Computed tomography pulmonary angiography (CTPA) for the detection of pulmonary embolism (PE) among trauma patients: a systematic review and meta-analysis.

Background And Objectives: Computed tomography pulmonary angiography (CTPA) is a standard imaging technique employed for the detection of pulmonary embolism (PE). This systematic review and meta-analysis aims to examine the prevalence of PE among the trauma patients undergoing CTPA.

Methods: A comprehensive search across PubMed, Scopus, Google Scholar, and Web of Science yielded 13 studies encompassing 5,570 individuals conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline.

Uniportal video-assisted thoracoscopy in pediatrics-initial experience.

Background: It has become apparent that the endoscopic surgeries are rapidly developing, and they have become an essential part of every specialty of surgery. Single port thoracoscopic surgery is developing, enhancing the advantages of muti-portal video-assisted thoracoscopic surgery (VATS). Although becoming a well-recognised approach for adult patients, extremely limited literature exists concerning uniportal VATS among pediatric cases.

Prevalence of diabetes and cardio-metabolic risk factors in young men in the United Arab Emirates: A cross-sectional national survey.

Introduction: The aim of the study was to determine the prevalence of cardio-metabolic risk factors in men under 30 in the United Arab Emirates.

Methods: This cross-sectional observational study included 33 327 Emirati men aged 18-29 attending an obligatory standardized medical examination between May 2015 and February 2017. Body mass index, fasting blood glucose, total cholesterol, triglycerides and blood pressure were assessed.

The role of apoptosis in acetaminophen hepatotoxicity.

Although necrosis is recognized as the main mode of cell death induced by acetaminophen (APAP) overdose in animals and humans, more recently an increasing number of publications, especially in the herbal medicine and dietary supplement field, claim an important contribution of apoptotic cell death in the pathophysiology. However, most of these conclusions are based on parameters that are not specific for apoptosis. Therefore, the objective of this review was to re-visit the key signaling events of receptor-mediated apoptosis and APAP-induced programmed necrosis and critically analyze the parameters that are being used as evidence for apoptotic cell death.

Protective effect of genetic deletion of pannexin1 in experimental mouse models of acute and chronic liver disease.

Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation.

Induction of mitochondrial biogenesis protects against acetaminophen hepatotoxicity.

Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h.

Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice.

Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes.

Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity.

Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia-reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity.

Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity.

Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.

Involvement of connexin43 in acetaminophen-induced liver injury.

Background And Aims: Being goalkeepers of liver homeostasis, gap junctions are also involved in hepatotoxicity. However, their role in this process is ambiguous, as gap junctions can act as both targets and effectors of liver toxicity. This particularly holds true for drug-induced liver insults.

Connexin32: a mediator of acetaminophen-induced liver injury?

Connexin32 is the building block of hepatocellular gap junctions, which control direct intercellular communication and thereby act as goalkeepers of liver homeostasis. This study was set up to investigate whether connexin32 is involved in hepatotoxicity induced by the analgesic and antipyretic drug acetaminophen. To this end, whole body connexin32 knock-out mice were overdosed with acetaminophen followed by sampling at different time points within a 24-h time frame.

Inhibitor of apoptosis signal-regulating kinase 1 protects against acetaminophen-induced liver injury.

Metabolic activation and oxidant stress are key events in the pathophysiology of acetaminophen (APAP) hepatotoxicity. The initial mitochondrial oxidative stress triggered by protein adduct formation is amplified by c-jun-N-terminal kinase (JNK), resulting in mitochondrial dysfunction and ultimately cell necrosis. Apoptosis signal-regulating kinase 1 (ASK1) is considered the link between oxidant stress and JNK activation.

Biomarkers distinguish apoptotic and necrotic cell death during hepatic ischemia/reperfusion injury in mice.

Hepatic ischemia/reperfusion (IRP) injury is a significant clinical problem during tumor-resection surgery (Pringle maneuver) and liver transplantation. However, the relative contribution of necrotic and apoptotic cell death to the overall liver injury is still controversial. To address this important issue with a standard murine model of hepatic IRP injury, plasma biomarkers of necrotic cell death such as micro-RNA 122, full-length cytokeratin 18 (FK18), and high-mobility group box 1 (HMGB1) protein and plasma biomarkers of apoptosis such as plasma caspase-3 activity and caspase-cleaved fragment of cytokeratin 18 (CK18) coupled with markers of inflammation (hyperacetylated HMGB1) were compared by histological features in hematoxylin and eosin-stained and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-stained liver sections.

Lithocholic acid feeding results in direct hepato-toxicity independent of neutrophil function in mice.

Lithocholic acid (LCA) supplementation in the diet results in intrahepatic cholestasis and bile infarcts. Previously we showed that an innate immune response is critical for cholestatic liver injury in the bile duct ligated mice. Thus, the purpose of this study was to investigate the role of neutrophils in the mechanism of liver injury caused by feeding mice a diet containing LCA.

Argininosuccinate synthetase as a plasma biomarker of liver injury after acetaminophen overdose in rodents and humans.

Context: New biomarkers are needed in acetaminophen (APAP) hepatotoxicity. Plasma argininosuccinate synthetase (ASS) is a promising candidate.

Objective: Characterize ASS in APAP hepatotoxicity.

Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans.

Following acetaminophen (APAP) overdose there is an inflammatory response triggered by the release of cellular contents from necrotic hepatocytes into the systemic circulation which initiates the recruitment of neutrophils into the liver. It has been demonstrated that neutrophils do not contribute to APAP-induced liver injury, but their role and the role of NADPH oxidase in injury resolution are controversial. C57BL/6 mice were subjected to APAP overdose and neutrophil activation status was determined during liver injury and liver regeneration.

The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation.

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communication channels which transfer cytotoxic mediators into neighboring hepatocytes and aggravate liver injury. However, these studies did not consider off-target effects of reagents used in these experiments, especially the gap junction inhibitor 2-aminoethoxy-diphenyl-borate (2-APB).

Fas receptor-deficient lpr mice are protected against acetaminophen hepatotoxicity due to higher glutathione synthesis and enhanced detoxification of oxidant stress.

Unlabelled: Acetaminophen (APAP) overdose is a classical model of hepatocellular necrosis; however, the involvement of the Fas receptor in the pathophysiology remains controversial. Fas receptor-deficient (lpr) and C57BL/6 mice were treated with APAP to compare the mechanisms of hepatotoxicity. Lpr mice were partially protected against APAP hepatotoxicity as indicated by reduced plasma ALT and GDH levels and liver necrosis.

Mouse strain-dependent caspase activation during acetaminophen hepatotoxicity does not result in apoptosis or modulation of inflammation.

Unlabelled: The mechanisms of acetaminophen (APAP)-mediated hepatic oncotic necrosis have been extensively characterized. However, it was recently demonstrated that fed CD-1 mice have a transient caspase activation which initiates apoptosis. To evaluate these findings in more detail, outbred (Swiss Webster, SW) and inbred (C57BL/6) mice were treated with APAP with or without pan-caspase inhibitor and compared to the apoptosis model of galactosamine (GalN)/endotoxin (ET).

Apoptosis-inducing factor modulates mitochondrial oxidant stress in acetaminophen hepatotoxicity.

Acetaminophen (APAP) overdose causes liver injury in humans and mice. DNA fragmentation is a hallmark of APAP-induced cell death, and nuclear translocation of apoptosis-inducing factor (AIF) correlates with DNA fragmentation after APAP overdose. To test the hypothesis that AIF may be a critical mediator of APAP-induced cell death, fasted male AIF-deficient Harlequin (Hq) mice and respective wild-type (WT) animals were treated with 200 mg/kg APAP.

Role of the Nalp3 inflammasome in acetaminophen-induced sterile inflammation and liver injury.

Acetaminophen (APAP) overdose is the leading cause of acute liver failure in the US and UK. Recent studies implied that APAP-induced injury is partially mediated by interleukin-1β (IL-1β), which can activate and recruit neutrophils, exacerbating injury. Mature IL-1β is formed by caspase-1, dependent on inflammasome activation.

Role of caspase-1 and interleukin-1beta in acetaminophen-induced hepatic inflammation and liver injury.

Acetaminophen (APAP) overdose can result in serious liver injury and potentially death. Toxicity is dependent on metabolism of APAP to a reactive metabolite initiating a cascade of intracellular events resulting in hepatocellular necrosis. This early injury triggers a sterile inflammatory response with formation of cytokines and innate immune cell infiltration in the liver.

Acetaminophen-induced hepatic neutrophil accumulation and inflammatory liver injury in CD18-deficient mice.

Background: Acetaminophen (APAP) hepatotoxicity is currently the most frequent cause of acute liver failure in the US and many European countries. Although intracellular signalling mechanisms are critical for hepatocellular injury, a contribution of inflammatory cells, especially neutrophils, has been suggested. However, conflicting results were obtained when using immunological intervention strategies.