Type III cryoglobulinemia (15-30% of cases) involves circulating polyclonal IgM protein with rheumatoid factor activity bound to polyclonal IgG and blood complement components; autoimmune diseases and, less commonly, hepatitis virus C infection or lymphoproliferative disorders are the cause of this type of croglobulinemia. Only types I and II are defined as plasma cell dyscrasias.Patients suffering type 1 cryoglobulinemia present with symptoms due to cold temperature-induce blood hyperviscosity and consequential interruptions of blood flow, e.g. skin lesions (lower extremity purpuric spots and papules, acrocyanosis, necrosis skin ulcers, livedo reticularis urticaria), peripheral neuropathy, blurred vision, loss of vision, hearing loss, headaches, confusion, transient ischemic attacks, chest pain, heart failure, glomerulonephritis, kidney failure, oral bleeding, and nasal bleeding. Rarely, patients may present with catastrophic decreases in blood flow to vital tissues and require emergency treatment. Symptomatic patients typically exhibit levels of a myeloma protein >5 gram/liter and can be diagnosed by simple observing the temperature-induced, reversible induction of serum precipitate formation. Patients, particularly those with catastrophic presentations, are treated with plasma exchange and/or plasmapharesis to reduce the load of circulating myeloma proteins and relieve acute symptoms. Patients with an overt malignancy are treated with the chemotherapy regimens used for Waldenstroms macroglobulinemia or multiply myeloma; patients with MGUS precursors to these diseases appear less responsive to these chemotherapeutic regimens.
Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. It is sold under the brand names Giazo, Colazal in the US and Colazide in the UK. It is also sold in generic form in the US by several generic manufacturers. It is usually administered as the disodium salt. Balsalazide releases mesalazine, also known as 5-aminosalicylic acid, or 5-ASA, in the large intestine. Its advantage over that drug in the treatment of ulcerative colitis is believed to be the delivery of the active agent past the small intestine to the large intestine, the active site of ulcerative colitis. It is in the category of disease-modifying antirheumatic drugs (DMARDs) family of medications. It is unclear exactly how it works. Synthesis
Ex 3 is actually for Ipsalazide. See Ex 4 for Balsalazide proper. Same protocol but uses β-Alanine. Starting material is 4-aminohippuric acid, obtained by coupling para-aminobenzoic acid and glycine. That product is then treated with nitrous acid to give the diazonium salt. Reaction of this species with salicylic acid proceeds at the position para to the phenol to give balsalazide. References
External links
"Balsalazide". Drug Information Portal. U.S. National Library of Medicine.