RESUMO
AIM: The relevance of the cytidine diphosphate-choline and Rho GTPases pathways in the pathogenesis of cancer has been previously demonstrated. We investigate by a case-control association study if genetics variants in these pathways are associated with risk of developing lung cancer. METHODS: Thirty-seven tag SNPs were evaluated as risk factor of NSCLC in 897 cases and 904 controls. RESULTS: Six SNPs were nominally associated with lung cancer risk, which were not significant after the Bonferroni correction for multiple comparisons. No association was observed with the remaining 31 analyzed SNPs, neither it was found significant in haplotype frequencies. CONCLUSIONS: Although the implication of the two pathways investigated in our study in carcinogenesis is well established, our null results suggest that common genetic variants in CDP-choline and Rho GTPases-related genes are not risk factors for lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Fosfolipídeos/metabolismo , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Colina Quinase/genética , Feminino , Haplótipos , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteínas rho de Ligação ao GTP/genéticaRESUMO
INTRODUCTION: Cyclooxygenase-2 (COX2) is an enzyme that plays a role in different stages of the carcinogenic process and has prognostic and predictive values that have not yet been established. The objective of this study was to evaluate the role of COX2 overexpression in advanced squamous cell carcinoma of the larynx that has been treated with a phonation conservation protocol. MATERIALS AND METHODS: This study included a retrospective analysis of 59 patients with resectable tumours that were treated with chemotherapy (CT) and/or radiation therapy (RT). The expression levels of COX2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor (VEGFR-2) in collected biopsy specimens were determined via immunohistochemistry. RESULTS: Forty-four percent of the included samples demonstrated overexpression of COX2. In the statistical analysis, COX2 overexpression did not correlate with other clinical or treatment efficacy prognostic factors; however, the median global survival (OS) of patients whose tumours expressed COX2 was 79 months, whereas COX2-negative patients had a median OS of only 38 months, although this finding did not reach statistical significance. The other analysed biological parameters did not demonstrate a significant relationship with COX2. CONCLUSIONS: COX2 overexpression was a common finding in our study. The results obtained did not reveal relationships with established prognostic categories; however, the difference in survival between patients with and without COX2 expression justifies the need for future prospective studies that utilise a larger patient sample size.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismo , Neoplasias Laríngeas/tratamento farmacológico , Fonação/efeitos dos fármacos , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/fisiopatologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
We report a previously healthy 73 years old woman, who was hospitalised with increasing dyspnea and signs of congestive heart failure. Echocardiography showed a normal left ventricular cavity with increased echogenicity of its walls and severe pulmonary hypertension. A lung ventilation/perfusion scintigraphy concluded that there was a low probability for pulmonary embolism. Coronary angiography was normal. A restrictive cardiomyopathy due to amyloid deposits was suspected. Myocardial pyrophosphate scintigraphy showed intense pyrophosphate uptake in the left ventricle wall. An abdominal fat tissue biopsy was positive for amyloid deposits
Assuntos
Humanos , Feminino , Idoso , Pirofosfato de Tecnécio Tc 99m , Amiloidose , Cardiomiopatias , Tomografia Computadorizada de Emissão de Fóton Único , Sensibilidade e Especificidade , CardiomiopatiasRESUMO
Various liquid chromatographic (LC) techniques for analyzing avermectin (Abamectin) were compared after extraction of residues from citrus fruit samples by matrix solid-phase dispersion (MSPD). LC with UV and fluorescence detection were used as also was LC coupled to the mass spectrometer by an electrospray interface. The results obtained by the three methods were compared in terms of sensitivity and selectivity. The combination of MSPD extraction and LC with fluorescence detection have made it possible to quantify 0.5 microg kg(-1) of Abamectin in 0.5 g of orange sample, with an overall average recovery of 94%. The procedure provides a simple and sensitive method for monitoring Abamectin residues in citrus fruit at the levels required by legislation.
Assuntos
Cromatografia Líquida/métodos , Citrus/química , Resíduos de Drogas/análise , Ivermectina/análise , Ivermectina/análogos & derivados , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria UltravioletaAssuntos
Infecção Hospitalar/microbiologia , Surtos de Doenças , Enterococcus faecium/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Resistência a Vancomicina , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Infecção Hospitalar/epidemiologia , Enterococcus faecium/efeitos dos fármacos , Feminino , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Pessoa de Meia-Idade , Unidade Hospitalar de Ginecologia e Obstetrícia , Fatores de RiscoRESUMO
OBJECTIVES: To evaluate the role of bcl-2 and apoptotic index in the progression from primary to metastatic breast carcinoma and their influence on prognosis. METHODS: bcl-2 expression was examined by immunohistochemistry and apoptotic index by in situ end-labelling in 116 surgical breast carcinomas and lymph node metastases from 50 patients. RESULTS: bcl-2 was observed in 69 cases (59.4%) of primitive carcinomas and 26 cases (65%) of metastatic breast carcinomas and there was agreement of bcl-2 expression between primary and metastatic sites except in 3 cases. bcl-2 expression was significantly associated with several favourable prognostic features, such as small tumour size (p = 0.03) and oestrogen and progesterone-receptor positivity (p < 0.01 and p < 0.001, respectively). A high apoptotic index was significantly associated with a number of poor prognostic factors, including poorly differentiated carcinomas, large tumour size, high Ki67 expression and high mitotic count (p < 0.001 in all cases). The mean apoptotic index was higher in lymph node metastasis than in primary carcinomas (1.19 vs. 0.69, p < 0.01). A low bcl-2 expression and a high apoptotic index were significantly associated with short-relapse free survival rates (p = 0.02 and p < 0.01, respectively), but only apoptotic extent provided independent prognostic information by multivariate analysis. CONCLUSIONS: The evaluation of bcl-2 expression and extent of apoptosis may provide useful prognostic information on breast cancer patients; however while increased apoptosis is strongly associated with the progression from primary carcinomas to lymph node metastases, bcl-2 does not seem to play a significant role in this process.
Assuntos
Apoptose , Neoplasias da Mama/genética , Carcinoma/genética , Genes bcl-2 , Adulto , Idoso , Mama/metabolismo , Doenças Mamárias/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma/mortalidade , Carcinoma/patologia , Fragmentação do DNA , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , PrognósticoRESUMO
The gene coding for bovine interferon-omega1 (BoIFN-omega1) was recently cloned and expressed at high levels in the yeast Pichia pastoris. The recombinant BoIFN-omega1 protein shows antiviral activity in different cell lines and has an antiluteolytic effect in cyclic ewes. In this article, we describe a method for purification of BoIFN-omega1 expressed in the methylotrophic yeast P. pastoris and characterization of its activity in vivo. The recombinant protein secreted to the culture medium had low activity because of self-aggregation. BoIFN-omega1 was solubilized using urea and desalting and finally purified by ion exchange chromatography on Q-Sepharose Fast Flow. The yield of purified product was approximately 300 mg/L of fermentation culture, with a specific antiviral activity of 10(8) IU/mg. Its purity was at least 80%. The biologic characterization of purified BoIFN-omega1 was determined by induction of an antiviral state on ewes challenged with 100 lethal doses (LD) of Aujeszky virus and by the extension of the corpus luteum life span and interestrous interval in cyclic cows. Ewes treated with 2 x 106 IU/kg BoIFN-omega1 were protected from Aujeszky virus infection. In cows receiving an intrauterine infusion of 1 mg BoIFN-omega1, equally distributed between the two uterine horns, twice daily from day 14 to day 22 of the experimental estrous cycle, the lifespan of the corpus luteum (25 vs. 19 days) and the interestrous intervals (26 vs. 21 days) were extended when compared with a control group (p < 0.05). We show that recombinant BoIFN-omega1 purified from P. pastoris has high antiviral activity and is an effective antiluteolytic agent in cattle.
Assuntos
Interferon Tipo I/farmacologia , Animais , Antivirais/farmacologia , Bovinos , Linhagem Celular , Manutenção do Corpo Lúteo/efeitos dos fármacos , Estro/efeitos dos fármacos , Feminino , Técnicas In Vitro , Interferon Tipo I/genética , Interferon Tipo I/isolamento & purificação , Masculino , Pichia/genética , Gravidez , Pseudorraiva/prevenção & controle , Proteínas Recombinantes , OvinosRESUMO
The recombinant Bm86-containing vaccine Gavac(TM) against the cattle tick Boophilus microplus has proved its efficacy in a number of experiments, especially when combined with acaricides in an integrated manner. However, tick isolates such as the Argentinean strain A, show low susceptibility to this vaccine. In this paper we report on the isolation of the Bm95 gene from the B. microplus strain A, which was cloned and expressed in the yeast Pichia pastoris producing a glycosylated and particulated recombinant protein. This new antigen was effective against different tick strains in a pen trial, including the B. microplus strain A, resistant to vaccination with Bm86. A Bm95-based vaccine was used to protect cattle against tick infestations under production conditions, lowering the number of ticks on vaccinated animals and, therefore, reducing the frequency of acaricide treatments. The Bm95 antigen from strain A was able to protect against infestations with Bm86-sensitive and Bm86-resistant tick strains, thus suggesting that Bm95 could be a more universal antigen to protect cattle against infestations by B. microplus strains from different geographical areas.
Assuntos
Antígenos/imunologia , Doenças dos Bovinos/prevenção & controle , Infestações por Carrapato/veterinária , Carrapatos/imunologia , Vacinas Sintéticas/imunologia , Animais , Formação de Anticorpos , Antígenos/genética , Sequência de Bases , Bovinos , Clonagem Molecular , Feminino , Lactação , Dados de Sequência Molecular , Pichia/genética , Proteínas Recombinantes/isolamento & purificação , Infestações por Carrapato/prevenção & controle , VacinaçãoRESUMO
The control of tick infestations and the transmission of tick-borne diseases remain a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant B. microplus gut antigen Bm86 have been developed. Our vaccine formulation (Gavac, Heber Biotec S.A., Havana, Cuba) has been registered and is commercially available in Cuba, Colombia, Dominican Republic, Brazil and Mexico. In controlled pen trials, Gavac has been effective for the control of artificial infestations of B. annulatus, B. decoloratus and chemical-sensitive and resistant B. microplus strains from Australia, Africa, America and Iran. In controlled field trials in Cuba, Brazil, Argentina and Mexico, Gavac has shown a 55-100% efficacy in the control of B. microplus infestations in grazing cattle 12-36 weeks after the first vaccination. Field trials under production conditions have been conducted in Cuba, Colombia, Brazil and Mexico in pure and cross-bred cattle herds. The application of Gavac has increased the time between acaricide treatments by an average of 32 /-21 days (P = 0.0005) resulting in important savings for the cattle industry. In Cuba, a cost-effectiveness analysis was conducted in more than 260000 animals. The cost-effectiveness analysis showed a 60% reduction in the number of acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of 23.4 dollars animal(-1) year (-1). These results clearly demonstrate the advantage of vaccination and support the application of Gavac for the control of Boophilus spp. infestations.
Assuntos
Vetores Aracnídeos/imunologia , Doenças dos Bovinos/prevenção & controle , Glicoproteínas de Membrana/imunologia , Proteínas Recombinantes , Controle de Ácaros e Carrapatos/métodos , Infestações por Carrapato/veterinária , Carrapatos/imunologia , Vacinação/veterinária , Vacinas Sintéticas/imunologia , Vacinas , Animais , Bovinos , Doenças dos Bovinos/economia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/parasitologia , Análise Custo-Benefício , Feminino , América Latina , Ensaios Clínicos Controlados Aleatórios como Assunto/veterinária , Infestações por Carrapato/economia , Infestações por Carrapato/epidemiologia , Infestações por Carrapato/imunologia , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , Vacinação/economia , Vacinas Sintéticas/economiaRESUMO
Throughout most of the twentieth century, tick infestations on cattle have been controlled with chemical acaricides, typically administered by dipping or spraying. This approach can cause environmental and residue problems and has created a high incidence of acaricide resistance within tick populations in the field. Recently we developed a vaccine against Boophilus microplus employing a recombinant Bm86 antigen preparation (Gavac), (Heber Biotec S.A., Havana, Cuba) which has been shown to induce a protective response in vaccinated animals. Here we show for the first time under field conditions a near 100% control of B. microplus populations resistant to pyrethroids and organophosphates, by an integrated system employing vaccination with Gavac and amidine treatments. This method effectively controls tick infestations while reducing the number of chemical acaricide treatments and consequently the rise of B. microplus populations resistant to chemical acaricides.
Assuntos
Amidinas , Doenças dos Bovinos/prevenção & controle , Glicoproteínas de Membrana/imunologia , Proteínas Recombinantes , Controle de Ácaros e Carrapatos/métodos , Infestações por Carrapato/veterinária , Carrapatos , Vacinas/imunologia , Animais , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/parasitologia , Resistência a Inseticidas , Inseticidas , México , Compostos Organofosforados , Piretrinas , Infestações por Carrapato/imunologia , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , VacinaçãoRESUMO
Recent developments in cattle tick control have incorporated the use of recombinant Bm86 vaccines against this ectoparasite. The vaccine developed by our group (Gavac) contains an antigen expressed in Pichia pastoris, and has been successfully employed for the control of tick infestations and transmission of tick-borne diseases. Here, we examined the safety and effect of the Gavac vaccine on reproductive parameters in cattle. Toxicity tests in mice and guinea pigs demonstrated the safety of Gavac. To study the adverse effects of vaccination on reproduction, a field trial involving 9,500 animals in Cuba was conducted. The cattle at 3 farms were vaccinated while those on a fourth farm were left unvaccinated and served as the control. Following vaccination, the control of tick infestation and the transmission of babesiosis were used to demonstrate the efficacy of the vaccine. No adverse effects were observed in any of the reproductive parameters studied when comparing the data before and after vaccination with Gavac and between the vaccinated farms and the control farm. These results demonstrate that under the conditions of our study vaccination with Gavac is safe for use on cattle.
Assuntos
Glicoproteínas de Membrana/imunologia , Proteínas Recombinantes , Reprodução , Controle de Ácaros e Carrapatos , Vacinas/efeitos adversos , Aborto Animal/etiologia , Animais , Babesiose/prevenção & controle , Babesiose/transmissão , Bovinos , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/transmissão , Feminino , Cobaias , Camundongos , Gravidez , Carrapatos/imunologia , Carrapatos/fisiologia , Vacinas/toxicidadeRESUMO
Tick infestations by Boophilus spp. constitute a major problem for the cattle industry in tropical and subtropical areas of the world. The use of traditional control methods has been only partially successful and tick infestations remain a serious problem. Recently, the gut antigen Bm86 was isolated from B. microplus. Recombinant preparations of this antigen have been used in vaccines for the control of B. microplus infestations. However, in several regions of the world, B. microplus coexists with other Boophilus species, mainly B. annulatus and B. decoloratus. Therefore, there is a need for the simultaneous control of infestations by different Boophilus species. To test the capacity of the P. pastoris-derived Bm86 antigen preparation (Gavac, Heber Biotec S.A., Havana) to control B. annulatus infestations, controlled experiments were conducted in Mexico and Iran. Cattle were vaccinated with Gavac or not vaccinated and then artificially infested with B. annulatus larvae. The results showed for the first time a high protection efficacy (> 99.9%) of Gavac in the control of B. annulatus infestations. These results support the application of Bm86-containing vaccines for the control of Boophilus spp. infestations.
Assuntos
Doenças dos Bovinos/prevenção & controle , Glicoproteínas de Membrana/imunologia , Infestações por Carrapato/imunologia , Vacinas/imunologia , Animais , Bovinos , Cuba , Feminino , Irã (Geográfico) , México , Proteínas Recombinantes/imunologia , Infestações por Carrapato/prevenção & controleRESUMO
The control of tick infestations and the transmission of tick-borne diseases remains a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant Boophilus microplus gut antigen Bm86 have been developed. These vaccines have been shown to control tick infestations in the field. However, extensive field studies investigating the efficacy and cost-effectiveness of vaccination have not been reported and are needed to appraise the effect of this new approach for tick control. Here is reported the results of the application of Gavac in a field trial including more than 260,000 animals in Cuba. In this study the correlation between the antibody response to vaccination and the effect on ticks fertility is determined. Physiological status of the animals was found to affect the primary response to vaccination but not the antibody titers after revaccination. A cost-effectiveness analysis showed a 60% reduction in the number acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of $23.4 animal-1 year-1. These results clearly demonstrate the advantage of vaccination and support the application of Gavac for tick control.
Assuntos
Doenças dos Bovinos/economia , Glicoproteínas de Membrana/imunologia , Proteínas Recombinantes , Infestações por Carrapato/veterinária , Carrapatos/imunologia , Vacinas/economia , Vacinas/imunologia , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Análise Custo-Benefício , Cuba , Feminino , Infestações por Carrapato/prevenção & controle , Vacinas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
The recombinant Bm86 tick antigen expressed in Pichia pastoris is obtained in a highly particulated form, as a distinguish feature of this expression system. This particulated protein, the active principle of the recombinant vaccine Gavac against the cattle tick, have shown high immunogenic and protective properties, probably associated with its own characteristics. To evaluate the effects of particulation on the properties of Bm86, three groups of calves were immunized with particulated or non-particulated recombinant Bm86 and the anti-Bm86 antibody response determined. Animals were challenged with a controlled tick infestation and the protective capacities of both proteins assessed. Humoral immune response and protection in cattle vaccinated with the particulated antigen were higher. These experiments suggested that particulation of the Bm86 expressed in P. pastoris is an important feature for the protective properties of the antigen in vaccine preparations.
Assuntos
Glicoproteínas de Membrana/imunologia , Pichia , Proteínas Recombinantes , Infestações por Carrapato/prevenção & controle , Carrapatos/imunologia , Vacinas/administração & dosagem , Animais , Bovinos , Masculino , Infestações por Carrapato/imunologia , Vacinas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
The gene coding for bIFN-omega 1 was isolated from bovine genomic DNA by polymerase chain reaction (PCR). Recombinant bIFN-omega 1 was expressed in the yeast Pichia pastoris and high levels of the recombinant protein (0.4 mg ml-1) were secreted to the culture media. The obtained bIFN-omega 1 showed a cross-species antiviral activity on four mammalian cell lines of calf, pig, hamster and human origin, but this activity was absent on Madin-Darby canine kidney (MDCK) cells. A delivery carrier was developed to permit a better release of bIFN-omega 1. When compared with a control group, an increase in 6 days in the corpus luteum lifespan was obtained in cyclic ewes following three interferon (IFN) intrauterine administrations on days 9, 10 and 11 post-estrus. In summary, these results demonstrated for the first time that biologically active recombinant bIFN-omega 1 was highly secreted by P. pastoris showing antiviral activity in different cell lines and an antiluteolytic effect in cyclic ewes, with no detrimental effects on the animals.
Assuntos
Interferon Tipo I/genética , Pichia/genética , Sequência de Aminoácidos , Animais , Antivirais/farmacologia , Bovinos , Linhagem Celular , Corpo Lúteo/fisiologia , Cricetinae , Cães , Eletroforese em Gel de Poliacrilamida , Feminino , Expressão Gênica , Humanos , Interferon Tipo I/metabolismo , Interferon Tipo I/farmacologia , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Progesterona/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Ovinos , Suínos , Útero/metabolismoAssuntos
Dengue Grave/complicações , Ruptura Esplênica/complicações , Adulto , Evolução Fatal , Feminino , HumanosAssuntos
Dermatomicoses/diagnóstico , Mucormicose/diagnóstico , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/cirurgia , Quimioterapia Combinada , Fluconazol/uso terapêutico , Humanos , Masculino , Mucorales/crescimento & desenvolvimento , Mucormicose/tratamento farmacológico , Mucormicose/cirurgia , Coxa da Perna/parasitologia , Coxa da Perna/cirurgiaRESUMO
A study was made of the dietary habits and intake of energy and nutrients of 127 elderly people aged between 65 and 95 (60 men and 67 women). The method employed involved the recording of food consumption over a period of five days. Subjects were divided into two groups according to body mass index: those who were overweight or obese (0) (BMI > or = 25 Kg/m2), who made up 60% of the experimental population, and those with normal bodyweight (NW) (BMI < 25 Kg/m2) (40%). The percentage of subjects who took no breakfast was somewhat higher amongst members of group 0 (5.6% compared to 3.9% of NW subjects). Further, the breakfast of 0 subjects was less varied, smaller and contributed less to daily energy intake and the covering of theoretical energy expenditure than did the breakfasts of NW subjects. 0 subjects also took less time over their breakfasts. More than half (58.8%) of NW subjects took what might be considered a satisfactory breakfast, i.e. this meal provided more than 20% of the total energy intake. Only 29.6% of 0 subjects took breakfasts of similar energetic value. NW subjects consumed greater quantities of sugars and fruits at breakfasts and also more carbohydrates, fibre, vitamin E and iron than did 0 subjects. The shorter length of time spent at breakfast by 0 subjects, their consumption of smaller and less varied breakfasts and the composition of the same, could indicate the existence of less healthy breakfast habits amongst the overweight and obese. This could be the reflection of inadequate food habits all round, or be a conditioning factor prompting 0 subjects to make poorer food choices for the rest of the day. Though some people omit breakfast in an attempt to control their weight, this is probably an inadvisable practice. The control of bodyweight might be more efficiently accomplished by taking an adequate breakfast and better distributing total calorie intake across the day, avoiding its concentration into one or two meals.