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1.
Front Cell Infect Microbiol ; 13: 1025359, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36743305

RESUMO

Current therapeutic ways adopted for the treatment of leishmaniasis are toxic and expensive including parasite resistance is a growing problem. Given this scenario, it is urgent to explore treatment alternatives for leishmaniasis. The aim of this study was to evaluate the effect of 3-phenyl-lawsone (3-PL) naphthoquinone on Leishmania (Viannia) braziliensis infection, both in vitro and in vivo, using two local routes of administration: subcutaneous (higher dose) and tattoo (lower dose). In vitro 3-PL showed low toxicity for macrophages (CC50 >3200 µM/48h) and activity against intracellular amastigotes (IC50 = 193 ± 19 µM/48h) and promastigotes (IC50 = 116 ± 26 µM/72h), in which induced increased ROS generation. Additionally, 3-PL up-regulated the production of cytokines such as tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-10 in infected macrophages. However, the anti-amastigote action was independent of nitric oxide production. Treatment of hamsters infected with L. (V.) braziliensis from one week after infection with 3-PL by subcutaneous (25 µg/Kg) or tattooing (2.5 µg/Kg) route, during 3 weeks (3 times/week) or 2 weeks (2 times/week) significantly decreased the parasite load (p<0.001) in the lesion. The reduction of parasite load by 3-PL treatment was comparable to reference drug meglumine antimoniate administered by the same routes (subcutaneous 1mg/Kg and tattoo 0.1mg/Kg). In addition, treatment started from five weeks after infection with 3-PL per tattoo also decreased the parasite load. These results show the anti-leishmanial effect of 3-PL against L. (V.) braziliensis and its efficacy by subcutaneous (higher dose) and tattoo (lower dose) routes. In addition, this study shows that drug delivery by tattooing the lesion allows the use of lower doses than the conventional subcutaneous route, which may support the development of a new therapeutic strategy that can be adopted for leishmaniasis.


Assuntos
Antiprotozoários , Leishmania braziliensis , Leishmaniose Cutânea , Naftoquinonas , Tatuagem , Cricetinae , Animais , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Carga Parasitária
2.
Anticancer Res ; 43(1): 359-367, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36585169

RESUMO

BACKGROUND/AIM: Prostate cancer (PCa) is one of the most common malignancies in adult men. LQB-118 is a pterocarpanquinone with antitumor activity toward prostate cancer cells. It inhibits cell proliferation by down-regulating cyclins D1 and B1 and up-regulating p21. However, the effects of LQB-118 on PCa cell migration are still unclear. Herein, the LQB-118 effects on PCa metastatic cell migration/invasion and its mechanism of action were evaluated. MATERIALS AND METHODS: PC3 cells were treated with LQB-118 or Paclitaxel (PTX), and cell migration (wound healing and Boyden chamber assays) and invasion (matrigel assay) were determined. The LQB-118 mechanisms were evaluated by αVßIII protein expression (flow cytometry), protein phosphorylation (Western blot), and mRNA expression (qPCR). RESULTS: LQB-118 impaired PCa cell migration and invasion, down-regulated Akt phosphorylation, and also reduced GSK3ß phosphorylation, through a FAK-independent pathway. Also, it was observed that LQB-118 controlled the invasiveness behavior by reducing matrix metalloproteinase-9 (MMP-9) and up-regulating reversion-inducing cysteine rich protein with Kazal motifs (Reck) mRNA levels. Interestingly, LQB-118 increased integrin αvßIII expression, but this effect was not related to its activation, since the cell adhesion ability was reduced after LQB-118 treatment. CONCLUSION: These data highlight novel LQB-118 mechanisms in prostate cancer cells. LQB-118 acts as a negative regulator of the Akt/GSK3 signaling pathway and can modulate PCa cell proliferation, death, and migration/invasion. The results also support the use of LQB-118 for the treatment of metastatic PCa, alone or combined with another chemotherapeutic agent, due to its demonstrated pleiotropic activities.


Assuntos
Metaloproteinase 9 da Matriz , Neoplasias da Próstata , Humanos , Masculino , Linhagem Celular Tumoral/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/farmacologia , Quinase 3 da Glicogênio Sintase/uso terapêutico , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Ligadas por GPI/efeitos dos fármacos , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro
3.
Rev. bras. cir. plást ; 36(4): 480-484, out.-dez. 2021. graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1365571

RESUMO

■ RESUMO A cutis verticis gyrata é uma moléstia que se caracteriza pela hipertrofia da pele do couro cabeludo, levando à formação de dobras e saculações que se assemelham aos giros do córtex cerebral. Acomete mais comumente o sexo masculino e se desenvolve após a puberdade. Pode ocorrer isoladamente ou em associação com uma variedade de condições e tratamentos subjacentes, incluindo distúrbios neuropsiquiátricos, anormalidades oculares ou condições inflamatórias. O manejo da doença pode incluir desde conduta conservadora com a assepsia correta das áreas de dobras bem como cirurgia, se solicitado por razões psicológicas ou estéticas. O presente estudo tem por objetivo relatar o caso de um paciente adulto com cutis verticis gyrata submetido a tratamento cirúrgico para ressecção completa da lesão, seguida de reconstrução com retalhos cutâneos e realização de enxertias seriadas, juntamente com curativo por pressão negativa a vácuo.


■ ABSTRACT Cutis verticis gyrata is a disease characterized by hypertrophy of the skin on the scalp, leading to the formation of folds and sacculations that resemble the gyrus of the cerebral cortex. It most commonly affects males and develops after puberty. It can occur alone or in association with various underlying conditions and treatments, including neuropsychiatric disorders, eye abnormalities, or inflammatory conditions. The disease management can range from conservative conduct with correct asepsis of the areas of folds and surgery if requested for psychological or aesthetic reasons. The present study aims to report the case of an adult patient with cutis verticis gyrata who underwent surgical treatment for complete resection of the lesion, followed by reconstruction with skin flaps and serial grafting, together with a vacuum negative pressure dressing.

4.
Radiology ; 298(3): E141-E151, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33170104

RESUMO

Background There is lack of guidance on specific CT protocols for imaging patients with coronavirus disease 2019 (COVID-19) pneumonia. Purpose To assess international variations in CT utilization, protocols, and radiation doses in patients with COVID-19 pneumonia. Materials and Methods In this retrospective data collection study, the International Atomic Energy Agency coordinated a survey between May and July 2020 regarding CT utilization, protocols, and radiation doses from 62 health care sites in 34 countries across five continents for CT examinations performed in patients with COVID-19 pneumonia. The questionnaire obtained information on local prevalence, method of diagnosis, most frequent imaging, indications for CT, and specific policies on use of CT in COVID-19 pneumonia. Collected data included general information (patient age, weight, clinical indication), CT equipment (CT make and model, year of installation, number of detector rows), scan protocols (body region, scan phases, tube current and potential), and radiation dose descriptors (CT dose index and dose length product). Descriptive statistics and generalized estimating equations were performed. Results Data from 782 patients (median age, 59 years [interquartile range, 15 years]) from 54 health care sites in 28 countries were evaluated. Less than one-half of the health care sites used CT for initial diagnosis of COVID-19 pneumonia and three-fourths used CT for assessing disease severity. CT dose index varied based on CT vendors (7-11 mGy; P < .001), number of detector rows (8-9 mGy; P < .001), year of CT installation (7-10 mGy; P = .006), and reconstruction techniques (7-10 mGy; P = .03). Multiphase chest CT examinations performed at 20% of sites (11 of 54) were associated with higher dose length product compared with single-phase chest CT examinations performed in 80% of sites (43 of 54) (P = .008). Conclusion CT use, scan protocols, and radiation doses in patients with coronavirus disease 2019 pneumonia showed wide variation across health care sites within the same and between different countries. Many patients were imaged multiple times and/or with multiphase CT scan protocols. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee in this issue.


Assuntos
COVID-19/diagnóstico por imagem , Protocolos Clínicos , Internacionalidade , Pulmão/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2
5.
Int Immunopharmacol ; 83: 106399, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32193104

RESUMO

LQB 118, a hydride molecule, has been described as an antineoplastic and antiparasitic drug. Recently, LQB118 was also shown to display anti-inflammatory properties using an LPS-induced lung inflammation model. However, LQB 118 effects on the inflammatory response induced by zymosan has not been demonstrated. In this study, swiss mice were LQB 118 intraperitoneally (i.p.) treated and zymosan was used to induce peritoneal inflammation. Peritoneal fluid was collected and used for cell counting and proinflammatory cytokines quantification (IL-1ß, IL-6, and TNF-α) by immunoenzymatic assay (ELISA). For in vitro studies, peritoneal macrophages zymosan-stimulated were used. Results demonstrated that LQB 118 treatment reduced polymorphonuclear cell migration and TNF-α, IL-1ß, and IL-6 levels in the peritoneal cavity. In macrophages, LQB 118 treatment display no cytotoxic effect and is also able to reduce cytokines levels. To investigate LQB 118 putative mechanism of action, TLR2, CD69, and P-p38 MAPK expression were evaluated. LQB 118 treatment reduced CD69 expression and p38 phosphorylation induced by zymosan. Furthermore, LQB 118 was able to negatively modulate TLR2 expression in the presence of inflammatory stimulus. Thus, our study provide new evidences for the mechanisms related to the anti-inflammatory effect of LQB 118 in vivo and in vitro.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Inflamação/tratamento farmacológico , Macrófagos/imunologia , Naftoquinonas/uso terapêutico , Peritônio/imunologia , Peritonite/tratamento farmacológico , Pterocarpanos/uso terapêutico , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Zimosan/imunologia
6.
Aesthet Surg J ; 40(1): NP21-NP31, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268530

RESUMO

BACKGROUND: In 1971, Ribeiro isolated a segment in the inferior pole of the ptotic breast, nourished by muscular perforating vessels, and moved it cranially to the posterior region of the remaining detached breast tissue, where it was fixed to the pectoral fascia. This maneuver created a flap with autologous implant function, independent from the rest of the breast's support, that maintained long-term mammary projection. OBJECTIVES: The objectives of this study were to measure the vertical movement of this flap 1 year after mammaplasty and to evaluate the factors involved. METHODS: The sample included 13 patients who had previously undergone bariatric surgery. The position of a titanium marker attached to the Ribeiro flap was compared on chest radiographs taken 1 day and 1 year after the mammaplasty. The significance level was set at 5%. RESULTS: All of the titanium markers moved 0.6 cm to 4.1 cm caudally during the study period (average, 2.4 cm ± 1.02 cm). The greater the weight loss after the plastic surgery, the further the marker's descent. Weight loss between bariatric surgery and plastic surgery, the vertical dimension of the ptotic breast tissue immediately before plastic surgery, the vertical extent of the nipple-areola complex elevation during mammaplasty, the Ribeiro flap thickness and volume, and the breast volume after mammaplasty were not associated with the vertical movement of the flap. CONCLUSIONS: The Ribeiro flap employed in mammaplasty of patients who previously underwent bariatric surgery undergoes ptosis that is exacerbated by weight loss after mammaplasty.


Assuntos
Cirurgia Bariátrica , Bariatria , Mamoplastia , Cirurgia Bariátrica/efeitos adversos , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamilos/cirurgia , Retalhos Cirúrgicos
7.
Int J Mol Sci ; 20(20)2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614718

RESUMO

Drug resistance represents a major issue in treating breast cancer, despite the identification of novel therapeutic strategies, biomarkers, and subgroups. We have previously identified the LQB-223, 11a-N-Tosyl-5-deoxi-pterocarpan, as a promising compound in sensitizing doxorubicin-resistant breast cancer cells, with little toxicity to non-neoplastic cells. Here, we investigated the mechanisms underlying LQB-223 antitumor effects in 2D and 3D models of breast cancer. MCF-7 and MDA-MB-231 cells had migration and motility profile assessed by wound-healing and phagokinetic track motility assays, respectively. Cytotoxicity in 3D conformation was evaluated by measuring spheroid size and performing acid phosphatase and gelatin migration assays. Protein expression was analyzed by immunoblotting. Our results show that LQB-223, but not doxorubicin treatment, suppressed the migratory and motility capacity of breast cancer cells. In 3D conformation, LQB-223 remarkably decreased cell viability, as well as reduced 3D culture size and migration. Mechanistically, LQB-223-mediated anticancer effects involved decreased proteins levels of XIAP, c-IAP1, and Mcl-1 chemoresistance-related proteins, but not survivin. Survivin knockdown partially potentiated LQB-223-induced cytotoxicity. Additionally, cell treatment with LQB-223 resulted in changes in the mRNA levels of epithelial-mesenchymal transition markers, suggesting that it might modulate cell plasticity. Our data demonstrate that LQB-223 impairs 3D culture growth and migration in 2D and 3D models of breast cancer exhibiting different phenotypes.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Pterocarpanos/farmacologia , Antineoplásicos/toxicidade , Movimento Celular , Proliferação de Células , Feminino , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Células MCF-7 , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Pterocarpanos/toxicidade , Esferoides Celulares/efeitos dos fármacos , Survivina/genética , Survivina/metabolismo , Células Tumorais Cultivadas , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
8.
Int J Oncol ; 55(6): 1396, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31545420

RESUMO

Subsequent to the publication of the above article, the authors have realized that there were errors associated with Figs. 1c and 2b. In Fig. 1c, the authors noted that the same data were incorrectly presented for the 'Untreated cells" and 'DMSO' dot­blot experiments. After having re­examined their source data, the authors were able to confirm that the data correctly shown for the 'Untreated cells' experiment had inadvertently been included in the Figure as the data for the 'DMSO' experiment. Additionally, in Fig. 2b, the authors noticed that the percentage of untreated cells with active caspase­3 was missing (the label for the 'No antibody' experiment). Corrected versions of Figs. 1 (including the correct data for the 'DMSO' dot blot) and 2 (with the label now incorporated) are shown opposite. Note that these changes do not affect the results or the conclusions reported in this paper, and all the authors agree to this correction. The authors apologize to the Editor and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Oncology 45: 1949­1958, 2014; DOI: 10.3892/ijo.2014.2615].

9.
Radiol. bras ; 49(3): 176-181, graf
Artigo em Inglês | LILACS | ID: lil-787595

RESUMO

Abstract The present review aims to offer an educational approach related to the limitations in the use of the effective dose mgnitude as a tool for the quantification of doses resulting from diagnostic applications of ionizing radiation. We present a critical analysis of the quantities accepted and currently used for dosimetric evaluation in diagnostic imaging procedures, based on studies published in the literature. It is highlighted the use of these quantities to evaluate the risk attributed to the procedure and to calculate the effective dose, as well as to determine its correct use and interpretation.


Resumo Este trabalho de revisão pretende oferecer uma abordagem educacional relacionada às limitações na utilização da grandeza dose efetiva como ferramenta para quantificação de doses decorrentes de aplicações em diagnóstico médico utilizando radiações ionizantes. Os autores apresentam uma análise crítica sobre as grandezas aceitas e utilizadas atualmente para a avaliação dosimétrica em procedimentos de diagnóstico médico por imagem, tendo como base estudos publicados na literatura. Destacam-se as formas de utilização dessas grandezas para a avaliação do risco atribuído ao procedimento e para o cálculo da dose efetiva e sua correta utilização e interpretação.

10.
Rev. bras. cir. plást ; 31(4): 586-590, 2016. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-827473

RESUMO

Perineal and gluteal regions may be affected by a wide spectrum of diseases, and the treatment may require extensive surgery and cause functional, aesthetic, and psychosocial damages at various levels. Wounds in the extensive perineal and gluteal regions after surgical treatment of neoplasia may represent a challenge in local reconstruction. Size, location, and availability of tissue around the lesion may hinder wound primary closure, requiring the use of one or more flaps. This article reports a case of reconstruction of the perineal and gluteal regions after oncological resection at the plastic surgery service of the Hospital das Clínicas at the Federal University of Minas Gerais. The muscle and fasciocutaneous flaps of the gluteus maximus and myocutaneous of the semimembranosus were used.


As regiões glútea e perineal podem ser afetadas por um variado espectro de doenças, cujo tratamento pode demandar extensas mutilações e acarretar em prejuízo funcional, estético e psicossocial em variados graus. Feridas extensas da região perineal e glútea após o tratamento cirúrgico de neoplasias podem representar um desafio para a reconstrução local. Tamanho, localização e disponibilidade de tecido em torno da lesão são fatores que podem impedir o seu fechamento primário, tornando necessário o uso de um ou mais retalhos. Este artigo relata um caso de reconstrução de períneo e região glútea após ressecção oncológica, no serviço de Cirurgia Plástica do Hospital das Clínicas da Universidade Federal de Minas Gerais (UFMG). Foram utilizados os retalhos muscular e fasciocutâneo de glúteo máximo e miocutâneo de semimembranoso.


Assuntos
Humanos , Masculino , Adulto , História do Século XXI , Períneo , Retalhos Cirúrgicos , Nádegas , Carcinoma de Células Escamosas , Procedimentos de Cirurgia Plástica , Protectomia , Períneo/anatomia & histologia , Períneo/cirurgia , Retalhos Cirúrgicos/cirurgia , Nádegas/anatomia & histologia , Carcinoma de Células Escamosas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Protectomia/métodos
11.
Parasitol Int ; 64(6): 622-31, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26335616

RESUMO

Toxoplasmosis is a widely disseminated disease caused by Toxoplasma gondii, an intracellular protozoan parasite. Standard treatment causes many side effects, such as depletion of bone marrow cells, skin rashes and gastrointestinal implications. Therefore, it is necessary to find chemotherapeutic alternatives for the treatment of this disease. It was shown that a naphthoquinone derivative compound is active against T. gondii, RH strain, with an IC50 around 2.5 µM. Here, three different naphthoquinone derivative compounds with activity against leukemia cells and breast carcinoma cell were tested against T. gondii (RH strain) infected LLC-MK2 cell line. All the compounds were able to inhibit parasite growth in vitro, but one of them showed an IC50 activity below 1 µM after 48 h of treatment. The compounds showed low toxicity to the host cell. In addition, these compounds were able to induce tachyzoite-bradyzoite conversion confirmed by morphological changes, Dolichus biflorus lectin cyst wall labeling and characterization of amylopectin granules in the parasites by electron microscopy analysis using the Thierry technique. Furthermore, the compounds induced alterations on the ultrastructure of the parasite. Taken together, our results point to the naphthoquinone derivative (LQB 151) as a potential compound for the development of new drugs for the treatment of toxoplasmosis.


Assuntos
Antiprotozoários/farmacologia , Naftoquinonas/farmacologia , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose Animal/tratamento farmacológico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Macaca mulatta , Microscopia Eletrônica , Relação Estrutura-Atividade , Toxoplasmose Animal/parasitologia
12.
Res. Biomed. Eng. (Online) ; 31(3): 249-256, July-Sept. 2015. graf
Artigo em Inglês | LILACS | ID: biblio-829437

RESUMO

Introduction:Brazil has seen a rise in the number of undergraduate courses in Medical Physics in recent years, as well as initiatives for the organization of graduation programs and clinical residencies in this multidisciplinary area. The purpose of the present study was to perform a data survey on academic training in Medical Physics in Brazil in the undergraduate, graduate, and residency levels until 2012.MethodsThe relevant information was requested for the leads of the training/teaching programs, which filled specific electronic forms. The data survey was accomplished by sending the forms to 38 educational institutions.ResultsThe majority (90%) of the contacted institutions returned their specific requested information. It was estimated an offer of 400 enroll admissions per year in the group of institutions that offer undergraduate programs in Medical Physics. Federal or state public educational institutions offer around 61% of these admissions and 39% are offered by private universities. The average number of candidate competition was estimated on 3.6 ± 3.9 applicants per place in undergraduate programs, and the student’s complete the courses in 5.1 ± 0.7 years. The average number of undergraduate degrees awarded per year is 10.6 ± 7.3. At least 80% of educational programs have compulsory internships in their curricula with average duration of 307 ± 99 hours. In the graduation programs it was verified that the average time for concluding the programs were 2.2 ± 0.2 years, 4.1 ± 0.2 years and 4.7 ± 0.6 years for the MSc, PhD and direct-PhD, respectively. The programs have CAPES ratings varying from 4 to 7. Finally, until 2012 the residence programs offered 31 positions per year and the professional development programs (not residence) provide 7 positions per year.ConclusionIt is understood that the presented numerical results offer a reliable scenario for the diagnosis of opportunities and scholarships distributions in each region of the country. These results may provide support for the improvement of resource distribution and the definition of public policies that can guide the adequacy of the distribution of courses in the three modalities of Medical Physics Education in the country.

13.
Int J Oncol ; 45(5): 1949-58, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25174716

RESUMO

Acute myeloid leukemia (AML) patients' outcome is usually poor, mainly because of drug resistance phenotype. The identification of new drugs able to overcome mechanisms of chemoresistance is essential. The pterocarpanquinone LQB-118 compound has been shown to have a potent cytotoxic activity in myeloid leukemia cell lines and patient cells. Our aim was to investigate if LQB-118 is able to target FoxO3a and FoxM1 signaling pathways while sensitizing AML cell lines. LQB-118 induced apoptosis in both AML cell lines HL60 (M3 FAB subtype) and U937 (M4/M5 FAB subtype). Cell death occurred independently of alterations in cell cycle distribution. In vivo administration revealed that LQB-118 was not cytotoxic to normal bone marrow-derived cells isolated from mice. LQB-118 induced FoxO3a nuclear translocation and upregulation of its direct transcriptional target Bim, in HL60 cells. However, LQB-118 induced FoxO3a nuclear exclusion, followed by Bim downregulation, in U937 cells. Concomitantly, LQB-118 exposure reduced FoxM1 and Survivin expression in U937 cells, but this effect was more subtle in HL60 cells. Taken together, our data suggest that LQB-118 has a selective and potent antitumor activity against AML cells with distinct molecular subtypes, and it involves differential modulation of the signaling pathways associated with FoxO3a and FoxM1 transcription factors.


Assuntos
Fatores de Transcrição Forkhead/biossíntese , Leucemia Mieloide Aguda/tratamento farmacológico , Naftoquinonas/administração & dosagem , Pterocarpanos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteína Forkhead Box M1 , Proteína Forkhead Box O3 , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Camundongos
14.
Rev. bras. cir. plást ; 29(3): 442-445, jul.-sep. 2014. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-743

RESUMO

A face representa uma estrutura importante nos seres humanos, devido a ser a parte mais visível do corpo e conter elementos delicados e complexos, que são essenciais em termos de beleza e funcionalidade. As reconstruções faciais, em áreas de grandes perdas de substâncias, permanecem como um desafio para os cirurgiões. Apresentam várias opções de reparo, todas com suas vantagens e desvantagens. Mostramos o caso de um paciente apresentando perda de substância de espessura total em região de bochecha, que foi submetido à associação de retalho mucoso e retalho cutâneo local, apresentando bom resultado e preservação funcional.


The face is an important structure, because it is the most visible part of the body and contains delicate and complex elements that are essential for aesthetics and functionality. Facial reconstruction of areas with substantial substance loss remains a surgical challenge. There are several repair options, with corresponding advantages and disadvantages. We present a case of a patient with substance loss of the total thickness of the cheek region who received mucosal and local skin flap surgery, with good results and functional preservation.


Assuntos
Humanos , Masculino , Adulto , História do Século XXI , Penicilinas , Atrofia , Retalhos Cirúrgicos , Relatos de Casos , Tonsilite , Bochecha , Síndrome da Imunodeficiência Adquirida , HIV , Procedimentos de Cirurgia Plástica , Difusão de Inovações , Face , Ossos Faciais , Antibacterianos , Penicilinas/uso terapêutico , Atrofia/cirurgia , Retalhos Cirúrgicos/cirurgia , Retalhos Cirúrgicos/transplante , Tonsilite/patologia , Tonsilite/tratamento farmacológico , Bochecha/cirurgia , Bochecha/patologia , Síndrome da Imunodeficiência Adquirida/patologia , Procedimentos de Cirurgia Plástica/métodos , Face/anormalidades , Face/cirurgia , Ossos Faciais/cirurgia , Antibacterianos/uso terapêutico
15.
Rev. bras. eng. biomed ; 29(1): 86-96, jan.-mar. 2013. graf, tab
Artigo em Inglês | LILACS | ID: lil-670976

RESUMO

The aim of this work is to simulate transmission data for different beam geometry and material composition in order to evaluate the effect of these parameters on transmission curves. The simulations are focused on outgoing spectra for shielding barriers used in PET facilities. The behavior of the transmission was evaluated as a function of the shielding material composition and thickness using Geant4 Monte Carlo code, version 9.2 p 03.The application was benchmarked for barited mortar and compared to The American Association of Physicists in Medicine (AAPM) data for lead. Their influence on the transmission curves as well the study of the influence of the shielding material composition and beam geometry on the outgoing spectra were performed. Characteristics of transmitted spectra, such as shape, average energy and Half-Value Layer (HVL), were also evaluated. The Geant4 toolkit benchmark for the energy resulting from the positron annihilation phenomena and its application in transmission curves description shown good agreement between data published by American Association on Physicists in Medicine task group 108 and experimental data published by Brasil. The transmission properties for different material compositions were also studied and have shown low dependency with the considered thicknesses. The broad and narrow beams configuration presented significant differences on the result. The fitting parameter for determining the transmission curves equations, according to Archer model is presented for different material. As conclusion were defined that beam geometry has significant influence and the composition has low influence on transmission curves for shielding design for the range of energy applied to PET.


O objetivo deste trabalho é simular dados de transmissão para feixes de diferentes geometria e composição de materiais, a fim de avaliar o efeito destes parâmetros em curvas de transmissão. As simulações estão focadas em espectros de saída para blindagem por barreiras utilizadas em instalações de PET. O comportamento da transmissão foi avaliado como uma função da composição do material de blindagem e de sua espessura, usando o código de Monte Carlo Geant4, versão 9.2 p 03. A aplicação foi validada para argamassa baritada e comparada com dados publicados pela Associação Americana de Físicos em Medicina (AAPM) para o chumbo. Foram realizadas avaliações da influência da geometria do feixe e da composição do material sobre os espectros de saída e sobre as curvas de transmissão. Características de transmissão dos espectros, tais como a forma, a energia média e a camada de semirredutora (HVL), também foram avaliadas. A ferramenta Geant4, para a energia resultante de fenômenos de aniquilação de pósitrons e sua aplicação na descrição de curvas de transmissão, mostrou boa concordância entre os dados publicados pelo grupo de trabalho 108 da Associação Americana de Físicos em Medicina e dados experimentais publicados no Brasil. As propriedades de transmissão para diferentes composições de materiais foram também estudadas e mostraram baixa dependência com as espessuras consideradas. A configuração de feixes largos e estreitos apresentaram diferenças significativas nos resultados. Os parâmetros de ajuste para a determinação das equações que representam as curvas de transmissão, de acordo com o modelo de Archer, são apresentados para diferentes materiais. Como conclusão, pode-se dizer que a geometria do feixe tem influência significativa e a composição tem pouca influência nas curvas de transmissão para projetos de blindagem para a faixa de energia aplicadas em PET.

16.
Vet Parasitol ; 186(3-4): 261-9, 2012 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-22177332

RESUMO

Toxoplasma gondii, the agent of Toxoplasmosis, is an obligate intracellular protozoan able to infect a wide range of vertebrate cells, including nonprofessional and professional phagocytes. Therefore, drugs must have intracellular activities in order to control this parasite. The most common therapy for Toxoplasmosis is the combination of sulfadiazine and pyrimethamine. This treatment is associated with adverse reactions, thus, the development of new drugs is necessary. In previous studies, naphthoquinone derivatives showed anti-cancer activity functioning as agents capable of acting on groups of DNA, preventing cancer cells duplication. These derivatives also display anti-parasitic activity against Plasmodium falciparum and Leishmania amazonensis. The derivative pterocarpanquinone tested in this work resulted from the molecular hybridization between pterocarpans and naphtoquinone that presents anti-tumoral and anti-parasitic activities of lapachol. The aim of this work was to determine if this derivative is able to change T. gondii growth within LLC-MK2 cells. The drug did not arrest host cell growth, but was able to decrease the infection index of T. gondii with an IC(50) of 2.5 µM. Scanning and transmission electron microscopy analysis showed morphological changes of parasites including membrane damage. The parasite that survived tended to encyst as seen by Dolichos biflorus lectin staining and Bag-1 expression. These results suggest that pterocarpanquinones are drugs potentially important for the killing and encystment of T. gondii.


Assuntos
Pterocarpanos/farmacologia , Toxoplasma/efeitos dos fármacos , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Fibroblastos/parasitologia , Macaca mulatta , Microscopia Eletrônica de Varredura , Estrutura Molecular , Pterocarpanos/química , Toxoplasma/ultraestrutura
17.
Acta Cir Bras ; 26(4): 314-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21808846

RESUMO

PURPOSE: To assess the viability of McFarlane skin flaps in rats with administration of sildenafil. METHODS: Twenty Wistar rats were distributed into two groups: Control (dorsal skin flap, subdermal application of saline solution at 0.9%) and Study (dorsal skin flap, subdermal application of sildenafil). Seven days after the surgery, flaps were photographed and graphically rendered. Then, they were analyzed with AutoCAD software. Three biopsies (proximal, medial and distal) of each flap were collected for histological analysis. RESULTS: Macroscopic analysis showed that animals of the study group had greater necrotic areas (p=0.003) in the dorsal skin flaps. Additionally, histological analysis of the distal third of these flaps showed a tendency to less granulated tissue formation in animals treated with sildenafil. CONCLUSION: Sildenafil subdermally was associated with lower viability of the random skin flap in rats.


Assuntos
Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Pele/efeitos dos fármacos , Sulfonas/farmacologia , Retalhos Cirúrgicos/patologia , Sobrevivência de Tecidos/efeitos dos fármacos , Animais , Biópsia , Procedimentos Cirúrgicos Dermatológicos , Feminino , Necrose/patologia , Purinas/farmacologia , Ratos , Ratos Wistar , Citrato de Sildenafila , Pele/patologia , Cicatrização
18.
Acta cir. bras ; 26(4): 314-319, July-Aug. 2011. ilus, tab
Artigo em Inglês | LILACS | ID: lil-594353

RESUMO

PURPOSE: To assess the viability of McFarlane skin flaps in rats with administration of sildenafil. METHODS: Twenty Wistar rats were distributed into two groups: Control (dorsal skin flap, subdermal application of saline solution at 0.9 percent) and Study (dorsal skin flap, subdermal application of sildenafil). Seven days after the surgery, flaps were photographed and graphically rendered. Then, they were analyzed with AutoCAD software. Three biopsies (proximal, medial and distal) of each flap were collected for histological analysis. RESULTS: Macroscopic analysis showed that animals of the study group had greater necrotic areas (p=0.003) in the dorsal skin flaps. Additionally, histological analysis of the distal third of these flaps showed a tendency to less granulated tissue formation in animals treated with sildenafil. CONCLUSION: Sildenafil subdermally was associated with lower viability of the random skin flap in rats.


OBJETIVO: Avaliar a viabilidade de retalhos cutâneos de ratos à McFarlane após a administração de sildenafil. MÉTODOS: Vinte ratos Wistar foram distribuídos em dois grupos: Controle (confecção do retalho cutâneo dorsal, aplicação subdérmica de solução salina a 0,9 por cento) e Estudo (confecção do retalho cutâneo dorsal, aplicação subdérmica de sildenafil). Sete dias após a operação, os retalhos foram fotografados e representados graficamente, para serem analisados com o programa AutoCad. Três biópsias (cranial, média e caudal) foram coletadas de cada retalho, para análise histológica. RESULTADOS: A análise macroscópica evidenciou que os animais do grupo Estudo apresentaram maiores áreas de necrose (p=0,003) nos retalhos cutâneos dorsais. Além disso, a análise histológica dos terços distais dos retalhos mostrou uma tendência à formação de menos tecido de granulação nos animais que receberam o sildenafil. CONCLUSÃO: O sildenafil subdérmico esteve associado com uma pior viabilidade tecidual dos retalhos cutâneos dorsais de ratos.


Assuntos
Animais , Feminino , Ratos , /farmacologia , Piperazinas/farmacologia , Pele/efeitos dos fármacos , Sulfonas/farmacologia , Retalhos Cirúrgicos/patologia , Sobrevivência de Tecidos/efeitos dos fármacos , Biópsia , Necrose/patologia , Purinas/farmacologia , Ratos Wistar , Pele/patologia , Pele/cirurgia , Cicatrização
19.
Radiol. bras ; 43(4): 241-248, jul.-ago. 2010. ilus, tab
Artigo em Português | LILACS | ID: lil-557977

RESUMO

OBJETIVO: Estudar a viabilidade de redução da dose de radiação em protocolos de aquisição de imagens de tomografia helicoidal em um hospital universitário. MATERIAIS E MÉTODOS: Foi realizado levantamento de dose de radiação de protocolos de tomografia com objetos simuladores e câmara de ionização. Foram propostas variações de kVp e mAs, determinando-se a média de ruído. Protocolos com valores de ruído menores ou iguais a 1 por cento foram submetidos à avaliação qualitativa de contraste e resolução espacial por três observadores. RESULTADOS: Foram realizados 22 testes de variações para o protocolo de crânio pediátrico, 26 para crânio adulto, 28 para abdome e 18 para tórax. A redução da dose conseguida variou entre 7,4-13 por cento para protocolo de crânio pediátrico, 3,8-25 por cento para crânio adulto, 9,6-34,3 por cento para abdome e 6,4-12 por cento para tórax. Notou-se também que a utilização de ferramentas de janelamento e zoom favoreceu o aceite das imagens pelos observadores. CONCLUSÃO: É possível reduzir os níveis de dose de radiação em até 34,4 por cento, comparativamente aos protocolos utilizados na rotina, mantendo-se o ruído em níveis aceitáveis. O uso de ferramentas de manipulação digital das imagens possibilitou a aceitação de imagens com níveis maiores de ruído, favorecendo o processo de redução de dose de radiação.


OBJECTIVE: To study the feasibility of reducing radiation dose in protocols for acquisition of helical computed tomography images in a University Hospital. MATERIALS AND METHODS: A survey of radiation doses in computed tomography protocols was performed with phantoms and ionization chamber. Changes in kVp and mAs were proposed, determining the average noise. Protocols with noise values 1 percent were submitted to qualitative assessment of contrast and spatial resolution by three observers. RESULTS: Tests of variations were performed with 22 protocols for pediatric skulls, 26 for adult skulls, 28 for abdomen, and 18 for chest. The reduction in dose achieved ranged between 7.4 percent and13 percent for pediatric skull, 3.8 percent and 25 percent for adult skull, 9.6 percent and 34.3 percent for abdomen, 6.4 percent and 12 percent for chest. It was also noted that the use of windowing and zoom tools supported the acceptance of images by the observers. CONCLUSION: Radiation dose levels can be reduced by up to 34.4 percent in comparison with routine protocols, keeping the noise at acceptable levels. The use of digital manipulation tools allowed the acceptance of images with higher noise levels, thus resulting in radiation dose reduction.


Assuntos
Humanos , Masculino , Feminino , Dosagem , Doses de Radiação , Relação Dose-Resposta à Radiação , Tomografia Computadorizada Espiral , Otimização de Processos , Razão Sinal-Ruído
20.
Rev. bras. eng. biomed ; 26(2): 105-120, ago. 2010. ilus, tab, graf
Artigo em Português | LILACS | ID: lil-619157

RESUMO

O presente trabalho consiste no estudo e aplicação do algoritmo FDK (Feldkamp-Davis-Kress) para a reconstrução de imagens tomográficas utilizando a geometria de feixe cônico, resultando na implementação de um sistema adaptado de tomografia computadorizada multicortes (TCMC). O algoritmo FDK é a base de algoritmos de retroprojeção filtrada utilizados nos equipamentos de TCMC comercializados atualmente. Para a aquisição das projeções, utilizou-se uma plataforma giratória com goniômetro acoplado, um equipamento de raios X e um detector digital tipo CCD (charge-coupled device). Para processar a reconstrução das imagens foi utilizado um computador com processador Pentium® XEONTM 3.0, no qual foi implementado o algoritmo FDK. Inicialmente foi aplicado o algoritmo FDK original, no qual se assume o caso físico ideal no processo de medições. Em seguida foram incorporadas ao algoritmo algumas correções de artefatos relacionados ao processo de medição das projeções, tais como a alteração do filtro utilizado na etapa que precede a retroprojeção, para aumentar a razão sinal ruído das imagens e uma correção digital da centralização do sistema de aquisição das projeções. Para a calibração do sistema utilizou-se um objeto com distribuição de coeficientes de atenuação linear (μ(r)) conhecida, que foi fabricado com esta finalidade. Por fim, o sistema de TCMC implementado foi utilizado na reconstrução tomográfica multicortes de um objeto não homogêneo, cuja distribuição μ(r) é desconhecida. Para avaliar a robustez do sistema e sua reprodutibilidade, foram analisados alguns aspectos das imagens reconstruídas, tais como: relação sinal ruído, concordância entre os valores de número CT medidos e determinados teoricamente, e a fidelidade na representação do objeto imageado. Durante a calibração do sistema foi verificada a relação linear entre o número CT e o coeficiente de atenuação linear dos materiais, o que valida a aplicação do sistema implementado para a caracterização...


This work consisted on the study and application of the FDK (Feldkamp- Davis-Kress) algorithm for tomographic image reconstruction using cone-beam geometry, resulting on the implementation of an adapted multi-slice computed tomography (MSCT) system. For the acquisition of the projections, a rotating platform coupled to a goniometer, an X-ray equipment and a digital image detector CCD (charge-coupled device) type were used. The FDK algorithm was implemented on a computer with a Pentium® XEONTM 3.0 processor, which was used for the reconstruction process. Initially, the original FDK algorithm was applied considering only the ideal physical conditions in the measurement process. Then some artifacts corrections related to the projections measurement process were incorporated. The implemented MSCT system was calibrated. A specially designed and manufactured object with a known linear attenuation coefficient distribution (μ(r)) was used for this purpose. Finally, the implemented MSCT system was used for multi-slice tomographic reconstruction of an inhomogeneous object, whose distribution μ(r) was unknown. Some aspects of the reconstructed images were analyzed to assess the robustness and reproducibility of the system. During the system calibration, a linear relationship between CT number and linear attenuation coefficients of materials was verified, which validate the application of the implemented multi-slice tomographic system for the characterization of linear attenuation coefficients of distinct several objects.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/tendências , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada de Feixe Cônico/tendências , Tomografia Computadorizada de Feixe Cônico , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/tendências , Diagnóstico por Imagem
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