Potassium ATP Research Articles

Clinical and molecular characteristics of infantile-onset diabetes mellitus in Egypt.

Purpose In patients diagnosed with diabetes mellitus (DM) before the age of 12 months, there is an increasing recognition of diabetes caused by single-gene mutations, also known as monogenic diabetes of infancy or neonatal DM (NDM). This study aimed to classify patients at Alexandria University Children’s Hospital (AUCH) diagnosed with infantile-onset DM into type 1 DM (T1DM) or NDM and to detect differences in molecular characteristics of NDM patients at our center in comparison to other countries.Methods This retrospective/prospective observational study was conducted on 39 patients diagnosed with infantile-onset DM (age of onset ≤1 year) at AUCH from January 2003 to November 2020. The patients were divided into 2 groups according to age at the onset of DM: ≤6 months and >6–12 months. Molecular testing was done in patients diagnosed with DM at ≤6 months and those with negative autoantibodies.Results Twelve patients were diagnosed with DM at age ≤6 months and 27 patients were diagnosed between 6–12 months. Seventeen patients (43.6%) had T1DM, whereas 9 patients (23.1%) had genetically confirmed NDM, including 3 harboring novel mutations. The most common genetic causes of NDM were EIF2AK3 mutations (n=3), followed by KCNJ11 (n=2) and ABCC8 (n=2). Other mutations included SLC19A2 (n=1) and INS (n=1). Three patients with potassium ATP channel mutations were transferred from insulin to sulfonylurea treatment.Conclusions It is essential to identify patients with NDM clinically and confirm the diagnosis by molecular testing to distinguish them from T1DM as it helps in refining their management, predicting prognosis, and guiding genetic counseling.

Antibacterial mechanism of apple phloretin on physiological and morphological properties of Listeria monocytogenes

Green bactericides are excellent strategies for reducing food spoilage. Phloretin was regarded as efficient, broad-spectrum and safe preservative, which showed enormous potential in food industry. Inhibitory mechanism of phloretin on Listeria monocytogenes was systematically elucidated through integrity of cell membrane, intracellular protein content, energy level, and nucleic acid morphological character. SEM and TEM results showed minimal injury of cell membrane, which was further proved by a leakage of potassium ions, ATP and little protein and nucleic acid. There were drastic reduction of intracellular or total protein and ATP compared to cell without phloretin treatment. However, the specific activity of hexokinase and isocitrate dehydrogenase were unaffected after phloretin treatment. From these results, we concluded that phloretin’s bacteriostatic mechanism is decreasing the intracellular protein content and energy level resulting from DNA aggregation. This finding was prospective to fully illustrate the phloretin’s mechanism and develop it into a natural preservative in food industry.

Antibacterial Mode of Action of the Daucus carota Essential Oil Active Compounds against Campylobacter jejuni and Efflux-Mediated Drug Resistance in Gram-Negative Bacteria.

Today, an alarming rise of bacterial gastroenteritis in humans resulting from consuming Campylobacter-tainted foods is being observed. One of the solutions for mitigating this issue may be the antibacterial activity of essential oils. In the present research, we propose to study the antibacterial activity against Campylobacter and other Gram-negative bacteria of Daucus carota essential oil and its active molecules. In addition, a few chemically synthesized molecules such as (E)-methylisoeugenol, Elemicin, and eugenol were also studied. The results showed that the essential oil itself and its most active component, (E)-methylisoeugenol, exhibited bactericidal effects. Similar effects were detected using purified and chemically synthesized molecules. Also, it was observed that the Daucus carota essential oil and its active molecules affected intracellular potassium and intracellular ATP contents in Campylobacter cells. Inhibition of the membrane bound FOF1-ATPase was also observed. Eventually, for the first time, the efflux mechanism of active molecules of Daucus carota essential oil was also identified in gamma proteobacteria and its specific antibacterial activity against Campylobacter jejuni was associated with the lack of this efflux mechanism in this species.

The mitochondrial K-ATP channel opener diazoxide upregulates STIM1 and Orai1 via ROS and the MAPK pathway in adult rat cardiomyocytes

BackgroundOpeners of mitochondrial adenosine triphosphate-dependent potassium (mKATP) channels like diazoxide increase reactive oxygen species (ROS) production in cardiac cells and reduce Ca2+ elevations produced by ischemia–reperfusion, protecting the heart from damage. In this study we tested the hypothesis that opening mKATP channels regulates expression of the major components of store-operated Ca2+ entry (SOCE) STIM1 and Orai1.ResultsQuantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot experiments showed that diazoxide increased expression of STIM1 and Orai1 at the mRNA and protein levels, respectively, in adult rat cardiomyocytes. Immunofluorescence analyses revealed that diazoxide also disrupted the striated distribution pattern of STIM1. These effects were prevented by the ROS scavenger N-acetyl cysteine (NAC), the mKATP channel antagonist 5-hydroxydecanoate (5-HD), or the protein synthesis inhibitor cycloheximide (CHX). Confocal microscopy revealed that diazoxide also led to nuclear translocation of the transcription factors c-Fos and NFκB, which was also blocked by NAC or 5-HD. Finally, the MAPK pathway inhibitor UO126 attenuated diazoxide-induced upregulation of STIM1 and Orai1 expression.ConclusionsOur results suggest that opening mitochondrial potassium ATP channels with diazoxide upregulates the expression of STIM1 and Orai1 by de novo synthesis by a mechanism that involves NFkB, c-Fos, and ROS via MAPK/ERK signaling.

Elucidation of the possible mechanism of analgesic action of methanol stem bark extract of Uapaca togoensis pax in mice

Ethnopharmacological relevanceUapaca togoensis is a medicinal plant used traditionally in Africa for the treatment of rheumatism, epilepsy, cough, pneumonia, vomitting and fever. Previously, the analgesic activity of its methanol stem bark extract has been scientifically demonstrated. However, the mechanism responsible for this activity remains to be investigated. Aim of the studyTo elucidate the possible mechanism(s) through which the methanol stem bark extract of Uapaca togoensis (MEUT) exhibits analgesic activity in mice. Materials and methodsAnalgesic activity of MEUT was evaluated using acetic acid-induced abdominal writhing test in mice at doses of 250, 500 and 1000 mg/kg orally. For the mechanistic studies, mice were pre-treated with Naloxone (2 mg/kg), Atropine (1 mg/kg), Yohimbine (1 mg/kg), Glibenclamide (10 mg/kg), Prazosin (1 mg/kg) and Yohimbine (1 mg/kg) 15 min prior to MEUT (1000 mg/kg) administration, then assessed using AAWT 1 h later. Data was analysed using One way Anova followed by Bonferroni post hoc test. ResultsThe extract (at the doses of 250, 500 and 1000 mg/kg) and morphine (10 mg/kg) significantly (p < 0.05) decreased the number of abdominal writhes. Naloxone (opioid receptor antagonist), Atropine (muscarinic receptor antagonist) and Glibenclamide (ATP-sensitive K+ channel blocker) significantly (p < 0.05) reversed the analgesic effect of MEUT. On the other hand, Prazosin and Yohimbine (α1 and α2 receptor antagonists respectively) had no effect on the analgesic action of MEUT. ConclusionThe results obtained from this study suggests the possible involvement of opioidergic, cholinergic and sensitive potassium ATP channel pathways in the analgesic activity of the methanol stem bark extract of Uapaca togoensis.

Central venous catheter-associated thrombosis in children with congenital hyperinsulinism

SummaryCongenital hyperinsulinism (CHI) is an important cause of severe hypoglycaemia in infancy. To correct hypoglycaemia, high concentrations of dextrose are often required through a central venous catheter (CVC) with consequent risk of thrombosis. We describe a series of six cases of CHI due to varying aetiologies from our centre requiring CVC for the management of hypoglycaemia, who developed thrombosis in association with CVC. We subsequently analysed the incidence and risk factors for CVC-associated thrombosis, as well as the outcomes of enoxaparin prophylaxis. The six cases occurred over a 3-year period; we identified an additional 27 patients with CHI who required CVC insertion during this period (n = 33 total), and a separate cohort of patients with CHI and CVC who received enoxaparin prophylaxis (n = 7). The incidence of CVC-associated thrombosis was 18% (6/33) over the 3 years, a rate of 4.2 thromboses/1000 CVC days. There was no difference in the frequency of genetic mutations or focal CHI in those that developed thromboses. However, compound heterozygous/homozygous potassium ATP channel mutations correlated with thrombosis (R2 = 0.40, P = 0.001). No difference was observed in CVC duration, high concentration dextrose or glucagon infused through the CVC. In patients receiving enoxaparin prophylaxis, none developed thrombosis or bleeding complications. The characteristics of these patients did not differ significantly from those with thrombosis not on prophylaxis. We therefore conclude that CVC-associated thrombosis can occur in a significant proportion (18%) of patients with CHI, particularly in severe CHI, for which anticoagulant prophylaxis may be indicated.Learning points:CVC insertion is one of the most significant risk factors for thrombosis in the paediatric population.Risk factors for CVC-associated thrombosis include increased duration of CVC placement, malpositioning and infusion of blood products.To our knowledge, this is the first study to evaluate CVC-associated thrombosis in patients with congenital hyperinsulinism (CHI).The incidence of CVC-associated thrombosis development is significant (18%) in CHI patients and higher compared to other neonates with CVC. CHI severity may be a risk factor for thrombosis development.Although effective prophylaxis for CVC-associated thrombosis in infancy is yet to be established, our preliminary experience suggests the safety and efficacy of enoxoaparin prophylaxis in this population and requires on-going evaluation.

Effect of sulfonylureas on attenuation of electrocardiographic ST- segment elevation during an acute myocardial infarction in diabetics

Background: Sulfonylureas are primarily used in the treatment of diabetes mellitus act by inhibiting ATP sensitive potassium ATP (K-ATP) channels. Similar channels are also present are also present in heart venticular muscle. Previous studies reveal that these drugs are able to reduce the electrocardiographic ST- segment elevation changes during an acute myocardial infarction. Hence, the present study was designed to evaluate the attenuating effect of sulfonylureas on ST- segment elevation in diabetic patients presenting with acute myocardial infarction.Methods: This cross sectional study included 73 diabetic patients presenting with the signs and symptoms of acute myocardial infarction of less than 24 hours duration along with CPK levels of more than 25 IU/L. Of them 5 were excluded from the study. The remaining 68 patients were included in the study, out of which 36 patients were in the study group (sulfonylurea group), and 32 patients were in the control group (non-sulfonylurea group).Results: No statistically significant difference was seen in the demographic parameters like age, sex, duration of diabetes mellitus and CPK levels (p&gt;0.05). Among 68 patients 38 patients were diagnosed as STEMI. The mean magnitude of ST-elevation in the study group (n=16) was 2.3±0.12 and in control group (n=22) patients it was 3.7±0.33. The percentage of NSTEMI was significantly higher in study group compared to control. Statistically significant difference (p&lt;0.05) was seen only between CPK level of range 25 and 100IU/L and mean magnitude of ST-segment elevation in STEMI patients. Significant difference in the mean magnitude of ST-segment elevation was observed in case of females among the study and control groups (p&lt;0.05).Conclusions: Sulfonylureas drugs play a significant role in attenuation of ST-segment in diabetic patients presenting with acute myocardial infarction. Further, large multicentric studies are required to confirm the exact correlation between sulfonylureas and ST-segment.

Molecular phylogeny of Pasiphaeidae (Crustacea, Decapoda, Caridea) reveals systematic incongruence of the current classification

Caridean shrimps constitute one of the most diverse groups of decapod crustaceans, notwithstanding their poorly resolved infraordinal relationships. One of the systematically controversial families in Caridea is the predominantly pelagic Pasiphaeidae, comprises 101 species in seven genera. Pasiphaeidae species exhibit high morphological disparity, as well as ecological niche width, inhabiting shallow to very deep waters (>4000m). The present work presents the first molecular phylogeny of the family, based on a combined dataset of six mitochondrial and nuclear gene markers (12S rDNA, 16S rDNA, histone 3, sodium–potassium ATPase α-subunit, enolase and ATP synthase β-subunit) from 33 species belonged to six genera of Pasiphaeidae with 19 species from 12 other caridean families as outgroup taxa. Maximum likelihood and Bayesian inference analyses conducted on the concatenated dataset of 2265bp suggest the family Pasiphaeidae is not monophyletic, with Psathyrocaris more closely related to other carideans than to the other five pasiphaeid genera included in this analysis. Leptochela occupies a sister position to the remaining genera and is genetically quite distant from them. At the generic level, the analysis supports the monophyly of Pasiphaea, Leptochela and Psathyrocaris, while Eupasiphae is shown to be paraphyletic, closely related to Parapasiphae and Glyphus. The present molecular result strongly implies that certain morphological characters used in the present systematic delineation within Pasiphaeidae may not be synapomorphies and the classification within the family needs to be urgently revised.

Neonatal Diabetes: Case Report of a 9-Week-Old Presenting Diabetic Ketoacidosis Due to an Activating ABCC8 Gene Mutation.

Context: Neonatal diabetes mellitus, a rare condition occurring in approximately 1 in 500 000 live births, is defined as insulin-requiring hyperglycemia presenting in the first months of life. Neonatal diabetes can be transient or permanent, with studies characterizing the condition as a monogenic disorder. Case Report: We describe a case of a 9-week-old infant with neonatal diabetes who presented in diabetic ketoacidosis due to a mutation affecting the ABCC8 gene that encodes the SUR1 subunit of the potassium ATP channel. Conclusion: This genetic diagnosis has therapeutic implications regarding the initiation of sulfonylurea administration as 85% of patients with neonatal diabetes due to ABCC8 gene mutations can be successfully treated with oral sulfonylurea treatment.

Altered potassium ATP channel signaling in mesenteric arteries of old high salt-fed rats.

[Purpose]Both aging and the consumption of a high salt diet are associated with clear changes in the vascular system that can lead to the development of cardiovascular disease; however the mechanisms are not clearly understood. Therefore, we examined whether aging and the consumption of excess salt alters the function of potassium ATP-dependent channel signaling in mesenteric arteries[Methods]Young (7 months) and old (29 months) Fischer 344 x Brown Norway rats were fed a control or a high salt diet (8% NaCl) for 12 days and mesenteric arteries were utilized for vascular reactivity measurements.[Results]Acetylcholine-induced endothelium relaxation was significantly reduced in old arteries (81 ± 4%) when compared with young arteries (92 ± 2%). Pretreatment with the potassium-ATP channel blocker glibenclamide reduced relaxation to acetylcholine in young arteries but did not alter dilation in old arteries. On a high salt diet, endothelium dilation to acetylcholine was significantly reduced in old salt arteries (60 ± 3%) when compared with old control arteries (81 ± 4%). Glibenclamide reduced acetylcholine-induced dilation in young salt arteries but had no effect on old salt arteries. Dilation to cromakalim, a potassium-ATP channel opener, was reduced in old salt arteries when compared with old control arteries.[Conclusion]These findings demonstrate that aging impairs endothelium-dependent relaxation in mesenteric arteries. Furthermore, a high salt diet alters the function of potassium-ATP-dependent channel signaling in old isolated mesenteric arteries and affects the mediation of relaxation stimuli.

Abstract 287: 5-Hydroxydecanoate, a Mitochondrial Selective KATP Antagonist, Blocks the Rescue Action of Lipid Emulsion in Bupivacaine-Induced Cardiotoxicity

Introduction: Lipid emulsion (intralipid) rescues Bupivacaine-induced cardiac toxicity. We have shown previously that glibenclamide, a non selective ATP potassium channel blocker abolishes the rescue action of intralipid. Here we explored the role of 5-Hydroxydecanoate (5-HD), a mitochondrial selective KATP antagonist in the intralipid-mediated rescue of bupivacaine overdose. Methods: Young male Sprague-Dawley rats (300-350 g) were anesthetized intraperitoneally with a mixture of ketamine (80 mg/kg) and xylazine (8 mg/kg), and ventilated with a ventilator. M-mode echocardiography were acquired throughout the experiment. In protocol-1 (n=5), asystole was induced by a single injection of bupivacaine (10mg/kg over 20 seconds, intravenously) and resuscitation with Intralipid 20% (5ml/kg bolus, and 0.5ml/kg/min maintenance) with chest compression was started immediately. In protocol-2 (n=8) rats were pre-treated with 5-HD (5 mg/kg, IV) 30 minutes prior to inducing asystole with bupivacaine. In both protocols the heart rate (HR), ejection fraction (EF) and fractional shortening (FS) were measured before inducing asystole (baseline), and at 1, 5 and 10 min after lipid treatment. A two way repeated measure analysis of variance (ANOVA) model was used for comparison of means. Values are mean ± SEM, n=5 rats/group, p&lt;0.05 significant. Results: In protocol-1, the baseline HR and EF were 321±21 and 72.3±4.6%. Bupivacaine resulted in asystole and intralipid therapy improved the heart rate and cardiac function within 10 min(HR=86±13beats/min at 1min, 216±10beats/min at 5 min, and 228±14beats/min at 10 min). The left ventricular systolic function fully recovered in all rats within 5 min of intralipid treatment (EF=72±5%, FS=42±4%). In protocol-2, there were no significant differences between HR and EF before (HR=324.6±16.5 beats/min, EF=78.0±2.8%) and 30 min after (HR=340.9±15.6 beats/min, EF=83.3±2.0%) 5-HD adminstration. However, 5-HD (5mg/kg), prevented the intralipid-induced rescue of bupivacaine overdose, as there was no recovery within 10 min of intralipid therapy. Conclusions: Pre-treatment with 5-HD prevents the lipid rescue of bupivacaine-induced cardiotoxicity suggesting that mitochondrial KATP channels are involved.

Protective Effects of Anesthetics on the Spinal Cord

Since several clinical data have suggested that the incidence of neurological deficit after aortic surgery has not changed appreciably over the last 50 years, anesthesiologists as well as vascular surgeons have attempted to resolve this clinically important issue by employing various strategies to prevent ischemic spinal cord injury. With respect to inhalational anesthetics, it is thought that isoflurane as well as sevoflurane preconditioning might provide neuroprotective effects against spinal ischemia via activation of TWIK-related K channels-1 or the potassium ATP channel. Glutamate receptor antagonists, including ketamine, could also potentially provide some neuroprotection against spinal ischemia. However, it seems likely that decreased glutamate release could produce more neuroprotective effects against spinal ischemia than a blockade of the glutamate receptor. Although barbiturate alone failed to protect the spinal cord, a controversial issue has been the possible neuroprotective effects associated with local anesthetics including tetracaine, lidocaine and bupivacaine. Clinical cases and experimental studies have indicated that neuraxial opioids might be capable of exacerbating neurological deficits even after a non-injurious interval of spinal ischemia. Inhaled nitric oxide (iNO) therapy (40-80ppm), a common treatment for pulmonary hypertension, has been reported to prevent ischemic brain injury in animal studies by selective dilation of collateral arterioles. The vasodilating effects of iNO on the central nervous system might enhance the "collateral network" in the spinal cord during aortic cross-clamp, potentially protecting the spinal cord. In conclusion, some anesthetics, especially inhalational anesthetics, may provide neuroprotective effects against spinal cord ischemia, but administration of neuraxial opioid after spinal cord ischemia might exacerbate neurological dysfunction.

Permanent neonatal diabetes mellitus due to an ABCC8 mutation: a case report.

Neonatal diabetes is a rare disorder with an incidence of about 1 in 100,000 live births. It is defined as diabetes diagnosed in the first 6 months of life and it is vital to differentiate this entity from type 1 diabetes to enable accurate diagnosis, prognosis, genetic counseling and treatment. We describe a case of permanent neonatal diabetes mellitus due to a novel mutation affecting the ABCC8 gene that encodes the SUR1 subunit of potassium ATP channel (KATP). This genetic diagnosis has therapeutic implications as patients can switch from insulin therapy to sulphonylurea, as described in this case report.

Serial assessment of biochemical changes in irradiated red blood cells

Transfusion associated graft vs host disease (TA-GVHD) is delayed effect of blood component therapy with a very high mortality rate. The use of irradiated blood components is the only proven method to prevent TA-GVHD in susceptible patients. Our study was designed to analyze the quality of irradiated PRBCs in terms of their biochemical parameters during a storage period up to 28 days post irradiation. A total of 80 PRBC units were analyzed, 40 units each stored in CPDA-1 and additive solution-SAGM. The units were evaluated serially for the following biochemical parameters, plasma/ supernatant potassium, sodium, pH, glucose, lactate, plasma/supernatant hemoglobin and red cell ATP. We further evaluated the differences in these parameters between units irradiated on day 1 and day 7 of storage and stored these units up to 28 days and 35 days respectively. Ten units in each group were used as control. The assessment was done at weekly intervals from the day of irradiation. Within each group of red cells, there was a rise in mean concentration of plasma potassium (K(+)) from day 1 to last day of storage. There was a highly significant difference (P<0.01) between irradiated and control units after first week of storage in both types of PRBCs. Irradiated CPDA-1 PRBC had significantly higher (K(+)) than irradiated SAGM PRBC. Intergroup comparison revealed significantly higher (P<0.05) mean hemoglobin in irradiated CPDA-1 PRBC as compared to SAGM PRBC. The mean pH was significantly higher (P<0.05) in irradiated CPDA-1 PRBC as compared to irradiated SAGM PRBC only on day 7 of storage. ATP levels significantly decreased in irradiated units as compared to control units. SAGM PRBCs had significantly higher (P<0.05) mean ATP concentration than CPDA-1PRBCs. Our study demonstrates that SAGM-PRBCs show better stability after irradiation compared to CPDA-1 PRBCs. The limits of safety for CPDA-1 PRBCs appear to be two weeks after irradiation. SAGM-PRBCs on the other hand show acceptable limits of safety up to three weeks of irradiation. The shelf life of irradiated PRBCs may vary depending upon the storage solution and day of irradiation.

Molecular mechanisms of ischemic preconditioning and postconditioning as putative therapeutic targets to reduce tumor survival and malignancy

In tumors intermittent hypoxia has been reported to be more representative than normoxia or continuous exposure to low oxygen concentrations. Intermittent hypoxia is thought to increase tumor resistance against both anti-cancer therapy and the sustained ischemia that randomly occurs because of the dynamic nature of tumor vasculature. Here, we hypothesize that the molecular mechanisms underlying intermittent hypoxia in tumor cells share some triggers, modulators, and end-effectors of the intermittent episodes of ischemia and reperfusion that characterize ischemic preconditioning and postconditioning. These are among the most effective maneuvers protecting cells from ischemia–reperfusion injury. If this hypothesis were confirmed, several well-investigated molecular mediators of pre/post-conditioning could be explored as therapeutic targets against tumor malignancy. For examples, drugs that completely block the cardioprotection induced by ischemic preconditioning, such as mitochondrial potassium ATP channel inhibitors or mitochondrial permeability transition pore openers, could be extraordinarily efficient in counteracting the adaptations of tumor cells and cancer stem cells to intermittent hypoxia. As a consequence, this strategy should be effective in blunting tumor capacity to progress toward malignancy and survive in ischemic conditions.

Vital dyes and virtual deaths

Dear Editor, In 2009 and 2012, Cell Death & Differentiation has published recommendations of the Nomenclature Committee on Cell Death (NCCD) for the Classification of cell death and Molecular definitions of cell death subroutines, respectively. Under the subtitle When is a cell ‘dead'?, and in an accompanying table entitled Molecular or morphological criteria to define dead cells, the 2009 paper featured a set of three criteria; the fulfillment of any single one is considered to indicate cell death.1 The first criterion in this list is Loss of plasma membrane integrity, and parameters commonly used to assess integrity of the plasma membrane were mentioned, namely exclusion from cells of vital dyes like trypan blue or propidium iodide. It should be noted that injuries of the plasma membrane may be transient. This is now widely accepted, and here some key publications related to this issue are reviewed. For instance, mechanical stress can cause lesions of the plasma membrane spanning several micrometers, but they can be rapidly repaired by calcium influx-dependent mechanisms.2 Similarly, plasma membrane perforation by various pore forming proteins may be reversible.3 Some pore-forming proteins, for example, streptolysin O, render cells permeable for vital dyes and even for macromolecules, whereas small pore-forming proteins like α-toxin of S. aureus form lesions too small to permit flux of these molecules. However, all kinds of membrane lesions cause a drop of potassium and cellular ATP concentrations, which however, may be reversible if reconstitution of membrane integrity is achieved in time. Transient plasma membrane damage may not only trigger transcriptional responses, and release of mediators,4 but also cell cycle progression.5 Therefore, loss of membrane integrity is not even a reliable predictor of imminent death. Cellular tools for mending perforated membranes are diverse and comprise calcium influx-dependent or calcium influx-independent mechanisms. However, vesicle traffic emerges as a common denominator of resealing processes,6, 7, 8 which appear to be evolutionarily conserved and operate in vivo.8 As all definitions of cell death are necessarily ‘package deals' with the tacit assumption that the observed changes are irreversible, investigators are facing the question for how long they have to observe an indicator of a presumed, irreversible process before they may actually regard it as such. As membrane repair depends on the energy consuming task of vesicle traffic, irreversibility of loss of membrane integrity may be ascertained when cellular ATP is depleted. Although more work is required to fully understand and appreciate the mechanisms and relevance of membrane repair, the available evidence warrants a reassessment of Loss of plasma membrane integrity in itself as a bona fide criterion to define cell death.

POSTCONDITIONING EFFECTS OF ORAL NICORANDIL TREATMENT ON PATIENTS WITH ACUTE ANTERIOR MYOCARDIAL INFARCTION

ObjectivesIn recent years, the development of thrombolysis and percutaneous coronary intervention (PCI) have positive impacts on outcome of the patients with acute myocardial infarction (AMI), but the reperfusion injury followed...

POSTCONDITIONING EFFECTS OF ORAL NICORANDIL TREATMENT ON PATIENTS WITH ACUTE ANTERIOR MYOCARDIAL INFARCTION

ObjectivesIn recent years, the development of thrombolysis and percutaneous coronary intervention (PCI) have positive impacts on outcome of the patients with acute myocardial infarction (AMI), but the reperfusion injury followed...

The antifungal effect of cellobiose lipid on the cells of Saccharomyces cerevisiae depends on carbon source

The cellobiose lipid of Cryptococcus humicola, 16-(tetra-O-acetyl-β-cellobiosyloxy)-2-hydroxyhexadecanoic acid, is a natural fungicide. Sensitivity of the cells of Saccharomyces cerevisiae to the fungicide depends on a carbon source. Cellobiose lipid concentrations inducing the leakage of potassium ions and ATP were similar for the cells grown in the medium with glucose and ethanol. However, the cells grown on glucose and ethanol died at 0.05 mg ml-1 and 0.2 mg ml-1 cellobiose lipid, respectively. Inorganic polyphosphate (PolyP) synthesis was 65% of the control with 0.05 mg ml-1 cellobiose lipid during cultivation on ethanol. PolyP synthesis was not observed during the cultivation on glucose at the same cellobiose lipid concentration. The content of longer-chain polyP was higher during cultivation on ethanol. We speculate the long-chained polyP participate in the viability restoring of ethanol-grown cells after treatment with the cellobiose lipid.

The role of Volatile Anesthetics in Cardioprotection: a systematic review

This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery.