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A 37-year-old woman who had previously been diagnosed with eosinophilia-myalgia syndrome associated with the use of tryptophan was admitted to a hospital with chest pain. She had no history of heart disease or any risk factors for coronary artery disease. A coronary angiogram showed that her left anterior descending coronary artery was obstructed. Her symptoms resolved after she was given nitrates and a calcium channel blocker, but she experienced severe chest pain a few days later. A repeat angiogram showed that her left anterior coronary artery was now obstructed in another area. A biopsy sample from her heart showed deposits of eosinophil granule proteins in the heart muscle. Eosinophils are a type of white blood cell. The concentration of tryptophan in her blood was normal, and her eosinophil level was also normal. Deposition of eosinophil granule proteins in various tissues may be responsible for the symptoms of eosinophilia-myalgia syndrome., We report a case of repeated coronary artery spasm with myocardial injury in a 37-year-old woman with the esonophilia-myalgia syndrome. This patient did not have a medical history of cardiac-related illness or risk factors for coronary artery disease. The presence of eosinophil granule major basic protein in otherwise normal-appearing myocardial tissue, along with normal plasma levels of trytophan metabolites, suggests that the mechanism of vasospasm in this patient might involve toxic eosinophil proteins or focal myocardial lesions, but not the production of excess tryptophan metabolites. (JAMA. 1992;267:2932-2934)

Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency. Am J Physiol Renal Physiol 279: F565-F572, 2000.--Marked increases in metabolites of the L-tryptophan-kynurenine pathway, L-kynurenine and quinolinic acid (Quin), were observed in serum and cerebrospinal fluid (CSF) of both the rat and human with renal insufficiency. The mechanisms responsible for their accumulation after renal insufficiency were investigated. In patients with chronic renal insufficiency, elevated levels of serum L-kynurenine and Quin were reduced by hemodialysis. In renal-insufficient rats, Quin and L-kynurenine levels in serum, brain, and CSF were also increased parallel to the severity of renal insufficiency. Urinary excretion of Quin (3.5-fold) and L-kynurenine (2.8-fold) was also increased. Liver L-tryptophan 2,3-dioxygenase activity (TDO), a rate-limiting enzyme of the kynurenine pathway, was increased in proportion to blood urea nitrogen and creatinine levels. Kynurenine 3-hydroxylase and quinolinic acid phosphoribosyltransferase were unchanged, but the activities of kynureninase, 3-hydroxyanthranilate dioxygenase, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) were significantly decreased. Systemic administrations of pyrazinamide (ACMSDase inhibitor) increased serum Quin concentrations in control rats, demonstrating that changes in body ACMSDase activities in response to renal insufficiency are important factors for the determination of serum Quin concentrations. We hypothesize the following ideas: that increased serum L-kynurenine concentrations are mainly due to the increased TDO and decreased kynureninase activities in the liver and increased serum Quin concentrations are due to the decreased ACMSDase activities in the body after renal insufficiency. The accumulation of CSF L-kynurenine is caused by the entry of increased serum L-kynurenine, and the accumulation of CSF Quin is secondary to Quin from plasma and/or Quin precursor into the brain. aminocarboxymuconate-semialdehyde decarboxylase; L-tryptophan 2,3-dioxygenase; kynureninase; pyrazinamide