Diluted benznidazole decreases side effects in animals infected by Trypanosoma cruzi and treated with benznidazole in ponderal dose

2021 ◽  
Vol 11 (40) ◽  
pp. 170-171
Author(s):  
Denise Lessa Aleixo ◽  
Fabiana Nabarro Ferraz ◽  
Miguel Spack ◽  
Gislaine Janaina S F Temporini ◽  
Camila Fernanda Brustolin ◽  
...  
Keyword(s):  
Side Effects ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
World Health ◽  
Adherence To Treatment ◽  
Treatment Control ◽  
Treatment Regimens ◽  
Health Organization ◽  
Important Progress ◽  
Better Than

Background: The infection caused by the protozoan Trypanosoma cruzi affects millions of people around the world and the benznidazole is the only drug available for the etiological treatment, despite the fact that its adverse effect makes the adherence to treatment more difficult. Taking advantage of the antiparasitic effect of benznidazole and minimizing its side effects, without causing discomfort symptoms to the patient, would be an important progress in the health care of individuals infected with T. cruzi. Aim: The aim of this study was to evaluate the effect of different treatment regimens using diluted and ponderal benznidazole, associated or not, in murine infection with T. cruzi. Methodology: A hundred male Swiss mice 28 – year – old infected with 1400 blood trypomastigotes of the Y strain of T. cruzi, were used in the experiment, divided into groups according to the treatment: Control (CI) - infected animals treated orally with 7% hydroalcoholic solution (vehicle of product preparation highly diluted) (N = 20); BZp - infected animals treated with BZ in ponderal dose (100 mg/kg/20days) from the detection of the infection (N = 20); BZh - infected animals treated with BZ highly diluted (30x) from the detection of the infection (N = 20), BZp+h - infected animals treated with a combination of BZ highly diluted (30x) + BZ in ponderal dose (100 mg / kg), from the detection of the infection (n= 20); BZp+hT4A - infected animals treated with the association of BZ in ponderal dose (100 mg / kg ) from the detection of the infection and BZ highly diluted (30x) four days after starting the treatment with BZp (N = 20). Clinical (body weight, water and food intake, amount of feces, temperature, aspect of the fur, mortality and survival time) and parasitological (total parasitemia and area under the parasitemia curve) parameters were evaluated. Results: It was observed a reduction of side effects associated with clinical improvement of the animals treated with the combination of BZ in ponderal dose and highly diluted given 4 days after (BZp+hT4A) or concurrently (BZp+h) with the beginning of the treatment with benznidazole in ponderal dose, with results statistically better than those observed in groups BZp, BZh e CI (p0.05). In the group treated only with the BZ ultradiluted (BZh) the parasitemia remained high, resulting in the death of all animals within a period of 20 days as observed in the CI. Conclusions: The reduction of side effects, the improvement of the clinical evolution and non-compromising the parasiticide effect, show that the association of the benznidazole medication in ponderal dose and highly diluted should be further explored. Keywords: Homeopathy, Trypanosoma cruzi, Side effects, Benznidazole References MINISTÉRIO DA SAÁDE. Secretaria de Vigilância em Saúde. Brazilian Consensus on Chagas Disease. Rev. Soc. Bras. Med. Trop. 2005; 38:7-29. WHO. World Health Organization. Sixty-third World Healthy. Assembly. Chagas disease: control and elimination. 2010.

Indeterminate Chagas’ disease: Trypanosoma cruzi strain and re-infection are factors involved in the progression of cardiopathy

2003 ◽  
Vol 104 (4) ◽  
pp. 415-420 ◽  
Author(s):  
Juan M. BUSTAMANTE ◽  
Héctor W. RIVAROLA ◽  
Alicia R. FERNÁNDEZ ◽  
Julio E. ENDERS ◽  
Ricardo FRETES ◽  
...  
Keyword(s):  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Infected Group ◽  
World Health ◽  
Cardiac Lesions ◽  
Health Organization ◽  
Host Parasite ◽  
Β Adrenergic Receptors ◽  
First Time

Chagas' disease is caused by Trypanosoma cruzi, which is transmitted by reduviid bugs. The World Health Organization has estimated that about 16–18 million people in the Americas are infected, and that more than 100 million are at risk. In the present study we have used a murine model to analyse if particular T. cruzi strains (Tulahuen strain and SGO-Z12 isolate from a chronic patient) and/or re-infection may determine, during the indeterminate phase of experimental Chagas' disease, changes that could explain the different evolution of cardiac lesions. Re-infected mice reached higher parasitaemias than those infected for the first time. The survival in the indeterminate phase of mice infected with Tulahuen strain was 50.0%, while the SGO-Z12-infected group presented a significantly higher survival rate (77.1%; P<0.01). The SGO-Z12-re-infected group showed a survival rate (70.9%) significantly higher than that of the Tulahuen-re-infected group (37.0%; P<0.01). Electrocardiographic abnormalities were found in 66% of Tulahuen-infected mice, while in SGO-Z12-infected group such abnormalities were found in only 36% of animals (P<0.01). The two groups exhibited similar percentages of electrocardiographic dysfunction on re-infection, although intraventricular blocks were more frequent in Tulahuen-re-infected mice (P<0.01). Hearts from infected or re-infected mice with either parasite showed mononuclear infiltrates. The SGO-Z12-re-infected and Tulahuen-re-infected groups exhibited a significantly diminished affinity (P<0.05) and a significantly increased density (P<0.05) of cardiac β-adrenergic receptors compared with the infected and non-infected groups. The indeterminate phase of Chagas' disease is defined as a prolonged period that is clinically silent, but the present findings show that different T. cruzi strains and re-infection are able to alter the host–parasite equilibrium, and these factors may be responsible for inducing progressive cardiopathy.

scholarly journals Compliance and Treatment Outcomes of Various Regimens for Trichomoniasis in Trinidad and Tobago

2019 ◽  
Vol 7 (10) ◽  
pp. 97
Author(s):  
Divakaruni ◽  
Mahabir ◽  
Orrett ◽  
Adidam ◽  
Venkata ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Trichomonas Vaginalis ◽  
Transmitted Disease ◽  
World Health ◽  
Sexually Transmitted ◽  
Treatment Regimens ◽  
Significant Difference ◽  
Compliance To Treatment ◽  
Health Organization

Trichomoniasis is the most common non-viral sexually transmitted disease (STD) globally and yet is not a reportable disease. Trichomonas vaginalis is an important source of reproductive morbidity and may increase risk of acquisition and transmission of human immunodeficiency viruses (HIV). The World Health Organization (WHO) and the Control Disease Center (CDC) recommend various regimens of nitroimidazole s for treatment. The common nitroimidazoles used for trichomoniasis are metronidazole and tinidazole, which vary in their cost, efficacy, and side effect profile. It is relevant to study these factors for better management of the patients. This study aimed to compare and study the efficacy, compliance of various treatment regimens, their outcomes, and side-effects for trichomoniasis, among STI clinic attendees in Trinidad. A clinical trial study was designed, and after obtaining the informed consent, a routine clinical examination was conducted and the swabs for trichomoniasis tests were collected for diagnosis from the 692 participants. Out of 692 participants, 82 patients with positive diagnosis of Trichomonas infection were treated according to the patient’s choice, using different drug regimens. Compliance to treatment, side effects, and outcome were evaluated. The prevalence of trichomoniasis in the population attending our STI clinic is 11.9% and prevalence of HIV is 9%. Of the total 82 participants for the treatment, 80% were females; nearly 90% of the patients belonged to age group 15–45 years, and over 60% were below 30 years. Among those diagnosed for Trichomonas vaginalis, 14.6% had coexistent HIV infection. The compliance with respect to single dose treatment was significantly better than the long-duration oral regimen and has a significant relation with side effects of the treatment. The outcome is generally better and comparable and shows no significant difference between different treatment regimens used in the study. Metronidazole and tinidazole are commonly used drugs in various regimens. Compliance is better with those treated with tinidazole and metronidazole single dose than with other groups. Outcome is comparable between these regimens, especially when combined with other important factors like abstinence and treatment of the partners. The treatment regimens mainly differed in the compliance side effects profile and duration of therapy, which suggests that to improve the compliance of the drugs with fewer side effects, short course regimen would be a preferred choice.

scholarly journals Capsaicin inhibits arginine kinase and exerts anti-Trypanosoma cruzi activity

2020 ◽  
Author(s):  
Edward A. Valera-Vera ◽  
Chantal Reigada ◽  
Melisa Sayé ◽  
Fabio A. Digirolamo ◽  
Mariana R. Miranda ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Arginine Kinase ◽  
Chronic Phase ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
Health Organization

ABSTRACTTrypanosoma cruzi is the causative agent of Chagas disease, considered within the list of twenty neglected diseases according to the World Health Organization. There are only two therapeutic drugs for Chagas disease, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority.T. cruzi arginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study from our laboratory, possible TcAK inhibitors were identified through computer simulations, resulting in the best-scoring compounds cyanidin derivatives and capsaicin. Considering these results, in this work we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak inhibition on the recombinant TcAK activity (IC50 ≈ 800 µM), it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50 = 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Epimastigotes that overexpress TcAK were 37% more resistant to capsaicin than wild type parasites, suggesting that trypanocidal activity could be due, in part, to the enzyme inhibition. However, the difference between the concentrations at which the enzyme is inhibited and the parasite death is caused implies the presence of other targets. In this sense, the prohibitin-2 and calmodulin were identified as other possible capsaicin targets. Capsaicin is a strong and selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower than benznidazole, the drug currently used for treating Chagas disease.

Synthesis of New Thiosemicarbazones and Semicarbazones Containing the 1,2,3-1H-triazole-isatin Scaffold: Trypanocidal, Cytotoxicity, Electrochemical Assays, and Molecular Docking

2019 ◽  
Vol 15 (3) ◽  
pp. 240-256 ◽  
Author(s):  
Bianca N.M. Silva ◽  
Policarpo A. Sales Junior ◽  
Alvaro J. Romanha ◽  
Silvane M.F. Murta ◽  
Camilo H.S. Lima ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Docking Studies ◽  
World Health ◽  
Neglected Diseases ◽  
Alkyl Aryl ◽  
Development Of Resistance ◽  
Health Organization

Background: Chagas disease, also known as American trypanosomiasis, is classified as one of the 17 most important neglected diseases by the World Health Organization. The only drugs with proven efficacy against Chagas disease are benznidazole and nifurtimox, however both show adverse effects, poor clinical efficacy, and development of resistance. For these reasons, the search for new effective chemical entities is a challenge to research groups and the pharmaceutical industry. Objective: Synthesis and evaluation of antitrypanosomal activities of a series of thiosemicarbazones and semicarbazones containing 1,2,3-1H triazole isatin scaffold. Method: 5&'-(4-alkyl/aryl)-1H-1,2,3-triazole-isatins were prepared by Huisgen 1,3-dipolar cycloaddition and the thiosemicarbazones and semicarbazones were obtained by the 1:1 reactions of the carbonylated derivatives with thiosemicarbazide and semicarbazide hydrochloride, respectively, in methanol, using conventional reflux or microwave heating. The compounds were assayed for in vitro trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Beyond the thio/semicarbazone derivatives, isatin and triazole synthetic intermediates were also evaluated for comparison. Results: A series of compounds were prepared in good yields. Among the 37 compounds evaluated, 18 were found to be active, in particular thiosemicarbazones containing a non-polar saturated alkyl chain (IC50 = 24.1, 38.6, and 83.2 &µM; SI = 11.6, 11.8, and 14.0, respectively). To further elucidate the mechanism of action of these new compounds, the redox behaviour of some active and inactive derivatives was studied by cyclic voltammetry. Molecular docking studies were also performed in two validated protein targets of Trypanosoma cruzi, i.e., cruzipain (CRZ) and phosphodiesterase C (TcrPDEC). Conclusion: A class of thio/semicarbazones structurally simple and easily accessible was synthesized. Compounds containing thiosemicarbazone moieties showed the best results in the series, being more active than the corresponding semicarbazones. Our results indicated that the activity of these compounds does not originate from an oxidation-reduction pathway but probably from the interactions with trypanosomal enzymes.

Zinc 1,2,4-triazolo[1,5-a]pyrimidine complexes: synthesis, structural characterization and their effect against Chagas disease

2021 ◽  
Vol 17 ◽  
Author(s):  
José M. Méndez-Arriaga ◽  
Erika Rubio-Mirallas ◽  
Miguel Quirós ◽  
Manuel Sánchez-Moreno
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
X Ray Diffraction ◽  
X Ray ◽  
Health Organization ◽  
The Third World

Background: The World Health Organization catalogues illnesses such as Chagas disease as neglected diseases, due the low investment in new drugs to fight them. The search for novel and non-side effects anti-parasitic compounds is one of the urgent needs of the Third World. The use of triazolopyrimidines and their metal complexes have demonstrated hopeful results in this field. Objective: This work studies the antiparasitic efficacy against Trypanosoma cruzi strains of a series of zinc triazolopyrimidine complexes. Method: A series of Zn complexes has been synthesized by the reaction between the triazolopyrimidine derivatives 7-amino-1,2,4-triazolo[1,5-a]pyrimidine (7atp) and 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) with Zn(SO4) • 7H2O, ZnCl2, and Zn(NO3)2 • 6H2O salts. The complexes have been analyzed by spectroscopic and thermal assays and X-ray diffraction methods have been used to dilucidate the crystalline structure of one of them. The antiparasitic efficacy was tested in vitro against Trypanosoma cruzi to compare the trypanocidal effect of different ligands and counteranions to fight Chagas disease. Results: The efficacy of these compounds against Trypanosoma cruzi has also been tested to compare the influence of different ligands and counteranions on the trypanocidal effect against Chagas disease. Conclusion: Antiproliferative tests corroborate the synergistic trypanocidal effect of the triazolopyrimidine coordination complexes.

scholarly journals Progress towards elimination of lymphatic filariasis in the Americas region

2020 ◽  
Vol 13 (Supplement_1) ◽  
pp. S33-S38
Author(s):  
Gilberto Fontes ◽  
Eliana Maria Mauricio da Rocha ◽  
Ronaldo Guilherme Carvalho Scholte ◽  
Rubén Santiago Nicholls
Keyword(s):  
Dominican Republic ◽  
Lymphatic Filariasis ◽  
Wuchereria Bancrofti ◽  
World Health ◽  
Vector Species ◽  
Effective Coverage ◽  
The Third ◽  
Assessment Survey ◽  
Health Organization ◽  
Important Progress

Abstract In South and Central America, lymphatic filariasis (LF) is caused by Wuchereria bancrofti, which is transmitted by Culex quinquefasciatus, the only vector species in this region. Of the seven countries considered endemic for LF in the Americas in the last decade, Costa Rica, Suriname and Trinidad and Tobago were removed from the World Health Organization list in 2011. The remaining countries, Brazil, Dominican Republic, Guyana and Haiti, have achieved important progress in recent years. Brazil was the first country in the Americas to stop mass drug administration (MDA) and to establish post-MDA surveillance. Dominican Republic stopped MDA in all LF-endemic foci: La Ciénaga and Southwest passed the third Transmission Assessment Survey (TAS) and the Eastern focus passed TAS-1 in 2018. Haiti passed the TAS and interrupted transmission in &gt;80% of endemic communes, achieving effective drug coverage. Guyana implemented effective coverage in MDAs in 2017 and 2018 and in 2019 scaled up the treatment for 100% of the geographical region, introducing ivermectin in the MDA in order to achieve LF elimination by the year 2026. The Americas region is on its way to eliminating LF transmission. However, efforts should be made to improve morbidity management to prevent disability of the already affected populations.

scholarly journals A Case of Polyneuropathy Following a Single Dose of Diethylcarbamazine and Albendazole During Mass Administration of Drug - A Case Report

1970 ◽  
Vol 1 (1) ◽  
pp. 56-58
Author(s):  
SC Kohli ◽  
UK Shrestha ◽  
VM Alurkar ◽  
A Maskey ◽  
M Parajuli ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Single Dose ◽  
Case Report ◽  
Side Effects ◽  
World Health Organization ◽  
Mass Drug Administration ◽  
World Health ◽  
Medical Sciences ◽  
The World ◽  
Health Organization

The global program to eliminate Lymphatic Filariasis created by The World Health organization in 1997 is based on mass administration of single annual doses of diethylcarbamazine ( DEC) plus albendazole in non African regions and of albendazole plus ivermectin in Africa. The usual side effects of DEC treatment include fever, chills, arthralgia, headaches, nausea, and vomiting. Albendazole is associated with relatively few side effects consisting of occasional nausea, vomiting, abdominal pain, headache, reversible alopecia, elevated aminotransferases and rarely leucopenia and rash. We report a case of polyneuropathy in a young individual following DEC and albendazole during mass drug administration. Keywords: Albendazole; DEC; Polyneuropathy. DOI: http://dx.doi.org/10.3126/njms.v1i1.5800   Nepal Journal of Medical Sciences. 2012; 1(1): 56-58

scholarly journals Study on Highly Active Anti- Retroviral Therapy: prescription pattern and side effects

2012 ◽  
Vol 26 (1) ◽  
pp. 12-18
Author(s):  
Sujata Sapkota ◽  
Rajani Shakya ◽  
Basudev Pandey
Keyword(s):  
Side Effects ◽  
Drug Regimen ◽  
World Health ◽  
Management Tools ◽  
Prescription Pattern ◽  
Highly Active ◽  
Regimen Change ◽  
Initial Regimen ◽  
Health Organization ◽  
Multiple Drugs

Since the introduction of Highly Active Anti Retroviral therapy (HAART) by World Health Organization in 1996, it has been the employed method of drug use in HIV management. Involvement of multiple drugs in the regimen, has also invited multiple complications and side effects is one of them. High chances of occurrence of side effects has called for the need of proper identification and therapy management tools for each HAART user and has highlighted the importance of individualized drug therapy. The aim of the study the prescription pattern of the HAART regimen; frequency of regimen change and its major causes; and the side- effects from HAART. The study was conducted in the ART Clinic of SukraRaj Tropical & Infectious Disease Hospital, Teku. 109 patients, who came to the clinic to refill their prescription, were interviewed by the researcher. After interview, medication file of each patient was reviewed to study the prescribed drug regimen, drug changes and identified reasons for the drug change (as identified by the physicians and recorded in patient medication file); reported side effect experience and laboratory reports were analyzed to study the effect of the HAART regimen on hemoglobin and Alanine Aminotransferase enzyme. The study revealed that the most prescribed HAART regimen constituted a combination of Zidovudine, Lamivudine and Nevirapine. 52% of the patients reported having experienced side effects from HAART. 23.85% patients had to have their initial regimen changed because of drug toxicity. Nausea (15.6%), vertigo (14.7%), decreased hemoglobin (11.9%), skin rash/ allergy (9.2%) were the major side effects experience reported by the patients. In addition to some side effects like nausea, vertigo etc; decrease in the level of hemoglobin after the initiation of HAART was evident. Decrease in Zidovudine containing regimen, during the regimen change was apparent and was mostly related to its hemoglobin lowering activity. DOI: http://dx.doi.org/10.3126/jnpa.v26i1.6630 JNPA. XXVI(1) 2012 12-18

scholarly journals Tuberculosis: Development of New Drugs and Treatment Regimens

2021 ◽  
Vol 7 (1) ◽  
pp. 36
Author(s):  
Soedarsono Soedarsono
Keyword(s):  
Treatment Guidelines ◽  
New Drugs ◽  
World Health ◽  
Health Crisis ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Repurposed Drugs ◽  
Latent Tb Infection ◽  
Health Organization ◽  
Who Guideline

Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.

Electroacupuncture reduces fibromyalgia pain by downregulating the TRPV1–pERK signalling pathway in the mouse brain

2020 ◽  
Vol 38 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Hsin-Cheng Hsu ◽  
Ching-Liang Hsieh ◽  
Kun-Ta Lee ◽  
Yi-Wen Lin
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Mouse Brain ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Signalling Pathway ◽  
World Health ◽  
Transient Receptor ◽  
Health Organization ◽  
Psychological Origin

Background: Acupuncture has been clinically recommended as a method of pain relief by the World Health Organization and is widely used by medical doctors. Fibromyalgia (FM) pain has a complex physiological and psychological origin and can be pharmacologically treated with duloxetine, milnacipran and pregabalin. However, these drugs produce undesirable side effects, such as headaches, nausea and diarrhoea. Acupuncture may serve as an effective alternative treatment for pain relief with few side effects. Aims: We hypothesised that acupuncture would reduce FM pain by influencing transient receptor potential cation channel subfamily V member 1 (TRPV1) and the downstream phosphorylated extracellular signal-regulated kinases (pERK), which are located in the central thalamus, amygdala and cortex. Methods: A FM mouse model was established by injecting two doses of acid saline into 32 female C57/B6 mice. The mice were then assigned to different subgroups (n=8 each) and treated with electroacupuncture (EA) or EA sham control. TRPV1 and pERK expression levels were measured using Western blotting and immunohistochemistry. Results: Our results demonstrated that the expression of TRPV1 and pERK in the thalamus, amygdala and somatosensory cortex was normal in the control mice, but significantly increased in FM mice; these FM-induced changes in expression were attenuated by EA. Conclusion: Our data suggest that EA can reverse the central sensitisation of the TRPV1-ERK signalling pathway in the mouse brain. Thus, our findings provide mechanistic evidence supporting the potential therapeutic efficacy of EA for treating FM pain.

Sign in / Sign up

Export Citation Format

Share Document