The TRPA1 Mediated Effects of Hydrogen Sulfide and Polysulfide Compounds on Animal Models of Acute And Chronic Inflammation

Amióta ismert, hogy a H2S endogén úton is termelődik a szervezetünkben és gazotranszmitterként funkcionál, élénk kutatások folynak biológiai hatásainak feltérképezésére. Azonban hamar kiderült, hogy a H2S komplex szerepet játszik a redox rendszerekben és számos további mediátor keletkezhet belőle. Jelenleg egy olyan látszólag egyszerű kérdés, mint a hidrogén-szulfid pontos kvantitatív meghatározása a biológiai rendszerekben is heves vitákat tud kelteni tudományos körökben. Kísérleteink során három különböző hidrogén-szulfid donor vegyület hatásait kívántuk vizsgálni két különböző jellegű, egy akut- és egy krónikus gyulladásos modellt alkalmazva

Effects of sulfide and polysulfides transmitted by direct or signal transduction-mediated activation of TRPA1 channels

Hydrogen sulfide (H2 S) is a gaseous mediator in various physiological and pathological processes, including neuro-immune-modulation, metabolic pathways, cardiovascular system, tumour growth, inflammation and pain etc. Nowadays hydrogen polysulfides (H2 Sn ) have turned up as signalling molecules modulating ion channels, transcription factors and protein kinases. Transient Receptor Potential (TRP) cation channels can be activated by mechanical, thermal or chemical triggers. Here, we review the current literature regarding biological actions of sulfide and polysulfide compounds mediated by TRP-s with special emphasis on the role of TRPA1. Notwithstanding, TRPA1 is a best-known ion channel in nociceptors. Considering its regulatory role, it should not be forgotten about the function of non-neuronal receptors. Although, previous papers have particularly demonstrated sulfide and polysulfide effects in different pathological circumstances and TRPA1-mediated processes have also been investigated intensively, our review attempts to present the first comprehensive overview about potential cross-talk between TRPA1 and sulfide-activated signalling pathways

The fluorescent dye 3,3′-diethylthiatricarbocyanine iodide is unsuitable for in vivo imaging of myelination in the mouse

There is a growing interest to use non-invasive optical imaging methods to study central nervous system diseases. The application of a myelin-binding fluorescent dye, 3,3-diethylthiatricarbocyanine iodide (DBT) was recently described for in vivo optical imaging of demyelination in the mouse. In the present study we aimed at adapting the method to our optical imaging systems, the IVIS Lumina II to measure epifluorescence and the fluorescent molecular tomograph (FMT) for 3-dimensional quantification of the fluorophore. Epifluorescent imaging was performed 5−30 min after DBT injection which was followed by FMT imaging at 40 min. Two mice also underwent micro-CT imaging in the FMT cassette for the purpose of FMT-CT co-registration. Ex vivo imaging of the brain and other tissues of the head and neck was carried out 1 h after injection. Both the FMT-CT co-registration and the ex vivo imaging of organs proved that DBT poorly crossed the blood-brain barrier. The dye did not accumulate in the myelin sheath of the sciatic nerve. In contrast, there was an intense accumulation in the pituitary and salivary glands. The FMT-CT co-registration unequivocally demonstrated that the signal localized to the head did not originate from beyond the blood-brain barrier. No myelin binding was demonstrated by the ex vivo imaging either. In conclusion, DBT is unsuitable for in vivo imaging of myelination due to its poor BBB penetration, accumulation in other structures of the head and neck region and lack of selective binding towards myelin in vivo

The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis

Various organosulfur compounds, such as dimethyl trisulfide (DMTS), display anti-inflammatory properties. We aimed to examine the effects of DMTS on acute pancreatitis (AP) and its mechanism of action in both in vivo and in vitro studies. AP was induced in FVB/n mice or Wistar rats by caerulein, ethanol-palmitoleic acid, or L-ornithine-HCl. DMTS treatments were administered subcutaneously. AP severity was assessed by pancreatic histological scoring, pancreatic water content, and myeloperoxidase activity measurements. The behaviour of animals was followed. Pancreatic heat shock protein 72 (HSP72) expression, sulfide, and protein persulfidation were measured. In vitro acinar viability, intracellular Ca 2+ concentration, and reactive oxygen species production were determined. DMTS dose-dependently decreased the severity of AP. It declined the pancreatic infiltration of leukocytes and cellular damage in mice. DMTS upregulated the HSP72 expression during AP and elevated serum sulfide and low molecular weight persulfide levels. DMTS exhibited cytoprotection against hydrogen peroxide and AP-inducing agents. It has antioxidant properties and modulates physiological but not pathophysiological Ca 2+ signalling. Generally, DMTS ameliorated AP severity and protected pancreatic acinar cells. Our findings indicate that DMTS is a sulfur donor with anti-inflammatory and antioxidant effects, and organosulfur compounds require further investigation into this potentially lethal disease

Amiodarone that has antibacterial effect against human pathogens may represent a novel catheter lock

Infection is one of the most feared hospital-acquired complications. Infusion therapy is frequently administered through a central line. Infusions facilitating bacterial growth may be a source of central line-associated bloodstream infections. On the other hand, medications that kill bacteria may protect against this kind of infection and may be used as a catheter lock.In this study, we examined the impact of amiodarone on bacterial growth. Amiodarone is used for controlling cardiac arrhythmias and can be administered as an infusion for weeks. Standard microbiological methods have been used to study the growth of laboratory strains and clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and multidrug-resistant Acinetobacter baumannii in amiodarone. The minimum inhibitory concentration (MIC) of amiodarone was determined. Bacterial growth from in use amiodarone syringes and giving sets was also investigated.Most examined strains were killed within 1 min in amiodarone. The other strains were killed within 1 h. The MICs of amiodarone were <0.5-32 μg/mL.Amiodarone infusion is unlikely to be responsible for bloodstream infections as contaminating bacteria are killed within 1 h. Amiodarone may also protect against central line infections if used as a catheter lock

Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

Transient receptor potential ankyrin 1 (TRPA1) non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs) are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM) liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS). In the frame of the present study, we set out to compare the participation of this mechanism in antinociceptive and anti-inflammatory effects of inorganic sodium POLY and DMTS in carrageenan-evoked hind-paw inflammation. Inflammation of murine hind paws was induced by intraplantar injection of carrageenan (3% in 30 µL saline). Animals were treated intraperitoneally with POLY (17 µmol/kg) or DMTS (250 µmol/kg) or their respective vehicles 30 min prior paw challenge and six times afterward every 60 min. Mechanical pain threshold and swelling of the paws were measured by dynamic plantar aesthesiometry and plethysmometry at 2, 4, and 6 h after initiation of inflammation. Myeloperoxidase (MPO) activity in the hind paws were detected 6 h after challenge by luminescent imaging. Mice genetically lacking TRPA1 ion channels, sst4 receptors and their wild-type counterparts were used to examine the participation of these proteins in POLY and DMTS effects. POLY counteracted carrageenan-evoked mechanical hyperalgesia in a TRPA1 and sst4 receptor-dependent manner. POLY did not influence paw swelling and MPO activity. DMTS ameliorated all examined inflammatory parameters. Mitigation of mechanical hyperalgesia and paw swelling by DMTS were mediated through sst4 receptors. These effects were present in TRPA1 knockout animals, too. DMTS inhibited MPO activity with no participation of the sensory neuron–SOM axis. While antinociceptive effects of POLY are transmitted by activation of peptidergic nerves via TRPA1, release of SOM and its effect on sst4 receptors, those of DMTS partially rely on SOM release triggered by other routes. SOM is responsible for the inhibition of paw swelling by DMTS, but TRPA1 does not contribute to its release. Modulation of MPO activity by DMTS is independent of TRPA1 and sst4

Helyi érzéstelenítők antibakteriális hatása = Antibacterial effect of local anaesthetics

Összefoglaló. Gyógyszereink egy részének jelentős, az eredeti alkalmazástól eltérő hatása is van. Ezek felismerése fontos, hogy elkerüljük a nem várt mellékhatásokat, vagy kihasználjuk ezeket a kedvező adottságokat. A helyi érzéstelenítők antibakteriális hatása 1909 óta ismert, de ennek több évtizeden keresztül nem tulajdonítottak jelentőséget. Az 1960-as években figyeltek fel először az álnegatív mikrobiológiai eredmények lehetőségére, helyi érzéstelenítőket használva a mintavételhez. Tanulmányok igazolták, hogy a bronchoszkópiás, seb-, bőr- vagy fül-, orr-, gégészeti bakteriológiai eredmények is érintve lehetnek. A ma is használt gyógyszerek közül a 0,5%-os bupivakainnak és a 2%-os lidokainnak van jelentős antibakteriális hatása Gram-pozitív és Gram-negatív baktériumokkal szemben, ami kifejezettebb 37 °C-on, mint szobahőmérsékleten. A legerősebb antibakteriális hatást a 0,5%-os bupivakain mutatta. A napi gyakorlatban alkalmazott koncentrációjuk magasabb, mint a különböző klinikai izolátumokkal szemben meghatározott minimális gátló koncentráció. Fenti tulajdonságaik alapján felmerült szerepük a kórházi sebfertőzések csökkentésében is. A hatásmechanizmus több pontja ismert, károsítják a sejthártya integritását, és több bakteriális enzim működését gátolják. Orv Hetil. 2021; 162(5): 171-176. Summary. Medications may have important impacts other than the original effect. It is important to know about these to avoid side effects or use these beneficial capabilities. The antibacterial effect of local anaesthetics has been known since 1909. For decades, no attention has been payed to this fact. In the 1960s, the high number of negative microbiological results when local anaesthetics were used before sampling drew attention to the possible antibacterial effect. Studies suggested that cultures from bronchoscopy, wound, skin or nasal samples may be affected. Bupivacaine 0,5% and lidocaine 2% have the most noticeable effect against both Gram-positive and Gram-negative bacteria. This impact is more pronounced at 37 °C than at room temperature. Bupivacaine 0,5% has the most pronounced effect. The concentration of local anaesthetics in daily routine is higher than the minimal inhibitory concentration against various clinical isolates. In the view of these results, they may contribute to reduce surgical site infections. There are known details regarding the mechanism of action. Local anaesthetics have target sites on cellular membrane and inhibit bacterial enzymes. Orv Hetil. 2021; 162(5): 171-176

Occurrence of hlyA and sheA Genes in Extraintestinal Escherichia coli Strains

The association of a hemolytic phenotype with the carriage of the α-hemolysin gene (hlyA) and/or the silent hemolysin gene (sheA or clyA) among 540 extraintestinal clinical isolates of Escherichia coli and 110 fecal isolates from healthy individuals was investigated. Though HlyA is an important virulence factor in extraintestinal E. coli infection, the role of SheA is not completely clarified. Two hemolytic sheA(+) E. coli strains that lacked hlyA and possessed no other hemolysin genes were identified. No hlyA(+) sheA(+) strains were identified, suggesting that there is possible incompatibility between hlyA and sheA in the chromosome of E. coli