A prospective cohort study on post COVID syndrome from a tertiary care centre in Sri Lanka.

There is a scarcity of follow-up data on post-COVID syndrome and its physical, psychological, and quality of life attributes, particularly from South Asian populations. This study was conducted to assess the prevalence, associations, and impact of the post-COVID syndrome among patients treated at a dedicated COVID-19 treatment unit. A prospective cohort study was conducted to follow-up patients with moderate to severe disease or mild disease with co-morbidities at 2 and 6 weeks, 3 and 6 months and 1 year from discharge. Clinical notes, an interviewer-administered questionnaire and six-item cognitive impairment, Montreal Cognitive Assessment, Fatigue (11-item Chalder) and EQ5D5L questionnaires were used for data collection. All patients had follow-up echocardiograms and symptomatic patients had biochemical and haematological investigations, chest x-rays, high-resolution computed tomography of chest and lung function tests. Among 153 patients {mean age 57.2 ± 16.3 years (83 (54.2% males)}, 92 (60.1%) got the severe disease. At least a single post-COVID symptom was reported by 119 (77.3%), 92 (60.1%), 54 (35.3%) and 25 (16.3%) at 6 weeks, 3 months, 6 months and 1 year respectively. Post-COVID symptoms were significantly associated with disease severity (p = 0.004). Fatigue was found in 139 (90.3%), 97 (63.4%) and 66 (43.1%) patients at 2, 6 and 12 weeks respectively. Dyspnoea {OR 1.136 (CI 95% 0.525-2.455)}, arthralgia {OR 1.83(CI 95% 0.96-3.503)} and unsteadiness {OR 1.34 (CI 95% 0.607-2.957)}were strongly associated with age above 60 years. Both genders were equally affected. In multivariable logistic regression, fatigue and anxiety/depression were associated with poor quality of life (QoL) (p = 0.014, p ≤ 0.001) in 6 weeks. In cardiac assessments, diastolic dysfunction (DD) was detected in 110 (72%) patients at 2 weeks and this number reduced to 64 (41.8%) at 12 weeks. The decline in diastolic dysfunction in elderly patients was significantly higher compared to young patients (p = 0.012). Most post-COVID symptoms, QoL and cognition improve during the first few months. The severity of the disease and older age are associated with post-COVID symptoms. Transient DD may contribute to cardiac symptoms of post-COVID syndrome, especially in elderly patients.

Dynamics of the orphan myosin MyoF over Trypanosoma cruzi life cycle and along the endocytic pathway.

Trypanosoma cruzi proliferative forms perform endocytosis through a specialized structure named the cytostome-cytopharynx complex (SPC). The SPC is a specialized invagination of the cell membrane that extends through the cell body towards the posterior regions, with its aperture close to the flagellar pocket. Recently, diverse proteins were found along the cytopharynx, including two myosin motors. One of these is the orphan myosin MyoF, that was proved to be essential for endocytosis in epimastigotes. However, the dynamics of MyoF localization along the endocytic pathway and through the T. cruzi life cycle remain unclear. Using CRISPR-Cas9 genome editing, we generated epimastigotes expressing MyoF fused to mNeonGreen from its endogenous locus. Using these cells, we observed that during the epimastigote cell cycle MyoF signal disappeared during G2, reappearing at early cytokinesis. Additionally, we show that MyoF localization during metacyclogenesis is compatible with the progressive disappearance of the SPC, being absent in metacyclic trypomastigotes. Detergent fractionation showed that MyoF was predominantly present in the insoluble fraction and immunolocalized at the SPC microtubules in whole-mount cytoskeleton preparations. Moreover, during tracer uptake through the SPC, MyoF followed the tracer along the endocytic pathway and was found in posterior compartments after 30 min. Taken together, the data suggest that MyoF may play a role not only at the cargo entry site but also along the endocytic pathway.

Dysregulation of placental ABC transporters in a murine model of malaria-induced preterm labor.

Malaria in Pregnancy (MiP) is characterized by placental accumulation of Plasmodium-infected erythrocytes, intrauterine growth restriction (IUGR) and preterm delivery (PTD). Placental ATP-binding cassette (ABC) transporters mediate the efflux of nutrients, cytokines and xenobiotics. The expression and activity of these transporters are highly responsive to infection. We hypothesized that MiP would perturb the expression of placental ABC transporters, promoting PTD. Peripheral blood, spleens, livers and placentas of pregnant mice, infected with Plasmodium berghei ANKA on gestational day (GD) 13.5, were collected and analyzed on GD18.5. The primary consequences of human MiP, including IUGR, PTD (20%) and placental inflammation, were recapitulated in our mouse model. Electron microscopy revealed attenuated presence of labyrinthine microvilli and dilated spongiotrophoblasts -granular endoplasmic reticulum cisternae. Additionally, a decrease in placental Abca1 (ABCA1), Abcb1b (P-glycoprotein), Abcb9 and Abcg2 (BCRP) expression was observed in MiP mice. In conclusion, MiP associated with PTD impairs placental ABC transporters' expression, potentially modulating placental nutrient, environmental toxin and xenobiotic biodistribution within the fetal compartment, and may, at some degree, be involved with pregnancy outcome in MiP.

Quantum corrections for the phase diagram of systems with competing order.

We use the effective potential method of quantum field theory to obtain the quantum corrections to the zero temperature phase diagram of systems with competing order parameters. We are particularly interested in two different scenarios: regions of the phase diagram where there is a bicritical point, at which both phases vanish continuously, and the case where both phases coexist homogeneously. We consider different types of couplings between the order parameters, including a bilinear one. This kind of coupling breaks time-reversal symmetry and it is only allowed if both order parameters transform according to the same irreducible representation. This occurs in many physical systems of actual interest like competing spin density waves, different types of orbital antiferromagnetism, elastic instabilities of crystal lattices, vortices in a multigap SC and also applies to describe the unusual magnetism of the heavy fermion compound URu2Si2. Our results show that quantum corrections have an important effect on the phase diagram of systems with competing orders.

Estresse e ajustamento conjugal de casais com filho(a) com Síndrome de Down / Stress and marital adjustament of couples with children with Down Syndrome

O presente estudo teve o objetivo de investigar estresse e ajustamento conjugal em 19 casais comum(a) filho(a) com síndrome de Down. As crianças tinham entre quatro e dez anos, sendo 11 do sexomasculino e 8 do sexo feminino. Utilizou-se o Questionário de Caracterização do Sistema Familiar,Dyadic Adjustment Scale em seu formato traduzido para a língua portuguesa do Brasil (Escala deAjustamento Diádico) e o ISSL para adultos. As mães são mais acometidas pelo estresse (n=11) doque os pais (n=7). Todas as mães percebem seu relacionamento conjugal como ajustado e somentedois pais o percebem como desajustado. Não foram encontradas associações significativas entreescores da EAD, sexo e idade dos genitores; e tempo de convivência do casal(AU)

Evaluation of mutagenic, teratogenic, and immunomodulatory effects of Annona nutans hydromethanolic fraction on pregnant mice.

Plants such as Annona nutans used in folk medicine have a large number of biologically active compounds with pharmacological and/or toxic potential. Moreover, pregnant women use these plants indiscriminately, mainly in the form of teas, without being aware of the harm that they could cause to the health of the embryo/fetus. Therefore, it is necessary to analyze the potential toxic effects of medicinal plants during gestation. The present study aimed to evaluate the effects of A. nutans hydromethanolic fraction leaves (ANHMF) on mutagenic and immunomodulatory activity, reproductive performance, and embryo-fetal development in pregnant female mice. The animals (N=50 female and 25 male) were divided into 5 groups: Control, Pre-treatment, Organogenesis, Gestational, and Pre+Gestational. The results indicate that ANHMF mainly contains flavonoid and other phenolic derivatives. It was found that it does not exhibit any mutagenic or immunomodulatory activity, and it does not cause embryo-fetal toxicity. Based on the protocols used in the present studies, our analyses confirm that it is safe to use ANHMF during pregnancy.

Silagem de híbridos de sorgo associado a percentagens de concentrado no desempenho de novilhos / Effect of sorghum hybrids silage associated to percentage of concentrate levels on the performance of steers

Avaliou-se o desempenho de novilhos alimentados em confinamento com silagem de híbridos de sorgo forrageiro e de duplo propósito associado a níveis de concentrado. Foram utilizados 60 novilhos, com idade inicial de 20 meses e peso corporal inicial de 322,45±5,58kg, distribuídos inteiramente ao acaso, nos seguintes tratamentos: três porcentagens de concentrado e dois tipos de silagem de sorgo. Foi verificada interação tipo de silagem versus porcentagem concentrado para consumo de matéria seca e ganho de peso médio diário, os quais aumentaram com o aumento de concentrado na dieta com silagem de sorgo forrageiro, mas não com silagem de sorgo duplo propósito. Os novilhos alimentados com silagem de sorgo forrageiro consumiram menos energia digestível (27,89Mcal/dia-1) que aqueles alimentados com silagem de sorgo duplo propósito (31,42Mcal/dia-1). A conversão alimentar média não foi alterada pelo tipo de silagem utilizada. O aumento da porcentagem de concentrado em dietas com volumoso de menor qualidade aumenta a eficiência biológica de bovinos confinados.

The feedlot performance of steers fed forage sorghum and double purpose hybrids silage associated with concentrate levels was evaluated. A total of 60 steers, initial age 20 months and body weight of 322.45±5.58kg, were randomized in the treatments: three concentrate levels and two types of sorghum silage. The interaction of sorghum silage versus concentrate levels was observed for dry matter intake and average daily weight gain, which increased with the increase concentrate level in diets with forage sorghum silage, but was not altered in diets with double purpose silage. Steers fed forage sorghum silage presented a lower average intake of digestible energy (27.89Mcal/day-1) than those fed double purpose sorghum silage (31.42Mcal/day-1). The average feed conversion was not affected by the type of silage used. The increase of concentrate level in diets with lower forage quality increases the biological efficiency of feedlot beef cattle.

Virtual medical and pedagogical applicability of human dermatome patterns: critical review of the literature

Dermatome is an area of skin supplied by the posterior (sensory) root of a spinal nerve derived from a single cord segment, which is a particular aspect of the peripheral distribution of sensory fibers. Its topographic study is important to identify nerve, radicular, or medullary damage. When mapped, these dermatomes are outlined on the body surface and their assessment poses a special challenge to physicians once the distinguished imaging methods are not concordant in some aspects. Computers have taken over increasingly importance as transmitters of anatomical information in both clinical and educational sceneries. The present study concerning the virtual teaching and learning of the human dermatome patterns carries out an update of the literature and its clinical and radiological applicability. Computed-based anatomy programs do not only complement conventional instructions methods, but also provide the groundbreaking means to represent, standardize, and disseminate knowledge of dermatomes. Computer-based programs capable of standardizing a tridimensional map of human dermatomes still need to be developed.

Evolutionary conservation of actin-binding proteins in Trypanosoma cruzi and unusual subcellular localization of the actin homologue.

The actin cytoskeleton controls pivotal cellular processes such as motility and cytokinesis, as well as cell-cell and cell-substrate interactions. Assembly and spatial organization of actin filaments are dynamic events regulated by a large repertoire of actin-binding proteins. This report presents the first detailed characterization of the Trypanosoma cruzi actin (TcActin). Protein sequence analysis and homology modelling revealed that the overall structure of T. cruzi actin is conserved and that the majority of amino-acid changes are concentrated on the monomer surface. Immunofluorescence assays using specific polyclonal antibody against TcActin revealed numerous rounded and punctated structures spread all over the parasitic body. No pattern differences could be found between epimastigotes and trypomastigotes or amastigotes. Moreover, in detergent extracts, TcActin was localized only in the soluble fraction, indicating its presence in the G-actin form or in short filaments dissociated from the microtubule cytoskeleton. The trypanosomatid genome was prospected to identify actin-binding and actin-related conserved proteins. The main proteins responsible for actin nucleation and treadmilling in higher eukaryotes are conserved in T. cruzi.

A case-control study of protection against tuberculosis by BCG revaccination in Recife, Brazil.

SETTING: Metropolitan region of Recife, Brazil. OBJECTIVE: To estimate the additional protection against tuberculosis (TB) provided by a second dose of bacille Calmette-Guérin (BCG) vaccine. DESIGN: Case-control study. Cases were cases of TB newly diagnosed by the TB control programme, independent of clinical form. Three matched neighbourhood controls were selected using a systematic routine, starting from the case's address. The matching was within the age groups 7-9, 10-14 and 15-19 years. RESULTS: Analysis was conducted among 169 cases and 477 controls. For the efficacy of BCG revaccination against TB overall, matched (crude) vaccine effectiveness (VE) was -3 (95% CI -50-29) and matched (adjusted) VE was 8 (95% CI -77-52). CONCLUSIONS: This study suggests that a second dose of BCG does not offer additional protection. Revaccination should not be offered. As large numbers of subjects are already vaccinated and vaccine appears to offer some protection in older subjects, further studies with larger sample sizes could investigate the potential efficacy of revaccination with BCG in the age group > or = 15 years.

Further studies on the structural analysis of the cuticle of Litomosoides chagasfilhoi (Nematoda: Filarioidea).

In order to obtain further information on the structural organization of the cuticle of nematodes, this structure was isolated from adult forms of the filariid Litomosoides chagasfilhoi. The purity of the fraction was determined by light and transmission electron microscopy, deep-etching, high resolution scanning electron microscopy, atomic force microscopy, immunocytochemistry, gel electrophoresis (SDS-PAGE) and Western blot. The epicuticle presented a rugous surface with parallel rows and several globular particles that could be involved in the absorption of nutrients and secretion of products. Analysis by SDS-PAGE of purified cuticles revealed five major polypeptides corresponding to 151, 41, 28, 13 and 11 kDa. A polyclonal antibody against a synthetic 18 amino-acid peptide that corresponds to the sequence of domain E of the Haemonchus contortus3A3 collagen gene recognized several protein bands on the Western blot of purified cuticle, and labeled all cuticular layers, as shown by immunocytochemistry.

Breastfeeding and early weaning practices in northeast Brazil: a longitudinal study.

OBJECTIVES: To describe breastfeeding practices from 0 to 12 months of age in 4 small towns that are representative of urban northeast Brazil and to identify factors associated with introduction of other milk in the first month of life. METHODS: From January to August 1998, 364 mothers were interviewed at delivery to ascertain antenatal care; delivery room practices; and their intentions regarding breastfeeding, pacifiers, and introduction of water, teas, and other milk. Their perceptions of home support and the advantages of breastfeeding also were assessed. Thereafter, daily information about feeding practices was collected at twice-weekly home visits. When other milk was started, a second interview was conducted to ascertain initial and current breastfeeding problems and use of a pacifier. Reasons for starting other milk were investigated using 5-point Likert scales. RESULTS: Mothers were positive toward breastfeeding, and 99% breastfed their new infant. Few intended to breastfeed exclusively, and in the first week 80% gave water/tea and 56% used a pacifier. The median duration of exclusive breastfeeding was 0 days, and the median age for starting other milk was 24 days. The median duration of breastfeeding was 65 days for mothers who started other milk within 1 month and 165 days for other mothers. After adjustment for confounding variables, the main factors associated with introduction of other milk within 1 month were pacifier use in the first week (odds ratio [OR], 4.01; 95% confidence interval [CI]: 2.07-7.78), intention to start other milk in the first month (OR, 3.79; 95% CI: 1.74-8.24), giving water/tea in the first week (OR, 3.07; 95% CI: 1.56-6.03), and leaving the maternity ward before breastfeeding was started (OR, 2.59; 95% CI: 1.34-5.04). CONCLUSION: Although breastfeeding is common in this community, it rarely is exclusive and takes place for a relatively short duration. Identification of risk factors for early introduction of other milk offers potential avenues for future intervention, including improvement of breastfeeding support in antenatal and maternity services.

Choline acetyltransferase detection in normal and denervated electrocyte from Electrophorus electricus (L.) using a confocal scanning optical microscopy analysis.

Acetylcholine is the neurotransmitter responsible for the transmission of impulses from cholinergic neurons to cells of innervated tissues. Its biosynthesis is catalyzed by the enzyme Choline acetyltransferase that is considered to be a phenotypically specific marker for cholinergic system. It is well known that the regulation of Choline acetyltransferase activity under physiological and pathological conditions is important for development and neuronal activities of cholinergic functions. We observed the distribution of Choline acetyltransferase in sections from the normal and denervated main electric organ sections of Electrophorus electricus (L.) by immunofluorescence using a anti-Choline acetyltransferase antibody. The animals were submitted to a surgical procedure to remove about 20 nerves and after 30 and 60 days, they were sacrificed. After 30 days, the results from immunohistochemistry demonstrated an increase on the Choline acetyltransferase distribution at denervated tissue sections when compared with the sections from the normal contralateral organ. A very similar labeling was observed between normal and denervated tissue sections of the animals after 60 days. However, Choline acetyltransferase activity (nmolesACh/ min/ mg of protein) in extracts obtained from electrocyte microsomal preparation, estimated by Fonnun's method (Fonnun 1975), was 70% lower in the denervated extracts.

Two special organelles found in Trypanosoma cruzi.

We review here two unique organelles from Trypanosoma cruzi. One of them is the acidocalcisome, cytoplasmic vacuoles containing a very high Ca2+ concentration and a Ca2+ - H+ translocating ATPase activity, present in all trypanosomatids. The other organelle is the reservosome, site of accumulation of endocytosed macromolecules, very rich in cysteine proteinase, that is present only in epimastigote forms of trypanosomes belonging to the Schyzotrypanum sub-genus.

Synthesis of vitellogenin by the follicle cells of Rhodnius prolixus.

The synthesis and secretion of vitellogenin by the ovary of Rhodnius prolixus was investigated. Using whole ovary or epithelial cells isolated from follicles of different sizes, it is shown that the follicle cells are a site of synthesis for this protein in the ovary. The ovaries or follicle cells were incubated in vitro with [(35)S]-methionine or (32)Pi and the secretion of newly synthesized ovarian vitellogenin (O-Vg) was estimated by the radioactivity associated with the immunoprecipitate or acid-precipitate proteins in the culture medium. The radioactive O-Vg was analyzed by SDS-PAGE followed by autoradiography or after elution from a DEAE-Toyopearl column. The presence of O-Vg inside the follicle cells was detected by immunofluorescence and immunogold labels. Both methods revealed strong labeling inside the follicle cells. While the capacity for total protein synthesis by the follicle cells was maximal during the early phase of vitellogenesis (in small follicles), the synthesis of O-Vg reached its peak during the late phase of oocyte growth, just before formation of the chorion. A possible role for ovarian vitellogenin in Rhodnius and its relationship with Vg synthesis by the fat body is discussed.

Purification of the paraflagellar rod of the trypanosomatid Herpetomonas megaseliae and identification of some of its minor components.

The paraflagellar rod (PFR) is a component of the flagellar cytoskeleton of trypanosomatid protozoa, representing a filamentous structure that runs alongside the common 9 + 2 microtubular axoneme. The high degree of ultrastructural complexity and organization of the PFR suggests that it might be formed by numerous biochemical components. However, biochemical analysis of the PFR has revealed, to date, a modest degree of complexity in what concerns both major and minor PFR proteins. In this paper the preparation of purified PFR fractions by a combination of conventional cell-fractionation procedures, non-ionic detergent treatment and limited proteolysis is described. Comparative SDS-PAGE analysis of the different purification steps indicates that the purified PFR fractions possess high amounts of the well-known major PFR proteins (77 and 83 kDa). Also, bands of 147, 139, 129 and 122 kDa are clearly enriched in such fractions and may correspond to minor PFR components. A slight enrichment in a specific fraction of a doublet of bands of 181/188 kDa suggest the participation of these proteins in the composition of the bridges between the PFR and the axoneme.

Phosphorylation and regulation of the Na+/H+ exchanger through mitogen-activated protein kinase.

We examined mitogen-activated protein kinase-mediated phosphorylation and activation of the Na+/H+ exchanger isoform type 1. A rabbit skeletal muscle extract was fractionated by FPLC chromatography. Four main fractions had the ability to phosphorylate the carboxyl-terminal region of NHE1. Western blot analysis and immunoprecipitation showed that three of these were associated with MAP kinase-dependent phosphorylation. Phosphorylation studies using purified MAP kinase showed that the region involved was the carboxyl-terminal 178 amino acids of the protein and that the stoichiometry was 1 phosphate/mol of protein. In-gel kinase assays showed that cytosolic extracts from smooth muscle cells also phosphorylate the carboxyl-terminal of NHE1 and that the MAP kinase-dependent phosphorylation could be activated by PDGF and AngII. Mutant cell lines with an inducible dominant negative MAP kinase showed decreased serum activation of Na+/H+ exchange but normal hypertonic activation of the protein. The results show that MAP kinase is intimately involved in regulation of the Na+/H+ exchanger, possibly through phosphorylation of one amino acid of the carboxyl-terminal cytosolic domain.

Characterization of the Na+/H+ exchanger in human choriocarcinoma (BeWo) cells.

We examined the expression and activity of the Na+/H+ exchanger in the human choriocarcinoma BeWo cell line. When treated with methotrexate, these cells differentiated from cytotrophoblast-like cells to enlarged multinucleate syncytiotrophoblast-like cells. There was no change in the apparent Km for Na+ between undifferentiated and differentiated cells. However, differentiated cells could transport more than five times the proton flux of undifferentiated cells. There was no difference in the Hill coefficient between undifferentiated and differentiated cells. However, the maximal flux (Jmax) for undifferentiated cells was higher than that for differentiated cells. Inhibition of Na+/H+ exchange activity by an amiloride analog and Hoe694 revealed a sensitive and a resistant component in both differentiated and undifferentiated cells. Northern blot analysis and immunocytochemistry suggested that the sensitive component was due to the NHE1 isoform of the protein while the resistant component was due to the NHE3 isoform. The NHE1 isoform was localized to the brush border membrane of BeWo cells and Western blot analysis showed that the NHE1 protein was more abundant in brush border membranes from differentiated BeWo cells compared to undifferentiated cells. The results show that BeWo cells contain the NHE1 and NHE3 isoforms of the Na+/H+ exchanger and that the NHE1 isoform is primarily localized to the brush border membrane.

Individual housing from rearing modifies the performance of young rats on the elevated plus-maze apparatus.

Previous studies from our laboratory have demonstrated that male and female rats exhibit a differential pattern of behavior in the elevated plus-maze as a function of age. In the present study, the influence of individual housing conditions on young animals treated with one of two classical anxioselective drugs, diazepam or pentylenetetrazole, was investigated in the elevated plus-maze. In Experiment I, males and females were housed for 30 days after weaning either individually or in groups, and tested in the elevated plus-maze at 60 days of age. In Experiment 2, the effects of diazepam (0.75 or 1.0 mg/kg) or of pentylenetetrazole (20 or 30 mg/kg) on the behavior of isolated or grouped rats were studied at 60 days of age in the elevated plus-maze. The results show that isolated housed animals tested with diazepam at 60 days of age exhibited increased frequency and time spent on the open arms of the apparatus compared to control rats. The effect of diazepam was not observed in grouped animals tested at 60 days of age. Pentylenetetrazole produced a decrease in the frequency and time spent on the open arms. This effect was more prominent in grouped animals. The results suggest that 60-day-old rats deprived of playfighting experience present high basal anxiety levels and also that rearing conditions (isolated or grouped) are able to interact with both anxiolytic and anxiogenic effects of experimental drugs.

Leishmania-induced tyrosine phosphorylation in the host macrophage and its implication to infection.

Tyrosine phosphorylation is an important mechanism of cell regulation and has been recently implicated in defense strategies against a variety of pathogens. We have investigated the involvement of protein tyrosine kinase activity in the Leishmania attachment, invasion and survival within macrophages, as well as promastigote ability to trigger tyrosine phosphorylation, which could contribute to leishmanicidal activity. Treatment of murine macrophage monolayers with genistein, herbimycin A, tyrphostin 25 or staurosporine prior to infection decreased parasite invasion in a dose-dependent manner. Contrary, addition of sodium orthovanadate, a protein tyrosine phosphatase inhibitor, phosphotyrosine and p-nitrophenyl phosphate to the interaction medium, significantly increased parasite binding and internalization, whereas phosphoserine and phosphothreonine had no effect. The phosphatase activity of intact promastigotes was greater than that of macrophages. Western blot analysis revealed tyrosine-phosphorylated bands from 198 to 28 kDa following macrophage challenge with promastigotes. Uninfected macrophages displayed no detectable tyrosine phosphorylated proteins, possibly indicating an inducible process, while in parasites it was constitutive, as seen by the presence of 42, 40 and 35 kDa phosphoproteins on the Leishmania lysates. Immunofluorescence and immunogold detection of phosphotyrosine residues in some promastigote-macrophage attachment areas, but not in the vicinity of ingested parasites, suggest that Leishmania-induced tyrosine phosphorylation is an early, local and short-lived event. Genistein treatment of Leishmania-infected cells significantly enhanced the parasite burden. This antagonist also diminished nitric oxide production in resting and interferon gamma/lipopolysaccharide-activated infected macrophages, which may account for the increased parasite survival. We propose that protein tyrosine kinase-linked pathways regulate the Leishmania promastigote invasion and the macrophage microbicidal activity.