Lipid thesaurismosis rheumatism. Joint manifestation during glucocerebrosidase deficiency (Gaucher's disease). Ultrastructural study of the synovial membrane]

Articular inflammatory involvement may be the first sign of gluocecerebrosidase deficiency (Gaucher's disease). Electron microscope study shows specific synovial storage lesions which explain arthritic manifestations. Furthermore presence of mitochondrial microcrystals, (apatite?), suggest microcrystal pathogenesis of Gaucher's arthritis.     

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.     

Lipid thesaurismosis rheumatism. Arthropathies in alpha galactosidase A deficiency (Fabry's disease). Ultrastructural study of the synovial membrane demonstrating microcrystals in the mitochondria of synoviocytes]

Articular manifestations may be the onset of genetic alpha galactosidase deficiency (Fabry's disease). Ultrastructural study shows typical osmiophilic lamellar inclusions of trihexosylceramides in synoviocytes, capillaries and adipocytes. Furthermore microcrystals identical to those seen in Gaucher's disease and type II hyperlipoproteinemia were observed in mitochondria and free in cytoplasm. These data suggest a microcrystalline pathogenesis of these arthropathies, as in gout and chondrocalcinosis, and what we have generally called crystallopathic arthropathies.     

Level of ecdysteroids in the hemolymph of the freshwater prawn,Macrobrachium rosenbergii (Crustacea: Decapoda) in relation to the phenomenon of cheliped autotomy in males

Summary Ecdysteroid titers were determined in the hemolymph of adult freshwater prawn,Macrobrachium rosenbergii, during various stages of the molt cycle, using radioimmunoassay. A comparison was made between hormone levels in males which undergo normal molt and dominant males of the population which periodically commit cheliped autotomy. The latter is a recently discovered phenomenon whereby a male voluntarily sheds off both its long claws at molt, once the ratio between body length and combined claw length reaches a ceiling level of about 13. Shortly before an autotomizing molt, hormone levels were about three times higher than on the eve of a normal molt.10 November 1986     

Antibodies to human serum amyloid P component eliminate visceral amyloid deposits

Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.