Impact of the catechol-O-methyltransferase Val158Met polymorphism on the pharmacokinetics of L-dopa and its metabolite 3-O-methyldopa in combination with entacapone.

In the pharmacotherapy of patients with Parkinson's disease (PD), entacapone reduces the peripheral metabolism of L-dopa to 3-O-methyldopa (3-OMD), thereby prolonging the half-life (t) of L-dopa and increasing the area under the concentration curve (AUC). The effect of entacapone on the pharmacokinetics of L-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. 3-OMD has a detrimental effect and results in a poor response to L-dopa treatment in patients with PD; however, the influence of this polymorphism on the production of 3-OMD remains unknown.

Oxicam-derived non-steroidal anti-inflammatory drugs suppress 1-methyl-4-phenyl pyridinium-induced cell death via repression of endoplasmic reticulum stress response and mitochondrial dysfunction in SH-SY5Y cells.

We have previously reported that oxicam-derived non-steroidal anti-inflammatory drugs (oxicam-NSAIDs), including meloxicam, piroxicam and tenoxicam, elicit protective effects against 1-methyl-4-phenyl pyridinium (MPP)-induced cell death in a fashion independent of cyclooxygenase (COX) inhibition. We have also demonstrated that oxicam-NSAIDs suppress the decrease in phosphorylation of Akt caused by MPP. The molecular mechanism through which oxicam-NSAIDs provide cytoprotection remains unclear.

Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells.

Paraquat is a commonly used herbicide; however, it is highly toxic to humans and animals. Exposure to paraquat causes severe lung damage, leading to pulmonary fibrosis. However, it has not been well clarified as how paraquat causes cellular damage, and there is no established standard therapy for paraquat poisoning.

Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model.

A series of oxicam non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be neuroprotective against 1-methyl-4-phenyl pyridinium in human neuroblastoma SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway independent of cyclooxygenase (COX) inhibition. The present study endeavored to establish this novel effect of meloxicam (MLX), an oxicam NSAID, in a mouse Parkinson's disease (PD) model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male C57BL/6 mice, which received MPTP (30 mg/kg/day; s.

Estimation of the duration after methamphetamine injection using a pharmacokinetic model in suspects who caused fatal traffic accidents.

When the population parameters of drug pharmacokinetics in the human body system are known, the time-course of a certain drug in an individual can generally be estimated by pharmacokinetics. In the present two cases where methamphetamine abusers were suspected to have inflicted mortalities in traffic accidents, the time-elapse or duration immediately after methamphetamine injection to the time when the accidents occurred became points of contention. In each case, we estimated the time-course of blood methamphetamine after the self-administration in the suspects using a 2-compartment pharmacokinetic model with known pharmacokinetic parameters from the literatures.

Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.

In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved.

HRD1 levels increased by zonisamide prevented cell death and caspase-3 activation caused by endoplasmic reticulum stress in SH-SY5Y cells.

Zonisamide, which is commonly prescribed at high doses (200-400 mg/day) for the treatment of partial seizures, has recently been used at a low dose (25 mg/day) for improving parkinsonian syndrome. However, the molecular mechanisms that underlie the antiparkinsonian effects of zonisamide have not been clarified. Here we show that low micromolar concentrations of zonisamide prevented cleavage of caspase-3 and cell death in human dopaminergic SH-SY5Y neuroblastoma cells that were subjected to endoplasmic reticulum stress induced by tunicamycin or 6-hydroxydopamine.

Detection of landiolol using high-performance liquid chromatography/fluorescence: a blood esterase-sensitive ultra-short-acting beta(1)-receptor antagonist.

Landiolol hydrochloride, a new adrenergic beta(1)-selective antagonist having an ultra-short half-life, is used to prevent tachyarrhythmia during surgery. Since landiolol is thought to be rapidly hydrolyzed to an inactivate metabolite by esterases, quantification of the drug concentration in the blood is impractical. The landiolol concentration in blood was halved within 5 min after blood sampling.

Characteristics of Asian/Pacific Islander Psychiatric Patients in a Public Metnal Health System.

PURPOSE OF THE PAPER. The purpose of this paper was to examine the general characteristics of Asian%divide;Pacific Islander patients in the Los Angeles County mental ehatlh system. SUMMARY OF METHODS UTILIZED.