Leishmania donovani Induces Multiple Dynamic Responses in the Metabolome Associated with Amastigote Differentiation and Maturation Inside the Human Macrophage.

Leishmania donovani infection of macrophages drives profound changes in the metabolism of both the host macrophage and the parasite, which undergoes different phases of development culminating in replication and propagation. However, the dynamics of this parasite-macrophage cometabolome are poorly understood. In this study, a multiplatform metabolomics pipeline combining untargeted, high-resolution CE-TOF/MS and LC-QTOF/MS with targeted LC-QqQ/MS was followed to characterize the metabolome alterations induced in L. donovani-infected human monocyte-derived macrophages from different donors at 12, 36, and 72 h post-infection. The set of alterations known to occur during Leishmania infection of macrophages, substantially expanded in this investigation, characterized the dynamics of the glycerophospholipid, sphingolipid, purine, pentose phosphate, glycolytic, TCA, and amino acid metabolism. Our results showed that only citrulline, arginine, and glutamine exhibited constant trends across all studied infection time points, while most metabolite alterations underwent a partial recovery during amastigote maturation. We determined a major metabolite response pointing to an early induction of sphingomyelinase and phospholipase activities and correlated with amino acid depletion. These data represent a comprehensive overview of the metabolome alterations occurring during promastigote-to-amastigote differentiation and maturation of L. donovani inside macrophages that contributes to our understanding of the relationship between L. donovani pathogenesis and metabolic dysregulation.

Dientes primarios verdes por hiperbilirubinemia / Dentes decíduos verdes por hiperbilirubinemia / Green deciduous teeth due to hyperbilirubinemia

Definida como una concentración sérica de bilirrubina, la hiperbilirrubinemia es una condición rara y puede ser causada por cualquier factor que eleve la carga de bilirrubina a ser metabolizada por el hígado. Así, la bilirrubina se distribuye por los tejidos corporales y se acumula en los tejidos duros, incluso, en los dientes primarios. El objetivo de este trabajo es relatar un caso clínico sobre la repercusión severa de la hiperbilirrubinemia en dientes primarios y sus manifestaciones bucales en la primera infancia, como dientes verdosos. Paciente del sexo masculino, 3 años y 8 meses, estuvo en clínica odontológica para evaluación de "manchas verdes en los dientes". En su historia médica se observó que nació prematuro y tuvo complicaciones posparto que evolucionaron para sepsis Dientes primarios verdes por hiperbilirrubinemiaIvana Aguiar Raposo,1..... Ronilza Matos,2.....• Marta Verônica Souto de Araujo,3..... •Tamara Kerber Tedesko,4.....José Carlos Pettorossi Imparato,5..... Revista de Odontopediatría Latinoamericana¹ São Leopoldo Mandic Campinas, Sao Paulo, Brasil.2 Universidade Paulista. 3 Universidade Federal de Pernambuco.4 Universidade Federal de Santa Maria.5 Universidade São Paulo - USP.Casos ClínicosDOI: 10.47990/alop.v11i2.304y, como consecuencia del uso de varios medicamentos, desarrolló un cuadro de hiperbilirrubinemia. El examen clínico dental constató la presencia de manchas verdes en los 20 dientes primarios, ausencia de lesión de caries, encías sanas y buena condición de higiene bucal. Se concluye que los altos niveles de bilirrubina desarrollados por el niño prematuro asociados a septicemia pueden llevar a la pigmentación verde (coloración intrínseca) en los dientes primarios durante el periodo de calcificación de los mismos (odontogénesis), incluso a la afectación de los dientes permanentes. Por eso, es relevante el conocimiento de la historia médica del niño desde el nacimiento para el establecimiento del diagnóstico y pronóstico de las alteraciones dentales

Defined as a serum bilirubin concentration, hyperbilirubinemia is a rare condition and can be caused by any factor that raises the bilirubin load to be metabolized by the liver. Thus, bilirubin is distributed throughout the body's tissues and accumulates in hard tissues, including primary teeth. The aim of this work is to report a clinical case about the severe repercussion of hyperbilirubinemia in primary teeth, and its early childhood manifestations, such as greenish teeth. A male patient, 3 years and 8 months old, attended the dental clinic for evaluation of "green spots on teeth". Medical history revealed that the child had premature birth and postpartum complications that evolved into sepsis, and due to the use of several drugs, developed hyperbilirubinemia. The dental clinical examination showed the presence of green spots on all 20 deciduous teeth, absence of carious lesions, healthy gums and good oral hygiene conditions. We conclude

Metaplastic breast carcinoma in a pregnant woman: case report / Carcinoma metaplásico da mama em uma gestante: relato de caso

Breast cancer is the most common malignant neoplasm diagnosed during pregnancy. Metaplastic carcinoma is a rare type of breast cancer, representing 1.5% out of all kinds. This is a case report of metaplastic carcinoma in a pregnant woman aged 39 years

O câncer de mama é a neoplasia maligna mais comumente diagnosticado durante a gestação. O carcinoma metaplásico é um tipo raro de câncer mamário que representa 1,5% de todos os tipos. A seguir, é relatado um caso de carcinoma metaplásico em gestante de 39 anos.

FoxN1-dependent thymic epithelial cells promote T-cell leukemia development.

T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphomas (T-LBL) are aggressive malignancies of thymocytes. The role of thymic microenvironmental cells and stromal factors in thymocyte malignant transformation and T-ALL development remains little explored. Here, using the TEL-JAK2 transgenic (TJ2-Tg) mouse model of T-ALL/LBL, which is driven by constitutive JAK/STAT signaling and characterized by the acquisition of Notch1 mutations, we sought to identify stromal cell alterations associated with thymic leukemogenesis. Immunofluorescence analyses showed that thymic lymphomas presented epithelial areas characterized by keratin (Krt) 5 and Krt8 expression, adjacently to epithelial-free areas negative for Krt expression. Both areas contained abundant laminin (extracellular matrix) and ER-TR7+ (fibroblasts) CD31+ (endothelial) and CD11c+ (dendritic) cells. Besides Krt5, Krt-positive areas harbored medullary thymic epithelial cells (TECs) labeled by Ulex europaeus agglutinin-1. By performing flow cytometry and RNA sequencing analyses of thymic lymphomas, we observed an enrichment in medullary TEC markers in detriment of cortical TEC markers. To assess whether TECs are important for T-ALL/LBL development, we generated TJ2-Tg mice heterozygous for the FoxN1 transcription factor nude null mutation (Foxn1+/nu). Strikingly, in TJ2-Tg;Foxn1+/nu compound mice, both emergence of malignant cells in preleukemic thymi and overt T-ALL onset were significantly delayed. Moreover, in transplantation assays, leukemic cell expansion within the thymus of recipient Foxn1+/nu mice was reduced as compared with control littermates. Since thymopoesis is largely normal in Foxn1+/nu mice, these results indicate that FoxN1 haploinsufficiency in TECs has a more profound impact in thymic leukemogenesis.

Depletion of enteroendocrine and mucus-secreting cells is associated with colorectal carcinogenesis severity and impaired intestinal motility in rats.

This study investigated the relationship between enteroendocrine and mucus-secreting cells distribution, the severity of colonic mucosal injury and intestinal motility in experimental colorectal carcinogenesis. Using a standardized murine model of colorectal carcinogenesis, eight-weeks-old female Wistar rats weighting 147.30 ± 29.15g were randomized into two groups receiving a subcutaneous injection of 0.9% saline (control) or the chemical carcinogen 1,2-dimethylhydrazine (DMH) at 20 mg/kg per week during 10 weeks. Aberrant crypt foci (ACF) were more frequent in DMH group compared to control group (P < 0.001). The number of enteroendocrine and mucus-secreting cells, and intestinal motility was reduced in DMH animals (P < 0.05). The distribution of enteric neurons was similar in both groups. In DMH animals there was a direct correlation between colonic motility and distribution of enteroendocrine (R(2) = 0.68, P < 0.05) and mucus-secreting cells (R(2) = 0.77, P < 0.05). Inverse correlation between the number of ACF, mucus-secreting cells (R(2) = -0.57, P < 0.05), and enteroendocrine cells (R(2) = -0.74, P < 0.05) was also observed. There was inverse correlation between the severity of the mucosal lesion, the number of mucus-secreting cells (R(2) = -0.83, P < 0.05) and enteroendocrine cells (R(2) = -0.96, P < 0.05). There was a direct correlation between nucleolar organizer regions (AgNOR) and ACF number (R(2) = 0.62; P < 0.01). Inverse correlation was also found between AgNOR, the number of mucus-secreting cells (R(2) = -0.76; P < 0.001), and enteroendocrine cells (R(2) = -0.86; P < 0.001). Taken together, the results indicated that colonic malignant transformation is related to depletion of mucus-secreting and enteroendocrine cells, which was a useful indicator of the evolutionary status of intestinal neoplasm, partially explaining the intestinal motility disorders in the early stages of colorectal carcinogenesis.

Plantas medicinais no tratamento de doenças respiratórias na infância: uma visão do saber popular / Medicinal plants in the treatment of respiratoty diseases in childhood: a view from popular knowledge

nvestiga o saber popular sobre o uso de plantas medicinais no tratamento de doenças respiratórias na infância. Estudo descritivo exploratório de natureza qualitativa, realizado em Juazeiro do Norte/CE com vinte e duas mães e/ou responsáveis de crianças usuárias da Estratégia Saúde da Família. A coleta de dados foi efetuada entre os meses de junho e julho de 2011 através de entrevista semiestruturada. Empregou-se a técnica do Discurso do Sujeito Coletivo para análise de dados. A pesquisa indicou que o saber popular tem grande significado e é amplamente aceito, sendo utilizado em algumas vezes em substituição aos medicamentos sintéticos. Ressaltou ainda, a relevância da transmissão cultural deste saber por gerações. Acreditamos na importância de que os profissionais da saúde discutam as práticas populares de saúde para que possam atuar de forma mais efetiva na resolução dos reais problemas de saúde, aliando o conhecimento popular ao científico e fortalecendo tais práticas.

Importância da avaliação pré-anestésica: relato de caso de paciente com apneia obstrutiva do sono / Importance of pre-anesthetic evaluation: case report of a patient with obstructive sleep apnea / Importancia de la evaluación preanestésica: relato de caso de paciente con apnea obstructiva del sueño

JUSTIFICATIVA E OBJETIVOS: O objetivo deste relato foi mostrar a importância da avaliação pré-anestésica na redução da morbimortalidade de pacientes cirúrgicos e alertar para os problemas e cuidados anestésicos associados com apneia obstrutiva do sono. RELATO DO CASO: Paciente masculino, 28 anos, obeso classe II, asmático, portador de apneia do sono, hipertenso, encaminhado ao ambulatório de pré-anestésico para avaliação de cirurgia de uvuloplastia sob anestesia geral. Após orientação sobre a apneia obstrutiva do sono, esclarecimento ao paciente quanto os riscos do procedimento e discussão com o cirurgião, optou-se por rever a indicação cirúrgica e adiar o procedimento. CONCLUSÕES: O ambulatório de pré-anestésico é de máxima importância na redução da morbimortalidade do paciente cirúrgico e, principalmente, na avaliação de pacientes com apneia obstrutiva do sono, revelando-se fundamental para a programação anestésico-cirúrgica, orientando condutas a serem tomadas e interferindo positivamente no prognóstico do paciente.

BACKGROUND AND OBJECTIVES: The objective of this report was to show the importance of pre-anesthetic assessment in reducing morbidity and mortality of surgical patients and alert to problems and anesthetic care associated with obstructive sleep apnea. CASE REPORT: This is a 28-year old male patient with class II obesity, sleep apnea, hypertension, referred to the pre-anesthetic outpatient clinic for evaluation of uvuloplasty under general anesthesia. After orientation on sleep apnea, explaining to the patient the risks associated with the procedure, and discussing with the surgeon, we decided to review the surgical indication and postpone the procedure. CONCLUSIONS: The pre-anesthetic outpatient clinic is extremely important in reducing morbidity as well as mortality of surgical patients and, especially, in evaluating patients with obstructive sleep apnea, showing to be fundamental for the anesthetic-surgical schedule, orienting conducts to be followed, and interfering positively on patient prognosis.

JUSTIFICATIVA Y OBJETIVOS: El objetivo de este relato fue mostrar la importancia de la evaluación preanestésica en la reducción de la morbimortalidad de pacientes quirúrgicos y alertar los problemas y cuidados anestésicos asociados con la apnea obstructiva del sueño. RELATO DEL CASO: Paciente masculino, 28 años, obeso, clase II, asmático, portador de apnea del sueño, hipertenso, derivado al ambulatorio de preanestesia para la evaluación de cirugía de uvuloplastia bajo anestesia general. Después de la orientación sobre la apnea obstructiva del sueño, de la aclaración al paciente en cuanto a los riesgos del procedimiento y de la discusión con el cirujano, decidimos analizar nuevamente la indicación quirúrgica y postergar el procedimiento. CONCLUSIONES: El ambulatorio de preanestésico es de máxima importancia para la reducción de la morbimortalidad del paciente quirúrgico y principalmente, para la evaluación de los pacientes con apnea obstructiva del sueño, siendo fundamental para la programación anestésico-quirúrgica, orientando las conductas que serán tomadas e interfiriendo positivamente en el pronóstico del paciente.

Controlling product selection in the photodissociation of formaldehyde: direct quantum dynamics from the S1 barrier.

Controlling the selectivity between H(2)+CO and H+HCO in the S(1)/S(0) nonadiabatic photodissociation of formaldehyde has been investigated using direct quantum dynamics. Simulations started from the S(1) transition state have suggested that a key feature for controlling the branching ratio of ground-state products is the size of the momentum given to the wavepacket along the transition vector. Our results show that letting the wavepacket fall down from the barrier to the conical intersection with no initial momentum leads to H(2)+CO, while extra momentum toward products favors the formation of H+HCO through the same conical intersection. Quantum dynamics results are interpreted in semiclassical terms with the aid of a Mulliken-like analysis of the final population distribution among both products and the reactant on each electronic state.

The molecular dissociation of formaldehyde at medium photoexcitation energies: A quantum chemistry and direct quantum dynamics study.

The mechanisms of radiationless decay involved in the photodissociation of formaldehyde into H(2) and CO have been investigated using complete active space self-consistent field (CASSCF) calculations and direct dynamics variational multiconfiguration Gaussian (DD-vMCG) quantum dynamics in the S(1), T(1), and S(0) states. A commonly accepted scheme involves Fermi Golden Rule internal conversion from S(1) followed by dissociation of vibrationally hot H(2)CO in S(0). We recently proposed a novel mechanism [M. Araujo et al., J. Phys. Chem. A 112, 7489 (2008)] whereby internal conversion and dissociation take place in concert through a seam of conical intersection between S(1) and S(0) after the system has passed through an S(1) transition barrier. The relevance of this mechanism depends on the efficiency of tunneling in S(1). At lower energy, an alternative scheme to internal conversion involves intersystem crossing via T(1) to regenerate the reactant before the S(0) barrier to dissociation. We propose here a previously unidentified mechanism leading directly to H(2) and CO products via T(1). This channel opens at medium energies, near or above the T(1) barrier to dissociation and still lower than the S(1) barrier, thus making T(1) a possible shortcut to molecular dissociation.

Antecedentes familiares de primeiro e segundo graus como fatores de risco para o câncer de mama: estudo caso-controle / First and second degree family history as a risk factor for breast cancer: a case-control study

Objetivo: No Brasil, observa-se significativo aumento na incidência do câncer de mama nos últimos anos. A história familiar positiva para câncer de mama é importante fator de risco para desenvolvimento dessa patologia. Conhecer fatores de risco para esse câncer é de grande importância para detecção e orientação precoce de famílias de alto risco. Método: Trata-se de estudo epidemiológico, retrospectivo, caso-controle, abrangendo instituições-referência para tratamento oncológico em Alagoas, Brasil, no período de janeiro de 2002 a abril de 2008. Foram incluídas mulheres entre 25 e 75 anos. A amostra foi constituída de 244 casos com confirmação histológica para câncer de mama e 276 controles com mamografia sem características de malignidade (BI-RADS 1 e 2) ou mamografia inconclusiva (BI-RADS 0) com ultrassonografia complementar e exame clínico normais. Resultados: Neste estudo, história familiar positiva de primeiro e/ou segundo graus de câncer de mama aumentou o risco de desenvolvimento dessa patologia (OR: 2,52; IC 95%: 1,53-4,21; p < 0,01). Dessas mulheres, 39% possuíam história familiar positiva de primeiro grau, 57%, antecedente familiar de segundo grau e 4%, história familiar de primeiro e segundo graus. A história familiar de primeiro grau isolada de câncer de mama aumentou o risco de desenvolvimento dessa patologia (OR: 3,81; IC 95%: 1,72-9,16; p < 0,01), enquanto a análise isolada da história familiar de segundo grau comportou-se como fator de risco, porém de maneira não estatisticamente significativa (OR: 1,89; IC 95%: 1,03-3,51; p = 0,0503). Conclusão: História familiar positiva para câncer de mama aumentou o risco de desenvolvimento dessa doença, entretanto, a história familiar de segundo grau isolada não foi estatisticamente significativa.

Objective: A relevant increase of breast cancer incidence was observed in Brazil in the last few years. An important risk factor for developing breast cancer is a positive family history of this disease. Method: The knowledge of breast cancer risk factors is a big step towards a meaningful preventive intervention. His is an epidemiological, retrospective, case-control study, involving institutions listed as reference for cancer treatment in Alagoas, Brazil during the period between January 2002 and April 2008. Women aged between 25 and 75 years old were included. He sample involved 244 cases with histological confirmation for breast cancer and 276 controls free of malignant characteristics at mammography (BI-RADS 1 and 2) or inconclusive mammography (BI-RADS 0) with normal ultrasound and clinical examination. Results: First and second degree family history of breast cancer increased the risk of breast neoplasm in our study (OR: 2.52; 95% CI 1.53-4.21; P < 0.01). According to our research, 39% of all woman with family history of breast cancer present only first degree family history, 57% only present second degree and 4% present both degrees. An isolated first degree family history increased risk of this cancer (OR: 3.81; 95% CI 1.72-9,16; p < 0.01), but isolated second degree history doesn't behave as a risk factor of this neoplasm (OR: 1.89; 95% IC 1.03-3.51; p = 0.0503). Conclusion: Patient reported of first degree family history of breast cancer increases the risk of developing disease. Isolated second degree history of breast cancer was a risk factor for acquire this neoplasm, but was not statistically significant, in our study.

The photochemistry of formaldehyde: internal conversion and molecular dissociation in a single step?

A novel, nonadiabatic reaction path for H2 + CO molecular dissociation of formaldehyde via an extended S1/S0 conical intersection seam has been mapped out using the CAS-SCF method with a full valence active space (10 electrons, 9 orbitals). Two conical intersection geometries have been optimized, CsCoIn, a saddle point in the intersection space, and C1CoIn, which is the lowest-energy crossing point. A minimum-energy path connecting these points along a seam has also been characterized. In addition to the conventional and "roaming-atom" mechanisms--where internal conversion takes place before ground-state dissociation--we suggest that a strictly nonadiabatic mechanism can operate, where internal conversion and dissociation take place in concert.

Apoptose em tiroidopatias hiperplásicas e neoplásicas / Apoptosis in hyperplasic and neoplasic thyroid diseases

A apoptose é um processo de morte celular que ocorre geralmente após a fragmentação progressiva do DNA e parece ser importante em tecidos normais e neoplásicos. Pouco é conhecido sobre a ocorrência da apoptose nas doenças da tiróide. A finalidade deste estudo é investigar um possível papel da apoptose no crescimento do carcinoma bem diferenciado de tiróide, usando um ensaio com nucleotidil transferase in situ (ENTIS), o qual detecta a fragmentação do DNA, para determinar a fre-qüência da apoptose no bócio colóide (BC), adenoma folicular (AF), carcinoma folicular (CF) e carcinoma papilar (CP). Os tecidos de BC (n=3), AF (n=2), CF (n=4) e CP (n=3) foram obtidos de ressecção cirúrgica em 12 pacientes. As células apoptóticas positivas (CAP) dentro do folículo tiroidiano e tecido neoplásico foram contadas em áreas de 1cm 2 . O teste T foi utilizado para testar a significância estatística. O número de CAPs foi significantemente maior (p<0,0001) nos BC e AF (24,4 +/- 8,2 CAP/cm 2 ) comparado com CF e CP (1,33 +/- 0,82 CAP/cm 2 ). Nenhuma diferença significativa foi vista no número de CAPs entre BC e AF e entre CF e CP. A apoptose pode desempenhar um importante papel na progressão do carcinoma bem diferenciado de tiróide, visto que no presente estudo o índice apoptótico foi muito baixo nessas neoplasias. A apoptose, diferentemente da necrose, é um processo ativo que poderia ser inibido ou induzido o que, neste caso, seria interessante para a terapêutica.

Síndrome de Youssef: relato de um caso / Youssef's syndrome: report of a case

É apresentado um caso de fístula vésico-uterina manifesto, com a clássica síndrome de Youssef. Discute-se brevemente o tratamento cirúrgico

Gestaçäo em mulheres com mais de 40 anos / Pregnancy in women with more than 40 years

Realizou-se um estudo retrospectivo pela análise de 62 prontuários de gestantes com mais de 40 anos que deram a luz no período de janeiro de 1982 a dezembro de 1984, comparando seus achados com os da literatura