Evaluation of Biocompatibility, Anti-Inflammatory, and Antinociceptive Activities of Pequi Oil-Based Nanoemulsions in In Vitro and In Vivo Models.

Pequi oil (Caryocar brasiliense) contains bioactive compounds capable of modulating the inflammatory process; however, its hydrophobic characteristic limits its therapeutic use. The encapsulation of pequi oil in nanoemulsions can improve its biodistribution and promote its immunomodulatory effects. Thus, the objective of the present study was to formulate pequi oil-based nanoemulsions (PeNE) to evaluate their biocompatibility, anti-inflammatory, and antinociceptive effects in in vitro (macrophages­J774.16) and in vivo (Rattus novergicus) models. PeNE were biocompatible, showed no cytotoxic and genotoxic effects and no changes in body weight, biochemistry, or histology of treated animals at all concentrations tested (90−360 µg/mL for 24 h, in vitro; 100−400 mg/kg p.o. 15 days, in vivo). It was possible to observe antinociceptive effects in a dose-dependent manner in the animals treated with PeNE, with a reduction of 27 and 40% in the doses of 100 and 400 mg/kg of PeNE, respectively (p < 0.05); however, the treatment with PeNE did not induce edema reduction in animals with carrageenan-induced edema. Thus, the promising results of this study point to the use of free and nanostructured pequi oil as a possible future approach to a preventive/therapeutic complementary treatment alongside existing conventional therapies for analgesia.

In Vivo Evaluation of DMSA-Coated Magnetic Nanoparticle Toxicity and Biodistribution in Rats: A Long-Term Follow-Up.

This work presents a long-term follow-up (300 days) of rats after a single intravenous injection of DMSA-coated magnetite nanoparticles (DMSA-MNP). The animals were systematically evaluated by hematological, biochemical, and ultrasound examinations, monitoring the same animal over time. In addition, oxidative stress evaluation, DMSA-MNP biodistribution, computerized tomography for ex vivo organs, and histopathology analysis were performed at the end of the experiment period. Overall, DMSA-MNP administration did not cause serious damage to the rats' health over the course of 300 days post-administration. All animals presented hematological parameters within the normal limits, and no alterations on serum creatinine, urea, ALT, and AST were related to DMSA-MNP administration. Liver and spleen showed no important alterations in any of the examinations. The kidneys of treated animals displayed intermittent pelvis dilation at ultrasound analysis, but without damage to the organ parenchyma after 300 days. The lungs of treated animals presented a light interalveolar septal thickening, but the animals did not present any clinical respiratory symptom. Nanoparticles were not detected in the vital organs of treated animals 300 days after administration. This work represents the first assessment of the long-term effects of DMSA-MNP and goes a step further on the safety of its use for biomedical applications.

New Prospects in Neutering Male Animals Using Magnetic Nanoparticle Hyperthermia.

Controlling populations of free-roaming dogs and cats poses a huge challenge worldwide. Non-surgical neutering strategies for male animals have been long pursued, but the implementation of the procedures developed has remained limited to date. As submitting the testes to high temperatures impairs spermatogenesis, the present study investigated localized application of magnetic nanoparticle hyperthermia (MNH) to the testicles as a potential non-surgical sterilization method for animals. An intratesticular injection of a magnetic fluid composed of manganese-ferrite nanoparticles functionalized with citrate was administered followed by testicle exposure to an alternate magnetic field to generate localized heat. Testicular MNH was highly effective, causing progressive seminiferous tubule degeneration followed by substitution of the parenchyma with stromal tissue and gonadal atrophy, suggesting an irreversible process with few side effects to general animal health.

Deciphering the Dynamics of Organic Nanoaggregates with AIEE Effect and Excited States: Lipophilic Benzothiadiazole Derivatives as Selective Cell Imaging Probes.

An aggregation-induced emission enhancement (AIEE) effect in fluorescent lipophilic 2,1,3-benzothiadiazole (BTD) derivatives and their organic nanoaggregates were studied. A set of techniques such as single-crystal X-ray, dynamic light scattering (DLS), electron paramagnetic resonance (EPR), UV-vis, fluorescence, and density functional theory (DFT) calculations have been used to decipher the formation/break (kinetics), properties, and dynamics of the organic nanoaggregates of three BTD small organic molecules. An in-depth study of the excited-state also revealed the preferential relaxation emissive pathways for the BTD derivatives and the dynamics associated with it. The results described herein, for the first time, explain the formation of fluorescent BTD nanoaggregate derivatives and allow for the understanding of their dynamics in solution as well as the ruling forces of both aggregation and break processes along with the involved equilibrium. One of the developed dyes could be used at a nanomolar concentration to selectively stain lipid droplets emitting an intense and bright fluorescence at the red channel. The other two BTDs could also stain lipid droplets at very low concentrations and were visualized preferentially at the blue channel.

Novel iron oxide nanocarriers loading finasteride or dutasteride: Enhanced skin penetration for topical treatment of alopecia.

In the present study, iron oxide nanoparticles, in the form of maghemite core coated with lauric acid (ION), were synthesized and loaded with finasteride (FIN) or dutasteride (DUT) as a novel drug delivery system for the topical treatment of alopecia. Additionally, developed formulations (FIN-ION and DUT-ION) were completely elaborated with components involved in the follicle metabolism, i.e., lauric acid, which acts as a 5α-reductase inhibitor, and iron which deficiency has been related to hair loss aggravation. Stability assessment conducted over the course of 90 days showed they are highly stable, with pH 7.4, constant EE% (>99%), and practically unchanged particle size and zeta potential. Besides drug distribution, the actual number of iron oxide nanoparticles, through a newly developed method using ferromagnetic resonance, was determined in each skin layer following permeation experiments. Despite the same donor concentration of colloids, nanoparticle distribution in the skin varied according to the loaded molecule. While DUT did not interfere with the nanoparticle natural tendency to accumulate within the hair follicle shafts, FIN presence hampered nanosystem interaction with the skin. Still, both formulations provided a higher skin drug penetration, compared to each respective control solution. Additionally, iron nanocarriers present a desirable visual characteristic, as the dark color aspect might instantly help disguise scarce hair follicle areas. These findings suggest the nanoformulations are highly promising for alopecia therapies.

Spontaneous and experimental poisoning by Froelichia humboldtiana in cattle / Intoxicação espontânea e experimental por Froelichia humboldtiana em bovinos

The aim of this work was to describe the epidemiological, clinical and pathological aspects of two outbreaks of spontaneous poisoning caused by Froelichia humboldtiana in cattle in Pernambuco, northeastern Brazil and reproduce experimentally this poisoning in cattle. Spontaneous poisonings of primary photosensitization occurred in two farms at the municipalities of Cachoeirinha and São Caetano and affected twenty-two adult bovines and two suckling calves after the rainy season. All bovines have recovered 21 days after they were removed from the pasture. To reproduce experimental poisoning, three cows and a calf were maintained in a pasture with 1ha composed by F. humboldtiana during 14 days. Clinical signs and skin lesions were similar in both spontaneous and experimental poisoning and consisted of cutaneous itching and hyperemia of non-pigmented areas of skin that evolved into edema, exudative dermatitis and extensive areas of skin necrosis. Serum levels of aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), total, direct and indirect bilirubin were normal in all cattle examined. Histologically, lesions consisted of epidermal necrosis, hyperkeratosis with large amounts of degenerate neutrophils and acanthosis. In the dermis, edema and inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells mainly around the blood vessels were observed. In the experimental group, clinical signs of photosensitization were observed after the third day of F. humboldtiana consumption. The suckling calf displayed mild clinical signs of photodermatitis on the 8th day of the experiment. It was estimated that the average consumption of F. humboldtiana necessary to initiate clinical signs in each adult bovine was 78kg.(AU)

Os objetivos deste trabalho foram descrever os aspectos epidemiológicos, clínicos e patológicos de dois surtos de intoxicação por Froelichia humboldtiana em bovinos em Pernambuco e reproduzir experimentalmente essa intoxicação em bovinos. Intoxicações espontâneas foram observadas após o início do período chuvoso nos municípios de Cachoerinha e São Caetano. Vinte e dois bovinos apresentaram sinais clínicos e lesões cutâneas compatíveis com fotossensibilização primária, dentre os quais, dois bezerros lactentes. Todos os bovinos se recuperaram totalmente cerca de 21 dias após serem retirados da pastagem. Para reproduzir experimentalmente a intoxicação, três vacas, uma delas com bezerro ao pé, foram mantidas em um piquete de 1ha composto por F. humboldtiana por 14 dias consecutivos. O quadro clínico e as lesões tegumentares, tanto nos bovinos intoxicados nos surtos espontâneos, quanto nos bovinos do experimento consistiram em prurido e hiperemia em áreas despigmentadas de pele, que evoluíam para edema, dermatite exsudativa e necrose de áreas extensas de pele. Em todos os bovinos examinados, os níveis séricos de aspartato aminotransferase (AST), gamaglutamiltransferase (GGT), bilirrubina total, direta e indireta estavam normais. Histologicamente, as lesões consistiram em necrose da epiderme, hiperqueratose com grande quantidade de neutrófilos degenerados e acantose. Na derme havia edema e infiltrado inflamatório composto por eosinófilos, linfócitos e plasmócitos principalmente ao redor dos vasos sanguíneos. Nos bovinos do experimento, sinais clínicos de fotossensibilização foram observados após o terceiro dia de consumo de F. humboldtiana. O bezerro lactente apresentou sinais clínicos leves de fotodermatite no 8º dia do experimento. Estimou-se que o consumo médio de matéria seca de F. humboldtiana necessário para iniciar os sinais clínicos em cada bovino adulto foi de 78kg.(AU)

Reverse Semi-Combustion Driven by Titanium Dioxide-Ionic Liquid Hybrid Photocatalyst.

Unprecedented metal-free photocatalytic CO2 conversion to CO (up to 228±48 µmol g-1 h-1) was displayed by TiO2@IL hybrid photocatalysts prepared by simple impregnation of commercially available P25-titanium dioxide with imidazolium-based ionic liquids (ILs). The high activity of TiO2@IL hybrid photocatalysts was mainly associated to (i) TiO2@IL red shift compared to the pure TiO2 absorption, and thus a modification of the TiO2 surface electronic structure; (ii) TiO2 with IL bearing imidazolate anions lowered the CO2 activation energy barrier. The reaction mechanism was postulated to occur via CO2 photoreduction to formate species by the imidazole/imidazole radical redox pair, yielding CO and water.

DFT analysis, spectroscopic study and biological activity of a newly synthesized benzoylhydrazone binuclear Cu(II) complex.

The current work reports a joint experimental and theoretical study of a novel Cu(II) complex [CuL(µ-CH3COO)]2, based on 2-acetylpyridine-benzoylhydrazone ligand (HL). The two Cu(II) atoms are five-coordinated, consisting of three NNO-donor atoms from the hidrazone ligand connected by acetate bridges. In addition to the structural analysis, the complete characterization includes magnetic susceptibility, elemental analysis, FT-IR and UV-Vis. Two different approaches of Density Functional Theory (DFT) with localized basis set and plane waves were performed. The theoretical calculations were used to optimize the complex geometry of the new structure allowing a better understanding of its spectroscopic properties with insights of most important interactions. Thereunto, we made a comparison between the following functionals: B3LYP, PBE1PBE, B3PW91, ω-B97XD, M06 (hybrids), CAM-B3LYP (long range hybrid), and B97-d (pure), using localized basis set, and for plane waves we used the PW91 functional. Considering the expected antifungal and antibacterial activity of hydrazone derivative ligand, the antimicrobial activity of HL and the complex [CuL(µ-CH3COO)]2 was tested against pathogenic Gram-positive and Gram-negative bacteria and fungi. The synthesized new structure of hydrazone complexed with copper (II) shows antimicrobial activity, and magnetic susceptibility results indicate weak antiferromagnetic coupling between the copper atoms.

Photocatalytic Reverse Semi-Combustion Driven by Ionic Liquids.

The simple photolysis of CO2 in aqueous solutions to generate CO and/or hydrocarbons and derivatives in the presence of a catalyst is considered to be a clean and efficient approach for utilizing CO2 as a C1 building block. Despite the huge efforts dedicated to this transformation using either semiconductors or homogeneous catalysts, only small improvements of the catalytic activity have been achieved so far. This article reports that simple aqueous solutions of organic salts-denominated as ionic liquids-can efficiently photo-reduce CO2 to CO without using photosensitizers or sacrificial agents. The system relies on the formation of the [CO2 ].- intermediate through homolytic C-C bond cleavage in a cation-CO2 adduct of imidazolium-based ionic liquids (ILs). The system continuously produced CO up to 2.88 mmol g-1 of IL after 40 h of irradiation by using an aqueous solution of 1-n-butyl-3-methylimidazolium-2-carboxylate (BMIm.CO2 ) IL, representing an apparent quantum yield of 3.9 %. The organophotocatalytic principles of our system may help to develop more simple and efficient organic materials for the production of solar fuels from CO2 under mild conditions, which represents a real alternative to those based on semiconductors and homogeneous metal-based catalysts.

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition.

Cytoglobin (Cygb) is a hexacoordinate protein, associated with the transport of oxygen, nitric oxide scavenging, tumor suppression and protection against oxidative stress and inflammation. This protein is expressed in brain areas including the preoptic area (POA) of the anterior hypothalamus, the region responsible for the regulation of body temperature. In this study, we show that Cygb is upregulated in the rat hypothalamus 2.5 h and 5 h after intravenous administration of lipopolysaccharide (LPS). We investigated the effect of treatment with Cygb in POA primary cultures stimulated with LPS for 4 h. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured and the results showed that Cygb reduced the concentrations of both cytokines. We further observed a decrease in immunoreactivity of the inflammatory transcription factor nuclear factor-κB (NF-κB), but not NF-IL6 and STAT3, in the nucleus of Cygb-treated POA cells. These findings suggest that Cygb attenuates the secretion of IL-6 and TNF-α in LPS-stimulated POA primary cultures via inhibition of the NF-κB signaling pathway, indicating that this protein might play an important role in the control of neuroinflammation and fever.

Increase of reactive oxygen species in different tissues during lipopolysaccharide-induced fever and antipyresis: an electron paramagnetic resonance study.

Fever is a regulated increase in body temperature and a component of the acute-phase response, triggered mainly after the invasion of pathogens in the body. Reactive oxygen species (ROS) are generated during the physiological and pathological processes, and can act as both signalling molecules as well as promoters of oxidative stress. Male Wistar rats, pretreated with oral doses of acetaminophen, celecoxib, dipyrone, or ibuprofen 30 min before an intravenous lipopolysaccharide (LPS) or sterile saline injection, showed a reduced febrile response in all animals tested. The formation of ROS in the fresh blood, liver, brown adipose tissue (BAT), and hypothalamus of febrile and antipyretic-treated animals was assessed by electron paramagnetic resonance using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). While the CM• concentrations remained unaltered in the blood samples examined 5 h after the induction of fever, we found increased CM• levels in the liver (in µM, saline: 290 ± 42; LPS: 512 ± 34), BAT (in µM, saline: 509 ± 79, LPS: 855 ± 79), and hypothalamus (in µM, saline: 292 ± 35; LPS: 467 ± 8) at the same time point. Importantly, none of the antipyretics were seen to alter the CM• accumulation profile. Data from this study suggest that there is an increased formation of ROS in the different tissues during fever, which may cause oxidative stress, and that the antipyretics tested do not interfere with ROS production.

Adenoma canalicular em lábio superior / Canalicular Adenoma in Upper Lip

O adenoma canalicular é uma neoplasia benigna incomum de glândulas salivares, que acomete principalmente as glândulas menores, com acentuada predileção pelo lábio superior. Essa neoplasia é mais prevalente em pacientes do sexo feminino, acima de 50 anos de idade. O objetivo deste trabalho é relatar um caso clínico de adenoma canalicular no lábio superior de uma paciente de 68 anos de idade, bem como rever a literatura pertinente. As características clínicas, hipóteses de diagnóstico, histopatologia, tratamento e prognóstico dessa neoplasia são apresentados e discutidos.

The canalicular adenoma is a rare benign salivary gland tumor that affects mainly the minor glands, with a marked predilection for the upper lip. This tumor is more prevalent in female patients above 50 years old. The objective of this study is to report on a case of canalicular adenoma in the upper lip of a 68 years old female patient and to review the pertinent literature. The clinical features, diagnostic hypotheses, histopathology, treatment and prognosis of this tumor are presented and discussed.

Highly efficient photodynamic therapy colloidal system based on chloroaluminum phthalocyanine/pluronic micelles.

Phthalocyanine derivatives comprise the second generation of photosensitizer molecules employed in photodynamic therapy (PDT) and have attracted much attention due to their outstanding photosensitizing performance. Most phthalocyanines are hydrophobic compounds that require association to drug delivery systems for clinical use. In this study, formulations of Pluronic F127 micelles incorporated with chloroaluminum phthalocyanine, or else F127/AlClPc, were produced at optimized conditions aiming at efficient and biocompatible PDT colloidal systems. Absorption/emission spectroscopies, as well as dynamic light scattering were performed to evaluate the optimum conditions for the F127 micelle formation and AlClPc incorporation. The micelles formation was attained with F127 concentrations ranging from 50 to 150mgmL(-1). At these conditions, AlClPc photosensitizer molecules were encapsulated into the hydrophobic micelle core and, therefore, readily solubilized in physiological medium (PBS pH 7.2). Encapsulation efficiency of about 90% resulted from different AlClPc concentrations. Identification of singlet oxygen production by irradiated F127/AlClPc formulations indicated good applicability for PDT. In vitro tests conducted with A549 human lung carcinoma cell line incubated with the F127/AlClPc formulations, at different AlClPc loadings, followed by only 18min of light irradiation (660nm LED, fluence of 25.3J/cm(2)), showed a cellular damage as high as 90% for rather low dosages of AlClPc (0.1-5.0µgmL(-1)). Further, no cytotoxicity occurred on non-irradiated cells. These findings suggest those F127/AlClPc formulations are highly promising for PDT applications, since they are easily prepared and the incubation and irradiation times are significantly shortened.

Proteomic Analysis of Neutrophil Priming by PAF.

Polymorphonuclear neutrophils are the main cells of the innate immunity inflammatory response. Several factors can activate or stimulate neutrophils, including platelet-activating factor (PAF), a lipid mediator. Some authors consider the activation induced by PAF priming because it triggers limited production of reactive oxygen species (ROS) and it amplifies the response of the cell to a subsequent activator. The stimulation is reversible, which is critical for modulating the inflammatory response. Exacerbated inflammatory responses lead to serious diseases, such as systemic inflammatory response syndrome (SIRS), among others. Characterizing the stimulation of neutrophils during the possible reversion or prevention of an exaggerated inflammatory response is critical for the development of control strategies. In this study, a proteomic approach was used to identify 36 proteins that differ in abundance between quiescent neutrophils and PAFstimulated neutrophils. The identified proteins were associated with increased DNA repair processes, calcium flux, protein transcription, cytoskeleton alterations that facilitate migration and degranulation, and the release of proinflammatory cytokines and proteins that modulate the inflammatory response. Some of the identified proteins have not been previously reported in neutrophils.

Facial soft tissues of mouth-breathing children: do expectations meet reality?

OBJECTIVE: To quantify the differences between the facial soft tissue morphology of severely obstructed mouth breathing (MB) and that of predominantly nasal breathing (NB) children. METHODS: Soft tissue measurements were performed in the lateral cephalograms of 64 severely obstructed MB children (mean age 6.7 ± 1.6) compared with 64 NB children (mean age 6.5 ± 1.3). Groups were paired by age, gender, skeletal maturation status and sagittal skeletal pattern. Based on the assumption of normality and homoscedasticity, comparison of the means and medians of soft tissue measurements between the two groups was performed. RESULTS: The facial convexity and anterior facial height ratio of MB were similar to NB children. The upper lip of MB children was protruded, and its base was thinner compared with NB; however, the length was not affected. The lower lip was shorter and more protruded in MB children. The nasolabial angle, nasal prominence, and chin thickness were smaller in MB children. CONCLUSIONS: The facial soft tissue of severely obstructed MB children is different than in NB children. Changes in lips, nasolabial angle, nasal prominence, and chin thickness are associated with severe airway obstruction in children.

Spatial and temporal analysis of stem bleeding disease in coconut palm in the state of Sergipe, Brazil.

Stem bleeding disease (resinosis) of coconut palm is caused by Thielaviopsis paradoxa and is very important in the state of Sergipe, Brazil. Understanding the epidemiological behavior of the disease is essential for establishing more efficient control strategies. Thus, we characterized the temporal progression and spatial distribution of stem bleeding in a commercial orchard under conditions of natural infection in the area of Neopolis, Sergipe. Three plots with 729 plants each were selected and evaluated every two months for stem bleeding incidence. In the temporal analysis, the monomolecular model gave the best fit to data on disease incidence, as it accurately showed the temporal dynamics of the disease during the experiment period. The spatial pattern of stem bleeding varied over time, with initial infections presenting random pattern and then evolving to aggregate pattern during evaluations. This indicates that the disease may have originated from the pathogen survival structures, followed by auto infections caused by dissemination from plant to plant, either by humans, by contact between roots, or by the vector Rhynchophorus palmarum.

Primary photosensitization in cattle caused by Froelichia humboldtiana.

Three outbreaks of primary photosensitization caused by Froelichia humboldtiana are reported in the semiarid region of the states of Pernambuco and Paraíba, in northeastern Brazil. The disease occurred from March to June 2011, affecting 27 bovines out of a total of 70. The main lesions consisted of dermatitis of the white skin, with edema and necrosis. All the bovines recovered after removal from the areas invaded by F. humboldtiana. To produce the disease experimentally, one bovine with white skin was placed for 14 days into an area with F. humboldtiana as the sole forage. This bovine presented photodermatitis on the third day of consumption. The serum concentrations of total, indirect, and conjugated bilirubin and the serum activities of gamma-glutamyl transferase (GGT) and aspartate-aminotransferase (AST) in the spontaneously affected cattle and in the experimental cattle remained within normal ranges. It is concluded that F. humboldtiana causes primary photosensitization in cattle in northeastern Brazil.

Genetic polymorphism of MUC7 in individuals with aggressive or chronic periodontitis.

Individuals with periodontitis exhibit differential expression of mucin-glycoprotein-2 (MG2), a protein encoded by the MUC7 gene. It is well known that MG2 exerts bactericidal activity as well as exhibiting genetic polymorphism involving a variable number of tandem repeats (VNTR). In the present study, we assessed the distribution of allelic variants of the MUC7 gene in 22 individuals with aggressive periodonitis, 68 with chronic periodonitis, and 87 without periodonitis. Oral mucosal cells were collected, the DNA was extracted, and specific primers were used to amplify the region encoding the MUC7 tandem repeats (TRs). Polymerase chain reaction products were subjected to electrophoresis and analyzed on polyacrylamide gels stained with silver nitrate. Although the percentage distribution of homozygosity (6-6TR) and heterozygosity (5-6TR) showed variation among the groups, the observed differences were not statistically significant (P > 0.05; Fisher's Exact Test). The present results indicate that the expression of different numbers of TRs in this salivary mucin in the oral environment does not interfere with the etiopathogenesis of aggressive or chronic periodontitis.

Mannose binding lectin gene polymorphisms and associated auto-immune diseases in type 1 diabetes Brazilian patients.

In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms (SNPs) in the augmented susceptibility to develop other autoimmune diseases in presence of type 1 diabetes (T1D) in a group of Brazilian patients. Patients were stratified for the presence of autoimmune diseases known to be associated with T1D, such as autoimmune thyroid disease (AITD) and celiac disease (CD), and compared with healthy controls (HC). Our findings suggest that MBL2 functional SNPs are more closely related to AITD than to T1D, being MBL2 SNPs frequencies in T1D patients not affected by AITD comparable to the HC ones, while significantly different between AITD patients and patients not affected by the disease. Thus, the association between MBL2 polymorphisms and T1D that we previously reported, seems to result from the stronger association of MBL2 SNPs with another autoimmune disease, the AITD, frequently associated with T1D.

Trypanosoma cruzi infection induces differential modulation of costimulatory molecules and cytokines by monocytes and T cells from patients with indeterminate and cardiac Chagas' disease.

Interactions between macrophages and lymphocytes through costimulatory molecules and cytokines are essential for mounting an efficient immune response and controlling its pathogenic potential. Here we demonstrate the immunomodulatory capacity of Trypanosoma cruzi, the causative agent of Chagas' disease, through its ability to induce differential expression of costimulatory molecules and cytokines by monocytes and T cells. Costimulatory molecule and cytokine modulation was evaluated using cells from noninfected individuals and from patients with the asymptomatic indeterminate form and those with the severe cardiac clinical form of Chagas' disease. Our results show that while exposure of monocytes to live T. cruzi leads to an increase in the frequency of CD80(+) monocytes in all groups, it decreases both the frequency and intensity of CD86 expression by monocytes from patients with the cardiac form but not from those with the indeterminate form. Conversely, exposure of lymphocytes to monocytes infected with T. cruzi increased the surface expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) by T cells from indeterminate but not from cardiac patients, compared to that from control patients. These data suggest that T. cruzi induces a potentially down-regulatory environment in indeterminate subjects, which is associated with higher CD80 and CTLA-4 expression. To test the functional importance of this modulation, we evaluated the expression of cytokines after in vitro infection. Although exposure of lymphocytes to parasite-infected monocytes induced high expression of inflammatory and anti-inflammatory cytokines by T cells in all groups, indeterminate patients displayed a higher ratio of monocytes expressing interleukin 10 than tumor necrosis factor alpha following infection than did controls. These data show the ability of T. cruzi to actively change the expression of costimulatory molecules and cytokines, suggesting molecular mechanisms for the differential clinical evolution of human Chagas' disease.