Navigating Social Waters: Understanding Theory-of-Mind Challenges in Patients with Mesial Temporal Lobe Epilepsy.

Background: Temporal lobe epilepsy is a common neurological disease that affects many areas of patients' lives, including social competence. The aim of the study was to assess theory of mind in patients with temporal lobe epilepsy and to investigate the demographic and clinical factors associated with this function. Methods: A total of 65 participants took part in the study, which included 44 patients with epilepsy and 21 demographically matched healthy individuals. The following neuropsychological tests were used to examine theory of mind: the Faux Pas Test, the Hinting Task, the Emotion Comprehension Test, and a cognitive function screen, the Montreal Cognitive Assessment. Results: Patients with epilepsy scored lower on all measures of the theory-of-mind tests. Moreover, in the clinical group, numerous moderate and strong correlations were found between the theory-of-mind tests and education, age at onset of epilepsy, lateralization of epileptic focus, cognitive status, and, to a lesser degree, number of anti-epileptic drugs, frequency of seizures, and age. In contrast, in the control group, significant correlations were found mostly between the theory-of-mind tests and sex, and, to a lesser degree, age. Education and cognitive functioning were not associated. Conclusions: Patients with epilepsy experience difficulties in theory of mind, which may have a negative impact on the quality of their social relationships. The level of theory-of-mind abilities correlates with particular clinical and demographic indicators. Recognizing these issues allows clinicians to implement tailored interventions, potentially improving patients' quality of life.

The benefits and disbenefits associated with cultural ecosystem services of urban green spaces.

Cultural ecosystem services (CES) and disservices shape landscape planning policy to a huge extent. We focus on the benefits and disbenefits associated with CES. The study aimed to explore the co-occurrence of the benefits and disbenefits associated with CES as well as the relationship between spatial and landscape characteristics and specific benefits and disbenefits. We conducted a map-based online questionnaire among visitors of two urban green spaces in Kraków, Poland (Wolski Forest and Jordan Park). Respondents were asked to map places visited and assign them benefits and disbenefits using indicator statements. We found three bundles of benefits (connection to nature, social bonding in nature and responsibility) and five to seven bundles of disbenefits (1). The experiences (e.g., strengthening social bonds) were more concentrated whereas the identities (e.g., reflection) were more blurred spatially owing to their individualistic nature (2). The relationship between benefits/disbenefits and landscape features showed a relatively weak correlation, with a more discernible pattern observed in the case of experiences and capabilities (3). Respondents perceived more human-related disbenefits (overcrowding, noise, rubbish), exhibiting a greater geographical concentration, especially in proximity to tourist attractions (4). The ecosystem-related disbenefits (insects, allergies) were less geographically concentrated (5). Furthermore, the study unveiled differences in the perception of disbenefits across seasons. Visitors of warmer months expressed concerns about overcrowding, insects, and allergies, while those exploring the study areas in winter indicated challenges associated with darkness and snow-covered paths (6). These are important implications for management to increase the comfort of visits to green spaces.

Determinants of the Quality of Life in Patients with Drug-Resistant Temporal Lobe Epilepsy: A Comparison of the Results before and after Surgery.

Drug-resistant temporal lobe epilepsy is associated with a reduction in the quality of life of patients. The aim of this study was to compare the quality of life before and after the surgical treatment of epilepsy and to assess factors that may affect the well-being of patients after surgery. The study involved 168 patients with drug-resistant temporal lobe epilepsy. All of them were examined twice: once before and again one year after surgery. Two questionnaires were used in the study: the Quality of Life in Epilepsy Inventory-Patient-Weighted and Hospital Anxiety and Depression Scale and one that collected data on selected demographic and clinical variables. The results showed that patients scored significantly higher in quality of life and lower in depression and anxiety after surgery; however, this only applied to patients with a good outcome of treatment (Engel Class I and Class II). Patients with an unfavorable outcome of surgical treatment (Engel Class III and Class IV) achieved significantly worse results in all examined variables. Correlational analysis showed a relationship between select aspects of quality of life and the level of depression and anxiety, as well as the frequency of seizures and age at epilepsy onset. There was no significant relationship with age, sex, education, or number of prescribed antiepileptic drugs. The study confirms the significant relationship between the quality of life and the effectiveness of surgical treatment, indicating the relationship between patients' well-being and selected clinical indicators.

In Vivo Study on Doxycycline Protective Mechanisms during Myocardial Ischemia Injury in Rats.

BACKGROUND: The fact that during myocardial ischemia/reperfusion (I/R) injury, myosin light chain 1 (MLC1) and troponin I (TnI) are degraded by matrix metalloproteases activity has already been well established in both in vitro and ex vivo studies. However, I/R injury is a complex issue based on several overlapping mechanisms. Increased activity of myosin light chain kinase and nitric oxide synthase due to oxidative stress leads to post-translational modifications of MLC1, thus leading to the increased degradation of these proteins. METHODS: Wistar rats were subjected to left anterior descending coronary artery occlusion. To measure the pharmacological effect of doxycycline, transthoracic echocardiography as well as biochemical tests, concentrations of TnI, LDH, MLC1, MMP-2 and MMP-9 were performed. Gelatinize activity and cytotoxicity level were also assessed; Results: I.p., administration of doxycycline before LAD occlusion surgery increased TnI and LDH content in the heart and decreased cytotoxicity. A reduction of MMP-2 and MMP-9 concentration and MMP-2 activity after administration of Doxy was also observed, as well as improvement in echocardiographic parameters just 7 days after surgery. CONCLUSIONS: Inhibition of MMPs by doxycycline, in vivo, may serve as a protective agent in future therapy.

What helps patients to prepare for and cope during awake craniotomy? A prospective qualitative study.

There is growing interest in awake craniotomies, but some clinicians are concerned that such procedures are poorly tolerated by patients. Therefore, we conducted a study to assess this phenomenon. In this prospective qualitative study, 68 patients who qualified for awake craniotomy were asked to complete the Hospital Anxiety and Depression Scale (HADS)-two days before the surgery and visual analogue scales (VAS) for pain and stress, two days before the surgery and again about two days after. In addition, after their surgery, they took part in a structured interview about what helped them prepare for and cope with the surgery. Most patients tolerated the awake surgery well, scoring low on stress and pain scales. They reported a lower level of stress during the surgery (when questioned afterwards) than before it. Intensity of stress before the surgery correlated negatively with age, positively with HADS anxiety score and positively with stress subsequently experienced during surgery. The level of stress during surgery was associated with stress experienced before the surgery, pain and HADS anxiety and depression scores. Severity of pain during the surgery was positively correlated with stress during surgery and HADS depression and anxiety scores before the surgery. There was no correlation between stress, pain, anxiety and depression and the location of the lesion. Patients have a high tolerance for awake craniotomy. Various factors have an impact on how well patients cope with the operation. Extensive preoperative preparation should be considered a key part of the procedure.

Simultaneous assessment of mechanical and electrical function in Langendorff-perfused ex-vivo mouse hearts.

Background: The Langendorff-perfused ex-vivo isolated heart model has been extensively used to study cardiac function for many years. However, electrical and mechanical function are often studied separately-despite growing proof of a complex electro-mechanical interaction in cardiac physiology and pathology. Therefore, we developed an isolated mouse heart perfusion system that allows simultaneous recording of electrical and mechanical function. Methods: Isolated mouse hearts were mounted on a Langendorff setup and electrical function was assessed via a pseudo-ECG and an octapolar catheter inserted in the right atrium and ventricle. Mechanical function was simultaneously assessed via a balloon inserted into the left ventricle coupled with pressure determination. Hearts were then submitted to an ischemia-reperfusion protocol. Results: At baseline, heart rate, PR and QT intervals, intra-atrial and intra-ventricular conduction times, as well as ventricular effective refractory period, could be measured as parameters of cardiac electrical function. Left ventricular developed pressure (DP), left ventricular work (DP-heart rate product) and maximal velocities of contraction and relaxation were used to assess cardiac mechanical function. Cardiac arrhythmias were observed with episodes of bigeminy during which DP was significantly increased compared to that of sinus rhythm episodes. In addition, the extrasystole-triggered contraction was only 50% of that of sinus rhythm, recapitulating the "pulse deficit" phenomenon observed in bigeminy patients. After ischemia, the mechanical function significantly decreased and slowly recovered during reperfusion while most of the electrical parameters remained unchanged. Finally, the same electro-mechanical interaction during episodes of bigeminy at baseline was observed during reperfusion. Conclusion: Our modified Langendorff setup allows simultaneous recording of electrical and mechanical function on a beat-to-beat scale and can be used to study electro-mechanical interaction in isolated mouse hearts.

Klotho inhibits IGF1R/PI3K/AKT signalling pathway and protects the heart from oxidative stress during ischemia/reperfusion injury.

Ischemia/reperfusion injury (IRI) of the heart involves the activation of oxidative and proapoptotic pathways. Simultaneously Klotho protein presents anti-aging, antiapoptotic and antioxidative properties. Therefore, this study aimed to evaluate the effect of Klotho protein on oxidative stress in hearts subjected to IRI. Isolated rat hearts perfused with the Langendorff method were subjected to ischemia, followed by reperfusion, in the presence or absence of recombinant rat Klotho protein. The factors involved in the activation of insulin-like growth factor receptor (IGF1R)/phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signalling pathway were evaluated. IRI caused activation of the IGF1R (p = 0.0122)/PI3K (p = 0.0022) signalling, as compared to the aerobic control group. Infusion supply of Klotho protein during IRI significantly reduced the level of phospho-IGF1R (p = 0.0436), PI3K (p = 0.0218) and phospho-AKT (p = 0.0020). Transcriptional activity of forkhead box protein O3 (FOXO3) was reduced (p = 0.0207) in hearts subjected to IRI, compared to aerobic control. Administration of Klotho decreased phosphorylation of FOXO3 (p = 0.0355), and enhanced activity of glutathione peroxidase (p = 0.0452) and superoxide dismutase (p = 0.0060) in IRI + Klotho group. The levels of reactive oxygen/nitrogen species (ROS/RNS) (p = 0.0480) and hydrogen peroxide (H2O2) (p = 0.0460), and heart injury (p = 0.0005) were significantly increased in hearts from the IRI group in comparison to the aerobic group. Klotho reduced NADPH oxidase 2 (NOX2) (p = 0.0390), ROS/RNS (p = 0.0435) and H2O2 (p = 0.0392) levels, and heart damage (p = 0.0286) in the hearts subjected to IRI. In conclusion, Klotho contributed to the protection of the heart against IRI and oxidative stress via inhibition of the IGF1R/PI3K/AKT pathway, thus can be recognized as a novel cardiopreventive/cardioprotective agent.

Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during Hypothermic Machine Perfusion in Rat Model.

Transplanted organs are subjected to harmful conditions through stopping blood flow, hypothermic storage of the graft, and subsequent reperfusion. In particular, kidneys donated from patients after cardiac arrest (DCD) are classified as more vulnerable to ischemia-reperfusion injury (IRI). Hypothermic machine perfusion is proposed as a solution for better kidney storage before transplantation, and it is a good platform for additional graft treatment. Antioxidants have gained interest in regenerative medicine due to their ability to scavenge reactive oxygen species (ROS), which play a key role in IRI. We evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted antioxidant, administered directly to the perfusing buffer. Rat kidneys were isolated, randomly classified into one of the following groups, donation after brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a hypothermic machine perfusion system. Subsequently, we detected levels of kidney injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and mitochondrial integrity) markers. We compared the activation of the apoptosis pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt ratio after drug administration. The length of warm ischemia time negatively impacts the graft condition. However, MitoQ added to the perfusing system as an 'on pump' therapy mitigates injury to the kidney before transplantation by inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential drug for DCD graft preconditioning.

Pain-depression relationship, quality of life and acceptance of illness among patients with Chiari malformation type I: A cross-sectional study.

Chiari malformation type I (CM-I) is a congenital anomaly of the hindbrain. The most common symptoms include suboccipital tussive headache, dizziness and neck pain. Recently there has been growing interest in the psychological and psychiatric aspects of functioning in patients with CM-I, which have a significant effect on treatment outcomes and quality of life (QoL). The aim of the study was to assess the severity of depressive symptoms and the QoL in patients with CM-I and to identify the main factors responsible for these phenomena. A total of 178 people participated in the study and were divided into 3 groups: patients with CM-I who had undergone surgery (n = 59); patients with CM-I who had not undergone surgery (n = 63); and healthy volunteers (n = 56). Psychological evaluation included a set of questionnaires: the Beck Depression Inventory II, the World Health Organization shortened version of the WHOQOL-100 quality of life questionnaire, the Acceptance of Illness Scale and the Beliefs about Pain Control Questionnaire. Results showed that the control group participants obtained significantly better results than both groups of CM-I patients in terms of all indicators of QoL, symptoms of depression, acceptance of illness, pain level (average and present) and perceived influence of doctors regarding coping with pain. Patients with CM-I (operated and non-operated) obtained similar results in most of the questionnaires and the QoL indices correlated significantly with the majority of the analyzed variables. Moreover, CM-I patients with higher depression scores described their pain as more severe and had a stronger belief that pain levels were not influenced by them but only by doctors, or that it could be controlled randomly; they were also less willing to accept their illness. CM-I symptoms affect the mood and QoL of patients. Psychological and psychiatric care should be the golden standard in managing this clinical group.

The Characteristics of the Reduction of Interference Effect during Dual-Task Cognitive-Motor Training Compared to a Single Task Cognitive and Motor Training in Elderly: A Randomized Controlled Trial.

Many studies have indicated a weakening in several areas of cognitive functioning associated with the normal ageing process. One of the methods supporting cognitive functions in older adults is dual-task training which is based on performing cognitive and motor exercises at the same time. The study aimed at examining the characteristics of dual-task training compared to single-task training in participants over 65 years of age. Sixty-five subjects took part in the study. They were randomly assigned to three groups: dual-task cognitive-motor training (CM), single-task cognitive training (CT), and single-task motor training (MT). The training program in all groups encompassed 4 weeks and consisted of three, 30-min meetings a week. Specialized software was designed for the study. The main indicators, such as orientation and planning time and the number of errors, were monitored during the whole training in all groups. The obtained results have shown that the dual-task training was associated with a significantly greater number of movement errors, but not with a longer task planning time compared to the single-task condition training. There was a decrease in the time needed to plan a path in the mazes by subjects training in the CM, CT, and MT groups. The results indicate that after each type of training, the number of errors and the time needed to plan the path decrease, despite the increasing difficulty of the tasks. The length of planning time was strongly correlated with the number of errors made by individuals in the CM group (r = 0.74, p = 0.04), compared to the ST group-for which the said correlation was not significant (r = 0.7, p = 0.06). The dual-task cognitive-motor training is more cognitively demanding compared to the single-task cognitive and motor training. It manifests in a greater number of errors, but it does not extend the orientation and planning time.

Monitored Anesthesia Care Protocol for Awake Craniotomy and Patient's Perspective on the Procedure.

OBJECTIVE: There is ongoing discussion on pros and cons in terms of different anesthesia protocols for awake craniotomy (AC) with direct brain stimulation. The aim of this study is to share our anesthesia protocol and present our patients' perspectives. METHODS: We conducted an analysis of prospectively collected data from 53 (54 procedures) consecutive patients. Most of the patients (50) underwent surgery due to primary brain lesions. Eight procedures were performed in patients with lesions in the nondominant hemisphere for language. Four of all procedures were reoperations, and one patient was operated on in awake conditions twice. The psychological evaluation of patients was performed 2 times: 2 days before and after surgery. A visual analog scale for pain and stress levels as well as structured interviews was used. RESULTS: Most patients tolerated ACwell. Patients reported that discomfort was mostly related to urinary catheter insertion, head holder placement, and temporal muscle detachment in cases of frontotemporal craniotomies. The intensity of stress measured with the visual analog scale before surgery was negatively associated with age and positively correlated with stress experienced in the operating room. In all patients, we were able to finish the procedure according to the monitored anesthesia care protocol without the need for conversion to general anesthesia. We observed 3 (5.6%) intraoperative seizures that required deepening of sedation. CONCLUSION: AC using the monitored anesthesia care protocol was a safe and well-tolerated procedure with satisfactory patient experience. Extensive preoperative preparation should be considered a key part of the procedure.

Klotho Protein Decreases MMP-Mediated Degradation of Contractile Proteins during Ischaemia/Reperfusion Injury to the Cardiomyocytes.

Ischaemia, followed by reperfusion, causes the generation of reactive oxygen species, overproduction of peroxynitrite, activation of matrix metalloproteinases (MMPs), and subsequently the degradation of heart contractile proteins in the cardiomyocytes. Klotho is a membrane-bound or soluble protein that regulates mineral metabolism and has antioxidative activity. This study aimed to examine the influence of Klotho protein on the MMP-mediated degradation of contractile proteins during ischaemia/reperfusion injury (IRI) to the cardiomyocytes. Human cardiac myocytes (HCM) underwent in vitro chemical IRI (with sodium cyanide and deoxyglucose), with or without the administration of recombinant Klotho protein. The expression of MMP genes, the expression and activity of MMP proteins, as well as the level of contractile proteins such as myosin light chain 1 (MLC1) and troponin I (TnI) in HCM were measured. Administration of Klotho protein resulted in a decreased activity of MMP-2 and reduced the release of MLC1 and TnI that followed in cells subjected to IRI. Thus, Klotho protein contributes to the inhibition of MMP-dependent degradation of contractile proteins and prevents injury to the cardiomyocytes during IRI.

Attention and working memory in patients with prolactinomas: a case-control study.

Prolactinomas (prolactin-secreting adenomas) are the most common type of hormone-secreting pituitary tumor. Mounting evidence indicates that excess prolactin impairs cognitive function, but specific assessments of attention in patients with prolactinomas are lacking. Case-control study gathered 54 participants-27 patients with prolactinoma and 27 healthy controls. Neuropsychological assessment included a comprehensive set of diagnostic methods for the evaluation of attention and working memory. Patients showed slower information processing, expressed as a longer working time on the d2 Test of Attention and Color Trails Test (CTT-2), and lower attention-switching shown in the CTT-2 and in two subtests of the Tests of Everyday Attention (Visual Elevator), and Telephone Search While Counting. Working memory disturbances were observed in Digit Span and Symbol Span tests. A level of prolactin correlated negatively with scores in some of the neuropsychological tests measuring attentional switching (Visual Elevator), spatial screening and working memory (CTT-2), spatial working memory (Symbol Span) and auditory-verbal working memory (Digit Span backwards). There were no significant correlations between cognitive performance and tumor size. In conclusion, patients with prolactinoma suffer from impaired cognitive functions, including attention and working memory. Comprehensive neuropsychological assessment should be a permanent element of the diagnostics of this group of patients.

Cortical and white matter anatomy relevant for the lateral and superior approaches to resect intraaxial lesions within the frontal lobe.

Despite being associated with high-order neurocognitive functions, the frontal lobe plays an important role in core neurological functions, such as motor and language functions. The aim of this study was to present a neurosurgical perspective of the cortical and subcortical anatomy of the frontal lobe in terms of surgical treatment of intraaxial frontal lobe lesions. We also discuss the results of direct brain mapping when awake craniotomy is performed. Ten adult cerebral hemispheres were prepared for white matter dissection according to the Klingler technique. Intraaxial frontal lobe lesions are approached with a superior or lateral trajectory during awake conditions. The highly eloquent cortex within the frontal lobe is identified within the inferior frontal gyrus (IFG) and precentral gyrus. The trajectory of the approach is mainly related to the position of the lesion in relation to the arcuate fascicle/superior longitudinal fascicle complex and ventricular system. Knowledge of the cortical and subcortical anatomy and its function within the frontal lobe is essential for preoperative planning and predicting the risk of immediate and long-term postoperative deficits. This allows surgeons to properly set the extent of the resection and type of approach during preoperative planning.

Silencing RNA for MMPs May Be Utilized for Cardioprotection.

Ischemia/reperfusion (I/R) injury is accompanied by an increase of matrix metalloproteinase 2 (MMP-2) activity, which degrades heart contractile proteins. The aim of the study was to investigate the effect of MMP-2 small interfering RNA (MMP-2 siRNA) administration on I/R heart. Isolated rat hearts perfused by the Langendorff method were subjected to I/R in the presence or absence of MMP-2 siRNA. The hemodynamic parameters of heart function were monitored. Lactate dehydrogenase (LDH) activity was measured in coronary effluents. Activity and concentration of MMPs in the hearts were measured. Concentration of troponin I (TnI) in coronary effluents was examined as a target for MMP-2 degradation. Recovery of heart mechanical function was reduced after I/R; however, administration of MMP-2 siRNA resulted in restoration of proper mechanical function (p < 0.001). LDH activity was decreased after the use of MMP-2 siRNA (p = 0.02), providing evidence for reduced cardiac damage. Both MMP-2 and MMP-9 syntheses as well as their activity were inhibited in the I/R hearts after siRNA administration (p < 0.05). MMP-2 siRNA administration inhibited TnI release into the coronary effluents (p < 0.001). The use of MMP-2 siRNA contributed to the improvement of heart mechanical function and reduction of contractile proteins degradation during I/R; therefore, MMP-2 siRNA may be considered a cardioprotective agent.

The cognitive and cognitive-motor training contribution to the improvement of different aspects of executive functions in healthy adults aged 65 years and above-A randomized controlled trial.

AIMS: The study aimed at examining the effectiveness of cognitive-motor dual-task and single-task cognitive training on executive and attention functions in participants over 65 years of age. METHODS: The study comprised 68 participants. They were randomly assigned to dual-task cognitive-motor training (DTT), single-task cognitive training (STT) or a control group (C). The training program in all groups encompassed 4 weeks and consisted of three, 30-min meetings a week. Specialized software was designed for the purposes of the study. Both before and after the training, the cognitive functioning was assessed using: Color Trials Test, Ruff Figural Fluency Test, Wisconsin Sorting Card Test, Digit Span, Verbal Fluency Test, Stroop Color-Word Test. RESULTS: After the cognitive-motor training, improvement was achieved in the control and inhibition of reactions. Moreover, after the cognitive training, improvements in abstract thinking and categorization were reported. CONCLUSION: Despite the small sample limitation, the preliminary result shows each form of the training supports a different aspect of executive functions but does not contribute to the improvement in attention.

Corrigendum to "Ameliorating Effect of Klotho Protein on Rat Heart during I/R Injury".

[This corrects the article DOI: 10.1155/2020/6427284.].

Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment.

BACKGROUND: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (Δ9-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if Δ9-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury. METHODS: Two experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent ex vivo/chemical in vitro I/R protocol with/without Δ9-THC treatment. The following parameters were measured: cell metabolic activity, morphology changes, cell damage as lactate dehydrogenase (LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant capacity (TAC) and heart hemodynamic parameters. RESULTS: Δ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (p < 0.05, N = 3-6). Cells subjected to I/R showed lower cytoplasmic LDH activity, and 10 µM Δ9-THC treatment reduced cell injury and increased LDH content (p = 0.019, N = 6-9). Morphology changes of HCM-spherical shape, vacuolisation of cytoplasm and swollen mitochondria-were inhibited due to Δ9-THC treatment. I/R condition affected cell viability, but 10 µM Δ9-THC decreased the number of dead cells (p = 0.005, N = 6-9). The total level of CERK was lower in the I/R group, reflecting oxidative/nitrosative stress changes. The administration of Δ9-THC effectively increased the production of CERK to the level of aerobic control (p = 0.028, N = 6-9). ROS level was significantly decreased in I/R cells (p = 0.007, N = 6-8), confirming oxidative stress, while administration of 10 µM Δ9-THC enhanced TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6-8). CONCLUSIONS: Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol.

The Klotho protein supports redox balance and metabolic functions of cardiomyocytes during ischemia/reperfusion injury.

BACKGROUND: Acute heart ischemia followed by reperfusion leads to overproduction of reactive oxygen/ /nitrogen species (ROS/RNS), disrupted expression of nitric oxide synthase (NOS) and unbalanced glucose metabolism. Klotho is a membrane-bound or soluble protein that exerts protective activity in many organs. While Klotho is produced mainly in the kidneys and brain, it has been recently proven that Klotho is expressed in the cardiomyocytes as well. This study aimed to show the influence of the Klotho protein on oxidative/nitrosative stress and metabolic function of the cardiomyocytes subjected to ischemia/reperfusion (I/R) injury. METHODS: Human cardiac myocytes underwent in vitro chemical I/R (with sodium cyanide and 2-deoxyglucose), in the presence or absence of the recombinant human Klotho protein. The present study included an investigation of cell injury markers, level of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), level of oxidative/nitrosative stress and metabolic processes of the cardiomyocytes. RESULTS: Administration of Klotho protein resulted in mitigation of injury, decreased level of NOX2 and NOX4, reduced generation of ROS/RNS and hydrogen peroxide (H2O2), decreased expression of inducible NOS and limited production of nitrates/nitrites in cells under I/R. Glucose uptake and lactate production in the cardiomyocytes subjected to I/R were normalized after Klotho supplementation. CONCLUSIONS: The Klotho protein participates in the regulation of redox balance and supports metabolic homeostasis of the cardiomyocytes and hence, contributes to protection against I/R injury.

Expression of atrial­fetal light chains in cultured human cardiomyocytes after chemical ischemia­reperfusion injury.

Atrial light chains (ALC1) are naturally present in adult heart atria, while ventricular light chains (VLC1) are predominant in ventricles. Degradation of VLC1 and re­expression of ALC1 in heart ventricles are associated with heart disorders in response to pressure overload. The aim of the current study was to investigate changes in myosin light chain expression after simulated ischemia and simulated reperfusion (sI/sR). Human cardiomyocytes (HCM) isolated from adult heart ventricles were subjected to chemical ischemia. The control group was maintained under aerobic conditions. Myocyte injury was determined by testing lactate dehydrogenase (LDH) activity. The gene expression of ALC1, VLC1 and MMP­2 were assessed by reverse transcription­quatitive PCR. Additionally, protein synthesis was measured using ELISA kits and MMP­2 activity was measured by zymography. The results revealed that LDH activity was increased in sI/sR cell­conditioned medium (P=0.02), confirming the ischemic damage of HCM. ALC1 gene expression and content in HCM were also increased in the sI/sR group (P=0.03 and P<0.001, respectively), while VLC1 gene expression after sI/sR was decreased (P=0.008). Furthermore, MMP­2 gene expression and synthesis were lower in the sI/sR group when compared with the aerobic control group (P<0.001 and P=0.03, respectively). MMP­2 activity was also increased in sI/sR cell­conditioned medium (P=0.006). In conclusion, sI/sR treatment led to increased ALC1 and decreased VLC1 expression in ventricular cardiomyocytes, which may constitute an adaptive mechanism to altered conditions and contribute to the improvement of heart function.