A high performance liquid chromatography method for simultaneous determination of rosiglitazone and gemfibrozil in human plasma.

A high performance liquid chromatography (HPLC) method was developed for the simultaneous determination of rosiglitazone and gemfibrozil in human plasma using alpha-asarone as an internal standard (IS). Plasma samples were pretreated by protein precipitation. The analytes were separated on a Macherey-Nagel Nucleodur C(18) (250 mm x 4.

Cocaine induces cell death and activates the transcription nuclear factor kappa-B in PC12 cells.

Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors.

General medications utilization and cost patterns in hospitalized children.

Unlabelled: Drug utilization in the in-patient setting can provide mechanisms to assess drug prescribing trends, efficiency and cost-effectiveness of hospital formularies and examine sub-populations such as children for which prescribing habits are different from adults.

Objectives: The aim of this descriptive study was to analyze general medication utilization patterns and costs excluding antimicrobials prescriptions and to compare two pediatric admission units in a tertiary care university hospital.

Methods: The total number of admitted children was 1,521 and 1,467 for the A and B admission units, respectively.

Quantification of isradipine in human plasma using LC-MS/MS for pharmacokinetic and bioequivalence study.

A highly sensitive and rapid method for the analysis of isradipine in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed. The procedure involves a simple liquid-liquid extraction of isradipine and amlodipine (IS, internal standard) with methyl-t-butyl ether after alkaline treatment and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 372.

Activity-dependent potentiation of calcium signals in spinal sensory networks in inflammatory pain states.

The second messenger calcium is a key mediator of activity-dependent neural plasticity. How persistent nociceptive activity alters calcium influx and release in the spinal cord is not well-understood. We performed calcium-imaging on individual cell bodies and the whole area within laminae I and II in spinal cord slices from mice in the naïve state or 24h following unilateral hindpaw plantar injection of complete Freund's adjuvant.

A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis.

Semaphorins and their receptors, plexins, carry out important functions during development and disease. In contrast to the well-characterized plexin A family, however, very little is known about the functional relevance of B-type plexins in organogenesis, particularly outside the nervous system. Here, we demonstrate that plexin B1 and its ligand Sema4d are selectively expressed in epithelial and mesenchymal compartments during key steps in the genesis of some organs.

Ultra-performance liquid chromatography-tandem mass spectrometry for the determination of lacidipine in human plasma and its application in a pharmacokinetic study.

A selective, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and validated for the quantification of lacidipine in human plasma. With nifedipine as an internal standard, sample pretreatment involved a simple liquid-liquid extraction with tert-butyl methyl ether of 1 ml plasma. The analysis was carried out on an Acquity UPLC BEH C18 column (50 mm x 2.

Effect of the novel antipsychotic drug perospirone on P-glycoprotein function and expression in Caco-2 cells.

Objective: Perospirone (PER) is a novel atypical antipsychotic drug for the treatment of schizophrenia and other psychotic disorders. The multidrug resistance transporter, P-glycoprotein (Pgp), is involved in the efflux transport of several antipsychotics across the blood-brain barrier (BBB). The aim of the present study was to evaluate the modulating effect of PER on both Pgp activity and expression in Caco-2 cell monolayers.

Inhibition of ADP-induced platelet aggregation by clopidogrel is related to CYP2C19 genetic polymorphisms.

1. Clopidogrel is one of the most important antithrombotic drugs but has different efficacies in different populations. The aim of the present study was to evaluate the contribution of CYP2C19 genetic polymorphisms to the inhibition of ADP-induced platelet aggregation by clopidogrel in healthy Chinese volunteers.

Determination of lovastatin in human plasma by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry and its application in a pharmacokinetic study.

A selective, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantitative determination of lovastatin in human plasma and its application in a pharmacokinetic study. With mycophenolate mofetil as internal standard, sample pretreatment involved a one-step extraction with tert-butyl methyl ether of 0.2 ml plasma.

Targeting C-reactive protein levels using high-dose atorvastatin before coronary artery bypass graft surgery.

Background: Statin medication exhibits pleiotropic properties, such as improvement of endothelial function.

Aim: To determine whether a high loading dose of atorvastatin prescribed before and after coronary artery bypass graft (CABG) surgery will attenuate the inflammatory response reflected in kinetic concentrations of C-reactive protein (CRP).

Methods: The individual area under the concentration-time curve (AUC) of CRP concentration was calculated for the first five days after CABG surgery and compared among three groups of patients: group A patients (n=16), who were on chronic statin therapy, were switched to an equivalent therapy of 20 mg atorvastatin daily for 120 h; group B patients (n=15), who were on chronic statin therapy, were switched to 80 mg atorvastatin daily (one dose 24 h before CABG surgery, one on the day of surgery and two further doses after surgery) followed by 40 mg/day up to 120 h after surgery; and group C patients (n=10), who were naive to statin therapy, underwent elective CABG surgery.

Chicken collagen type II reduces articular cartilage destruction in a model of osteoarthritis in rats.

Aim: To evaluate the therapeutic effects of domestic chicken collagen type II (CCII) on rat osteoarthritis (OA) and analyze concomitant changes in the level of Matrix metalloproteinase (MMP)-13, MMP-9, Cathepsin K and their mRNA as well as the tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA in articular cartilage of osteoarthritic rats.

Methods: Osteoarthritis models were surgically induced. Morphology of articular cartilage was done by haematoxylin and eosin staining and Mankin score was calculated, immunohistochemistry of MMP-13, MMP-9 and Cathepsin K was done by ABC method while the mRNA level for MMP-13, MMP-9, cathepsin K as well as TIMP-1 was evaluated by RT-PCR method.

Determination of talinolol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry: application to pharmacokinetic study.

A rapid and sensitive method for determination and screening in human plasma of talinolol is described using propranolol as the internal standard. The analytes in plasma were extracted by liquid-liquid extraction using methyl t-butyl ether. After removed and dried the upper organic phase, the extracts were reconstituted with a fixed volume of buffer of ammonium acetate and acetonitrile (60:40, v/v).

Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).

A rapid, sensitive and specific method to determination of ambroxol in human plasma using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-MS/ESI) was described. Ambroxol and the internal standard (I.S.

A molecular basis of analgesic tolerance to cannabinoids.

Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets in after repeated dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist-induced downregulation and intracellular trafficking of cannabinoid receptors, but little is known about the molecular mechanisms involved. We show here that the type 1 cannabinoid receptor (CB1) interacts physically with G-protein-associated sorting protein 1 (GASP1), a protein that sorts receptors in lysosomal compartments destined for degradation.

An improved high-performance liquid chromatographic method with a solid-phase extraction for the determination of piperacillin and tazobactam: application to pharmacokinetic study of different dosage in Chinese healthy volunteers.

An improved HPLC method was developed for the determination of piperacillin and tazobactam in human plasma and pharmacokinetic study in Chinese healthy volunteers. Piperacillin and tazobactam in human plasma were extracted by solid-phase extraction and separated on a C(18) column and detected at 220 nm. The mobile phase for piepracillin consisted of 0.

Brain blood flow SPET imaging in heroin abusers.

To assess whether chronic heroin abuse may generate vascular central nervous deficits, we studied the profile of vascular alterations in 17 heroin addicts (14 males mean age 31 years, range 23-39 years and 3 females mean age 33 years, range 30-35 years) before and, in one of them, 10 weeks after an ultra-rapid heroin detoxification. Using the functional technique of single-photon emission tomography (SPET) with 740 MBq of (99m)Tc-hexametazine (HMPAO) and computational brain-mapping techniques by means of a Talairach analysis, we determined the pattern of vascular brain alterations associated with chronic heroin abuse. Compared with controls, subjects who had used heroin chronically showed a decrease of global brain perfusion that was more significant in the frontal cortex-mainly in orbito-frontal regions, as well as in the occipital and temporal lobes.

Synaptic scaffolding protein Homer1a protects against chronic inflammatory pain.

Glutamatergic signaling and intracellular calcium mobilization in the spinal cord are crucial for the development of nociceptive plasticity, which is associated with chronic pathological pain. Long-form Homer proteins anchor glutamatergic receptors to sources of calcium influx and release at synapses, which is antagonized by the short, activity-dependent splice variant Homer1a. We show here that Homer1a operates in a negative feedback loop to regulate the excitability of the pain pathway in an activity-dependent manner.

Regulation of motor performance and striatal function by synaptic scaffolding proteins of the Homer1 family.

Intracellular calcium mobilization and signaling mechanisms triggered by activation of synaptic glutamate receptors in the striatum are important modulators of neurotransmission in striatal circuits. However, the expression and functions of scaffolding proteins anchoring glutamate receptors at striatal synapses have not been addressed so far. The long-form Homer1 proteins, Homer1b/c, assemble group I metabotropic glutamate receptors (mGluR1/5) in large macromolecular complexes with sources of calcium influx and release at synapses as well as with components of the NMDA receptor complex at the neuronal cell membrane.

Association of single nucleotide polymorphisms in the promoter region of the pro-opiomelanocortin gene (POMC) with low bone mineral density in adult women.

Among multiple factors influencing osteoporosis, genetic variations involved in bone-mineral metabolism can affect risks predisposing to the disease onset. Here, we studied single-nucleotide polymorphisms (SNPs) in the pro-opiomelanocortin (POMC) gene for possible association with bone mineral density (BMD) among 384 adult Japanese women and observed significant correlation between adjusted BMD and three SNPs in the promoter region (r>0.14, p<0.

Non-genomic cell growth inhibition by progesterone. cell cycle retardation and induction of cell death.

Background: Non-genomic mechanisms have been proposed to play a role in progesterone-dependent cell growth inhibition.

Materials And Methods: The human cell line C-4I, derived from a squamous carcinoma of the uterine cervix, was progesterone receptor-negative. The culture medium contained 10% (v/v) fetal calf serum and the cells, growing in monolayer, were exposed to various progesterone concentrations.

Nitric oxide synthase (NOS)-interacting protein interacts with neuronal NOS and regulates its distribution and activity.

Mechanisms governing the activity of neuronal nitric oxide synthase (nNOS), the major source of nitric oxide (NO) in the nervous system, are not completely understood. We report here a protein-protein interaction between nNOS and NOSIP (nitric oxide synthase-interacting protein) in rat brain in vivo. NOSIP and nNOS are concentrated in neuronal synapses and demonstrate significant colocalization in various regions of the central and peripheral nervous systems.

Administration of estrogen shortly after ovariectomy mimics the anti-nociceptive action and change in 5-HT1A-like receptor expression induced by calcitonin in ovariectomized rats.

Although many clinical reviews are consistent with the view that hormone replacement therapy should be recommended for increasing bone mass of osteoporotic patients, calcitonin administration is preferable to hormone replacement therapy for the alleviation of pain accompanying osteoporosis, despite the fact that osteoporosis and the accompanying pain are accelerated by the reduction in estrogen levels. Distinct from the clinical view, animal studies have shown that estrogen treatment reduces ovariectomy-induced hyperalgesia, although the mechanism of this phenomenon is unknown. The discrepancy in clinical and animal study outcomes may be due to the timing of administration of estrogen after depletion of the hormone.

Conditional gene deletion in primary nociceptive neurons of trigeminal ganglia and dorsal root ganglia.

The use of Cre-loxP technology for conditional mutagenesis in pain pathways had been restricted by the unavailability of mice expressing Cre recombinase selectively in functionally distinct components of the nociceptive system. Here we describe the generation of transgenic mouse lines which express Cre recombinase selectively in sensory ganglia using promoter elements of the Na(v)1.8 gene (Scn10a).

TorsinA, the gene linked to early-onset dystonia, is upregulated by the dopaminergic toxin MPTP in mice.

Early-onset torsion dystonias are caused by a mutation in TorsinA, a protein widely expressed in the nervous system. Here we report the cloning of the murine TorsinA cDNA and a mRNA in situ hybridization analysis of the expression patterns of TorsinA over developmental periods relevant to the etiology of early-onset dystonias. Several studies have demonstrated a functional involvement of the nigrostriatal dopaminergic system in pathological mechanisms underlying dystonia.