Publications by authors named "Thiermann H"

The highly blistering sulfur mustard analogue agent T (bis(2-chloroethylthioethyl) ether), also known as O-mustard or oxy-mustard, is a common impurity in military grade sulfur mustard (SM) and a component of mixtures such as "HT" that are still found in old munitions. Together with sesquimustard (Q), it is the most important SM analogue and tightly regulated as a Schedule 1 chemical under the Chemical Weapons Convention. We report the adducts of T with nucleophilic Cys and other residues in human serum albumin (HSA) formed in vitro.

View Article and Find Full Text PDF
Article Synopsis
  • Sulfur mustard (SM) is a toxic chemical agent that causes severe skin lesions and impairs wound healing, with no current effective treatments available.
  • Research identified a pathomechanism involving the miRNA miR-497-5p and survivin, which leads to keratinocyte dysfunction after SM exposure.
  • Inhibiting miR-497-5p improved keratinocyte proliferation and differentiation, and using lipid-nanoparticles to deliver the inhibitor promoted skin recovery in human biopsies, suggesting potential therapeutic strategies for SM exposure.
View Article and Find Full Text PDF

Introduction: Scientific societies aim to provide a collective voice and unified stance on important issues. The Clinical Toxicology Recommendations Collaborative was formed in 2016 to develop evidence- and consensus-based recommendations for the management of patients exposed to common and/or serious poisonings for which the management is unclear or controversial.

Organization: The Clinical Toxicology Recommendations Collaborative is led jointly by the American Academy of Clinical Toxicology, the Asia Pacific Association of Medical Toxicology, and the European Association of Poison Centres and Clinical Toxicologists.

View Article and Find Full Text PDF

We herein present for the first time the phosphylated (*) tetrapeptide (TP)-adduct GlyGluSerAla generated from butyrylcholinesterase (BChE) with proteinase K excellently suited for the verification of exposure to toxic organophosphorus nerve agents (OPNA). Verification requires bioanalytical methods mandatory for toxicological and legal reasons. OPNA react with BChE by phosphonylation of the active site serine residue (Ser) forming one of the major target protein adducts for verification.

View Article and Find Full Text PDF

VX is a highly toxic organophosphorus nerve agent that reacts with a variety of endogenous proteins such as serum albumin under formation of adducts that can be targeted by analytical methods for biomedical verification of exposure. Albumin is phosphonylated by the ethyl methylphosphonic acid moiety (EMP) of VX at various tyrosine residues. Additionally, the released leaving group of VX, 2-(diisopropylamino)ethanethiol (DPAET), may react with cysteine residues in diverse proteins.

View Article and Find Full Text PDF

Isolated organ models are a versatile tool for pharmacological and toxicological research. Small bowel has been used to assess the inhibition of smooth muscle contraction by opioids. In the present study, we set out to establish a pharmacologically stimulated rat bowel model.

View Article and Find Full Text PDF

We herein present for the first time a micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (μLC-ESI MS/HR MS) procedure to detect phosphonylated tyrosine (Tyr) and lysine (Lys) residues obtained from human hair exposed to organophosphorus nerve agents (OPNA). In general, toxic OPNA react with endogenous blood proteins causing the formation of adducts representing well-known targets for biomedical analysis to prove exposure. In contrast, no protein-derived biomarker has been introduced so far to document local exposure of hair.

View Article and Find Full Text PDF

An important target in toxicology is the ion channel known as human transient receptor potential ankyrin 1 (hTRPA1). It is triggered by a variety of chemicals, including the alkylating chemical warfare agent sulfur mustard (SM). The activation potentials of structural analogs including O- and sesquimustard, nitrogen mustards (HN1, HN2, and HN3), and related chemotherapeutic drugs (bendamustine, cycylophosphamide, and ifosfamide) were examined in the current study.

View Article and Find Full Text PDF

Motor neurons (MNs) derived from human-induced pluripotent stem cells (hiPSC) hold great potential for the treatment of various motor neurodegenerative diseases as transplantations with a low-risk of rejection are made possible. There are many hiPSC differentiation protocols that pursue to imitate the multistep process of motor neurogenesis . However, these often apply viral vectors, feeder cells, or antibiotics to generate hiPSC and MNs, limiting their translational potential.

View Article and Find Full Text PDF

Organophosphorus compounds (OPCs) are highly toxic compounds that can block acetylcholine esterase (AChE) and thereby indirectly lead to an overstimulation of muscarinic and nicotinic acetylcholine receptors (nAChRs). The current treatment with atropine and AChE reactivators (oximes) is insufficient to prevent toxic effects, such as respiratory paralysis, after poisonings with various OPCs. Thus, alternative treatment options are required to increase treatment efficacy.

View Article and Find Full Text PDF

Transient receptor potential (TRP) channels are important in the sensing of pain and other stimuli. They may be triggered by electrophilic agonists after covalent modification of certain cysteine residues. Sulfur mustard (SM) is a banned chemical warfare agent and its reactivity is also based on an electrophilic intermediate.

View Article and Find Full Text PDF

Chronic wounds, skin blisters, and ulcers are the result of skin exposure to the alkylating agent sulfur mustard (SM). One potential pathomechanism is senescence, which causes permanent growth arrest with a pro-inflammatory environment and may be associated with a chronic wound healing disorder. SM is known to induce chronic senescence in human mesenchymal stem cells which are subsequently unable to fulfill their regenerative function in the wound healing process.

View Article and Find Full Text PDF

In the recent past, the blister agent sulfur mustard (SM) deployed by the terroristic group Islamic State has caused a huge number of civilian and military casualties in armed conflicts in the Middle East. The vaporized or aerolized agent might be inhaled and have direct contact to skin and hair. Reaction products of SM with plasma proteins (adducts) represent well-established systemic targets for the bioanalytical verification of exposure.

View Article and Find Full Text PDF

Sulfur mustard (SM, bis[2-chloroethyl]-sulfide) is a banned chemical warfare agent deployed in the violent conflict in the Middle East poisoning humans and animals. For legal reasons, bioanalytical methods are mandatory proving exposure to SM. Reaction products (adducts) of SM with endogenous proteins, for example, serum albumin (SA), are valuable long-lived targets for analysis.

View Article and Find Full Text PDF

Organophosphorus (OP) nerve agents were used for chemical warfare, assassination, and attempted murder of individuals. Therefore, forensic methods are required to identify known and unknown incorporated OP poisons. Serum is tested for the presence of covalent reaction products (adducts) of the toxicant with, e.

View Article and Find Full Text PDF

In poisoning with organophosphorus compounds (OP), patients can only profit from the regeneration of acetylcholinesterase, when the poison load has dropped below a toxic level. Every measure that allows an increase of synaptic acetylcholinesterase (AChE) activity at the earliest is essential for timely termination of the cholinergic crisis. Only drug-induced reactivation allows fast restoration of the inhibited AChE.

View Article and Find Full Text PDF

The biologically stable and highly toxic organophosphorus nerve agent (OP) VX poses a major health threat. Standard medical therapy, consisting of reactivators and competitive muscarinic receptor antagonists, is insufficient. Recently, two engineered mutants of the Brevundimonas diminuta phosphotriesterase (PTE) with enhanced catalytic efficiency (k/K = 21 to 38 × 10 M min) towards VX and a preferential hydrolysis of the more toxic P(-) enantiomer were described: PTE-C23(R152E)-PAS(100)-10-2-C3(I106A/C59V/C227V/E71K)-PAS(200) (PTE-2), a single-chain bispecific enzyme with a PAS linker and tag having enlarged substrate spectrum, and 10-2-C3(C59V/C227V)-PAS(200) (PTE-3), a stabilized homodimeric enzyme with a double PASylation tag (PAS-tag) to reduce plasma clearance.

View Article and Find Full Text PDF
Article Synopsis
  • OP poisons, like certain nerve agents and pesticides, can seriously harm people by stopping a key enzyme in the body called acetylcholinesterase from working.
  • Scientists use special tests to find markers in blood that show if someone has been exposed to these poisons.
  • The methods for testing these markers have been accepted by an international organization that works to ban chemical weapons, and new ways to improve these tests are being explored.
View Article and Find Full Text PDF

Organophosphorus compound pesticides (OP) are widely used in pest control and might be misused for terrorist attacks. Although acetylcholinesterase (AChE) inhibition is the predominant toxic mechanism, OP may induce pneumonia and formation of lung edema after poisoning and during clinical treatment as life-threatening complication. To investigate the underlying mechanisms, rat precision-cut lung slices (PCLS) were exposed to the OP parathion, malathion and their biotransformation products paraoxon and malaoxon (100-2000 µmol/L).

View Article and Find Full Text PDF

Precision-cut lung slices (PCLS) are used as ex vivo model of the lung to fill the gap between in vitro and in vivo experiments. To allow optimal utilization of PCLS, possibilities to prolong slice viability via cold storage using optimized storage solutions were evaluated. Rat PCLS were cold stored in DMEM/F-12 or two different preservation solutions for up to 28 days at 4°C.

View Article and Find Full Text PDF
Article Synopsis
  • Scientists are studying how a dangerous chemical called sulfur mustard (SM) affects proteins in our body, especially how it attaches to them.
  • A special technique called 2D-thiol-DIGE helps find out if proteins, like transthyretin (TTR), are changed when exposed to SM or a similar chemical (CEES).
  • The research found that a specific part of TTR can be reliably tested to see if someone has been exposed to SM, which may help in medical testing for safety.
View Article and Find Full Text PDF

Creatine kinase (CK) catalyzes the formation of phosphocreatine from adenosine triphosphate (ATP) and creatine. The highly reactive free cysteine residue in the active site of the enzyme (Cys) is considered essential for the enzymatic activity. In previous studies we demonstrated that Cys is targeted by the alkylating chemical warfare agent sulfur mustard (SM) yielding a thioether with a hydroxyethylthioethyl (HETE)-moiety.

View Article and Find Full Text PDF
Article Synopsis
  • - Poisoning from Nerium oleander and Thevetia peruviana is prevalent in Southeast Asia due to their toxic cardiac glycosides, which can inhibit Na/K-ATPase and potentially lead to deadly heart arrhythmias.
  • - The study utilized hiPSC-derived cardiomyocytes and a microelectrode array to evaluate the cardiac effects of various compounds from oleander, revealing that all compounds reduced field potential duration and caused beat arrest at certain concentrations.
  • - The tested substances were ranked for their cardiac effects, with neriifolin being the most potent, followed by oleandrin, digitoxigenin, and peruvoside, while thevetin A had no arrhythmic effects up to 100
View Article and Find Full Text PDF

Sulfur mustard (SM) is a banned chemical warfare agent recently used in the Syrian Arab Republic conflict causing erythema and blisters characterized by complicated and delayed wound healing. For medical and legal reasons, the proof of exposure to SM is of high toxicological and forensic relevance. SM reacts with endogenous human serum albumin (HSA adducts) alkylating the thiol group of the cysteine residue C, thus causing the addition of the hydroxyethylthioethyl (HETE) moiety.

View Article and Find Full Text PDF

In analogy to the fluoride-induced regeneration of butyrylcholinesterase (BChE) inhibited by nerve agents a method was developed and optimized for whole blood samples. Compared to the plasma method, regeneration grade was found to be higher for cyclosarin (GF), i-butylsarin from VR, and n-butylsarin from CVX, but lower for sarin (GB), fluorotabun from tabun (GA), and ethylsarin from VX. Regeneration grade of soman (GD) is the same for both matrices because it is released from serum albumin and not from cholinesterases.

View Article and Find Full Text PDF