Uremic leontiasis ossea, a rare presentation of severe renal osteodystrophy secondary to hyperparathyroidism.

Renal osteodystrophy is a common complication of end-stage renal failure patients. It's most severe osseous complication is characterized by massive thickening of the cranial vault and facial bones, called uremic leontiasis ossea (ULO), with only few cases reported in the literature. A case of a 47-year-old female patient with ULO is presented. Physical examination showed enlargement of the jaws, which hinders proper ventilation and feeding. The computed tomography examination showed marked osseous proliferation in the jaws causing severe bony expansion and loss of normal bony architecture in the skull and the skull base. The most relevant clinical, histopathological and laboratory findings are discussed. The uremic leontiasis ossea causes significant aesthetic and functional changes. Correct diagnosis and management of the factors responsible for the development of bone lesions due to altered bone metabolism are key factors. The maxillofacial surgeon must have the proper knowledge of patient's medical condition and bone maturation status to address an adequate surgical strategy.

Growth inhibitory effects of 3'-nitro-3-phenylamino nor-beta-lapachone against HL-60: a redox-dependent mechanism.

In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO(2)) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF(4)) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO(2). QPhNO(2) caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO(2) treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry.

Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y -14 en lesiones apicales asociadas con periodontitis apical asintomática / Immunodetection of matrix metalloproteinases (MMPs)-2, -9, -13 and -14 in periapical lesions associated with asymptomatic apical periodontitis

La periodontitis apical asintomática (PAa) es una patología infecciosa caracterizada por destrucción ósea perirradicular asociada a un proceso inflamatorio crónico y producción de mediadores inflamatorios, entre los cuales se encuentran las metaloproteinasas de matriz extracelular (MMPs). Entre éstas, las MMPs-13, -14, -2 y -9, son producidas por el tejido óseo y degradan sinérgicamente el colágeno tipo I, principal componente de los tejidos periodontales, y gelatina, producto de la degradación y desnaturación del colágeno. El objetivo de este estudio fue determinar el patrón de expresión de las MMPs-2, -9, -13 y -14 en granulomas periapicales (GPAs), quistes radiculares inflamatorios (QRIs) y ligamento periodontal sano (LS). Materiales y Métodos: Se seleccionaron 12 pacientes con diagnóstico clínico de PAa e indicación de exodoncia a partir de los cuales se obtuvieron biopsias de lesiones periapicales (LPAs). Como controles, se seleccionaron 7 individuos con indicación de exodoncia de premolares por ortodoncia, obteniéndose biopsias de LS. Se efectuó el diagnóstico anátomo-patológico de los especímenes y se caracterizó la expresión de las MMPs en estudio mediante inmunohistoquímica. Resultados: Las MMPs en estudio sólo se detectaron en GPAs y QRIs, y se inmunolocalizaron principalmente en el infiltrado inflamatorio de éstos. Adicionalmente, la MMP-2 se identificó en fibroblastos del tejido conectivo. Conclusiones: MMPs-2, -9, -13 y -14 se expresan predominantemente en el infiltrado inflamatorio de las LPAs y no en LS, y por tanto se sugiere la participación de estos mediadores en la patogénesis de la PAa.

Asymptomatic apical periodontitis (aAP) is an infectious disease characterized by perirradicular bone destruction associated with chronic inflammation and release of inflammatory mediators, such as matrix metalloproteinases (MMPs). MMPs-13, -14 and -2, -9 are bone-expressed enzymes that can synergistically degrade collagen I, the main component of periodontal extracellular matrix, and gelatin, the product of degradation and denaturation of collagen. The aim of this study was to characterize the expression pattern of MMPs-2, -9, -13, and -14 in periapical granulomas (PGs), radicular cysts (RCs) and healthy periodontal ligament (PDL). Materials and Methods: Individuals with clinical diagnosis of aAP and indication of extraction were selected (N=12), and biopsies of periapical lesions (PLs) were obtained. For controls, 7 subjects with indication of premolar extraction for orthodontic reasons were selected, and PDL biopsies were obtained. Samples were diagnosed by anatomopathological examination and immunohistochemical staining was carried out to characterize MMPs expression. Results: MMPs-2, -9, -13 and -14 detection was limited to PLs and were localized mainly to inflammatory infiltrate on both, PGs and RCs. Additionally, MMP-2 was immunolocalized to fibroblasts from the connective tissue. Conclusions: Whereas MMPs-2, -9, -13 and -14 were not detected in healthy periodontal ligament, they were highly expressed on inflammatory infiltrate from PGs and RCs, suggesting a role of these mediators in aAP pathogenesis.

Carcinoma verrucoso oral: reporte de un caso clínico y revisión de 20 casos del Instituto de Referencia en Patología Oral (IREPO), Chile / Oral verrucous carcinoma: a case report and review of 20 cases of the Oral Pathology Referral Institute (IREPO), Chile

El carcinoma verrucoso (CV) es una variante rara del carcinoma de células escamosas con características morfológicas y comportamiento específico. El presente estudio relata el caso de una paciente de género femenino, de 68 años de edad, que presenta un carcinoma verrucoso en lengua, indoloro y con 8 meses de evolución. Además, se realizó una breve revisión de casos clínicos del Instituto de Referencia en Patología Oral (IREPO) de la Facultad de Odontología de la Universidad de Chile, diagnosticados entre enero de 1984 y octubre de 2010, encontrándose 20 casos, con un promedio de edad de 70 años, localizados con mayor frecuencia en encía inferior y lengua.

Verrucous carcinoma (VC), a rare variant of squamous cell carcinoma is an established entity with distinctive morphology and specific clinical behavior. The present study describe a case report of a 68-year-old women who presented a tongue verrucous carcinoma, asymptomatic, that had about 8 months of evolution. A brief review of VC cases diagnosed in Oral Pathology Referral Institute (IREPO), Faculty of Odontology, University of Chile, between 1984 and 2010. It was found 20 cases of verrucous carcinoma with a median age of70-years-old, the most common places were lower gingiva and tongue.

Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from beta-lapachone.

Three naphthoimidazoles presenting aromatic groups attached to the imidazole ring were the most active against trypomastigotes of Trypanosoma cruzi between 45 derivatives from beta-lapachone. N1 is active against the three forms of the parasite. In this work, we investigated N2 and N3 and analyzed the effect of the three derivatives on metacyclogenesis, endocytosis, and cell cycle. In epimastigotes, N2 and N3 blocked the cell cycle, inhibited succinate cytochrome c reductase, metacyclogenesis, and induced damage to mitochondrion, Golgi, and reservosomes. In treated trypomastigotes, there were alterations in the mitochondrion, nucleus and kinetoplast, and DNA fragmentation. Preincubation with cysteine protease inhibitors reversed the effect of N1, N2, and N3. Such reversion and ultrastructural alterations suggest the involvement of autophagy in parasite death. Ultrastructural, flow cytometry, and biochemical studies suggest that naphthoimidazoles interferes with the energetic metabolism and induces DNA fragmentation.

Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol: combining drugs imposes different artificial checkpoints.

Ablation of tumor colonies was seen in a wide spectrum of human carcinoma cells in culture after treatment with the combination of beta-lapachone and taxol, two low molecular mass compounds. They synergistically induced death of cultured ovarian, breast, prostate, melanoma, lung, colon, and pancreatic cancer cells. This synergism is schedule dependent; namely, taxol must be added either simultaneously or after beta-lapachone. This combination therapy has unusually potent antitumor activity against human ovarian and prostate tumor prexenografted in mice. There is little host toxicity. Cells can commit to apoptosis at cell-cycle checkpoints, a mechanism that eliminates defective cells to ensure the integrity of the genome. We hypothesize that when cells are treated simultaneously with drugs activating more than one different cell-cycle checkpoint, the production of conflicting regulatory signaling molecules induces apoptosis in cancer cells. beta-Lapachone causes cell-cycle delays in late G(1) and S phase, and taxol arrests cells at G(2)/M. Cells treated with both drugs were delayed at multiple checkpoints before committing to apoptosis. Our findings suggest an avenue for developing anticancer therapy by exploiting apoptosis-prone "collisions" at cell-cycle checkpoints.

Release of mitochondrial cytochrome C in both apoptosis and necrosis induced by beta-lapachone in human carcinoma cells.

BACKGROUND: There are two fundamental forms of cell death: apoptosis and necrosis. Molecular studies of cell death thus far favor a model in which apoptosis and necrosis share very few molecular regulators. It appears that apoptotic processes triggered by a variety of stimuli converge on the activation of a member of the caspase family, such as caspase 3, which leads to the execution of apoptosis. It has been suggested that blocking of caspase activation in an apoptotic process may divert cell death to a necrotic demise, suggesting that apoptosis and necrosis may share some upstream events. Activation of caspase is preceded by the release of mitochondrial cytochrome C. MATERIALS AND METHODS: We first studied cell death induced by beta-lapachone by MTT and colony-formation assay. To determine whether the cell death induced by beta-lapachone occurs through necrosis or apoptosis, we used the PI staining procedure to determine the sub-G1 fraction and the Annexin-V staining for externalization of phophatidylserine. We next compared the release of mitochondrial cytochrome C in apoptosis and necrosis. Mitochondrial cytochrome C was determined by Western blot analysis. To investigate changes in mitochondria that resulted in cytochrome C release, the mitochondrial membrane potential (delta psi) was analyzed by the accumulation of rhodamine 123, a membrane-permeant cationic fluorescent dye. The activation of caspase in apoptosis and necrosis were measured by using a profluorescent substrate for caspase-like proteases, PhiPhiLuxG6D2. RESULTS: beta-lapachone induced cell death in a spectrum of human carcinoma cells, including nonproliferating cells. It induced apoptosis in human ovary, colon, and lung cancer cells, and necrotic cell death in four human breast cancer cell lines. Mitochondrial cytochrome C release was found in both apoptosis and necrosis. This cytochrome C release occurred shortly after beta-lapachone treatment when cells were fully viable by trypan blue exclusion and MTT assay, suggesting that cytochrome C release is an early event in beta-lapachone induced apoptosis as well as necrosis. The mitochondrial cytochrome C release induced by beta-lapachone is associated with a decrease in mitochondrial transmembrane potential (delta psi). There was activation of caspase 3 in apoptotic cell death, but not in necrotic cell death. This lack of activation of CPP 32 in human breast cancer cells is consistent with the necrotic cell death induced by beta-lapachone as determined by absence of sub-G1 fraction, externalization of phosphatidylserine. CONCLUSIONS: beta-lapachone induces either apoptotic or necrotic cell death in a variety of human carcinoma cells including ovary, colon, lung, prostate, and breast, suggesting a wide spectrum of anti-cancer activity in vitro. Both apoptotic and necrotic cell death induced by beta-lapachone are preceded by a rapid release of cytochrome C, followed by the activation of caspase 3 in apoptotic cell death but not in necrotic cell death. Our results suggest that beta-lapachone is a potential anti-cancer drug acting on the mitochondrial cytochrome C-caspase pathway, and that cytochrome C is involved in the early phase of necrosis.

Evaluation of some organic compounds on bloodstream forms of Trypanosoma cruzi

Accidental transmission of Chagas' disease to man by blood transfusion is a serious problem in Latin-America. This paper describes the testing of several synthetic, semi-synthetic, and natural compounds for their activity against blood trypomastigotes in vitro at 4-C. The compounds embody several types of chemical structures: benzoquinone, naphthoquinone, anthracenequinone, phenanthrenequinone, imidazole, piperazine, quinoline, xanthene, and simple benzenic and naphthalenic derivates. Some of them are for the first time tested against Trypanosoma cruzi. The toxic effect these compounds on this parasite was done by two quite distinct sets of experiments. In one set, the compounds were added to infected blood as ethanolic solution. In this situation the most active one was a furan-1, 2-naphthoquinone, in the same range as gentian violet, a new fact to be considered in the assessment of structure-activity relationships in this class of compounds. In other set, we tentatively evaluated the biological activity of water insoluble compounds by adding them in a pure form without solvent into infected blood. In this way some appear to be very active and it was postulated that the effectiveness of such compounds must result from interactions between them and specific blood components

[The prevalence of iron deficiency in pregnant women at their first consultation in health centers in a metropolitan area, Brazil. Etiology of anemia]. / Prevalência de deficiência de ferro em gestantes de primeira consulta em centros de saúde de área metropolitana, Brasil. Etiologia da anemia.

Three hundred and sixty-three pregnant women enrolled in the Pregnancy Medical Care Program of S. Paulo Health Department in the district of Butantan, S. Paulo city, Brazil, were studied at their first routine consultation between April and October, 1988. Their average age was 25 and 65.9% of them belonged to families with a monthly income below US$50.00 per capita. Only 3.1% presented an income above US$150.00 per capita. Taking the minimum transferrin saturation threshold of 15% as determining iron deficiency, a 4.6% prevalence of iron deficiency was observed in the first trimester, 17.3% in the second trimester and 42.8% in the third trimester, resulting in an overall prevalence of 12.4%. There was no significant difference between prevalences of iron deficiency according to the number of pregnancies. The prevalence of iron deficiency was higher in women presenting incomes below US$50.00 per capita.

[Selection by means of KB cells of substances and extracts potentially active in cancer chemotherapy]. / Seleção por meio de células KB de substâncias e extratos potencialmente ativos em quimioterapia do câncer.

Several synthetic, semi-synthetic and natural compounds as well as plant extracts were screened for their growth inhibition activity on KB cells. The most active ones were naphthoquinones and derivatives of pyrido [4,3-b]carbazole alkaloids, with inhibition dose (ID50) less than 4 micrograms/ml. Of the crude extracts of several plants screened, Vellozia caput-ardeae showed to be the most active.

Um novo metodo para a purificacao do fator de von Willebrand. / A new method of purification of von Willebrand factor

O fracionamento do plasma humano para a obtencao de concentrado de fator de von Willebrand forneceu resultados superiores aos do esquema III quando se utilizou o aminoacido glicina. O esquema anteriormente empregado (esquema III) consistia em preparar um CRIO, precipita-lo com polietilenoglicol (PEG 1) e, depois, precipitar novamente com polietilenoglicol (PEG 2). Nas experiencias ora relatadas, o esquema de fracionamento (esquema IV) foi semelhante ao esquema III, exceto pela introducao da fase Glicina imediatamente apos a fase PEG 1. Com esta modificacao, o grau de purificacao da amostra final subiu de 130 para 550 vezes, embora a recuperacao da atividade do fator de von Willebrand tenha caido

Estudo da coagulacao em um caso de hepatite de Labrea. / Coagulation in a case of Labrea hepatitis

Um caso de hepatite de Labrea nos possibilitou um estudo do comportamento dos fatores da coagulao nessa doenca. O objetivo principal foi estudar a coagulacao do sangue, visando: 1. conhecer os niveis dos fatores da coagulacao na febre negra 2.contribuir para o melhor conhecimento da doenca, principalmente no que se refere as manifestacoes de hemorragia; 3. tentar correlacionar a gravidade do quadro clinico e prognostico a intensidade das alteracoes dos fatores da coagulacao.Os resultados evidenciaram uma alteracao acentuada da crase sanguinea, sugerindo que, alem do quadro infeccioso, o paciente desenvolveu, igualmente, uma sindrome de coagulacao intravascular disseminada

Purificacao do fator de von Willebrand. I - Fracionamento inicial do plasma. / Purification of the von Willebrand factor. I - Initial plasma fractionation

Este e o primeiro de uma serie de outros trabalhos sobre a purificacao do fator de von Willebrand. O objetivo deste primeiro trabalho e relatar a experiencia dos autores com o fracionamento do plasma a fim de obter um concentrado (PEG 2) altamente purificado, rico em atividade de vWF. Tres esquemas de fracionamento do plasma foram estudados. O Esquema I consistiu em precipitar o plasma a 22oC, por duas vezes, com uma solucao de polietilenoglicol (PEG) a 25g%. O Esquema II foi semelhante ao Esquema I, exceto que se utilizou a temperatura de 4oC para as precipitacoes com PEG.Para o Esquema III de fracionamento, acrescentou-se a fase de precipitacao pelo Crio ao Esquema II. A comparacao dos resultados revelou que o Esquema III de fracionamento foi o melhor, uma vez que o grau de purificacao (130 vezes) e a recuperacao da atividade do vWF (70%) aumentaram acentuadamente

Metabolismo do acido folico na malaria. / Folic acid metabolism in malaria

O estudo de 27 pacientes infectados pelo Plasmodium falciparum comparado com pessoas aparentemente sadias mostra: a) diminuicao do folato no soro dos pacientes infectados; b) diminuicao do folato serico nos primeiros 8 dias que seguiram ao tratamento, interpretados como sendo devido a mobilizacao pela eritropoiese compensadora; c) folato eritrocitico normal