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1.
Mol Biol Rep ; 51(1): 174, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252353

RESUMO

BACKGROUND: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins. The present study aimed to demonstrate whether cfDNA not associated with EV induces cell transformation and tumorigenesis. METHODS: Supernatant of the SW480 human colon cancer cell line was processed by ultracentrifugation to obtain a soluble fraction (SF) and a fraction associated with EV (EVF). Primary murine embryonic fibroblast cells (NIH3T3) underwent passive transfection with these fractions, and cell proliferation, cell cycle, apoptosis, cell transformation, and tumorigenic assays were performed. Next, cfDNA was analyzed by electronic microscopy, and horizontal transfer was assessed by human mutant KRAS in recipient cells via PCR and recipient cell internalization via fluorescence microscopy. RESULTS: The results showed that the SF but not the EVF of cfDNA induced proliferative and antiapoptotic effects, cell transformation, and tumorigenesis in nude mice, which were reduced by digestion with DNAse I and proteinase K. These effects were associated with horizontal DNA transfer and cfDNA internalization into recipient cells. CONCLUSIONS: The results suggest pro-tumorigenic effects of cfDNA in the SF that can be offset by enzyme treatment. Further exploration of the horizontal tumor progression phenomenon mediated by cfDNA is needed to determine whether its manipulation may play a role in cancer therapy.


Assuntos
Ácidos Nucleicos Livres , Humanos , Animais , Camundongos , Ácidos Nucleicos Livres/genética , Camundongos Nus , Células NIH 3T3 , Carcinogênese , DNA
2.
Public Health ; 215: 94-99, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36652788

RESUMO

OBJECTIVES: The purpose of this study was to compare case fatality rates (CFRs) and odds for mortality by risk factors of patients with COVID-19 in Mexico, before, during and after the implementation of the national COVID-19 vaccination programme. STUDY DESIGN: A large database including COVID-19 monitoring cases was used to perform an observational retrospective study. METHODS: The Chi-squared test and multivariate logistic regression analyses were applied to data from COVID-19-positive patients in Mexico. Data were analysed over 3 years, 2020, 2021 and 2022, corresponding with pre-, during and post-vaccination periods. The unadjusted odds ratios and 95% confidence interval were used to estimate the risk factors for COVID-19 mortality in each of the years. RESULTS: Statistically significant differences in CFR and odds ratio were found in the studied years, favouring postvaccination period. Significant changes in CFR by age, sex and main comorbidities indicated changes in the epidemic dynamics after the implementation of the COVID-19 vaccination campaign. The likelihood of death increased for hospitalised cases and for patients who were middle-aged or older in 2021 and 2022, whereas the odds of death associated with sex and comorbidities remained similar or reduced over the 3 years. CONCLUSIONS: Implementation of the COVID-19 vaccination programme during 2021 showed positive consequences on CFR. The increased odds of dying in hospitalised patients are likely to be due to the unvaccinated proportion of patients.


Assuntos
COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Programas de Imunização , México/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Vacinação , Idoso
3.
Hum Reprod ; 31(9): 1970-80, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27402911

RESUMO

STUDY QUESTION: Does advanced maternal age (AMA) in mice affect cardiometabolic health during post-natal life in offspring derived from an assisted reproduction technology (ART) procedure? SUMMARY ANSWER: Offspring derived from blastocysts collected from aged female mice displayed impaired body weight gain, blood pressure, glucose metabolism and organ allometry during post-natal life compared with offspring derived from blastocysts from young females; since all blastocysts were transferred to normalized young mothers, this effect is independent of maternal pregnancy conditions. WHAT IS KNOWN ALREADY: Although studies in mice have shown that AMA can affect body weight and behaviour of offspring derived from natural reproduction, data on the effects of AMA on offspring cardiometabolic health during post-natal development are not available. Given the increasing use of ART to alleviate infertility in women of AMA, it is pivotal to develop ART-AMA models addressing the effects of maternal aging on offspring health. STUDY DESIGN, SIZE, DURATION: Blastocysts from old (34-39 weeks) or young (8-9 weeks) C57BL/6 females mated with young CBA males (13-15 weeks) were either subjected to differential cell staining (inner cell mass and trophectoderm) or underwent embryo transfer (ET) into young MF1 surrogates (8-9 weeks) to produce young (Young-ET, 9 litters) and old (Old-ET, 10 litters) embryo-derived offspring. Offspring health monitoring was carried out for 30 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: All animals were fed with standard chow. Blood pressure was measured at post-natal Weeks 9, 15 and 21, and at post-natal Week 30 a glucose tolerance test (GTT) was performed. Two days after the GTT mice were killed for organ allometry. Blastocyst cell allocation variables were evaluated by T-test and developmental data were analysed with a multilevel random effects regression model. MAIN RESULTS AND THE ROLE OF CHANCE: The total number of cells in blastocysts from aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean ± SEM: 34.5 ± 2.1 versus 29.6 ± 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 ± 0.8 versus 33.4 ± 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9-15 in males (Week 9: 108.5 ± 3.13 versus 100.8 ± 1.5 mmHg, Week 15: 112.9 ± 3.2 versus 103.4 ± 2.1 mmHg) and Week 15 in females (115.9 ± 3.7 versus 102.8 ± 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 ± 0.4 versus 17.8 ± 1.16 mmol/l) and their spleen weight (88.2 ± 2.6 ± 105.1 ± 4.6 mg) and several organ:body weight ratios (g/g × 10(3)) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 ± 0.06 versus 4.4 ± 0.08), lungs (4.4 ± 0.1 versus 5.0 ± 0.1), spleen (2.4 ± 0.06 versus 3.2 ± 0.1) and liver (36.4 ± 0.6 versus 39.1 ± 0.9). LIMITATIONS, REASONS FOR CAUTION: Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans). WIDER IMPLICATIONS OF THE FINDINGS: Our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for women of AMA undergoing assisted reproduction, including surrogacy programmes. STUDY FUNDING/COMPETING INTERESTS: This work was supported through the European Union FP7-CP-FP Epihealth programme (278418) to T.P.F. and the BBSRC (BB/F007450/1) to T.P.F. The authors have no conflicts of interest to declare.


Assuntos
Blastocisto/fisiologia , Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Idade Materna , Técnicas de Reprodução Assistida , Fatores Etários , Animais , Feminino , Teste de Tolerância a Glucose , Masculino , Camundongos
4.
Porcine Health Manag ; 9(1): 3, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36721224

RESUMO

BACKGROUND: This study explores the possibility of using infrared thermography to estimate the onset of parturition in sows. Infrared camera (IRC) and infrared laser thermometer (IRT) were used to obtain the auricular skin temperature of sows along with rectal temperatures, from approximately one week before the anticipated farrowing until 24 h post-partum. Three commercial piglet producing farms were included in the study. RESULTS: There were large variations in observed auricular skin temperature, both by IRC and IRT per time point. Graphical exploration of the observed auricular skin temperature measured by the two methods showed the same parallel patterns, although temperatures measured by IRC were higher at any time point compared to IRT. Auricular skin thermography revealed a clear increase in temperatures before farrowing. Statistical analyses, adjusting for differences between farms, sow activity and respiration rate, confirmed this increase. When controlling for these variables, and comparing the baseline temperatures to temperatures at farrowing, the difference was 3.9 and 4.1 °C measured with IRT and IRC, respectively. The greatest increase, of more than 2 °C, was found between 16 and 8 h and 8 to 4 h before farrowing. Rectal temperature increased by 0.5 °C in the same time interval and reached a temperature peak after farrowing. CONCLUSION: Sows showed a more than 2 °C increase in auricular skin temperature, measured by either IRC or IRT, 8 to16 hours before the first piglet was born. Hence, monitoring auricular skin temperatures of sows using infrared thermography one week before expected farrowing may provide a baseline temperature for each sow from which a sudden rise is indicative of parturition in the following 8 to 16 h. This may lead to more efficient allocation of human assistance during farrowing time and thereby improve farrowing management and the welfare of sows and their offspring.

5.
Reproduction ; 141(1): 91-103, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20926690

RESUMO

The hypothesis that high concentrations of IGF1 can impair embryo development was investigated in a bovine in vitro model to reflect conditions in polycystic ovary syndrome (PCOS) patients. Embryos were either cultured in the absence or presence of a physiological (100  ng/ml) or supraphysiological (1000  ng/ml) IGF1 concentration. Cell allocation, apoptosis, transcript and protein expression of selected genes involved in apoptosis, glucose metabolism and the IGF system were analysed. Supraphysiological IGF1 concentration did not improve blastocyst formation over controls, but induced higher levels of apoptosis, decreased TP53 protein expression in the trophectoderm and increased the number of cells in the inner cell mass (ICM). The increase in ICM cells corresponded with an increase in IGF1 receptor (IGF1R) protein in the ICM. A small, but significant, percentage of blastocysts displayed a hypertrophic ICM, not observed in controls and virtually absent in embryos treated with physiological concentrations of IGF1. Physiological IGF1 concentrations increased total IGF1R protein expression and upregulated IGFBP3 transcripts leading to an increase in blastocyst formation with no effects on cell number or apoptosis. In conclusion, the results support the hypothesis of detrimental effects of supraphysiological IGF1 concentrations on early pregnancy. However, our results do not support the premise that increased apoptosis associated with high levels of IGF1 is mediated via downregulation of the IGF1R as previously found in preimplantation mouse embryos. This in vitro system with the bovine preimplantation embryo reflects critical features of fertility in PCOS patients and could thus serve as a useful model for in-depth mechanistic studies.


Assuntos
Apoptose , Blastocisto/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptor IGF Tipo 1/metabolismo , Animais , Apoptose/genética , Blastocisto/patologia , Massa Celular Interna do Blastocisto/metabolismo , Massa Celular Interna do Blastocisto/patologia , Bovinos , Técnicas de Cultura Embrionária , Metabolismo Energético/genética , Feminino , Fertilização in vitro , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento , Glucose/metabolismo , Humanos , Hipertrofia , Marcação In Situ das Extremidades Cortadas , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , RNA Mensageiro/metabolismo , Receptor IGF Tipo 1/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Reproduction ; 137(2): 161-80, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19029343

RESUMO

IGF1 plays an important role in bovine follicular growth, acquisition of oocyte competence and embryo viability. Current data also indicate a critical role for IGF1 in both the ovarian response and the embryo yield following the superovulatory treatments. IGF1 can have either positive or negative effects on embryo viability which is related to the concentration of IGF1 induced by superovulation treatment. These effects impact either on oocyte competence or directly on the embryo. Concentrations in the physiological range appear to result in the production of higher quality embryos, mainly due to the mitogenic and the anti-apoptotic activities of IGF1. However, high superovulatory responses are associated with decreased embryo viability and a concomitant increase in apoptosis. Studies in mice suggest that this increase in apoptosis is related to the downregulation of the IGF1 receptor in the embryo associated with high IGF1 concentrations. Strategies capable of controlling the IGF1 concentrations could be one approach to improve superovulation responses. A range of possible approaches for research within the IGF system in gonadotrophin-stimulated cattle is discussed in this review, including the possible use of superovulated female cattle as an alternative animal experimental model for research on reproductive disorders in humans associated with abnormal IGF1 concentrations.


Assuntos
Embrião de Mamíferos/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Superovulação/fisiologia , Animais , Apoptose/fisiologia , Blastocisto/fisiologia , Bovinos , Embrião de Mamíferos/metabolismo , Feminino , Mitose/fisiologia , Folículo Ovariano/fisiologia , Gravidez
7.
Domest Anim Endocrinol ; 35(4): 325-42, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18703307

RESUMO

Insulin-like growth factor-I (IGF-I) plays a pivotal role in cattle fertility, acting as a monitoring signal that allows reproductive events to occur when nutritional conditions for successful reproduction are reached. However, endocrine IGF-I is not a predictor of reproductive events, but rather an indirect estimator of the suitability of the animal to achieve the reproductive event in question. Although measuring circulating IGF-I concentrations might not have any clinical application in the cattle industry, endocrine IGF-I screening will continue to be important for the study of interactions between nutrition and reproduction. In addition, endocrine IGF-I screening could be used as an ancillary test for the selection of cattle for high reproductive potential, especially in herds of high genetic merit for milk production, in which a decline in fertility has been identified.


Assuntos
Bovinos/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Reprodução/fisiologia , Animais , Sistema Endócrino/fisiologia , Ciclo Estral/fisiologia , Feminino , Período Pós-Parto/fisiologia , Gravidez , Maturidade Sexual/fisiologia
8.
Animal ; 12(s2): s363-s371, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30139395

RESUMO

Epidemiological studies in humans and animal models (including ruminants and horses) have highlighted the critical role of nutrition on developmental programming. Indeed, it has been demonstrated that the nutritional environment during the periconceptional period and foetal development can altered the postnatal performance of the resultant offspring. This nutritional programming can be exerted by maternal and paternal lineages and can affect offspring beyond the F1 generation. Alterations in epigenetic mechanisms have been proposed as the causative link behind the programming trajectories observed in the offspring. Although a clear cause-effect relationship between epigenetic modifications during early development and later offspring phenotype has not been demonstrated in livestock species, strong associations have been reported for some epigenetic marks (e.g. messenger RNA) that are worth exploring as possible predictors of future offspring phenotype. In this review, we shortly describe the main epigenetic mechanisms studied so far in mammals (i.e. mainly in the mouse) thought to be associated with developmental programming, and discuss the few studies available in mammalian herbivores (e.g. cattle) showing the effect of nutrition on epigenetic marks and the associated phenotype. Clearly, there is a need to develop research on nutritional strategies capable of modulating the epigenetic machinery with positive influence on the phenotype of livestock herbivores. This type of research is needed to alleviate the challenges currently faced by the livestock industry (e.g. impaired fertility of high-yielding dairy cows). This in turn will have a positive influence on animal welfare and productivity of livestock enterprises.


Assuntos
Epigênese Genética , Mamíferos/genética , Estado Nutricional , Animais , Bovinos , Feminino , Desenvolvimento Fetal , Herbivoria , Gado , Mamíferos/embriologia , Mamíferos/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Fenótipo , Gravidez , Ruminantes
9.
Eur J Pharm Sci ; 102: 35-45, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28188909

RESUMO

Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity.


Assuntos
Antirreumáticos , Medicamentos Biossimilares , Infliximab , Animais , Antirreumáticos/farmacocinética , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite/tratamento farmacológico , Artrite/metabolismo , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/farmacologia , Medicamentos Biossimilares/uso terapêutico , Células CHO , Células Cultivadas , Cricetulus , Citocinas/genética , Citocinas/metabolismo , Selectina E/metabolismo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Infliximab/farmacocinética , Infliximab/farmacologia , Infliximab/uso terapêutico , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Molécula 1 de Adesão de Célula Vascular/metabolismo
10.
Theriogenology ; 64(9): 1977-94, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15936811

RESUMO

The objective was to determine if a single measurement of plasma insulin-like growth factor-1 (IGF-1) could predict the number of viable embryos obtained from donors and the likelihood of pregnancy in recipients in multiple ovulation and embryo transfer (MOET) programs in cattle. The embryo yields from 101 embryo recoveries were examined in maiden Holstein heifers (n=75) and multiparous Holstein cows (lactating cows n=20, dry cows n=6). Donors were super stimulated with FSH and embryo recovery was done non-surgically 7 days after artificial insemination. Embryos were classified according to the IETS criteria. Pregnancy rates in 100 maiden Holstein heifer recipients were analysed. Recipients were on day 7+/-1 of the estrous cycle at transfer. Pregnancy diagnosis was carried out at day 30 (PD 30) and rechecked at day 60 (PD 60) after transfer. Blood samples from coccygeal vessels taken at the time of embryo recovery (donors) and transfer (recipients) were analysed for IGF-1, insulin, beta-hydroxybutyrate (beta-OHB), non-esterified fatty acids (NEFA), urea and cholesterol. There was a negative correlation between the number of viable embryos and insulin (r=-0.33, P=0.025) in donor heifers. In donor cows, the number of viable embryos was correlated with IGF-1 (r=0.43, P=0.028) and cholesterol (r=-0.43, P=0.027). In recipients, PD30 and PD 60 were not affected by any of the circulating parameters analysed. Insulin, IGF-1 and cholesterol only explained 8.9, 13.9 and 15.8% of the variation in the production of viable embryos, respectively. Several factors affect MOET programs and under the circumstances of the present study the usefulness of hormonal and metabolic profiles as predictors of the outcome of this biotechnology was limited.


Assuntos
Biomarcadores/sangue , Bovinos/fisiologia , Transferência Embrionária/veterinária , Embrião de Mamíferos , Fator de Crescimento Insulin-Like I/análise , Indução da Ovulação/veterinária , Ácido 3-Hidroxibutírico/sangue , Animais , Colesterol/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Hormônio Foliculoestimulante/administração & dosagem , Inseminação Artificial/veterinária , Insulina/sangue , Ovulação , Gravidez , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/veterinária , Ureia/sangue
11.
Actas Urol Esp ; 29(9): 905-8, 2005 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-16353779

RESUMO

Intratesticular epidermoid cysts are rare tumours that constitute one percent of all testicular masses. They are bening lesions that make differential diagnosis from malignant testicular tumours difficult. The absence of serum markers elevation and ultrasound imaging could support these lesions being bening epidermoid cysts, and in that case, conservative surgery is adequate. We present the case of a 22 years old patient who complains of a left testicular mass. In this case ultrasound diagnosis was non-specific and a left radical inguinal orchiectomy was performed.


Assuntos
Cisto Epidérmico/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Adulto , Humanos , Masculino , Cuidados Pré-Operatórios , Ultrassonografia
12.
Domest Anim Endocrinol ; 51: 27-45, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25498236

RESUMO

During episodes of undernutrition and overnutrition the mammalian preimplantation embryo undergoes molecular and metabolic adaptations to cope with nutrient deficits or excesses. Maternal adaptations also take place to keep a nutritional microenvironment favorable for oocyte development and embryo formation. This maternal-embryo communication takes place via several nutritional mediators. Although adaptive responses to malnutrition by both the mother and the embryo may ensure blastocyst formation, the resultant quality of the embryo can be compromised, leading to early pregnancy failure. Still, studies have shown that, although early embryonic mortality can be induced during malnutrition, the preimplantation embryo possesses an enormous plasticity that allows it to implant and achieve a full-term pregnancy under nutritional stress, even in extreme cases of malnutrition. This developmental strategy, however, may come with a price, as shown by the adverse developmental programming induced by even subtle nutritional challenges exerted exclusively during folliculogenesis and the preimplantation period, resulting in offspring with a higher risk of developing deleterious phenotypes in adulthood. Overall, current evidence indicates that malnutrition during the periconceptional period can induce cellular and molecular alterations in preimplantation embryos with repercussions for fertility and postnatal health.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Desenvolvimento Embrionário/fisiologia , Fertilização/fisiologia , Desnutrição/veterinária , Complicações na Gravidez/veterinária , Adaptação Fisiológica , Animais , Bovinos , Doenças dos Bovinos/fisiopatologia , Feminino , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Desnutrição/complicações , Desnutrição/fisiopatologia , Fenômenos Fisiológicos da Nutrição Materna , Folículo Ovariano/crescimento & desenvolvimento , Hipernutrição/fisiopatologia , Hipernutrição/veterinária , Gravidez , Complicações na Gravidez/fisiopatologia
13.
J Dev Orig Health Dis ; 6(5): 377-83, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25952250

RESUMO

The early embryo and periconceptional period is a window during which environmental factors may cause permanent change in the pattern and characteristics of development leading to risk of adult onset disease. This has now been demonstrated across small and large animal models and also in the human. Most evidence of periconceptional 'programming' has emerged from maternal nutritional models but also other in vivo and in vitro conditions including assisted reproductive treatments, show consistent outcomes. This short review first reports on the range of environmental in vivo and in vitro periconceptional models and resulting long-term outcomes. Second, it uses the rodent maternal low protein diet model restricted to the preimplantation period and considers the stepwise maternal-embryonic dialogue that comprises the induction of programming. This dialogue leads to cellular and epigenetic responses by the embryo, mainly identified in the extra-embryonic cell lineages, and underpins an apparently permanent change in the growth trajectory during pregnancy and associates with increased cardiometabolic and behavioural disease in adulthood. We recognize the important advice of David Barker some years ago to investigate the sensitivity of the early embryo to developmental programming, an insight for which we are grateful.


Assuntos
Embrião de Mamíferos/citologia , Embrião de Mamíferos/fisiologia , Epigenômica , Fenômenos Fisiológicos da Nutrição Materna , Adulto , Animais , Feminino , Humanos , Gravidez
14.
Lung Cancer ; 34(2): 185-94, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11679177

RESUMO

Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.


Assuntos
Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Ciclina D1/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Umbeliferonas/farmacologia , Biotransformação , Divisão Celular , Relação Dose-Resposta a Droga , Humanos , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
15.
Actas Urol Esp ; 24(10): 840-2, 2000.
Artigo em Espanhol | MEDLINE | ID: mdl-11199305

RESUMO

We present a 41 years old male, treated with trazodone because of depression. He was seen at our Andrology unit for a 72 hours evolutioned priapism. We review the literature and submit this paper for publication because it is an uncommon pathology.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Priapismo/induzido quimicamente , Trazodona/efeitos adversos , Adulto , Humanos , Masculino
16.
Actas Urol Esp ; 24(10): 836-9, 2000.
Artigo em Espanhol | MEDLINE | ID: mdl-11199304

RESUMO

Prostatic carcinoma may be diagnosed by the clinic manifestations or by the symptoms for locoregional disemination and distance metastasis. The lymphatic system is the first metastatic station, which is affected in a high percentage of cases. Event it may simulate lymphoproliferatives process and it si uncommon the lymphatic macroaffectation at first. In theses cases, the histologic and immunohistochemical study by the determination of prostatic specific antigen in lymph nodes can provice the diagnosis. Treatment of these tumors is palliative with hormonotherapy. Prognosis is bad with a low survival at five years.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Próstata/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade
17.
Actas Urol Esp ; 24(9): 715-20, 2000 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-11132442

RESUMO

OBJECTIVE: To evaluate the usefulness of the NMP-22 test in the diagnosis of bladder cancer; to calculate the ideal cutoff and to compare the results among NMP-22, voided urine cytology and cystoscopy. MATERIAL AND METHODS: 166 patients having clinical suspicious of bladder cancer or in follow-up due to a previous one. The exclusions criteria were: other urological conditions, radiotherapy in the last three months, systemic chemotherapy in the last month, recent vesical trauma or indwelling catheter. Prior cystoscopy a recent voided urinary sample was sent to the pathology and biochemistry laboratory to perform cytology and NMP-22. A TUR was performed in patients with bladder tumour. The cutoff was calculated with ROC curves. For each test we calculate sensitivity, specificity, positive and negative predictive value. We use the McNemar test to compare the results, all of which are expressed with a confidence interval of 95%. RESULTS: The ideal cutoff was 6 U/ml. We have a global sensitivity of 82.75% for NMP-22 and 67.9 for cytology (p = 0.0118); the specificity was 80% and 94.12% respectively (p = 0.0018). By grade the sensitivity was 72.22% G1, 70.97% G2 and 100% G3 for NMP-22 and 44.44%, 58.06% and 90.62% for cytology. By stage it was 68.42% Ta, 83.33% T1 and 100 T2 or more for NMP-22 and 36.84%, 75% and 85.71% for cytology. With the cystoscopy we obtained a 100% sensitivity and 89.41% specificity. CONCLUSIONS: The NMP-22 is a useful test for the diagnosis of bladder cancer; is more sensitive and less specific than cytology. We think it can replace the cytology in the diagnosis and follow-up of bladder cancer. The ideal cutoff is 6 U/ml.


Assuntos
Biomarcadores Tumorais/urina , Proteínas Nucleares/urina , Neoplasias da Bexiga Urinária/urina , Idoso , Área Sob a Curva , Reações Falso-Positivas , Humanos , Sensibilidade e Especificidade
18.
Actas Urol Esp ; 28(1): 7-12, 2004 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-15046474

RESUMO

OBJECTIVE: To evaluate diagnostic techniques, treatment and follow-up in 94 patients affected of upper urinary tract tumor. PATIENTS AND METHOD: From 1978 to december 2002 we operated 105 patients due to upper urinary tract tumor, although only 94 are valid for analysis. Mean age was 65 years and 85% were man. Haematuria was the most frequent symptom. RESULTS: Urography (93%), ecography (77%) and CT (67%) were the most used diagnostic techniques. Pelvic tumor was the most frequent (71%) and total nephroureterectomy including bladder cuff the chosen treatment (76.4%). Previous or simultaneous bladder tumor was observed in 23% cases and delayed in 30%. With a mean follow-up of 76 months the patient survival is 53%. CONCLUSIONS: Due to the high frequence of previous, simultaneous or delayed bladder tumors, the upper urinary tract tumor should be considered as a panurothelial disease, worsening the outcome of this kind of tumors.


Assuntos
Neoplasias Renais , Neoplasias Ureterais , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/terapia
19.
Actas Urol Esp ; 23(5): 417-23, 1999 May.
Artigo em Espanhol | MEDLINE | ID: mdl-10427816

RESUMO

OBJECTIVES: To analyze our results in the surgery of the stress urinary incontinence in women with the Raz's techniques, to assess the association among continence and factors like surgical technique, grade of incontinence and urethral pressure profile. MATERIAL AND METHODS: We do a retrospective study of 88 operations in 81 patients between the first of January 1990 and the thirty-one of December 1998. We describe the patients, previous treatments, grade of incontinence ans urodynamics data. We analyze the pre and post-operative complications. The outcome is evaluated by the Kaplan-Meier method, and the results are compared by the log rank test. RESULTS: 11 patients had a previous surgery and 7 had done physiotherapy; the grade of incontinence was 1 in 7 patients, 2 in 56 and 3 in 18. There were neither significative difference between UPP and abdominal leak point pressure and grade of incontinence nor between those parameters and continence. We did the Raz 1 technique in 67 patients, Raz 2 in 3, Raz 3 in 18. There were no significant difference among them. There are a progressive loose in the continence rate along the two first years; after that the continence rates are stabilized about 75%. The complications rate was scarce, except for the postoperative urinary retention, that reached the 20.45%. CONCLUSIONS: Our results are similar to those cited in the bibliography, mainly in the Spanish one. The highest rate of failure is in the two first years.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/métodos , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Humanos , Complicações Intraoperatórias/epidemiologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Incontinência Urinária por Estresse/fisiopatologia , Urodinâmica
20.
Actas Urol Esp ; 24(8): 685-8, 2000 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-11103511

RESUMO

The schwannoma is a tumor resulting from the Schwann cells of neural shwath, being its retroperitoneal localization quite unusual. This tumor is clinically unspecified and in most of the cases it originates symptoms coming from the compression of the close structures when its localization is retroperitoneal. Its diagnosis is quite often fortuitous being confirmed by anatomopathological study afterwards. The treatment is surgical radical exeresis with subsequent followup. We report a new case of this uncommon retroperitoneal pathology in a female patient showing a nonspecific clinic. Two years after the surgery she remains asymptomatic without any radiological evidence of recidive.


Assuntos
Neurilemoma/patologia , Neoplasias Retroperitoneais/patologia , Adulto , Feminino , Humanos
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