Worldwide, the effect of climatic variations has become a great challenge in poultry production. As global climate is changing, it alters the environmental temperatures, precipitation patterns and ...atmospheric carbon dioxide. Poultry farming mainly depends on climatic conditions such as temperature and humidity. Several factors can be involved but heat stress is one of most important environmental factor influencing a wide range of chickens performances including reduced feed intake which, in turn, affects growth rate, body weight, meat quality, egg quality, egg production, semen quality and fertility; these negative influences result in great economic losses. Heat stress associated food safety issues have gained special importance due to public awareness and an abundance of available scientific information. Environmental modifications (early heat conditioning, open sheds and cooling systems) and nutritional strategies (early feed restriction, electrolyte, vitamin and mineral balance) cannot satisfy the special needs of stressed poultry. Therefore, there exists a crucial need to explore effective strategies including genetic markers to enhance thermo-tolerance and productivity of poultry birds in hot regions of the world.
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Heat stress induces oxidative stress, and reduces antioxidant defenses of birds, which may affect poultry-production performance. Dietary antioxidants may protect against heat stress. We evaluated ...the effect of increasing concentrations of dietary curcumin on antioxidant parameters of hens under high-temperature conditions for nine weeks. Roman laying hens (n = 336, 22 weeks old, 1420 g weight) were divided into three treatment groups. The first group served as a thermo-neutral control (kept at 25 ± 1 °C). The second group was exposed to high temperatures (32 ± 1 °C, 6 h/day), and fed a basal diet. The third group was further divided into five groups, and all were exposed to high temperatures (32 ± 1 °C, 6 h/day) and provided a basal diet supplemented with 100, 150, 200, 250, 300 mg/kg curcumin (H1, H2, H3, H4, H5). All treatments included four replicates of 12 hens. Total superoxide dismutase (SOD) activity was significantly higher in H2 and H3 groups, and total antioxidant capacity (T-AOC) was higher in H2, H3, and H5 groups. Catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly higher in the H3 group. Malondialdehyde concentrations were lower in curcumin supplemented hens compared to control groups hens. Hens in all curcumin treatment groups had slightly (but non-significantly) higher activities of CAT, SOD, GSH-Px, and T-AOC in liver, heart, and lung tissues, compared to heat stressed control group. It is concluded that dietary curcumin given to laying hens under heat stress may enhance their antioxidant status, and ameliorate stressful environmental conditions.
•Poultry farming has performed a leading role in the livestock sector in some parts of the world.•Poultry birds are facing big challenges due to increasing the global temperature.•Dietary Curcumin has potential to reduce the adverse impacts of heat stress in the poultry.
The future development in mobility resource ownership is of great interest as the individual mobility behavior has critical impacts on transport infrastructure, land use, energy consumption, and ...environmental issues, such as greenhouse gas emissions and local air pollutants. Analysis and forecasts of mobility resource ownership as needed for example in transport modelling or forecast studies, however, usually employ data of the latest national travel surveys available. Therefore, changes in mobility resource ownership over time are often ignored. Estimating logit-based decision models on the large scale Swiss national travel survey data for 2000 and 2010, the study identifies determinants of mobility resource ownership for the main mobility resources (driving licenses, car availability, general abonnement travel tickets, and half fare travel tickets), identifying also significant changes over time. The predictor variables comprise socio-economic and socio-demographic variables, spatial structure features, and mobility resource specific characteristics. Our results show that age, sex, income, the size of the community, and geographical region influence mobility resource ownership in both years, 2000 and 2010. Furthermore, car-based and public transport-based mobility resources are substitutes for each other. Between 2000 and 2010 a behavioral change is observed for selected sub-populations: In 2010 women and persons above 40 years old are more likely to own a driving license and have a car available than in 2000. In addition, the positive effect of income on driving license and car ownership becomes smaller over time. Finally the previously neglected variables, such as household structure, employment status and level of education are found to be significant in the explanation of mobility resource ownership.
Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects.
To report the 12-month extension of a phase II trial evaluating the efficacy, safety and ...tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS).
In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study.
27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51). All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated.
Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months.
ClinicalTrials.gov NCT01111656.
210Pb (T1/2=22.2 y) is an important source of background in rare event searches, such as neutrinoless double-β decay and dark matter direct detection experiments. In this paper, the capabilities of ...the A.E. Lalonde AMS Laboratory at the University of Ottawa for 210Pb measurements are discussed.
For fluoride targets, the blank 210Pb/206Pb ratio was in the 10−14 to 10−13 range, but (PbF3)− current output was lower and less stable. For oxide targets, (PbO2)− current output showed better stability, despite a significant difference in current output for commercial PbO and processed samples, and background studies suggested a background not much higher than that of the fluoride targets. Both target materials showed, therefore, good performance for 210Pb Accelerator Mass Spectrometry assay.
Measurements of Kapton ultra-thin films were performed. 90% C.L. upper limits for the 210Pb specific activity in the range of 0.74–2.8 Bq/kg were established for several Kapton HN films.
Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only ...slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy.
ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug.
This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial.
ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.
Discovery of small molecule CD40-TRAF6 inhibitors Zarzycka, Barbara; Seijkens, Tom; Nabuurs, Sander B ...
Journal of chemical information and modeling,
02/2015, Letnik:
55, Številka:
2
Journal Article
Recenzirano
The CD154-CD40 receptor complex plays a pivotal role in several inflammatory pathways. Attempts to inhibit the formation of this complex have resulted in systemic side effects. Downstream inhibition ...of the CD40 signaling pathway therefore seems a better way to ameliorate inflammatory disease. To relay a signal, the CD40 receptor recruits adapter proteins called tumor necrosis factor receptor-associated factors (TRAFs). CD40-TRAF6 interactions are known to play an essential role in several inflammatory diseases. We used in silico, in vitro, and in vivo experiments to identify and characterize compounds that block CD40-TRAF6 interactions. We present in detail our drug docking and optimization pipeline and show how we used it to find lead compounds that reduce inflammation in models of peritonitis and sepsis. These compounds appear to be good leads for drug development, given the observed absence of side effects and their demonstrated efficacy for peritonitis and sepsis in mouse models.
To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic ...pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy.
This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28.
ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx.
The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.
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