RESUMO
DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic multiscale nature requires chemistry and quantum physics to understand the structure and quantum informatics to explain its operation as a perfect quantum computer. Here, we present theoretical results of DNA that allow a better description of its structure and the operation process in the transmission, coding, and decoding of genetic information. Aromaticity is explained by the oscillatory resonant quantum state of correlated electron and hole pairs due to the quantized molecular vibrational energy acting as an attractive force. The correlated pairs form a supercurrent in the nitrogenous bases in a single band π -molecular orbital ( π -MO). The MO wave function ( Φ ) is assumed to be the linear combination of the n constituent atomic orbitals. The central Hydrogen bond between Adenine (A) and Thymine (T) or Guanine (G) and Cytosine (C) functions like an ideal Josephson Junction. The approach of a Josephson Effect between two superconductors is correctly described, as well as the condensation of the nitrogenous bases to obtain the two entangled quantum states that form the qubit. Combining the quantum state of the composite system with the classical information, RNA polymerase teleports one of the four Bell states. DNA is a perfect quantum computer.
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Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.
Assuntos
Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Telomerase , Animais , Humanos , Ratos , Estreptozocina , CicatrizaçãoRESUMO
Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.
Assuntos
Humanos , Animais , Ratos , Telomerase , Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Cicatrização , EstreptozocinaRESUMO
Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student's t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.
Assuntos
Adaptação Fisiológica/fisiologia , Diabetes Mellitus Experimental/patologia , Junção Neuromuscular/patologia , Análise e Desempenho de Tarefas , Animais , Diabetes Mellitus Experimental/fisiopatologia , Masculino , Camundongos , Junção Neuromuscular/fisiopatologia , Ratos , Ratos WistarRESUMO
Phaeohyphomycosis is a group of infections caused by pigmented, black, dematiaceous fungi and is responsible for cutaneous, superficial and deep mycoses, disseminated infection and brain abscesses. The primary agents involved include Alternaria spp., Exophiala spp. and Cladophialophora spp. Invasive systemic presentation is rare and in most cases is associated with immunosuppression; for this reason, reported cases of Alternaria spp. infection are scarce. This report describes the case of a 66-year-old man with a history of renal transplantation from a cadaveric donor 1 year ago, which was considered as the primary risk factor. The characteristics of the infection, procedures performed, microbiological findings and treatment provided are described.
RESUMO
Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student's t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.
Assuntos
Animais , Masculino , Coelhos , Ratos , Análise e Desempenho de Tarefas , Adaptação Fisiológica/fisiologia , Diabetes Mellitus Experimental/patologia , Junção Neuromuscular/patologia , Ratos Wistar , Diabetes Mellitus Experimental/fisiopatologia , Junção Neuromuscular/fisiopatologiaRESUMO
BACKGROUND: 68 Ga-PSMA-PET has an increasing importance in the evaluation of prostate cancer patients due to its high sensitivity and specificity in identifying neoplastic lesions in the clinical setting of elevated prostate-specific antigen (PSA). The objective of this study was to calculate the whole-body tumor burden using volumetric quantification of lesions detected in 68Ga-PSMA-PET of prostate cancer patients with biochemical recurrence and correlate these findings with clinical and image parameters. METHODS: Each patient had their 68Ga-PSMA-PET analyzed for the presence of neoplastic lesions. Their PSA levels and clinical information were recorded. In positive cases, the tumor burden (TL-PSMA) was calculated with a semi-automatic software and manually, and the results are analyzed and tested. RESULTS: We analyzed 100 prostate cancer patients, mean age of 69.9 ± 9.7 years and a median PSA of 1.73 ng/dL. 68Ga-PSMA-PET identified neoplastic lesions in 72% of them. The median TL-PSMA was 55.95 ml (1.1-28,080 ml). TL-PSMA and PSA were strongly correlated (rho = 0.71, p < 0.0001, 95% CI 0.60-0.80). TL-PSMA and PSA levels groups had a significant correlation and TL-PSMA and Gleason score were independent variables associated with PSA levels (p < 0.05). CONCLUSION: TL-PSMA strongly and independently correlates with PSA levels in prostate cancer patients and could be used as a biomarker to separate them into groups with high or low tumor burden, instead of considering only the number of lesions.
Assuntos
Ácido Edético/análogos & derivados , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , Recidiva , Estudos RetrospectivosRESUMO
The aim of this study was to compare muscle strength in male subjects with type 2 diabetes mellitus (DM2) with and without low plasma testosterone levels and assess the relationship between muscle strength, testosterone levels, and proinflammatory cytokines. Males (75) aged between 18 and 65 years were divided into 3 groups: control group that did not have diabetes and had a normal testosterone plasma level (>250 ng/dL), DnormalTT group that had DM2 with normal testosterone levels, and the DlowTT group that had DM2 and low plasma testosterone levels (<250 ng/dL). The age (means±SD) of the groups was 48.4±10, 52.6±7, and 54.6±7 years, respectively. Isokinetic concentric and isometric torque of knee flexors and extensors were analyzed by an isokinetic dynamometer. Plasma testosterone and proinflammatory cytokine levels were determined by chemiluminescence and ELISA, respectively. Glycemic control was analyzed by glycated hemoglobin (HbA1C). In general, concentric and isometric torques were lower and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß plasma levels were higher in the groups with diabetes than in controls. There was no correlation between testosterone level and knee torques or proinflammatory cytokines. Concentric and isometric knee flexion and extension torque were negatively correlated with TNF-α, IL-6, and HbA1C. IL-6 and TNF-α were positively correlated with HbA1C. The results of this study demonstrated that muscle strength was not associated with testosterone levels in men with DM2. Low muscle strength was associated with inflammatory markers and poor glycemic control.
Assuntos
Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Força Muscular/fisiologia , Testosterona/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Contração Isométrica/fisiologia , Joelho , Masculino , Pessoa de Meia-Idade , Torque , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
La presente investigación tuvo como objetivo establecer la frecuencia de aislamiento de las diferentes especies de estafilococos y determinar la resistencia antimicrobiana de las cepas aisladas. Se realizó un estudio retrospectivo, en cepas aisladas en el Centro de Referencia Bacteriológica del Servicio Autónomo Hospital Universitario de Maracaibo, durante el período enero 2011 diciembre 2015. Se obtuvo un porcentaje de aislamiento para S. aureus del 61,36% y 38,64% para coagulasa negativa, observándose mayor frecuencia de aislamiento en el área de hospitalización para ambos grupos de microorganismos. Las muestras de piel y tejidos blandos representaron las principales fuentes de aislamiento para S. aureus; mientras que para el grupo coagulasa negativa, fueron las muestras de sangre. Todas las cepas fueron sensibles a los glicopéptidos. La resistencia para los b-lactámicos fue acentuada para ambos grupos bacterianos, mostrando variabilidad para macrólidos y lincosamidas y para los restantes antibióticos probados, se encontraron bajos porcentajes de resistencia. Los resultados demuestran que S. aureus es la especie más frecuente del género; seguida de S. epidermidis y S. haemolyticus entre coagulasa negativa. Ambos grupos de microorganismos expresan fenotipos de resistencia a penicilina y eritromicina, sensibilidad a vancomicina y teicoplanina y susceptibilidad variable al resto de antibióticos evaluados.
The objective of the present investigation was to establish the frequency of isolation of the different species of staphylococci and to determine the antimicrobial resistance of the isolated strains. A retrospective study was carried out in isolated strains at the Bacteriological Reference Center of the Autonomous Service of the University Hospital of Maracaibo during the period January 2011 to December 2015. A percentage of isolation was obtained for S. aureus of 61.36% and 38,64% for coagulase negative, showing a higher frequency of isolation in the hospitalization area for both groups of microorganisms. Skin and soft tissue samples represented the main sources of isolation for S. aureus; while for the coagulase negative group, they were blood samples. All strains were sensitive to glycopeptides. Resistance for ß-lactams was accentuated for both bacterial groups, showing variability for macrolides and lincosamides and for the remaining antibiotics tested, low percentages of resistance were found. The results show that S. aureus is the most frequent species of the genus; followed by S. epidermidis and S. haemolyticus, among coagulase negative. Both groups of microorganism express phenotypes of resistance to penicillin and erythromycin, sensitivity to vancomycin and teicoplanin and variable susceptibility to the rest of evaluated antibiotics.
RESUMO
The aim of this study was to compare muscle strength in male subjects with type 2 diabetes mellitus (DM2) with and without low plasma testosterone levels and assess the relationship between muscle strength, testosterone levels, and proinflammatory cytokines. Males (75) aged between 18 and 65 years were divided into 3 groups: control group that did not have diabetes and had a normal testosterone plasma level (>250 ng/dL), DnormalTT group that had DM2 with normal testosterone levels, and the DlowTT group that had DM2 and low plasma testosterone levels (<250 ng/dL). The age (means±SD) of the groups was 48.4±10, 52.6±7, and 54.6±7 years, respectively. Isokinetic concentric and isometric torque of knee flexors and extensors were analyzed by an isokinetic dynamometer. Plasma testosterone and proinflammatory cytokine levels were determined by chemiluminescence and ELISA, respectively. Glycemic control was analyzed by glycated hemoglobin (HbA1C). In general, concentric and isometric torques were lower and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β plasma levels were higher in the groups with diabetes than in controls. There was no correlation between testosterone level and knee torques or proinflammatory cytokines. Concentric and isometric knee flexion and extension torque were negatively correlated with TNF-α, IL-6, and HbA1C. IL-6 and TNF-α were positively correlated with HbA1C. The results of this study demonstrated that muscle strength was not associated with testosterone levels in men with DM2. Low muscle strength was associated with inflammatory markers and poor glycemic control.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Testosterona/sangue , Citocinas/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Força Muscular/fisiologia , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Mediadores da Inflamação/sangue , Torque , Contração Isométrica/fisiologia , JoelhoRESUMO
Studies have suggested that total energy intake and diet composition affect lifespan and ageing. A high-fat diet induces oxidative stress and affects the development of diseases. In contrast, antioxidants are capable of reducing its harmful effects. Yerba mate beverages are an important source of antioxidants, but there is scarce knowledge about their effects on suppressing fat accumulation. Here, we investigated the compounds present in yerba mate extracts and assessed their effects on Drosophila melanogaster given a high cholesterol diet. LS-ESI-MS analysis showed the presence of matesaponins, phenolic compounds and methylxanthines in all of the examined extracts. In Drosophila, under extract treatment conditions, the mean lifespan was significantly extended from 38 to 43 days, there was an increase in the ability to support induced stress and decrease in lipid peroxidation products. Moreover, yerba mate extracts recovered the glutathione S-transferases (GST) activity and reduced the cholesterol level. Taken together, our results support that extracts can extend lifespan by reducing the detrimental effect of a high-fat diet in D. melanogaster, and this outcome can be associated with the compound content in the extracts. This study improves the understanding of natural interventions that reduce stress-induced oxidative damage, which is fundamental in promoting healthy ageing.
Assuntos
Animais , Extratos Vegetais/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ilex paraguariensis/química , Drosophila melanogaster/fisiologia , Longevidade/efeitos dos fármacos , Antioxidantes/farmacologia , Estresse Oxidativo/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Dieta Hiperlipídica , Longevidade/fisiologiaRESUMO
Studies have suggested that total energy intake and diet composition affect lifespan and ageing. A high-fat diet induces oxidative stress and affects the development of diseases. In contrast, antioxidants are capable of reducing its harmful effects. Yerba mate beverages are an important source of antioxidants, but there is scarce knowledge about their effects on suppressing fat accumulation. Here, we investigated the compounds present in yerba mate extracts and assessed their effects on Drosophila melanogaster given a high cholesterol diet. LS-ESI-MS analysis showed the presence of matesaponins, phenolic compounds and methylxanthines in all of the examined extracts. In Drosophila, under extract treatment conditions, the mean lifespan was significantly extended from 38 to 43 days, there was an increase in the ability to support induced stress and decrease in lipid peroxidation products. Moreover, yerba mate extracts recovered the glutathione S-transferases (GST) activity and reduced the cholesterol level. Taken together, our results support that extracts can extend lifespan by reducing the detrimental effect of a high-fat diet in D. melanogaster, and this outcome can be associated with the compound content in the extracts. This study improves the understanding of natural interventions that reduce stress-induced oxidative damage, which is fundamental in promoting healthy ageing.
Assuntos
Antioxidantes/farmacologia , Drosophila melanogaster/fisiologia , Ilex paraguariensis/química , Longevidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Dieta Hiperlipídica , Drosophila melanogaster/crescimento & desenvolvimento , Longevidade/fisiologia , Estresse Oxidativo/fisiologiaRESUMO
We aimed to induce and inhibit HO-1, ascertaining its effect on infection rate, parasite load and the levels of superoxide, reactive oxygen species (ROS), nitric oxide (NO), TNF-alpha and IL-10 in cultured macrophages from healthy dogs infected by Leishmania infantum. Macrophages obtained from 15 healthy dogs were cultured alone or infected with L. infantum, with or without association of HO-1 inducer and inhibitor. The infection rate and the parasite load were determined by the number of infected macrophages and number of promastigotes per macrophage, respectively. HO-1 levels and gene expression, as well as IL-10 and TNF-alpha levels were also measured in these cultures. Superoxide, ROS and NO levels in macrophages were measured through flow cytometry. Induction of HO-1 increased the infection rate and parasite load, while its inhibition decreased the infection rate and IL-10 production. There was a positive correlation between HO-1 and infection rate or parasite load. Increased infection rate was associated with decreased superoxide, ROS and NO levels. Induction of HO-1 metabolism in dogs infected by L. infantum is possibly one of the mechanisms responsible for increasing the infection of macrophages, mainly through reduction in the oxidative and nitrosative metabolisms of these cells.
Assuntos
Heme Oxigenase-1/metabolismo , Leishmania infantum/fisiologia , Leishmaniose Visceral/veterinária , Macrófagos/parasitologia , Carga Parasitária , Animais , Células Cultivadas , Doenças do Cão/parasitologia , Cães , Expressão Gênica , Heme Oxigenase-1/antagonistas & inibidores , Interleucina-10/genética , Interleucina-10/metabolismo , Óxido Nítrico/metabolismo , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.
Assuntos
Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Subpopulações de Linfócitos T/metabolismo , Adulto , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/imunologia , Citometria de Fluxo , Humanos , Imunidade Celular , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estatísticas não Paramétricas , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Citocinas/sangue , Subpopulações de Linfócitos T/metabolismo , Diabetes Mellitus Tipo 2/sangue , Valores de Referência , Proteína C-Reativa/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Estudos de Casos e Controles , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Estatísticas não Paramétricas , Contagem de Linfócitos , Diabetes Mellitus Tipo 2/imunologia , Citometria de Fluxo , Imunidade CelularRESUMO
With the limitations of surgical reconstructive procedures, the growing number of gunshot wounds, burns, and work accidents in Mexico that result in complex facial deformities leaves only 1 option-face transplantation. The National Institute of Medical Sciences and Nutrition "Salvador Zubiran" (INCMNSZ) has performed transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb transplantation in Latin America in 2012. We are willing to continue in this manner toward conducting face transplantation at our institute. To this end, we identified and solved various challenges. The 1st challenge was acceptance and inclusion of vascularized composite allotransplantation (VCA) within general Mexican health law and approval of the face transplantation procedure. Subsequently, the health ministry provided a license to INCMNSZ to perform the procedure. The 2nd challenge concerned who would pay for the procedure. The costs will be paid by the patient (1st-party payer), social security institutions (2nd-party payers), and the health ministry (3rd-party payer). The 3rd challenge was to maintain ongoing surgical training of the team using cadavers. The fourth challenge was to locate donors; toward this end, we developed a campaign for promoting face donation in social media, making a comic book, and training organ and tissue coordinators to further VCA. Thus, INCMNSZ has the legal, administrative, medical, and surgical wherewithal to accomplish face transplantation.
Assuntos
Face/cirurgia , Traumatismos Faciais/cirurgia , Transplante de Face/métodos , Doadores de Tecidos , Cadáver , Traumatismos Faciais/epidemiologia , Humanos , Incidência , México/epidemiologia , Alotransplante de Tecidos Compostos Vascularizados/métodosRESUMO
La endometriosis consiste en la presencia ectópica de glándulas endometriales y células estromales fuera de la cavidad uterina (principalmente en ovarios y superficies de órganos internos de la cavidad pélvica). Es uno de los desórdenes ginecológicos benignos más comunes en las mujeres que están en edad reproductiva. Hay diversas teorías para explicar la endometriosis. La más aceptada es la denominada "menstruación retrógrada". Las mujeres con endometriosis presentan dolor en la región pélvica-abdominal, dismenorrea, dispareunia, mucho sangrado en la menstruación, dolor pélvico no-menstrual, dolor al ovular, disquecia, disuria, fatiga crónica y sub-fertilidad. Diversos estudios han relacionado la endometriosis con aparición de cáncer ovárico, con un desarrollo de carcinomas en 5% - 10% de los casos de mujeres con endometriomas ováricos. El desarrollo efectivo de estrategias terapéuticas para el control de la endometriosis depende de una correcta identificación de los patrones epigenéticos y de genes candidatos, que serían el blanco en los tratamientos.
Endometriosis consists in the ectopic presence of endometrial glands and stromal cells outside the uterine cavity (mainly in ovaries and on the surface of internal organs of the pelvic cavity). It is one of the most common benign gynecological disorders in reproductive-age women. There are various theories to explain endometriosis. The most widely accepted theory is known as "retrograde menstruation". Common endometriosis symptoms include pelvic or abdominal pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, non-menstrual pelvic pain, ovulation pain, dyschezia, dysuria, chornic fatigue syndrome, and fertility problems. Various studies have associated endometriosis with the onset of ovarian cancer, with carcinoma development in 5 to 10% of women with ovarian endometriomas. The successful development of therapeutic strategies to control endometriosis depends on a correct identification of the epigenetic patterns and gene candidates to be targeted by treatment.
A endometriose consiste na presencia ectópica de glândulas endometriais e células estromais fora da cavidade uterina (principalmente em ovários e superfícies de órgãos internos da cavidade pélvica). É um dos desordens ginecológicos benignos mais comuns nas mulheres que estão em idade reprodutiva. Há diversas teorias para explicar a endometriose. A mais aceitada é a denominada "menstruação retrógrada". As mulheres com endometriose apresentam dor na região pélvica-abdominal, dismenorreia, dispareunia, muito sangrado na menstruação, dor pélvico não-menstrual, dor ao ovular, disquesia, disúria, fatiga crónica e subfertilidade. Diversos estudos hão relacionado a endometriose com aparição de câncer ovárico, com um desenvolvimento de carcinomas em 5% - 10% dos casos de mulheres com endometriomas ováricos. O desenvolvimento efetivo de estratégias terapêuticas para o controle da endometriose depende de uma correta identificação dos padrões epigenéticos e de genes candidatos, que seriam o alvo nos tratamentos.
Assuntos
Humanos , Genética , Fenótipo , Terapêutica , Células Estromais , Endometriose , Genótipo , Infertilidade , Menstruação , Distúrbios MenstruaisRESUMO
Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
Assuntos
Humanos , Descontaminação/métodos , Geobacillus stearothermophilus/efeitos dos fármacos , Peróxido de Hidrogênio/administração & dosagem , Controle de Infecções/métodosRESUMO
Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
Assuntos
Administração Metronômica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptor ErbB-2 , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Síndrome Mão-Pé/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Gradação de Tumores , Paclitaxel/administração & dosagem , Pneumonia/etiologia , Estudos Prospectivos , Receptores de Estrogênio/análise , TrastuzumabRESUMO
Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.