Regenerating Rat Liver: Correlations Between Estrogen Receptor Localization and Deoxyribonucleic Acid Synthesis

Estrogen receptor activity was quantitated in the cytosol and nucleus of normal rat liver and in regenerating rat liver at several time intervals after 75% hepatectomy. Cytosolic estradiol binding in regenerating liver decreases at 12, 24, and 48 h after hepatectomy and at 48 h is 30% of that in normal rat liver. Nuclear estrogen binding 48 h after surgery is elevated fivefold over normal values. No alterations in affinity of the receptor for estrogen have been observed. Specificity studies indicate that the estrogen receptors from both normal and regenerating liver were similar and are highly specific for estrogens. These changes in cellular distribution of receptors parallel increases in nuclear deoxyribonucleic acid synthesis and mitotic indices in the liver. © 1984, American Gastroenterological Association. All rights reserved

May antitransglutaminase levels predict severity of duodenal lesions in adults with celiac disease?

Background and Objective: Pediatric guidelines on celiac disease (CD) state that children with anti‐transglutaminase antibodies (TGAs) >×10 upper limit of normal (ULN) may avoid endos-copy and biopsy. We aimed to evaluate whether these criteria may be suitable for villous atrophy diagnosis in CD adults. Materials and Methods: We retrospectively enrolled patients with CD aged >18 years. TGAs were expressed as xULN. Duodenal lesions were classified as atrophic or non-atrophic according to Marsh‐Oberhuber. Fisher’s exact and t‐test were used for variables compari-son. Receiver operating characteristics (ROC) curve analysis was performed with estimation of area under the curve (AUC), sensitivity, specificity, and positive and negative predictive value (PPV/NPV). Results: One hundred and twenty‐one patients were recruited. Sixty patients (49.6%) had TGA >×10 ULN, and 93 (76.8%) had villous atrophy. The cut‐off of >×10 ULN had sensitivity = 53.7%, specificity = 64.3%, PPV = 83.3%, and NPV = 29.5% to predict atrophy. Therefore, considering pediatric criteria, in 50 (41.3%) patients, biopsy could have been avoided. Patient subgroup with atrophy had higher TGA levels despite being not significant (37.2 ± 15.3 vs. 8.0 ± 1.3 ULN, p = 0.06). In adults, a slightly better diagnostic performance was obtained using a cut‐off of TGA >×6.2 ULN (sensitivity = 57.1%, specificity = 65.6%, and AUC = 0.62). Conclusions: Despite our confirmation that villous atrophy is linked to high TGA levels, CD and atrophy diagnosis based only on serology is not reliable in adults

HBsAg clearance by Peg-interferon addition to a long-term nucleos(t)ide analogue therapy.

The ideal endpoint of hepatitis B virus (HBV) antiviral therapy is HBsAg loss, a difficult goal to obtain, especially in HBeAg negative patients. Herein, we report the results obtained by the addition of peg-interferon α-2a to a long-lasting nucleos(t)ide analogue therapy in a HBeAg negative, genotype D patient with steadily HBV-DNA negative/HBsAg positive values. In 2002, our Caucasian 44-year-old male patient received lamivudine and, 4 years later, added adefovir because of a virological breakthrough. In 2011, considering his young age, liver stiffness (4.3 kPa) and HBsAg levels (3533 IU/mL), we added Peg-interferon α-2a for six months (3 in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferon α-2a monotherapy). A decrease of HBsAg levels was observed after 1 mo (1.21 log) of Peg-interferon and 3 mo (1.88 log) after the discontinuation of all drugs. Later, a complete clearance of HBsAg was obtained with steadily undetectable HBV-DNA serum levels (< 9 IU/mL). HBsAg clearance by the addition of a short course of Peg-interferon α-2a represents an important result with clinical and pharmaco-economic implications, considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment

The perplexity of targeting genetic alterations in hepatocellular carcinoma

Genetic heterogeneity is a well-recognized feature of hepatocellular carcinoma (HCC). The coexistence of multiple genetic alterations in the same HCC nodule contributes to explain why gene-targeted therapy has largely failed. Targeting of early genetic alterations could theoretically be a more effective therapeutic strategy preventing HCC. However, the failure of most targeted therapies has raised much perplexity regarding the role of genetic alterations in driving cancer as the main paradigm. Here, we discuss the methodological and conceptual limitations of targeting genetic alterations and their products that may explain the limited success of the novel mechanism-based drugs in the treatment of HCC. In light of these limitations and despite the era of the so-called “precision medicine,” prevention and early diagnosis of conditions predisposing to HCC remain the gold standard approach to prevent the development of this type of cancer. Finally, a paradigm shift to a more systemic approach to cancer is required to find optimal therapeutic solutions to treat this disease

A Finite Element Implementation of a Coupled Diffusion-Deformation Theory for Elastomeric Gels

The theory of Chester and Anand (2011) for fluid diffusion and large deformations of elastomeric gels is implemented as a user-defined element (UEL) subroutine in the commercial finite element software package ABAQUS. A specialized form of the constitutive equations and the governing partial differential equations of the theory are summarized, and the numerical implementation is described in detail. To demonstrate the robustness of the numerical implementation a few illustrative numerical simulation examples for axisymmetric, plane strain, and three-dimensional geometries are shown. For educational purposes, and also to facilitate the numerical implementation of other coupled multiphysics theories, the source code for the UEL is provided as an online supplement to this paper.National Science Foundation (U.S.) (NSF CMMI-1063626

Structure of Turbulence in Katabatic Flows below and above the Wind-Speed Maximum

Measurements of small-scale turbulence made over the complex-terrain atmospheric boundary layer during the MATERHORN Program are used to describe the structure of turbulence in katabatic flows. Turbulent and mean meteorological data were continuously measured at multiple levels at four towers deployed along the East lower slope (2-4 deg) of Granite Mountain. The multi-level observations made during a 30-day long MATERHORN-Fall field campaign in September-October 2012 allowed studying of temporal and spatial structure of katabatic flows in detail, and herein we report turbulence and their variations in katabatic winds. Observed vertical profiles show steep gradients near the surface, but in the layer above the slope jet the vertical variability is smaller. It is found that the vertical (normal to the slope) momentum flux and horizontal (along the slope) heat flux in a slope-following coordinate system change their sign below and above the wind maximum of a katabatic flow. The vertical momentum flux is directed downward (upward) whereas the horizontal heat flux is downslope (upslope) below (above) the wind maximum. Our study therefore suggests that the position of the jet-speed maximum can be obtained by linear interpolation between positive and negative values of the momentum flux (or the horizontal heat flux) to derive the height where flux becomes zero. It is shown that the standard deviations of all wind speed components (therefore the turbulent kinetic energy) and the dissipation rate of turbulent kinetic energy have a local minimum, whereas the standard deviation of air temperature has an absolute maximum at the height of wind-speed maximum. We report several cases where the vertical and horizontal heat fluxes are compensated. Turbulence above the wind-speed maximum is decoupled from the surface, and follows the classical local z-less predictions for stably stratified boundary layer.Comment: Manuscript submitted to Boundary-Layer Meteorology (05 December 2014

Severe anaemia after gastric biopsy in an infant with eosinophilic gastritis

Background: Eosinophilic gastrointestinal disorders (EGID) are characterized by eosinophilic inflammation and are subclassified according to the affected site(s) as eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis. Clinical presentation includes dyspeptic symptoms, vomiting, abdominal pain, diarrhoea and gastrointestinal bleeding. Peripheral eosinophilia is usually found but is not required for the diagnosis. The treatment is based on dietary elimination therapy, consisting of removal of common food triggers, most frequently cow's milk in infants. Corticosteroids are used as first line drug therapy in EG if dietary therapy fails to achieve an adequate clinical response or is impractical. Case presentation: A four month old infant was admitted for an episode of melena and hematemesis. An esophagogastroduodenoscopy showed haemorrhagic gastritis with ulcerative lesions and fibrin. A significant gastric bleeding was noted after the procedure. The gastric mucosa biopsies showed an eosinophilic infiltration. Conclusions: A clinically relevant anaemia is a quite rare complication in infants with eosinophilic gastritis and a biopsy may worsen bleeding, to a potentially severe level of low haemoglobin. In infants with low haemoglobin levels and suspect eosinophilic gastritis a watchful follow up after the biopsy should be considered, as well as the possibility of postponing the biopsy to reduce the bleeding risk

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Trace metal distributions in Posidonia oceanica and sediments from Taranto Gulf (Ionian Sea, Southern Italy)

Distribution of metals (Hg, Pb, Sn, Cu, Cd and Zn) was determined in sediments and in different tissues of Posidonia oceanica collected from San Pietro Island, Taranto Gulf (Ionian Sea, Southern Italy). In seagrass, results, compared with metal concentrations in sediments, showed that the highest concentrations of Hg, Pb, Sn and Cu were found in the roots, while in the green leaves were found the highest levels of Cd and Zn. Instead the lowest metal concentrations were found in the basal part of the leaf. Levels of  metals in the leaves were similar to those found by other authors in uncontaminated areas of the Mediterranean Sea. Mercury levels in roots were correlated to levels in sediments. This could demonstrate the plant memorizes sediments contamination . This study reinforces the usefulness and the relevance of Posidonia oceanica as an indicator of spatial metal contamination and an interesting tool for environmental quality evaluation

Influence of Polyphenol Levels on the Perception of Aroma in Vitis vinifera cv. Malbec wine

The aim of this study was to explore the effect of two ranges of polyphenols naturally present in Malbec wine,high concentrations (4.5-7.2 g/L) and low (1.4-3.2 g/L), on the perception of aroma. Samples with a maximumethanol level of 13.5% were taken from the fermentation tanks before the clarification and filtration process. AQuantitative Descriptive Analysis of wines was assessed by ten trained assessors, and HS-SPME-GC-MS andphysicochemical analyses were performed. The intensities of fruity (P < 0.01), citrus (P < 0.01), strawberry (P< 0.05), cooked fruit (P < 0.01) and floral (P < 0.01) aromas decreased when the level of polyphenols increased.Neither volatile compounds nor physicochemical analyses were significant in the two groups of wines