Search results for: cardiac myosin binding protein-C

Authors: Ratna Farida Soenarto, Anas Alatas, Made Ryan Kharmayani

Abstract:

Background: Conventional ultrafiltration (CUF) system was shown to be helpful in reducing anti-inflammatory mediators for patients who underwent open heart surgery. Additionally, modified ultrafiltration (MUF) has been shown to reduce anti-inflammatory mediators further while reducing interstitial fluid volume at the same time. However, there has been minimal data concerning the efficacy of combining both ultrafiltration methods. This study aims to compare inflammation marker, vascular resistance, and cardiac index on CUF+MUF patients with CUF only patients undergoing open heart surgery. Method: This is a single blind randomized controlled trial on patients undergoing open heart surgery between June 2021 - October 2021 in CiptoMangunkusumo National Referral Hospital and Jakarta Heart Hospital. Patients wererandomized using block randomization into modified ultrafiltration following conventional ultrafiltration (CUF+MUF) and conventional ultrafiltration (CUF) only. Outcome assessed in this study were 24-hoursinterleukin-6 levels, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), and cardiac index. Results: A total of 38patients were included (19 CUF+MUF and 19 CUF subjects). There was no difference in postoperative IL-6 level between groups (p > 0.05).No difference in PVR was observed between groups.Higher difference in SVR was observed in CUF+MUF group (-646 vs. -261dyn/s/cm-5, p < 0.05). Higher cardiac index was observed on CUF+MUF group (0.93 vs. 0.48, p < 0.05). Conclusion: Patients undergoing open heart surgery with modified ultrafiltration following conventional ultrafiltration had similar systemic inflammatory response and better cardiac response than those having conventional ultrafiltration.

Keywords: open-heart, CUF, MUF, SVR, PVR, IL-6

Procedia PDF Downloads 130

Authors: Kh. Dehkordi, R. Sharifi Gholam, S. Arshadi

Abstract:

Objective: Oxidative stress is produced under diabetic conditions and possibly causes various forms of tissue damage inpatients with diabetes. Antioxidants defend against the harmful effect of free radicals, which are associated with heart disease, cancer, arthritis, aging and many other diseases1). Antioxidants are very stable molecules capable of neutralizing free radicals by donating an electron to them.The aim of this study was to examine the effect of swimming training, fenugreek seed extract and glibenclamide on plasma glucose and cardiac antioxidants activity in diabetic rats. Design: For this purpose, fifty male wistar rats were divided into five groups, two groups of control rats (diabetic control [DC] and healthy control [HC]), one group of endurance swimming training (EST), one group of fenugreek seed extract highdose (F1, 1.74 g/kg b.w), one group of fenugreek seed extract middle dose (F2, 0.87 g/kg b.w), one group of glibenclamide (G, 0.5 mg/kg b.w). Materials and Methods: Diabetes induced by streptozotocine (STZ), data was analyzed using the one-way ANOVA followed by a Tukey test. Significance level was 0.05. Results: All of the groups' exception of HC showed significant decrease in body weight (P < 0.05), but the diabetic control and swimming training group exhibited a more decrease. All of the groups have shown a significant decrease in plasma glucose than DC group (P < 0.05) but this reduction was more in G group than DC no HC group. S, G and HC groups have shown significant increase in cardiac antioxidant than DC group (P < 0.05) but there wasn't significant difference in other groups (P > 0.05). Conclusion: The present results indicate that regular swimming training lead to decrease in plasma glucose and enhanced cardiac antioxidants in diabetic rats.

Keywords: swimming, glucose, cardiac, antioxidants

Procedia PDF Downloads 273

Authors: Daniel F. Bohorquez, Luis M. Agudelo, Henry H. León

Abstract:

Heart rate variability (HRV) is defined as the temporary variation between heartbeats or RR intervals (distance between R waves in an electrocardiographic signal). This distance is currently a recognized biomarker. With the analysis of the distance, it is possible to assess the sympathetic and parasympathetic nervous systems. These systems are responsible for the regulation of the cardiac muscle. The analysis allows health specialists and researchers to diagnose various pathologies based on this variation. For the acquisition and analysis of HRV taken from a cardiac electrical signal, electronic equipment and analysis software that work independently are currently used. This complicates and delays the process of interpretation and diagnosis. With this delay, the health condition of patients can be put at greater risk. This can lead to an untimely treatment. This document presents a single portable device capable of acquiring electrocardiographic signals and calculating a total of 19 HRV metrics. This reduces the time required, resulting in a timelier intervention. The device has an electrocardiographic signal acquisition card attached to a microcontroller capable of transmitting the cardiac signal wirelessly to a mobile device. In addition, a mobile application was designed to analyze the cardiac waveform. The device calculates the RR and different metrics. The application allows a user to visualize in real-time the cardiac signal and the 19 metrics. The information is exported to a cloud database for remote analysis. The study was performed under controlled conditions in the simulated hospital of the Universidad de la Sabana, Colombia. A total of 60 signals were acquired and analyzed. The device was compared against two reference systems. The results show a strong level of correlation (r > 0.95, p < 0.05) between the 19 metrics compared. Therefore, the use of the portable system evaluated in clinical scenarios controlled by medical specialists and researchers is recommended for the evaluation of the condition of the cardiac system.

Keywords: biological signal análisis, heart rate variability (HRV), HRV metrics, mobile app, portable device.

Procedia PDF Downloads 155

Authors: H. Booke, R. Nordmeier

Abstract:

Sudden cardiac arrest is sometimes eye-witnessed by kids. Mostly, their (grand-)parents are affected by sudden cardiac arrest, putting these kids under enormous psychological pressure: Although they are more than desperate to help, they feel insecure and helpless and are afraid of causing harm rather than realizing their chance to help. Even years later, they may blame themselves for not having helped their beloved ones. However, the absolute majority of school children - at least in Germany - is not educated to provide first aid. Teaching young kids (5th grade) in basic life support thus may help to save lives while washing away the kids' fear from causing harm during cardio-pulmonary resuscitation. A teaching of circulatory and respiratory (patho-)physiology, followed by hands-on training of basic life support for every single child, was offered to each school in our district. The teaching was performed by anesthesiologists, and the program was called 'kids can save lives'. However, before enrollment in this program, the entire class must have had lessons in biology with a special focus on heart and circulation as well as lung and gas exchange. More than 1.000 kids were taught and trained in basic life support, giving them the knowledge and skills to provide basic life support. This may help to reduce the rate of failure to provide first aid. Therefore, educating young kids in basic life support may not only help to save lives, but it also may help to prevent any feelings of guilt because of not having helped in cases of eye-witnessed sudden cardiac arrest.

Keywords: teaching, children, basic life support, cardiac arrest, CPR

Procedia PDF Downloads 101

Authors: Awad G. Abdellatif, Huda M. Gargoum, Abdelkader A. Debani, Mudafara Bengleil, Salmin Alshalmani, N. El Zuki, Omran El Fitouri

Abstract:

In this study, the administration of 660 mg/kg of the ethanolic extract of the Alhgigraecorum (camel thorn) to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. The histopathological investigation also confirmed that camel thorn extract protects the liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand, the cardiac toxicity produced by adriamycin was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with an unexpected increase in the cardiac toxicity–induced by adriamycin in rodents.

Keywords: ethanolic, alhgigraecorum, tetrachloride, acetaminophen

Procedia PDF Downloads 478

Authors: Visith Siriphuwanun, Yodying Punjasawadwong, Suwinai Saengyo, Kittipan Rerkasem

Abstract:

Objective: To determine incidences and factors associated with perioperative cardiac arrest in trauma patients who received anesthesia for emergency surgery. Design and setting: Retrospective cohort study in trauma patients during anesthesia for emergency surgery at a university hospital in northern Thailand country. Patients and methods: This study was permitted by the medical ethical committee, Faculty of Medicine at Maharaj Nakorn Chiang Mai Hospital, Thailand. We clarified data of 19,683 trauma patients receiving anesthesia within a decade between January 2007 to March 2016. The data analyzed patient characteristics, traumas surgery procedures, anesthesia information such as ASA physical status classification, anesthesia techniques, anesthetic drugs, location of anesthesia performed, and cardiac arrest outcomes. This study excluded the data of trauma patients who had received local anesthesia by surgeons or monitoring anesthesia care (MAC) and the patient which missing more information. The factor associated with perioperative cardiac arrest was identified with univariate analyses. Multiple regressions model for risk ratio (RR) and 95% confidence intervals (CI) were used to conduct factors correlated with perioperative cardiac arrest. The multicollinearity of all variables was examined by bivariate correlation matrix. A stepwise algorithm was chosen at a p-value less than 0.02 was selected to further multivariate analysis. A P-value of less than 0.05 was concluded as statistically significant. Measurements and results: The occurrence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was 170.04 per 10,000 cases. Factors associated with perioperative cardiac arrest in trauma patients were age being more than 65 years (RR=1.41, CI=1.02–1.96, p=0.039), ASA physical status 3 or higher (RR=4.19–21.58, p < 0.001), sites of surgery (intracranial, intrathoracic, upper intra-abdominal, and major vascular, each p < 0.001), cardiopulmonary comorbidities (RR=1.55, CI=1.10–2.17, p < 0.012), hemodynamic instability with shock prior to receiving anesthesia (RR=1.60, CI=1.21–2.11, p < 0.001) , special techniques for surgery such as cardiopulmonary bypass (CPB) and hypotensive techniques (RR=5.55, CI=2.01–15.36, p=0.001; RR=6.24, CI=2.21–17.58, p=0.001, respectively), and patients who had a history of being alcoholic (RR=5.27, CI=4.09–6.79, p < 0.001). Conclusion: Incidence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was very high and correlated with many factors, especially age of patient and cardiopulmonary comorbidities, patient having a history of alcoholic addiction, increasing ASA physical status, preoperative shock, special techniques for surgery, and sites of surgery including brain, thorax, abdomen, and major vascular region. Anesthesiologists and multidisciplinary teams in pre- and perioperative periods should remain alert for warning signs of pre-cardiac arrest and be quick to manage the high-risk group of surgical trauma patients. Furthermore, a healthcare policy should be promoted for protecting against accidents in high-risk groups of the population as well.

Keywords: perioperative cardiac arrest, trauma patients, emergency surgery, anesthesia, factors risk, incidence

Procedia PDF Downloads 143

Authors: German Hernandez-Alonso, Antonio Lazcano, Arturo Becerra

Abstract:

Until today, viruses remain controversial and poorly understood; about their origin, this problem represents an enigma and one of the great challenges for the contemporary biology. Three main theories have tried to explain the origin of viruses: regressive evolution, escaped host gene, and pre-cellular origin. Under the perspective of the escaped host gene theory, it can be assumed a cellular origin of viral components, like protein RNA-binding domains. These universal distributed RNA-binding domains are related to the RNA metabolism processes, including transcription, processing, and modification of transcripts, translation, RNA degradation and its regulation. In the case of viruses, these domains are present in important viral proteins like helicases, nucleases, polymerases, capsid proteins or regulation factors. Therefore, they are implicated in the replicative cycle and parasitic processes of viruses. That is why it is possible to think that those domains present low levels of divergence due to selective pressures. For these reasons, the main goal for this project is to create a catalogue of the RNA-binding domains found in all the available viral proteomes, using bioinformatics tools in order to analyze its evolutionary process, and thus shed light on the general virus evolution. ProDom database was used to obtain larger than six thousand RNA-binding domain families that belong to the three cellular domains of life and some viral groups. From the sequences of these families, protein profiles were created using HMMER 3.1 tools in order to find distant homologous within greater than four thousand viral proteomes available in GenBank. Once accomplished the analysis, almost three thousand hits were obtained in the viral proteomes. The homologous sequences were found in proteomes of the principal Baltimore viral groups, showing interesting distribution patterns that can contribute to understand the evolution of viruses and their host-virus interactions. Presence of cellular RNA-binding domains within virus proteomes seem to be explained by closed interactions between viruses and their hosts. Recruitment of these domains is advantageous for the viral fitness, allowing viruses to be adapted to the host cellular environment.

Keywords: bioinformatics tools, distant homology, RNA-binding domains, viral evolution

Procedia PDF Downloads 360

Authors: Leonardo Juan Ramírez López, Javier Oswaldo Rodriguez Velasquez

Abstract:

We have designed a Holter that measures the heart´s activity for over 24 hours, implemented a prediction methodology, and generate alarms as well as indicators to patients and treating physicians. Various diagnostic advances have been developed in clinical cardiology thanks to Holter implementation; however, their interpretation has largely been conditioned to clinical analysis and measurements adjusted to diverse population characteristics, thus turning it into a subjective examination. This, however, requires vast population studies to be validated that, in turn, have not achieved the ultimate goal: mortality prediction. Given this context, our Insight Research Group developed a mathematical methodology that assesses cardiac dynamics through entropy and probability, creating a numerical and geometrical attractor which allows quantifying the normalcy of chronic and acute disease as well as the evolution between such states, and our Tigum Research Group developed a holter device with 12 channels and advanced computer software. This has been shown in different contexts with 100% sensitivity and specificity results.

Keywords: attractor , cardiac, entropy, holter, mathematical , prediction

Procedia PDF Downloads 142

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

Procedia PDF Downloads 60

Authors: Han-Bin Kim, Sooim Shin, Moonsung Choi

Abstract:

There is a growing interest in introducing a desired functional group on enzymes in the field of protein engineering. In here, various redox centers were newly created using histidine tag, which is widely used for protein purification, plus cobalt in one of cupredoxins, amicyanin. The coordination of Cobalt-His tag and reactivity of the Co²⁺ loaded His-tag also were characterized. 3xHis-tag, 6xHis-tag, and 9xHis-tag were introduced on amicyanin by site-directed mutagenesis, and then Co²⁺ was loaded on each His-tagged amicyanin. The spectral changes at 330 nm corresponding to cobalt binding on His-tag site indicated the binding ratio of 3xHis-tag, 6xHis-tag, and 9xHis-tag to cobalt as 1:1, 1:2, 1:3 respectively. Based on kinetic studies of binding cobalt to 3xHis-tag, 6xHis-tag, and 9xHis-tagged amicyanin, the nature of the sites was elucidated. In addition, internal electron transfer properties between Cu¹⁺ site and engineered site of amicyanin were determined. These results provide insight into improvement of metal coordination and alternation of the redox properties of metal as a new catalytic site on proteins.

Keywords: amicyanin, cobalt, histidine, protein engineering

Procedia PDF Downloads 143

Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

Abstract:

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

Procedia PDF Downloads 218

Authors: Xing Lu, Yi-ming Wu, Yan-hong Zhu, Zhen-feng Chen, Hong Liang, Yan Peng

Abstract:

[Eu(BMQ)2(NO3)3(CH3OH)(H2O)] (1),and [Er(BMQ)2(NO3)3(CH3OH)(H2O)] (2),were synthesized. Compounds 1 and 2 exhibit a certain extent cytotoxicity against Hep G2, Hela 229, MGC80-3 and BEL-7404 cell lines invitro, with IC50 values in the14.51±1.41μM to 52.49±4.01μM range. Compound 1 exhibited significantly enhanced cytotoxicity against MGC80-3 cell line, comparing with free 3-(1H-benzimidazol-2-yl)-6-methyl-2(1H)- quinolinone. The binding abilities of 1 to DNA were stronger than that of 2. Intercalation is the most probable binding mode for both the complexes.

Keywords: quinolinone, Eu(II) complex, Er(III) complex, cytotoxicity.

Procedia PDF Downloads 569

Authors: Lingxia Li, Frédéric Schnell, Shuzhe Ding, Solène Le Douairon Lahaye

Abstract:

Background: The risk of sudden cardiac arret/death (SCA/D) in athletes is controversial. There is a lack of meta-analyses assessing the sex differences in the risk of SCA/D in competitive athletes. Purpose: The aim of the present study was to evaluate sex differences in the incidence of SCA/D in competitive athletes using meta-analyses. Methods: The systematic review was registered in the PROSPERO database (registration ID: CRD42023432022) and was conducted according to the PRISMA guidelines. PubMed, Embase, Scopus, SPORT Discus and Cochrane Library were searched up to July 2023. To avoid systematic bias in data pooling, only studies with data for both sexes were included. Results: From the 18 included studies, 2028 cases of SCA/D were observed (males 1821 (89.79%), females 207 (10.21%)). The age ranges from the adolescents (<26 years) to the elderly (>45 years). The incidence in male athletes was 1.32/100,000 AY (95% CI: [0.90, 1.93]) and in females was 0.26/100,000 AY (95% CI: [0.16, 0.43]), the incidence rate ratio (IRR) was 6.43 (95% CI: [4.22, 9.79]). The subgroup synthesis showed a higher incidence in males than in females in both age groups <25 years and ≤35 years, the IRR was 5.86 (95% CI: [4.69, 7.32]) and 5.79 (95% CI: [4.73, 7.09]), respectively. When considering the events, the IRR was 6.73 (95%CI: [3.06, 14.78]) among studies involving both SCA/D events and 7.16 (95% CI: [4.93, 10.40]) among studies including only cases of SCD. The available clinical evidence showed that cardiac events were most frequently seen in long-distance running races (26, 35.1%), marathon (16, 21.6%) and soccer (10, 13.5%). Coronary artery disease (14, 18.9%), hypertrophic cardiomyopathy (8, 10.8%), and arrhythmogenic right ventricular cardiomyopathy (7, 9.5%) are the most common causes of SCA/D in competitive athletes. Conclusion: The meta-analysis provides evidence of sex differences in the incidence of SCA/D in competitive athletes. The incidence of SCA/D in male athletes was 6 to 7 times higher than in females. Identifying the reasons for this difference may have implications for targeted the prevention of fatal evets in athletes.

Keywords: incidence, sudden cardiac arrest, sudden cardiac death, sex difference, athletes

Procedia PDF Downloads 43

Authors: Sergey Kholodkevich, Tatiana Kuznetsova

Abstract:

The objective assessment of ecological state of water ecosystems is impossible without the use of biological methods of the environmental monitoring capable in the integrated look to reveal negative for biota changes of quality of water as habitats. Considerable interest for the development of such methods of environmental quality control represents biomarker approach. Measuring systems, by means of which register cardiac activity characteristics, received the name of bioelectronic. Bioelectronic systems are information and measuring systems in which animals (namely, benthic invertebrates) are directly included in structure of primary converters, being an integral part of electronic system of registration of these or those physiological or behavioural biomarkers. As physiological biomarkers various characteristics of cardiac activity of selected invertebrates have been used in bioelectronic system.lChanges in cardiac activity are considered as integrative measures of the physiological condition of organisms, which reflect the state of the environment of their dwelling. Greatest successes in the development of tools of biological methods and technologies of an assessment of surface water quality in real time. Essential advantage of bioindication of water quality by such tool is a possibility of an integrated assessment of biological effects of pollution on biota and also the expressness of such method and used approaches. In the report the practical experience of authors in biomonitoring and bioindication of an ecological condition of sea, brackish- and freshwater areas is discussed. Authors note that the method of non-invasive cardiac activity monitoring of selected invertebrates can be used not only for the advancement of biomonitoring, but also is useful in decision of general problems of comparative physiology of the invertebrates.

Keywords: benthic invertebrates, physiological state, heart rate monitoring, water quality assessment

Procedia PDF Downloads 693

Authors: Helan Satish, M. Ramasubba Reddy

Abstract:

The simulation of an endocardial cell for gene mutation in the cardiac sodium ion channel NaV1.5, encoded by SCN5A gene, is discussed. The characterization of Brugada Syndrome by loss of function effect on SCN5A mutation due to L812Q mutant present in the DII-S4 transmembrane region of the NaV1.5 channel protein and its effect in an endocardial cell is studied. Ten Tusscher model of human ventricular action potential is modified to incorporate the changes contributed by L812Q mutant in the endocardial cells. Results show that BrS-associated SCN5A mutation causes reduction in the inward sodium current by modifications in the channel gating dynamics such as delayed activation, enhanced inactivation, and slowed recovery from inactivation in the endocardial cell. A decrease in the inward sodium current was also observed, which affects depolarization phase (Phase 0) that leads to reduction in the spike amplitude of the cardiac action potential.

Keywords: SCN5A gene mutation, sodium channel, Brugada syndrome, cardiac arrhythmia, action potential

Procedia PDF Downloads 103

Authors: Hyun Chang Kim, Yong Hun Jung, Kyung Woon Jeung

Abstract:

Background: From the viewpoint of cardiac pump theory, the area of the left ventricle (LV) subjected to compression increases as the LV lies closer to the sternum, possibly resulting in higher blood flow in patients with LV closer to the sternum. However, no study has evaluated LV position during cardiac arrest or its relationship with hemodynamic parameters during cardiopulmonary resuscitation (CPR). The objectives of this study were to determine whether the position of the LV relative to the anterior-posterior axis representing the direction of chest compression shifts during cardiac arrest and to examine the relationship between LV position and hemodynamic parameters during CPR. Methods: Subcostal view echocardiograms were obtained from 15 pigs with the transducer parallel to the long axis of the sternum before inducing ventricular fibrillation (VF) and during cardiac arrest. Computed tomography was performed in three pigs to objectively observe LV position during cardiac arrest. LV position parameters including the shortest distance between the anterior-posterior axis and the mid-point of the LV chamber (DAP-MidLV), the shortest distance between the anterior-posterior axis and the LV apex (DAP-Apex), and the area fraction of the LV located on the right side of the anterior-posterior axis (LVARight/LVATotal) were measured. Results: DAP-MidLV, DAP-Apex, and LVARight/LVATotal decreased progressively during untreated VF and basic life support (BLS), and then increased during advanced cardiovascular life support (ACLS). A repeated measures analysis of variance revealed significant time effects for these parameters. During BLS, the end-tidal carbon dioxide and systolic right atrial pressure were significantly correlated with the LV position parameters. During ACLS, systolic arterial pressure and systolic right atrial pressure were significantly correlated with DAP-MidLV and DAP-Apex. Conclusions: LV position changed significantly during cardiac arrest compared to the pre-arrest baseline. LV position during CPR had significant correlations with hemodynamic parameters.

Keywords: heart arrest, cardiopulmonary resuscitation, heart ventricle, hemodynamics

Procedia PDF Downloads 163

Authors: Harish Rajak, Swati Singh

Abstract:

A series of novel pyrimidine based semicarbazone were designed and synthesized on the basis of semicarbazone based pharmacophoric model to satisfy the structural prerequisite crucial for antiepileptic activity. The semicarbazones based pharmacophoric model consists of following four essential binding sites: (i) An aryl hydrophobic binding site with halo substituent; (ii) A hydrogen bonding domain; (iii) An electron donor group and (iv) Another hydrophobic-hydrophilic site controlling the pharmacokinetic features of the anticonvulsant. The aryl semicarbazones has been recognized as a structurally novel class of compounds with remarkable anticonvulsant activity. In the present study, all the test semicarbazones were subjected to molecular docking using Glide v5.8. Some of the compounds were found to interact with ARG192, GLU270 and THR353 residues of 1OHV protein, present in GABA-AT receptor. The chemical structures of the synthesized molecules were characterized by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. The neurotoxicity was evaluated in mice by the rotorod test. The attempts were also made to establish structure-activity relationships among synthesized compounds. The results of the present study confirmed that the pharmacophore model with four binding sites is essential for antiepileptic activity.

Keywords: pyrimidine, semicarbazones, anticonvulsant activity, neurotoxicity

Procedia PDF Downloads 231

Authors: Agnieszka Krzemińska, Katarzyna Świderek, Vicente Molinier, Piotr Paneth

Abstract:

In order to understand in details the interactions between ligands and the enzyme isotope effects were studied between clinically used drugs that bind in the active site of Human Immunodeficiency Virus Reverse Transcriptase, HIV-1 RT, as well as triazole-based inhibitor that binds in the allosteric pocket of this enzyme. The magnitudes and origins of the resulting binding isotope effects were analyzed. Subsequently, binding isotope effect of the same triazole-based inhibitor bound in the active site were analyzed and compared. Together, these results show differences in binding origins in two sites of the enzyme and allow to analyze binding mode and place of newly synthesized inhibitors. Typical protocol is described below on the example of triazole ligand in the allosteric pocket. Triazole was docked into allosteric cavity of HIV-1 RT with Glide using extra-precision mode as implemented in Schroedinger software. The structure of HIV-1 RT was obtained from Protein Data Bank as structure of PDB ID 2RKI. The pKa for titratable amino acids was calculated using PROPKA software, and in order to neutralize the system 15 Cl- were added using tLEaP package implemented in AMBERTools ver.1.5. Also N-terminals and C-terminals were build using tLEaP. The system was placed in 144x160x144Å3 orthorhombic box of water molecules using NAMD program. Missing parameters for triazole were obtained at the AM1 level using Antechamber software implemented in AMBERTools. The energy minimizations were carried out by means of a conjugate gradient algorithm using NAMD. Then system was heated from 0 to 300 K with temperature increment 0.001 K. Subsequently 2 ns Langevin−Verlet (NVT) MM MD simulation with AMBER force field implemented in NAMD was carried out. Periodic Boundary Conditions and cut-offs for the nonbonding interactions, range radius from 14.5 to 16 Å, are used. After 2 ns relaxation 200 ps of QM/MM MD at 300 K were simulated. The triazole was treated quantum mechanically at the AM1 level, protein was described using AMBER and water molecules were described using TIP3P, as implemented in fDynamo library. Molecules 20 Å apart from the triazole were kept frozen, with cut-offs established on range radius from 14.5 to 16 Å. In order to describe interactions between triazole and RT free energy of binding using Free Energy Perturbation method was done. The change in frequencies from ligand in solution to ligand bounded in enzyme was used to calculate binding isotope effects.

Keywords: binding isotope effects, molecular dynamics, HIV, reverse transcriptase

Procedia PDF Downloads 407

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

Abstract:

There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

Procedia PDF Downloads 211

Authors: Fahad Raj Khan, Suleman Khan

Abstract:

There is a lack of consensus about the predictive value of raised blood glucose levels in terms of major adverse cardiac events (MACEs) in non-diabetic patients admitted for acute decompensated heart failure. The purpose of this research was to examine the long-term prognosis of acute decompensated heart failure (ADHF) in non-diabetic persons who had increased blood glucose levels, i.e., stress hyperglycemia, at the time of their ADHF hospitalization. The research involved 650 non-diabetic patients. Based on their admission stress hyperglycemia, they were divided into two groups.ie with and without (SHGL). The two groups' one-year outcomes for major adverse cardiac events (MACEs) were compared, and key predictors of MACEs were discovered. For statistical analysis, the two-tailed Mann-Whitney U test, Fisher's exact test, and binary logistic regression analysis were utilized. SHGL was found in 353 (54.3%) individuals. It was more frequent in men than in women. About 27% of patients with SHGL had previously been admitted for ADHF. Almost 62% were hypertensive, whereas 14 % had CKD. MACEs were significantly predicted by SHGL, HTN, prior hospitalization for ADHF, CKD, and cardiogenic shock upon admission. SHGL at the time of ADHF admission, independent of DM status, may be a predictive indication of MACEs.

Keywords: stress hyperglycemia, acute heart failure, major adverse cardiac events, MACEs

Procedia PDF Downloads 74

Authors: Usha Kiran, M. Z. Abdin

Abstract:

Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.

Keywords: osmotin, cell signaling modulator, bioinformatic tools, protein

Procedia PDF Downloads 243

Authors: Slawomir Pilip, Michal Wasilewski, Daniel Celinski, Leszek Szpakowski, Grzegorz Michalak

Abstract:

The aim of the study was to evaluate the effectiveness of cardiopulmonary resuscitation taken by Medical Emergency Teams (MET) at the place of an accident including the usage of mechanical chest compression systems. In the period of January-May 2017, there were 137 cases of a sudden cardiac arrest in a chosen region of Eastern Poland with 360.000 inhabitants. Medical records and questionnaires filled by METs were analysed to prove the effectiveness of cardiopulmonary resuscitations that were considered to be effective when an early indication of spontaneous circulation was provided and the patient was taken to hospital. A chest compression system used by METs was applied in 60 cases (Lucas3 - 34 patients; Auto Pulse - 24 patients). The effectiveness of cardiopulmonary resuscitation among patients who were employed a chest compression system was much higher (43,3%) than the manual cardiac massage (36,4%). Thus, the usage of Lucas3 chest compression system resulted in 47% while Auto Pulse was 33,3%. The average ambulance arrival time could have had a significant impact on the subsequent effectiveness of cardiopulmonary resuscitation in these cases. Ambulances equipped with Lucas3 reached the destination within 8 minutes, and those with Auto Pulse needed 12,1 minutes. Moreover, taking effective basic life support (BLS) by bystanders before the ambulance arrival was much more frequent for ambulances with Lucas3 than Auto Pulse. Therefore, the percentage of BLS among the group of patients who were employed Lucas3 by METs was 26,5%, and 20,8% for Auto Pulse. The total percentage of taking BLS by bystanders before the ambulance arrival resulted in 25% of patients who were later applied a chest compression system by METs. Not only was shockable cardiac rhythm obtained in 47% of these cases, but an early indication of spontaneous circulation was also provided in all these patients. Both Lucas3 and Auto Pulse were evaluated to be significantly useful in improving the effectiveness of cardiopulmonary resuscitation by 97% of Medical Emergency Teams. Therefore, implementation of chest compression systems essentially makes the cardiopulmonary resuscitation even more effective. The ambulance arrival time, taking successful BLS by bystanders before the ambulance arrival and the presence of shockable cardiac rhythm determine an early indication of spontaneous circulation among patients after a sudden cardiac arrest.

Keywords: cardiac arrest, effectiveness, mechanical chest compression systems, resuscitation

Procedia PDF Downloads 228

Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

Abstract:

Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

Procedia PDF Downloads 103

Authors: Yin Hua Zhang

Abstract:

Cardiac metabolism is essential in myocardial contraction. In addition to glucose, fatty acids (FA) are essential in producing energy in the myocardium since FA-dependent beta-oxidation accounts for > 70-90% of cellular ATP under resting conditions. However, metabolism shifts from FAs to glucose utilization during disease progression (e.g. hypertrophy and ischemic myocardium), where glucose oxidation and glycolysis become the predominant sources of cellular ATP. At advanced failing stage, both glycolysis and beta-oxidation are dysregulated, result in insufficient supply of intracellular ATP and weakened myocardial contractility. Undeniably, our understandings of myocyte function in healthy and diseased hearts are based on glucose (10 mM)-dependent metabolism because glucose is the “sole” metabolic substrate in most of the physiological experiments. In view of the importance of FAs in cardiovascular health and diseases, we aimed to elucidate the impacts of FA supplementation on myocyte contractility and evaluate cellular mechanisms those mediate the functions in normal heart and with pathological stress. In particular, we have investigated cardiac excitation-contraction (E-C) coupling in the presence and absence of FAs in normal and hypertensive rat left ventricular (LV) myocytes. Our results reveal that FAs increase mitochondrial activity, intracellular [Ca²+]i, and LV myocyte contraction in healthy LV myocytes, whereas FA-dependent cardiac inotropyis attenuated in hypertension. FA-dependent myofilament Ca²+ desensitization could be fundamental in regulating [Ca²+]i. Collectively, FAs supplementation resets cardiac E-C coupling scheme in healthy and diseased hearts.

Keywords: hypertension, fatty acid, heart, calcium

Procedia PDF Downloads 83

Authors: D. Bhowmik, Y. Tian, Q. Yin, F. Zhu

Abstract:

Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.

Keywords: Kaposi's sarcoma-associated herpesvirus, KSHV, cGAS, DNA binding, inhibition

Procedia PDF Downloads 109

Authors: D. F. Zeynalov, T. V. Kartseva, O. V. Sorokin

Abstract:

Currently, approaches to assess cardiointervalography are based on the calculation of data variance intervals RR. However, they do not allow the evaluation of features related to a period of the cardiac cycle, so how electromechanical phenomena during cardiac subphase are characterized by differently directed changes. Therefore, we have proposed a method of subphase analysis of the cardiac cycle, developed in the department of hominal physiology Novosibirsk State Medical University to identify the features of the dispersion subphase of the cardiac cycle. In the present paper we have examined the 5-minute intervals cardiointervalography (CIG) to isolate RR-, QT-, ST-ranges in healthy children and children with acute respiratory diseases (ARD) in comparison. It is known that primary school-aged children suffer at ARD 5-7 times per year. Consequently, it is one of the most relevant problems in pediatrics. It is known that the spectral indices and indices of temporal analysis of heart rate variability are highly sensitive to the degree of intoxication during immunological process. We believe that the use of subphase analysis of heart rate will allow more thoroughly evaluate responsiveness of the child organism during the course of ARD. The study involved 60 primary school-aged children (30 boys and 30 girls). In order to assess heart rhythm regulation, the record CIG was used on the "VNS-Micro" device of Neurosoft Company (Ivanovo) for 5 minutes in the supine position and 5 minutes during active orthostatic test. Subphase analysis of variance QT-interval and ST-segment was performed on the "KardioBOS" software Biokvant Company (Novosibirsk). In assessing the CIG in the supine position and in during orthostasis of children with acute respiratory diseases only RR-intervals are observed typical trend of general biological reactions through pressosensitive compensation mechanisms to lower blood pressure, but compared with healthy children the severity of the changes is different, of sick children are more pronounced indicators of heart rate regulation. But analysis CIG RR-intervals and analysis subphase ST-segment have yielded conflicting trends, which may be explained by the different nature of the intra- and extracardiac influences on regulatory mechanisms that implement the various phases of the cardiac cycle.

Keywords: acute respiratory diseases, cardiointervalography, subphase analysis, cardiac cycle

Procedia PDF Downloads 253

Authors: R. P. Hewawasam, A. F. Dulhunty

Abstract:

The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

Procedia PDF Downloads 267

Authors: Parnaz Boodagh, Danila Vella, Antonio Damore, Laura Modica De Mohac, Sang-Ho Ye, Garret Coyan, Gaetano Burriesci, William Wagner, Federica Cosentino

Abstract:

The use of cardiac patches is among the main therapeutic solution for cardiovascular diseases, a leading mortality cause in the world with an increasing trend, responsible of 19 millions deaths in 2020. Several classes of biomaterials serve that purpose, both of synthetic origin and biological derivation, and many bioengineered treatment alternatives were proposed to satisfy two main requirements, providing structural support and promoting tissue remodeling. The objective of this paper is to compare the mechanical properties and the characterization of four cardiac patches: the Adeka, PhotoFix, CorPatch, and CardioCel patches. In vitro and in vivo tests included: biaxial, uniaxial, ball burst, suture retention for mechanical characterization; 2D surface topography, 3D volume and microstructure, and histology assessments for structure characterization; in vitro test to evaluate platelet deposition, calcium deposition, and macrophage polarization; rat right ventricular outflow tract (RVOT) models at 8- and 16-week time points to characterize the patch-host interaction. Lastly, the four patches were used to produce four stented aortic valve prosthesis, subjected to hydrodynamic assessment as well as durability testing to verify compliance with the standard ISO.

Keywords: cardiac patch, cardiovascular disease, cardiac repair, blood contact biomaterial

Procedia PDF Downloads 117

Authors: Matthew Cameron, Stephen Yang, Latifa Al Kharusi, Adam Gosselin, Anissa Chirico, Pouya Gholipour Baradari

Abstract:

Background: Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for the potential to increase baseline hemoglobin and decrease the incidence of red blood cell (RBC) transfusion during cardiac surgery. This study's main objective was to evaluate the evidence for iron administration in cardiac surgery patients for its effect on the incidence of perioperative RBC transfusion. Methods: This systematic review protocol was registered with PROSPERO (CRD42020161927) on Dec. 19th, 2019, and was prepared as per the PRISMA guidelines. MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar were searched for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. Each abstract was independently reviewed by two reviewers using predefined eligibility criteria. The primary outcome was perioperative RBC transfusion, with secondary outcomes of the number of RBC units transfused, change in ferritin level, reticulocyte count, hemoglobin, and adverse events, after iron administration. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the primary and secondary outcomes were analyzed with a random-effects model. Results: Out of 1556 citations reviewed, five studies (n = 554 patients) met the inclusion criteria. The use of iron demonstrated no difference in transfusion incidence (RR 0.86; 95% CI 0.65 to 1.13). There was a low heterogeneity between studies (I²=0%). The trial sequential analysis suggested an optimal information size of 1132 participants, which the accrued information size did not reach. Conclusion: The current literature does not support the routine use of iron supplementation before cardiac surgery; however, insufficient data is available to draw a definite conclusion. A critical knowledge gap has been identified, and more robust RCTs are required on this topic.

Keywords: cardiac surgery, iron, iron supplementation, perioperative medicine, meta-analysis, systematic review, randomized controlled trial

Procedia PDF Downloads 108

Authors: Krishnamoorthy Shanmugaraj, Malaichamy Ilanchelian

Abstract:

Ascorbic acid is an essential component in the diet of humans, and also is a typical long used pharmaceutical agent. In the present contribution, we have carried out a detailed study on the binding interaction of ascorbic acid (AA) with bovine hemoglobin (BHb) using steady state emission, time resolved fluorescence, UV-Vis absorption, circular dichroism (CD), Fourier transform infra-red (FT-IR) and three dimensional emission (3D) spectral studies. The results from the emission spectral studies unveiled that the quenching of BHb emission by AA is attributed to the formation of a complex in the ground state (static in nature) after correcting for inner filter effect. The binding parameters calculated from corrected emission quenching data revealed that BHb exhibited a significant binding affinity towards AA. Moreover, AA induced tertiary and secondary conformational changes of BHb were monitored by UV-Vis absorption, CD, FT-IR and 3D emission spectral studies. The results presented here will help to further understand the credible mechanism of BHb-AA system which is expected to provide insights into conformational and microenvironmental changes of BHb.

Keywords: ascorbic acid, bovine hemoglobin, circular dichroism, three dimensional emission spectral studies

Procedia PDF Downloads 939