EFFECTS OF EXFLORATION ON PLANT METABOLISM.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
S Austin
Publications and source records attributed to S Austin.
Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway.
Long-term deficiency of cobalamin or folate causes a demyelinating disease of the brain and spinal cord. A reduced supply of methyl groups has been implicated as its cause. To examine the mechanisms of demyelination in human beings, we have studied three children with sequential inborn errors of the methyl-transfer pathway. One child had abnormal methylfolate metabolism, one abnormal methylcobalamin metabolism, and one hypermethioninaemia probably caused by methionine adenosyltransferase deficiency. Magnetic resonance imaging of the brain and measurement of cerebrospinal-fluid concentrations of 5-methyltetrahydrofolate, methionine, and S-adenosylmethionine were carried out before and after 6-12 months of appropriate treatment. Each patient had abnormal myelination before treatment; the scans suggested demyelination. The only consistent biochemical abnormality in the cerebrospinal fluid was a low concentration of S-adenosylmethionine. Treatment led to substantial clinical improvement, apparent remyelination, and increases in cerebrospinal-fluid S-adenosylmethionine concentration into the normal range. Cerebrospinal-fluid concentrations of S-adenosylmethionine and methionine were significantly lower in eight other children with errors of the methyl-transfer pathway than in an age-matched reference population (mean [95% confidence interval] standard deviation score -1.81 [0.57], p less than 0.001 for S-adenosyl methionine and -1.82 [0.19], p less than 0.001 for methionine). The concentrations of these metabolites increased to within the reference range on treatment. We have shown that demyelination is associated with cerebrospinal-fluid S-adenosylmethionine deficiency and that restoration of S-adenosylmethionine is associated with remyelination.
5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
The effect of enteral glutamine deprivation and supplementation on the structure of rat small-intestine mucosa during a systemic injury response.
BACKGROUND: An aseptic model of tissue injury (the induction of abscesses by subcutaneous injections of turpentine) was used to examine the proposal that changes in glutamine metabolism lead to structural damage in the epithelium of the small intestine during the systemic response to injury and to investigate the role of dietary glutamine in the maintenance of mucosal structure in the small intestine of control and injured rats. METHODS: Glutamine-free and glutamine-rich (3.6% glutamine by weight) diets were fed to rats before and during an acute-phase response to injury. Pair-fed groups of animals enabled an independent assessment to be made of the effects of the associated dietary restriction on the mucosal epithelium. RESULTS: Adaptive increases in villus height and crypt depth were seen in response to 4 days of feeding of the glutamine diet. Pair-feeding (30% dietary restriction) of either diet induced mucosal atrophy (loss of wet weight and nitrogen) without changes in villus height or crypt depth in the proximal tercile of the small intestine. Systemic injury, however, had no effect on the weight or nitrogen content of the mucosa (relative to pair-feeding). Gross histologic appearance, villus height, and crypt depth were also unchanged by the response to injury. CONCLUSIONS: The study provided no evidence to support the proposal that alterations in the availability of dietary glutamine during systemic injury (induced by turpentine injections) lead to structural damage to the epithelium.
Animals↗
COX-2 inhibitors and the cardiovascular system.
Cyclooxygenase-2 selective inhibitors (coxibs) represent a new class of non steroidal anti-inflammatory drugs that exhibit preference for inhibition of cyclooxygenase-2 (COX-2), the COX isoform thought to account largely for prostanoid formation in inflammation. We review the divergent incidence of cardiovascular events derived from the two large clinical trials of coxibs, the Vioxx Gastrointestinal Outcomes Research Trial (VIGOR) and the Celecoxib Long-term Arthritis Safety Study (CLASS), in the context of current understanding of relevant clinical and basic pharmacology. The incidence of cardiovascular events was higher in patients receiving rofecoxib than in those receiving naproxen in VIGOR and did not differ between the groups in CLASS. By contrast, while the primary gastrointestinal (GI) endpoint comparison favored rofecoxib in VIGOR, no significant difference in the incidence of the primary GI endpoint was evident between celecoxib and two NSAID comparators not attained in CLASS. The cardiovascular results in VIGOR may have resulted from chance, a cardioprotective effect of naproxen, or suppression of prostacyclin but not thromboxane on rofecoxib. Differences in cardiovascular outcome between the two trials may also have resulted either from chance, or from aspects of the trial design (such as the use of aspirin by roughly one-fifth of the participants in CLASS), or from differences in the COX-2 selectivity or other pharmacology of the coxibs. Individuals who warrant low-dose aspirin for cardioprotection may have less likelihood of a GI event if they combine aspirin with rofecoxib, rather than a traditional NSAID. However, evidence addressing directly this hypothesis is currently unavailable. On the other hand, coxib consumption alone does not currently warrant initiation of a cardioprotective regimen, such as low-dose aspirin.
Anti-Inflammatory Agents, Non-Steroidal↗