Cinematic reflectometry using QIKR, the quite intense kinetics reflectometer.

The Quite Intense Kinetics Reflectometer (QIKR) will be a general-purpose, horizontal-sample-surface neutron reflectometer. Reflectometers measure the proportion of an incident probe beam reflected from a surface as a function of wavevector (momentum) transfer to infer the distribution and composition of matter near an interface. The unique scattering properties of neutrons make this technique especially useful in the study of soft matter, biomaterials, and materials used in energy storage. Exploiting the increased brilliance of the Spallation Neutron Source Second Target Station, QIKR will collect specular and off-specular reflectivity data faster than the best existing such machines. It will often be possible to collect complete specular reflectivity curves using a single instrument setting, enabling "cinematic" operation, wherein the user turns on the instrument and "films" the sample. Samples in time-dependent environments (e.g., temperature, electrochemical, or undergoing chemical alteration) will be observed in real time, in favorable cases with frame rates as fast as 1 Hz. Cinematic data acquisition promises to make time-dependent measurements routine, with time resolution specified during post-experiment data analysis. This capability will be deployed to observe such processes as in situ polymer diffusion, battery electrode charge-discharge cycles, hysteresis loops, and membrane protein insertion into lipid layers.

Oncological Safety of Autologous Fat Grafting in Breast Reconstruction after Mastectomy for cancer: A case-control study.

OBJECTIVE: The use of autologous fat grafting in the context of breast reconstruction is still a matter of controversy. The objective of this study was to compare the local relapse rate in women who had a fat grafting session in the context of breast reconstruction after breast cancer management, to those who had breast reconstruction without fat grafting. METHODS: We performed a retrospective, monocentric, case-control study from January 2007 to December 2017 in our hospital. The cases included women who underwent breast reconstruction with autologous fat grafting and controls, undergoing breast reconstruction without fat grafting. We compared survival and local recurrence between the two groups. RESULTS: 412 women were included: 109 (26.5%) in the lipofilling group and 303 women (73.5%) in the "no lipofilling" group. In the overall study population, lipofilling did not appear to be a predictive factor for recurrence, HR = 1.39 [0.63 - 3.06], p = 0.41; or a predictive factor for overall survival, HR = 0.84 [0.23 - 3.02], p = 0.79, or for distant metastases, HR = 1.10 [0.43 - 2.79], p = 0.84. In contrast, in the subgroup of women treated for invasive cancer, the multivariate analysis showed that lipofilling in this context was an independent predictive factor for local recurrence (HR= 5.06 [1.97 - 10.6], p = 0.04). CONCLUSION: we found an increased risk of local recurrence after lipofilling in women who were managed for invasive breast cancer. This suggests that special consideration should be given to women who have had invasive breast cancer before lipofilling.

Histopathology of Andean Potato (Solanum tuberosum Andigenum group) varieties parasitized by the false root-knot nematode, Nacobbus aberrans / Histopatologia de variedades de batata andina (Solanum tuberosum grupo Andigenum) parasitadas pelo falso nematóide das galhas, Nacobbus aberrans

Abstract Landraces of the Solanum tuberosum Andigenum group are abundant and diverse. They are a valuable genetic resource possessing resistance to pests, diseases, and environmental stresses. In the Andean region, populations of the false root-knot nematode Nacobbus aberrans became specialized to infect native potatoes, being one of the major limiting factors affecting this crop. A better understanding of the host plant-parasite interactions is important in order to select tolerant or resistant plants to be included in management programs. Despite the close of association of N. aberrans with potato, and the great diversity of the S. tuberosum Andigenum group, few histopathological studies have been conducted. The aim of this work was to analyze histological alterations induced by different Argentine populations of the nematode in naturally infested roots of four Andean potato varieties (Collareja, Negra Imilla, Ojo de Señorita and Colorada). All the varieties showed hyperplastic tissue in the central zone of galls, where syncytia developed in close association with the nematode female. Syncytia were composed of modified hyperplastic tissue and parenchyma xylem cells. The results showed differences among varieties in their response to nematode populations, with Ojo de Señorita and Negra Imilla being the most susceptible ones. This study is the first describing histopathological alterations induced by N. aberrans in susceptible Andean potato landraces.

Resumo As variedades de Solanum tuberosum grupo Andigenum são abundantes e diversas, além de serem uma fonte importante de recursos genéticos antea resistência de pragas, doenças e estresse ambiental. Na região andina, populações de Nacobbus aberrans se especializaram em parasitar batatas nativas e representam o principal fator limitante que afeta a produção desse cultivo. Um melhor entendimento da interação hospedeiro-parasita é importante para a seleção de plantas tolerantes ou resistentes a serem incluídas nos programas de manejo. Apesar da íntima associação de N. aberrans com a batata e a grande diversidade de S. tuberosum grupo Andigenum, os estudos histopatológicos desenvolvidos são limitados. O objetivo do presente trabalho foi analisar as alterações histológicas de raízes de quatro variedades de batata andina (Collareja, Negra Imilla, Ojo de Señorita e Colorada) parasitadas naturalmente por distintas populações argentinas do nematóide. Em todas as variedades se observou tecido hiperplásico na zona central das galhas onde, também, se desenvolveram os sincícios em íntima relação com as fêmeas do nematóide. Os sincícios estavam constituídos por tecido hiperplásico modificado e por células parenquimáticas do xilema. Os resultados mostraram diferenças entre as variedades de batata frente às populações do nematóide, sendo Ojo de Señorita e Negra Imilla as que evidenciaram maior susceptibilidade. Este estudo constitui a primeira avaliação da histopalogia induzida por N. aberrans em variedades suscetíveis de batata andina.

Histopathology of Andean Potato (Solanum tuberosum Andigenum group) varieties parasitized by the false root-knot nematode, Nacobbus aberrans.

Landraces of the Solanum tuberosum Andigenum group are abundant and diverse. They are a valuable genetic resource possessing resistance to pests, diseases, and environmental stresses. In the Andean region, populations of the false root-knot nematode Nacobbus aberrans became specialized to infect native potatoes, being one of the major limiting factors affecting this crop. A better understanding of the host plant-parasite interactions is important in order to select tolerant or resistant plants to be included in management programs. Despite the close of association of N. aberrans with potato, and the great diversity of the S. tuberosum Andigenum group, few histopathological studies have been conducted. The aim of this work was to analyze histological alterations induced by different Argentine populations of the nematode in naturally infested roots of four Andean potato varieties (Collareja, Negra Imilla, Ojo de Señorita and Colorada). All the varieties showed hyperplastic tissue in the central zone of galls, where syncytia developed in close association with the nematode female. Syncytia were composed of modified hyperplastic tissue and parenchyma xylem cells. The results showed differences among varieties in their response to nematode populations, with Ojo de Señorita and Negra Imilla being the most susceptible ones. This study is the first describing histopathological alterations induced by N. aberrans in susceptible Andean potato landraces.

Histopathology of Andean Potato (Solanum tuberosum Andigenum group) varieties parasitized by the false root-knot nematode, Nacobbus aberrans

Abstract Landraces of the Solanum tuberosum Andigenum group are abundant and diverse. They are a valuable genetic resource possessing resistance to pests, diseases, and environmental stresses. In the Andean region, populations of the false root-knot nematode Nacobbus aberrans became specialized to infect native potatoes, being one of the major limiting factors affecting this crop. A better understanding of the host plant-parasite interactions is important in order to select tolerant or resistant plants to be included in management programs. Despite the close of association of N. aberrans with potato, and the great diversity of the S. tuberosum Andigenum group, few histopathological studies have been conducted. The aim of this work was to analyze histological alterations induced by different Argentine populations of the nematode in naturally infested roots of four Andean potato varieties (Collareja, Negra Imilla, Ojo de Señorita and Colorada). All the varieties showed hyperplastic tissue in the central zone of galls, where syncytia developed in close association with the nematode female. Syncytia were composed of modified hyperplastic tissue and parenchyma xylem cells. The results showed differences among varieties in their response to nematode populations, with Ojo de Señorita and Negra Imilla being the most susceptible ones. This study is the first describing histopathological alterations induced by N. aberrans in susceptible Andean potato landraces.

Resumo As variedades de Solanum tuberosum grupo Andigenum são abundantes e diversas, além de serem uma fonte importante de recursos genéticos antea resistência de pragas, doenças e estresse ambiental. Na região andina, populações de Nacobbus aberrans se especializaram em parasitar batatas nativas e representam o principal fator limitante que afeta a produção desse cultivo. Um melhor entendimento da interação hospedeiro-parasita é importante para a seleção de plantas tolerantes ou resistentes a serem incluídas nos programas de manejo. Apesar da íntima associação de N. aberrans com a batata e a grande diversidade de S. tuberosum grupo Andigenum, os estudos histopatológicos desenvolvidos são limitados. O objetivo do presente trabalho foi analisar as alterações histológicas de raízes de quatro variedades de batata andina (Collareja, Negra Imilla, Ojo de Señorita e Colorada) parasitadas naturalmente por distintas populações argentinas do nematóide. Em todas as variedades se observou tecido hiperplásico na zona central das galhas onde, também, se desenvolveram os sincícios em íntima relação com as fêmeas do nematóide. Os sincícios estavam constituídos por tecido hiperplásico modificado e por células parenquimáticas do xilema. Os resultados mostraram diferenças entre as variedades de batata frente às populações do nematóide, sendo Ojo de Señorita e Negra Imilla as que evidenciaram maior susceptibilidade. Este estudo constitui a primeira avaliação da histopalogia induzida por N. aberrans em variedades suscetíveis de batata andina.

Evaluating the solid electrolyte interphase formed on silicon electrodes: a comparison of ex situ X-ray photoelectron spectroscopy and in situ neutron reflectometry.

This work details the in situ characterization of the interface between a silicon electrode and an electrolyte using a linear fluorinated solvent molecule, 0.1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in deuterated dimethyl perfluoroglutarate (d6-PF5M2) (1.87 × 10(-2) mS cm(-1)). The solid electrolyte interphase (SEI) composition and thickness determined via in situ neutron reflectometry (NR) and ex situ X-ray photoelectron spectroscopy (XPS) were compared. The data show that SEI expansion and contraction (breathing) during electrochemical cycling were observed via both techniques; however, ex situ XPS suggests that the SEI thickness increases during Si lithiation and decreases during delithiation, while in situ NR suggests the opposite. The most likely cause of this discrepancy is the selective removal of SEI components (top 20 nm of the SEI) during the electrode rinse process, which is required to remove the electrolyte residue prior to ex situ analysis, demonstrating the necessity of performing SEI characterization in situ.

Small-molecule inhibitors at the PSD-95/nNOS interface protect against glutamate-induced neuronal atrophy in primary cortical neurons.

Glutamate and nitric oxide (NO) are important regulators of dendrite and axon development in the central nervous system. Excess glutamatergic stimulation is a feature of many pathological conditions and manifests in neuronal atrophy and shrinkage with eventual neurodegeneration and cell death. Here we demonstrate that treatment of cultured primary cortical rat neurons for 24h with glutamate (500µM) or N-methyl-d-aspartate (NMDA) (100-500µM) combined with glycine suppresses neurite outgrowth. A similar reduction of neurite outgrowth was observed with the NO precursor l-arginine and NO donor sodium nitroprusside (SNP) (100 and 300µM). The NMDA-receptor (NMDA-R) antagonists ketamine and MK-801 (10nM) counteracted the NMDA/glycine-induced reduction in neurite outgrowth and the neuronal NO synthase (nNOS) inhibitor 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) (100nM) counteracted both the NMDA/glycine and l-arginine-induced decreases in neurite outgrowth. Furthermore, targeting soluble guanylate cyclase (sGC), a downstream target of NO, with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10µM) also protected against l-arginine-induced decreases in neurite outgrowth. Since the NMDA-R is functionally coupled to nNOS via the postsynaptic protein 95kDa (PSD-95), inhibitors of the PSD-95/nNOS interaction were tested for their ability to protect against glutamate-induced suppression in neurite outgrowth. Treatment with the small-molecule inhibitors of the PSD-95/nNOS interface 2-((1H-benzo[d] [1,2,3]triazol-5-ylamino) methyl)-4,6-dichlorophenol (IC87201) (10 and 100nM) and 4-(3,5-dichloro-2-hydroxy-benzylamino)-2-hydroxybenzoic acid (ZL-006) (10 and 100nM) attenuated NMDA/glycine-induced decreases in neurite outgrowth. These data support the hypothesis that targeting the NMDA-R/PSD-95/nNOS interaction downstream of NMDA-R promotes neurotrophic effects by preventing neurite shrinkage in response to excess glutamatergic stimulation. The PSD-95/nNOS interface may be an attractive target for treating deficits in neuronal outgrowth and atrophy associated with excessive glutamatergic neurotransmission in neurodevelopmental and neurodegenerative conditions.

Quebec Integrated Chronic Disease Surveillance System (QICDSS), an innovative approach.

INTRODUCTION: With the growing burden of chronic diseases, surveillance will play an essential role in improving their prevention and control. The Institut national de santé publique du Québec has developed an innovative chronic disease surveillance system, the Quebec Integrated Chronic Disease Surveillance System (QICDSS). We discuss the primary features, strengths and limitations of this system in this report. METHODS: The QICDSS was created by linking five health administrative databases. Updated annually, it currently covers the period from January 1, 1996, to March 31, 2012. The operational model comprises three steps: (1) extraction and linkage of health administrative data according to specific selection criteria; (2) analysis (validation of case definitions essentially) and production of surveillance measures; and (3) data interpretation, submission and dissemination of information. The QICDSS allows the surveillance of the following chronic diseases: diabetes, cardiovascular diseases, respiratory diseases, osteoporosis, osteoarticular diseases, mental disorders, Alzheimer's disease and related disorders. The system also lends itself to the analysis of multimorbidity and polypharmacy. RESULTS: For 2011-2012, the QICDSS contained information on 7 995 963 Quebecers with an average age of 40.8 years. Of these, 95.3% met at least one selection criterion allowing the application of case definitions for chronic disease surveillance. The actual proportion varied with age, from 90.1% for those aged 19 years or less to 99.3% for those aged 65 years or over. CONCLUSION: The QICDSS provides a way of producing population-based data on the chronic disease burden, health services and prescription drug uses. The system facilitates the integrated study of several diseases in combination, an approach rarely implemented until now in the context of population surveillance. The QICDSS possesses all the essential features of a surveillance system and supports the dissemination of information to public health decision-makers for future actions.

TITRE: Le Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), une approche novatrice. INTRODUCTION: Avec l'accroissement du fardeau des maladies chroniques, la surveillance est fondamentale pour améliorer la prévention et la prise en charge de ces dernières. L'Institut national de santé publique du Québec a donc développé un système novateur de surveillance des maladies chroniques, le Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), dont les principales caractéristiques, les forces et les limites sont présentées ici. MÉTHODOLOGIE: Le SISMACQ est le résultat du jumelage de cinq fichiers médicoadministratifs. Mises à jour annuellement, ses données couvrent actuellement la période du 1er janvier 1996 au 31 mars 2012. Trois étapes en caractérisent le modèle opérationnel : 1) l'extraction et le jumelage des données médico-administratives grâce à divers critères de sélection; 2) les analyses (principalement la validation des définitions) et la production des mesures de surveillance et 3) l'interprétation, le dépôt et la diffusion de l'information. Le SISMACQ permet actuellement l'étude des maladies chroniques suivantes : diabète, maladies cardiovasculaires, maladies respiratoires, ostéoporose, maladies ostéoarticulaires, troubles mentaux et Alzheimer et maladies apparentées. Il permet également l'analyse de la multimorbidité et de la polypharmacie. RÉSULTATS: Pour 2011-2012, le SISMACQ contenait des données sur 7 995 963 Québécois, et leur moyenne d'âge était de 40,8 ans. Parmi eux, 95,3 % répondaient à au moins un critère de sélection permettant l'application de définitions de cas pour la surveillance des maladies chroniques. Cette proportion variait avec l'âge : de 90,1 % chez les Québécois de 19 ans et moins à 99,3 % chez ceux de 65 ans et plus. CONCLUSION: Le SISMACQ permet la production de données, à l'échelle de la population, sur le fardeau de plusieurs maladies chroniques, sur l'utilisation des services de santé et sur la consommation de médicaments. Il rend possible l'étude intégrée de la combinaison de plusieurs maladies, une approche jusqu'à présent rarement mise en oeuvre dans un contexte de surveillance populationnelle. Le SISMACQ répond aux attributs essentiels d'un système de surveillance et aide à la diffusion de l'information auprès des décideurs en vue d'actions en santé publique.

Response inhibition and elevated parietal-cerebellar correlations in chronic adolescent cannabis users.

The ability to successfully inhibit an inappropriate behaviour is a crucial component of executive functioning and its impairment has been linked to substance dependence. Cannabis is the most widely used illicit drug in adolescence and, given the accelerated neuromaturation during adolescence, it is important to determine the effects of cannabis use on neurocognitive functioning during this developmental period. In this study, a cohort of adolescent heavy cannabis users and age-matched non-cannabis-using controls completed a Go/No-Go paradigm. Users were impaired in performance on the task but voxelwise and region-of-interest comparisons revealed no activation differences between groups. Instead, an analysis of correlation patterns between task-activated areas revealed heightened correlation scores in the users between bilateral inferior parietal lobules and the left cerebellum. The increased correlation activity between these regions was replicated with resting state fMRI data and was positively correlated with self-reported, recent cannabis usage. The results suggests that the poorer inhibitory control of adolescent cannabis users might be related to aberrant connectivity between nodes of the response inhibition circuit and that this effect is observable in both task-induced and intrinsic correlation patterns. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.

Cyst of the common bile duct in a cat.

A cyst of the common bile duct (CBD) is reported in a 9-year-old cat that presented with a 1-week history of anorexia, weight loss and vomiting. Diagnosis was established by ultrasound examination and laparotomy, and was ultimately confirmed by histological analysis. Chronic cholangitis and an Escherichia coli species were detected concurrently according to the histopathological findings and bile culture, respectively. The case was managed by suturing the borders of the ostium of the cyst over a stent, using a temporary cholecystostomy tube and antibiotic therapy. At 7 months following the surgery, the cat was in excellent physical condition with no clinical evidence of recurrence of cholangitis or of the cyst after ultrasonographic evaluation. According to the human literature, cysts of the CBD require treatment because of their common association with cholangitis, pancreatitis, and cystic rupture. We were unable to confirm a link between the cyst and cholangitis in this case. It is possible that detection of this anomaly was an incidental finding unrelated to bacterbilia. Histological examination of cyst tissue is mandatory for a definitive diagnosis and to differentiate it from neoplasia. This is the first description of a cyst of the CBD in the cat.

Effect of an endurance-like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: application to medication control.

REASONS FOR PERFORMING STUDY: Equine antidoping rules were established to prevent a horse's performance being altered after the administration of prohibited substances, including approved drugs used for legitimate treatment. Veterinarians have to advise owners or trainers on appropriate withholding times to guarantee that their horses may safely compete after drug administration. In order to propose tailored withdrawal times, several horse organisations released detection time (DT) values, for the main veterinary drugs used in horses. One of the possible limits to the information provided by published DTs in horses is the fact that they are determined from classic pharmacokinetic studies performed at rest under laboratory conditions. In field conditions, training and exercise programmes may have an influence on drug elimination. METHODS: Dexamethasone (DMX) and phenylbutazone (PBZ) have been quantified in plasma and urine after solid phase extraction. The kinetic disposition of DXM (8 microg/kg) and PBZ (8 mg/kg) administered by i.v. route in 8 horses, was investigated in rest conditions and during a standardised 3 h test exercise according to a cross-over design. OBJECTIVES: The aim of the present study was to compare the kinetic disposition of 2 test drugs, DMX and PBZ in rest vs. exercising conditions. RESULTS: It was shown in 8 horses that a sustained 3 h of mild exercise slightly decreased the plasma clearance of both drugs (about 25% for DXM and 37% for PBZ) and this is mainly explained by the significant decrease of the corresponding hepatic clearance. In addition, as the volume of distribution was correlatively decreased, the plasma terminal half-life, which is a hybrid parameter of plasma clearance and volume of distribution, remains unchanged overall. CONCLUSION AND POTENTIAL RELEVANCE: Establishing DTs or withdrawal times (WTs) are relevant as plasma and urine half-lives, but not clearance, are the main determinants of DT length. Veterinarians may realistically decide upon a WT for a legitimate drug based on the corresponding DT obtained under resting conditions providing this drug has a low hepatic extraction ratio and a safety margin is added to allow for all possible sources of variability.

Validation of a transendoscopic glandular and nonglandular gastric biopsy technique in horses.

REASONS FOR PERFORMING STUDY: In order to study the evolution of histopathological and immunohistochemical changes in the gastric mucosa of horses with EGUS (equine gastric ulcer syndrome), a feasible, useful, valid and safe in vivo gastric biopsy technique is required. OBJECTIVES: To determine the average gastric mucosal healing time following endoscopic gastric biopsy sampling, and evaluate the feasibility, safety and usefulness of samples obtained by this method for histopathological analysis. METHODS: Six mature mares from the Faculté de Médecine Vétérinaire research herd were used. Transendoscopic gastric biopsy was performed on Days 0 and 9 using a flexible forceps with oval and fenestrated jaws to obtain gastric mucosal samples from 4 different sites: cardia (C), fundus (F), margo plicatus (MP) and glandular mucosa (GL). A maximum of 4 samples per site was taken and processed routinely for histopathology, evaluated by a pathologist. On Days 1-4 and 9-11 the lesions created by the biopsies were evaluated by gastroscopy. Lesions were evaluated over time based on a score from 0-4, where 4 was the most severe. RESULTS: Biopsy samples could be obtained from all targeted sites except C. No abnormal clinical signs were observed up to 7 days post biopsy. The average biopsy lesion scores decreased significantly with time for all sites. The average lesion score was significantly higher for the MP compared to the other sites at Days 1 and 2. Samples taken from the nonglandular portion of the stomach were considered inadequate for histopathology, while those taken from the glandular mucosa were adequate. CONCLUSION: The transendoscopic gastric biopsy technique described here is a feasible, safe and useful technique for obtaining samples from the equine gastric glandular mucosa. Although biopsy samples could be obtained from several areas in the nonglandular mucosa, these were very small, took longer to heal and were not considered adequate for histopathological evaluation, and another technique should therefore be validated.

Evaluating solutions to sponsorship bias.

More than 40 primary studies, and three recent systematic reviews and meta-analyses, have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. Industry sponsorship biases published scientific research in favour of the sponsors, a result of the strong interest commercial sponsors have in obtaining favourable results. Three proposed remedies to this problem are widely agreed upon among those concerned with the level of sponsorship bias: financial disclosure, reporting standards and trial registries. This paper argues that all of these remedies either fail to address the mechanisms by which pharmaceutical companies' sponsorship leads to biased results-design bias, multiple trials with predictable outcomes, fraud, rhetorical effects and publication bias-or else only inadequately address those mechanisms. As a result, the policies normally proposed for dealing with sponsorship bias are unable to eliminate it. Only completely separating public clinical research from pharmaceutical industry funding can eliminate sponsorship bias.

Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1.

Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses. Tiludronate and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1) were measured in plasma and urine. There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of the CRI was 103% (not significantly different) that of the 10 daily i.v. bolus doses. Cumulative urine tiludronate excretion could not be compared between groups because of poor sensitivity of the assay in urine. Plasma and urine CTX-1 levels were not different between groups throughout the study. However, interindividual variations were greater in group 1 than in group 2. A significant decrease in CTX-1 levels was observed in plasma after the first administration in group 1, but not in urine; while in group 2, a significant decrease in CTX-1 concentrations was observed after treatment in both plasma and urine. In conclusion, both dosage regimens of tiludronate produced similar plasma exposure and pharmacological effects in adult healthy horses.

Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease.

BACKGROUND: Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD. METHODS: Twenty-eight male patients with COPD were divided into an overweight/obese group [ n = 16, body mass index (BMI) = 33.5 +/- 4.2 kg/m(2)] and normal weight group (n = 12, BMI = 21.1 +/- 2.6 kg/m(2)). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured. RESULTS: Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume(1): 51 +/- 19% versus 31 +/- 12% predicted, respectively, P < 0.01). The metabolic syndrome was diagnosed in 50% of overweight/obese patients and in none of the normal weight patients. TNF-alpha, IL-6 and leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight. CONCLUSIONS: The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities.

Comparative oxidative metabolic profiles of clomipramine in cats, rats and dogs: preliminary results from an in vitro study.

The objectives of this in vitro study were to describe cytochrome-dependent metabolism of clomipramine in canine and feline microsomes, compare metabolic profiles between cats, rats and dogs, and investigate a potential gender-related difference in metabolic activity between male and female cats. Pooled liver microsomes were incubated with clomipramine, where species and gender-specific reactions were initiated by the addition of a nicotinamide adenine dinucleotide phosphate regenerating system and quenched with methanol at 0, 5, 15, 30, 45 and 60 min, and 0, 30, 60, 90, 120, 180, 240 and 360 min respectively. Liquid chromatography tandem mass spectrometry was used to measure clomipramine and its metabolites. Preliminary results showed that cat microsomes biotransformed clomipramine slower and less efficiently than rat and dog microsomes. Moreover, gender differences in metabolic profiles suggested that male cat microsomes may be less efficient demethylators and hydroxylators than female cat microsomes. As gender metabolic differences may carry clinical significance for this antidepressant, further studies are warranted.

One-step method for catheterising the jugular vein of cats to enable repeated blood sampling.

A one-step method for catheterising the jugular vein of cats for taking multiple blood samples was developed, with the aid of radiography, to determine an appropriate internal catheter length for adult cats. The effects of multiple blood sampling and heparin flushes on the cats' haematocrit and blood total solids were also assessed. Seven healthy adult cats were used. A total of 128 of 132 (97 per cent) blood samples were collected successfully through a 19 G, 30.5 cm catheter introduced as a central venous catheter and maintained in place during two periods of 48 hours. The haematocrit and total solids were significantly decreased in all the cats, but no clinically significant blood loss or coagulation disorders were observed.

Pharmacological effects of tiludronate in horses after long-term immobilization.

INTRODUCTION: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical biomarkers of bone metabolism and on bone density and structure in an experimental model of disuse osteoporosis induced by cast application in horses. METHODS: Two groups of eight horses were immobilized during 8 weeks. The first group (P-group) received a placebo, and the second group (T-group) received tiludronate 1 mg/kg by slow IV infusion. Both treatments were administered twice, 28 days apart. Immobilization consisted of stall rest with the left forelimb packed in a fiberglass cast. It was followed by a 4-week remobilization period and an 8-week standardized training protocol. One biomarker of bone resorption, the C-telopeptides of type I collagen cross-links (CTX-1) and one biomarker of bone formation, the bone isoenzyme of alkaline phosphatase (bone ALP), were assessed. Metacarpus III (MCIII) bone mineral density (BMD) and speed of sound (SOS) were evaluated respectively by dual energy X-ray absorptiometry (DEXA) and quantitative ultrasonography (QUS). Lameness was regularly assessed during the remobilization and training periods. Group- and time-related effects were tested by analysis of variance on repeated measurements. RESULTS: A rapid, transient and significant decrease in CTX-1 concentration was seen after each treatment in the T-group only. No significant differences between groups were seen in the evolution of bone ALP activity. At the end of the experiment, the loss of MCIII BMD measured by DEXA in the immobilized limb was significantly less in the T-group than in the P-group. The MCIII SOS measured by QUS did not significantly vary within or between groups throughout the study. DISCUSSION AND CONCLUSIONS: Tiludronate was found to significantly reduce bone resorption during immobilization, as well as to prevent long-term osteopenia in the immobilized limb. Disuse osteopenia did not affect the lateral superficial cortex of MCIII.

Efficacy of licofelone in dogs with clinical osteoarthritis.

To evaluate the effect of licofelone, an arachidonic acid substrate with combined inhibitory activity against 5-lipoxygenase and cyclooxygenases 1 and 2, a double-blind, randomised and placebo-controlled study was conducted in 33 client-owned dogs that were lame owing to hindlimb osteoarthritis. Seventeen of the dogs received a placebo and 16 were treated with 2.5 mg/kg licofelone twice a day for 28 days. The dogs' lameness was assessed on a visual analogue scale (vas), and by force plate analyses at baseline and 14 and 28 days after starting the treatment. After 14 days the mean (se) change in peak vertical force in the licofelone-treated dogs (1.7 [0.8] per cent bodyweight) was significantly greater (P<0.05) than in the placebo-treated dogs (-0.3 [0.6] per cent bodyweight), and after 28 days the difference had increased. In contrast, the dogs' lameness, as assessed by the vas values, had decreased significantly over baseline in both the treated and control groups.

Effects of physiological covariables on pharmacokinetic parameters of clomipramine in a large population of cats after a single oral administration.

This study was conducted to confirm an interindividual variability in pharmacokinetic parameters of clomipramine in a large population of cats and to identify potential covariables that would explain the presence of such pharmacokinetic variability after a single dose of Clomicalm. Clomipramine hydrochloride was administered orally according to a weight-dose chart from 0.32 to 0.61 mg/kg, to 76 cats and five blood samples were then taken by direct venipuncture at 1, 3, 6, 12, and 24 h. Plasma concentrations of clomipramine and desmethylclomipramine (DCMP) were measured by LC-MS/MS. The Standard Two-Stage technique was used to assess differences and detect correlations between pharmacokinetic parameter estimates and individual covariables. A large interindividual variability in all pharmacokinetic parameters (CV% 64-124) was detected. Statistically significant gender-related differences were detected in MR and Cl/F, where female cats had a higher mean MR (0.53) and faster Cl/F (0.36 L/h.kg) than males (0.36 and 0.21 L/h.kg, respectively). No correlation could be found between clomipramine AUC0-24 h or DCMP AUC0-24 h and sedation scores. Further feline studies are required to assess these findings after multiple dosing of clomipramine and DCMP to allow clinical extrapolation.