Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of high-dose cytosine arabinoside (HiDAC) given as a three-hour intravenous infusion at 3 g/m2 were studied in five patients with acute leukemia during relapse and/or remission of their disease. Apparent steady state plasma levels of ara-C during 13 infusions averaged 115 +/- 32 microM. Upon cessation of the infusion, cytosine arabinoside (ara-C) was rapidly cleared from the plasma. The apparent postinfusion kinetics of ara-C were triexponential with a distribution half-life of 16 minutes and elimination half-lives of 1.8 hours and six hours. Total clearance averaged 86 L per hour and mean residence time averaged 0.47 hours. Disease status (relapse or remission) had no apparent effect on the pharmacokinetic characteristics of ara-C. Peak levels of ara-U averaged 310 microM and the metabolite had an average apparent elimination half-life of 3.75 hours. Despite the persistence of ara-U at about 100 microM at the time of administration of subsequent infusions of ara-C, there was no further accumulation of ara-U in the plasma with repetitive infusions of HiDAC. In vitro studies indicate that ara-U can exert an inhibitory effect on deoxycytidine (dCyd) deaminase activity. The ratio of the Ki of ara-U to the Km of ara-C for cytidine (Cyd)-dCyd deaminase is 40:1; however, during the gamma phase of ara-C elimination, the ratio of ara-U:ara-C in plasma is at least 100:1. Thus, a retardation of systemic catabolism of ara-C by ara-U is possible. Two to three hours after the termination of the HiDAC infusion, the ara-C cerebrospinal fluid: plasma ratio is 1-3:1, a feature of potential therapeutic significance. The slower elimination of ara-C from the CSF may also contribute to the plasma gamma half-life.
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PMID:Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia. 666 93

The adenosine-deaminase (ADA) activity was evaluated in CSF samples from 263 patients with AIDS. An elevated ADA activity in CSF was found in patients with: antibodies to toxoplasmosis, syphilis or cytomegalovirus; Cryptococcus neoformans or their antigens; tuberculous meningitis; lymphoma. There was no statistical difference among all these groups in respect to ADA activity. However, the ADA activity in CSF from AIDS patients without CSF changes other than HIV antibodies, even unspecific changes, was not elevated. This may suggest that ADA is related to AIDS associated pathologies activity rather than to HIV infection itself.
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PMID:[Adenosine deaminase in the cerebrospinal fluid of patients with acquired immunodeficiency syndrome]. 872 68

This is the first large series, comprising 50 patients who suffered a total of 164 episodes, of pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis (PMP syndrome). Onset of PMP was between the ages of 14 and 39 years and was most frequent in males (68%). Eight males (24%) and five females (31%) had a personal history of migraine. One-quarter had had a viral-like illness up to 3 weeks prior to the onset of the syndrome. The clinical picture consisted of one to 12 episodes of changing variable neurological deficits accompanied by moderate-to-severe headache and occasionally fever. The headaches were described as predominantly throbbing and bilateral with variable duration (mean, 19 h). The mean duration of the transient neurological deficits was 5 h. Sensory symptoms were most common (78% of episodes), followed by aphasic (66%) and motor (56%) symptoms. Visual symptoms appeared in only 12% of episodes. The most frequent combinations were motor aphasia plus sensory and motor right hemibody symptoms (19% of episodes), motor aphasia plus right sensory symptoms (10%) and isolated right (9%) or left (9%) sensory symptoms. All patients were asymptomatic between episodes and following the symptomatic period (maximum duration 49 days). Lymphocytic pleocytosis ranged from 10 to 760 lymphocytic cells/mm3 CSF (mean, 199). In CSF, protein was increased in 96% of patients, IgG was normal in 80% of cases and oligoclonal bands were not found. Adensoine deaminase values were slightly above normal in two out of 16 patients tested. Extensive microbiological determinations, including viral HIV and borrelia serologies, were negative. Brain CT and MRI were always within normal limits, while EEG frequently showed focal slowing. Conventional cranial angiography was performed on 12 patients. In only one were there abnormalities suggestive of localized vascular inflammation, coincident with the focal neurological symptoms. Two patients developed PMP symptoms immediately after angiography. SPECT, performed on only three patients in the symptomatic period, revealed focal areas of decreased uptake consistent with the clinical symptoms. PMP aetiology remains a mystery; chronic arachnoiditis, viral meningoencephalitis or migraine are not plausible aetiological explanations. Because a number of patients had had a prodromic viral-like illness, we hypothesize here that such a viral infection could activate the immune system, thereby producing antibodies that would induce an aseptic inflammation of the leptomeningeal vasculature, possibly accounting for this clinical picture.
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PMID:Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis. A report of 50 cases. 1672 88

The aim of the article is to describe the principal findings among patients with M.tuberculosis and M. bovis CNS infection. Mycobacterium tuberculosis is one of the most common infectious agents that cause death and neurological sequelae around the world. Most of the complications of CNS TB can be attributed to a delay in the diagnosis. Unfortunately, there are no specific diagnostic tools to support an early diagnosis. Other prognostic factors different from delay in treatment have not been identified. Clinical, radiological and laboratory characteristics were analyzed retrospectively from the medical files of all the patients admitted with the diagnoses of tuberculosis. Of 215 patients admitted with systemic tuberculosis, 64 (30%) had a neurological infection. Positive cultures were found in 54 (84%) cases, 18 (33%) in the CSF and the rest in other fluids or tissues. Adenosin deaminase (ADA) enzyme determination was more sensitive than M. tuberculosis PCR in the CSF for supporting an early diagnosis. In addition to a later clinical stage and treatment lag, positive CSF cultures (P=0.001) and the presence of M. bovis (P=0.020) were prognostic factors for a worse outcome. Neither older age, the presence of tuberculomas versus meningeal enhancement, or HIV co-infection, was associated to a worse prognosis. The isolation of M. bovis subspecies was more common that previously reported, and it was associated to the development of parenchymal lesions (P=0.032) when compared to M. tuberculosis. In this study, positive CSF cultures for M. tuberculosis and further identifying M. bovis species were additional prognostic factors for worse outcome. Positive cultures in systemic fluids other than CSF, even when the patient had no obvious systemic manifestations, and ADA determination in the CSF were noteworthy diagnostic tools for the diagnosis.
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PMID:Importance of differentiating Mycobaterium bovis in tuberculous meningitis. 2236 76