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Experimental Parasitology Sep 2017Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of... (Review)
Review
Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors.
Topics: Animals; Antiprotozoal Agents; Apicomplexa; Benzimidazoles; Humans; Imidazoles; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Protozoan Infections; Pyridines
PubMed: 28065755
DOI: 10.1016/j.exppara.2017.01.001 -
Parasitology Jul 2016Blood parasites are considered some of the most significant pathogens for the conservation of penguins, due to the considerable morbidity and mortality they have been... (Review)
Review
Blood parasites are considered some of the most significant pathogens for the conservation of penguins, due to the considerable morbidity and mortality they have been shown to produce in captive and wild populations of these birds. Parasites known to occur in the blood of penguins include haemosporidian protozoans (Plasmodium, Leucocytozoon, Haemoproteus), piroplamid protozoans (Babesia), kinetoplastid protozoans (Trypanosoma), spirochete bacteria (Borrelia) and nematode microfilariae. This review provides a critical and comprehensive assessment of the current knowledge on these parasites, providing an overview of their biology, host and geographic distribution, epidemiology, pathology and implications for public health and conservation.
Topics: Animals; Bird Diseases; Geography; Haemosporida; Nematoda; Nematode Infections; Parasites; Plasmodium; Protozoan Infections, Animal; Spheniscidae; Trypanosoma; Trypanosomiasis
PubMed: 27253438
DOI: 10.1017/S0031182016000251 -
European Journal of Clinical... Nov 2016Secretory diarrhea is a historically known serious health implication around the world which primarily originates through pathogenic microorganisms rather than... (Review)
Review
Secretory diarrhea is a historically known serious health implication around the world which primarily originates through pathogenic microorganisms rather than immunological or genetical disorders. This review highlights infective mechanisms of non-inflammatory secretory diarrhea causing pathogens, known therapeutics and their efficacy against them. These non-inflammatory diarrheal pathogens breach cell barriers, induce inflammation, disrupt fluid secretion across the epithelium by alteration in ion transport by faulting cystic fibrosis transmembrane conductance regulator (CFTR), calcium activated chloride channels and ion exchanger functions. Currently, a variety of prevention strategies have been used to treat these symptoms like use of antibacterial drugs, vaccines, fluid and nutritional therapy, probiotics and prebiotics as adjuncts. In progression of the need for a therapy having quick physiological effects, withdrawing the symptoms with a wide and safe therapeutic index, newer antisecretory agents like potent inhibitors, agonists and herbal remedies are some of the interventions which have come into light through greater understanding of the mechanisms and molecular targets involved in intestinal fluid secretion. Although these therapies have their own pros and cons inside the host, the quest for new antisecretory agents has been a successful elucidation to reduce burden of diarrheal disease.
Topics: Bacterial Infections; Chemoprevention; Diarrhea; Humans; Immunization; Probiotics; Protozoan Infections; Virus Diseases
PubMed: 27473379
DOI: 10.1007/s10096-016-2726-5 -
Trends in Parasitology May 2020Inflammasomes are cytosolic complexes that assemble in response to cellular stress or upon sensing microbial molecules, culminating in cytokine processing and an... (Review)
Review
Inflammasomes are cytosolic complexes that assemble in response to cellular stress or upon sensing microbial molecules, culminating in cytokine processing and an inflammatory form of cell death called pyroptosis. Inflammasomes are usually composed of a sensor molecule, an adaptor protein, and an inflammatory caspase, such as Caspase-1, which cleaves and activates multiple substrates, including Gasdermin-D, pro-IL-1β, and pro-IL-18. Ultimately, inflammasome activation promotes inflammation and restriction of the microbial infection. In recent years, many studies have addressed the role of inflammasomes during fungal, bacterial, viral, and parasitic diseases, revealing sophisticated aspects of the host-pathogen interaction. In this review, we summarize recent advances on inflammasome activation in response to intracellular parasites, including Leishmania spp., Plasmodium spp., Trypanosoma cruzi, and Toxoplasma gondii.
Topics: Animals; Eukaryota; Host-Pathogen Interactions; Humans; Inflammasomes; Leishmaniasis; Malaria; Protozoan Infections; Research; Toxoplasmosis; Trypanosomiasis
PubMed: 32298633
DOI: 10.1016/j.pt.2020.02.006 -
Archiv Der Pharmazie Feb 2022Neglected tropical diseases are a diverse group of communicable diseases that are endemic in low- or low-to-middle-income countries located in tropical and subtropical... (Review)
Review
Neglected tropical diseases are a diverse group of communicable diseases that are endemic in low- or low-to-middle-income countries located in tropical and subtropical zones. The number and availability of drugs for treating these diseases are low, the administration route is inconvenient in some cases, and most of them have safety, efficacy, or adverse/toxic reaction issues. The need for developing new drugs to deal with these issues is clear, but one of the most drastic consequences of this negligence is the lack of interest in the research and development of new therapeutic options among major pharmaceutical companies. Positive changes have been achieved over the last few years, although the overall situation remains alarming. After more than one decade since the original work reviewing antiprotozoal agents came to light, now it is time to question ourselves: How has the scenario for the treatment of protozoal diseases such as malaria, leishmaniasis, human African trypanosomiasis, and American trypanosomiasis changed? This review covers the last decade in terms of the drugs currently available for the treatment of these diseases as well as the clinical candidates being currently investigated.
Topics: Animals; Antiprotozoal Agents; Drug Development; Humans; Neglected Diseases; Protozoan Infections
PubMed: 34661935
DOI: 10.1002/ardp.202100338 -
Journal of Feline Medicine and Surgery Jul 2015Hepatozoonosis of domestic cats has been reported in several countries, mainly as a subclinical infection. (Review)
Review
OVERVIEW
Hepatozoonosis of domestic cats has been reported in several countries, mainly as a subclinical infection.
DISEASE AGENT
Infection has been described mostly in areas where canine infection is present and, in recent years, Hepatozoon felis has been identified as a distinct species by molecular techniques. The vector for feline hepatozoonosis remains unknown and the pathogenesis has not been elucidated.
INFECTION IN CATS
Feline hepatozoonosis is mainly a subclinical infection and few cases have been reported with clinical signs. The diagnosis of hepatozoonosis in cats can be made by observation of parasite gamonts in blood smears, parasite meronts in muscles by histopathology, and detection of parasite DNA in blood and tissue by PCR.
DISEASE MANAGEMENT
The treatment of choice is not known, but single cases have been treated with doxycycline or oxytetracycline and primaquine. Although the mode of transmission and the type of vector is not known, preventive treatment against blood-sucking vectors (fleas and ticks) is advised.
Topics: Animal Welfare; Animals; Cat Diseases; Cats; Flea Infestations; Practice Guidelines as Topic; Protozoan Infections, Animal; Veterinary Medicine
PubMed: 26101318
DOI: 10.1177/1098612X15589879 -
Radiologic Technology Sep 2016Waterborne diseases associated with polluted recreational and potable waters have been documented for more than a century. Key microbial protozoan parasites, such as... (Review)
Review
Waterborne diseases associated with polluted recreational and potable waters have been documented for more than a century. Key microbial protozoan parasites, such as Cryptosporidium and Giardia, are causative agents for gastrointestinal disease worldwide. Although not a first-line diagnostic approach for these diseases, medical imaging, such as radiography, computed tomography, magnetic resonance imaging, ultrasonography, and nuclear medicine technologies, can be used to evaluate patients with long-term effects. This article describes protozoan pathogens that affect human health, treatment of common waterborne pathogen-related diseases, and associated medical imaging.
Topics: Diagnosis, Differential; Diagnostic Imaging; Feces; Humans; Intestines; Protozoan Infections
PubMed: 27601690
DOI: No ID Found -
Biomolecules Oct 2022The complement system exerts crucial functions both in innate immune responses and adaptive humoral immunity. This pivotal system plays a major role dealing with... (Review)
Review
The complement system exerts crucial functions both in innate immune responses and adaptive humoral immunity. This pivotal system plays a major role dealing with pathogen invasions including protozoan parasites. Different pathogens including parasites have developed sophisticated strategies to defend themselves against complement killing. Some of these strategies include the employment, mimicking or inhibition of host's complement regulatory proteins, leading to complement evasion. Therefore, parasites are proven to use the manipulation of the complement system to assist them during infection and persistence. Herein, we attempt to study the interaction´s mechanisms of some prominent infectious protozoan parasites including , , , and dealing with the complement system. Moreover, several crucial proteins that are expressed, recruited or hijacked by parasites and are involved in the modulation of the host´s complement system are selected and their role for efficient complement killing or lysis evasion is discussed. In addition, parasite's complement regulatory proteins appear as plausible therapeutic and vaccine targets in protozoan parasitic infections. Accordingly, we also suggest some perspectives and insights useful in guiding future investigations.
Topics: Animals; Parasites; Leishmania; Trypanosoma; Plasmodium; Complement System Proteins; Protozoan Infections
PubMed: 36358913
DOI: 10.3390/biom12111564 -
Expert Opinion on Drug Discovery Aug 2016Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs... (Review)
Review
INTRODUCTION
Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications.
AREAS COVERED
Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail.
EXPERT OPINION
Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.
Topics: Animals; Antiprotozoal Agents; Drug Design; Genomics; High-Throughput Screening Assays; Humans; Molecular Targeted Therapy; Parasites; Proteomics; Protozoan Infections
PubMed: 27238605
DOI: 10.1080/17460441.2016.1195945 -
Mediators of Inflammation 2015
Topics: Animals; Chagas Disease; Humans; Leishmaniasis; Malaria; Protozoan Infections; Toxoplasmosis
PubMed: 25873762
DOI: 10.1155/2015/504951