scholarly journals A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents

1984 ◽  
Vol 79 (2) ◽  
pp. 221-225 ◽  
Author(s):  
Leny S. Filardi ◽  
Zigman Brener

A method is described which permits to determine in vivo an in a short period of time (4-6 hours) the sensitivity of T. cruzo strains to known active chemotherapeutic agents. By using resistant- and sensitive T. cruzi stains a fairly good correlation was observed between the results obtained with this rapid method (which detects activity against the circulating blood forms) and those obtained with long-term schedules which involve drug adminstration for at least 20 consecutive days and a prolonged period of assessment. This method may be used to characterize susceptibility to active drugs used clinically, provide infomation on the specific action against circulating trypomastigotes and screen active compounds. Differences in the natural susceptibility of Trypanosoma cruzi strains to active drugs have been already reported using different criteria, mostly demanding long-term study of the animal (Hauschka, 1949; Bock, Gonnert & Haberkorn, 1969; Brener, Costa & Chiari, 1976; Andrade & Figueira, 1977; Schlemper, 1982). In this paper we report a method which detects in 4-6 hours the effect of drugs on bloodstream forms in mice with established T. cruzi infections. The results obtained with this method show a fairly good correlation with those obtained by prolonged treatment schedules used to assess the action of drugs in experimental Chagas' disease and may be used to study the sensitivity of T. cruzi strains to active drugs.

1999 ◽  
Vol 73 (11) ◽  
pp. 9256-9265 ◽  
Author(s):  
Matthias Schweizer ◽  
Hubertus Schleer ◽  
Michael Pietrek ◽  
Jürgen Liegibel ◽  
Valeria Falcone ◽  
...  

ABSTRACT The genetic variability of the envelope surface domain (SU) of simian foamy virus (FV) of African green monkeys was studied. To assess the interindividual diversity of FV, isolates were obtained from 19 animals living together in a monkey house. The monkeys had been imported from Kenya prior to being placed in long-term housing in the research institute. In addition, a simian FV isolate and proviral DNA were obtained from an animal caretaker infected in this setting. DNA of the complete SU (1779 to 1793 bp) was analyzed by PCR and sequencing. The sequences revealed four clusters with high homologies (>95%). Between the clusters, divergencies ranged from 3 to 25%. Obviously, the clusters reflect four different strains or subtypes of simian FV type 3 that were prevalent in the colony. In contrast to lentiviruses, hypervariable regions could not be detected in the FV SU. Furthermore, to analyze the intraindividual diversity of FV, we investigated the virus population within an individual monkey at a given time point and its evolution over 13 years. For this purpose, 22 proviral SU clones generated by PCR from one oral swab and seven isolates obtained from the same animal between 1982 and 1995 were examined. These sequences revealed exceptionally high homology rates (99.5 to 100%), and only a minimal genetic drift was recognized within the series of isolates. In conclusion, the low in vivo divergency of FV SU suggests that genetic variability is not important for the maintenance of FV persistence.


2003 ◽  
Vol 254-256 ◽  
pp. 695-698
Author(s):  
R.L. Mourão ◽  
Herman S. Mansur ◽  
F.R. Tay ◽  
L. Dlanza

1987 ◽  
Vol 64 (3) ◽  
pp. 354-360 ◽  
Author(s):  
Leda Maria Cummings ◽  
Paulo César Cotrim ◽  
JoséFranco da Silveira

2011 ◽  
Vol 30 (3) ◽  
pp. 335-340 ◽  
Author(s):  
Jonathan R. Pribaz ◽  
Nicholas M. Bernthal ◽  
Fabrizio Billi ◽  
John S. Cho ◽  
Romela Irene Ramos ◽  
...  

2009 ◽  
Vol 206 (4) ◽  
pp. 751-760 ◽  
Author(s):  
Kylie E. Webster ◽  
Stacey Walters ◽  
Rachel E. Kohler ◽  
Tomas Mrkvan ◽  
Onur Boyman ◽  
...  

Via a transcription factor, Foxp3, immunoregulatory CD4+CD25+ T cells (T reg cells) play an important role in suppressing the function of other T cells. Adoptively transferring high numbers of T reg cells can reduce the intensity of the immune response, thereby providing an attractive prospect for inducing tolerance. Extending our previous findings, we describe an in vivo approach for inducing rapid expansion of T reg cells by injecting mice with interleukin (IL)-2 mixed with a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2–IL-2 mAb complexes for a short period of 3 d induces a marked (>10-fold) increase in T reg cell numbers in many organs, including the liver and gut as well as the spleen and lymph nodes, and a modest increase in the thymus. The expanded T reg cells survive for 1–2 wk and are highly activated and display superior suppressive function. Pretreating with the IL-2–IL-2 mAb complexes renders the mice resistant to induction of experimental autoimmune encephalomyelitis; combined with rapamycin, the complexes can also be used to treat ongoing disease. In addition, pretreating mice with the complexes induces tolerance to fully major histocompatibility complex–incompatible pancreatic islets in the absence of immunosuppression. Tolerance is robust and the majority of grafts are accepted indefinitely. The approach described for T reg cell expansion has clinical potential for treating autoimmune disease and promoting organ transplantation.


2021 ◽  
Vol 8 (1) ◽  
pp. 5-7
Author(s):  
Santhwana A ◽  
Venkitachalam R ◽  
Sridhu Prakash

A total of 20 bird species belongs to 7 orders and 11 families were recorded in Dharmadam estuary in Kannur district. The record of migratory bird Eurasian Curlew and two species near threatened birds within a short period of study and this record indicate that Dharmadam estuary may be attracting more number of migratory bird species. A long-term study is needed to understand the seasonal variation of the bird species in Dharmadam estuary in Kannur district.


2003 ◽  
Vol 47 (1) ◽  
pp. 223-230 ◽  
Author(s):  
Max Jean de Ornelas Toledo ◽  
Maria Terezinha Bahia ◽  
Cláudia M. Carneiro ◽  
Olindo Assis Martins-Filho ◽  
Michel Tibayrenc ◽  
...  

ABSTRACT The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2596-2596
Author(s):  
Li Liu ◽  
Bradley S. Fletcher

Abstract Gene therapy in adult hemophilia A mice is known to generate a robust immune response against the newly produced FVIII protein. This phenomenon has been extensively reported for both viral and non-viral vectors. T cell activation promotes the proliferation of B cells that produce antibodies against FVIII (inhibitors) leading to a loss of circulating FVIII protein and activity. Approaches to attenuate this immune response have included the use of cytotoxic chemotherapeutic agents (such as cyclophosphamide) or the use of antibodies or soluble fusion proteins that prevent T cell activation (such as the fusion protein between the cytotoxic T lymphocyte-associated antigen 4 and the immunoglobulin heavy chain, CTLA-4-Ig). Recently, the mechanism by which CTLA-4-Ig exerts its effect has been elucidated and is thought to involve tryptophan catabolism by upregulation of the enzyme indoleamine 2,3-dioxygenase (IDO). Catabolites of tryptophan degradation, such as kynurenine, have been shown to block T cell proliferation and promote T cell apoptosis. Here we report that hydrodynamic co-administration of Sleeping Beauty transposons encoding both FVIII and IDO are able to attenuate, but not fully block, inhibitor formation. With this approach, long term expression of FVIII at therapeutic levels (∼10% of normal) can be achieved in adult animals without the need for additional immune suppression. Only in animals receiving FVIII and IDO together can we detect FVIII protein by western blot at 24 weeks. Serum kynurenine levels are slightly elevated after gene delivery in animals receiving the IDO gene, but fall to within normal levels by 24 weeks. These results suggest that modulation of the levels of tryptophan catabolites in vivo can influence the formation of FVIII inhibitors.


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