RESUMO
The effects of 17ß-estradiol (E2) or estradiol benzoate (EB) on PGF2α release were studied in bred-non-pregnant and pregnant Nelore beef heifers. The day of timed artificial insemination (TAI) was designated day 0 (D0), and a single treatment was given on D14. All heifers also received an intravaginal P4 device on D14, and were randomly assigned to three groups: Control (C, P4 device only, n = 12); E2 (1 mg E2 + 9 mg P4, n = 10); or EB (1 mg, n = 10). Blood samples were collected hourly for 8 hours after treatment (Hours 0-8) to measure plasma concentrations (pg/mL) of a PGF2α metabolite (PGFM). The P4 device was removed on D22 and pregnancy was diagnosed on D28. Pregnancy rate was not different among groups (C, n = 7/12; E2, n = 5/10; EB, n = 5/10). More (P < 0.05) heifers had a CV-identified prominent PGFM pulse (peak of > 100 pg/mL) in E2 group (6/10) than in EB (1/10) and C (0/12) groups. Hourly concentration of PGFM for Hours 0 to 8 showed significant effects of group and hour and an interaction of group by hour but did not show an interaction of group or hour with pregnancy status. In preliminary post-hoc analyses, PGFM concentrations during Hours 0 to 8 and pulse characteristics were analyzed within each pregnancy status. For the non-pregnant heifers, a group-by-hour interaction was detected tentatively indicating an increase (P < 0.005) in PGFM concentrations in E2 group from Hours 4 to 6 and in EB group at Hours 5 and 6. Maximum PGFM concentration during Hours 0 to 8 did not differ (P > 0.1) between E2 (124 ± 23) and EB (110 ± 30) groups, but was greater (P < 0.05) in each group than in C (32 ± 3). Furthermore, PGFM concentrations of pulses at the peak, amplitude, and area under pulse curve (pg/mL/h) were greater (P < 0.05) in E2 group than in C group whereas the EB group did not differ (P > 0.1) from the other groups. For pregnant heifers, no effects of group, hour, or their interaction were detected in PGFM concentrations during the hourly sessions, except that maximum PGFM concentration was greater (P < 0.05) in E2 than in EB and C groups. In addition, the number of prominent pulses was greater in E2 group than in Control or EB groups. In conclusion, PGFM increased earlier and in greater concentration combined for bred-non-pregnant and pregnant heifers treated 14 days after TAI with 1 mg E2 plus 9 mg P4 than with 1 mg EB. Tentatively, a positive effect for each of E2 and EB on PGFM concentrations was attenuated in pregnant heifers.
Assuntos
Estradiol , Progesterona , Animais , Bovinos , Dinoprosta/metabolismo , Estradiol/farmacologia , Sincronização do Estro , Feminino , Inseminação Artificial/veterinária , GravidezRESUMO
Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.
Assuntos
Anemia de Diamond-Blackfan/patologia , Células-Tronco Hematopoéticas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Anemia de Diamond-Blackfan/dietoterapia , Anemia de Diamond-Blackfan/genética , Animais , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Dioxóis/farmacologia , Dioxóis/uso terapêutico , Modelos Animais de Doenças , Eritropoese/efeitos dos fármacos , Eritropoese/genética , Humanos , Camundongos , Camundongos Transgênicos , Mutação , Cultura Primária de Células , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Quinolinas/farmacologia , Quinolinas/uso terapêutico , RNA Interferente Pequeno/metabolismo , Proteínas Ribossômicas/genéticaRESUMO
INTRODUCTION: We evaluated the usefulness of xeno-Biosheets, an in-body tissue architecture-induced bovine collagenous sheet, as repair materials for abdominal wall defects in a beagle model. MATERIALS AND METHODS: Biosheets were prepared by embedding cylindrical molds into subcutaneous pouches of three Holstein cows for 2-3 months and stored in 70% ethanol. The Biosheets were 0.5 mm thick, cut into 2 cm × 2 cm, and implanted to replace defects of the same size in the abdominal wall of nine beagles. The abdominal wall and Biosheets were harvested and subjected to histological evaluation at 1, 3, and 5 months after implantation (n = 3 each). RESULTS: The Biosheet and bovine pericardiac patch (control) were not stressed during the suture operation and did not split, and patches were easily implanted on defective wounds. After implantation, the patch did not fall off and was not perforated, and healing was observed nacroscopically in all cases. During the first month of implantation, accumulation of inflammatory cells was observed along with decomposition around the Biosheet. Decomposition was almost complete after 3 months, and the Biosheet was replaced by autologous collagenous connective tissue without rejection. After 5 months, the abdominal wall muscle elongated from the periphery of the newly formed collagen layer and the peritoneum was formed on the peritoneal cavity surface. Regeneration of almost all layers of the abdominal wall was observed. However, almost all pericardium patches were remained even at 5 months with inflammation. CONCLUSION: Bovine Biosheets requiring no special post-treatment can be useful as off-the-shelf materials for abdominal wall repair.
Assuntos
Parede Abdominal/cirurgia , Implantes Absorvíveis , Bioprótese , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Implantação de Prótese/métodos , Animais , Bovinos , Colágeno/administração & dosagem , Modelos Animais de Doenças , Cães , Regeneração Tecidual Guiada/métodos , Pericárdio/transplante , Estudo de Prova de Conceito , Telas Cirúrgicas , Alicerces Teciduais , Transplante HeterólogoRESUMO
A retrospective study was performed to determine the efficacy of a tethering procedure developed to achieve a more rigid fixation and more reliable outcome in patients with refractory dislocation of the temporomandibular joint. The cases of eight patients with dementia and systemic diseases who underwent this technique were reviewed. In these eight patients, the condyles of 13 joints were ligated using wire between screws placed in the eminence and condylar head. Additional screw-wire ligations were applied to reinforce the restraint of movement in five of the 13 joints with suspected uncontrolled dislocation. The procedure was performed successfully, and the patients were followed-up for an average of 25months. In one patient, dislocation recurred 1year postoperatively due to wire breakage. The five joints in which a double set of screw-wire tethering was applied showed no recurrence or wire disturbance. This technique may, therefore, have short-term efficacy in cases that are refractory to standard procedures, although the material used for ligation should be investigated further. This approach can contribute to the quality of life of patients, particularly those with a short life-expectancy.
Assuntos
Parafusos Ósseos , Fios Ortopédicos , Luxações Articulares/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Luxações Articulares/complicações , Ligadura , Masculino , Qualidade de Vida , Estudos Retrospectivos , Transtornos da Articulação Temporomandibular/complicações , Resultado do TratamentoRESUMO
Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Glote/patologia , Neoplasias Laríngeas/radioterapia , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host MÏ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected MÏ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient MÏ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL. Furthermore, necrosis is associated with stabilization of hexokinase II on the mitochondria as well as cyclophilin D-dependent mitochondrial permeability transition. Collectively, these events upregulate the level of reactive oxygen species to induce necrosis. Thus, in Mtb-infected MÏ, mitochondria are an essential platform for induction of necrosis by activating RIPK3 function and preventing caspase 8-activation.
Assuntos
Caspase 8/metabolismo , Macrófagos/patologia , Mitocôndrias/metabolismo , Mycobacterium tuberculosis/fisiologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Tuberculose/imunologia , Proteína bcl-X/metabolismo , Animais , Carga Bacteriana , Permeabilidade da Membrana Celular , Células Cultivadas , Peptidil-Prolil Isomerase F , Ciclofilinas/metabolismo , Modelos Animais de Doenças , Hexoquinase , Humanos , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína bcl-X/genéticaRESUMO
PURPOSE: The purpose of this study was to assess the effects of recent surgical rib fixation and establish its indications not only for flail chest but also for multiple rib fractures. METHODS: Between 2007 and 2015, 187 patients were diagnosed as having multiple rib fractures in our institution. After the propensity score matching was performed, ten patients who had performed surgical rib fixation and ten patients who had treated with non-operative management were included. Categorical variables were analyzed with Fischer's exact test and non-parametric numerical data were compared using the Mann-Whitney U test. Wilcoxon signed-rank test was performed for comparison of pre- and postoperative variables. All statistical data are presented as median (25-75 % interquartile range [IQR]) or number. RESULTS: The surgically treated patients extubated significantly earlier than non-operative management patients (5.5 [1-8] vs 9 [7-12] days: p = 0.019). The duration of continuous intravenous narcotic agents infusion days (4.5 [3-6] vs 12 [9-14] days: p = 0.002) and the duration of intensive care unit stay (6.5 [3-9] vs 12 [8-14] days: p = 0.008) were also significantly shorter in surgically treated patients. Under the same ventilating conditions, the postoperative values of tidal volume and respiratory rate improved significantly compared to those values measured just before the surgery. The incidence of pneumonia as a complication was significantly higher in non-operative management group (p = 0.05). CONCLUSIONS: From the viewpoints of early respiratory stabilization and intensive care unit disposition without any complications, surgical rib fixation is a sufficiently acceptable procedure not only for flail chest but also for repair of severe multiple rib fractures.
Assuntos
Técnicas de Apoio para a Decisão , Fraturas Múltiplas/cirurgia , Escala de Gravidade do Ferimento , Pontuação de Propensão , Fraturas das Costelas/cirurgia , Adolescente , Adulto , Idoso , Feminino , Tórax Fundido/cirurgia , Fraturas Múltiplas/diagnóstico por imagem , Fraturas Múltiplas/patologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/patologia , Adulto JovemRESUMO
Nanomaterials are frequently used in microelectronics, cosmetics, and sunscreens. Platinum reagents are commonly used in disease diagnosis, cosmetics, and the food industry. Although research into the development of nanomaterialbased drug delivery systems has yielded promising results, the toxicity of these materials is not fully understood. We investigated the toxicity and drug interactions of 1- and 8-nm diameter platinum nanoparticles (nPt1 and nPt8, respectively) in mice. Acute hepato-renal toxicity of intravenously administered platinum nanoparticles was evaluated biochemically and histologically. Dose-dependent increases in serum markers of hepato-renal function (serum aminotransferases and blood urea nitrogen) were observed following administration of nPt1, whereas nPt8 had no effect, even at 20 mg/kg. Moreover, nPt1 induced interleukin (IL)-6 and IL-1ß production 3 and 6 hours after administration. The effect of nPts on drug-induced toxicity was evaluated in mice injected intraperitoneally with carbon tetrachloride or cisplatin, with or without intravenous administration of platinum nanoparticles. All treatments in the absence of nanoparticles were non-lethal and resulted in moderate toxicity. However, exacerbated toxicity was observed in mice injected with carbon tetrachloride or cisplatin together with nPt1, but not in mice co-injected with nPt8. We found that nPt1 cause hepato-renal damage, and the effect is enhanced by chemical inducers of hepatotoxicity and nephrotoxicity. This is the first report demonstrating that nPt1 not only are hepatotoxic and nephrotoxic but also exacerbate drug toxicity. These findings will be useful for future nanotechnology and nanoscience research.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Nanopartículas Metálicas/toxicidade , Platina/toxicidade , Alanina Transaminase/sangue , Animais , Antineoplásicos/toxicidade , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Tetracloreto de Carbono/toxicidade , Cisplatino/toxicidade , Relação Dose-Resposta a Droga , Interações Medicamentosas , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Interleucina-6/biossíntese , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da PartículaRESUMO
We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F4 in the two groups were 2.83 COI in patients with hepatitis B and 5.03 COI in patients with hepatitis C (P=.0046). The median WFA+ -M2BP values in F3 or more in the two groups were 1.79 COI in patients with hepatitis B and 3.79 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F2 or more in the two groups were 1.49 COI in the hepatitis B cohort and 3.19 COI in the hepatitis C group (P<.0001). Among five liver fibrosis markers, WFA+ -M2BP had the highest correlation coefficient (rs =.629) in terms of correlation with the degree of fibrosis in the patients with hepatitis C and had the second highest rs value (.415) in the hepatitis B group. Although WFA+ -M2BP could be a useful indicator of liver fibrosis, WFA+ -M2BP levels in the two groups significantly differed even in the same degree of fibrosis. Individual cut-off values in each aetiology for the degree of fibrosis should be determined.
Assuntos
Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/metabolismo , Hepatite B Crônica/patologia , Hepatite C Crônica/patologia , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/metabolismo , Lectinas de Plantas/metabolismo , Receptores de N-Acetilglucosamina/metabolismo , Soro/química , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Adulto JovemRESUMO
Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and embryo development, embryonic stem cell, and induced pluripotent stem cell maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and examined its biological activity and effects on oocytes during IVM in the domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92% with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia coli was readily soluble and after purification showed bioactivity in maintaining the undifferentiated state of mouse embryonic stem cells and enhancing the proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL fLIF induced cumulus expansion with or without FSH and EGF (P < 0.05). The rate of metaphase II oocytes was also improved with 100-ng/mL fLIF (P < 0.05). We therefore confirmed the successful production for the first time of biologically active fLIF and revealed its effects on oocytes during IVM in the domestic cat. Feline LIF will further improve reproduction and stem cell research in the feline family.
Assuntos
Gatos/fisiologia , Escherichia coli/metabolismo , Fator Inibidor de Leucemia/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Embrião de Mamíferos/citologia , Fibroblastos/fisiologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Fator Inibidor de Leucemia/genética , PlasmídeosRESUMO
PURPOSE: To compare the feasibilities and efficacies of the total extraperitoneal (TEP) technique and laparotomy for incarcerated obturator hernia repair. METHODS: All study subjects were diagnosed with incarcerated obturator hernia, preoperatively and TEP was performed as for TEP groin hernia repair. The incarcerated intestine was retracted into the peritoneal cavity with the hernia sac. The obturator foramen was then covered with a rectangular mesh (9 × 13 cm), which also covered the internal inguinal ring, Hesselbach's triangle, and the femoral ring. Non-ischemia of the incarcerated bowel was confirmed laparoscopically. In patients undergoing laparotomy, the obturator foramen was closed by continuous sutures, and no prosthesis was used. We recorded the length of hospital stay, operative time, amount of intraoperative bleeding, and postoperative complications. RESULTS: Twenty-two patients underwent obturator hernia repair in our hospital between January 2000 and December 2012, of whom 10 were treated with laparotomy and the remaining 12 via TEP. Three patients undergoing TEP were converted to laparotomy. The operation time was significantly longer in the conversion group compared with either the laparotomy or the TEP groups. There was no difference between the laparotomy and TEP groups regarding intraoperative bleeding. Patients who underwent TEP without conversion had a significantly shorter hospital stay than those who underwent laparotomy or required conversion. CONCLUSIONS: TEP provides a suitable approach for incarcerated obturator hernia repair, with favorable results regarding hospital stay. TEP is a feasible, minimally invasive technique for the repair of incarcerated obturator hernias.
Assuntos
Hérnia do Obturador/cirurgia , Herniorrafia/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Hérnia do Obturador/complicações , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Laparoscopia/métodos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. METHODS: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. RESULTS: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. CONCLUSIONS: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
Assuntos
Ciclina G2/fisiologia , Desoxicitidina/análogos & derivados , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos , Linhagem Celular Tumoral , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
The objectives of the current experiment were to determine the effects of 2 prepartum stocking densities on milk yield, concentration of metabolites during the peripartum period, and health and reproductive parameters of dairy cows. Jersey cows enrolled in the experiment at 254±3 d of gestation were balanced for parity (nulliparous vs. parous) and previous lactation projected 305-d mature equivalent milk yield (parous) and assigned to 1 of 2 treatments: 80% headlock stocking density (80SD; 38 animals/48 headlocks) and 100% headlock stocking density (100SD; 48 animals/48 headlocks). The number of experimental units was 8 (4 replicates and 2 pens/treatment per replicate). In total, 154 nulliparous and 184 parous animals were enrolled in the 80SD treatment and 186 nulliparous and 232 parous animals were enrolled in the 100SD treatment. At the start of each replicate, treatments were switched within pen. Cows were milked thrice daily and monthly milk yield, fat and protein content, and somatic cell count data were recorded up to 155 d postpartum. Plasma nonesterified fatty acid concentration was measured weekly, from -18±3 to 17±3 d relative to calving, and plasma ß-hydroxybutyrate was measured weekly, from 1±2 to 17±3 d relative to calving. Cows were examined 1, 4±1, 7±1, 10±1, and 13±1 d relative to calving for diagnosis of uterine diseases. Blood was sampled for determination of progesterone concentration and resumption of ovarian cycles 35±3 and 45±3 d relative to calving. Average headlock (74.1±0.4 vs. 94.5±0.3%) and stall (80.8±0.4 vs. 103.1±0.4%) stocking density was lower for the 80SD treatment compared with the 100SD treatment. Treatment did not affect incidence of retained fetal membranes (80SD=5.1, 100SD=7.8%), metritis (80SD=21.2, 100SD=16.7%), acute metritis (80SD=9.9, 100SD=9.4%), and vaginal purulent discharge (80SD=5.8, 100SD=7.9%). Concentrations of nonesterified fatty acids (80SD=251.5±6.1, 100SD=245.9±5.6µmol/L) and ß-hydroxybutyrate (80SD=508.2±14.3, 100SD=490.9±13.6µmol/L) were not different between treatments. Treatment had no effect on percentage of cows removed from the herd on the first 60 d postpartum (80SD=6.1, 100SD=5.1%) and on rate of removal from the herd up to 305 d postpartum 80SD=referent, 100SD [adjusted hazard ratio (95% confidence interval)]=1.02 (0.75, 1.38). Percentages of cows pregnant to first (80SD=41.9, 100SD=48.4%) and second (80SD=49.3, 100SD=42.0%) postpartum AI were not different between treatments. Finally, treatment did not affect energy-corrected milk yield up to 155 d postpartum (80SD=33.8±0.5, 100SD=33.4±0.5kg/d). In herds with weekly or twice weekly movement of new cows to the prepartum pen and separate housing of nulliparous and parous animals, a target stocking density of 100% of headlocks on the day of movement is not expected to affect health, metabolic, reproductive, and productive parameters.
Assuntos
Doenças dos Bovinos/epidemiologia , Bovinos/fisiologia , Endometrite/veterinária , Leite/metabolismo , Placenta Retida/veterinária , Reprodução , Ácido 3-Hidroxibutírico/sangue , Animais , Comportamento Animal , Contagem de Células , Endometrite/epidemiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Incidência , Lactação , Modelos Logísticos , Paridade , Período Periparto , Placenta Retida/epidemiologia , Densidade Demográfica , Período Pós-Parto , Gravidez , Progesterona/sangueRESUMO
The purpose of this study is to assess the role of the protein kinase A (PKA) in regulating uptake of dehydroepiandrosterone sulfate (DHEAS), an estrogen precursor, by syncytiotrophoblasts. Forskolin, a PKA activator, significantly increased [(3)H]DHEAS uptake and the mRNA expression levels of organic anion transporter (OAT) 4 and CYP19A1 in choriocarcinoma JEG-3 cells, while other steroid sulfate transporters present in the placenta showed no change in expression level. KT5720, a PKA inhibitor, attenuated these effects of forskolin. Accordingly, the PKA pathway appears to play an important role in estrogen synthesis by cooperatively regulating OAT4 and steroidogenic enzymes in syncytiotrophoblasts.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Estrogênios/biossíntese , Trofoblastos/metabolismo , Linhagem Celular Tumoral , Humanos , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismoRESUMO
Somatic mutation of RUNX1 is implicated in various hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia (AML), and previous studies using mouse models disclosed its critical roles in hematopoiesis. However, the role of RUNX1 in human hematopoiesis has never been tested in experimental settings. Familial platelet disorder (FPD)/AML is an autosomal dominant disorder caused by germline mutation of RUNX1, marked by thrombocytopenia and propensity to acute leukemia. To investigate the physiological function of RUNX1 in human hematopoiesis and pathophysiology of FPD/AML, we derived induced pluripotent stem cells (iPSCs) from three distinct FPD/AML pedigrees (FPD-iPSCs) and examined their defects in hematopoietic differentiation. By in vitro differentiation assays, FPD-iPSCs were clearly defective in the emergence of hematopoietic progenitors and differentiation of megakaryocytes, and overexpression of wild-type (WT)-RUNX1 reversed most of these phenotypes. We further demonstrated that overexpression of mutant-RUNX1 in WT-iPSCs did not recapitulate the phenotype of FPD-iPSCs, showing that the mutations were of loss-of-function type. Taken together, this study demonstrated that haploinsufficient RUNX1 allele imposed cell-intrinsic defects on hematopoietic differentiation in human experimental settings and revealed differential impacts of RUNX1 dosage on human and murine megakaryopoiesis. FPD-iPSCs will be a useful tool to investigate mutant RUNX1-mediated molecular processes in hematopoiesis and leukemogenesis.
Assuntos
Transtornos Plaquetários/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Hematopoese/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucemia Mieloide Aguda/genética , Mutação , Animais , Transtornos Plaquetários/patologia , Diferenciação Celular/genética , Análise Mutacional de DNA , Feminino , Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Imunofenotipagem , Células-Tronco Pluripotentes Induzidas/patologia , Leucemia Mieloide Aguda/patologia , Masculino , Megacariócitos/metabolismo , Megacariócitos/patologia , Camundongos , Linhagem , FenótipoRESUMO
PURPOSE: To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. SUBJECTS AND METHODS: Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. RESULTS: Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking. CONCLUSION: Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.
Assuntos
Deficiência de Ácido Ascórbico/complicações , Ácido Ascórbico/sangue , Encefalopatias/etiologia , Encéfalo/patologia , Carotenoides/deficiência , Tocoferóis/sangue , Deficiência de Vitamina E/complicações , Idoso , Antioxidantes/metabolismo , Encefalopatias/patologia , Carotenoides/sangue , Deficiências Nutricionais/complicações , Feminino , Avaliação Geriátrica , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Fatores Sexuais , Vitaminas/sangueRESUMO
Binding properties are important for meat products and are substantially derived from the heat-induced gelation of myosin. We have shown that myosin is solubilized in a low ionic strength solution containing L-histidine. To clarify its processing characteristics, we investigated properties and structures of heat-induced gels of myosin solubilized in a low ionic strength solution containing L-histidine. Myosin in a low ionic strength solution formed transparent gels at 40-50°C, while myosin in a high ionic strength solution formed opaque gels at 60-70°C. The gel of myosin in a low ionic strength solution with L-histidine showed a fine network consisting of thin strands and its viscosity was lower than that of myosin in a high ionic strength solution at 40-50°C. The rheological properties of heat-induced gels of myosin at low ionic strength are different from those at high ionic strength. This difference might be caused by structural changes in the rod region of myosin in a low ionic strength solution containing L-histidine.
Assuntos
Histidina/química , Temperatura Alta , Miosinas/química , Nefelometria e Turbidimetria , Concentração Osmolar , Soluções/químicaRESUMO
OBJECTIVE: The aim of this study was to compare two different automated biopsy needles, a fully automated biopsy needle (Monopty; Bard, Covington, GA) and a semi-automated biopsy needle (Temno; Bauer Medical, Clearwater, FL), for lung biopsy. METHODS: 50 consecutive percutaneous lung biopsies using the Monopty needle between June 2006 and January 2007 and 66 consecutive lung biopsies for 1 nodule in each session using the Temno needle between February 2007 and August 2008 were performed under CT fluoroscopic guidance followed by histopathological evaluation. RESULTS: In 42/50 lung biopsies performed with the Monopty needle and 54/66 lung biopsies performed with the Temno needle, the final diagnosis was confirmed by independent surgical pathological findings or clinical follow-up. Sufficient samples for histopathological evaluation were obtained in all 50 (100%) biopsies using the Monopty needle and in 55 (83.3%) of the 66 biopsies using the Temno needle (p<0.01). Accurate diagnosis was achieved in 41 (97.6%) of 42 biopsies using the Monopty needle and in 45 (83.3%) of 54 biopsies using the Temno needle (p=0.04). Biopsy-induced complications were pneumothorax, haemoptysis and haemothorax in 44.0%, 10.0% and 6.0% of biopsies, respectively, using the Monopty needle and in 48.3%, 8.3% and 3.3%, respectively, using the Temno needle. CONCLUSION: There is a possibility that a fully automated biopsy needle such as the Monopty is more useful for CT scan-guided lung biopsy than semi-automated biopsy needles.
Assuntos
Biópsia por Agulha/instrumentação , Neoplasias Pulmonares/patologia , Pulmão/patologia , Agulhas , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/efeitos adversos , Biópsia por Agulha/métodos , Feminino , Fluoroscopia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Radiografia Intervencionista/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: A blood pressure drop after bevacizumab administration and its clinical significance have not been previously reported. METHODS: Blood pressure data at 0, 90, and 180 min after a total of 162 bevacizumab administrations in 81 advanced colorectal cancer patients were retrospectively investigated. RESULTS: Twenty-five patients (30%) demonstrated an average temporary drop of 20 mm Hg or more in systolic blood pressure. We classified these 25 patients as group A and the others as group B. Median time-to-treatment failure (TTF) was significantly longer in group A than in group B (291 vs 162 days; P=0.02). Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A than in group B (36% vs 4%; P<0.01). CONCLUSION: This study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Hipotensão/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bevacizumab , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de TratamentoRESUMO
Pure mucinous carcinoma of the breast is a histological type of invasive carcinoma and generally shows a slow growth pattern. Rapid growth and intratumoural haemorrhage are rare and there have been no reports presenting such a clinical course and associated radiographic findings. We report a case with atypical rapidly enlarging mucinous carcinoma of the breast after trauma, in which MRI closely reflected the histopathological background and was thought to be useful for differential diagnosis from other highly malignant breast tumours.