Pyridoxin-dependentní epilepsie je autozomálně recesivně dědičné onemocnění, které se prenatálně, neonatálně a v časném dětství do 3 let projevuje farmakorezistentními epileptickými záchvaty. Jde o dědičné poruchy metabolizmu pyridoxinu asociované s mutacemi v genech ALDH7A1 nebo ALDH4A1. Podobným onemocněním je pyridoxal-fosfát dependentní epilepsie (neonatální epileptická encefalopatie) podmíněná mutacemi v PNPO genu. Pyridoxin-dependentní epilepsie jsou úspěšně léčitelné vysokými dávkami pyridoxinu. Pyridoxal-fosfát dependentní epilepsie jsou na terapii pyridoxinem refrakterní, ale reagují na léčbu pyridoxal-fosfátem. Diagnostika obou jednotek je založena na genetickém a biochemickém vyšetření.
Pyridoxine dependent epilepsy is a rare autosomal recessive hereditary disorder causing a severe intractable epileptic seizures presenting typically in prenatal and neonatal period, rarely in early infancy (age up to 3 years). Pyridoxine dependent epilepsy, caused by metabolic disturbance of pyridoxine, is associated with mutations in ALDH7A1 or ALDH4A1 gene. Similar condition, pyridoxal-phosphate dependent epilepsy (also called neonatal epileptic encephalopathy), is caused by mutations in PNPO gene. Pyridoxine dependent epilepsy is successfully treatable using high doses of pyridoxine. Neonatal epileptic encephalopathy is refractory to pyridoxine administration, however responses to treatment with pyridoxal-phosphate. The diagnosis of both pyridoxine dependent epilepsy and neonatal epileptic encephalopathy is based on biochemical and genetic examinations.
- Klíčová slova
- pyridoxal-fosfát, neonatální epileptická encefalopatie,
- MeSH
- aldehyddehydrogenasa genetika MeSH
- diagnostické techniky molekulární metody využití MeSH
- dítě MeSH
- elektroencefalografie využití MeSH
- lidé MeSH
- nemoci novorozenců genetika metabolismus MeSH
- novorozenec MeSH
- pyridoxalfosfát aplikace a dávkování metabolismus MeSH
- pyridoxin aplikace a dávkování metabolismus MeSH
- vitamin B6 aplikace a dávkování škodlivé účinky MeSH
- záchvaty diagnóza farmakoterapie genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
Coronary artery bypass graft (CABG) surgery is frequently performed and effective; however, perioperative complications related to ischemia-reperfusion injury, including myocardial infarction (MI), remain common and result in significant morbidity and mortality. MC-1, a naturally occurring pyridoxine metabolite and purinergic receptor antagonist, prevents cellular calcium overload and may reduce ischemia-reperfusion injury. Phase 2 trial data suggest that MC-1 may reduce death or MI in high-risk patients undergoing CABG surgery. OBJECTIVE: To assess the efficacy and safety of MC-1 administered immediately before and for 30 days after surgery in patients undergoing CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: The MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II Trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery with cardiopulmonary bypass enrolled between October 2006 and September 2007 at 130 sites in Canada, the United States, and Germany. INTERVENTIONS: Patients received either MC-1, 250 mg/d (n = 1519), or matching placebo (n = 1504) immediately before and for 30 days after CABG surgery. MAIN OUTCOME MEASURES: The primary efficacy outcome was cardiovascular death or nonfatal MI, defined as a creatine kinase (CK) MB fraction of at least 100 ng/mL or new Q waves through postoperative day 30. RESULTS: The primary efficacy outcome occurred in 140 of 1510 patients (9.3%) in the MC-1 group and 133 of 1486 patients (9.0%) in the placebo group (risk ratio, 1.04; 95% confidence interval, 0.83-1.30; P = .76). All-cause mortality was higher among patients assigned to MC-1 than placebo at 4 days (1.0% vs 0.3%; P = .03) but was similar at 30 days (1.9% vs 1.5%; P = .44). There was no difference in the 8- to 24-hour CK-MB area under the curve between the MC-1 and placebo groups (median, 270 [interquartile range, 175-492] vs 268 [interquartile range, 170-456] hours x ng/mL; P = .11). CONCLUSION: In this population of intermediate- to high-risk patients undergoing CABG surgery, MC-1 did not reduce the composite of cardiovascular death or nonfatal MI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402506
- MeSH
- antagonisté purinergního receptoru P2 MeSH
- blokátory kalciových kanálů aplikace a dávkování terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- infarkt myokardu etiologie prevence a kontrola MeSH
- kardiopulmonální bypass MeSH
- koronární bypass mortalita škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- purinergní receptory P2 MeSH
- pyridoxalfosfát aplikace a dávkování terapeutické užití MeSH
- reperfuzní poškození myokardu etiologie prevence a kontrola MeSH
- riziko MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- abstrakty MeSH
