Linifanib alone and in combination with metronomic chemotherapy is active on cutaneous T-cell lymphoma cells by targeting the AKT/mTOR signaling pathway.

Cutaneous T-cell lymphomas (CTCLs) are a rare and heterogeneous subset of skin-localized, non-Hodgkin lymphomas. Our aim was to evaluate the in vitro antitumor activity of the multi-kinase inhibitor linifanib, either alone or in combination with metronomic vinorelbine (mVNR) or etoposide (mETO), on CTCL cells. In vitro proliferation assay and Luminex analysis showed that long-term, daily exposure of linifanib significantly inhibited the proliferation of the human CTCL cell line HH, in a concentration-dependent manner (IC = 48.

Cannabis and Driving: Developing Guidelines for Safety Policies.

Introduction: The dynamism in the regulatory frameworks concerning the consumption of cannabinoids has placed their effects on cognitive and psychomotor skills at the center of the scientific debate. In consideration of the potential repercussions on public safety, particular attention has been focused on the impairment of driving skills, opening up the need to specifically regulate driving under the effects of cannabinoids.

Pharmacokinetics: Both native cannabinoids and metabolites show a long positivity at low concentrations in the biological fluids, especially in the case of chronic consumption.

Multiple osteomata from medieval Tuscany, Italy (ca. 10-12 AD).

Objective: To explore the possible etiology of multiple osteomata on a skull and long bones from an individual from a medieval site in Tuscany, Italy.

Materials: Human skeletal remains dating to the 10-12 century AD from the parish church of S. Pietro in Pava, in the province of Siena (Tuscany, Central Italy).

Pharmacokinetics of Bedrocan®, a cannabis oil extract, in fasting and fed dogs: An explorative study.

The aim of this study was to explore the pharmacokinetics of the two main active compounds (THC and CBD) contained in the cannabis oil extract Bedrocan® in fasting and fed dogs. Bedrocan® (20% delta-9-tetrahydrocannabinol [THC] and 0.5% cannabidiol [CBD]) was administered at 1.

A novel fast method for aqueous derivatization of THC, OH-THC and THC-COOH in human whole blood and urine samples for routine forensic analyses.

A novel aqueous in situ derivatization procedure with propyl chloroformate (PCF) for the simultaneous, quantitative analysis of Δ -tetrahydrocannabinol (THC), 11-hydroxy-Δ -tetrahydrocannabinol (OH-THC) and 11-nor-Δ -tetrahydrocannabinol-carboxylic acid (THC-COOH) in human blood and urine is proposed. Unlike current methods based on the silylating agent [N,O-bis(trimethylsilyl)trifluoroacetamide] added in an anhydrous environment, this new proposed method allows the addition of the derivatizing agent (propyl chloroformate, PCF) directly to the deproteinized blood and recovery of the derivatives by liquid-liquid extraction. This novel method can be also used for hydrolyzed urine samples.

Voltage-operated potassium (Kv) channels contribute to endothelium-dependent vasorelaxation of carvacrol on rat aorta.

Objectives: Carvacrol, a monoterpene widely present in nature, is commonly used in the food industry and in cosmetics, besides to possess a plethora of pharmacological properties, among these also in vitro vasorelaxing effects and in vivo hypotensive responses. Although in rat aortic rings carvacrol evoked a vasodilatation both in the presence and in the absence of endothelium, in preparations with intact endothelial layer its vasoactive response markedly improved.

Methods: This study aimed at investigating the mechanism of action responsible for the endothelial component of the carvacrol-induced vasorelaxing response observed in rat isolated aortic rings.

A Direct Aqueous Derivatization GSMS Method for Determining Benzoylecgonine Concentrations in Human Urine.

A sensitive and reliable method for extraction and quantification of benzoylecgonine (BZE) and cocaine (COC) in urine is presented. Propyl-chloroformate was used as derivatizing agent, and it was directly added to the urine sample: the propyl derivative and COC were then recovered by liquid-liquid extraction procedure. Gas chromatography-mass spectrometry was used to detect the analytes in selected ion monitoring mode.

Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling.

Simultaneous determination of morphine, codeine and 6-acetyl morphine in human urine and blood samples using direct aqueous derivatisation: validation and application to real cases.

Opiates play a relevant role in forensic toxicology and their assay in urine or blood is usually performed for example in workplace drug-testing or toxicological investigation of drug impaired driving. The present work describes two new methods for detecting morphine, codeine and 6-monoacethyl morphine in human urine or blood using a single step derivatisation in aqueous phase. Propyl chloroformate is used as the dramatizing agent followed by liquid-liquid extraction and gas-chromatography-mass spectroscopy to detect the derivatives.

The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury.

Naringenin (NAR), flavonoid abundant in the genus Citrus, has been reported to interact with the large-conductance calcium-activated potassium channels (BK). Since activators of BK channels expressed in cardiac mitochondria trigger protective effects in several models of myocardial ischemia/reperfusion (I/R), this work aimed to evaluate the potential cardioprotective effects of NAR and the involvement of mitochondrial BK channels. In an in vivo model of acute infarct in rats, NAR (100mg/kg i.

Fatal acute poisoning from massive inhalation of gasoline vapors: case report and comparison with similar cases.

We describe a case of an acute lethal poisoning with hydrocarbons resulting from massive accidental inhalation of gasoline vapors. The victim, a 50-year-old man was found unconscious inside a control room for the transport of unleaded fuel. Complete autopsy was performed and showed evidence of congestion and edema of the lungs.

Development and validation of a new GC-MS method for the detection of tramadol, O-desmethyltramadol, 6-acetylmorphine and morphine in blood, brain, liver and kidney of Wistar rats treated with the combination of heroin and tramadol.

Heroin is one of the most dangerous abused drugs in the world. Tramadol is an additive recently found at high concentration levels in street heroin seizures in Egypt. This substance could affect the usual analytical method for the detection of heroin and metabolites, as well as the pharmacokinetic and disposition of single analytes.

Identification and quantification of phenobarbital in a mummified body 10 years after death.

This article reports the determination of phenobarbital in the mummified body of a 56-year-old man found completely mummified 10 years after his death. When alive, he was being treated for epilepsy with phenobarbital, and the recent analyses, performed with both immunochemical techniques and gas chromatography with mass spectrometry (GC-MS), have revealed the presence of this substance in various tissues: the mean content of barbiturate in the mummified liver tissue was 93 μg/g, 216 μg/g in the heart, 17 μg/g in the lungs, 12 μg/g in muscles, and 31 μg/g in the skin. Preliminary screening tests with immunochemical techniques to evaluate the presence of other drugs were also performed.

Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers.

Aims: To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies.

Methods: Thirty-eight patients received 500 mg/mq(2) CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.

Novel method for simultaneous aqueous in situ derivatization of THC and THC-COOH in human urine samples: validation and application to real samples.

The present work describes the validation of a novel aqueous in situ derivatization procedure with trimethyloxonium tetrafluoroborate (TMO) as methylating agent for the simultaneous, quantitative analysis of Δ(9)-tetrahydrocannabinol (THC) and 11-nor-Δ(9)-tetrahydrocannabinol carboxylic acid (THC-COOH) in human urine. The derivatizing agent is directly added to the urine sample and the methyl-derivatives are then recovered by liquid-liquid extraction procedure. Gas chromatography-mass spectrometry was used to detect the derivatives in selected ion monitoring mode.

(+/-)-Naringenin as large conductance Ca(2+)-activated K+ (BKCa) channel opener in vascular smooth muscle cells.

Unlabelled: BACKGROUND AND PURPOSE. The aim of this study was to investigate, in vascular smooth muscle cells, the mechanical and electrophysiological effects of (+/-)-naringenin.

Experimental Approach: Aorta ring preparations and single tail artery myocytes were employed for functional and patch-clamp experiments, respectively.

Essential oils of commonly used plants as inhibitors of peroxynitrite-induced tyrosine nitration.

The essential oils obtained from fifteen relevant and commonly used plants belonging to Cruciferae, Lamiaceae, Lauraceae, Apiaceae, and Zingiberaceae were screened using an in vitro model of peroxynitrite-induced tyrosine nitration. Almost complete inhibition of 3-nitrotyrosine formation (91% at 300 microg/ml) was achieved only with the essential oil obtained from the leaves of Laurus nobilis. 1,8-Cineol, accounting for a 50% of this essential oil, which resulted as inactive in this model, thus evidencing a major role for the minor volatile compounds present in the leaves.

In vitro activity of the essential oil of Cinnamomum zeylanicum and eugenol in peroxynitrite-induced oxidative processes.

The essential oil obtained from the bark of Cinnamomum zeylanicum Blume (Lauraceae) and three of its main components, eugenol, (E)-cinnamaldehyde, and linalool (representing 82.5% of the total composition), were tested in two in vitro models of peroxynitrite-induced nitration and lipid peroxidation. The essential oil and eugenol showed very powerful activities, decreasing 3-nitrotyrosine formation with IC50 values of 18.

Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels.

A flavonoid-rich diet has been associated with a lower incidence of cardiovascular diseases, probably because of the antioxidant and vasoactive properties of flavonoids. Indeed, many flavonoids show vasorelaxing properties, due to different and often not yet completely clarified mechanisms of action. Among them, the activation of vascular potassium channels has been indicated as a possible pathway, accounting, at least in part, for the vasodilatory action of some flavonoid derivatives, such as apigenin and dioclein.

Vasodilator activity of Michelia figo Spreng. (Magnoliaceae) by in vitro functional study.

The methanolic extract of leaves of Michelia figo Spreng. (Magnoliaceae), as well as several purified fractions, showed a concentration-dependent vasorelaxing effect on aortic rings endothelium-deprived and pre-contracted by norepinephrine (NE). For further pharmacological investigation on the mechanism of action, the fraction S4 was selected, since it showed the best vasodilator properties.