AMBROZIN, Alessandra R. P. et al. New Pyrone and Quinoline Alkaloid from Almeidea rubra and their Trypanocidal Activity. J. Mex. Chem. Soc [online]. 2005, vol.49, n.2, pp.196-201. ISSN 1870-249X.. The investigation of the ethyl acetate fraction of methanol extract from leaves of Almeidea rubra A. St.-Hil. (Rutaceae) afforded two new compounds 4-methoxy-6-[2-(methylamino)phenyl]-2H-pyran-2-oneand rel-(7R,8R)-8-[(E)-3-hydroxy-3-methyl-1-butenyl]-4,8-dimethoxy-5,6,7,8-tetrahydrofuro[2,3-b]quinoline-7-yl acetate, along with the known compounds arborinine, N-methyl-1-hydroxy-3-methoxyacridone, skimmianine, kokusagine, isodutaduprine, isoskimmianine, and isokokusagine. Their structures were established based on their spectral data, and for the new compounds these data are described herein. Additionally, these compounds were assayed on the tripomastigote forms of Trypanosoma cruzi showing moderate trypanocidal activity.. Keywords : Almeidea rubra; Rutaceae; alkaloids; trypanocidal activity. ...
Buy, download and read Experimental Chemotherapy V4 ebook online in PDF format for iPhone, iPad, Android, Computer and Mobile readers. Author: R Schnitzer. ISBN: 9780323143301. Publisher: Elsevier Science. Experimental Chemotherapy, Volume IV: Chemotherapy of Neoplastic Diseases, Part I focuses on the use of chemotherapy to counteract neoplastic ailments. The book first discusses the chemotherapy of neo
The trypanocidal activity of bortezomib was determined with T. brucei bloodstream forms 427-221a while the general cytotoxicity of the drug was evaluated with human myeloid leukaemia HL-60 cells. The tests were analysed by the Alamar Blue assay as described previously [14]. In brief, cells were seeded in 24-well plates in a final volume of 1 ml of appropriate culture medium (trypanosomes: Baltz medium plus 16.7% heat-inactivated foetal bovine serum [15]; HL-60 cells: RPMI 1640 plus 16.7% heat-inactivated foetal bovine serum) containing various concentration of bortezomib and 1% DMSO. Wells containing medium and 1% DMSO served as controls. The initial densities were 104/ml for trypanosomes and 105/ml for HL-60 cells. After 24 h incubation, 100 μl Alamar Blue (11.11 mg resazurin sodium salt in 100 ml PBS) was added and the cells were incubated for a further 48 h so that the total incubation time was 72 h. Then, the plates were read on a microplate reader using a test wavelength of 570 nm and a ...
... Definition Ethanium is a trypanocidal agent and possible antiviral agent that are widely used in experimental cell biology and biochemistry. Ethid
One of the most promising new targets for trypanocidal drugs to emerge in recent years is the cyclic AMP (cAMP) phosphodiesterase (PDE) activity encoded by TbrPDEB1 and TbrPDEB2. These genes were genetically confirmed as essential, and a high-affinity inhibitor, CpdA, displays potent antitrypanosomal activity. To identify effectors of the elevated cAMP levels resulting from CpdA action and, consequently, potential sites for adaptations giving resistance to PDE inhibitors, resistance to the drug was induced. Selection of mutagenized trypanosomes resulted in resistance to CpdA as well as cross-resistance to membrane-permeable cAMP analogues but not to currently used trypanocidal drugs. Resistance was not due to changes in cAMP levels or in PDEB genes. A second approach, a genome-wide RNA interference (RNAi) library screen, returned four genes giving resistance to CpdA upon knockdown. Validation by independent RNAi strategies confirmed resistance to CpdA and suggested a role for the identified cAMP ...
The Scientific World Journal is a peer-reviewed, Open Access journal that publishes original research, reviews, and clinical studies covering a wide range of subjects in science, technology, and medicine. The journal is divided into 81 subject areas.
A dose-dependent trypanocidal activity of propolis extract was observed in vitro. All trypomastigotes were killed 1 h after incubation with 10 μg mL−1 of the extract. In vivo, the concentrations of 100, 200, 300 and 400 mg kg−1 administered orally for 10 consecutive days showed no curative effect, and the rats died from the disease. However, rats treated with the two highest concentrations of propolis extract showed higher longevity than the other groups ...
This study is for people who have advanced cancer for which standard chemotherapy did not work or for which there are no reliably, effective treatments.. AQ4N is an experimental chemotherapy that is thought to target tumor areas with low oxygen content and low blood supply; tumor areas that are usually the most resistant to standard chemotherapy and radiation treatment. AQ4N may be beneficial in cancer treatment by interfering with a protein that is required for cells to grow and divide, causing tumors to die or to delay their growth.. All patients in this study will receive AQ4N. The dose will be increased for each new patient or group of patients until the maximum tolerated dose is reached. ...
Treatment of stomach cancer with an experimental chemotherapy drug after surgery improved survival rates for Japanese patients, a new study found. The results o
Recently, the World Health Organization approved the nifurtimox-eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we h
BioAssay record AID 523194 submitted by ChEMBL: Antitrypanosomal activity against Trypanosoma cruzi amastigotes infected in mouse peritoneal macrophages assessed as endocytic index after 4 day.
It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide.. ...
BioAssay record AID 378804 submitted by ChEMBL: Antitrypanosomal activity against Trypanosoma cruzi Tulahuen C4 infected in african green monkey Vero cells assessed as growth inhibition of trypomastigotes by beta-galactosidase reporter gene assay.
A Preliminary Trypanocidal Study of Natural and Synthetic Supplementation of Zinc and Magnesium in Combination with Diminazene Aceturate in Wistar Rats
In this study, we were able to achieve a 4-fold reduction in the amount of benznidazole required to significantly reduce blood and tissue parasite burdens by combining the low-dose benznidazole with a recombinant vaccine candidate, Tc24 C4, formulated with a synthetic Toll-like 4 receptor agonist, E6020, in a squalene oil-in-water emulsion. Additionally, vaccination induced a robust parasite-speci...
Study of the in Vitro Antiplasmodial, Antileishmanial and Antitrypanosomal Activities of Medicinal Plants from Saudi Arabia. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Two enzyme-linked immunosorbent assays (ELISA) for the determination of homidium in serum of treated cattle have been developed and evaluated. One is a direct competition (Assay 1) and the other an indirect competition assay (Assay 2). Both assays are highly sensitive with a limit of detection of 0.1 ng homidium per mL serum. Homidium levels were measurable in serum of cattle for over 2 months following administration of a single intramuscular (i.m.) dose at 1 mg/kg bodyweight. The level of sensitivity afforded by these assays makes them potentially useful tools in the pharmacokinetic evaluation of homidium and for invetigating drug resistance or causes of drug failure. Assay 2 was chosen as being most suitable for further studies ...
Alves, Renata Tom et al. Trypanocidal activity of Brazilian plants against epimastigote forms from Y and Bolivia strains of Trypanosoma cruzi. Rev. bras. farmacogn., June 2012, vol.22, no.3, p.528-534. ISSN 0102- ...
by Moraes CB, White KL, Braillard S, Perez C, Goo J, Gaspar L, Shackleford DM, Cordeiro-da-Silva A, Thompson RC, Freitas-Junior L, Charman SA, Chatelain E.
The goal of this clinical research study is to find out if switching from a standard chemotherapy combination to a more intensive experimental combination, based on imaging scans, will improve response to treatment in patients with Hodgkin lymphoma (HL). The safety of this experimental chemotherapy combination will also be studied.
Sigma-Aldrich offers abstracts and full-text articles by [S T de Macedo-Silva, G Visbal, J A Urbina, W de Souza, J C F Rodrigues].
Recent studies have shown that Benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, modulates pro-inflammatory cytokines and nitric oxide (NO) release in activated macrophages by blocking NF-κB through inhibition of IKK in vitro. As so far, little is known about the mechanism by which BZL provokes the inhibition of inflammatory response in sepsis in vivo, we aimed to deline ...
Raputia praetermissa (Engler) Emmerich is a tree found only in the Forest Reserve Adolpho Ducke, Amazonas, Brazil. The genus Raputia was originally described by Engler and many species were included in this genus, but in 1978, Emmerich proposed three new genera Neoraputia, Raputiarana e Sigmathantus in order to accommodate six species, four belonging to the genus Raputia, which is assigned into the tribe Cuspariae, and two that had not been described yet. From our knowledge no previous phytochemical work has been reported on Raputia. Therefore, this study describes phytochemical and chemosystematic investigation and the search of compounds with trypanocidal and leishmanicidal activity from roots of R. praetermissa. The phytochemical work involved crude extract preparation, followed by fractionation and isolation of compounds thorough different chromatography methods. Spectroscopic analyses permitted the identification of them and the results showed the presence of new substances in addition to ...
The disease has an acute and chronic stage. The acute stage is not associated with symptoms in 95% of cases. Symptoms that do appear can include fever or swelling around the site where the parasite entered the body. While the acute stage does not often cause significant morbidity, children and immunosuppressed individuals have a higher risk of mortality.. The disease enters into the chronic stage post-infection, which can be a few weeks or longer after the acute stage. Many infected people remain asymptomatic for life. However, chronic infection can lead to serious complications and potentially death in an estimated 20-30% of infected individuals, usually 10-30 years after the initial infection. Complications include cardiovascular, gastrointestinal and neurological diseases.. ...
Literature References: Ergosterol biosynthesis inhibitor. Prepn: A. Hubele, P. Riebli, GB 2098607 (1982 to Ciba-Geigy). Properties and antifungal activity: W. Ruess et al., Brighton Crop Prot. Conf. - Pests Dis. 1988, 543. Field studies: A. J. Leadbeater et al., ibid. 917; A. B. Bassi, Jr. et al., Br. Crop Prot. Counc. Monogr. 57, 91 (1994). Uptake and translocation in crops: H. Dahmen, T. Staub, Plant Dis. 76, 523 (1992). ...
Hargrove, John W., Ouifki, Rachid, Kajanguri, Damian, Vale, Glyn A. and Torr, Stephen J. (2012) Modeling the control of Trypanosomiasis using Trypanocides or insecticide-treated livestock. PLOS Neglected Tropical Diseases, 6 (5):e1615. ISSN 1935-2727 (Print), 1935-2735 (Online) (doi:10.1371/journal.pntd.0001615) ...
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Introduction Women with Chagas disease receiving treatment with nifurtimox are discouraged from breast feeding. Many patients who would receive treatment with nifurtimox live in extreme poverty, have limited access to resources such as clean water and baby formula and may not have safe alternatives to breast milk.. Aim We aimed to estimate, using limited available pharmacokinetics data, potential infant exposure to nifurtimox through breast milk.. Methods Original nifurtimox plasma concentrations were obtained from published studies. Pharmacokinetic parameters were estimated using non-linear mixed-effect modelling with NONMEM V.VI. A total of 1000 nifurtimox plasma-concentration profiles were simulated and used to calculate the amount of drug that an infant would be exposed to, if breast fed 150 ml/kg/day.. Results Breast milk concentrations on the basis of peak plasma levels (1361 ng/ml) and milk-plasma ratio were estimated. We calculated infant nifurtimox exposure of a breastfed infant of a ...
Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal
This study evaluates the effectiveness of fexinidazole administered to patients with g-HAT at all stages of the disease. The aim of the present study is to provide additional information on the effectiveness and safety of fexinidazole and to assess its use under conditions as close as possible to those in real life, both in patients treated on an out-patient basis and in the hospital setting, depending on clinical ...
Leishmaniasis and trypanosomiasis are protozoan diseases caused respectively by the kinetoplastid protozoan Leishmania parasites transmitted by the female phlebotomine sa..
Unfortunately, one century after its discovery (Chagas 1909), Chagas disease still affects millions of poor people in several Latin American countries...
New formulation for weight-adjusted treatment of pediatric Chagas patients age 0-18 targets most vulnerable patient group / Submission based on results of CHICO (CHagas disease In Children treated with NifurtimOx) phase III clinical study of nifurtimox in pediatric patients with Chagas disease as well as pre-clinical data / Fight against Neglected Tropical Diseases part of Bayers Sustainability Strategy
New formulation for weight-adjusted treatment of pediatric Chagas patients age 0-18 targets most vulnerable patient group / Submission based on results of CHICO (CHagas disease In Children treated with NifurtimOx) phase III clinical study of nifurtimox in pediatric patients with Chagas disease as well as pre-clinical data / Fight against Neglected Tropical Diseases part of Bayers Sustainability Strategy
Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis ...
In most instances of acute T cruzi infection, a specific diagnosis is not made because of the nonspecific nature of the signs and symptoms and because most cases occur in poor people who have limited ... more
Accepted 22 April 2009. Code Number: oc09127 ABSTRACT. Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914) and up to the drugs currently in use (nifurtimox and benznidazole), along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles), in separate form. Several diseases such as tuberculosis, leprosy and AIDS only came under control after they were treated with associations of drugs with different mechanisms of action. This not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .To this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i) nifurtimox (8 mg/kg/day) + benznidazole (5 mg/kg/day) x 60 consecutive days; (ii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + allopurinol (8-10 mg/kg/day) x 60 days and (iii) ...
Title: Perspectives for New Drugs Against Trypanosomiasis and Leishmaniasis. VOLUME: 2 ISSUE: 5. Author(s):Michael P. Barrett and Ian H. Gilbert. Affiliation:University of Glasgow,Institute of Biomedical and Life Sciences, Division of Infection&Immunity, The Joseph Black Building, Glasgow, G12 8QQ, U.K.. Keywords:trypanosomiasis, leishmaniasis, phenanthridinium compound, trypanocidal drugs, megazol. Abstract: Diseases caused by pathogenic trypanosomatids cause great suffering throughout the developing world. New drugs for these diseases are urgently needed. Recent technological advances have permitted the identification and validation of numerous drug targets in these organisms. However, efforts to develop inhibitors of these targets, that may then be taken forward for development into new drugs, have been comparatively scarce. In this review we discuss the design, synthesis and evaluation of inhibitors of two drug targets in trypanosomatids, 6- phosphogluconate dehydrogenase, the third enzyme ...
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The heart is the most commonly affected organ in persons with chronic Chagas disease.{ref55}{ref56}{ref57}{ref58} Autopsy may reveal marked bilateral ventricular enlargement, often involving the right... more
Definition : Molecular assay reagents intended to identify Trypanosoma cruzi, a species of protozoon of the suborder Trypanosomatina, by detecting specific genetic information of the deoxyribonucleic acid (DNA) of the target parasite. Trypanosoma cruzi parasites cause Chagas disease (American trypanosomiasis) in humans, characterized by an erythematous nodule (i.e., chagoma) appearing within a few days at the site of the inoculation. These parasites are transmitted to humans via insects, either from other humans or from animals (e.g., cats, dogs, rodents).. Entry Terms : "Trypanosoma cruzi Reagents, Identification" , "Trypanosoma cruzi Detection/Identification Reagents" , "Trypanosoma Species Reagents, Identification" , "American Trypanosomiasis Diagnostic Reagents" , "Sleeping Sickness Diagnostic Reagents" , "Trypanosomosis Diagnostic Reagents" , "Trypanosoma Species Detection/Identification Reagents" , "Chagas Disease Diagnostic Reagents" , "Reagents, Molecular Assay, Infection, Parasite, ...
Author Summary Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi and represents a major public health problem in Latin America. Furthermore, growing human population movements extend the disease distribution to regions outside the South American continent. Accurate diagnosis is crucial in patient care and in preventing transmission through blood transfusion, organ transplantation, or vertical transmission from mother to child. Routine diagnosis of Trypanosoma cruzi infection generally is based on detection of the hosts antibodies against the parasite. However, antibody detection tests are liable to specificity problems and are of limited use in assessing treatment outcome and congenital infections. The introduction of the polymerase chain reaction (PCR) to amplify specific DNA sequences opened promising diagnostic perspectives. Despite its reported high sensitivity and specificity, broad use of the PCR technique in diagnosis of Chagas disease is hampered by
Bark used as expectorant and for asthma.. • In Africa, bark root used for pulmonary problems; leaf for leprosy, and flower for kidney ailments and as diuretic.. • In West Nigeria, leaves and stems soaked and boiled in water, used for skin rashes. (see source study). • In India, reported Mawasi tribal use of flowers for diarrhea. (see source study). Scientific studies on the benefits and uses of the monkey tail. • Antimicrobial:. Studies of leaf extracts isolated gallic acid, corilagin and geranin responsible for antimicrobial activity.. • Trypanocidal/ antiprotozoal agent:. Aqueous extract of Acalypha hispida leaves suggest trypanocidal effect.. • Anti-ulcer / Anti-tumor:. Studies yielded geraniin and dehydroellagitannins which suggest diverse biological properties including anti-ulcer and anti-tumor effects, antibacterial activity against helicobacter pylori and antifungal activity.. • Phytochemicals:. Phytochemical studies yield phenolics, flavonoids, hydroxyanthraquinones and ...
Background and Objectives: There is urgent need of search for alternative compounds for chemotherapy of African trypanosomiasis, a disease of major economic and public health importance. The current study investigated the phytochemical composition and in vitro antitrypanosomal activity of aqueous and methanolic leaf extracts of Clutia abyssinica (C. abyssinica) against Trypanosoma congolense (T. congolense) isolated from natural infection of cattle. Materials and Methods: The aqueous and methanol extracts were screened for various secondary metabolites using standard methods. The in vitro antitrypanosomal assay was carried out by monitoring the extract concentrations of 4, 2, 1, 0.4 and 0.2 mg mL-1 for cessation or reduction in motility of trypanosomes followed by inoculation of incubation mixtures to healthy mice and monitoring development of infection for 21 days. Results: Phytochemical screening revealed presence of alkaloids, anthraquinones, flavonoids, glycosides, phenolic compounds, ...
The dissociation of histone proteins a-d from the chromatin ofTrypanosoma brucei brucei procyclic culture forms was investigated by removing the proteins f
During the chronic stage of Chagas disease a 160 kDa antigen appears in the blood of patients and remains detectable many years after the onset of the disease. This antigen is secreted by the trypomastigote form of the parasite while it is undetectable in the epimastigote form. We report here that the chronic 160 kDa exoantigen is encoded by a gene family (CEA 160 family). We describe the cloning and partial nucleotide sequence of a gene (CEA 160-1) belonging to the CEA160 family. Comparison of the gene sequence with other sequences present in the databases revealed homologies with several Trypanosoma cruzi surface antigens. Highest amino acid identity (59%) was with members of a family containing epitopes that mimic nervous tissues (Van Voorhis et al. 1993). Another related group (18-22% amino acid identity) comprises proteins of 85 or 160 kDa sharing an amino acid motif that is conserved among bacterial neuraminidases (Fouts et al. 1991; Pollevick et al. 1991; Kahn et al. 1991; Takle & Cross, ...
The human and veterinary disease complex known as African trypanosomiasis continues to inflict significant global morbidity, mortality, and economic hardship. Drug resistance and toxic side effects of old drugs call for novel and unorthodox strategies for new and safe treatment options. We designed methyltriazenyl purine prodrugs to be rapidly and selectively internalized by the parasite, after which they disintegrate into a nontoxic and naturally occurring purine nucleobase, a simple triazene-stabilizing group, and the active toxin: a methyldiazonium cation capable of damaging DNA by alkylation. We identified 2-(3-acetyl-3-methyltriazen-1-yl)-6-hydroxypurine (compound 1) as a new lead compound, which showed submicromolar potency against Trypanosoma brucei, with a selectivity index of >500, and it demonstrated a curative effect in animal models of acute trypanosomiasis. We investigated the mechanism of action of this lead compound and showed that this molecule has significantly higher ...
Abstract This paper considers the practical problem in experimental chemotherapy where several treatment groups are compared with a control group in a multivariate covariance analysis and the observed data of mice are subjected to multiple comparison test. Mice infected with 50 cercariae of Schistosoma mansoni in unequal group sizes are challenged with some doses of Zingiber officinale extracts, Cremophore and Praziquantel. Data are available for the number of male and female parasites, weights of liver and intestine, and egg per gramme liver and intestine tissues. Proposed herein are multiple testing procedures such as, Tukey, Scheffe and Bonferroni based on two-sample statistics, each comparing an individual treatment with the control, for determining which treatments are more effective than the control. Newman-Keul s test corrobarates exactly with Bonferroni test s result, in the further analysis. ...
Coconut oil was victimized during that era of erroneous dogma that demonized saturated fats, including butter, and created the unhealthy trans-fatty acid hydrogenated unsaturated fat industry, which included margarine. Saturated fats have been resurrected from the trash bin of forbidden foods over the past decade or so with proven health merits.. Now that the fog of junk science dogma has lifted, more and more health conscious folks are finding saturated fats, especially coconut oil, are beyond just safe. They are healthy and medicinal. Several published but unpublicized studies have been conducted and are in progress regarding palm or coconut oils medicinal properties.. One of the most profound studies that you probably havent read or heard about involves cancer. It was conducted by Australian researchers and published in the January 2014 journal Chemotherapy under "experimental chemotherapy". It was an in vitro (test tube, petri dish) study on human colon or colorectal cancer ...
Vaniqa generic is a medication for the reduction of growth facial hair. It contains the active formulation of Eflornithine substance that is also available in its generic form.