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Although neurokinin 1 receptor antagonists prevent ethanol (EtOH)-induced gastric lesions, the mechanisms by which EtOH releases substance P (SP) and SP damages the mucosa are unknown. We hypothesized that EtOH activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to release SP, which stimulates epithelial neurokinin 1 receptors to generate damaging reactive oxygen species (ROS). SP release was assayed in the mouse stomach, ROS were detected using dichlorofluorescein diacetate, and neurokinin 1 receptors were localized by immunofluorescence. EtOH-induced SP release was prevented by TRPV1 antagonism. High dose EtOH caused lesions, and TRPV1 or neurokinin 1 receptor antagonism and neurokinin 1 receptor deletion inhibited lesion formation. Coadministration of low, innocuous doses of EtOH and SP caused lesions by a TRPV1-independent but neurokinin 1 receptor-dependent process. EtOH, capsaicin, and SP stimulated generation of ROS by superficial gastric epithelial cells expressing neurokinin 1 receptors by a neurokinin 1 receptor-dependent mechanism. ROS scavengers prevented lesions induced by a high EtOH dose or a low EtOH dose plus SP. Gastric lesions are caused by an initial detrimental effect of EtOH, which is damaging only if associated with TRPV1 activation, SP release from sensory nerves, stimulation of neurokinin 1 receptors on epithelial cells, and ROS generation.

Phytoplankton account for approximately 50% of global primary production, form the trophic base of nearly all marine ecosystems, are fundamental in trophic energy transfer and have key roles in climate regulation, carbon sequestration and oxygen production. Boyce et al.1 compiled a chlorophyll index by combining in situ chlorophyll and Secchi disk depth measurements that spanned a more than 100-year time period and showed a decrease in marine phytoplankton biomass of approximately 1% of the global median per year over the past century. Eight decades of data on phytoplankton biomass collected in the North Atlantic by the Continuous Plankton Recorder (CPR) survey2, however, show an increase in an index of chlorophyll (Phytoplankton Colour Index) in both the Northeast and Northwest Atlantic basins3,4,5,6,7 (Fig. 1), and other long-term time series, including the Hawaii Ocean Time-series (HOT)8, the Bermuda Atlantic Time Series (BATS)8 and the California Cooperative Oceanic Fisheries Investigations (CalCOFI)9 also indicate increased phytoplankton biomass over the last 20–50 years. These findings, which were not discussed by Boyce et al.1, are not in accordance with their conclusions and illustrate the importance of using consistent observations when estimating long-term trends.

Nine chippers were tested for particle size distribution, in order to a) see how chips produced with these machines matched the quality specifications set by the district heating plants of Northeastern Italy and b) detect significant differences between machines. The benchmark was set by collecting chip samples from fourteen district heating plants in the region of interest. The effect of operator skill was minimized and all machines were fed with the same assortment: logs, supplied in lengths varying between 2.4 and 6 m. All logs had similar moisture contents, which typically ranged between 33 and 37 % on a fresh weight base. Mobile in-woods chippers fed with limb-free logs produce high-quality chips, whose particle size distribution matches that of the best chips normally fed to the Italian district heating plants. Indeed, all the tested machines produced chip samples containing almost no oversize particles, very little fines (0.5 to 1 %), and a large majority of chips within the 3-45mm range (95 to 99 %), except the auger-equipped Laimet, which is designed to produce larger chips. There were statistically significant differences between machines and machine types, which were not affected by possible variations of the tree species processed.

AbstractHand, foot, and mouth disease (HFMD) is an enterovirus‐mediated condition that predominantly affects children under 5 years of age. The tendency for outbreaks to peak in warmer summer months suggests a relationship between HFMD and weather patterns. We reviewed the English‐language literature for articles describing a relationship between meteorological variables and HFMD. Seventy‐two studies meeting criteria were identified. A positive, statistically significant relationship was identified between HFMD cases and both temperature (61 of 67 studies, or 91.0%, reported a positive relationship) [CI 81.8–95.8%, P = 0.0001] and relative humidity (41 of 54 studies, or 75.9%) [CI 63.1–85.4%, P = 0.0001]. No significant relationship was identified between HFMD and precipitation, wind speed, and/or sunshine. Most countries reported a single peak of disease each year (most commonly early Summer), but subtropical and tropical climate zones were significantly more likely to experience a bimodal distribution of cases throughout the year (two peaks a year; most commonly late spring/early summer, with a smaller peak in autumn). The rising global incidence of HFMD, particularly in Pacific Asia, may be related to climate change. Weather forecasting might be used effectively in the future to indicate the risk of HFMD outbreaks and the need for targeted public health interventions.

We previously reported that laminin immunoreactivity in mouse mammary epithelium is altered shortly after whole-body irradiation with 0.8 Gy from 600 MeV/nucleon iron ions but is unaffected after exposure to sparsely ionizing radiation. This observation led us to propose that the effect could be due to protein damage from the high ionization density of the ion tracks. If so, we predicted that it would be evident soon after radiation exposure in basement membranes of other tissues and would depend on ion fluence. To test this hypothesis, we used immunofluorescence, confocal laser scanning microscopy, and image segmentation techniques to quantify changes in the basement membrane of mouse skin epidermis. At 1 h after exposure to 1 GeV/nucleon iron ions with doses from 0.03 to 1.6 Gy, neither the visual appearance nor the mean pixel intensity of laminin in the basement membrane of mouse dorsal skin epidermis was altered compared to sham-irradiated tissue. This result does not support the hypothesis that particle traversal directly affects laminin protein integrity. However, the mean pixel intensity of laminin immunoreactivity was significantly decreased in epidermal basement membrane at 48 and 96 h after exposure to 0.8 Gy 1 GeV/nucleon iron ions. We confirmed this effect with two additional antibodies raised against affinity-purified laminin 1 and the E3 fragment of the long-arm of laminin 1. In contrast, collagen type IV, another component of the basement membrane, was unaffected. Our studies demonstrate quantitatively that densely ionizing radiation elicits changes in skin microenvironments distinct from those induced by sparsely ionizing radiation. Such effects may might contribute to the carcinogenic potential of densely ionizing radiation by altering cellular signaling cascades mediated by cell-extracellular matrix interactions.

The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50-100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2-3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across hairless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.

Alcohol and alcoholic beverages may have different effects on pancreatic secretion and hormone release in humans. To test this hypothesis we studied the effects of an alcohol solution and a glucose solution and compared them with those of alcoholic beverages on postprandial pancreatic secretion and release of gastrin, trypsin, and cholecystokinin in 6 healthy nonalcoholic male volunteers. Pancreatic enzyme secretion was measured in duodenal aspirate, plasma trypsin, and gastrin by radioimmunoassay and cholecystokinin by bioassay. The meal plus glucose significantly stimulated pancreatic enzyme secretion, release of gastrin and cholecystokinin, and caused no changes in plasma trypsin. The alcohol solution and all beverages added to the meal caused similar increases in alcohol blood levels and significantly less pancreatic enzyme secretion compared with the meal plus glucose. Plasma trypsin levels remained unchanged. Compared with the meal plus glucose, wine and beer caused a significantly higher release of gastrin, and beer also released significantly more cholecystokinin. Inhibition of pancreatic enzyme secretion stimulated by a meal in nonalcoholics is a common effect of alcohol and alcoholic beverages despite some differences on release of gastrointestinal peptides. This effect may have some implications in the pathogenesis of alcoholic pancreatitis.