RESUMO
OBJECTIVE: To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants. METHODS: Placenta and membranes were collected from preterm deliveries (<37 weeks gestational age) and evaluated for histological chorioamnionitis (HCA). Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique. RESULTS: Ninety-five infants (43 males) born prematurely (median gestational age 34.2 weeks) were recruited. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored HCA Grade 1, and 11(12%) HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (pâ=â0.012 for FEF50, pâ=â0.014 for FEF25-75 and pâ=â0.32 for FEV0.5). Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25-75 and p<0.05 for FEV0.5). Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males. CONCLUSIONS: Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease.
Assuntos
Corioamnionite/fisiopatologia , Recém-Nascido Prematuro/fisiologia , Pulmão/fisiopatologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Gravidez , Ventilação Pulmonar , Caracteres SexuaisRESUMO
Hemorrhagic cystitis (HC) is a common side effect observed in patients under chemotherapy with cyclophosphamide (CYP). The urotoxic side effects of CYP are attributed to the metabolic compound acrolein, and can be partially prevented by the uroprotector agent 2-mercaptoethene sulfate (Mesna). The present study analyzed the anti-inflammatory and the antinociceptive effects of compounds MV8608 and MV8612 obtained from Mandevilla velutina in the rat model of CYP-induced HC. Male Wistar rats were used (six to eight per group, 220-250 g). HC was induced by a single administration of CYP (100 mg/kg, ip). Three behavioral parameters--breathing rate, closing of the eyes, and specific posture--were used as nociception indexes, and scored at different time intervals (15-180 min) after cystitis induction. As inflammatory parameters, hemorrhage presence, edema formation, and bladder weight were determined at 24 h after CYP administration. The neutrophil migration was assessed by means of myeloperoxidase (MPO activity), 4 h after cystitis induction. As expected, Mesna treatment was able to reduce in a significant manner all the inflammatory and the nociceptive parameters induced by CYP. Of note, the administration of MV8608 significantly inhibited the hemorrhage formation and the neutrophil recruitment, while the MV8612 treatment markedly reduced the bladder weight, without interfering with neutrophil influx. Interestingly, the treatment with either MV8608 or MV8612 markedly reduced the nociceptive responses. The present results clearly indicate that MV8608 and MV8612 might represent important alternatives to prevent side effects, especially the nociception, following chemotherapy with CYP.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Apocynaceae/química , Ciclofosfamida/efeitos adversos , Cistite/prevenção & controle , Glicosídeos/uso terapêutico , Hemorragia/prevenção & controle , Esteroides/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Cistite/induzido quimicamente , Cistite/patologia , Modelos Animais de Doenças , Glicosídeos/farmacologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Masculino , Mesna/uso terapêutico , Tamanho do Órgão/efeitos dos fármacos , Medição da Dor , Peroxidase/metabolismo , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Esteroides/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/enzimologia , Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To evaluate sensitivity, specificity and positive and negative predictive values (PPV, NPV) of anti-p16(INK4a) in cervical cytology. STUDY DESIGN: A case-control study was conducted in a reference center for cervical pathology. Cytology slides were collected in a standard way with Ayre spatula and Cytobrush. The slides were interpreted by 2 independent pathologists (P1, P2). The cases (n = 61) represented all cervical examinations that had resulted in a biopsy with the diagnosis of CIN 1, 2 or 3 or squamous cell carcinoma. Controls (n = 87) included all examinations with negative cytology (Papanicolaou) and negative colposcopy. RESULTS: The sensitivity for the histologic diagnosis of CIN 2, 3 (n = 23) was 100% and 95.7% (P1, P2), respectively. The NPV for CIN 2 or worse was 100% (P1) and 98.9% (P2). The sensitivity for the diagnosis of CIN 1 was 77.8% (P1) and 58.3% (P2). The NPV for CIN 1 or worse was 90.6% (P1) and 82% (P2). The K index between the 2 pathologists was 0.74. CONCLUSIONS: Our results suggest that the antibody anti-p16(INK4a) could contribute as an adjuvant tool in the follow-up of cervical intraepithelial lesions when the cytology sample is collected in the standard way.
Assuntos
Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Teste de Papanicolaou , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Adulto , Estudos de Casos e Controles , Colposcopia , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/metabolismoRESUMO
OBJECTIVE: To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation. METHODS: To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens. RESULTS: Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi. CONCLUSIONS: Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.
Assuntos
Indutores da Angiogênese/uso terapêutico , Artérias Brônquicas/fisiologia , Terapia Genética/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Indutores da Angiogênese/metabolismo , Animais , Cães , Humanos , Imuno-Histoquímica/métodos , Fluxo Sanguíneo Regional/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma has a poor long-term prognosis. Experimental models are necessary to understand not only its biologic behavior, but also the early pancreatic lesions known as pancreatic intraepithelial neoplasia (PanIN) and to develop new treatments. The aim of this study was to evaluate pancreatic carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) implantation in mice according to the PanIN classification system. METHODS: Ninety male, Mus musculus, CF-1 mice underwent a median laparotomy and 1 mg of DMBA was implanted into the proximal pancreas held in place by a purse-string suture. Mice were killed after 30 and 60 days after which the excised pancreata were fixed in formalin, embedded in paraffin, and stained with hematoxylin-eosin for histologic analysis. The specimens were evaluated blind by 2 pathologists for the presence of the following histology: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, and PanIN-3, and adenocarcinoma. RESULTS: In the 30-day group, pathologic evaluation showed 4 (17%) reactive hyperplasia, 16 (67%) PanIN lesions, and 4 (17%) adenocarcinomas. In the 60-day group, there were 10 (27%) specimens with reactive hyperplasia, 13 (35%) with PanIN lesions, and 14 (38%) with adenocarcinomas. The difference between groups was statistically significant (P<.05). All pancreata with adenocarcinoma had concomitant PanIN lesions. CONCLUSIONS: The DMBA experimental model in mice induces PanIN lesions and ductal adenocarcinoma that have similar histology to that of human pancreatic cancer. This model may be useful for study of pancreatic carcinogenesis, particularly the molecular progression of early pancreatic ductal lesions.
Assuntos
9,10-Dimetil-1,2-benzantraceno , Carcinoma in Situ/induzido quimicamente , Carcinoma Ductal Pancreático/induzido quimicamente , Modelos Animais de Doenças , Neoplasias Pancreáticas/induzido quimicamente , Animais , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Masculino , Camundongos , Neoplasias Pancreáticas/patologiaRESUMO
Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were randomized to receive either lansoprazole, amoxicillin, and clarithromycin or lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed at baseline and at 3 and 12 months. There was an overall trend, although not statistically significant, for a benefit of H. pylori eradication. Of the patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement, versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis, it was found that of the patients without endoscopic gastric erosions, 15 of 34 (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic improvement (P = 0.015). Helicobacter pylori eradication did not prove to be clinically beneficial, although a tendency to symptomatic benefit was detected. Further studies are necessary to confirm the implications of endoscopic gastric erosions in these patients.
Assuntos
Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Dispepsia/tratamento farmacológico , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Omeprazol/análogos & derivados , 2-Piridinilmetilsulfinilbenzimidazóis , Adolescente , Adulto , Idoso , Anti-Infecciosos/uso terapêutico , Biópsia , Brasil/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Dispepsia/etiologia , Dispepsia/patologia , Endoscopia Gastrointestinal , Feminino , Seguimentos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/complicações , Gastrite/microbiologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Prevalência , Estudos Prospectivos , Inibidores da Bomba de Prótons , Resultado do TratamentoRESUMO
We used 550 Braford and 214 Brangus-Ibagé bulls to study the association between Y chromosome morphology and the evaluation of breeding-soundness, karyotyping and breeding records were used to assess Y chromosome morphology. In general, no direct association was detected between the individual type of Y chromosome and reproductive fitness as previously estimated through breeding soundness examination. The type of breeding strategy used to form the synthetic breeds was also analyzed. The Braford breed is about 3/8 Zebu (Bos taurus indicus) and 5/8 Hereford (Bos taurus taurus) but when the breeding strategy used 1/4 Zebu animals to produce Braford bulls which were 3/8 Zebu a greater percentage of the bulls had to be culled due to reproductive problems. Our study shows that certain interactions between genotypes can be detrimental to the reproductive efficiency of 3/8 Zebu animals and that breeding strategies avoiding or favoring certain genotypes can be used to reduce the percentage of bulls from synthetic breeds that are culled due to problems with semen quality.