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1.
Rev. Soc. Bras. Med. Trop ; 53: e20190477, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057272

ABSTRACT

Abstract INTRODUCTION: Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model. METHODS Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection. RESULTS All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples. CONCLUSIONS: Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.


Subject(s)
Animals , Rats , Triazoles/administration & dosage , Trypanocidal Agents/administration & dosage , Chagas Disease/drug therapy , Parasitemia/drug therapy , Nitroimidazoles/administration & dosage , Acute Disease , DNA, Protozoan , Rats, Wistar , Disease Progression , Disease Models, Animal , Drug Therapy, Combination , Parasite Load
2.
Rev. Soc. Bras. Med. Trop ; 51(2): 133-140, Mar.-Apr. 2018. tab
Article in English | LILACS | ID: biblio-897057

ABSTRACT

Abstract Chagas disease is a protozoan infection that was identified over a century ago. No drugs are available to treat the indeterminate and determinate chronic phases of the disease. Success of a drug design is dependent on correct biological evaluation. Concerning new drug designs for Chagas disease, it is essential to first identify the most effective, existing, experimental chronic protocols that can be used for comparison purposes. Here, we present a literature review regarding experimental models with chronic Chagas disease to evaluate the efficacy of benznidazole (BZN). We searched literature published in PubMed and Web of Science databases, using these keywords: animal model, BZN, Chagas disease, T. cruzi, and chronic phase, with no timeframe limitations. We excluded articles involving acute phase animal models and/or those without BZN treatment. The selected studies were conducted using different BZN concentrations (10mg-100mg) involving several different periods (5-70 days). Concentrations and durations of use are directly related to side effects, but do not prevent chronic tissue lesions. BZN use during the late/chronic phases of Chagas disease is unable to eliminate amastigote forms present in infected tissues. This study suggests the administration of a lower BZN concentration (<100mg/kg/day) during the chronic phase of the animal model, as this had been reported to result in fewer side effects.


Subject(s)
Animals , Trypanocidal Agents/administration & dosage , Chagas Disease/drug therapy , Dose-Response Relationship, Drug , Nitroimidazoles/administration & dosage , Chronic Disease , Disease Models, Animal , Mice
4.
Rev. Soc. Bras. Med. Trop ; 51(1): 52-56, Jan.-Feb. 2018. graf
Article in English | LILACS, SES-SP, SESSP-IDPCPROD, SES-SP | ID: biblio-897053

ABSTRACT

Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.


Subject(s)
Animals , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Parasitic Sensitivity Tests , Amiodarone/pharmacology , Nitroimidazoles/pharmacology , Trypanocidal Agents/administration & dosage , Dose-Response Relationship, Drug , Drug Combinations , Amiodarone/administration & dosage , Mice , Nitroimidazoles/administration & dosage
5.
Rev. Soc. Bras. Med. Trop ; 49(6): 713-720, Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-829676

ABSTRACT

Abstract: INTRODUCTION: Chagas disease currently affects 5.7 million people in Latin America and is emerging in non-endemic countries. There is no consensus concerning the efficacy of trypanocidal therapy for patients with the chronic form of the disease. We evaluated cardiac function and sociodemographic, clinical, and serologic characteristics of a group of asymptomatic Trypanosoma cruzi-seropositive former blood donors, and compared the effects of benznidazole treatment applied for different lengths of time. METHODS: Blood donors who screened positive for T. cruzi between 1998 and 2002 were recruited 10 years later for follow-up (n = 244); 46 individuals had received treatment. Three subjects had terminated treatment prematurely. The remaining 43 individuals were divided into two groups: individuals who had received benznidazole therapy for 50-60 days (n = 28; BT ≤60 group) or more than 60 days (n = 15; BT >60). Serologic assays, biochemical tests, electrocardiographic, echocardiographic, and clinical examinations were performed on all participants. Parasite loads were determined by qualitative and quantitative polymerase chain reaction. RESULTS: Parasitemia was significantly reduced in the BT ≤60 and BT >60 groups compared with the untreated group. There were no differences in epidemiologic profiles or clinical, biochemical, electrocardiographic, or echocardiographic data between any of the groups. CONCLUSIONS: Despite elimination or significant reduction in parasitemia in patients with chronic Chagas disease who received benznidazole, there was no clinical difference between those who were treated for >60 days and those treated for a shorter duration. Furthermore, the adverse effects of benznidazole appear to be less severe than previous reports would suggest.


Subject(s)
Humans , Male , Female , Adult , Trypanocidal Agents/administration & dosage , Blood Donors , Chagas Disease/drug therapy , Parasitemia/parasitology , Nitroimidazoles/administration & dosage , Time Factors , Clinical Protocols , Polymerase Chain Reaction , Chronic Disease , Cross-Sectional Studies , Treatment Outcome , Chagas Disease/parasitology , Asymptomatic Infections , Parasite Load , Middle Aged
6.
Mem. Inst. Oswaldo Cruz ; 111(3): 218-221, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-777373

ABSTRACT

Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Chagas Disease/drug therapy , Nitroimidazoles/pharmacokinetics , Trypanocidal Agents/pharmacokinetics , Trypanosoma cruzi/drug effects , Chemistry, Pharmaceutical , Chagas Disease/metabolism , Follow-Up Studies , Nitroimidazoles/administration & dosage , Nitroimidazoles/blood , Real-Time Polymerase Chain Reaction , Trypanocidal Agents/administration & dosage , Trypanocidal Agents/blood , Trypanosoma cruzi/isolation & purification
7.
Rev. Soc. Bras. Med. Trop ; 48(5): 629-632, Sept.-Oct. 2015. tab, graf
Article in English | LILACS | ID: lil-763335

ABSTRACT

ABSTRACTA woman had been followed since 1957 for acute phase Chagas disease. Parasitological and serological tests were positive, and treatment included benznidazole in 1974. Following treatment, parasitological test results were negative and conventional serology remained positive until 1994, with subsequent discordant results (1995-1997). The results became consistently negative since 1999. She had an indeterminate chronic form until 1974. Only two minor and transitory nonspecific alterations on electrocardiogram were noted, with the last nine records normal until June 2014. This case confirms the possibility of curing chronic disease and suggests the benefit of specific treatments for preventing long-term morbidity.


Subject(s)
Aged , Female , Humans , Chagas Disease/drug therapy , Nitroimidazoles/administration & dosage , Trypanocidal Agents/administration & dosage , Acute Disease , Chronic Disease , Follow-Up Studies , Time Factors , Trypanosoma cruzi/immunology
8.
Int. j. high dilution res ; 14(3): 10-19, 2015.
Article in English | LILACS | ID: lil-783288

ABSTRACT

Although several diseases are treated by toxic drugs, their side effects may hamper adherence to the therapy. The aim of this study is to evaluate the effect of the association of ponderal benznidazole (BZ) with its ultra-high diluted (UHD) formula on clinical and parasitological parameters of mice infected by Trypanosoma cruzi (T. cruzi). 24 non-isogenic Swiss mice were divided into groups: CI – infected animals treated with 7% alcohol; BZp – infected animals treated with BZ (500 mg/ kg) from the beginning of infection; BZp+d – infected animals treated with ponderal BZ and with UHD BZ, which started to be administered four days after the beginning of treatment with ponderal BZ; CNI - group of non-treated and non-infected animals. The UHD medicine was prepared according to Phamacopoeia until 30x. The different treatment schedules were statistically compared through parasitological and clinical parameters. The group BZp+d displayed more favorable clinical evolution than the group BZp, with improvement of mass gain, feed conversion and water intake, presenting data approximated to CNI group. The significant increase of the body temperature of BZp+d group indicates an activation of the immune system which was not observed in the other groups. Moreover, the anti-parasitic effect of the ponderal drug was maintained in all parasitological parameters of this group. By reducing the side effects and maintaining the action of the ponderal drug, the combination of toxic drugs with their UHD formula could be considered a way of improving efficacy of the treatment...


A infecção por Trypanossoma cruzi é um problema de saúde pública e o único medicamento disponível no Brasil é o benznidazol (BZ), com efeitos limitados e tóxicos. Estudos anteriores com BZ na dose de 200 mg/kg indicaram que a administração de BZ diluído (30d) controla os efeitos tóxicos da droga em dose ponderal, sem alterar a sua ação terapêutica. Sob essa perspectiva e considerando a ação do BZ dose dependente, aumentar a quantidade de droga administrada significaria uma melhora na eficácia do tratamento. Portanto, este trabalho teve como objetivo avaliar o efeito do BZ ponderal (BZP), na dose de 500 mg/kg associado com BZ diluído (BZD) nos parâmetros clínicos de camundongos infectados por T. cruzi. Em estudo cego, controlado e randomizado, foram utilizados 23 camundongos suíços, machos, com 8 semanas divididos em grupos: CNI - Não infectados e não tratados; CI - Infectados e tratados com álcool 7 %; BZP - Infectados tratados com BZ (500 mg/kg de peso/ animal) a partir do início da infecção; BZP + BZD - Infectados e tratados com a associação de BZP e BZD. Os medicamentos foram administrados por gavagem (0,2 mL/ dia/ animal). O BZP foi administrado a partir da constatação da infecção. O BZ diluído foi preparado de acordo com a Farmacopeia Homeopática Brasileira e administrado 4 dias após o início do tratamento com BZP. Os parâmetros clínicos, avaliados diariamente, incluíram: peso, consumo de ração e água, temperatura e quantidade de excretas. A análise clínica apontou melhores resultados nos grupos BZP e BZP + BZD, mostrando melhor evolução de peso, consumo de ração, água e excretas quando comparado aos grupos não tratados (p< 0.05)...


Subject(s)
Animals , Rats , High Potencies , Homeopathy , Nitroimidazoles/administration & dosage , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/parasitology , Toxicity/adverse effects
9.
Recife; s.n; 2015. 73 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-772858

ABSTRACT

Atualmente o Brasil apresenta 3 milhões de indivíduos portadores da cardiomiopatia chagásica. Porém, tratamento etiológico com o fármaco Benzonidazol (BZ) na fase crônica da doença ainda não está elucidado. Acredita-se que a recomendação do BZ nessa fase, pode prevenir ou retardar a evolução clínica da cardiomiopatia na Doença Chagas (DC). Assim o objetivo do estudo é avaliar a produção de quimiocinas e expressão de seus receptores em Células mononucleares do sangue periférico - PBMC (de portadores crônicos da doença de Chagas) submetidas in vitro ao tratamento com BZ, após a infecção com T.cruzi. Foram selecionados 11 pacientes na fase crônica da doença. Amostras de sangue desses pacientes foram coletadas para obtenção de PBMC, em que foram cultivadas em placas de cultivo na concentração de 106 células/ml por poço. Após a adesão das células aderentes (principalmente macrófagos), as células não aderentes (principalmente linfócitos) foram removidas e as formas tripomastigotas foram adicionadas ao cultivo para infecção das células aderentes. Subsequente a incubação, as células não aderentes foram adicionadas novamente ao cultivo juntamente com o fármaco Bz (1µg/mL), ficando um co-cultivo de células aderentes infectadas com T.cruzi, células não aderentes e o BZ (C+T+BZ). As placas de cultura foram incubadas por períodos de 24h e 5 dias. Para uma análise fidedigna da ação do BZ nas células aderentes e não aderentes foi necessário a criação dos controles: células (C), células e tripomastigotas (C+T) e células e o BZ (C+BZ). Após o cultivo, foram coletados os sobrenadantes das culturas, para avaliação da produção de quimiocinas (CCL2, CXL9, CXL10, CCL5 e CXCL8) por CBA (Cytometric Bead Array). Posteriormente foi realizada a imunofenotipagem...


Subject(s)
Humans , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Receptors, Chemokine , Trypanosoma cruzi , Trypanocidal Agents/therapeutic use , Cells, Cultured , Chronic Disease , Nitroimidazoles/administration & dosage , Trypanocidal Agents/administration & dosage
11.
Article in English | IMSEAR | ID: sea-157569

ABSTRACT

Periodontal infections and related conditions like Chronic Gingivitis, Chronic Periodontitis, Pericoronitis, Peridontal & Periapical Abscess are common clinical problems, but sometimes Gingivitis and Periodontitis can be acute also. These all are generally treated by scaling and root planning, but studies have reported that despite conventional periodontal therapy certain sites continue to show periodontal tissue destruction. These periodontal infections can be controlled by antibiotics which are effective against Gram-negative aerobic and anaerobic bacteria and has good penetration in periodontal tissues. Objective: The purpose of the present study was to compare the efficacy and tolerability of a fixed dose combination of Satranidazole (300 mg) plus Ofloxacin (200 mg) versus fixed dose combination of Ornidazole (500 mg) plus Ofloxacin (200 mg) for the treatment of periodontal infections. Methods : One hundred and twelve adult patients (59 females and 53 males) with moderate to advanced periodontitis were enrolled and given fixed dose combination of Satranidazole (300 mg) plus Ofloxacin (200 mg) or Ornidazole (500 mg) plus Ofloxacin (200 mg) orally two times daily. Clinical assessment like Gingival Index, Periodontal Index, Mobility Index and VAS Score were done before and after the treatment. Clinical evaluation was performed on 3rd and 5th day after treatment. Results : At the baseline the values for Gingival Index, Periodontal Index, Mobility Index and VAS Score were comparable in both the groups. Both the treatment group have shown attenuation of Gingival Index, Periodontal Index, Mobility Index and VAS Score. However, treatment with Satranidazole plus Ofloxacin showed significantly (p< 0.05) better improvement in all clinical parameters compared to Ornidazole plus Ofloxacin treatment. Treatment with Satranidazole plus Ofloxacin was well tolerated and no serious adverse event was observed. 6 patients (15%) with Ornidazole plus Ofloxacin have shown side effects, which resulted in discontinuation of therapy. These side effects include allergy, nausea, vomiting & acidity. Conclusion : This study concludes that efficacy and tolerability of fixed dose combination of Satranidazole (300 mg) plus Ofloxacin (200 mg) is better than fixed dose combination of Ornidazole (500 mg) plus Ofloxacin (200 mg) in treatment of periodontal infections.


Subject(s)
Adolescent , Child , Child, Preschool , Drug Combinations , Humans , Nitroimidazoles/administration & dosage , Nitroimidazoles/analogs & derivatives , Nitroimidazoles/pharmacology , Ofloxacin/administration & dosage , Ofloxacin/pharmacology , Ornidazole/administration & dosage , Ornidazole/pharmacology , Periodontal Diseases/drug therapy , Periodontal Index
12.
Rev. Soc. Bras. Med. Trop ; 43(2): 182-187, Mar.-Apr. 2010. ilus, tab
Article in Portuguese | LILACS | ID: lil-545774

ABSTRACT

INTRODUÇÃO: A doença de Chagas, causada pelo Trypanosoma cruzi, é tratada com benzonidazol, tendo o inconveniente de apresentar efetividade parcial e alta toxicidade, que varia desde reações de hipersensibilidade a aplasia medular. O objetivo foi descrever e avaliar a ocorrência de reações adversas em pacientes chagásicos em tratamento com benzonidazol em Fortaleza, Ceará. MÉTODOS: Estudo descritivo prospectivo envolvendo 32 pacientes chagásicos crônicos tratados com benzonidazol entre janeiro de 2005 e abril de 2006. Dados sociodemográficos e clínicos foram coletados de questionários, entrevistas e exames laboratoriais. As amostras de sangue foram coletadas antes, com 30 e 60 dias de tratamento. RESULTADOS: Reações adversas foram relatadas em 28 (87,5 por cento) pacientes tratados, tendo sido as mais frequentes: prurido (50 por cento), formigamento (43,8 por cento), fraqueza muscular (37,5 por cento) e rash cutânea (31,3 por cento). Dos 28 pacientes com reações adversas, oito (28,57 por cento) interromperam o tratamento. Reações adversas que culminaram com a suspensão do tratamento foram formigamento sete (87,5 por cento) ou erupção cutânea cinco (62,5 por cento). Observou-se aumento discreto dos níveis de aminotransferases durante o tratamento em (9,4 por cento) pacientes. CONCLUSÕES: Concluindo, o acompanhamento farmacoterapêutico dos pacientes chagásicos é de grande relevância na prevenção e detecção precoce das reações adversas a medicamentos.


INTRODUCTION: Chagas disease is caused by Trypanosoma cruzi and treated with benznidazole (BNZ). This drug has the troublesome features of presenting partial effectiveness and high toxicity ranging from hypersensitivity reactions to medullary aplasia. The objective here was to describe and evaluate the occurrence of adverse reactions in Chagas disease patients treated with benznidazole in Fortaleza, Ceará. METHODS: This was a prospective descriptive study involving 32 chronic Chagas patients treated with benznidazole between January 2005 and April 2006. Sociodemographic and clinical data were collected through questionnaires, interviews and laboratory tests. Blood samples were collected before treatment and after 30 and 60 days of treatment. RESULTS: Adverse reactions were reported in 28 patients (87.5 percent) patients and the most frequent of these were pruritus (50 percent), prickling (43.8 percent), muscle weakness (37.5 percent) and skin rash (31.3 percent). Out of the 28 patients with adverse reactions, eight (28.57 percent) discontinued their treatment. The adverse reactions that culminated with discontinuation of the treatment were prickling (7; 87.5 percent) or skin eruptions (5; 62.5 percent). There was a slight increase in aminotransferase levels during the treatment in 9.4 percent of the patients. CONCLUSIONS: Following up the drug therapy administered to Chagas patients is of great importance for prevention and early detection of adverse reactions to drugs.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Chagas Disease/drug therapy , Nitroimidazoles/adverse effects , Trypanocidal Agents/adverse effects , Chronic Disease , Longitudinal Studies , Nitroimidazoles/administration & dosage , Severity of Illness Index , Socioeconomic Factors , Trypanocidal Agents/administration & dosage , Young Adult
13.
Mem. Inst. Oswaldo Cruz ; 104(supl.1): 319-324, July 2009.
Article in English | LILACS, SES-SP | ID: lil-520894

ABSTRACT

Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project - Benznidazole Evaluation for Interrupting Trypanosomiasis - is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease.


Subject(s)
Animals , Humans , Chagas Cardiomyopathy/drug therapy , Clinical Trials as Topic , Nitroimidazoles/administration & dosage , Trypanocidal Agents/administration & dosage , Chagas Cardiomyopathy/parasitology , Chronic Disease , Double-Blind Method , Drug Administration Schedule , Evidence-Based Medicine , Nitroimidazoles/therapeutic use , Patient Selection , Pilot Projects , Trypanocidal Agents/therapeutic use
14.
Rev. panam. infectol ; 7(2): 33-38, abr.-jun. 2005. tab
Article in Spanish | LILACS, SES-SP | ID: lil-414680

ABSTRACT

Las trichomonas vaginales fueron descritas por primera vez por Donné en 1836, pero no es hasta 1950 que es relacionada con las enfermedades de transmisión sexual. Trichomonas vaginalis es el más sencillo de todos los parásitos protozoos. Sólo existe en forma de trofozoito. Es unicelular y cosmopolita y se localiza en el tracto genitourinario de la mujer y el hombre. Según la Organización Mundial de la Salud (OMS) se tiene un estimado anual de 180 000000 de personas afectadas en el planeta. Se asocia con cervicitis, colpitis, enfermedad inflamatoria pélvica y uretritis. Además de haberse encontrado relación con resultados perinatales desfavorables como: bajo peso al nacer, parto pretermino y sepsis perinatal. Otro aspecto de interes es su asociación con otras enfermedades de transmisión sexual, como las moniliasis, las vaginosis bacterianas, infecciones por HPV, VIH SIDA y papiloma virus. Muchos han sido los medios de diagnóstico utilizados para este protozoos desde las escuelas que la diagnóstican y tratan por la clínica hasta otro que han ido mas allá de los medios convencionales de diagnóstico y han creado clip de diagnósticos rápidos. Igualmente se han probado varios tipos de tratamientos, pero los que mejor resultados han dado son los que se logran con tratamientos con los 5 imidazoles; no obstante, hay ya evidencias que reportan pobres resultados perinatológicos en los casos que se trata la entidad, sobre todo si es en las formas asintomáticas


Subject(s)
Humans , Male , Female , Sexually Transmitted Diseases , Trichomonas vaginalis/pathogenicity , Trichomonas Infections/diagnosis , Trichomonas Infections/epidemiology , Trichomonas Infections/therapy , Trichomonas Infections/transmission , Nitroimidazoles/administration & dosage , Diagnostic Techniques and Procedures
15.
Mem. Inst. Oswaldo Cruz ; 100(2): 213-219, Apr. 2005. tab, graf
Article in English | LILACS | ID: lil-410862

ABSTRACT

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZÎs association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45 percent and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 æg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70 percent, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.


Subject(s)
Animals , Humans , Rats , Blood Proteins/drug effects , Nitroimidazoles/pharmacokinetics , Trypanocidal Agents/pharmacokinetics , Drug Interactions , Liposomes , Lipoproteins/drug effects , Nitroimidazoles/administration & dosage , Nitroimidazoles/toxicity , Permeability , Rats, Wistar , Trypanocidal Agents/administration & dosage , Trypanocidal Agents/toxicity , Trypanosoma cruzi/drug effects
17.
Medicina (B.Aires) ; 64(1): 1-6, 2004. tab, graf
Article in Spanish | LILACS | ID: lil-366623

ABSTRACT

Se realizó un ensayo clínico controlado, multicéntrico, a triple ciego, para evaluar si el tratamiento oral combinado del ácido tióctico (AT), reduce la incidencia de los efectos secundarios asociados al tratamiento con benznidazol (BZ) en pacientes infectados con Trypanosoma cruzi. Cuatro esquemas fueron asignados al azar pareados por edad, administrando placebo o AT por vía oral a razón de 50-100 mg día a dosis e intervalos variables (con y sin período pre-inducción) en combinación con BZ a dosis de 5 mg/kg/día por 30 días. Se realizaron evaluaciones en los días 10, 20, 37 y 52 de iniciado el tratamiento. Fueron enrolados 249 pacientes con edades entre 15 y 44 años. El 70.3% de los pacientes completó el tratamiento y el 17.7% restante debió suspender la medicación por causas relacionadas al BZ. La proporción de personas afectadas por al menos un efecto adverso, fue semejante entre los 4 grupos: entre 54.8 y 58%, aunque en ninguno de ellos resultó de carácter grave. Las manifestaciones clínicas adversas fueron: exantema morbiliforme (28%); prurito (13.6%); cefalea (8%); epigastralgia (6.2%); fiebre (6.2%); astenia (4.3%); náuseas (4.0%); mialgias (4.3%); vómitos (3.2%); otros (21.5%). La incidencia de experiencias adversas no difirió significativamente entre los 4 esquemas terapéuticos, ni entre los diferentes intervalos de edad de los pacientes. La asociación con ácido tióctico no demostró prevenir las manifestaciones de intolerancia a este agente. No obstante, la administración de BZ en un ciclo mensual único a pacientes infectados logró una elevada tasa de adherencia al tratamiento ambulatorio.


Subject(s)
Humans , Animals , Male , Female , Adolescent , Adult , Antioxidants/adverse effects , Chagas Disease/drug therapy , Nitroimidazoles/adverse effects , Thioctic Acid/adverse effects , Trypanocidal Agents/adverse effects , Administration, Oral , Age Distribution , Antioxidants/administration & dosage , Drug Combinations , Nitroimidazoles/administration & dosage , Thioctic Acid/administration & dosage , Trypanocidal Agents/administration & dosage , Trypanosoma cruzi/drug effects
19.
Rev. méd. Hosp. Gen. Méx ; 62(3): 172-5, jul.-sept. 1999. tab
Article in Spanish | LILACS | ID: lil-266181

ABSTRACT

Estudio clínico, prospectivo, longitudinal, abierto, experimental de asignación aleatoria. Se estudiaron pacientes mediante endoscopia y prueba rápida de ureasa para infección activa por Helicobacter pylory, causante de dispepsia ulcerativa o no. Se distribuyeron en tres grupos. El grupo I, recibió nitazoxanida 1 g + subcitrato de bismuto 240 mg más 30 mg de lansoprazol cada 12 horas por siete días. El grupo II recibió nitazoxanida 500 mg más subcitrato de bismuto 120 mg más 30 mg de lansoprazol cada 12 horas durante 14 días. El grupo III recibió nitazoxanida 1 g + subcitrato de bismuto 240 mg más 30 mg de lansoprazol cada 12 horas por 14 días. Los pacientes fueron evaluados a los 14 días y a las seis semanas mediante prueba de aliento con carbono 14, para sustentar cura bacteriológica. El grupo I incluyó 29 sujetos, hubo erradicación de H. pylori en el 41.37 por ciento. El grupo II lo conformaron 28 sujetos, registrándose erradicación en el 75 por ciento. El grupo III incluyó 29 pacientes, entre los cuales se registro erradicación en el 83 por ciento. El diagnóstico más frecuente en los tres grupos fue gastritis, entre éstos casos se alcanzó 86 por ciento de erradicación, y duodenitis, 83 por ciento de erradicación. La úlcera péptica más frecuente fue la duodenal y lugo la gástrica; en el grupo II se alcanzó un 100 por ciento de erradicación. Los efectos colaterales (dolor epigástrico, náusea, coluria y cefalea) fueron mínimos y no obligaron a suspender el tratamiento. Se concluye que nitazoxanida más subcitrato de bismuto más lansoprazol tiene alta tasa de erradicación (87 por ciento); es seguro, bien tolerado y muestra eficacia en el tratamiento de la enfermedad acidopéptica asociada a infección por Helicobacter pylori


Subject(s)
Humans , Male , Female , Adult , Microbial Sensitivity Tests , Helicobacter pylori/drug effects , Helicobacter Infections/therapy , Treatment Outcome , Dyspepsia/diagnosis , In Vitro Techniques , Urease , Bismuth/administration & dosage , Bismuth/therapeutic use , Prospective Studies , Longitudinal Studies , Endoscopy , Nitroimidazoles/administration & dosage , Nitroimidazoles/therapeutic use , Data Interpretation, Statistical , Microbiological Techniques
20.
Medicina (B.Aires) ; 59(supl.2): 166-70, 1999.
Article in Spanish | LILACS | ID: lil-242251

ABSTRACT

Desde la década de 1930 fue investigado el tratamiento específico de la enfermedad de Chagas. Las metas del tratamiento específico contra la infección por Trypanosoma cruzi, son a nivel individual, eliminar el parásito y disminuir la probabilidad de desarrollar la enfermedad. A fines de los años '60 y principios de los '70, dos compuestos químicos fueron evaluados por ensayos clínicos en Argentina: Nifurtimox y Benznidazol. Después de la aprobación de su uso por la Autoridad de regulación del Ministerio de Salud, en 1983 fue escrita y aprobada la primera Norma para el tratamiento de la infección por T. cruzi. Esta Norma recomendó procedimentos para tratar los casos en Fase Aguda de enfermedad de Chagas. Debido a la publicación de nueva información que soporta la utilización de estas drogas para el tratamiento de casos en fase indeterminada de la enfermedad de Chagas, en 1997 la Norma original fue revisada y fue aprobado un nuevo procedimiento (Resolución Secretaría de programas de Salud/Ministério de Salud y Acción Social de la Nación Nº 28/99). Actualmente el tratamiento es recomendado en: 1) Todo paciente en Fase Aguda de la enfermedad de Chagas, 2) Niños y adolescentes en fase Indeterminada de la enfermedad de Chagas. 3) Pacientes adultos en fase indeterminada o con una forma cardíaca incipiente asintomática de la enfermedad de Chagas. 4) accidentes con material contaminado en laboratorio o durante cirugías. 5) Donante o receptor en trasplante de órganos. Es necesario realizar el acompañamiento médico y laboratorio clínico general durante el tratamiento para monitorear al paciente. La titulación de anticuerpos específicos con antígenos monoespecíficos mostró ser un marcador apropiado para la eficacia terapéutica.


Subject(s)
Adult , Child , Humans , Adolescent , Chagas Disease/drug therapy , Nifurtimox/administration & dosage , Nitroimidazoles/administration & dosage , Trypanocidal Agents/administration & dosage , Argentina , Drug Administration Schedule
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