Search

Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in -vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime., Competing Interests: Enter: The authors have declared that no competing interests exist.

Background: Trypanosoma cruzi has a high genetic and biological diversity and has been subdivided into seven genetic lineages, named TcI-TcVI and TcBat. DTUs TcI-TcII-TcV and TcVI are agents of ChD in different regions of Latin America. Due to population movements, the disease is an emergent global public health problem. Thus, the aim of this study was to quantify the parasitic load and identify the presence of T. cruzi DTUs in 101 Latin American immigrants with chronic ChD, residing in Barcelona, Spain., Methodology / Principal Findings: 5ml of peripheral blood were collected in guanidine/EDTA from each patient for DNA extraction, quantification of the parasitic load and genotyping. A great variation of the parasitic load of the patients was verified: from 0.001 to 22.2 T. cruzi DNA (fg) / Blood DNA (ng). In patients from Bolivia the parasitic load was 3.76±4.43 T. cruzi DNA (fg) / Blood DNA (ng) (mean ± SD), in patients of other countries was 0.95±1.38 T. cruzi DNA (fg) / Blood DNA (ng). No statistically significant difference was observed in the parasitic load between patients with the indeterminate and cardiac forms of ChD (p = 0,57). Parasite genotyping was performed by multilocus conventional PCR. In patients from Bolivia there was a nearly equal prevalence of DTUs TcV (27/77), TcII/TcV/TcVI (26/77), and TcII/TcVI (22/77). TcVI was detected in only 2 samples (2/77). A higher prevalence of TcII/TcVI (19/24) was verified in patients of other countries, with low prevalence of TcII/TcV/TcVI (4/24) and TcV (1/24)., Conclusions/significance: In this study, low/medium parasitic load was found in all patients evaluated. Our data corroborate previous conclusions indicating that patients from the Bolivia, living in Spain, are predominantly infected by TcV, and TcVI DTUs. On the other hand, in Non-Bolivians patients TcII/TcVI predominated. Surprisingly, in our cohort of 101 patients no infection by TcI DTU was observed., Competing Interests: The authors have declared that no competing interests exist.

Industrial laundries have water as one of their main inputs and they release effluents in large amounts, with a high polluting load, which are usually discarded into the environment, or they are insufficiently treated for release into the neighboring water bodies. The aim of this study was to evaluate the efficiencies of the biological treatments in an industrial textile laundry and their environmental impact on the surface waters of the stream where the dump is usually made, by using cytotoxicity tests on the meristematic root cells of Allium cepa L. The results have shown, for the most part, that the treated effluents over a period of 24 h showed reductions in their mitotic index. The treatments on the raw effluents showed cytotoxic effects when compared to control, with cell division recoveries after 24 h in the waters. Cytotoxic effects were additionally observed in the stream waters, at a point before the dump, indicating that they received a pollutant load, before the effluent disposal site of the evaluated industrial laundry. Notably, the treatments that were being applied by the industrial laundry were effective throughout the processing, reducing the concentrations of the toxic substances. When considering the data presented, it is now understood that there is a constant need for the evaluation of industrial effluents, as well as for the waters of the streams and the rivers that receive these disposals, in order to preserve and maintain the quality of the waters, the organisms, and consequently, the ecosystems.

Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses.

Objective: Little is known about the impact of neoadjuvant chemotherapy on cell-mediated immunity in patients with advanced cervical cancers., Patients and Methods: We have studied 24 patients with advanced cervical cancer submitted to neoadjuvant chemotherapy (CT) using cis-platinum (100 mg/m(2)/cycle) and bleomycin (30 mg/cycle). The cell-mediated immunity parameters available before and after CT were NK cells, CD4(+)/CD28 and CD8(+)/CD28 T-lymphocyte numbers, PBMC cytotoxicity, and modification of this parameter with "in vitro" addition of IL-12., Results: The number of NK cells was higher before CT (P < 0.008) in 13 patients who presented a good clinical response to treatment, compared to 11 patients with a poor clinical response. In addition, PBMC cytotoxicity (P < 0.001), CD4(+) and CD8(+) T-lymphocyte values (P < 0.0047), and CD8(+)/CD28(+) cells were also higher in the group with a good response compared with the group with a poor response. Addition of IL-12 to the medium increased the lytic capacity of PBMC after CT only in the group with a good clinical response (P < 0.05)., Conclusions: NK cell numbers, CD8(+) T-cell levels, and CD8(+)/CD28(+) cell levels can be used as prognostic factors before CT. Our results suggest that patients with a poor response have lower lytic activity per NK cell and are refractory to IL-12 stimulation, probably as a result of the reduced expression of IL-12 receptors or of an intracellular defect in the mechanism of transduction. These observations also provide support for human clinical trials of IL-12 and neoadjuvant CT in patients with cervical cancer., (Copyright 2000 Academic Press.)

Antibody-dependent cellular cytotoxicity mediated by granulocytes (ADGC) or lymphocytes (ADLC) was assessed in 23 patients with chronic Chagas disease. The results of ADGC against T. cruzi were normal. ADLC against chicken erythrocytes was significantly reduced in patients as compared with normal controls. Possible causes of this abnormality were investigated.