Neutral rhodol-based dyes expressing localization in mitochondria.

Neutral rhodol-based red emitters are shown to efficiently localize in mitochondria, as demonstrated by confocal microscopy and co-localization studies. A simple model is proposed to explain the localization mechanism of neutral molecules. The model takes into account the strong coupling between the molecular dipole moment and the electric field of the inner mitochondrial membrane.

Redox Regulation of Mitochondrial Potassium Channels Activity.

Redox reactions exert a profound influence on numerous cellular functions with mitochondria playing a central role in orchestrating these processes. This pivotal involvement arises from three primary factors: (1) the synthesis of reactive oxygen species (ROS) by mitochondria, (2) the presence of a substantial array of redox enzymes such as respiratory chain, and (3) the responsiveness of mitochondria to the cellular redox state. Within the inner mitochondrial membrane, a group of potassium channels, including ATP-regulated, large conductance calcium-activated, and voltage-regulated channels, is present.

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs.

We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review. A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events.

Lack of activity of the mitochondrial large-conductance calcium-regulated potassium channels in senescent vascular smooth muscle cells.

A limited number of studies have shown functional changes in mitochondrial ion channels in aging and senescent cells. We have identified, for the first time, mitochondrial large-conductance calcium-regulated potassium channels in human smooth muscle mitochondria. This channel, with a conductance of 273 pS, was regulated by calcium ions and membrane potential.

Predictors of Recovery Following Lumbar Microdiscectomy for Sciatica: A Systematic Review and Meta-Analysis of Observational Studies.

Chronic post-surgical pain is reported by up to 40% of patients after lumbar microdiscectomy for sciatica, a complaint associated with disability and loss of productivity. We conducted a systematic review of observational studies to explore factors associated with persistent leg pain and impairments after microdiscectomy for sciatica. We searched eligible studies in MEDLINE, Embase, and CINAHL that explored, in an adjusted model, predictors of persistent leg pain, physical impairment, or failure to return to work after microdiscectomy for sciatica.

The volume of infusion fluids correlates with treatment outcomes in critically ill trauma patients.

Background: Appropriate fluid management is essential in the treatment of critically ill trauma patients. Both insufficient and excessive fluid volume can be associated with worse outcomes. Intensive fluid resuscitation is a crucial element of early resuscitation in trauma; however, excessive fluid infusion may lead to fluid accumulation and consequent complications such as pulmonary edema, cardiac failure, impaired bowel function, and delayed wound healing.

A sensitive zinc probe operating enhancement of excited-state intramolecular charge transfer.

Novel highly sensitive fluorescent probes for zinc cations based on the diketopyrrolopyrrole scaffold were designed and synthesized. Large bathochromic shifts (≈80 nm) of fluorescence are observed when the Zn-recognition unit (di-(2-picolyl)amine) is bridged with the fluorophore possessing an additional pyridine unit able to participate in the coordination process. This effect originates from the dipolar architecture and the increasing electron-withdrawing properties of the diketopyrrolopyrrole core upon addition of the cation.

Topical clonidine for neuropathic pain in adults.

Background: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist that has been used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs has been gaining interest since the beginning of the century, as it may limit adverse events without loss of analgesic efficacy.

Use of Continuous Veno-Venous Hemodialysis (CVVHD) in Treatment of a Polytrauma Patient with Severe Hemophilia A.

BACKGROUND There are very few reports in the literature worldwide on how to deliver continuous renal replacement therapy (CRRT) to patients with multi-organ trauma and severe hemophilia A. The aim of this case report is to describe successful multidisciplinary, intensive treatment of a patient with multi-organ trauma suffering from severe hemophilia A with the use of continuous veno-venous hemodialysis with regional citrate anticoagulation (Ci-Ca CVVHD). CASE REPORT We report a case of a 47-year-old man with severe hemophilia A, who had multi-organ trauma as a result of a serious traffic accident and was admitted to the Trauma Centre of Emergency and Disaster Medicine in Krakow, Poland in critical condition.

Probing the flux of mitochondrial potassium using an azacrown-diketopyrrolopyrrole based highly sensitive probe.

The diketopyrrolopyrrole bearing an aza-18-crown-6 as a binding unit as well as a PPh group is highly sensitive towards K and localizes selectively in mitochondria of cardiac H9C2 cells. Fast efflux/influx of mitochondrial K can be observed upon stimulation with nigericin.

Alternative Targets for Modulators of Mitochondrial Potassium Channels.

Mitochondrial potassium channels control potassium influx into the mitochondrial matrix and thus regulate mitochondrial membrane potential, volume, respiration, and synthesis of reactive oxygen species (ROS). It has been found that pharmacological activation of mitochondrial potassium channels during ischemia/reperfusion (I/R) injury activates cytoprotective mechanisms resulting in increased cell survival. In cancer cells, the inhibition of these channels leads to increased cell death.

Red emissive sulfone-rhodols as mitochondrial imaging agents.

The controlled hydrolysis of sulfone-rhodamines affords a series of core-modified red-emitting rhodols, the fluorescence of which is sensitive to solvent polarity with pronounced bathochromic shifts recorded in both DMSO and CH3CN combined with an up to 8-fold increase in the fluorescence quantum yield.

Atorvastatin and pravastatin stimulate nitric oxide and reactive oxygen species generation, affect mitochondrial network architecture and elevate nicotinamide N-methyltransferase level in endothelial cells.

Statins belong to the most often prescribed medications, which efficiently normalise hyperlipidaemia and prevent cardiovascular complications in obese and diabetic patients. However, beside expected therapeutic results based on the inhibition of 3-hydroxyl-3-methylglutaryl-CoA reductase, these drugs exert multiple side effects of poorly understood characteristic. In this study, side effects of pravastatin and atorvastatin on EA.

Mitochondrial Potassium Channels as Druggable Targets.

Mitochondrial potassium channels have been described as important factors in cell pro-life and death phenomena. The activation of mitochondrial potassium channels, such as ATP-regulated or calcium-activated large conductance potassium channels, may have cytoprotective effects in cardiac or neuronal tissue. It has also been shown that inhibition of the mitochondrial Kv1.

Perioperative restrictive versus goal-directed fluid therapy for adults undergoing major non-cardiac surgery.

Background: Perioperative fluid management is a crucial element of perioperative care and has been studied extensively recently; however, 'the right amount' remains uncertain. One concept in perioperative fluid handling is goal-directed fluid therapy (GDFT), wherein fluid administration targets various continuously measured haemodynamic variables with the aim of optimizing oxygen delivery. Another recently raised concept is that perioperative restrictive fluid therapy (RFT) may be beneficial and at least as effective as GDFT, with lower cost and less resource utilization.

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited.

Perioperative Immunosuppression and Risk of Cancer Progression: The Impact of Opioids on Pain Management.

Opioids comprise an important group of drugs used in cancer pain pharmacotherapy. In recent years, more and more studies have emerged indicating the potentially immunosuppressive effects of opioid analgesics and their serious consequences, including the risk of cancer progression. The identification of these risks has prompted a search for other effective, and most importantly, safer methods of perioperative analgesic management.

Pharmacotherapy of pain in cancer patients - recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons.

Guidelines for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as "pain", "cancer", "pharmacotherapy", "analgesics", and similar.

cGMP-Elevating Compounds and Ischemic Conditioning Provide Cardioprotection Against Ischemia and Reperfusion Injury via Cardiomyocyte-Specific BK Channels.

Background: The nitric oxide-sensitive guanylyl cyclase/cGMP-dependent protein kinase type I signaling pathway can afford protection against the ischemia/reperfusion injury that occurs during myocardial infarction. Reportedly, voltage and Ca-activated K channels of the BK type are stimulated by cGMP/cGMP-dependent protein kinase type I, and recent ex vivo studies implicated that increased BK activity favors the survival of the myocardium at ischemia/reperfusion. It remains unclear, however, whether the molecular events downstream of cGMP involve BK channels present in cardiomyocytes or in other cardiac cell types.

[What we don't know about mitochondrial potassium channels?].

In the current work the authors present the most interesting, yet not fully understood issues regarding origin, function and pharmacology of the mitochondrial potassium channels. There are eight potassium channels known to contribute to the potassium permeability of the inner mitochondrial membrane: ATP-regulated channel, calcium-regulated channels of large, intermediate and small conductance, voltage-regulated Kv1.3 and Kv7.

Percutaneous techniques versus surgical techniques for tracheostomy.

Background: Tracheostomy formation is one of the most commonly performed surgical procedures in critically ill intensive care participants requiring long-term mechanical ventilation. Both surgical tracheostomies (STs) and percutaneous tracheostomies (PTs) are used in current surgical practice; but until now, the optimal method of performing tracheostomies in critically ill participants remains unclear.

Objectives: We evaluated the effectiveness and safety of percutaneous techniques compared to surgical techniques commonly used for elective tracheostomy in critically ill participants (adults and children) to assess whether there was a difference in complication rates between the procedures.

SERCA, complex I of the respiratory chain and ATP-synthase inhibition are involved in pleiotropic effects of NS1619 on endothelial cells.

A large conductance potassium (BKCa) channel opener, NS1619 (1,3-dihydro-1- [2-hydroxy-5-(trifluoromethyl) phenyl]-5-(trifluoromethyl)-2H-benzimidazole-2-one), is well known for its protective effects against ischemia-reperfusion injury; however, the exact mode of its action remains unclear. The aim of this study was to characterize the effect of NS1619 on endothelial cells. The endothelial cell line EA.

Topical clonidine for neuropathic pain.

Background: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs is currently gaining interest, as it may limit adverse events without loss of analgesic efficacy.