Early detection of M. leprae by qPCR in untreated patients and their contacts: results for nasal swab and palate mucosa scraping.

To verify if the hard palate mucosa can be a site of relevance in the early molecular detection of Mycobacterium leprae in leprosy cases and their household contacts and if there is a correlation of results in nasal swab with those of the scraping of the palate mucosa. The quantitative polymerase chain reaction technique was used. Sample included 78 patients with untreated leprosy (G1), their 54 household contacts (G2), and 80 healthy individuals for the negative control (G3). The presence of M. leprae in both G1 and G2 was observed with the nasal swab and the palate mucosa scrapings methods, and it was shown that the sensitivity between the qPCR exams for RLEP and 85B genes is equivalent, with no statistically significant differences (G1 positivity of 35% in the hard palate mucosa and 44% for the nasal one, p = 0.3731 and for G2 of 31 and 38%, respectively, p = 0.6774). Results support the fact that the buccal mucosa and nasal mucosa may be important sites of primary infection of leprosy with repercussion in the transmission chain and that asymptomatic household contacts are heavily harbored by the causative agent of leprosy, which has a critical significance in the prevention and control action of this disease, since the evaluation of these sites arises as of importance in the early detection of M. leprae. Close monitoring and chemoprophylaxis of household contacts appear to be critical to attain interruption of the transmission of leprosy in endemic countries.

Regulatory T cells in the actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions. METHODS: The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects. RESULTS: The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-ß (TGF-ß), and low IFN-γ were detected in the potentially malignant lesions. CONCLUSION: Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment.

Seroreactivity to new Mycobacterium leprae protein antigens in different leprosy-endemic regions in Brazil.

New Mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (MDT) monitoring. This study describes seroreactivity to M. leprae proteins among participants from three highly endemic leprosy areas in Brazil: central-western Goiânia/Goiás (GO) (n = 225), Rondonópolis/Mato Grosso (MT) (n = 764) and northern Prata Village/Pará (PA) (n = 93). ELISA was performed to detect IgG to proteins (92f, 46f, leprosy IDRI diagnostic-1, ML0405, ML1213) and IgM to phenolic glycolipid-I (PGL-I). Multibacillary (MB) leprosy had positive rates for PGL-I that were similar to those for proteins; however, some anti-PGL-I-negative subjects were positive for proteins, suggesting that adding protein antigen to PGL-I can enhance the sensitivity of MB leprosy detection. In MT, different degrees of seroreactivity were observed and ranked for MB, former patients after MDT, paucibacillary (PB) leprosy, household contact (HHC) and endemic control (EC) groups. The seroreactivity of PB patients was low in GO and MT. HHCs from different endemic sites had similar IgG antibody responses to proteins. 46f and 92f were not recognised by most tuberculosis patients, ECs or HHCs within GO, an area with high BCG vaccination coverage. Low positivity in EC and HHC was observed in PA and MT. Our results provide evidence for the development of an improved serologic test that could be widely applicable for MB leprosy testing in Brazil.

Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L1) expression in patients with actinic cheilitis and oral squamous cell carcinoma.

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4+PD-1+ and CD8+PD-1+ lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8+PD1+ in PBMC when compared with controls. On the other hand, increased frequency of CD4+ and CD8+ T cells expressing PD-1(+) accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-γ and higher levels of TGF-ß were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.

Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment.

Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that >80% of CD4(+)CD25(+) T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4(+)CD25(+) T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-gamma production when compared with CD4(+)CD25(+) T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4(+)CD25(-) T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-gamma and induced IL-10 and TGF-beta secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.

Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.

Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis.

Papillary cystadenoma of the minor salivary gland of the lower lip.

A case report of the papillary cystadenoma from minor salivary gland in lower lip of a 54-year-old man is described.

Leprosy patients: neurotrophic factors and axonal markers in skin lesions.

Neurotrophins are growth factors with crucial roles in neural pathophysiology. These mediators functionally modulate nociceptive fibers, and changes in neurotrophins expression have been correlated with early loss of nociception in leprosy. This study investigated the expression of NGF, BDNF, and NT3 in dermal nerves of leprosy patients. Characterization of Remak bundles was achieved by p75(NTR), and axonal markers NF-L and PGP 9.5 immunostaining. Clinical parameters of neural impairment have been evaluated by Semmes-Wenstein monofilaments. Our findings demonstrated decrease of NGF in borderline leprosy, when compared to control specimens. Similar results were observed in PGP 9.5 expression (borderline: p<0.001 and lepromatous: p<0.05) and NF-L (lepromatous: p<0.05), suggesting advanced Remak bundles degeneration in multibacillary leprosy. It has also been observed positive correlation between p75(NTR) and PGP 9.5, indicating association between Schwann cells and axons in Remak bundles. Present data indicate that neurotrophins imbalance may participate in the establishment of peripheral nerve damage.

Leprosy patients: neurotrophic factors and axonal markers in skin lesions / Pacientes com hanseníase: fatores neurotróficos e marcadores axonais em lesões de pele

Neurotrophins are growth factors with crucial roles in neural pathophysiology. These mediators functionally modulate nociceptive fibers, and changes in neurotrophins expression have been correlated with early loss of nociception in leprosy. This study investigated the expression of NGF, BDNF, and NT3 in dermal nerves of leprosy patients. Characterization of Remak bundles was achieved by p75NTR, and axonal markers NF-L and PGP 9.5 immunostaining. Clinical parameters of neural impairment have been evaluated by Semmes-Wenstein monofilaments. Our findings demonstrated decrease of NGF in borderline leprosy, when compared to control specimens. Similar results were observed in PGP 9.5 expression (borderline: p<0.001 and lepromatous: p<0.05) and NF-L (lepromatous: p<0.05), suggesting advanced Remak bundles degeneration in multibacillary leprosy. It has also been observed positive correlation between p75NTR and PGP 9.5, indicating association between Schwann cells and axons in Remak bundles. Present data indicate that neurotrophins imbalance may participate in the establishment of peripheral nerve damage.

Neurotrofinas são fatores de crescimento com papel fundamental na fisiopatologia neural. Esses mediadores modulam funcionalmente fibras nociceptivas. Mudanças em sua expressão têm sido relacionadas à perda precoce da nocicepção na hanseníase. Este estudo investigou a expressão de NGF, BDNF e NT3 em nervos dérmicos de pacientes hansenianos. A caracterização de fibras nervosas não mielinizadas foi feita por p75NTR e marcadores axonais NF-L e PGP 9.5. Os parâmetros clínicos de dano neural foram avaliados por monofilamentos Semmes-Wenstein. Nossos achados demonstram diminuição de NGF nos pacientes dimorfos em comparação aos controles. Resultados similares foram observados para PGP 9.5 (dimorfos: p<0,001; virchowianos: p<0,05) e NF-L (virchowianos: p<0.05), sugerindo degeneração avançada das terminações nervosas na hanseníase multibacilar. Foi observada correlação positiva entre p75NTR e PGP 9.5, indicando associação entre células de Schwann e axônios em fibras nervosas não mielinizadas. Os resultados indicam que o desequilíbrio na expressão das neurotrofinas pode participar do dano neural periférico.

Seroreactivity to new Mycobacterium leprae protein antigens in different leprosy-endemic regions in Brazil

New Mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (MDT) monitoring. This study describes seroreactivity to M. leprae proteins among participants from three highly endemic leprosy areas in Brazil: central-western Goiânia/Goiás (GO) (n = 225), Rondonópolis/Mato Grosso (MT) (n = 764) and northern Prata Village/Pará (PA) (n = 93). ELISA was performed to detect IgG to proteins (92f, 46f, leprosy IDRI diagnostic-1, ML0405, ML1213) and IgM to phenolic glycolipid-I (PGL-I). Multibacillary (MB) leprosy had positive rates for PGL-I that were similar to those for proteins; however, some anti-PGL-I-negative subjects were positive for proteins, suggesting that adding protein antigen to PGL-I can enhance the sensitivity of MB leprosy detection. In MT, different degrees of seroreactivity were observed and ranked for MB, former patients after MDT, paucibacillary (PB) leprosy, household contact (HHC) and endemic control (EC) groups. The seroreactivity of PB patients was low in GO and MT. HHCs from different endemic sites had similar IgG antibody responses to proteins. 46f and 92f were not recognised by most tuberculosis patients, ECs or HHCs within GO, an area with high BCG vaccination coverage. Low positivity in EC and HHC was observed in PA and MT. Our results provide evidence for the development of an improved serologic test that could be widely applicable for MB leprosy testing in Brazil.

The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

The aim of the present study was to examine the effect of a diet rich in synthetic PEtn on the metabolism macrophages of tumor-bearing mice. The results demonstrated that PEtn increased the animals' survival time. In addition, the treated animals released smaller amounts of hydrogen peroxide (H2O2) and nitric oxide (NO) than the non-treated animals, particularly after day 14. From the results it could be concluded that H2O2 and NO were important in the modulation of neoplastic growth, and pointed to a promising role of PEtn in the control of human neoplasms.

Mycobacterium leprae downregulates the expression of PHEX in Schwann cells and osteoblasts

Neuropathy and bone deformities, lifelong sequelae of leprosy that persist after treatment, result in significant impairment to patients and compromise their social rehabilitation. Phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) is a Zn-metalloendopeptidase, which is abundantly expressed in osteoblasts and many other cell types, such as Schwann cells, and has been implicated in phosphate metabolism and X-linked rickets. Here, we demonstrate that Mycobacterium leprae stimulation downregulates PHEX transcription and protein expression in a human schwannoma cell line (ST88-14) and human osteoblast lineage. Modulation of PHEX expression was observed to a lesser extent in cells stimulated with other species of mycobacteria, but was not observed in cultures treated with latex beads or with the facultative intracellular bacterium Salmonella typhimurium. Direct downregulation of PHEX by M. leprae could be involved in the bone resorption observed in leprosy patients. This is the first report to describe PHEX modulation by an infectious agent.

Considerações sobre o envolvimento da cavidade bucal na hanseníase / Considerations on oral cavity involvement in leprosy

As lesões causadas pela proliferação do Mycobacterium leprae (M. leprae) foram significantemente reduzidas nos últimos anos com a detecção precoce de casos novos.Consequentemente, as lesões maxilofaciais e da mucosa bucal passaram ser cada vez menos relatadas. A despeito de ser menos evidente, a infecção da cavidade bucal pelo M. leprae pode revelar detalhes importantes a respeito da transmissibilidade e imunopatogenia da hanseníase.A associação entre a infecção da mucosa bucal e a perda óssea alveolar, bem como a participação da resposta imune local na proteção contra a doença, ainda são tópicos de pesquisa não explorados totalmente. Infelizmente, o tratamento da hanseníase não possibilitou a prevenção total de suas seqüelas, nem impediu transmissão dessa doença. As razões acima justificam rever algumas perguntas não respondidas do passado.

Lesions secondary to Mycobacterium leprae (M. leprae) proliferation have been significantly abbreviated in recent years due to early detection of new cases of leprosy. Consequently, oral and maxillofacial lesions have been each time less reported. In spite of been less evident, the infection of oral cavity by M. leprae may reveal important details regarding the transmission and immunopathology of leprosy. The association between oral mucosal infection and alveolar bone loss, as well as the role of local immune response in protection against this pathogen, are still not fully explored. Unfortunately, the treatment of leprosy did not allow the full prevention of sequels neither hindered the transmission of this disease. The reasons above justify reviewing some unanswered questions of the past.

Early detection of M. leprae by qPCR in untreated patients and their contacts: results for nasal swab and palate mucosa scraping

To verify if the hard palate mucosa can be a site of relevance in the early molecular detection of Mycobacterium leprae in leprosy cases and their household contacts and if there is a correlation of results in nasal swab with those of the scraping of the palate mucosa. The quantitative polymerase chain reaction technique was used. Sample included 78 patients with untreated leprosy (G1), their 54 household contacts (G2), and 80 healthy individuals for the negative control (G3). The presence of M. leprae in both G1 and G2 was observed with the nasal swab and the palate mucosa scrapings methods, and it was shown that the sensitivity between the qPCR exams for RLEP and 85B genes is equivalent, with no statistically significant differences (G1 positivity of 35% in the hard palate mucosa and 44% for the nasal one, p = 0.3731 and for G2 of 31 and 38%, respectively, p = 0.6774). Results support the fact that the buccal mucosa and nasal mucosa may be important sites of primary infection of leprosy with repercussion in the transmission chain and that asymptomatic household contacts are heavily harbored by the causative agent of leprosy, which has a critical significance in the prevention and control action of this disease, since the evaluation of these sites arises as of importance in the early detection of M. leprae. Close monitoring and chemoprophylaxis of household contacts appear to be critical to attain interruption of the transmission of leprosy in endemic countries

Mycobacterium leprae-induced insulin-like growth factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages

Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis.

Distúrbios angioproliferativos bucais e cutâneos: correlações histopatológicas e expressão de mediadores angiogênicos / Oral and cutaneous angioproliferative diseases: histopathologic correlations and expression of angiogenic mediators

A mucosa bucal e a pele podem apresentar distúrbios vasculares proliferativos com comportamento biológico variado. Para classificar tais lesões foram adotados critérios etiopatogênicos e a avaliação desses critérios em grupos específicos de lesões angioproliferativas pode contribuir para o diagnóstico e tratamento das mesmas. O objetivo desse estudo retrospectivo foi caracterizar as principais lesões angioproliferativas da mucosa bucal, comparando-as com os mesmos tipos de lesões cutâneas, em relação aos achados histopatológicos e à expressão endotelial do fator de crescimento fibroblástico básico (FGFb) e do receptor p75 para neurotrofinas (p75NTR). Foram utilizados espécimes arquivados em blocos parafinados, divididos conforme o diagnóstico microscópico em seis grupos: (I) malformações venosas; (II) malformações linfáticas; (III) granulomas piogênicos; (IV) hemangiomas capilares; (V) hemangiomas arteriovenosos; (VI) sarcomas de Kaposi. Cada grupo foi subdividido em dois grupos quanto a sua localização bucal e cutânea. Os padrões microscópicos das lesões angioproliferativas bucais e cutâneas de nossa amostra são similares e podem ser classificadas sob os mesmos parâmetros. No entanto, alguns grupos apresentaram diferenças quanto ao estádio de maturação das lesões, em relação à incidência e principalmente em relação à expressão dos mediadores estudados. A diferença na expressão de FGFb e p75NTR, observada entre os grupos bucais e cutâneos dos mesmos tipos de lesões, permitiunos concluir que a evolução da angiogênese na mucosa bucal e na pele não é necessariamente mediado pelos mesmos fatores. Tais diferenças abrem perspectivas para pesquisas futuras e abordagens terapêuticas baseadas em tecnologias moleculares.

The oral mucosa and the skin may present proliferative vascular diseases with varied biological behavior. To classify such lesions, pathogenic criteria were adopted in specific groups of vascular lesions. The objective of this retrospective study was to characterize the main oral vascular lesions, comparing them with the same types of cutaneous lesions. The histopathologic findings were compared, as well as the endothelial expression of basic fibroblastic growth factor (FGFb) and p75 neurotrophin receptor (p75NTR). Paraffin embedded specimens were purchased and divided, according to microscopic diagnostic, into six groups: (I) venous malformations; (II) lymphatic malformations; (III) pyogenic granulomas; (IV) capillary hemangiomas; (V) arteriovenous hemangiomas; (VI) Kaposi sarcomas. Each group was divided in two subgroups of oral and cutaneous location. The microscopic data demonstrated that oral and cutaneous vascular lesions, in our sample, are similar and they can be classified under the same parameters. However, some groups presented differences related to maturation stage, incidence, and expression FGFb and p75NTR. These differences allowed us to conclude that the evolution of angiogenic process inside oral mucosa and in the skin, not necessarily is mediated by the same biological factors. Such differences open perspectives for future researches and therapeutic approaches, based on molecular technologies.

Leprosy patients: neurotrophic factors and axonal markers in skin lesions / Pacientes com hanseníase: fatores neurotróficos e marcadores axonais em lesões de pele

Neurotrophins are growth factors with crucial roles in neural pathophysiology. These mediators functionally modulate nociceptive fibers, and changes in neurotrophins expression have been correlated with early loss of nociception in leprosy. This study investigated the expression of NGF, BDNF, and NT3 in dermal nerves of leprosy patients. Characterization of Remak bundles was achieved by p75NTR, and axonal markers NF-L and PGP 9.5 immunostaining. Clinical parameters of neural impairment have been evaluated by Semmes-Wenstein monofilaments. Our findings demonstrated decrease of NGF in borderline leprosy, when compared to control specimens. Similar results were observed in PGP 9.5 expression (borderline: p<0.001 and lepromatous: p<0.05) and NF-L (lepromatous: p<0.05), suggesting advanced Remak bundles degeneration in multibacillary leprosy. It has also been observed positive correlation between p75NTR and PGP 9.5, indicating association between Schwann cells and axons in Remak bundles. Present data indicate that neurotrophins imbalance may participate in the establishment of peripheral nerve damage.

Neurotrofinas são fatores de crescimento com papel fundamental na fisiopatologia neural. Esses mediadores modulam funcionalmente fibras nociceptivas. Mudanças em sua expressão têm sido relacionadas à perda precoce da nocicepção na hanseníase. Este estudo investigou a expressão de NGF, BDNF e NT3 em nervos dérmicos de pacientes hansenianos. A caracterização de fibras nervosas não mielinizadas foi feita por p75NTR e marcadores axonais NF-L e PGP 9.5. Os parâmetros clínicos de dano neural foram avaliados por monofilamentos Semmes-Wenstein. Nossos achados demonstram diminuição de NGF nos pacientes dimorfos em comparação aos controles. Resultados similares foram observados para PGP 9.5 (dimorfos: p<0,001; virchowianos: p<0,05) e NF-L (virchowianos: p<0.05), sugerindo degeneração avançada das terminações nervosas na hanseníase multibacilar. Foi observada correlação positiva entre p75NTR e PGP 9.5, indicando associação entre células de Schwann e axônios em fibras nervosas não mielinizadas. Os resultados indicam que o desequilíbrio na expressão das neurotrofinas pode participar do dano neural periférico.

Seroreactivity to new Mycobacterium leprae protein antigens in different leprosy-endemic regions in Brazil

New Mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (MDT) monitoring. This study describes seroreactivity to M. leprae proteins among participants from three highly endemic leprosy areas in Brazil: central-western Goiânia/Goiás (GO) (n = 225), Rondonópolis/Mato Grosso (MT) (n = 764) and northern Prata Village/Pará (PA) (n = 93). ELISA was performed to detect IgG to proteins (92f, 46f, leprosy IDRI diagnostic-1, ML0405, ML1213) and IgM to phenolic glycolipid-I (PGL-I). Multibacillary (MB) leprosy had positive rates for PGL-I that were similar to those for proteins; however, some anti-PGL-I-negative subjects were positive for proteins, suggesting that adding protein antigen to PGL-I can enhance the sensitivity of MB leprosy detection. In MT, different degrees of seroreactivity were observed and ranked for MB, former patients after MDT, paucibacillary (PB) leprosy, household contact (HHC) and endemic control (EC) groups. The seroreactivity of PB patients was low in GO and MT. HHCs from different endemic sites had similar IgG antibody responses to proteins. 46f and 92f were not recognised by most tuberculosis patients, ECs or HHCs within GO, an area with high BCG vaccination coverage. Low positivity in EC and HHC was observed in PA and MT. Our results provide evidence for the development of an improved serologic test that could be widely applicable for MB leprosy testing in Brazil

The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

The aim of the present study was to examine the effect of a diet rich in synthetic PEtn on the metabolism macrophages of tumor-bearing mice. The results demonstrated that PEtn increased the animals' survival time. In addition, the treated animals released smaller amounts of hydrogen peroxide (H2O2) and nitric oxide (NO) than the non-treated animals, particularly after day 14. From the results it could be concluded that H2O2 and NO were important in the modulation of neoplastic growth, and pointed to a promising role of PEtn in the control of human neoplasms.

Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L-1) expression in patients with actinic cheilitis and oral squamous cell carcinoma

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4+PD-1+ and CD8+PD-1+ lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8+PD1+ in PBMC when compared with controls. On the other hand, increased frequency of CD4+ and CD8+ T cells expressing PD-1(+) accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-γ and higher levels of TGF-ß were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.