Implementation of Basic Patient Safety Protocols: a quality improvement project.

Objective: To analyze the effect of an improvement project on the implementation of Basic Patient Safety Protocols in Brazilian public hospitals.

Method: This is an intervention study aimed at comparing measurements before-and-after the implementation of an improvement project in 35 public hospitals across three Brazilian regions, between July 2021 and September 2023. The intervention consisted of a set of activities to support the implementation of six Basic Patient Safety Protocols, with semimonthly collection of indicators.

Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH inhibitors.

A previously discovered DHODH inhibitor series was further improved by replacing the cyclopentene ring by aromatic heterocycles. Different isomers of these compounds were prepared by the directed ortho-metallation procedure. The compounds are more active than the corresponding cyclopentene analogs and show potent effects on PBMC's proliferation.

SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors.

Novel DHODH inhibitors were developed based on a previously described series by introduction of heteroatoms into the cyclopentene ring and hydroxyl groups attached to it. Also, the hydrophobic biphenyl side chain was replaced with benzyloxy phenyl groups. Activities on human, rat, and mouse enzymes indicate a species specificity of these inhibitors.

2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists.

A series of 2-alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles were synthesized and evaluated for their 5-HT6 activity. The most potent agonist in this series was 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole with an IC50=7.4 nM in 3H-LSD binding and an EC50=1.

Attenuation of methamphetamine induced dopaminergic neurotoxicity by flupirtine: microdialysis study on dopamine release and free radical generation.

Flupirtine is a triaminopyridine derived centrally acting analgetic, which has been found to display neuroprotective effects in models of excitotoxic cell damage, global, and focal ischemia, but no direct interaction with any component of the N-methyl-D-aspartate (NMDA) and glutamate triggered Ca(2+)-channel. Additionally flupirtine shows potent antioxidant effects in isolated mitochondria and cell culture. Work in models of monoamine depletion and neuroleptic induced catalepsy in rats suggests a interaction of flupirtine with the dopaminergic neurotransmitter system as well.

Clustering of isochorismate synthase genes menF and entC and channeling of isochorismate in Escherichia coli.

There are two isochorismate synthase genes entC and menF in Escherichia coli. They encode enzymes (isochorismate synthase, EC 5.4.

Iron chelating, antioxidant and cytoprotective properties of dopamine receptor agonist; apomorphine.

There have been many attempts to discover neuroprotective drugs for the treatment of Parkinson's disease (PD). Many of these compounds either do not cross the blood brain barrier or are not very effective in the 6-hydroxydopamine or MPTP (N-methyl-4-phenyl-1,2,3,6-terahydropyridine) models of PD. We have examined several compounds including dopamine receptor agonist bromocritine, lisuride, pergolide and R-apomorphine for their neuroprotective action against the above neurotoxins in PC12 and dopamine neuroblastoma cell lines in culture and in vivo.

Free radical scavengers: chemical concepts and clinical relevance.

Free radicals are involved in the pathology of many CNS disorders, like Parkinson's disease, Alzheimer's disease, or stroke. This discovery lead to the development of many radical scavengers for the clinical treatment of neurodegenerative diseases. In this review, the different chemical concepts for free radical scavenging will be discussed: nitrons, thiols, iron chelators, phenols, and catechols.

Potent neuroprotective and antioxidant activity of apomorphine in MPTP and 6-hydroxydopamine induced neurotoxicity.

Apomorphine is a potent radical scavenger and iron chelator. In vitro apomorphine acts as a potent iron chelator and radical scavenger with IC50 of 0.3 microM for iron (2.

Antioxidant properties of the triaminopyridine, flupirtine.

Flupirtine is a triaminopyridine-derived centrally acting analgesic, which interacts with mechanisms of noradrenergic pain modulation. Recently, it has been found to display neuroprotective effects in various models of excitotoxic cell damage, global and focal ischemia. Although this profile suggests that flupirtine acts as an antagonist of the N-methyl-D-aspartate (NMDA) and glutamate-triggered Ca2+ channel, there is no direct interaction with the receptor.

Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine.

A significant body of evidence has been provided to support the hypothesis that oxidant stress may be responsible for the degeneration of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease. Apomorphine, a dopamine D1/D2-receptor agonist in the clinical therapy of Parkinson's disease, has been found to be a potent antioxidant and to prevent free radical reaction in rat brain mitochondrial fraction. In this article we show that 1-10 microM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H2O2 (0.

Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine.

A significant body of evidence has been provided to support the hypothesis that oxidant stress may be responsible for the degeneration of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease. Apomorphine, a dopamine D1/D2-receptor agonist in the clinical therapy of Parkinson's disease, has been found to be a potent antioxidant and to prevent free radical reaction in rat brain mitochondrial fraction. In this article we show that 1-10 microM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H2O2 (0.

The potential role of iron chelators in the treatment of Parkinson's disease and related neurological disorders.

Neurodegeneration is characterized by a marked accumulation of iron in the affected brain regions. The reason for this is still unknown. In this article we review the available data on the possible involvement of iron and mediated oxidative stress in the aetiology of Parkinson's disease and related disorders.

Mechanism of 6-hydroxydopamine neurotoxicity.

The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) has recently been found to be formed endogenously in patients suffering from Parkinson's disease. In this article, we highlight the latest findings on the biochemical mechanism of 6-OHDA toxicity. 6-OHDA has two ways of action: it easily forms free radicals and it is a potent inhibitor of the mitochondrial respiratory chain complexes I and IV.

Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction.

Ergoline-derived dopamine receptor agonists, like pergolide or bromocryptine, have recently attracted attention as potential neuroprotective drugs. The classical mixed type dopamine D1 and D2 receptor agonist apomorphine, although used clinically in the therapy of Parkinson's disease, has never been examined for any properties related to neuroprotection. In this paper, we examine the effects of 0.

Toxic aldehydes formed by lipid peroxidation. I. Sensitive, gas chromatography-based stereoanalysis of 4-hydroxyalkenals, toxic products of lipid peroxidation.

An efficient analytical method is presented that does not only allow to detect and quantify 4-hydroxyalkenals, but for the first time provides a tool to look at the enantiomeric ratio of these interesting lipid peroxidation products. It involves acetylation as the only derivatization step, which can be carried out under mild conditions with acetic anhydride and gas chromatography on a chiral permethyl cyclodextrin phase. All biologically important homologues (C5-C9) can be selectively observed in a single chromatographic run.