Aspirin use is associated with lower indices of liver fibrosis among adults in the United States.

BACKGROUND: Recent animal studies have shown that platelets directly activate hepatic stellate cells to promote liver fibrosis, whereas anti-platelet agents decrease liver fibrosis. It is unknown whether platelet inhibition by aspirin prevents liver fibrosis in humans. AIM: To examine the association between aspirin use and liver fibrosis among adults with suspected chronic liver disease. METHODS: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey III. We identified 1856 individuals with suspected chronic liver disease (CLD). The degree of liver fibrosis was determined using four validated fibrosis indices and a composite index. RESULTS: The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS [0.24 standard deviation (s.d.) units lower; 95% CI -0.42 to -0.06, P = 0.009]. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected CLD compared to those without (-0.23 vs. -0.03 s.d. units; P interaction = 0.05). The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices (P = 0.002-0.08) in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses. CONCLUSIONS: The use of aspirin was associated with significantly lower indices of liver fibrosis among US adults with suspected chronic liver diseases. Aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis.

Radioxenon detections in the CTBT international monitoring system likely related to the announced nuclear test in North Korea on February 12, 2013.

Observations made in April 2013 of the radioxenon isotopes (133)Xe and (131m)Xe at measurement stations in Japan and Russia, belonging to the International Monitoring System for verification of the Comprehensive Nuclear-Test-Ban Treaty, are unique with respect to the measurement history of these stations. Comparison of measured data with calculated isotopic ratios as well as analysis using atmospheric transport modeling indicate that it is likely that the xenon measured was created in the underground nuclear test conducted by North Korea on February 12, 2013, and released 7-8 weeks later. More than one release is required to explain all observations. The (131m)Xe source terms for each release were calculated to 0.7 TBq, corresponding to about 1-10% of the total xenon inventory for a 10 kt explosion, depending on fractionation and release scenario. The observed ratios could not be used to obtain any information regarding the fissile material that was used in the test.

Localized eczema herpeticum with unilateral ocular involvement.

We report a case of eczema herpeticum with unilateral ocular involvement in a 16-year-old boy. The patient has had a mild form of atopic dermatitis (AD) since early childhood. Why AD patients are prone to herpes simplex virus (HSV) infections is still unclear. Ocular pathologic findings in these cases are rarely reported.

Rationale and targets for antifibrotic therapies.

We have made striking progress in our understanding of the biochemistry and cell biology that underlies liver fibrosis and cirrhosis, including the development of strategies and agents to prevent and reverse fibrosis and incipient cirrhosis. However, translation of this knowledge into clinical practice has been hampered by the limitation of many in vitro and in vivo models to confirm mechanisms and to test antifibrotic agents, as well as the lack of sensitive methodologies to quantify the degree of liver fibrosis and the dynamics of fibrosis progression or reversal. Furthermore, while cirrhosis and subsequent decompensation are accepted hard clinical end-points, fibrosis and fibrosis progression alone are merely plausible surrogates for future clinical deterioration. This review focuses on basic mechanisms that underlay liver fibrosis progression and reversal and optimized strategies for preclinical antifibrotic drug development and validation. Therapies include several drugs that are of proven safety for other indications, agents that interfere with major fibrogenic or fibrolytic mechanisms, targeted drug delivery to the fibrogenic liver cells, and their potential combinations with hepatocyte or stem cell replenishment.

Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice.

BACKGROUND AND AIMS: Coeliac disease is a common small intestinal inflammatory disorder that results from a breach of intestinal tolerance to dietary gluten proteins, driven by gluten-reactive effector T cells. We aimed to assess the pathogenic role of gluten-reactive T cells and to generate a model of gluten-induced enteropathy. METHODS: CD4+CD25- T cell fractions were adoptively transferred into lymphopenic mice, leading to "baseline" small intestinal inflammation. RESULTS: Rag1-/- recipients of gliadin-presensitised CD4+CD45RBlowCD25- T cells, but not CD4+CD45RBhigh naive T cells, gained less weight and suffered from more severe duodenitis when challenged with oral gluten than recipients on gluten-free diet, or recipients of control (ovalbumin)-presensitised T cells. This was accompanied by deterioration of mucosal histological features characteristic of coeliac disease, and increased Th1/Th17 cell polarisation in the duodenum and the periphery. Interestingly, reintroduction of a gluten-free diet led to weight gain, improvement of histological duodenitis, and a decrease in duodenal interferon gamma and interleukin 17 transcripts. Moreover, B cell-competent nude recipients of gliadin-presensitised CD4+CD45RBlowCD25- T cells produced high levels of serum anti-gliadin immunoglobulin A (IgA) and IgG1/IgG2c only when challenged with oral gluten. CONCLUSIONS: CD4+ T cell immunity to gluten leads to a breach of oral gluten tolerance and small intestinal pathology in lymphopenic mice, similar to human coeliac disease. This model will be useful for the study of coeliac disease pathogenesis, and also for testing novel non-dietary therapies for coeliac disease.

The hedgehog pathway regulates remodelling responses to biliary obstruction in rats.

BACKGROUND: Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following biliary decompression, suggesting that it may also be involved in the repair of biliary damage. The hedgehog (Hh) pathway becomes activated in liver after bile duct ligation (BDL), and might modulate hepatic remodelling because Hh ligands are potent morphogens. OBJECTIVE: To study the induction of the Hh pathway during progression and resolution of biliary fibrosis, and to clarify whether Hh signalling regulates accumulation of bile duct progenitor cells. DESIGN AND MAIN OUTCOME MEASURES: Livers from rats with BDL were examined by quantitative real-time polymerase chain reaction analysis and immunohistochemistry to identify factors that might stimulate Hh signalling. BDL rats were subjected to Roux-en-Y hepaticojejunostomy (R-Y) to relieve biliary obstruction in order to determine whether these factors and Hh signalling declined as ductular populations and concomitant fibrosis regressed. Cultures of immature ductular cells were treated with putative Hh inducers and Hh ligands to confirm their functional relevance. RESULTS: BDL increased expression of platelet-derived growth factor-BB (PDGF-BB) and sonic hedgehog (Shh), downregulated hedgehog-interacting protein (Hip), activated Hh signalling, and expanded populations of Hh-responsive ductular cells that expressed pancyotkeratin, a liver progenitor cell marker. After R-Y, Hip remained suppressed, expression of PDGF-BB and Shh gradually declined, and populations of hedgehog-responsive ductular cells regressed. In cultured ductular cells, PDGF-BB treatment induced Shh expression, and incubation with Shh inhibited apoptotic activity. CONCLUSIONS: These results identify a mechanism for activation of the Hh pathway during cholestasis and suggest that Hh signalling regulates ductular cell accumulation after biliary injury.

p27(SJ), a novel protein in St John's Wort, that suppresses expression of HIV-1 genome.

Transcription of the HIV-1 genome is controlled by the cooperation of viral regulatory proteins and several host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, (LTR). Here, we describe the identification of a novel protein, p27(SJ), present in a laboratory callus culture of Hypericum perforatum (St John's Wort) that suppresses transcription of the HIV-1 genome in several human cell types including primary culture of microglia and astrocytes. p27(SJ) associates with C/EBPbeta, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27(SJ) with C/EBPbeta and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27(SJ) forces its entry into the nucleus and diminishes the capacity of p27(SJ) to suppress Tat activity, but does not alter its ability to suppress C/EBPbeta activation of the LTR. Results from binding assays showed the inhibitory effect of p27(SJ) on C/EBPbeta interaction with DNA. Finally, our results demonstrate that expression of p27(SJ) decreases the level of viral replication in HIV-1-infected cells. These observations suggest the potential for the development of a therapeutic advance based on p27(SJ) protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.

Intercomparison experiments of systems for the measurement of xenon radionuclides in the atmosphere.

Radioactive xenon monitoring is one of the main technologies used for the detection of underground nuclear explosions. Precise and reliable measurements of (131m)Xe, (133g)Xe, (133m)Xe, and (135g)Xe are required as part of the International Monitoring System for compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). For the first time, simultaneous testing of four highly sensitive and automated fieldable radioxenon measurement systems has been performed and compared to established laboratory techniques. In addition to an intercomparison of radioxenon monitoring equipment of different design, this paper also presents a set of more than 2000 measurements of activity concentrations of radioactive xenon made in the city of Freiburg, Germany in 2000. The intercomparison experiment showed, that the results from the newly developed systems agree with each other and the equipment fulfills the fundamental requirements for their use in the verification regime of the CTBT. For 24-h measurements, concentrations as low as 0.1 mBqm(-3) were measured for atmospheric samples ranging in size from 10 to 80 m(3). The (133)Xe activity concentrations detected in the ambient air ranged from below 1 mBqm(-3) to above 100 mBqm(-3).

Antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 in cholesterol-fed rabbits with thyroid inhibition.

OBJECTIVE: The aim of this study was to investigate the antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 (estra-1,3,5(10),8-tetraene-3, 17 alpha-diol), having a non-feminizing effect and high antioxidant potential, in male rabbits. EXPERIMENTAL DESIGN: Male White-Russian rabbits weighing 2.1-2.6 kg were fed either a standard or a high-cholesterol (200 mg/kg) diet, with thyroid function-inhibiting thiouracil (20 mg/kg) combined with cholic acid (40 mg/kg) administered daily in sunflower oil for 3 months. During the last month of the study, estrogens were administered by gavage at a dose of 0.02 or 0.1 mg/kg. RESULTS AND CONCLUSIONS: All three estrogens exerted remarkable antiatherosclerotic effects. Decreases in serum and aortic-wall lipid parameters and the index of atherogenicity were dependent on estrogen dose. Morphological evaluation of the aortic wall (height of plaques, size of plaque relative to aortic half-circumference) showed only weak therapeutic effects with all three estrogens. It is an open question whether the treatment period was too short to reverse the above changes. On the other hand, the data clearly suggest that 17 alpha-estradiol and J811 offer new perspectives for the prevention of atherosclerosis in men, which is similar to that found with 17 beta-estradiol in women.

Lichenoid dermatitis in 3 professional footballers.

We describe 3 professional footballers who developed lichenoid dermatitis over a short period of time. Clinically, the eruption in all 3 of them can be classified as lichenoid photodermatitis. We suggest an influence of possible contact allergens or photo-active substances. Histologic evidence points to features of classical lichen planus with purpura, typical of lichen aureus (purpuricus), but showing some clinical and morphological differences.

Detection and clinical significance of functional intrapulmonary vascular anastomoses in patients with chronic nonspecific lung diseases.

In 60 patients with chronic nonspecific lung diseases, both pulmonary circulation systems were examined simultaneously by catheterization and selective angiography of bronchial and lesser circulation vessels. The value of regional oxy- and barometric measurements for the diagnostics of left-to-right shunts in the lesser circulation was proved. Complex angiological examinations of both lung circulation systems helped reveal the basic variations of intrapulmonary anastomoses in both systems in patients with chronic nonspecific lung diseases. The formation of intrapulmonary anastomoses in such patients led to regional hyperoxygenation and to pulmonary arterial hypertension in the lesser circulation (in 18% of the patients), and to functional blockade of the perfusion (in 47% of the patients) of the affected segments, lobes, or the whole lung, which phenomenon substantially influenced the clinical course of the disease.

Semiconductor lasers.

The developments in the field of semiconductor lasers (p-n junction, excited by electron beam and by optical pumping) are considered. Especially emphasized is the problem of the application of the p-n junction laser as a high speed switching element.