Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct

We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 ± 3.4 vs. 4.1 ± 0.3 mmHg, and reduced plasma sodium concentrations (142.2 ± 1.6 vs. 149.1 ± 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 ± 53%, n=12) relative to sham-operated controls (100 ± 13%, n=14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective.Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 ± 28% of sham levels, n=6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF

The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines.

The single-cell gel electrophoresis (comet) assay was used to measure radiation-produced DNA double-strand breaks (dsbs) in a series of seven cervical tumour cell lines (ME180, HT3, C33A, C41, SiHa, MS751 and CaSki). The proportion of DNA dsbs was measured immediately after radiation treatment (initial damage) and 16 h later after incubation at 37 degrees C (residual damage). Linear dose-response curves were seen for initial (slopes 0.23-0.66) and residual (slopes 0.16-0.87) DNA dsbs. Neither of the slopes of the linear regression analysis on the initial and on the residual DNA dsbs dose-response curves (range 0-80 Gy) correlated with SF2 (surviving fraction at 2 Gy) measured after high- (HDR) or low-dose-rate (LDR) irradiation. An association was evident between SF2 after HDR and LDR irradiation and the ratio of the absolute level of initial and residual damage after a single dose of 60 Gy. However, a significant correlation was found between HDR (r= -0.78, P = 0.04) and LDR (r = -0.86, P = 0.03) SF2 values and the ratio of the slopes of the initial and residual DNA dsbs dose-response curves (range 0.47-0.99), representing the fraction of DNA damage remaining. These results indicate that the neutral comet assay can be used to predict radiosensitivity of cervical tumour cell lines by assessing the ratio of initial and residual DNA dsbs

A comet assay of DNA damage and repair in K562 cells after photodynamic therapy using haematoporphyrin derivative, methylene blue and meso-tetrahydroxyphenylchlorin.

Single-cell electrophoresis (comet assay) has been used to evaluate DNA damage and repair in the human myeloid leukaemia cell line K562 after low-dose (predominantly sub-lethal) treatments of hyperthermia and photodynamic therapy (PDT). Three different photosensitizers were examined: haematoporphyrin derivative (HpD), methylene blue (MB) and meso-tetrahydroxyphenylchlorin (mTHPC). None of the drugs in the absence of light, nor in light alone, resulted in detectable DNA damage. However, a significant amount of DNA damage was detected immediately after treatment with haematoporphyrin derivative or methylene blue PDT compared with drug-only or light-only treatments; no residual level of DNA damage was evident for either drug following a 4-h post-treatment incubation at 37 degrees C. No significant DNA damage was detected after meso-tetrahydroxyphenylchlorin PDT or hyperthermia either immediately or 4 h after treatment. We conclude that the alkaline comet assay can be applied as an effective screening assay for DNA damage induced by a range of laser therapies

Social network centrality predicts dietary decisions in a wild bird population

How individuals balance costs and benefits of group living remains central to understanding sociality. In relation to diet, social foraging provides many advantages but also increases competition. Nevertheless, social individuals may offset increased competition by broadening their diet and consuming novel foods. Despite the expected relationships between social behavior and dietary decisions, how sociality shapes individuals’ novel food consumption remains largely untested in natural populations. Here, we use wild great tits to experimentally test how sociality predicts dietary decisions. We show that individuals with more social connections have higher propensity to use novel foods compared to socially peripheral individuals, and this is unrelated to neophobia, observations, and demographic factors. These findings indicate sociable individuals may offset potential costs of competition by foraging more broadly. We discuss how social environments may drive behavioral change in natural populations, and the implications for the causes and consequences of social strategies and dietary decisions

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

Gross solids from combined sewers in dry weather and storms, elucidating production, storage and social factors

Variation in rates of sanitary hygiene products, toilet tissue and faeces occurring in sewers are presented for dry and wet weather from three steep upstream urban catchments with different economic, age and ethnic profiles. Results show, for example, that total daily solids per capita from the low income and ageing populations are almost twice that from high income or ethnic populations. Relative differences are verified through independent questionnaires. The relationship between solids stored in sewers prior to storms, antecedent dry weather period and the proportion of roof to total catchment area is quantified. A full solids' flush occurs when storm flows exceed three times the peak dry weather flow. The data presented will assist urban drainage designers in managing pollution caused by the discharge of sewage solids

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (£2132) and tegafur with uracil (£3385) were lower than costs for the intravenous Mayo regimen (£3593) and infusional regimens on the de Gramont (£6255) and Modified de Gramont (£3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens