scholarly journals ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

2014 ◽  
Vol 56 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Elsy Nalleli Loria-Cervera ◽  
Fernando Jose Andrade-Narvaez
Keyword(s):  
Animal Models ◽  
Human Disease ◽  
Public Health Problem ◽  
Leishmania Species ◽  
Experimental Models ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Major Public Health Problem ◽  
Wild Rodents ◽  
Experimental Conditions

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis

2021 ◽  
Author(s):  
Thalia Pacheco-Fernandez ◽  
Greta Volpedo ◽  
Chaitenya Verma ◽  
Abhay R. Satoskar
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Public Health Problem ◽  
Host Immune Response ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Major Public Health Problem ◽  
Wide Range ◽  
Vector Borne ◽  
Leishmania Parasites

Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.

scholarly journals Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2233 ◽  
Author(s):  
Salameh ◽  
Morel ◽  
Zeilani ◽  
Déchelotte ◽  
Marion-Letellier
Keyword(s):  
Growth Failure ◽  
Public Health Problem ◽  
Nutritional Intervention ◽  
Experimental Models ◽  
Major Public Health Problem ◽  
Gut Function ◽  
Environmental Enteric Dysfunction ◽  
Clinical Models ◽  
Novel Therapeutic Strategies ◽  
The Impact

: Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.

scholarly journals Distribution of Leishmania Infection in Humans, Animal Reservoir Hosts and Sandflies in Golestan Province, Northeastern Iran: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Omid MOZAFARI ◽  
Aioub SOFIZADEH ◽  
Hamid Reza SHORAKA
Keyword(s):  
Visceral Leishmaniasis ◽  
Random Effect ◽  
Random Effect Model ◽  
Leishmania Species ◽  
Control Measures ◽  
Leishmania Infection ◽  
Wild Rodents ◽  
Animal Reservoir ◽  
Pooled Prevalence ◽  
Golestan Province

Background: Leishmaniasis is one of the most important parasitic diseases in the Golestan Province, northeastern Iran. In this study, we summarize the results of studies on the disease and its causative agent Leishmania in humans, vectors and reservoirs in the Golestan Province, Iran. Methods: We retrieved all articles related to leishmaniasis in the Golestan Province, northern Iran from 1994 to 2018 in various databases including PubMed, Scopus and Web of Science. Articles in Persian were retrieved from the IranMedex, SID and Magiran. Reference lists of relevant articles were also hand-searched. Local active researchers in the field of leishmaniasis were contacted to avoid missing any relevant articles. Overall, 54 papers were extracted, later evaluated by two research team members based on inclusion criteria. All analyses were performed using the Stata 14 software. Pooled prevalence was calculated using the metaprop command and a random-effect model. The I² statistic was used for measuring heterogeneity of studies. Results: Ten articles in the province were related to detection of Leishmania species in patients with suspected cutaneous or visceral leishmaniasis. Fifteen articles were dedicated to identification of Leishmania species in disease reservoirs and five articles were about detection of the parasite in sand flies. The pooled prevalence of L. major in patients with acute ulcer, wild rodents and sandflies was 83%, 29% and 11%, respectively. Conclusion: Our findings highlight the need for implementation of control measures among the reservoirs of both cutaneous and visceral leishmaniasis in the Golestan Province, Iran.

scholarly journals Pathogenesis of Cerebral Malaria: Recent Experimental Data and Possible Applications for Humans

2001 ◽  
Vol 14 (4) ◽  
pp. 810-820 ◽  
Author(s):  
Jinning Lou ◽  
Ralf Lucas ◽  
Georges E. Grau
Keyword(s):  
Endothelial Cells ◽  
Cerebral Malaria ◽  
Public Health Problem ◽  
Major Complication ◽  
Experimental Models ◽  
Soluble Form ◽  
Recent Experimental Data ◽  
Major Public Health Problem

SUMMARY Malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. Experimental models represent useful tools to better understand the mechanisms of this syndrome. Here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. In particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome, implying that the transmembrane form of TNF may be more important than the soluble form of the cytokine. It has also been shown that in addition to differences in immune responsiveness between genetically resistant and susceptible mice, there are marked differences at the level of the target cell of the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a paradoxical role of platelets has been proposed. Indeed, platelets appear to be pathogenic rather than protective in inflammatory conditions because they can potentiate the deleterious effects of TNF. More recently, it has been shown that interactions among platelets, leukocytes, and endothelial cells have phenotypic and functional consequences for the endothelial cells. A better understanding of these complex interactions leading to vascular injury will help improve the outcome of cerebral malaria.

scholarly journals mTOR Kinase: A Possible Pharmacological Target in the Management of Chronic Pain

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Lucia Lisi ◽  
Paola Aceto ◽  
Pierluigi Navarra ◽  
Cinzia Dello Russo
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Mammalian Target Of Rapamycin ◽  
Public Health Problem ◽  
Experimental Models ◽  
Major Public Health Problem ◽  
Major Mechanism ◽  
Mtor Kinase ◽  
Pain Transmission ◽  
Pharmacological Target

Chronic pain represents a major public health problem worldwide. Current pharmacological treatments for chronic pain syndromes, including neuropathic pain, are only partially effective, with significant pain relief achieved in 40–60% of patients. Recent studies suggest that the mammalian target of rapamycin (mTOR) kinase and downstream effectors may be implicated in the development of chronic inflammatory, neuropathic, and cancer pain. The expression and activity of mTOR have been detected in peripheral and central regions involved in pain transmission. mTOR immunoreactivity was found in primary sensory axons, in dorsal root ganglia (DRG), and in dorsal horn neurons. This kinase is a master regulator of protein synthesis, and it is critically involved in the regulation of several neuronal functions, including the synaptic plasticity that is a major mechanism leading to the development of chronic pain. Enhanced activation of this pathway is present in different experimental models of chronic pain. Consistently, pharmacological inhibition of the kinase activity turned out to have significant antinociceptive effects in several experimental models of inflammatory and neuropathic pain. We will review the main evidence from animal and human studies supporting the hypothesis that mTOR may be a novel pharmacological target for the management of chronic pain.

scholarly journals Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 594 ◽  
Author(s):  
Daniela Pellegrino ◽  
Daniele La Russa ◽  
Alessandro Marrone
Keyword(s):  
Risk Factors ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Public Health Problem ◽  
Kidney Damage ◽  
Major Public Health Problem ◽  
Altered Expression ◽  
Oxidative Balance ◽  
Increased Risk

Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors’ laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors.

scholarly journals Sodium-Hydrogen Exchanger Isoform-1 Inhibition: A Promising Pharmacological Intervention for Resuscitation from Cardiac Arrest

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1765 ◽  
Author(s):  
Raúl J. Gazmuri ◽  
Jeejabai Radhakrishnan ◽  
Iyad M. Ayoub
Keyword(s):  
Cardiac Arrest ◽  
Animal Models ◽  
Myocardial Dysfunction ◽  
Sudden Cardiac Arrest ◽  
Cardiac Activity ◽  
Public Health Problem ◽  
Left Ventricular ◽  
Pharmacological Intervention ◽  
Major Public Health Problem ◽  
Electrical Stability

Out-of-hospital sudden cardiac arrest is a major public health problem with an overall survival of less than 5%. Upon cardiac arrest, cessation of coronary blood flow rapidly leads to intense myocardial ischemia and activation of the sarcolemmal Na+-H+ exchanger isoform-1 (NHE-1). NHE-1 activation drives Na+ into cardiomyocytes in exchange for H+ with its exchange rate intensified upon reperfusion during the resuscitation effort. Na+ accumulates in the cytosol driving Ca2+ entry through the Na+-Ca2+ exchanger, eventually causing cytosolic and mitochondrial Ca2+ overload and worsening myocardial injury by compromising mitochondrial bioenergetic function. We have reported clinically relevant myocardial effects elicited by NHE-1 inhibitors given during resuscitation in animal models of ventricular fibrillation (VF). These effects include: (a) preservation of left ventricular distensibility enabling hemodynamically more effective chest compressions, (b) return of cardiac activity with greater electrical stability reducing post-resuscitation episodes of VF, (c) less post-resuscitation myocardial dysfunction, and (d) attenuation of adverse myocardial effects of epinephrine; all contributing to improved survival in animal models. Mechanistically, NHE-1 inhibition reduces adverse effects stemming from Na+–driven cytosolic and mitochondrial Ca2+ overload. We believe the preclinical work herein discussed provides a persuasive rationale for examining the potential role of NHE-1 inhibitors for cardiac resuscitation in humans.

scholarly journals Human leishmaniasis in Brazil: A general review

2018 ◽  
Vol 64 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Laís Anversa ◽  
Monique Gomes Salles Tiburcio ◽  
Virgínia Bodelão Richini-Pereira ◽  
Luis Eduardo Ramirez
Keyword(s):  
Public Health ◽  
Health Problem ◽  
Human Disease ◽  
Public Health Problem ◽  
Clinical Spectrum ◽  
Major Public Health Problem ◽  
General Review ◽  
Host Parasite Interactions ◽  
Human Leishmaniasis ◽  
Host Parasite

Summary Leishmaniasis is a disease with ample clinical spectrum and epidemiological diversity and is considered a major public health problem. This article presents an overview of the transmission cycles, host-parasite interactions, clinical, histological and immunological aspects, diagnosis and treatment of various forms of the human disease.

scholarly journals Antitumor Activity of Monoterpenes Found in Essential Oils

2014 ◽  
Vol 2014 ◽  
pp. 1-35 ◽  
Author(s):  
Marianna Vieira Sobral ◽  
Aline Lira Xavier ◽  
Tamires Cardoso Lima ◽  
Damião Pergentino de Sousa
Keyword(s):  
Public Health ◽  
Antitumor Activity ◽  
Essential Oils ◽  
Genetic Disease ◽  
Public Health Problem ◽  
Mechanisms Of Action ◽  
Experimental Models ◽  
Major Public Health Problem ◽  
Bioactive Substances ◽  
Chemical Structures

Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.

The Leishmanioses

2011 ◽  
Author(s):  
Marina Gramiccia
Keyword(s):  
South America ◽  
Cutaneous Lesion ◽  
Public Health Problem ◽  
Leishmania Species ◽  
Neglected Diseases ◽  
Major Public Health Problem ◽  
Phlebotomine Sandflies ◽  
Wide Range ◽  
Behavioural Factors ◽  
Visceral Leishmaniosis

Leishmanioses are a large group of parasitic diseases range over the intertropical zones of America and Africa, and extend into temperate regions of South America, Southern Europe and Asia. The clinical aspect of the diseases is wide ranging from a simple, self-resolving cutaneous lesion to the potentially fatal visceral leishmaniosis, known as kala-azar. In numerous underdeveloped countries leishmanioses remain a major public health problem representing one of the most neglected diseases. Among 15 well-recognized Leishmania species known to infect humans, 13 have definite zoonotic nature, which include agents of visceral, cutaneous and mucocutaneous forms of the disease in both the Old and New Worlds. Mammal reservoir hosts belong to the marsupalia, edentata, carnivora, hyracoidea, and rodentia, maintaining sylvatic zoonotic foci in the deserts of Africa and Asia, the forests of South and Central America, as well as synanthropic foci in the Mediterranean basin and much of South America. Although the known vectors are all phlebotomine sandflies, these have a wide range of specific habits and habitats. The complexity of this group of infections has only recently been appreciated and is still being worked out. Currently, leishmanioses show a wider geographical distribution than previously known, with increased global incidence of human disease. Environmental, demographic and human behavioural factors contribute to the changing leishmaniosis landscape, which basically include increasing risk factors for zoonotic cutaneous leishmanioses, and new scenarios associated with the zoonotic entity of visceral leishmaniosis. In comparison with the anthroponotic entities of leishmaniosis, limited progresses were made for the control of the zoonotic ones, consisting mainly in new tools developed for the control of L. infantum in the canine reservoir.

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