Drug metabolism and hypersensitivity reactions to drugs.

Purpose Of Review: The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs.

Recent Findings: The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response.

Heme Oxygenase 1 and 2 Common Genetic Variants and Risk for Essential Tremor.

Several reports suggested a role of heme oxygenase genes 1 and 2 (HMOX1 and HMOX2) in modifying the risk to develop Parkinson disease (PD). Because essential tremor (ET) and PD share phenotypical and, probably, etiologic factors of the similarities, we analyzed whether such genes are related with the risk to develop ET. We analyzed the distribution of allelic and genotype frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 single nucleotide polymorphisms, as well as the presence of copy number variations of these genes in 202 subjects with familial ET and 747 healthy controls.

Study of perfusion changes in the optic disc of patients with fibromyalgia syndrome using new colorimetric analysis software.

Purpose: We measured the amount of hemoglobin at the optic nerve head of fibromyalgia (FM) patients using new colorimetric analysis software. We also investigated whether perfusion defects of the optic nerve head in patients with FM lead to tissue atrophy and corresponding retinal nerve fiber layer (RNFL) thinning measured by optical coherence tomography (OCT).

Methods: We recruited for this cross-sectional study 118 FM patients and 76 sex- and age-matched healthy controls.

Pharmacogenomics of cyclooxygenases.

Cyclooxygenases (COX-1 and COX-2) are key enzymes in several physiopathological processes. Many adverse drugs reactions to NSAIDs are attributable to COX-inhibition. The genes coding for these enzymes (PTGS1 and PTGS2) are highly variable, and variations in these genes may underlie the risk of developing, or the clinical evolution of, several diseases and adverse drug reactions.

Both respiration and photosynthesis determine the scaling of plankton metabolism in the oligotrophic ocean.

Despite its importance to ocean-climate interactions, the metabolic state of the oligotrophic ocean has remained controversial for >15 years. Positions in the debate are that it is either hetero- or autotrophic, which suggests either substantial unaccounted for organic matter inputs, or that all available photosynthesis (P) estimations (including (14)C) are biased. Here we show the existence of systematic differences in the metabolic state of the North (heterotrophic) and South (autotrophic) Atlantic oligotrophic gyres, resulting from differences in both P and respiration (R).

The potential of LINGO-1 as a therapeutic target for essential tremor.

Introduction: LINGO-1 is a negative regulator of neuronal survival, oligodendrocyte differentiation and axonal outgrowth and regeneration, because it interacts with diverse growth factor receptors blocking or inhibiting their action. Consistent findings obtained in vitro and in animal models suggest that anti-LINGO-1 therapy may be useful in neurodegenerative disorders such as multiple sclerosis (MS), Parkinson's disease or essential tremor (ET). Moreover, genetic and pathological evidence provide a robust link between LINGO-1 and ET.

Analysis of optic disk color changes in Alzheimer's disease: a potential new biomarker.

Purpose: In the present study, we evaluated changes in the retinal nerve fiber layer (RNFL) and optic disk color (i.e., the level of paleness as an indirect sign of axonal loss) in patients with Alzheimer's disease (AD) compared with healthy controls.

Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine.

Background: Histamine has been implicated in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the diamine oxidase gene (DAO; chromosome 7q36.1, involved in histamine metabolism) and the risk for migraine.

Measuring hemoglobin levels in the optic disc of Parkinson's disease patients using new colorimetric analysis software.

Objective. To evaluate a new method of measuring hemoglobin (Hb) levels and quantifying the color changes in the optic nerve head of Parkinson's disease (PD) patients. We also compared differences in retinal nerve fiber layer (RNFL) thicknesses obtained using spectral domain optical coherence tomography (OCT) device between PD group and healthy group.

TREM2 R47H variant and risk of essential tremor: a cross-sectional international multicenter study.

Introduction: Essential tremor (ET) is the most frequent movement disorder in adults. Its pathophysiology is not clearly understood, however there is growing evidence showing common etiologic factors with other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases (AD, PD). Recently, a rare p.

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease.

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes.

Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application.

Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in patients with multiple sclerosis. Here, we describe the emergence of an idea to quantify these optic disc color changes in multiple sclerosis patients. We recruited 12 multiple sclerosis patients with previous optic neuritis attack and obtained photographs of their optic discs.

Drug and xenobiotic biotransformation in the blood-brain barrier: a neglected issue.

Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB) has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to the BBB as a drug-metabolizing barrier.

An association study between Heme oxygenase-1 genetic variants and Parkinson's disease.

The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system.

Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome.

Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population.

Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole.

Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals.

Contact topical anesthesia for strabismus surgery in adult patients.

Objective: To analyze the effectiveness and usefulness of contact topical anesthesia in strabismus surgery in adult patients.

Material And Methods: A prospective study was conducted on 20 patients undergoing strabismus surgery using contact topical anesthesia and sedation with remifentanil. The intensity of pain was recorded using a numeric pain rating scale at the time of anesthesia implementation, during the surgical procedure, 30 min afterwards, and during the first postoperative day.

Biomolecular structure manipulation using tailored electromagnetic radiation: a proof of concept on a simplified model of the active site of bacterial DNA topoisomerase.

We report on the viability of breaking selected bonds in biological systems using tailored electromagnetic radiation. We first demonstrate, by performing large-scale simulations, that pulsed electric fields cannot produce selective bond breaking. Then, we present a theoretical framework for describing selective energy concentration on particular bonds of biomolecules upon application of tailored electromagnetic radiation.

Clinical practice guidelines for translating pharmacogenomic knowledge to bedside. Focus on anticancer drugs.

The development of clinical practice recommendations or guidelines for the clinical use of pharmacogenomics data is an essential issue for improving drug therapy, particularly for drugs with high toxicity and/or narrow therapeutic index such as anticancer drugs. Although pharmacogenomic-based recommendations have been formulated for over 40 anticancer drugs, the number of clinical practice guidelines available is very low. The guidelines already published indicate that pharmacogenomic testing is useful for patient selection, but final dosing adjustment should be carried out on the basis of clinical or analytical parameters rather than on pharmacogenomic information.