505771 No free full text.

Abstract: OBJECTIVE: To evaluate the outcome of pregnancies of normal women married to men with familial Mediterranean fever (FMF), some of whom took colchicine during the conception with their wives. PATIENTS AND METHODS: We followed the outcome of pregnancies and deliveries of 60 wives of FMF patients; 53 of the husbands were taking colchicine during that time. As a control group we screened the outcome of pregnancy and delivery from 230 healthy women married to healthy men. RESULTS: The 60 FMF patients- wives had 222 pregnancies, of which 206 ended in term delivery with 209 live births. Sixteen pregnancies ended in spontaneous abortions (7%). Three of the newborns in the study group were born with congenital malformations. In the control group, of 788 pregnancies, 127 ended in abortions (16%). Six of the newborns were born with congenital malformations. The rate of the late abortions (second trimester) in both groups was comparable. CONCLUSIONS: The results of our study indicates that neither FMF nor colchicine increases the rate of abortions or congenital malformations. Therefore we believe that there is no need to discontinue colchicine treatment in men with FMF before the conception with their wives.

Ben-Chetrit E, Berkun Y, Ben-Chetrit E, Ben-Chetrit A. · Department of Medicine, Hadassah University Hospital, POB 12000, Jerusalem, Israel. · Semin Arthritis Rheum. · Pubmed #15505771 No free full text.

Abstract: OBJECTIVE: To evaluate the outcome of pregnancies of normal women married to men with familial Mediterranean fever (FMF), some of whom took colchicine during the conception with their wives. PATIENTS AND METHODS: We followed the outcome of pregnancies and deliveries of 60 wives of FMF patients; 53 of the husbands were taking colchicine during that time. As a control group we screened the outcome of pregnancy and delivery from 230 healthy women married to healthy men. RESULTS: The 60 FMF patients- wives had 222 pregnancies, of which 206 ended in term delivery with 209 live births. Sixteen pregnancies ended in spontaneous abortions (7%). Three of the newborns in the study group were born with congenital malformations. In the control group, of 788 pregnancies, 127 ended in abortions (16%). Six of the newborns were born with congenital malformations. The rate of the late abortions (second trimester) in both groups was comparable. CONCLUSIONS: The results of our study indicates that neither FMF nor colchicine increases the rate of abortions or congenital malformations. Therefore we believe that there is no need to discontinue colchicine treatment in men with FMF before the conception with their wives.

Ben-Chetrit E, Fischel R, Hinz B, Levy M. · FMF Clinic, Department of Medicine, Hadassah University Hospital, POB 12000, Jerusalem, Israel. · Rheumatol Int. · Pubmed #14963695 No free full text.

Abstract: OBJECTIVE: The aim of this study was to test whether colchicine and hydroxychloroquine have an inhibitory effect on cyclo-oxygenases (COX). METHODS: Measurement of COX-1 and COX-2 activity was performed by using whole blood assay. Serum thromboxane (TXA) and plasma prostaglandin 2 (PGE2) levels were determined using a commercially available enzyme immunoassay kit. Celecoxib, etodolac, and nimesulide were also tested as controls. Since the study was intended to find a qualitative effect rather than a quantitative relationship between the drugs and the enzymes, we used higher concentrations than the therapeutic range. RESULTS: Colchicine did not have an inhibitory effect on cyclo-oxygenases. Hydroxychloroquine had a mild inhibitory effect in a relatively high concentration. As expected, celecoxib, etodolac, and nimesulide did have an inhibitory effect on the cyclo-oxygenases. CONCLUSIONS: Neither colchicine nor hydroxychloroquine exert their anti-inhibitory effect through inhibition of cyclo-oxygenases.

Abedat S, Urieli-Shoval S, Shapira E, Calko S, Ben-Chetrit E, Matzner Y. · Hematology Unit, Hadassah Hospitals, Mount Scopus, Israel. · Isr Med Assoc J. · Pubmed #11802319 links to  free full text

Abstract: BACKGROUND: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients. OBJECTIVE: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1 beta, TNF-alpha, IFN-alpha, IFN-gamma) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures. METHODS: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines. RESULTS: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR assays enabled estimation of MEFV induction by the cytokines at 10-100-fold and could not be further increased by concomitant addition of colchicine. CONCLUSION: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between the ability of colchicine to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

Ben-Chetrit E, Ben-Chetrit A. · Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel. · BJOG. · Pubmed #11305548 No free full text.

Abstract: OBJECTIVE: To study the prevalence, the nature and the genotype correlation of menstruation associated familial Mediterranean fever attacks. METHODS: One hundred and forty-one female patients with familial Mediterranean fever were studied. A questionnaire regarding the presence and nature of menstruation associated with familial Mediterranean fever was designed and filled in by the authors during the patients' visits to the familial Mediterranean fever clinic. The patients who had a positive history for this manifestation were analysed for their familial Mediterranean fever mutations. RESULTS: Ten out of 141 familial Mediterranean fever female patients (7%) had menstruation-associated familial Mediterranean fever attacks. These patients varied in their disease age of onset and disease duration. Increase of colchicine dose, daily or during the perimenstrual period or oral contraceptives were beneficial in preventing these familial Mediterranean fever attacks. No correlation was found with specific mutations causing familial Mediterranean fever. CONCLUSIONS: Menstruation-associated familial Mediterranean fever attacks are relatively uncommon. They are not related to the age of the women, the chronicity of their disease or to the mutations they bear. Various therapeutic approaches have to be tried in order to abolish these attacks. A decrease in oestrogen level during menstruation may have a role in this unique manifestation of familial Mediterranean fever.