Development of Two Charge-Transfer Complex Spectrophotometric Methods for Determination of Tofisopam in Tablet Dosage Form

Purpose: To develop an easy, fast and sensible spectrophotometric method for determination of tofisopam in tablet dosage form.Methods: Tofisopam as n-electron donor is react with two π-acceptors namely: chloranilic acid (ChA), and 7,7,8,8 tetracyanoquinodimethane (TCNQ) to form charge-transfer complexes. The obtained complexes were tested spectrophotometrically at 520 and 824 nm for ChA and TCNQ, respectively. The optimal conditions affecting the reaction status were surveyed and optimized, and the results compared with Japanese Pharmacopeia method.Results: The calibration curve were obeyed Beer`s low in the ranges 25 – 125 and 30 – 150 μg/mL for ChA and TCNQ, respectively. The lower limit of detection was 8.0 and 10.0 μg/m for ChA and TCNQ, respectively. The slope and intercept of the calibration graphs were 0.0025 and 0.011, and 0.0115 and -0.237 for ChA and TCNQ, respectivelyConclusion: The proposed methods have successfully been applied to determination of tofisopam with good accuracy and precision. The methods are accurate as the Japanese pharmacopeial method amd may be applied for routine analysis in quality control laboratories.Keywords: Charge-transfer complex, Tofisopam, Chloranilic acid, Tetracyanoquinodimethane, Spectrophotometr

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature

Brugada syndrome is an inherited cardiac channelopathy arising from mutations in voltage-gated cardiac sodium channels. Idiopathic epilepsy portrays a coalescent underlying pathophysiological mechanism pertaining to the premature excitation of neuronal voltage-gated ion channels resulting in the disruption of presynaptic neurons and the unregulated release of excitatory neurotransmitters. The coexistence of epilepsy and Brugada syndrome may be explained by mutations in voltage-gated ion channels, which are coexpressed in cardiac and neural tissue. Moreover, the incidence of sudden unexpected death in epilepsy has been associated with malignant cardiac arrhythmias in the presence of mutations in voltage-gated ion channels. Lamotrigine is an antiepileptic drug that inhibits neuronal voltage-gated sodium channels, thus stabilizing neural impulse propagation and controlling seizure activity in the brain. However, lamotrigine has been shown to inhibit cardiac voltage-gated sodium channels resulting in a potential arrhythmogenic effect and the ability to unmask Brugada syndrome in genetically susceptible individuals. We are reporting a case of a 27-year-old male patient with a background of presumed idiopathic epilepsy who was initiated on lamotrigine therapy resulting in the unmasking of Brugada syndrome and the onset of syncopal episodes. This case provides further evidence for the arrhythmogenic capacity of lamotrigine and highlights the relationship between epilepsy and Brugada syndrome. In this report, we aim to review the current literature regarding the associations between epilepsy and Brugada syndrome and the impact of lamotrigine therapy on such patients

Prevalence of coronary artery disease and its risk factors in Majmaah City, Kingdom of Saudi Arabia

ObjectiveThis study was carried out with an aim to outline the prevalence of coronary artery diseases, its risk of one region of the Saudi Arabia.MethodsA retrospective observational study conducted across five secondary medical centers located in the city of Majmaah. Hospital medical records and ministry of health records were screened over a 6-month period for data on patients admitted for Coronary artery disease (CAD). Data collected included sociodemographic characteristics, medical profile, and laboratory findings.ResultsA total of 327 participants were included in this study with a median age of 64 and the majority being male participants (59.8%). The majority were married, held a primary school degree and earned a salary for living. A large number (82.9%) were hypertensive and diabetic (66.7%) and one-fourth had a previous MI (25.1%). A large number (73.7%) had heart failure with a mean ejection fraction of 44% (SD = 13). The causes of heart failure were mainly ischemic (56.3%) and hypertensive (28.1%). Readmission rates at 30 and 90 days then at 6 and 12 months were 22, 53.8, 68.8, and 75.8%, respectively. The mortality rates at the same time intervals were 5.5, 8.9, 14.1, and 22.9%, respectively. Predictors of readmission are age, CCI, and NYHA class.ConclusionCoronary artery disease is the leading cause of heart failure. End stage CAD can have similar results in terms of readmission and mortality as heart failure. Future research should target patients in different stages of the condition and monitor their comorbidities which may impact the study findings

Influenza co-infection associated with severity and mortality in COVID-19 patients

Abstract Background In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. Methods Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. Results We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38–8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08–2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). Conclusions Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality

Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-β, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-β, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy

Hyaluronic Acid Coated Chitosan Nanoparticles Reduced the Immunogenicity of the Formed Protein Corona

Abstract Studying the interactions of nanoparticles (NPs) with serum proteins is necessary for the rational development of nanocarriers. Optimum surface chemistry is a key consideration to modulate the formation of the serum protein corona (PC) and the resultant immune response. We investigated the constituent of the PC formed by hyaluronic acid-coated chitosan NPs (HA-CS NPs). Non-decorated chitosan NPs (CS NPs) and alginate-coated chitosan NPs (Alg-CS NPs) were utilized as controls. Results show that HA surface modifications significantly reduced protein adsorption relative to controls. Gene Ontology analysis demonstrates that HA-CS NPs were the least immunogenic nanocarriers. Indeed, less inflammatory proteins were adsorbed onto HA-CS NPs as opposed to CS and Alg-CS NPs. Interestingly, HA-CS NPs differentially adsorbed two unique anti-inflammatory proteins (ITIH4 and AGP), which were absent from the PC of both controls. On the other hand, CS and Alg-CS NPs selectively adsorbed a proinflammatory protein (Clusterin) that was not found on the surfaces of HA-CS NPs. While further studies are needed to investigate abilities of the PCs of only ITIH4 and AGP to modulate the interaction of NPs with the host immune system, our results suggest that this proof-of-concept could potentially be utilized to reduce the immunogenicity of a wide range of nanomaterials

One-year real-world outcomes for patients undergoing transcatheter mitral valve repair: the Gulf MTEER registry (GULF Mitral Transcatheter Edge to Edge Repair)

Background Severe mitral regurgitation (MR) with left ventricular dysfunction portends worse outcomes. Over the course of the last two decades, transcatheter repair of the mitral valve offered an alternative therapeutic modality for those deemed inoperable or high risk. Landmark studies such as the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation and Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation trials have shown conflicting results with respect to all-cause death and heart failure rehospitalisations. The Gulf Mitral Transcatheter Edge to Edge Repair registry (Gulf MTEER registry) is a regional registry that captured outcomes in those undergoing transcatheter repair of the mitral valve. The objectives of this study were to describe the baseline characteristics of patients undergoing transcatheter mitral valve repair in the Gulf region and estimate the cardiovascular effects of the mitral transcatheter therapies in routine practice.Methods The Gulf MTEER registry is an observational, multicentre, retrospective registry that enrolled all patients undergoing transcatheter repair of the mitral valve from four of the Gulf countries (Saudi Arabia, Kuwait, Bahrain, Oman) between 1 January 2017 and 31 December 2019. Baseline characteristics, echocardiographic parameters and immediate procedural success were reported. The primary outcome was a composite of death and rehospitalisations at 1 year. The secondary outcomes were the individual components of the composite endpoint; that is, death and rehospitalisations at 1 year as well as residual or recurrent MR or worsening New York Heart Association class and a need for repeat repair.Results A total of 176 patients were enrolled. Men constituted 56.3% of the total. At 1 year the primary outcome occurred in 21.1% (95% CI 15.6, 27.9). The secondary outcomes of death occurred in 5.4% (CI 2.9, 10.0) and rehospitalisations occurred in 16.9% (CI 11.9, 23.3). Univariate analysis revealed that the odds of having death or re-hospitalisation was two times higher if the effective regurgitant orifice (ERO) >40 mm2 irrespective of the therapy.Conclusions The Gulf MTEER registry is the first registry in the Gulf region defining the patient population receiving MTEER therapies and evaluating 1-year outcomes. This is a low risk cohort with a high rate of immediate procedural success and low rate of all-cause death and rehospitalisations at 1 year. The odds of an event was two times higher if the ERO ≥40 mm2 with only a signal to higher odds for low left ventricular ejection fraction and larger end systolic dimension

The gulf implantable cardioverter-defibrillator registry: Rationale, methodology, and implementation

Background: The implantable cardioverter-defibrillator (ICD) is effective in the prevention of sudden cardiac death in high-risk patients. Little is known about ICD use in the Arabian Gulf. We designed a study to describe the characteristics and outcomes of patients receiving ICDs in the Arab Gulf region. Methods: Gulf ICD is a prospective, multi-center, multinational, and observational study. All adult patients 18 years or older, receiving a de novo ICD implant and willing to sign a consent form will be eligible. Data on baseline characteristics, ICD indication, procedure and programing, in-hospital, and 1-year outcomes will be collected. Target enrollment is 1500 patients, which will provide adequate precision across a wide range of expected event rates. Results: Fifteen centers in six countries are enrolling patients (Saudi Arabia, United Arab Emirates, Kuwait, Oman, Bahrain, and Qatar). Two-thirds of the centers have dedicated electrophysiology laboratories, and in almost all centers ICDs are implanted exclusively by electrophysiologists. Nearly three-quarters of the centers reported annual ICD implant volumes of ≤150 devices, and pulse generator replacements constitute <30% of implants in the majority of centers. Enrollment started in December 2013, and accrual rate increased as more centers entered the study reaching an average of 98 patients per month. Conclusions: Gulf ICD is the first prospective, observational, multi-center, and multinational study of the characteristics and, the outcomes of patients receiving ICDs in the Arab Gulf region. The study will provide valuable insights into the utilization of and outcomes related to ICD therapy in the Gulf region