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Biomolecules Sep 2021is a free-living amoeba (FLA) that is commonly known as the "brain-eating amoeba." This parasite can invade the central nervous system (CNS), causing an acute and... (Review)
Review
is a free-living amoeba (FLA) that is commonly known as the "brain-eating amoeba." This parasite can invade the central nervous system (CNS), causing an acute and fulminating infection known as primary amoebic meningoencephalitis (PAM). Even though PAM is characterized by low morbidity, it has shown a mortality rate of 98%, usually causing death in less than two weeks after the initial exposure. This review summarizes the most recent information about , its pathogenic molecular mechanisms, and the neuropathological processes implicated. Additionally, this review includes the main therapeutic strategies described in case reports and preclinical studies, including the possible use of immunomodulatory agents to decrease neurological damage.
Topics: Animals; Antiprotozoal Agents; Brain; Central Nervous System Protozoal Infections; Humans; Inflammation; Naegleria fowleri
PubMed: 34572533
DOI: 10.3390/biom11091320 -
Molecules (Basel, Switzerland) Mar 2020For decades, nucleosides and nucleotides have formed the cornerstone of antiviral, antiparasitic and anticancer therapeutics and have been used as tools in exploring...
For decades, nucleosides and nucleotides have formed the cornerstone of antiviral, antiparasitic and anticancer therapeutics and have been used as tools in exploring nucleic acid structure and function [...].
Topics: Anti-Bacterial Agents; Antiprotozoal Agents; Antiviral Agents; Computational Biology; Humans; Nucleic Acids; Nucleosides; Nucleotides
PubMed: 32230805
DOI: 10.3390/molecules25071526 -
Tidsskrift For Den Norske Laegeforening... Feb 2021Leishmaniasis is a rare but potentially severe tropical infectious disease, and Norwegian clinicians are generally unfamiliar with its diagnosis and treatment. This...
BACKGROUND
Leishmaniasis is a rare but potentially severe tropical infectious disease, and Norwegian clinicians are generally unfamiliar with its diagnosis and treatment. This study aimed to investigate the number of cases diagnosed, performance of diagnostic methods and treatment of leishmaniasis at five university hospitals in Norway.
MATERIAL AND METHOD
The number of cases, diagnosis and treatment of suspected leishmaniasis were registered prospectively in the period March 2014 - September 2017 at the university hospitals of Bergen, Oslo, Stavanger, Trondheim and Tromsø.
RESULTS
A total of 13 patients with leishmaniasis were registered in the period. Visceral leishmaniasis was diagnosed in two patients infected in the Mediterranean region, after 7 and 8 weeks with symptoms. The diagnosis was made by serology as well as microscopy and/or polymerase chain reaction tests (PCR) on spleen, blood and bone marrow. Both patients were treated effectively with liposomal amphotericin B. Cutaneous leishmaniasis was diagnosed in 11 patients, and samples from 10 of these tested positive with PCR. Two patients were infected with potentially mucotropic species. Liposomal amphotericin B was the first-line choice for all those who received treatment, but one patient recovered only after local therapy with sodium stibogluconate.
INTERPRETATION
Assessment of visceral leishmaniasis was undertaken according to international guidelines. The patients were diagnosed late in the disease course, presumably because the disease is rare and not well known in Norway. Cutaneous leishmaniasis was diagnosed with PCR, but none of the patients received local treatment as the first-line choice, as recommended in suitable cases, presumably because the drugs are not readily available in Norway and many clinicians are unfamiliar with the route of administration with local infiltration.
Topics: Antiprotozoal Agents; Bone Marrow; Humans; Leishmaniasis, Visceral; Mediterranean Region; Norway
PubMed: 33624958
DOI: 10.4045/tidsskr.19.0171 -
Ugeskrift For Laeger Apr 2024Leishmaniasis is transmitted by sandflies and involves cutaneous, mucocutaneous, or visceral disease. Sporadic, imported cases in Denmark emphasize the need for greater... (Review)
Review
Leishmaniasis is transmitted by sandflies and involves cutaneous, mucocutaneous, or visceral disease. Sporadic, imported cases in Denmark emphasize the need for greater awareness. The incidence is stable with at least ten verified cases per year. Diagnostic methods include PCR- and antibody tests with a high positivity rate for PCR (17%) and a low positivity rate for antibody (1.4%). The latter should be used only when visceral disease is suspected. Immunosuppressed patients are at particular risk. Treatment strategies are chosen according to the severity of the condition, as argued in this review.
Topics: Humans; Denmark; Leishmaniasis; Communicable Diseases, Imported; Antiprotozoal Agents; Polymerase Chain Reaction; Leishmaniasis, Cutaneous
PubMed: 38704708
DOI: 10.61409/V09230568 -
Clinical Microbiology and Infection :... Oct 2020
Topics: Adult; Amphotericin B; Antiprotozoal Agents; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male
PubMed: 32439594
DOI: 10.1016/j.cmi.2020.05.003 -
Current Opinion in Infectious Diseases Oct 2021Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is... (Review)
Review
PURPOSE OF REVIEW
Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is associated with diarrhea, malnutrition, growth stunting, cognitive deficits, and oral vaccine failure in children living in low-resource settings.
RECENT FINDINGS
Various drug discovery approaches have generated promising lead candidates. The repurposed antimycobacterial drug clofazimine was tested in Malawian HIV patients with cryptosporidiosis but was ineffective. Target-based screens identified inhibitors of lysyl-tRNA synthetase, phenylalanyl-tRNA synthetase, methionyl-tRNA synthetase, and calcium-dependent protein kinase 1. Phenotypic screens led to discovery of a phosphatidylinositol 4-kinase inhibitor, the piperazine MMV665917, and the benzoxaborole AN7973. The relationship between pharmacokinetic properties and in-vivo efficacy is gradually emerging. A pathway to clinical trials, regulatory approval, and introduction has been proposed but additional work is needed to strengthen the route.
SUMMARY
Several lead compounds with potent activity in animal models and a favorable safety profile have been identified. A sustained effort will be required to advance at least one to clinical proof-of-concept studies. The demonstrated risk of resistance indicates multiple candidates should be advanced as potential components of a combination therapy.
Topics: Animals; Antiprotozoal Agents; Cryptosporidiosis; Cryptosporidium; Diarrhea; HIV Infections; Humans
PubMed: 34261904
DOI: 10.1097/QCO.0000000000000761 -
Molecules (Basel, Switzerland) Jan 2021Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis... (Review)
Review
Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties. Some of them are now widely used in clinical medicine. All polycyclic endoperoxides presented in this article demonstrate antiprotozoal activity and can be divided into three groups. The third group includes endoperoxides, which show weak antiprotozoal activity with a reliability of up to 70%, and this group includes only 1.1% of metabolites. The second group includes the largest number of endoperoxides, which are 65% and show average antiprotozoal activity with a confidence level of 70 to 90%. Lastly, the third group includes endoperoxides, which are 33.9% and show strong antiprotozoal activity with a confidence level of 90 to 99.6%. Interestingly, artemisinin and its analogs show strong antiprotozoal activity with 79 to 99.6% confidence against obligate intracellular parasites which belong to the genera Plasmodium, Toxoplasma, Leishmania, and Coccidia. In addition to antiprotozoal activities, polycyclic endoperoxides show antitumor activity in the proportion: 4.6% show weak activity with a reliability of up to 70%, 65.6% show an average activity with a reliability of 70 to 90%, and 29.8% show strong activity with a reliability of 90 to 98.3%. It should also be noted that some polycyclic endoperoxides, in addition to antiprotozoal and antitumor properties, show other strong activities with a confidence level of 90 to 97%. These include antifungal activity against the genera Aspergillus, Candida, and Cryptococcus, as well as anti-inflammatory activity. This review provides insights on further utilization of polycyclic endoperoxides by medicinal chemists, pharmacologists, and the pharmaceutical industry.
Topics: Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Antiprotozoal Agents; Biological Products; Humans; Peroxides
PubMed: 33525706
DOI: 10.3390/molecules26030686 -
Communications Biology Nov 2022Theileria parasites are responsible for devastating cattle diseases, causing major economic losses across Africa and Asia. Theileria spp. stand apart from other...
Theileria parasites are responsible for devastating cattle diseases, causing major economic losses across Africa and Asia. Theileria spp. stand apart from other apicomplexa parasites by their ability to transform host leukocytes into immortalized, hyperproliferating, invasive cells that rapidly kill infected animals. The emergence of resistance to the theilericidal drug Buparvaquone raises the need for new anti-Theileria drugs. We developed a microscopy-based screen to reposition drugs from the open-access Medicines for Malaria Venture (MMV) Pathogen Box. We show that Trifloxystrobin (MMV688754) selectively kills lymphocytes or macrophages infected with Theileria annulata or Theileria parva parasites. Trifloxystrobin treatment reduced parasite load in vitro as effectively as Buparvaquone, with similar effects on host gene expression, cell proliferation and cell cycle. Trifloxystrobin also inhibited parasite differentiation to merozoites (merogony). Trifloxystrobin inhibition of parasite survival is independent of the parasite TaPin1 prolyl isomerase pathway. Furthermore, modeling studies predicted that Trifloxystrobin and Buparvaquone could interact distinctly with parasite Cytochrome B and we show that Trifloxystrobin was still effective against Buparvaquone-resistant cells harboring TaCytB mutations. Our study suggests that Trifloxystrobin could provide an effective alternative to Buparvaquone treatment and represents a promising candidate for future drug development against Theileria spp.
Topics: Cattle; Animals; Parasites; Antiprotozoal Agents; Theileria annulata
PubMed: 36380082
DOI: 10.1038/s42003-022-03981-x -
Marine Drugs Apr 2022This review is devoted to the study of the biological activity of polyether ionophores produced by bacteria, unicellular marine algae, red seaweeds, marine sponges, and... (Review)
Review
This review is devoted to the study of the biological activity of polyether ionophores produced by bacteria, unicellular marine algae, red seaweeds, marine sponges, and coelenterates. Biological activities have been studied experimentally in various laboratories, as well as data obtained using QSAR (Quantitative Structure-Activity Relationships) algorithms. According to the data obtained, it was shown that polyether toxins exhibit strong antibacterial, antimicrobial, antifungal, antitumor, and other activities. Along with this, it was found that natural polyether ionophores exhibit such properties as antiparasitic, antiprotozoal, cytostatic, anti-mycoplasmal, and antieczema activities. In addition, polyethers have been found to be potential regulators of lipid metabolism or inhibitors of DNA synthesis. Further study of the mechanisms of action and the search for new polyether ionophores and their derivatives may provide more effective therapeutic natural polyether ionophores for the treatment of cancer and other diseases. For some polyether ionophores, 3D graphs are presented, which demonstrate the predicted and calculated activities. The data presented in this review will be of interest to pharmacologists, chemists, practical medicine, and the pharmaceutical industry.
Topics: Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Humans; Ionophores; Neoplasms
PubMed: 35621943
DOI: 10.3390/md20050292 -
Scientific Reports Jan 2021Three new compounds (1-3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the...
Three new compounds (1-3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the first example of an esterified polycyclic polyprenylated acylphloroglucinol that features a unique tricyclo-[4.3.1.1]-undecane skeleton. Compound 2 is a fairly simple MPAP, but with an unexpected cycloheptane ring decorated with prenyl substituents, and compound 3 has an unusual 5,5-spiroketal lactone core. Their structures were determined by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, HRESI-TOFMS). Absolute configurations were established by ECD calculations, and the absolute structure of 2 was confirmed by a single crystal determination. Plausible biogenetic pathways of compounds 1-3 were also proposed. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and Plasmodium falciparum and cytotoxicity against rat myoblast (L6) cells were determined. Compound 1 showed a moderate activity against T. brucei and P. falciparum, with IC values of 3.07 and 2.25 μM, respectively.
Topics: Antiprotozoal Agents; Biological Products; Biosynthetic Pathways; Hypericum; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Plant Extracts; Structure-Activity Relationship
PubMed: 33446755
DOI: 10.1038/s41598-020-79305-y