Synergistic effects of bombesin and epidermal growth factor on cancers.

Bombesin and gastrin-releasing peptide act as autocrine mitogens in various cancers. Bombesin antagonist RC-3095 inhibited growth in some cancers and slowed the progression of premalignant lesions, possibly by down-regulating epidermal growth factor (EGF) receptors. Since the EGF receptor mitogen response involves tyrosine kinase stimulation, we tested the hypotheses that bombesin stimulates, and RC-3095 inhibits, phosphorylation; EGF and bombesin promote the phosphorylation of the same substrates; and EGF and bombesin act synergistically on phosphorylation. Therefore, in vitro assays for phosphorylation were performed in the presence or absence of EGF, bombesin, RC-3095, and combinations in samples derived from tumor, tissue surrounding tumor, cell lines, and normal and transforming tissue derived from the 9,10-dimethyl-1,2-benzanthracene-induced squamous cell lesions of the hamster cheek pouch. Bombesin increased, and RC-3095 decreased, phosphorylation in these samples. In the human hepatoma sample and surrounding tissue, these ligands altered the phosphorylation of the same substrates affected by EGF. EGF and bombesin stimulated phosphorylation synergistically in the hamster samples and the hepatoma. Bombesin-induced phosphorylation was greater in tissue surrounding the hepatoma, whereas RC-3095 was more effective in inhibiting phosphorylation in the hepatoma itself. This cancer, therefore, could be endogenously stimulated by gastrin-releasing peptide. These observations support the hypothesis that bombesin stimulates growth of tissues and tumors by amplifying the phosphorylation response to EGF. The growth inhibitory response to RC-3095, or other bombesin analogues, of individual tumors may be prognosed by in vitro phosphorylation assays using the samples from the patient's tumor

Assessing the efficacy and cost of detergents used in a primary care automated washer disinfector

Background: Cleaning of re-usable medical devices is a critical control point in the decontamination cycle, although defined end-points of the process are controversial. Objective: Investigate cleaning efficacy and cost of different detergent classes in an automated washer disinfector (AWD) designed for dental practice. Methods: Loads comprised test soiled dental hand instruments in cassettes and extraction forceps. Residual protein assayed using the International standard method (ISO 15883-5:2005) 1% SDS elution with ortho-phthalaldehyde (OPA) or GBox technology (on instrument OPA analysis). Short (60 minutes) and long (97 minutes) AWD cycles were used with four different classes of detergents, tap water and reverse osmosis water. Results: SDS elution analysis (N = 612 instruments) demonstrated four detergents with both wash cycles achieved equivalent cleanliness levels and below a threshold of 200 μg protein/instrument. GBox methodology (N = 575) using UK Department of Health threshold of 5 μg/instrument side demonstrated that tap water performed with the greatest efficacy for all types of instruments and cycle types. Conclusions: Using International standard methodology, different detergent classes had equivalence in cleaning efficacy. Cheaper detergents used in this study performed with similar efficacy to more expensive solutions. Findings emphasise the importance of validating the detergent (type and concentration) for each AWD

Про водогосподарський комплекс Криму

В статье дается определение понятия "водохозяйственный комплекс региона". Приводятся количественные и качественные характеристики состояния развития этой отрасли в АРК. Делаются выводы и предложения относительно повышения эффективности функционирования отрасли, улучшению качества предоставляемых услуг.У статті дається визначення поняття "водогосподарський комплекс регіону". Приводяться кількісні і якісні характеристики стану розвитку цієї галузі в АРК. Робляться висновки й пропозиції щодо підвищення ефективності функціонування галузі, поліпшенню якості надаваних послуг.There is given the definition of concept "a water complex of the region" in this article. Quantitative are resulted and qualitative behaviors of a condition of development of this area in АRК. The conclusions and proposals concerning increase of efficiency of operation of area, improvement of the quality of rendered services are done

A Performance Analysis on Pressure Loss and Airflow Diffusion in a Chamber with Perforated V-Profile Diffuser Designed for Air Handling Units (AHUs)

Outlet cross-sectional area of fans used in air handling units is smaller than cross-sectional area of chambers which are located next to the fan. In order to ensure efficiently operating of the air handling units, it is required that the air flows through a perforated diffuser to create a uniform air diffusion from fan outlet to following chamber with a minimum pressure loss and uniform velocity distribution. In this concept, numerical simulations and experiments were performed for the chamber with perforated V-profile diffuser, which is often used in air handling units because of its simple geometry and easy manufacturing. Pressure losses were firstly obtained experimentally for different air velocities in the chamber. Then a performance analysis on the air flow diffusion and pressure losses inside chamber with perforated V-profile diffuser for different geometric parameters such as entry length, apex angle, geometry and pattern of hole, plate thickness, porosity and surface roughness has been carried out numerically. It is seen that the experimental results validated with the numerical turbulence model results

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Advanced model compounds for understanding acid-catalyzed lignin depolymerization : identification of renewable aromatics and a lignin-derived solvent

This work was funded by the EP/J018139/1, EP/K00445X/1 grants (NJW and PCJK), an EPSRC Doctoral Prize Fellowship (CSL), and the European Union (Marie Curie ITN ‘SuBiCat’ PITN-GA-2013-607044, CWL, NJW, PCJK, PJD, KB, JdeV).The development of fundamentally new approaches for lignin depolymerization is challenged by the complexity of this aromatic biopolymer. While overly simplified model compounds often lack relevance to the chemistry of lignin, the direct use of lignin streams poses significant analytical challenges to methodology development. Ideally, new methods should be tested on model compounds that are complex enough to mirror the structural diversity in lignin but still of sufficiently low molecular weight to enable facile analysis. In this contribution, we present a new class of advanced (β-O-4)-(β-5) dilinkage models that are highly realistic representations of a lignin fragment. Together with selected β-O-4, β-5, and β–β structures, these compounds provide a detailed understanding of the reactivity of various types of lignin linkages in acid catalysis in conjunction with stabilization of reactive intermediates using ethylene glycol. The use of these new models has allowed for identification of novel reaction pathways and intermediates and led to the characterization of new dimeric products in subsequent lignin depolymerization studies. The excellent correlation between model and lignin experiments highlights the relevance of this new class of model compounds for broader use in catalysis studies. Only by understanding the reactivity of the linkages in lignin at this level of detail can fully optimized lignin depolymerization strategies be developed.PostprintPeer reviewe

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

A practical approach to vitamin and mineral supplementation in food allergic children

The management of food allergy in children requires elimination of the offending allergens, which significantly contribute to micronutrient intake. Vitamin and mineral supplementation are commonly suggested as part of dietary management. However a targeted supplementation regime requires a complete nutritional assessment, which includes food diaries. Ideally these should be analysed using a computerised program, but are very time consuming. We therefore set out to evaluate current practice of vitamin and mineral supplementation in a cohort of children with non-Immunoglobulin E (IgE) mediated food allergies

Genetic screening and democracy: lessons from debating genetic screening criteria in the Netherlands

Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor’s office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When prenatal screening for all pregnant women became conceivable, the potential increase in scale made social and ethical concerns relevant for the whole of society. Whereas genetic testing in clinical genetic practice was widely accepted, prenatal screening at a population level met with unease. Concerns were raised regarding social pressure to screen: the sum of individual choice might result in a ‘collective eugenics’. The government’s involvement also raised suspicion: actively offering screening evoked associations with eugenic population policies from the first half of the 20th century. By reconstructing elements of policy and public debate on prenatal screening in the Netherlands from the past 30 years, this article discusses how the government has gradually changed its role in balancing the interest of the individual and the collective on genetic reproductive issues. Against a background of increasing knowledge about and demand for prenatal screening among the population, governmental policy changed from focusing on protection by banning screening toward facilitating screening in a careful and ethically sound way by providing adequate information, decision aids and quality assessment instruments. In the meanwhile, invigorating democracy in public debate may entail discussing concepts of ‘the good life’ in relation to living with or without impairments and dealing with genetic information about oneself or one’s offspring