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Human antiparasitic drugs

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https://www.readbyqxmd.com/read/29317890/enterobius-vermicularis-in-the-endometrium-of-the-uterus-a-case-report
#1
Biserka Pigac, Silvija Mašić, Valentina Mašić
Enterobius vermicularis is an intestinal nematode of humans and the most common helminth infection. Main transmission path is direct contact between infected and uninfected person meaning ingestion of the eggs. Human infections are usually asymptomatic or manifest as perianal itching. Although ectopic locations are uncommon, Enterobius can occasionally be detected in appendix, kidney, male urinary tract and female genital tract. We present a case from Varaždin General Hospital, Varaždin, Croatia in 2012, involving a 90-yr-old female patient who underwent hysterectomy leading to accidental finding of E...
October 2017: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/29317800/leishmaniasis-in-humans-drug-or-vaccine-therapy
#2
REVIEW
Masoud Ghorbani, Ramin Farhoudi
Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29296196/antitumor-effects-of-the-antiparasitic-agent-ivermectin-via-inhibition-of-yes-associated-protein-1-expression-in-gastric-cancer
#3
Sho Nambara, Takaaki Masuda, Miki Nishio, Shotaro Kuramitsu, Taro Tobo, Yushi Ogawa, Qingjiang Hu, Tomohiro Iguchi, Yousuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Akira Suzuki, Koshi Mimori
Yes-associated protein 1 (YAP1) acts as an oncogene through dephosphorylation and nuclear translocation, and nuclear accumulation of YAP1 is associated with poor prognosis in gastric cancer (GC). We previously identified ivermectin, an antiparasitic drug, as a YAP1 inhibitor. Here, we aimed to clarify whether ivermectin had antitumor effects on GC through inhibition of YAP1. First, we evaluated the antiproliferative effects of ivermectin on human GC cells using in vitro proliferation assays and a xenograft mouse model...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29170085/the-modelling-studies-determing-the-mode-of-action-of-anthelmintics-inhibiting-in-vitro-tpp-of-anisakis-simplex-s-l
#4
Elżbieta Łopieńska-Biernat, Tomasz Molcan, Łukasz Paukszto, Jan Paweł Jastrzębski, Kamil Myszczyński
The trehalose-6-phosphate phosphatase (TPP) enzyme is involved in the synthesis of trehalose, the main sugar in the energy metabolism of nematodes. TPP is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. The presence of conserved active sites of TPP in closely related nematodes and its absence in humans makes it a promising target for antiparasitic drugs. In the present study, homology modeling, molecular docking and MD simulation techniques were used to explore the structure and dynamics of TPP...
November 20, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/29167671/immune-checkpoint-targets-for-host-directed-therapy-to-prevent-and-treat-leishmaniasis
#5
REVIEW
Rajiv Kumar, Shashi Bhushan Chauhan, Susanna S Ng, Shyam Sundar, Christian R Engwerda
Leishmaniasis encompasses a group of diseases caused by protozoan parasites belonging to the genus Leishmania. These diseases range from life threatening visceral forms to self-healing cutaneous lesions, and each disease manifestations can progress to complications involving dissemination of parasites to skin or mucosal tissue. A feature of leishmaniasis is the key role host immune responses play in disease outcome. T cells are critical for controlling parasite growth. However, they can also contribute to disease onset and progression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29092797/gold-nanoparticles-against-parasites-and-insect-vectors
#6
REVIEW
Giovanni Benelli
Nanomaterials are currently considered for many biological, biomedical and environmental purposes, due to their outstanding physical and chemical properties. The synthesis of gold nanoparticles (Au NPs) is of high interest for research in parasitology and entomology, since these nanomaterials showed promising applications, ranging from detection techniques to drug development, against a rather wide range of parasites of public health relevance, as well as on insect vectors. Here, I reviewed current knowledge about the bioactivity of Au NPs on selected insect species of public health relevance, including major mosquito vectors, such as Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus...
October 29, 2017: Acta Tropica
https://www.readbyqxmd.com/read/29016295/ignoring-the-itch-the-global-health-problem-of-scabies
#7
Lola V Stamm, Lindsay C Strowd
Infestation with Sarcoptes scabiei var. hominis is a common human parasitic affliction endemic in tropical developing countries. Scabies is transmitted by close person-person contact, and outbreaks have been reported in reception centers for asylum seekers. Scabies presents clinically as extremely pruritic excoriated papules and linear burrows in the skin. This infestation predisposes to bacterial skin infections that can result in serious complications affecting the kidneys and possibly the heart. Treatment of individuals with scabies and their close contacts involves the use of antiparasitic agents...
October 2, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28973981/effect-of-moxidectin-on-bed-bug-feeding-development-fecundity-and-survivorship
#8
Chen Zha, Changlu Wang, Johnathan Michael Sheele
The common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), is a blood-feeding ectoparasite which experienced world-wide resurgence during recent decades. The control of bed bugs is often challenging, due to their cryptic nature and resistance to commonly used insecticides. In this study, we evaluated the effect of the antiparasitic drug moxidectin on bed bug survival, reproduction, and development. The LC50 (lethal concentration to kill half the members of a tested population) of moxidectin against bed bug male adults, female adults, and large nymphs were 52...
September 30, 2017: Insects
https://www.readbyqxmd.com/read/28935948/novel-scaffolds-for-inhibition-of-cruzipain-identified-from-high-throughput-screening-of-anti-kinetoplastid-chemical-boxes
#9
Emir Salas-Sarduy, Lionel Urán Landaburu, Joel X Karpiak, Kevin P Madauss, Juan José Cazzulo, Fernán Agüero, Vanina Eder Alvarez
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910741/drug-susceptibility-testing-in-microaerophilic-parasites-cysteine-strongly-affects-the-effectivities-of-metronidazole-and-auranofin-a-novel-and-promising-antimicrobial
#10
David Leitsch
The microaerophilic parasites Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia annually cause hundreds of millions of human infections which are treated with antiparasitic drugs. Metronidazole is the most often prescribed drug but also other drugs are in use, and novel drugs with improved characteristics are constantly being developed. One of these novel drugs is auranofin, originally an antirheumatic which has been relabelled for the treatment of parasitic infections. Drug effectivity is arguably the most important criterion for its applicability and is commonly assessed in susceptibility assays using in vitro cultures of a given pathogen...
September 5, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28869864/immunopegliposomes-for-the-targeted-delivery-of-novel-lipophilic-drugs-to-red-blood-cells-in-a-falciparum-malaria-murine-model
#11
Ernest Moles, Silvia Galiano, Ana Gomes, Miguel Quiliano, Cátia Teixeira, Ignacio Aldana, Paula Gomes, Xavier Fernàndez-Busquets
Most drugs currently entering the clinical pipeline for severe malaria therapeutics are of lipophilic nature, with a relatively poor solubility in plasma and large biodistribution volumes. Low amounts of these compounds do consequently accumulate in circulating Plasmodium-infected red blood cells, exhibiting limited antiparasitic activity. These drawbacks can in principle be satisfactorily dealt with by stably encapsulating drugs in targeted nanocarriers. Here this approach has been adapted for its use in immunocompetent mice infected by the Plasmodium yoelii 17XL lethal strain, selected as a model for human blood infections by Plasmodium falciparum...
August 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28811376/in-vivo-loss-of-function-screens-identify-kpnb1-as-a-new-druggable-oncogene-in-epithelial-ovarian-cancer
#12
Michiko Kodama, Takahiro Kodama, Justin Y Newberg, Hiroyuki Katayama, Makoto Kobayashi, Samir M Hanash, Kosuke Yoshihara, Zhubo Wei, Jean C Tien, Roberto Rangel, Kae Hashimoto, Seiji Mabuchi, Kenjiro Sawada, Tadashi Kimura, Neal G Copeland, Nancy A Jenkins
Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has not been changed significantly during several decades. To seek new therapeutic targets for EOC, we performed an in vivo dropout screen in human tumor xenografts using a pooled shRNA library targeting thousands of druggable genes. Then, in follow-up studies, we performed a second screen using a genome-wide CRISPR/Cas9 library. These screens identified 10 high-confidence drug targets that included well-known oncogenes such as ERBB2 and RAF1, and novel oncogenes, notably KPNB1, which we investigated further...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28811324/the-transcriptional-program-functional-heterogeneity-and-clinical-targeting-of-mast-cells
#13
REVIEW
Gökhan Cildir, Harshita Pant, Angel F Lopez, Vinay Tergaonkar
Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen-immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions...
September 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28755871/cyclohexene-fused-1-3-oxazines-with-selective-antibacterial-and-antiparasitic-action-and-low-cytotoxic-effects
#14
Maria R M de Brito, Walter J Peláez, Martín S Faillace, Gardenia C G Militão, Jackson R G S Almeida, Gustavo A Argüello, Zsolt Szakonyi, Ferenc Fülöp, Maria C Salvadori, Fernanda S Teixeira, Rivelilson M Freitas, Pedro L S Pinto, Ana C Mengarda, Marcos P N Silva, Ademar A Da Silva Filho, Josué de Moraes
Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC)...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28740612/3-hydroxykynurenine-a-tryptophan-metabolite-generated-during-the-infection-is-active-against-trypanosoma-cruzi
#15
Carolina P Knubel, Constanza Insfran, Fernando F Martinez, Cintia Diaz Lujan, Ricardo E Fretes, Martin G Theumer, Laura Cervi, Claudia C Motran
The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC50 values in the micromolar concentration range, while the IC50 values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28715108/ivermectin-activates-girk-channels-in-a-pip2-dependent-g%C3%AE-%C3%AE-independent-manner-and-an-amino-acid-residue-at-the-slide-helix-governs-the-activation
#16
I-Shan Chen, Michihiro Tateyama, Yuko Fukata, Motonari Uesugi, Yoshihiro Kubo
KEY POINTS: Ivermectin (IVM) is a widely used antiparasitic drug in humans and pets which activates glutamate-gated Cl(-) channel in parasites. It is known that IVM binds to the transmembrane domains (TMs) of several ligand-gated channels, such as Cys-loop receptors and P2X receptors. We found that the G-protein-gated inwardly rectifying K(+) (GIRK) channel, especially GIRK2, is activated by IVM directly in a Gβγ -independent manner, but the activation is dependent on phosphatidylinositol-4,5-biphosphate (PIP2 )...
September 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#17
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28605319/medicinal-mushrooms-in-human-clinical-studies-part-i-anticancer-oncoimmunological-and-immunomodulatory-activities-a-review
#18
Solomon P Wasser
More than 130 medicinal functions are thought to be produced by medicinal mushrooms (MMs) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemic, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, antidiabetic, and other effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelia, and cultured broth. Special attention has been paid to mushroom polysaccharides...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/28552793/artichoke-leaf-extract-protects-liver-of-schistosoma-mansoni-infected-mice-through-modulation-of-hepatic-stellate-cells-recruitment
#19
Shaimaa Ahmed Sharaf El-Deen, Reham Mustafa Brakat, Asmaa Shams El Dein Mohamed
Schistosomiasis is the second most common human parasitic disease worldwide. It is responsible for 300000 deaths per year. Liver fibrosis is the main pathology of schistosomiasis and its complications are the major cause of death in infected cases. Unfortunately, the therapeutic dose of praziquantel (PZQ) - the main drug treatment - doesn't markedly affect fibrosis. In the present study, antiparasitic and hepatoprotective properties of artichoke leaf extract (ALE) were tested on mice experimentally infected with Schistosoma mansoni (S...
July 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28502250/antiplasmodial-dihetarylthioethers-target-the-coenzyme-a-synthesis-pathway-in-plasmodium-falciparum-erythrocytic-stages
#20
Thomas Weidner, Leonardo Lucantoni, Abed Nasereddin, Lutz Preu, Peter G Jones, Ron Dzikowski, Vicky M Avery, Conrad Kunick
BACKGROUND: Malaria is a widespread infectious disease that threatens a large proportion of the population in tropical and subtropical areas. Given the emerging resistance against the current standard anti-malaria chemotherapeutics, the development of alternative drugs is urgently needed. New anti-malarials representing chemotypes unrelated to currently used drugs have an increased potential for displaying novel mechanisms of action and thus exhibit low risk of cross-resistance against established drugs...
May 15, 2017: Malaria Journal
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