Sodium chloride transport of normal and dietary enlarged rat cecum in vitro

Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed CI in excess of Na with a small short-circuit current (Isc). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate Ise change. Inhibitor studies (mucosal amiloride 10(-3) and 10(-4) M; mucosal 4,4-diisolhiocyanatostilbene-2,2-disulfonic acid 5 x 10(-5) M;serosal furosemide 10(-3) M;serosal ouabain 10(-3) M) suggested that normal cecal NaCl absorption involves electroneutral Na/N and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum

Systemic Lupus Erythematosus:Electron Microscopic Localization Of In Vivo Bound Globulins at the Dermal-Epidermal Junction**From the 1st Department of Dermatology, University of Vienna, A-1090 Vienna, Austria.

An anti-human globulin antibody-peroxidase conjugate has been used to demonstrate the ultrastructural localization of globulins at the dermal-epidermal junction in the skin of a patient with systemic lupus erythematosus. The globulin deposits are confined to the most superficial layers of the dermis immediately subjacent to the basal cells; they spare the epidermis and exhibit no preferential affinity to preexisting structures but they do coat collagen fibres. The basal lamina is, therefore, not the only antigenic site to which these globulins are directed

Stereochemical errors and their implications for molecular dynamics simulations

<p>Abstract</p> <p>Background</p> <p>Biological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function. Molecular dynamics simulations of biomolecules have increasingly become an integral part of biophysical research. However, stereochemical errors in biomolecular structures can have a dramatic impact on the results of simulations.</p> <p>Results</p> <p>Here we illustrate the effects that chirality and peptide bond configuration flips may have on the secondary structure of proteins throughout a simulation. We also analyze the most common sources of stereochemical errors in biomolecular structures and present software tools to identify, correct, and prevent stereochemical errors in molecular dynamics simulations of biomolecules.</p> <p>Conclusions</p> <p>Use of the tools presented here should become a standard step in the preparation of biomolecular simulations and in the generation of predicted structural models for proteins and nucleic acids.</p

Oncogenic c-H-ras deregulates survivin expression: An improvement for survival

AbstractSurvivin protein accomplishes two basic functions: cell cycle regulation and control of apoptosis. It is only expressed in G2/M phase and it influences rescue pathways in apoptosis-induced cells. Overexpression of constitutive active c-H-ras in HeLa, or induction of c-H-ras in a stable HeLaDiR cell line, led to sustained survivin expression in all cell cycle phases and even protected cells from drug induced apoptosis. siRNA-mediated silencing of survivin reversed this protection. Here we link the anti-apoptotic property of survivin to its cell cycle (in)dependent regulation via the activity of oncogenic c-H-ras

Urinary Excretion of Mercapturic Acids of the Rodent Carcinogen Methyleugenol after a Single Meal of Basil Pesto: A Controlled Exposure Study in Humans

Methyleugenol (ME), found in numerous plants and spices, is a rodent carcinogen and is classified as “possibly carcinogenic to humans”. The hypothesis of a carcinogenic risk for humans is supported by the observation of ME-derived DNA adducts in almost all human liver and lung samples examined. Therefore, a risk assessment of ME is needed. Unfortunately, biomarkers of exposure for epidemiological studies are not yet available. We hereby present the first detection of N-acetyl-l-cysteine conjugates (mercapturic acids) of ME in human urine samples after consumption of a popular ME-containing meal, pasta with basil pesto. We synthesized mercapturic acid conjugates of ME, identified the major product as N-acetyl-S-[3′-(3,4-dimethoxyphenyl)allyl]-l-cysteine (E-3′-MEMA), and developed methods for its extraction and LC–MS/MS quantification in human urine. For conducting an exposure study in humans, a basil cultivar with a suitable ME content was grown for the preparation of basil pesto. A defined meal containing 100 g of basil pesto, corresponding to 1.7 mg ME, was served to 12 participants, who collected the complete urine at defined time intervals for 48 h. Using d6-E-3′-MEMA as an internal standard for LC–MS/MS quantification, we were able to detect E-3′-MEMA in urine samples of all participants collected after the ME-containing meal. Excretion was maximal between 2 and 6 h after the meal and was completed within about 12 h (concentrations below the limit of detection). Excreted amounts were only between 1 and 85 ppm of the ME intake, indicating that the ultimate genotoxicant, 1′-sulfooxy-ME, is formed to a subordinate extent or is not efficiently detoxified by glutathione conjugation and subsequent conversion to mercapturic acids. Both explanations may apply cumulatively, with the ubiquitous detection of ME DNA adducts in human lung and liver specimens arguing against an extremely low formation of 1′-sulfooxy-ME. Taken together, we hereby present the first noninvasive human biomarker reflecting an internal exposure toward reactive ME species

Polycentric governance for small water supply systems: A case study in Kajiado, Kenya

The Water Integrity Network (WIN) conducted a study focusing on credible evidence on the impact of the Integrity Management Toolbox on Small Water Supply Systems at two levels, principally at the service delivery, governance and compliance with applicable rules and regulations. The subject of evaluation was the water supply system and the management model by which the water system is run (community group or water service provider) in Kajiado County, a pastoralist area that is mainly occupied by the Masaai. The evaluation considered differences in how the Integrity Management Toolbox was applied and compared these with the changes (service delivery, governance and compliance) achieved. From the findings, Water Integrity Network will draw lessons from implementation experience and make recommendations to improve effectiveness of the Integrity Management Toolbox on the quality of service delivery, governance improvements and compliance.

The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas

Objective Since the first introduction of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score, significant progress has been made with regard to surgical treatment options for cartilage defects, as well as magnetic resonance imaging (MRI) of such defects. Thus, the aim of this study was to introduce the MOCART 2.0 knee score — an incremental update on the original MOCART score — that incorporates this progression. Materials and Methods The volume of cartilage defect filling is now assessed in 25% increments, with hypertrophic filling of up to 150% receiving the same scoring as complete repair. Integration now assesses only the integration to neighboring native cartilage, and the severity of surface irregularities is assessed in reference to cartilage repair length rather than depth. The signal intensity of the repair tissue differentiates normal signal, minor abnormal, or severely abnormal signal alterations. The assessment of the variables "subchondral lamina," "adhesions," and "synovitis" was removed and the points were reallocated to the new variable "bony defect or bony overgrowth." The variable "subchondral bone" was renamed to "subchondral changes" and assesses minor and severe edema-like marrow signal, as well as subchondral cysts or osteonecrosis-like signal. Overall, a MOCART 2.0 knee score ranging from 0 to 100 points may be reached. Four independent readers (two expert readers and two radiology residents with limited experience) assessed the 3 T MRI examinations of 24 patients, who had undergone cartilage repair of a femoral cartilage defect using the new MOCART 2.0 knee score. One of the expert readers and both inexperienced readers performed two readings, separated by a four-week interval. For the inexperienced readers, the first reading was based on the evaluation sheet only. For the second reading, a newly introduced atlas was used as an additional reference. Intrarater and interrater reliability was assessed using intraclass correlation coefficients (ICCs) and weighted kappa statistics. ICCs were interpreted according to Koo and Li; weighted kappa statistics were interpreted according to the criteria of Landis and Koch. Results The overall intrarater (ICC = 0.88, P < 0.001) as well as the interrater (ICC = 0.84, P < 0.001) reliability of the expert readers was almost perfect. Based on the evaluation sheet of the MOCART 2.0 knee score, the overall interrater reliability of the inexperienced readers was poor (ICC = 0.34, P < 0.019) and improved to moderate (ICC = 0.59, P = 0.001) with the use of the atlas. Conclusions The MOCART 2.0 knee score was updated to account for changes in the past decade and demonstrates almost perfect interrater and intrarater reliability in expert readers. In inexperienced readers, use of the atlas may improve interrater reliability and, thus, increase the comparability of results across studies

Early onset of treatment effects with oral risperidone

BACKGROUND: The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. METHODS: In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. RESULTS: Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. CONCLUSION: Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration

Airborne observations of peroxy radicals during the EMeRGe campaign in Europe

In this study, airborne measurements of the sum of hydroperoxyl (HO$_2$) and organic peroxy (RO$_2$) radicals that react with nitrogen monoxide (NO) to produce nitrogen dioxide (NO$_2$), coupled with actinometry and other key trace gases measurements, have been used to test the current understanding of the fast photochemistry in the outflow of major population centres. The measurements were made during the airborne campaign of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) project in Europe on board the High Altitude and Long Range Research Aircraft (HALO). The measurements of RO$^∗_2$ on HALO were made using the in situ instrument Peroxy Radical Chemical Enhancement and Absorption Spectrometer (PeRCEAS). RO$^∗_2$ is to a good approximation the sum of peroxy radicals reacting with NO to produce NO$_2$. RO$^∗_2$ mixing ratios up to 120 pptv were observed in air masses of different origins and composition under different local actinometric conditions during seven HALO research flights in July 2017 over Europe. Radical production rates were estimated using knowledge of the photolysis frequencies and the RO$^∗_2$ precursor concentrations measured on board, as well as the relevant rate coefficients. Generally, high RO$^∗_2$ concentrations were measured in air masses with high production rates. In the air masses investigated, RO$^∗_2$ is primarily produced by the reaction of O$^1$D with water vapour and the photolysis of nitrous acid (HONO) and of the oxygenated volatile organic compounds (OVOCs, e.g. formaldehyde (HCHO) and glyoxal (CHOCHO)). Due to their short lifetime in most environments, the RO$^∗_2$ concentrations are expected to be in a photostationary steady state (PSS), i.e. a balance between production and loss rates is assumed. The RO$^∗_2$ production and loss rates and the suitability of PSS assumptions to estimate the RO$^∗_2$ mixing ratios and variability during the airborne observations are discussed. The PSS assumption for RO$^∗_2$ is considered robust enough to calculate RO$^∗_2$ mixing ratios for most conditions encountered in the air masses measured. The similarities and discrepancies between measured and PSS calculated RO$^∗_2$ mixing ratios are discussed. The dominant terminating processes for RO$^∗_2$ in the pollution plumes measured up to 2000 m are the formation of nitrous acid, nitric acid, and organic nitrates. Above2000 m, HO$_2$–HO$_2$ and HO$_2$–RO$_2$ reactions dominate the RO$^∗_2$ removal. RO$^∗_2$ calculations by the PSS analytical expression inside the pollution plumes probed often underestimated the measurements. The underestimation is attributed to the limitations of the PSS equation used for the analysis. In particular, this expression does not account for the yields of RO$^∗_2$ from the oxidation and photolysis of volatile organic compounds, VOCs, and OVOCs other than those measured during the EMeRGe research flights in Europe. In air masses with NO mixing ratios ≤ 50 pptv and low VOC/NO ratios, the RO$^∗_2$ measured is overestimated by the analytical expression. This may be caused by the formation of H$_2$O and O$_2$ from OH and HO$_2$, being about 4 times faster than the rate of the OH oxidation reaction of the dominant OVOCs considered