Cytoadhesion of Plasmodium falciparum-Infected Red Blood Cells Changes the Expression of Cytokine-, Histone- and Antiviral Protein-Encoding Genes in Brain Endothelial Cells.

Malaria remains a significant global health problem, mainly due to Plasmodium falciparum, which is responsible for most fatal infections. Infected red blood cells (iRBCs) evade spleen clearance by adhering to endothelial cells (ECs), triggering capillary blockage, inflammation, endothelial dysfunction and altered vascular permeability, prompting an endothelial transcriptional response. The iRBC/HBEC-5i model, where iRBCs present IT4var04 (VAR2CSA) on their surface, was used to analyze the effects of iRBC binding on ECs at different temperature (37°C vs.

Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans.

Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream transforming growth factor-β3, and perturbation of liver tissue homeostasis.

Estimated Dermal Penetration of Tetrachlorvinphos (TCVP) in Humans Based on Modeling and and Data.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient in some collars for dogs and cats. The objective of this study was to provide a refined estimate of dermal penetration of TCVP in humans using predictions as well as and data. The dermal absorption of TCVP was previously studied in the rat and shown to be saturable, ranging from 21.

The chlorophenoxy herbicide MCPA: a mechanistic basis for the observed differences in toxicological profile in humans and rats versus dogs.

Metabolism data for MCPA in rat, dog and human shows a single oral dose is quantitatively and rapidly absorbed with evidence of non-linear kinetics at >100 mg/kg bw. The extent of metabolism is low and consistent between rat and human, with substantially higher metabolic conversion in dog. Parent accounts for 50%-67% dose in rat, ∼40% in human and 2%-27% in dog.

Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling.

Although external concentrations are more readily quantified and often used as the metric for regulating and mitigating exposures to environmental chemicals, the toxicological response to an environmental chemical is more directly related to its internal concentrations than the external concentration. The processes of absorption, distribution, metabolism, and excretion (ADME) determine the quantitative relationship between the external and internal concentrations, and these processes are often susceptible to saturation at high concentrations, which can lead to nonlinear changes in internal concentrations that deviate from proportionality. Using generic physiologically-based pharmacokinetic (PBPK) models, we explored how saturable absorption or clearance influence the shape of the internal to external concentration (IEC) relationship.

In silico predictions of absorption of MDI substances after dermal or inhalation exposures to support a category based read-across assessment.

Methylenediphenyl diisocyanate (MDI) substances used polyurethane production can range from their simplest monomeric forms (e.g., 4,4'-MDI) to mixtures of the monomers with various homologues, homopolymer, and prepolymer derivatives.

[Endoscopic Ultrasound Drainage of the Gallbladder in Acute Cholecystitis in Patients at High Surgical Risk].

Background: The standard treatment for acute cholecystitis is laparoscopic cholecystectomy. Alternative procedures are used for patients at high surgical risk. Percutaneous drainage is widely available.

Health-Related Quality of Life and Mental Health after Surgical Treatment of Hepatocellular Carcinoma in the Era of Minimal-Invasive Surgery: Resection versus Transplantation.

Laparoscopic liver resection (LLR) is an increasingly relevant treatment option for patients with resectable hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) has been considered optimal treatment for HCC in cirrhosis, but is challenged by rising organ scarcity. While health-related quality of life (HRQoL) and mental health are well-documented after OLT, little is known about HRQoL in HCC patients after LLR.

Weight of evidence analysis of the tumorigenic potential of 1,3-dichloropropene supports a threshold-based risk assessment.

1,3-Dichloropropene (1,3-D; CAS #542-75-6) is a fumigant used for preplant treatment of soil to control parasitic nematodes and manage soil borne diseases for numerous fruit, vegetable, field and tree and vine crops across diverse global agricultural areas. In the USA, 1,3-D has historically been classified by the U.S.

Review of the pharmacokinetics and metabolism of triclopyr herbicide in mammals: Impact on safety assessments.

A review of pharmacokinetic and metabolism studies show that triclopyr is well absorbed from the oral route in numerous species (≥80%), primarily as parent compound. Absorption is quite rapid in rats, dogs and human volunteers. Plasma or blood clearance is also rapid (t 3-9 h), except for dog (12-96 h).

Milan criteria in the MELD era-is it justifiable to extend the limits for orthotopic liver transplantation?

Background: The Milan criteria (MC) are widely used for the indication of liver transplantation (LTx) in hepatocellular carcinoma (HCC). Good long-term results have also been reported following LTx for patients exceeding the MC. In this article, we compare the overall and recurrence-free survival of our patients fulfilling and exceeding the MC according to the post-transplant histopathological results.

Successful surgical management of hepatic alveolar echinococcosis by inductive therapy with albendazole - a case report.

We report the case of a 65-year-old female patient with hepatic alveolar echinococcosis (AE) caused by Echinococcus multilocularis. This infrequent zoonosis has a considerable morbidity and mortality. The malignant appearing hepatic mass was initially misdiagnosed as cholangiocarcinoma of the right hepatic lobe (segments VII, VIII, and IVa, sized 10.

Current Treatment of Colorectal Liver Metastasis as a Chronic Disease.

Background/aim: The treatment of colorectal liver metastases is challenging and requires multidisciplinary strategies. Unfortunately, only 25% of patients with colorectal liver metastases are eligible for liver resection. Due to the variety of therapeutic approaches, this percentage has increased; however, at the same time, the definition of resectability has become complex.

Metabolic Basis for Nonlinearity in 1,3-Dichloropropene Toxicokinetics and Use in Setting a Kinetically-derived Maximum Inhalation Exposure Concentration in Mice.

1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week).

Segmental intrahepatic cholestasis as a technical complication of the transjugular intrahepatic porto-systemic shunt.

Background: Segmental intrahepatic cholestasis caused by transjugular intrahepatic portosystemic shunt (TIPS) (SIC-T), is a rare complication of this technique and only referred by case reports. Thus, we conducted a systematic, retrospective analysis to provide evidence regarding prevalence and consequences of this TIPS-induced bile duct compression.

Aim: To assess prevalence and outcome of SIC-T in a large TIPS-cohort.

Tissue-based miRNA mapping in alcoholic liver cirrhosis: different profiles in cirrhosis with or without hepatocellular carcinoma.

Alcoholic liver cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). The importance of tumour-associated cirrhosis in the development or progression of HCC is not understood. MiRNAs are important regulators for HCC development, but their role in HCC due to alcoholic liver cirrhosis is unclear.

Hepatitis B Vaccination in Patients with Liver Cirrhosis Evaluated for Liver Transplantation - A Simple Intervention Ensures High Adherence.

BACKGROUND There is an unmet need to improve the HBV vaccination status in patients with chronic liver diseases. Primary care physicians and outpatient hepatologists often fail to vaccinate as recommended. Thus, new strategies to improve the HBV vaccination rate are required.

The ADME profile of the fungicide tricyclazole in rodent via the oral route: A critical review for human health safety assessment.

Herein, we publish data from regulatory studies investigating the oral ADME (absorption, distribution, metabolism, excretion) of tricyclazole in vivo, in silico and in vitro. The oral route is relevant to human dietary exposure assessment. Tricyclazole is readily absorbed and highly bioavailable in rodents (>86%) with indication of saturation of absorption at high doses.

Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study.

Background & Aims: Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors.

Methods: We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database.

Power of computed-tomography-defined sarcopenia for prediction of morbidity after pancreaticoduodenectomy.

Background: The goal of our study was to evaluate the current approach in prediction of postoperative major complications after pancreaticoduodenectomy (PD), especially symptomatic pancreatic fistula (POPF), using parameters derived from computed tomography (CT).

Methods: Patients after PD were prospectively collected in a database of the local department of surgery and all patients with CT scans available were assessed in this study. CT parameters were measured at the level of the intervertebral disc L3/L4 and consisted of the areas of the visceral adipose tissue (A), the diameters of the pancreatic parenchyma (DPP) and the pancreatic duct (DPD), the areas of ventral abdominal wall muscle (A), psoas muscle (A), paraspinal muscle (A), total muscle (A), as well as the mean muscle attenuation (MA) and skeletal muscle index (SMI).

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

Background: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity.

Aim: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT).

PBTK model for assessment of operator exposure to haloxyfop using human biomonitoring and toxicokinetic data.

Physiologically-based toxicokinetic (PBTK) models are mathematical representations of chemical absorption, distribution, metabolism and excretion (ADME) in animals. Each parameter in a PBTK model describes a physiological, physicochemical or biochemical process that affects ADME. Distributions can be assigned to the model parameters to describe population variability and uncertainty.

Loss of paraspinal muscle mass is a gender-specific consequence of cirrhosis that predicts complications and death.

Background: Loss of skeletal muscle mass is a recognised complication with a prognostic impact in patients with cirrhosis.

Aim: To explore in a retrospective analysis which muscle compartment most reliably predicts the occurrence of cirrhosis-associated complications and if there are gender-related differences.

Methods: 795 patients with cirrhosis listed for liver transplantation between 2001 and 2014 met the inclusion and exclusion criteria including an abdominal CT scan (±200).