scholarly journals Developments in Diagnosis and Antileishmanial Drugs

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Prachi Bhargava ◽  
Rajni Singh
Keyword(s):  
Cell Biology ◽  
Mammalian Cells ◽  
Drug Targets ◽  
Neglected Tropical Diseases ◽  
Diagnostic Methods ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Recent Developments ◽  
Antileishmanial Drug ◽  
Early Case

Leishmaniasis ranks the third in disease burden in disability-adjusted life years caused by neglected tropical diseases and is the second cause of parasite-related deaths after malaria; but for a variety of reasons, it is not receiving the attention that would be justified seeing its importance. Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genusLeishmania. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1–1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. Improvements in diagnostic methods for early case detection and latest combitorial chemotherapeutic methods have given a new hope for combating this deadly disease. The cell biology ofLeishmaniaand mammalian cells differs considerably and this distinctness extends to the biochemical level. This provides the promise that many of the parasite’s proteins should be sufficiently different from hosts and can be successfully exploited as drug targets. This paper gives a brief overview of recent developments in the diagnosis and approaches in antileishmanial drug discovery and development.

scholarly journals Methods for protein delivery into cells: from current approaches to future perspectives

2020 ◽  
Vol 48 (2) ◽  
pp. 357-365
Author(s):  
Chalmers Chau ◽  
Paolo Actis ◽  
Eric Hewitt
Keyword(s):  
Single Molecule ◽  
Cell Biology ◽  
Protein Delivery ◽  
Mammalian Cells ◽  
Cultured Cells ◽  
Cellular Damage ◽  
Future Perspectives ◽  
Chemically Modified ◽  
Recent Developments ◽  
Direct Delivery

The manipulation of cultured mammalian cells by the delivery of exogenous macromolecules is one of the cornerstones of experimental cell biology. Although the transfection of cells with DNA expressions constructs that encode proteins is routine and simple to perform, the direct delivery of proteins into cells has many advantages. For example, proteins can be chemically modified, assembled into defined complexes and subject to biophysical analyses prior to their delivery into cells. Here, we review new approaches to the injection and electroporation of proteins into cultured cells. In particular, we focus on how recent developments in nanoscale injection probes and localized electroporation devices enable proteins to be delivered whilst minimizing cellular damage. Moreover, we discuss how nanopore sensing may ultimately enable the quantification of protein delivery at single-molecule resolution.

scholarly journals Physics Comes to the Aid of Medicine—Clinically-Relevant Microorganisms through the Eyes of Atomic Force Microscope

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 969
Author(s):  
Mateusz Cieśluk ◽  
Piotr Deptuła ◽  
Ewelina Piktel ◽  
Krzysztof Fiedoruk ◽  
Łukasz Suprewicz ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antimicrobial Agents ◽  
Antimicrobial Treatment ◽  
Point Of View ◽  
Diagnostic Methods ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Force Microscopy ◽  
Atomic Force ◽  
Recent Developments

Despite the hope that was raised with the implementation of antibiotics to the treatment of infections in medical practice, the initial enthusiasm has substantially faded due to increasing drug resistance in pathogenic microorganisms. Therefore, there is a need for novel analytical and diagnostic methods in order to extend our knowledge regarding the mode of action of the conventional and novel antimicrobial agents from a perspective of single microbial cells as well as their communities growing in infected sites, i.e., biofilms. In recent years, atomic force microscopy (AFM) has been mostly used to study different aspects of the pathophysiology of noninfectious conditions with attempts to characterize morphological and rheological properties of tissues, individual mammalian cells as well as their organelles and extracellular matrix, and cells’ mechanical changes upon exposure to different stimuli. At the same time, an ever-growing number of studies have demonstrated AFM as a valuable approach in studying microorganisms in regard to changes in their morphology and nanomechanical properties, e.g., stiffness in response to antimicrobial treatment or interaction with a substrate as well as the mechanisms behind their virulence. This review summarizes recent developments and the authors’ point of view on AFM-based evaluation of microorganisms’ response to applied antimicrobial treatment within a group of selected bacteria, fungi, and viruses. The AFM potential in development of modern diagnostic and therapeutic methods for combating of infections caused by drug-resistant bacterial strains is also discussed.

scholarly journals Cutaneous Leishmaniasis: The Complexity of Host’s Effective Immune Response against a Polymorphic Parasitic Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Áurea Gabriel ◽  
Ana Valério-Bolas ◽  
Joana Palma-Marques ◽  
Patrícia Mourata-Gonçalves ◽  
Pedro Ruas ◽  
...  
Keyword(s):  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Neglected Tropical Diseases ◽  
Well Being ◽  
World Health ◽  
Disability Adjusted Life ◽  
Life Years ◽  
The Face ◽  
Health Organization

This review is aimed at providing a comprehensive outline of the immune response displayed against cutaneous leishmaniasis (CL), the more common zoonotic infection caused by protozoan parasites of the genus Leishmania. Although of polymorphic clinical presentation, classically CL is characterized by leishmaniotic lesions on the face and extremities of the patients, which can be ulcerative, and even after healing can lead to permanent injuries and disfigurement, affecting significantly their psychological, social, and economic well-being. According a report released by the World Health Organization, the disability-adjusted life years (DALYs) lost due to leishmaniasis are close to 2.4 million, annually there are 1.0–1.5 million new cases of CL, and a numerous population is at risk in the endemic areas. Despite its increasing worldwide incidence, it is one of the so-called neglected tropical diseases. Furthermore, this review provides an overview of the existing knowledge of the host innate and acquired immune response to cutaneous species of Leishmania. The use of animal models and of in vitro studies has improved the understanding of parasite-host interplay and the complexity of immune mechanisms involved. The importance of diagnosis accuracy associated with effective patient management in CL reduction is highlighted. However, the multiple factors involved in CL epizoology associated with the unavailability of vaccines or drugs to prevent infection make difficult to formulate an effective strategy for CL control.

New Approaches to the Microscopic Imaging of Trypanosoma brucei

2004 ◽  
Vol 10 (5) ◽  
pp. 621-636 ◽  
Author(s):  
Mark C. Field ◽  
Clare L. Allen ◽  
Vivek Dhir ◽  
David Goulding ◽  
Belinda S. Hall ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Control Strategies ◽  
Microscopic Analysis ◽  
Current Control ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Technical Advances ◽  
Public Health Strategies

Protozoan parasites are fearsome pathogens responsible for a substantial proportion of human mortality, morbidity, and economic hardship. The principal disease agents are members of the orders Apicomplexa (Plasmodium, Toxoplasma, Eimeria) and Kinetoplastida (Trypanosomes, Leishmania). The majority of humans are at risk from infection from one or more of these organisms, with profound effects on the economy, social structure and quality of life in endemic areas; Plasmodium itself accounts for over one million deaths per annum, and an estimated 4 × 107 disability-adjusted life years (DALYs), whereas the Kinetoplastida are responsible for over 100,000 deaths per annum and 4 × 106 DALYs. Current control strategies are failing due to drug resistance and inadequate implementation of existing public health strategies. Trypanosoma brucei, the African Trypanosome, has emerged as a favored model system for the study of basic cell biology in Kinetoplastida, because of several recent technical advances (transfection, inducible expression systems, and RNA interference), and these advantages, together with genome sequencing efforts are widely anticipated to provide new strategies of therapeutic intervention. Here we describe a suite of methods that have been developed for the microscopic analysis of T. brucei at the light and ultrastructural levels, an essential component of analysis of gene function and hence identification of therapeutic targets.

scholarly journals Neglected Tropical Diseases (NTDs) - A Snapshot of Research

2021 ◽  
pp. 6-12
Author(s):  
Partha Paul ◽  
Dipu Podder ◽  
Arup Kumar ◽  
Md. Ataur Rahman ◽  
Md. Hajbiur Rahman ◽  
...  
Keyword(s):  
Neglected Tropical Diseases ◽  
Negative Impact ◽  
Years Of Life Lost ◽  
Tropical Diseases ◽  
Health Food ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Newborn Child ◽  
Development Outcomes ◽  
Years Lived With Disability

More than a billion people-one-sixth of the earth's population is infected with one or more neglected tropical diseases (NTDs) in developing countries. Over the past decade, interests in NTDs have resurged as these are a barrier to achieving broader human development outcomes (e.g., improved newborn, child and maternal health, food, and nutritional safety). Several national and international organizations (such as the WHO, USAID, CDC, and others) concentrate on NTDs and fighting to control or prevent them. This review describes a brief introduction to NTDs, the global burden of the diseases in terms of disability-adjusted life years (DALYs), years lived with disability (YLDs) and years of life lost (YLLs). This paper also reviews the negative impact of these diseases on global economies and discusses strategies for public health to prevent and eliminate these diseases, the achievements and challenges that can be achieved to address adversity there.

Optogenetics for gene expression in mammalian cells

2015 ◽  
Vol 396 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Konrad Müller ◽  
Sebastian Naumann ◽  
Wilfried Weber ◽  
Matias D. Zurbriggen
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Mammalian Cells ◽  
Expression System ◽  
Molecular Switches ◽  
Central Research ◽  
Spatiotemporal Resolution ◽  
Cellular Processes ◽  
Recent Developments ◽  
Expression In Mammalian Cells

Abstract Molecular switches that are controlled by chemicals have evolved as central research instruments in mammalian cell biology. However, these tools are limited in terms of their spatiotemporal resolution due to freely diffusing inducers. These limitations have recently been addressed by the development of optogenetic, genetically encoded, and light-responsive tools that can be controlled with the unprecedented spatiotemporal precision of light. In this article, we first provide a brief overview of currently available optogenetic tools that have been designed to control diverse cellular processes. Then, we focus on recent developments in light-controlled gene expression technologies and provide the reader with a guideline for choosing the most suitable gene expression system.

scholarly journals The human hookworm vaccine: recent updates and prospects for success

2015 ◽  
Vol 89 (5) ◽  
pp. 540-544 ◽  
Author(s):  
M.E. Bottazzi
Keyword(s):  
Neglected Tropical Diseases ◽  
Control Strategies ◽  
New Technology ◽  
Preventive Chemotherapy ◽  
Research And Innovation ◽  
New Public Health ◽  
New Public ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Disease Study

AbstractApproximately 440 million people globally are afflicted by hookworm disease, one of the 17 WHO-recognized neglected tropical diseases (NTDs). The iron-deficiency anaemia attributed to this disease contributes to at least 3.2 million disability-adjusted life years (DALYs) according to the Global Burden of Disease Study 2010. The current WHO-recommended control strategies rely primarily on mass drug administration or preventive chemotherapy. However, evidence is starting to accumulate confirming that preventive chemotherapy alone will not be sufficient to reduce the reinfection rates of hookworm, especially in areas of heavy transmission. The global health and research community is currently building a consensus stressing the need for the advancement of research and innovation to bridge the gaps and identify new public health interventions for diseases such as hookworm and other NTDs. This paper presents the strategies used by the Sabin Vaccine Institute Product Development Partnership (Sabin PDP) in their ongoing endeavour for the development of a human hookworm vaccine. Recent updates and the current prospects for success of an effective human hookworm vaccine, as a new technology to be linked to or combined with drug interventions, are presented.

The Role of nitro (NO2-), chloro (Cl), and fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds

2020 ◽  
Vol 21 ◽  
Author(s):  
Boniface Pone ◽  
Ferreira Igne Elizabeth
Keyword(s):  
Chagas Disease ◽  
Mammalian Cells ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Pharmacokinetic Studies ◽  
Scientific Publications ◽  
Antitrypanosomal Activity ◽  
Chemical Groups

: Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas disease are among the most severe NTDs, and are caused by the Leishmania sp, and Trypanosoma cruzi, respectively. Glucantime, pentamidine and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance, and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, which chemical groups are known to improve the biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluoro-synthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth to mention that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro- and chloro-groups in the compound backbone. All in all, nitro and h0alogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts on in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies, and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.

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