Effects of interrupting the enterohepatic circulation in amatoxin intoxications.

Background: Interruption of the enterohepatic circulation is regarded as an effective way to treat patients with amatoxin poisoning. Nonetheless, its effectiveness has not yet been systematically evaluated. Therefore, we performed a systematic review to investigate the role of enterohepatic circulation on patient outcome and clinical laboratory values.

Unexpected -Induced Hematotoxicity-Results from a Retrospective Study.

Introduction: poisoning is a serious health problem with a mortality rate of 10-40%. Poisonings are characterized by severe liver and kidney toxicity. The effect of poisonings on hematological parameters has not been systematically evaluated thus far.

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.

poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of poisonings. In this study, we investigated the effects of the main toxins of , α- and β-amanitin, on hematopoietic cell viability in vitro.

Amanitin intoxication: effects of therapies on clinical outcomes - a review of 40 years of reported cases.

Background And Aims: poisoning causes severe liver damage which may be potentially fatal. Several treatments are available, but their effectiveness has not been systematically evaluated. We performed a systematic review to investigate the effect of the most commonly used therapies: N-acetylcysteine (NAC), benzylpenicillin (PEN), and silibinin (SIL) on patient outcomes.

Managing intoxications with nicotine-containing e-liquids.

Introduction: Nicotine is an addictive and poisonous agent. The recent development of e-cigarettes has caused a new demand for highly concentrated nicotine-containing solutions. These concentrated nicotine solutions have also increased the risk of nicotine overdoses.

Basement membranes in obstructive pulmonary diseases.

Increased and changed deposition of extracellular matrix proteins is a key feature of airway wall remodeling in obstructive pulmonary diseases, including asthma and chronic obstructive pulmonary disease. Studies have highlighted that the deposition of various basement membrane proteins in the lung tissue is altered and that these changes reflect tissue compartment specificity. Inflammatory responses in both diseases may result in the deregulation of production and degradation of these proteins.

Laminin α4 contributes to airway remodeling and inflammation in asthma.

Airway inflammation and remodeling are characteristic features of asthma, with both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the α2-chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma.

Flucloxacillin Results in Suboptimal Plasma Voriconazole Concentrations.

Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis).

An acute oral intoxication with haloperidol decanoate.

Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy for schizophrenia and mood disorders formulated as an ester for intramuscular injection. Cases of oral haloperidol decanoate intoxications have not been described in literature. In this report, we present for the first time a case of an oral ingestion of haloperidol decanoate of a young woman who presented to the emergency department following an intentional oral ingestion of 1 ampoule of haloperidol decanoate 100mg.

Therapeutic Drug Monitoring of Posaconazole: an Update.

Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and intravenous formulation with improved pharmacokinetic properties have been introduced recently. Due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised to ensure adequate exposure and improve clinical response for posaconazole.

L-thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1.

Hypothyroidism may reduce, whereas hyperthyroidism may aggravate, asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway smooth muscle (ASM) mass, may be involved.

Integrins: therapeutic targets in airway hyperresponsiveness and remodelling?

Integrins are a group of transmembrane heterodimeric proteins that mediate cell-cell and cell-extracellular matrix (ECM) interactions. Integrins have been under intense investigation for their role in inflammation in asthma. Clinical trials investigating integrin antagonists, however, have shown that these compounds are relatively ineffective.

Focal adhesion kinase regulates collagen I-induced airway smooth muscle phenotype switching.

Increased extracellular matrix (ECM) deposition and airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma. Recently, we demonstrated that the ECM protein collagen I, which is increased surrounding asthmatic ASM, induces a proliferative, hypocontractile ASM phenotype. Little is known, however, about the signaling pathways involved.

Cross-talk between transforming growth factor-β₁ and muscarinic M₂ receptors augments airway smooth muscle proliferation.

Transforming growth factor-β₁ (TGF-β₁) is a central mediator in tissue remodeling processes, including fibrosis and airway smooth muscle (ASM) hyperplasia, as observed in asthma. The mechanisms underlying this response, however, remain unclear because TGF-β₁ exerts only weak mitogenic effects on ASM cells. In this study, we hypothesized that the mitogenic effect of TGF-β₁ on ASM is indirect and requires prolonged exposure to allow for extracellular matrix (ECM) deposition.

Distinct PKA and Epac compartmentalization in airway function and plasticity.

Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases characterized by airway obstruction, airway inflammation and airway remodelling. Next to inflammatory cells and airway epithelial cells, airway mesenchymal cells, including airway smooth muscle cells and (myo)fibroblasts, substantially contribute to disease features by the release of inflammatory mediators, smooth muscle contraction, extracellular matrix deposition and structural changes in the airways. Current pharmacological treatment of both diseases intends to target the dynamic features of the endogenous intracellular suppressor cyclic AMP (cAMP).

Phenotype modulation of airway smooth muscle in asthma.

The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory mediators. This plasticity occurs due to intrinsic or acquired abnormalities in ASM cells, and these abnormalities or predisposition of the ASM cell may alter the ASM response and in some cases recapitulate disease hallmarks of asthma.

Functional phenotype of airway myocytes from asthmatic airways.

In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still remains speculative. What is known of an 'asthmatic' ASM cell, is its ability to contribute to the hallmarks of asthma such as bronchoconstriction (contractile phenotype), inflammation (synthetic phenotype) and ASM hyperplasia (proliferative phenotype).

Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target.

Since ancient times, anticholinergics have been used as a bronchodilator therapy for obstructive lung diseases. Targets of these drugs are G-protein-coupled muscarinic M(1), M(2) and M(3) receptors in the airways, which have long been recognized to regulate vagally-induced airway smooth muscle contraction and mucus secretion. However, recent studies have revealed that acetylcholine also exerts pro-inflammatory, pro-proliferative and pro-fibrotic actions in the airways, which may involve muscarinic receptor stimulation on mesenchymal, epithelial and inflammatory cells.

Glucocorticosteroids and β₂-adrenoceptor agonists synergize to inhibit airway smooth muscle remodeling.

Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to increased airway narrowing in asthma. Increased ASM mass may be caused by exposure to mitogens, including platelet-derived growth factor (PDGF) and collagen type I, which induce a proliferative, hypocontractile ASM phenotype. In contrast, prolonged exposure to insulin induces a hypercontractile phenotype.

Functional consequences of human airway smooth muscle phenotype plasticity.

Background And Purpose: Airway smooth muscle (ASM) phenotype plasticity, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to increased ASM mass and airway hyper-responsiveness in asthma. Further, increased expression of collagen I has been observed within the ASM bundle of asthmatics. Previously, we showed that exposure of intact bovine tracheal smooth muscle (BTSM) to collagen I induces a switch from a contractile to a hypocontractile, proliferative phenotype.

Protein kinase A and the exchange protein directly activated by cAMP (Epac) modulate phenotype plasticity in human airway smooth muscle.

Background And Purpose: Platelet-derived growth factor (PDGF) modulates the airway smooth muscle (ASM) 'contractile' phenotype to a more 'proliferative' phenotype, resulting in increased proliferation and reduced contractility. Such phenotypic modulation may contribute to airway remodelling in asthma. We have previously shown that the cAMP effector molecules, protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac) inhibited PDGF-induced phenotypic modulation in bovine ASM.