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Summary: Background. Evidence regarding drug provocation test (DPT) with chemotherapeutic agents is scarce. The aim of our study is to describe the experience of DPT in patients with a history of hypersensitivity reactions (HSRs) to antineoplastic and biological agents. Methods. This was an eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemotherapy who were submitted to DPT. Anamnesis, skin tests (ST) and DPT were analyzed. Patients with a negative DPT were submitted to at least one regular supervised administration (RSA). Patients with positive DPT or HSR during RSA were offered rapid drug desensitization (RDD). Results. A total of 54 patients were submitted to DPT. The most common suspected drugs were platins (n = 36), followed by taxanes (n = 11). Most initial reactions were classified as grade II (n = 39) according to Brown's grading system. ST with platinum (n = 35), taxanes (n = 10) and biological agents (n = 4) were negative, except for one intradermal test with paclitaxel, which was positive. A total of 64 DPTs were performed. Eleven percent of all DPTs were positive (platins (n = 6), doxorubicin (n = 1)). Of the 57 RSA with the culprit drugs, 2 were positive (platins). The diagnosis of hypersensitivity was confirmed by DPT/RSA in 9 patients. All patients with positive DPT/RSA presented HSRs of equal or less severity than the initial one. Conclusions. DPT followed by RSA allowed to exclude HSRs in 45 patients (55 culprit drugs). DPT before desensitization prevents non-hypersensitivity patients from undergoing RDD. In our study DPT was safe, all reactions were managed by an allergist.
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Objetivou-se testar a vitrificação de ovários de camundongos do ICTB/Fiocruz. Inicialmente, fez-se coleta e maturação in vitro dos oócitos de ovários a fresco e vitrificados, bem como avaliação de estruturas no cultivo embrionário, pós-fertilização in vitro. Fêmeas B6D2F1 foram eutanasiadas para remoção dos ovários (n=60) e divididas em três grupos: grupo 1 (n=30 animais) - oócito de ovários vitrificados, maturados e fertilizados in vitro (120 fragmentos); grupo 2 (n=15) (controle 1) - oócitos coletados a fresco, maturados e fertilizados in vitro; e grupo 3 (n=15) (controle 2) - oócitos maturados in vivo e fertilizados in vitro. A técnica foi verificada no desenvolvimento embrionário in vitro, que foi avaliado pelo teste de qui-quadrado (BioStat 5.0). Recuperaram-se 123, 224 e 328 oócitos nos G1, G2 e G3, respectivamente. Observaram-se diferenças significativas nas taxas de clivagem às 24 horas (embriões ≥ 2 células) entre G1 (8%) e G2 (32%) (P<0,1) e G1 e G3 (49%) (P<0,05), mas não entre G2 e G3 (P>0,05). Para blastocistos, às 96 horas, os grupos G1, G2 e G3 apresentaram, respectivamente, 6%, 11% e 46%, diferindo significativamente entre eles (P<0,05). A vitrificação de ovários, a maturação oocitária e a fertilização in vitro são alternativas para a produção de embriões de camundongos in vitro.(AU)
This work aimed test ovarian vitrification of hybrid mouse from ICTB/Fiocruz. Protocol collection and oocyte in vitro maturation from fresh and vitrified ovaries was established and embryos were evaluated after fertilization. B6D2F1 females were euthanized for ovarian removal (n= 60) and divided into 3 groups: G1 (n= 30) - ovaries fragmented (n= 120), vitrified, matured and fertilized; G2 (n= 15) - in vitro fertilization of oocytes matured in vitro from fresh ovaries; G3 (n= 15) - ampulla region oocytes in vitro fertilizated. Viability was verified by thawing, oocyte in vitro maturation and fertilization. In vitro embryo development of each group was evaluated by Chi-square test (BioStat 5.0). 123, 224 and 328 oocytes were recovered from G1, G2 and G3, respectively. Significant differences were observed in cleavage rates at 24 hours (embryos with 2 cells or more) between G1 (8%) and G2 (32%) (P< 0.1) and G1 and G3 (49%) (P< 0.05) but not between G2 and G3 (P> 0.05). Blastocysts at 96 hours presented 6%, 11% and 46%, respectively for G1, G2 and G3, differing significantly (P< 0.05). Ovary vitrification, oocyte in vitro maturation and in vitro fertilization were available for the production of in vitro mouse embryos.(AU)
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Animales , Femenino , Ratones , Ovario , Desarrollo Embrionario , Vitrificación , Fertilización In Vitro , Técnicas de Maduración In Vitro de los Oocitos/veterinariaRESUMEN
Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)
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Humanos , Enfermedades Cardiovasculares/prevención & control , Evaluación Nutricional , Nutrición, Alimentación y DietaRESUMEN
BACKGROUND: Aerobic training (AT) decreases airway inflammation in asthma, but the underlying cellular and molecular mechanisms are not completely understood. Thus, this study evaluated the participation of SOCS-JAK-STAT signaling in the effects of AT on airway inflammation, remodeling and hyperresponsiveness in a model of allergic airway inflammation. METHODS: C57Bl/6 mice were divided into Control (Co), Exercise (Ex), HDM (HDM), and HDM+Exercise (HDM+ Ex). Dermatophagoides pteronyssinus (100ug/mouse) were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49. AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52. RESULTS: AT inhibited HDM-induced total cells (p<0.001), eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in BAL, and eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (p<0.001), IL-5 (p<0.001), IL-13 (p<0.001), CXCL1 (p<0.01), IL-17 (p<0.01), IL-23 (p<0.05), IL-33 (p<0.05), while increased IL- 10 (p<0.05). Airway collagen fibers (p<0.01), elastic fibers p<0.01) and mucin (p<0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6,25mg/ml (p<0.01), 12,5mg/mL (p<0.01), 25mg/mL (p<0.01) and 50mg/mL (p<0.01). Mechanistically, AT reduced the expression of STAT6 (p<0.05), STAT3 (p<0.001), STAT5 (p<0.01) and JAK2 (p<0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (p<0.001) was upregulated in leukocytes and in epithelial cells, SOCS2 (p<0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (p<0.05) and in epithelial cells (p<0.001). CONCLUSIONS: AT reduces asthma phenotype involving SOCSJAK- STAT signaling.
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Asma/metabolismo , Quinasas Janus/metabolismo , Condicionamiento Físico Animal , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Animales , Modelos Animales de Enfermedad , Eosinófilos/citología , Interleucinas/metabolismo , Linfocitos/citología , Cloruro de Metacolina , Ratones , Ratones Endogámicos C57BL , Neutrófilos/citología , Hipersensibilidad Respiratoria/metabolismoRESUMEN
Phenomenon of mosaic expression at cellular level is widely presented in tissues and organs of transgenic animals. The communication is concerned a study of the mosaics in transgenic mice carrying the lacZ reporter-gene under control of the bovine and goat alpha-S1-casein genes with 5'-flanked sequences of various ex-tent: pCLZ1--721bp, pCLZ2-- 2001 bp and pCLZ3 3409 bp constructs. Five transgenic founders were generated by injection of the recombinant DNA into zygotes: pCLZ 1 - N 16, pCLZ2 - N 37 and pCLZ3 N 7, N 36, and N 48. Positive for J3-galactosidase activity cells were detected in lactating mammary glands of all transgenic females, however, distribution of the positive cells was variable. We observed two types of mosaics: clonal or "lobule" type with positive cells filling the whole of the globule or stochastic type with single positive cells scattered over one or different lobules. Two types of mosaics were characteristic of all the transgenic animals, although, females carrying the pCLZ2 transgene showed "lobule" type more often than transgenic animals with the transgenes pCLZ and pCLZ3. It is suggested that the stochastic type of mosaics occurs in the cells at terminal stage of differentiation, whereas the <
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Caseínas/genética , Genes Reporteros , Mosaicismo , Transgenes , beta-Galactosidasa/genética , Animales , Bovinos , Proteínas de Escherichia coli/genética , Femenino , Expresión Génica , Cabras , Glándulas Mamarias Animales/metabolismo , Ratones , Ratones Transgénicos , Glándulas Salivales/metabolismoRESUMEN
Estudou-se o efeito da concentração espermática e período de incubação e da interação dessas características sobre a fecundação in vitro (FIV) usando-se sêmen de touros Guzerá. Oócitos (n=1146) maturados in vitro foram divididos em tratamentos objetivando a FIV, em esquema fatorial 3×2×2 (três touros - A, B e C, duas concentrações espermáticas - 2 e 4×10(6) espermatozóides/ml e dois tempos de incubação 12 e 18 horas). Utilizaram-se espermatozóides viáveis obtidos por swin-up. A FIV foi realizada em meio fert-talp com heparina, em incubadora com 5 por cento de CO2 e 95 por cento de umidade, a 38,5°C. Após incubação, 50 por cento dos oócitos foram fixados e corados para determinação das taxas de penetração, fecundação monoespermática e poliespermia. O restante foi co-cultivado com células da granulosa em meio CR2aa por oito dias, avaliando-se a taxa de clivagem e a produção de blastocisto. Houve maior taxa de penetração (P<0,05) na concentração de 4×10(6) espermatozóides/ml por 18 horas (64 por cento), e não se observou diferença (P>0,05) entre os demais tratamentos. A taxa de poliespermia foi maior (P<0,05) na concentração espermática de 4×10(6), independente do tempo de incubação. Na concentração espermática mais alta, a taxa de poliespermia foi maior no tempo de incubação de 18 horas (P<0,05). O touro A apresentou menor (P<0,05) taxa de poliespermia em relação aos demais. Ainda, no touro A a taxa de clivagem foi maior (P<0,05) que no touro B, enquanto o C mostrou-se semelhante tanto ao A quanto ao B. O tempo de incubação, a concentração espermática e a interação das variáveis influenciaram as taxas de penetração e poliespermia, sem interferir na taxa de fecundação monoespermática e na produção de blastocistos.
The effects of sperm concentration, incubation period and their interaction on in vitro fertilization (IVF) using sperm of Guzera bulls were evaluated. In vitro matured oocytes (n=1146) were allotted to IVF treatments in a factorial scheme 3×2×2 - three bulls (A, B and C), two sperm concentrations (2 and 4×10(6) spermatozoa/ml) and two incubation periods (12 and 18h). Viable spermatozoa were obtained by swim-up. The IVF was performed using in Fert-Talp medium with heparin, on incubator with 5 percent CO2 and 95 percent humidity, at 38.5°C. After the incubation, 50 percent of oocytes were fixed and stained to determine penetration, monospermic fecundation and polyspermy rates. The remainder was co-cultured with granulosa cells in CR2 medium for eight days to evaluate cleavage and embryo production rates. The penetration rate was higher (P<0.05) for sperm concentration of 4×10(6) spermatozoa/ml incubated for 18 hours (64 percent), and no differences (P>0.05) among remainder treatments were observed. The polyspermic rate (P<0.05) was higher for higher sperm concentration and incubation period. Bull A showed the lowest (P<0.05) polyspermy rate. Bulls A and C showed higher (P<0.05) cleavage than bull B. Incubation period, sperm concentration, and interaction of these two factors influenced penetration and polyspermy rates, without any effect on monospermic fecundation rates and embryos production.
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Bovinos , Estructuras Embrionarias/metabolismo , Fertilización In Vitro/métodos , Oocitos/crecimiento & desarrollo , Semen/metabolismoRESUMEN
Two constructs were devised, containing the full-length gene of the human granulocyte colony-stimulating factor (G-CSF) fused with the 5' and 3' flanking promoter sequences of bovine alpha-S1-casein gene. Both constructs contained a 1518-bp fragment that included exons 18 and 19 and 320 bp of the 3' flanking region of bovine gene @CSN1S1, but differed in size of the 5' flanking sequences, which were of 721 bp, and exon 1 in construct pGCm1 and 2001 bp and exon 1 and intron 1 in construct pGCm2. With both constructs, transgenic mice were produced. The transgene expression was assessed using RT-PCR and immunochemically from the production of human G-CSF in milk of lactating females. Secretion of human G-CSF into the milk varied in a wide range, from 0.8 microg/ml to over 1 mg/ml, in mice with construct pGCml and was low (up to 60 microg/ml) or absent in mice with construct pGCm2. G-CSF glycosylation was incomplete in mice with transgene pGCml and complete in mice with pGCm2. G-CSF of transgenic mouse milk was shown to stimulate the formation and growth of granulocyte-containing colonies in human umbilical blood cell culture and be close or identical in physiological activity to the natural human G-CSF.
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Expresión Génica , Factor Estimulante de Colonias de Granulocitos/metabolismo , Lactancia/fisiología , Modificación Traduccional de las Proteínas/genética , Transgenes/fisiología , Animales , Bovinos , Células Cultivadas , Femenino , Sangre Fetal/citología , Sangre Fetal/fisiología , Glicosilación , Factor Estimulante de Colonias de Granulocitos/genética , Factor Estimulante de Colonias de Granulocitos/farmacología , Humanos , Ratones , Ratones Transgénicos , Células Progenitoras Mieloides/citología , Células Progenitoras Mieloides/fisiología , Proteínas RecombinantesRESUMEN
The present work has been prepared having as its source a renewed reading of the Editorials from REBEn written in the years of 1970 to 1980. To the intention of plucking from in-between lines motivations, attitudes, values, beliefs, inclinations, ideologies, and principles, not always so clearly seen when the product of a reading destituted from the systematic effort of method, we have coupled the option of contents analysis considered to be an aggregate of techniques. Methodology encompassed three stages in the analysis work: preanalysis, analytical description, and inferential interpretation. Expected results included moving beyond the manifest contents, and gave rise to the visualization of latent contents. Such an inferential dimension allowed to recognize how bright or "golden" (Dourados) these Editorials are, above all because they irradiate real values, in addition to the formal ones. These interpretations have not discharged the use of the subjective dimension when establishing the relation between the Golden of the Editorial's author and what issues from the ensemble of the analyzed Editorial production.