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Abstract A fatality due to the ingestion of solution containing phenol and o-cresol is described. The pathological findings were typical of acute substantial poisoning. Blood, urine and stomach content were [...]

Ursodeoxycholic acid (UDCA) is considered the first-choice therapy for cholestatic disorders. To enhance solubility and exploit specific transporters in liver, we synthesized a new galactosyl pro-drug of UDCA (UDCAgal). Ethinylestradiol (EE)-induced cholestasis was used to study and compare the effects of UDCAgal with UDCA on bile flow, hepatic canalicular efflux transporter expression, and inflammation. UDCAgal resulted quite stable both at pH 7.4 and 1.2 and regenerated the parent drug after incubation in human plasma. Its solubility, higher than UDCA, was pH- and temperature-independent. UDCAgal displayed a higher cell permeation compared to UDCA in liver HepG2 cells. Moreover, in cholestatic rats, UDCAgal showed a higher potency compared to UDCA in reducing serum biomarkers (AST, ALT, and ALP) and cytokines (TNF-α and IL-1β). The higher effect of UDCAgal on the increase in bile salt export pump and multidrug resistance-associated protein 2 transcription indicated an improved spillover of bile acids from the liver. UDCAgal showed a reduction in CCL2, as well as TNF-α, IL-1β, and cyclooxygeanse-2 mRNAs, indicating a reduction in hepatic neutrophil accumulation and inflammation. Moreover, UDCAgal, similarly to UDCA, heightens bile flow and modulates biliary acids secretion. These results indicate that UDCAgal has a potential in the treatment of cholestatic disease.

Aceclofenac is a popular analgesic, antipyretic, and nonsteroidal anti-inflammatory drug (NSAID) used for prolonged treatment (at least three months) in musculoskeletal disorders. It is characterized by several limitations such as poor water solubility and low oral bioavailability. The main side-effect of aceclofenac, as well as all NSAIDs, is the gastrotoxicity; among other adverse effects, there is the risk of bleeding since aceclofenac reversibly inhibits platelet aggregation. With the aim to reduce these drawbacks, we have designed, synthesized, and characterized, both in vitroand in vivo, an orally administrable pro-drug of aceclofenac (ACEgal). ACEgal was obtained by conjugating carboxyl group with the 6-OH group of d-galactose; its structure was confirmed by X-ray powder diffractometry. The pro-drug was shown to be stable at 37 °C in simulated gastric fluid (SGF-without pepsin, pH = 1.2) and moderately stable in phosphate buffered saline (PBS, pH = 7.4). However, it hydrolyzed in human serum with a half-life (t1/2) of 36 min, producing aceclofenac. Furthermore, if compared to its parent drug, ACEgal was four-times more soluble in SGF. To predict human intestinal absorption, cell permeability in a Caco-2 model of aceclofenac and ACEgal was determined. Anti-inflammatory, analgesic, and ulcerogenic activities have been investigated in vivo. In addition, oxidative stress parameters (thiobarbituric acid reactive substances, TBARS, and glutathione, GSH) and platelet antiaggregatory activity both of parent drug and pro-drug were evaluated. Results clearly showed that the conjugation of aceclofenac to a galactose molecule improves physicochemical, toxicological (at gastric and blood level), and pharmacological profile of aceclofenac itself without changing intestinal permeability and antiplatelet activity (in spite the new sugar moiety).

Purpose: This paper bridges the gap between theory and practice in the application of the Income Stabilisation Tool (IST). With an application to the dairy sector, the purpose of this paper is to propose methodology for the quantification of reference income when farm structural change occurs and estimate the role of farm attributes on the probability of income loss, offering an ex anteevaluation of farm resilience to risk. Design/methodology/approach: Based on a balanced Farm Accountancy Network farm-level panel ranging from 2008 to 2014, three hypotheses of reference income calculation are tested to assess whether farms structural changes over the years significantly affect the level of IST indemnification. The role of farm characteristics on the probability of an income reduction is then evaluated by estimating a multinomial logit model. Findings: Results show that farms’ structural changes significantly affect IST indemnities and need to be considered in calculating the reference income. The estimated model suggests that farm characteristics significantly affect the probability of a severe income drop and hence risk resilience. Extensive livestock systems seem to reduce the probability of an income drop, while farms in upland areas managed by young farmers seem to experience increased risk exposure. Originality/value: The research provides one of the first attempts to define risk profile of dairy farms by modelling the probability of an income reduction on observable attributes. Indeed, among different sectors, dairy farms emerge as the main candidates for the application of the IST.

Among energy storage systems, Liquid Air Energy Storage (LAES) is attractive because of high energy density, ease of being scaled up, absence of geographical constraints, mature technology and use of safe materials/working fluids. This work presents a critical review of LAES system configurations in the literature to identify the criteria behind their conceptual development. The goal is achieved following the HEATSEP methodology, which allowed identifying a common thread in the evolution of all LAES configurations in the literature based on very few layouts, named “basic configurations”. The optimization of these few layouts, taking into account all possible internal heat transfers, provides a unique and comprehensive overview of existing configurations in spite of their seemingly great complexity. This picture clearly indicates the link between topology and performance improvement and provides insight into the limits of the maximum possible performance gain over the existing literature. The optimal results show that the margin for improvement is quite narrow. In the case of a complete thermal integration between charge and discharge phases with the addition of Organic Rankine Cycle system a gain from 61.9 % to 64.3 % is obtained over the best performing configuration in the literature.

The intake of several substances by pregnant women could be hazardous to the fetus and mother's health: many substances can cross the placenta and reach the fetal compartment, causing adverse outcomes. Consequently, to accurately measure the presence of xenobiotics in fetal matrices, sensitive and specific bioanalytical methods are necessary: this would allow the assessment of fetal exposure to substances which, although licit, can be dangerous for the fetal and child's growth. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry method for the simultaneous determination and quantitation of caffeine and acetaminophen in amniotic fluid. Amniotic fluid is a quite complex biological matrix and, as such, it requires a purification step prior to analysis. The extraction method has been optimized by comparing three different commercially available SPE cartridges (Supel™ Select HLB, Phenomenex Strata C18-E, and Agilent ABS Elut-NEXUS), and a liquid/liquid extraction with acetonitrile. A reverse-phase HPLC with a C18 column and gradient elution program was used. MS detection was carried out in MRM mode. Quantitation was performed using the internal standard method. Validation parameters were very satisfactory. The high selectivity and sensitivity of the method (LOQ < 9.5 ng mL−1, and LOD < 3.3 ng mL−1) allowed us to determine target analytes even in small amounts. Precision, matrix effect, and stability were also evaluated. The whole validated method has finally been applied to the analysis of 194 real samples of human amniotic fluid obtained from pregnant women (15–21 weeks of gestation) in order to monitor the effective intake of target analytes: 96% of the examined women consumed caffeine during pregnancy while a lower percentage (20%) showed acetaminophen intake. The whole procedure is simple and easy to perform with minimal sample preparation and short analysis time.

AbstractThe serotonin receptor 7 (5-HT7-R) plays important functional roles in learning and memory, in regulation of mood and circadian rhythmicity. LP-211 is a new selective agonist, belonging to 1-arylpiperazine category. We report studies aimed to evaluate the modulatory effect of a subchronic regimen on behavioral/molecular parameters. At low dose [0.25 mg/kg intraperitoneally (i.p.)], LP-211 induced a 6-h anticipated wake up in adult mice (with no temporal landmark by constant light), acting as nonphotic stimulus for ‘internal clock’ resetting. In standard 12:12-h light/dark cycle, a subchronic effect (5–6 days at 0.25 mg/kg, once per day) was observed: delayed wake up, reduced peak of locomotor activity and no evidence for brain cellular proliferation after ex vivoanalysis. Other studies in rats were aimed to investigate long-term effects of developmental LP-211 administration into adulthood. Subchronic LP-211 (0.125 mg/kg i.p. once per day during the prepuberal phase) reduced l-glutamate, N-methyl-d-aspartate receptor 1 and dopamine transporter within the ventral striatum. With LP-211 (0.25 mg/kg i.p. once per day during the postpuberal phase), clear reductions were observed in the immunoreactivity of serotonin transporter and dopaminergic D2 receptors in the ventral and dorsal striatum, respectively. Subchronic LP-211 in rats and mice appears to be a suitable tool for studying the role of 5-HT7-R in sleep disorders, emotional/motivational regulations, attentive processes and executive functions.

To determine the incidence of tinea capitisin São Paulo, Brazil, an investigation was performed in Private and Public Pediatrics Service involving 4,500 children from 0 to 15 years old during 5 years (1996–2000). Samples were taken from 132 children with suspected fungal infection of the scalp, for direct microscopy and culture. Tineaof scalp was mycologically confirmed in 112 patients (85%). Males were more affected than females in all age groups. Children below 8 years old accounted for more than 75% of the occurrences. Only three cases of tinea capitiswere diagnosed in children from 12 to 15 years of age. Tinea capitiswas prevalent in 103 cases (91.96%); inflammatory kerion type lesions were diagnosed in 9 patients (8.04%). Microsporum canis(70.5%) and Trichophyton tonsurans(23.2%) were the most common agents followed by T. mentagrophytes(3.6%), M. gypseum(1.8%) and T. rubrum(0.9%).

A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC50 value of 31.4 M. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper [1] decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.

The macrocyclic antibiotics represent a relatively new class of chiral selectors in CE, HPLC, and TLC. We have examined the use of the macrocyclic antibiotic vancomycin as a chiral selector in HPLC for the separation of 1,4‐dihydropyridines (DHPs) calcium antagonists (CAs). Chromatographic data of six 1,4‐dihydropyridine calcium channel blockers obtained on the vancomycin chiral stationary phase (Chirobiotic V) were compared with those obtained on an α1‐acid glycoprotein (AGP) HPLC stationary phase. Optimization of pH and organic modifier was carried out in order to modulate the retention properties of each system. All chiral neutral DHPs were resolved on the AGP column, whereas on Chirobiotic V only basic DHPs showed a split peak. The analytical chromatographic procedure on Chirobiotic V proved suitable for semipreparative separation, since the separation factor on the analytical column was high enough to obtain pure enantiomers with high yields. Chirality 15:494–497, 2003. © 2003 Wiley‐Liss, Inc.

A detailed analysis of Rosmarinus officinalis L. essential oil from Sardinia and Corsica (α-pinene/verbenone/bornyl acetate chemotype) was carried out using GC–RI, GC–MS and ¹³C-NMR, on the bulk sample or after repeated chromatography. Fifty-eight compounds were identified. The antimicrobial activity of two Sardinian samples was investigated and both exhibited a moderate antibacterial activity. Gram-positive bacteria were more sensitive (MIC 2.5–4 mg/ml) than Gram-negative bacteria. Killing time experiments demonstrated that prolonged times (60 min) are needed to completely inactivate the bacterial inoculum. Copyright © 2001 John Wiley & Sons, Ltd.

A detailed analysis of Rosmarinus officinalisL. essential oil from Sardinia and Corsica (α‐pinene/verbenone/bornyl acetate chemotype) was carried out using GC–RI, GC–MS and 13C‐NMR, on the bulk sample or after repeated chromatography. Fifty‐eight compounds were identified. The antimicrobial activity of two Sardinian samples was investigated and both exhibited a moderate antibacterial activity. Gram‐positive bacteria were more sensitive (MIC 2.5–4 mg/ml) than Gram‐negative bacteria. Killing time experiments demonstrated that prolonged times (60 min) are needed to completely inactivate the bacterial inoculum. Copyright © 2001 John Wiley & Sons, Ltd.

We report our experience of using a forehead flap to repair the defect left by the excision of skin tumoursin the medial canthal region involving both eyelids in three patients. Both eyelids and the inner canthus were reconstructed using a myofascial flap taken from the forehead, combined with septal chondro-mucosal grafts, oral mucosa and skin grafts. After a careful anatomical study of the vascularisation of the frontal region, we used only the frontal myofascial portion, a part of the forehead muscle vascularised by the deep branch of the supraorbital artery and by the supratroclear artery; the skin left behind is adequately nourished by the fine mesh of anastomoses in the area between the two supratroclear arteries, the supraorbital artery and the terminal vessels of the superficial temporal artery. The particularly thin, elastic and resistant features of this flap enabled us to repair a loss of substance in a difficult area with a successful outcome in terms of morphology, function and cosmetic appearance.

The dynamics of a passive tracer in the velocity field of four identical point vortices, moving under the influence of their self-induced advection, is investigated. Of interest is the change in mixing and transport properties of the tracer for the three different classes of vortex motion: periodic, quasi-periodic and chaotic. As a consequence of conservation laws, the vortex motion is confined to a finite region of phase space; therefore, the tracer phase space can be partitioned into an inner and an outer region. We find that in the case of quasi-periodic vortex motion the tracer phase space exhibits a well-defined barrier to transport between the central chaotic region and the outer region, where the trajectories are regular. In the case of chaotic vortex motion the barrier becomes permeable. The particle dynamics goes through an intermittent behaviour, where forays into the central region alternate with trapping in outer annular orbits. In the far field, an estimate of diffusion rates is made through a multipole expansion of the tracer velocity field. We make use of a specific stochastic model for the tracer velocity field which predicts no diffusion for the case of quasi-periodic vortex motion and, for the case of chaotic vortex motion, a diffusion rate that goes to zero at large distances from the vortex cluster.

AbstractThe oil from inforescences of Hypericum perforatumvar. angustifoliumgrowing wild and harvested in Sardinia (Italy) was analyzed by GC and GC/MS. The major compounds in the oil were 2-methyloctane (21.1%), germacrene D (17.6%) and α-pinene (15.8%).

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reaction of the aromatic amines (I) with the carboxylic chlorides (II) or the sulfonyl chloride (IV) gives the carboxamides (III) or the sulfonamides (V).