Cardiotoxicity of Fluoropyrimidines: Epidemiology, Mechanisms, Diagnosis, and Management

Cancer is a growing public health problem; it is responsible annually for millions of deaths worldwide. Fluoropyrimidines are highly effective and commonly prescribed anti-neoplastic drugs used in a wide range of chemotherapy regimens against several types of malignancies. 5-fluorouracil and its prodrugs affect neoplastic cells in multiple ways by impairing their proliferation, principally through the inhibition of thymidylate synthase. Fluoropyrimidine-induced cardiotoxicity was described more than 50 years ago, but many details such as incidence, mechanisms, and treatment are unclear and remain disputed. Severe cardiotoxicity is not only life-threatening, but also leads to withdrawal from an optimal chemotherapy regimen and decreases survival rate. Differences in the frequency of cardiotoxicity are explained by different chemotherapy schedules, doses, criteria, and populations. Proposed pathophysiological mechanisms include coronary vasospasm, endothelial damage, oxidative stress, Krebs cycle disturbances, and toxic metabolites. Such varied pathophysiology of the cardiotoxicity phenomenon makes prevention and treatment more difficult. Cardiovascular disturbances, including chest pain, arrhythmias, and myocardial infarction, are among the most common side effects of this class of anti-neoplastic medication. This study aims to summarize the available data on fluoropyrimidine cardiotoxicity with respect to symptoms, incidence, metabolism, pathophysiological mechanism, diagnosis, management, and resistance.

Download Full-text

An uncommon case of venomous snake bite complicated by intracranial haemorrhage

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20202124 ◽

2020 ◽

Vol 7 (6) ◽

pp. 1029

Author(s):

Anant Parasher ◽

Prabhat Gautam Roy ◽

Soumya Inamadar

Keyword(s):

Intracranial Haemorrhage ◽

Public Health Problem ◽

Neurological Complications ◽

Snake Bite ◽

Rural Populations ◽

Neurological Sequelae ◽

Venomous Snake ◽

Wide Range ◽

Life Threatening ◽

Uncommon Case

Snake bite is a widespread and neglected public health problem in tropical and subtropical countries, where rural populations are mainly affected. Although venomous snake bite may lead to a wide range of complications, life-threatening neurological complications such as Intracerebral Haemorrhage (ICH) are rare and infrequently documented in literature. Here we discuss the case of a 64-year-old man who developed ICH following a viper bite, and the neurological sequelae that followed after management.

Download Full-text

Carbon Dots for Bacterial Detection and Antibacterial Applications-A Minireview

Current Pharmaceutical Design ◽

10.2174/1381612825666191216150948 ◽

2020 ◽

Vol 25 (46) ◽

pp. 4848-4860 ◽

Cited By ~ 2

Author(s):

Anisha Anand ◽

Gopinathan Manavalan ◽

Ranju Prasad Mandal ◽

Huan-Tsung Chang ◽

Yi-Ru Chiou ◽

...

Keyword(s):

Optical Properties ◽

Carbon Dots ◽

Antibacterial Effect ◽

Bacterial Detection ◽

High Brightness ◽

Photo Catalysis ◽

Wide Range ◽

Prevention And Treatment ◽

Low Toxicity ◽

Conventional Antibiotics

: The prevention and treatment of various infections caused by microbes through antibiotics are becoming less effective due to antimicrobial resistance. Researches are focused on antimicrobial nanomaterials to inhibit bacterial growth and destroy the cells, to replace conventional antibiotics. Recently, carbon dots (C-Dots) become attractive candidates for a wide range of applications, including the detection and treatment of pathogens. In addition to low toxicity, ease of synthesis and functionalization, and high biocompatibility, C-Dots show excellent optical properties such as multi-emission, high brightness, and photostability. C-Dots have shown great potential in various fields, such as biosensing, nanomedicine, photo-catalysis, and bioimaging. This review focuses on the origin and synthesis of various C-Dots with special emphasis on bacterial detection, the antibacterial effect of CDots, and their mechanism.

Download Full-text

Nanoparticles and Its Implications in HIV/AIDS Therapy

Current Drug Discovery Technologies ◽

10.2174/1570163816666190620111652 ◽

2020 ◽

Vol 17 (4) ◽

pp. 448-456 ◽

Cited By ~ 1

Author(s):

Victor B. Oti

Keyword(s):

Direct Injection ◽

Oral Intake ◽

Public Health Problem ◽

Antiretroviral Drugs ◽

The Body ◽

Viral Agent ◽

Treatment And Prevention ◽

Prevention And Treatment ◽

Hiv Aids

The use of Antiretroviral drugs in treating HIV/ AIDS patients has enormously increased their life spans with serious disadvantages. The virus infection still remains a public health problem worldwide with no cure and vaccine for the viral agent until now. The use of nanoparticles (NPs) for the treatment and prevention of HIV/AIDS is an emerging technology of the 21st century. NPs are solid and colloid particles with 10 nm to <1000 nm size range; although, less than 200 nm is the recommended size for nanomedical usage. There are NPs with therapeutic capabilities such as liposomes, micelles, dendrimers and nanocapsules. The particle enters the body mainly via oral intake, direct injection and inhalation. It has been proven to have potentials of advancing the prevention and treatment of the viral agent. Certain NPs have been shown to have selftherapeutic activity for the virus in vitro. Strategies that are novel are emerging which can be used to improve nanotechnology, such as genetic treatment and immunotherapy. In this review, nanoparticles, the types and its characteristics in drug delivery were discussed. The light was furthermore shed on its implications in the prevention and treatment of HIV/AIDS.

Download Full-text

Beehive Products as Antibacterial Agents: A Review

Antibiotics ◽

10.3390/antibiotics10060717 ◽

2021 ◽

Vol 10 (6) ◽

pp. 717

Author(s):

Rita Abou Nader ◽

Rawan Mackieh ◽

Rim Wehbe ◽

Dany El El Obeid ◽

Jean Marc Sabatier ◽

...

Keyword(s):

Antibacterial Activity ◽

Honey Bee ◽

Antibacterial Agents ◽

Royal Jelly ◽

Biological Activities ◽

Vital Role ◽

Bee Venom ◽

Bacterial Strains ◽

Wide Range ◽

Life Threatening

Honeybees are one of the most marvelous and economically beneficial insects. As pollinators, they play a vital role in every aspect of the ecosystem. Beehive products have been used for thousands of years in many cultures for the treatment of various diseases. Their healing properties have been documented in many religious texts like the Noble Quran and the Holy Bible. Honey, bee venom, propolis, pollen and royal jelly all demonstrated a richness in their bioactive compounds which make them effective against a variety of bacterial strains. Furthermore, many studies showed that honey and bee venom work as powerful antibacterial agents against a wide range of bacteria including life-threatening bacteria. Several reports documented the biological activities of honeybee products but none of them emphasized on the antibacterial activity of all beehive products. Therefore, this review aims to highlight the antibacterial activity of honey, bee venom, propolis, pollen and royal jelly, that are produced by honeybees.

Download Full-text

Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome

International Journal of Molecular Sciences ◽

10.3390/ijms22041617 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1617

Author(s):

Jimin Xu ◽

Judith Berastegui-Cabrera ◽

Marta Carretero-Ledesma ◽

Haiying Chen ◽

Yu Xue ◽

...

Keyword(s):

Potent Inhibitor ◽

Antiviral Drug ◽

Human Adenovirus ◽

Yield Reduction ◽

Respiratory Illnesses ◽

Molecule Inhibitor ◽

Wide Range ◽

Ic50 Values ◽

Life Threatening ◽

Salicylamide Derivatives

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

Download Full-text

Chromosomal Locus That Affects Pathogenicity of Rhodococcus fascians

Journal of Bacteriology ◽

10.1128/jb.184.4.1112-1120.2002 ◽

2002 ◽

Vol 184 (4) ◽

pp. 1112-1120 ◽

Cited By ~ 51

Author(s):

Danny Vereecke ◽

Karen Cornelis ◽

Wim Temmerman ◽

Mondher Jaziri ◽

Marc Van Montagu ◽

...

Keyword(s):

Krebs Cycle ◽

Malate Synthase ◽

Habitat Modification ◽

Signal Molecules ◽

In Planta ◽

Chromosomal Locus ◽

Physiological Alterations ◽

Rhodococcus Fascians ◽

Wide Range ◽

Symptomatic Tissue

ABSTRACT The gram-positive plant pathogen Rhodococcus fascians provokes leafy gall formation on a wide range of plants through secretion of signal molecules that interfere with the hormone balance of the host. Crucial virulence genes are located on a linear plasmid, and their expression is tightly controlled. A mutant with a mutation in a chromosomal locus that affected virulence was isolated. The mutation was located in gene vicA, which encodes a malate synthase and is functional in the glyoxylate shunt of the Krebs cycle. VicA is required for efficient in planta growth in symptomatic, but not in normal, plant tissue, indicating that the metabolic requirement of the bacteria or the nutritional environment in plants or both change during the interaction. We propose that induced hyperplasia on plants represents specific niches for the causative organisms as a result of physiological alterations in the symptomatic tissue. Hence, such interaction could be referred to as metabolic habitat modification.

Download Full-text

Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0414 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Michele Mussap ◽

Vassilios Fanos

Keyword(s):

Molecular Mechanisms ◽

Vascular Dysfunction ◽

Asymptomatic Infection ◽

Multiple Organ ◽

Therapeutic Interventions ◽

Patient Specific ◽

Wide Range ◽

Life Threatening ◽

The Individual ◽

Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

Download Full-text

Main approaches to treatment of hypoxia in acute respiratory distress syndrome, bacterial and viral pneumonia (part III)

Medical alphabet ◽

10.33667/2078-5631-2021-4-38-55 ◽

2021 ◽

pp. 38-55

Author(s):

A. V. Vlasenko ◽

E. A. Evdokimov ◽

E. P. Rodionov

Keyword(s):

Respiratory Failure ◽

Distress Syndrome ◽

Experimental Studies ◽

Viral Pneumonia ◽

Medical Technologies ◽

Clinical Observations ◽

Wide Range ◽

Prevention And Treatment ◽

High Degree

The paper summarizes data on modern approaches to the diagnosis, prevention and treatment of severe acute parenchymal respiratory failure of various origins, including ARDS due to bacterial viral pneumonia. The work is based on the data of modern well-organized studies, analysis of international clinical guidelines with a high degree of evidence, as well as the results of our own long-term experimental studies and clinical observations of the treatment of patients with ARDS of various origins, including viral pneumonia of 2009, 2016, 2020. Scientifically grounded algorithms for prevention, differential diagnosis and personalized therapy of severe acute respiratory failure using innovative medical technologies and a wide range of respiratory and adjuvant treatment methods have been formulated. The authors tried to adapt as much as possible the existing current recommendations for the daily clinical practice of anesthesiologists and resuscitators.

Download Full-text

ANTIBIOTIC SUSCEPTIBILITY PATTERN OF STAPHYLOCOCCOUS AUREUS ISOLATED FROM VARIOUS CLINICAL SPECIMENS OF TERTIARY CARE HOSPITAL IN TIRUPATI.

10.36106/ijsr/2117632 ◽

2021 ◽

pp. 14-15

Author(s):

Indira Ananthapadmanab asamy ◽

V. Pavani Sai Mounika ◽

K. Vijayakumar ◽

C.H. Srinivasa Rao

Keyword(s):

Antimicrobial Susceptibility ◽

Tertiary Care ◽

Care Hospital ◽

Susceptibility Pattern ◽

Clinical Specimens ◽

Antimicrobial Susceptibility Pattern ◽

Wide Range ◽

Life Threatening ◽

Mrsa Infection ◽

Systemic Infections

INTRODUCTION: Staphylococcus aureus causes a wide range of infections including skin and soft tissue infections to life-threatening systemic infections like sepsis, endocarditis. This study ais to evaluate the antimicrobial susceptibility pattern of S.aurues among various clinical specimens. METHODS: The study included 326 S.aurues, isolated from various clinical specimens which were subjected to antimicrobial susceptibility testing as per CLSI guidelines. RESULTS: Among the 326 isolates, the highest were from pus specimens (47.85%), and was from Orthopaedics department (28.53%). Among the isolates, 219 (67.17%) were Methicilin resistant. All isolates were sensitive to Vancomycin, and all urine isolates were sensitive to Nitrofurantoin. The highest resistance was towards Penicillin (87.42%), Erythromycin (85.28), and Ciprooxacin (83.13%). CONCLUSION: The most effective way to prevent MRSA infection in every hospital is by performing continuous surveillance of antibiotic resistance and by following an effetive antibiotic policy.

Download Full-text

Updates and Advances: Pediatric Musculoskeletal Infection Imaging Made Easier for Radiologists and Clinicians

Seminars in Musculoskeletal Radiology ◽

10.1055/s-0041-1723004 ◽

2021 ◽

Vol 25 (01) ◽

pp. 167-175

Author(s):

Michael S. Furman ◽

Ricardo Restrepo ◽

Supika Kritsaneepaiboon ◽

Bernard F. Laya ◽

Domen Plut ◽

...

Keyword(s):

Clinical Practice ◽

Imaging Techniques ◽

Daily Clinical Practice ◽

Infants And Children ◽

Imaging Evaluation ◽

Musculoskeletal Infection ◽

Wide Range ◽

Life Threatening ◽

Optimal Patient Management

AbstractInfants and children often present with a wide range of musculoskeletal (MSK) infections in daily clinical practice. This can vary from relatively benign superficial infections such as cellulitis to destructive osseous and articular infections and life-threatening deep soft tissue processes such as necrotizing fasciitis. Imaging evaluation plays an essential role for initial detection and follow-up evaluation of pediatric MSK infections. Therefore, a clear and up-to-date knowledge of imaging manifestations in MSK infections in infants and children is imperative for timely and accurate diagnosis that, in turn, can result in optimal patient management. This article reviews an up-to-date practical imaging techniques, the differences between pediatric and adult MSK infections, the spectrum of pediatric MSK infections, and mimics of pediatric MSK infections encountered in daily clinical practice by radiologists and clinicians.

Download Full-text