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1.
J Environ Manage ; 302(Pt A): 114052, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34741950

RESUMEN

Climate change and the accumulation of surface fuel are leading to global changes in the occurrence of increasingly severe fires. In light of current budgetary constraints, prescribed fire can be a very cost-efficient tool for both reducing wildfire hazards and managing fire-prone landscapes. However, despite its widespread use in some countries, social and administrative constraints arise when applied at the European or larger scales. Science-based knowledge concerning fire behavior, fuel load reduction, and tree impacts is required to support the use of prescribed fire. Spatial ignition patterns can increase or decrease the spread rate, flame length, and flame residence time according to the objectives of a prescribed fire. This work aims to analyze fire behavior using different fire ignition patterns (strip-heading fire, flanking fire, and spot-heading fire) and meteorological and fuel conditions. Seventy-seven observations or sampling units using twenty-three prescribed fires were established for fire monitoring. Non-linear models based on environmental variables were fitted for the spread rate and flame length. Our study proposes a novel way of sharing scientific knowledge in relation to the most common distances between ignition lines and ignition points used in the southern Iberian Peninsula. The spread rate and flame length can be increased in strip-heading fire, by more than 3.5-fold and more than 1.95-fold, respectively, by modifying only the distance between ignition lines. Flanking fire could lead to a decrease in the spread rate by approximately half. Although spot-heading fire can reduce the spread rate by more than 78% and flame length by more than 41%, the highest distances between points could increase the flame residence time by 39-132%. This research seeks to achieve a trade-off between fire intensity and the impacts of fire on trees, soil, and surface roots.


Asunto(s)
Incendios , Pinus , Incendios Forestales , Bosques , Árboles
2.
Ann Oncol ; 30(2): 281-289, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30657853

RESUMEN

BACKGROUND: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis. RESULTS: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01905657.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias Pulmonares/mortalidad , Manejo de Especímenes/métodos , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Docetaxel/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Pronóstico , Tasa de Supervivencia , Adulto Joven
3.
Ann Oncol ; 23(11): 2919-2924, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22782333

RESUMEN

BACKGROUND: This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials. PATIENTS AND METHODS: Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared. RESULTS: PCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52-0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018). CONCLUSIONS: PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.


Asunto(s)
Irradiación Craneana , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Tasa de Supervivencia , Resultado del Tratamiento
4.
Sci Total Environ ; 675: 520-530, 2019 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-31030158

RESUMEN

Disturbance events play an important role in ecosystem services management and species biodiversity. In this sense, species biodiversity may constitute a large proportion of the total ecosystem value, mainly in natural protected areas. The present research proposes a methodology for the economic valuation of flagship species; the value of charismatic species was estimated using two complementary approaches based on recovery programs and contingent valuation method (CVM). While recovery programs approach is related to government expenditure, CVM is associated with survey results according to the society's willingness to pay. There are significant differences between both approaches as flagship species are highly valued by the society. In this sense, a difference of 43.75% on the species value can be found depending on the scenario of CVM (all respondents or only affirmative respondents). Our research was done on the integration of economic tools and wildfire severity of two burned areas in order to evaluate the effects caused in their habitat and, as a consequence, in the food chain. The results obtained from both the studied areas emphasized the importance of wildfire impacts on flagship species (209,619.08-445,495.88 € from Doñana wildfire and 634.68-5792.98 € from Segura wildfire) which are often omitted in valuation reports. The use of Geographic Information Systems helps to identify flagship species impacts per unit area (74.89-159.17 €/ha from Doñana wildfire and 0.76-6.98 €/ha from Segura wildfire) and to prioritize restoration activities on the most susceptible areas. This methodology could be extrapolated to any territory and spatial resolution based on the revision of the questionnaires regarding flagship species. The availability of cartography of flagship species´ susceptibility could play a critical role in budget optimization and the decision-making process on restoration planning.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Incendios Forestales/economía , Biodiversidad , Región Mediterránea
5.
Oncogene ; 36(50): 6919-6928, 2017 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-28869603

RESUMEN

Overexpression of DNMT1 and KIT is prevalent in lung cancer, yet the underlying molecular mechanisms are poorly understood. While the deregulated activation of DNMT1 or KIT has been implicated in lung cancer pathogenesis, whether and how DNMT1 and KIT orchestrate lung tumorigenesis are unclear. Here, using human lung cancer tissue microarrays and fresh frozen tissues, we found that the overexpression of DNMT1 is positively correlated with the upregulation of KIT in tumor tissues. We demonstrated that DNMT1 and KIT form a positive regulatory loop, in which ectopic DNMT1 expression increases, whereas targeted DNMT1 depletion abrogates KIT signaling cascade through Sp1/miR-29b network. Conversely, an increase of KIT levels augments, but a reduction of KIT expression ablates DNMT1 transcription by STAT3 pathway leading to in-parallel modification of the DNA methylation profiles. We provided evidence that KIT inactivation induces global DNA hypomethylation, restores the expression of tumor suppressor p15INK4B through promoter demethylation; in turn, DNMT1 dysfunction impairs KIT kinase signaling. Functionally, KIT and DNMT1 co-expression promotes, whereas dual inactivation of them suppresses, lung cancer cell proliferation and metastatic growth in vitro and in vivo, in a synergistic manner. These findings demonstrate the regulatory and functional interplay between DNA methylation and tyrosine kinase signaling in propelling tumorigenesis, providing a widely applicable approach for targeting lung cancer.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1/fisiología , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas c-kit/fisiología , Animales , Línea Celular Tumoral , Metilación de ADN , Humanos , Neoplasias Pulmonares/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/fisiología , Factor de Transcripción Sp1/fisiología , Proteína p53 Supresora de Tumor/fisiología
6.
Cell Death Discov ; 2: 16003, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27551498

RESUMEN

Apoptosis culminates in secondary necrosis due to lack of ATP. Cancer stem cells form spheres after apoptosis by evoking the blebbishield emergency program. Hence, determining how blebbishields avoid secondary necrosis is crucial. Here we demonstrate that N-Myc and VEGFR2 control transformation from blebbishields, during which oligomers of K-Ras, p27, BAD, Bax, and Bak boost glycolysis to avoid secondary necrosis. Non-apoptotic cancer cells also utilize oligomers to boost glycolysis, which differentiates the glycolytic function of oligomers from their apoptotic action. Smac mimetic in combination with TNF-α or TRAIL but not in combination with FasL abrogates transformation from blebbishields by inducing secondary necrosis. Thus blebbishield-mediated transformation is dependent on glycolysis, and Smac mimetics represent potential candidates to abrogate the blebbishield emergency program.

7.
Cell Death Differ ; 23(4): 707-22, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26494468

RESUMEN

Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Daño del ADN , Resistencia a Antineoplásicos , Efrina-B2/metabolismo , Transición Epitelial-Mesenquimal , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Efrina-B2/genética , Femenino , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
8.
Endocrinology ; 119(4): 1502-9, 1986 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-3757901

RESUMEN

Relaxin and progesterone secretion by aging corpora lutea (days 90-120) was examined in pregnant and lactating gilts compared with that in hysterectomized animals. The length of pregnancy is about 115 days in pigs. Unmated gilts were hysterectomized on day 6 (estrus = day 0). From days 90-101, relaxin concentrations in peripheral plasma remained consistently low in pregnant gilts (range, 0.7-1.5 ng/ml) and less (P less than 0.05) than those in hysterectomized animals (range, 0.9-3.5 ng/ml). Relaxin increased abruptly (P less than 0.01) to a peak of 66 ng/ml in pregnant gilts and 37 ng/ml in hysterectomized animals. Relaxin peaked in pregnant animals at 113 +/- 0.7 days (+/- SE) and in hysterectomized gilts at 113 +/- 0.7 days; gestation length averaged 114 +/- 0.8 days. In pregnant gilts, relaxin decreased from a peak of 66 to 11 ng/ml within 1 day and remained low (less than 1.0 ng/ml) in these lactating dams until day 120. In hysterectomized gilts, peak relaxin also decreased abruptly from 37 to 4.2 ng/ml, but remained consistently greater (P less than 0.05) than that in lactating dams. Although there were abrupt shifts in relaxin concentrations within 20 min, there was no evidence for consistent episodic relaxin release between days 112-116. Plasma progesterone concentrations were consistently greater (P less than 0.05) in hysterectomized than in pregnant gilts from days 102-110. Progesterone decreased abruptly in prepartum gilts (days 111-114) from 16 to 1.2 ng/ml and remained low during lactation (0.5 ng/ml). In hysterectomized animals, it decreased abruptly on days 110-113, ranging from 20-12 ng/ml, and remained at this lower level until day 120. These results clearly indicate that a precisely timed peak release of relaxin and coincident decrease in progesterone secretion occur in unmated hysterectomized gilts at the same time as those found a few hours preceding parturition during normal pregnancy. These abrupt shifts in relaxin and progesterone secretion on days 112-113 in both hysterectomized and pregnant gilts may be regulated autonomously from within the ovary or from the central nervous system and pituitary gland.


Asunto(s)
Cuerpo Lúteo/metabolismo , Histerectomía , Progesterona/metabolismo , Relaxina/metabolismo , Animales , Estro/fisiología , Femenino , Trabajo de Parto/fisiología , Lactancia/fisiología , Embarazo , Porcinos , Factores de Tiempo
9.
Endocrinology ; 124(3): 1294-304, 1989 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2917512

RESUMEN

Porcine corpora lutea persist beyond 150 days in hysterectomized animals compared with about 114 days during normal pregnancy. To explore the mechanism(s) regulating the peak release of relaxin and secretion of progesterone by aging corpora lutea and to examine the direct effect of purified porcine (p) PRL on such corpora lutea, hypophysial stalk transection (HST), hypophysectomy (HYPOX) with or without PRL replacement, and sham operation control (SOC) were conducted on day 110 (estrus = day 0) on purebred Yorkshire gilts that were hysterectomized on days 6-8. The pPRL (0.5 mg every 6 h daily) or PBS (0.5 ml every 6 h daily) was given iv from days 110-120. HYPOX + pPRL, HYPOX + PBS, HST + PBS, and SOC + PBS formed four experimental groups. Peak relaxin concentrations in peripheral plasma (mean values ranged from 22-24 ng/ml) occurred on about day 113 for all groups [113.4 +/- 0.3 days (+/- SE)] regardless of the different surgical interventions. After peak release, relaxin decreased steadily in the HYPOX + PBS group, falling to less than 1.0 ng/ml by 6 days later, whereas relaxin in other groups remained elevated (approximately 7 ng/ml). In the HYPOX plus PBS group, progesterone decreased abruptly, remaining below 1 ng/ml from 1 week onward, lower (P less than 0.01) than that in controls (approximately 19 ng/ml); in the HYPOX + pPRL group, progesterone levels (approximately 17 ng/ml) remained similar (P greater than 0.05) to those in controls (approximately 19 ng/ml) and the HST + PBS group (approximately 15 ng/ml). These results clearly reveal that the pituitary gland plays no direct role in regulating the timed peak release of relaxin from aging corpora lutea in hysterectomized gilts and that the peak release of relaxin on about day 113 is preprogrammed and inherent within such aging luteal cells. This study provides strong evidence that purified pPRL maintains both relaxin and progesterone secretion as well as the morphology of aging corpora lutea for at least 10 days after hypophysectomy in hysterectomized gilts.


Asunto(s)
Cuerpo Lúteo/fisiología , Hipofisectomía , Hipófisis/fisiología , Progesterona/metabolismo , Prolactina/fisiología , Relaxina/metabolismo , Animales , Cuerpo Lúteo/efectos de los fármacos , Femenino , Histerectomía , Ovario/anatomía & histología , Hipófisis/anatomía & histología , Prolactina/farmacología , Porcinos , Factores de Tiempo
10.
J Thorac Cardiovasc Surg ; 110(2): 427-35, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7637361

RESUMEN

Our goal was to identify the most appropriate material for right ventricle-pulmonary artery conduits in growing animals. We used 100 lambs that were 3 to 4 weeks old (mean weight 11.7 kg). Follow-up was up to 24 months. Group I received plain tubular conduits: (1) Dacron knitted fabric, (2) collagen-coated knitted fabric, (3) Milliknit and Microknit material, (4) woven Dacron fabric, (5) three-dimensional Dacron fabric (crossweave 500 and 800), or (6) polytetrafluoroethylene. Group II received either a (1) woven Dacron fabric conduit with a built-in tissue valve or (2) polytetrafluoroethylene graft with a built-in St. Jude Medical valve. We did angiograms and catheterizations every 3 to 6 months and killed the lambs at 6, 12, 18, or 24 months. Tubular Dacron fabric woven or knitted grafts, regardless of matrix, pore size, thickness, or coating, caused formation of a thick acellular pseudointima buildup, which led to progressive obstruction starting as early as 3 months. Polytetrafluoroethylene grafts in groups I and II showed the formation of thin inner and outer capsules (0.5 mm) and none developed obstruction despite wall calcification. Conduits of woven Dacron fabric with a built-in tissue valve degenerated rapidly, leading to calcification thrombosis and obstruction within 3 months; no lamb survived 12 months. Polytetrafluoroethylene conduits with a St. Jude Medical valve in lambs receiving anticoagulants remained free of obstruction and continued to function well. It appears that synthetic conduits of polytetrafluoroethylene perform well in either of the situations here tested and may be the best choice at present.


Asunto(s)
Prótesis Vascular , Ventrículos Cardíacos/cirugía , Arteria Pulmonar/cirugía , Animales , Cateterismo Cardíaco , Prótesis Valvulares Cardíacas , Ventrículos Cardíacos/diagnóstico por imagen , Docilidad , Tereftalatos Polietilenos , Politetrafluoroetileno , Porosidad , Arteria Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugía , Radiografía , Ovinos , Función Ventricular Derecha , Presión Ventricular
11.
Lung Cancer ; 46(2): 215-26, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15474670

RESUMEN

BACKGROUND: Prognosis following a diagnosis of primary lung cancer is very poor and varies significantly even after adjusting for known predictors. Inherent and acquired gene alterations could cause failure in lung cancer treatment and patient survival. To search for potential molecular markers with significant and independent predictive value in lung cancer survival, we applied oligo-nucleotide microarray analysis, along with patients' phenotypic profile, in a case-control study. The focus of this report is on the methodology used in the identification of potential genes as prognostic factors. METHODS: Selected from 304 patients at Mayo Clinic, 18 stage I squamous cell lung cancer patients who died within 2 years (high-aggressive) or lived beyond 5 years (low-aggressive) were included in this study. Both a one-to-one matched design (paired) and a two-group design (grouped) were utilized. Matching variables were age, gender, tumor size and grade, smoking status, and treatment. Two-GeneChip-array sets from Affymetrix (HG-U133) were used. We applied multiple analytic approaches including Dchip (Harvard University), SAM (Stanford University), ArrayTools (US National Cancer Institute), and MAS5 (Affymetrix); and integrated multiple results to generate the final candidate genes for further investigation. We evaluated the consistency across the methods and the effects of matched versus grouped design on the results. RESULTS: Using the same pre-processed data under the same criteria for type I error and fold-change in expression intensity, results are 94-100% concordant in the list of significant genes by Dchip and by ArrayTools, and 53% concordant between the paired and the grouped analysis. If using differently pre-processed data, the concordance rate is under 6% even by the same analytic tool. Combining results from all analyses, we found 23 potentially important genes that may distinguish the high- versus low-aggressive squamous cell tumors of the lung. CONCLUSION: Given the generally low consistency of results across analytic algorithms and study design, poor agreement is expected from different investigators reporting candidate genes for the same endpoint. A well-designed study with a carefully planned analytic strategy is critical. We are in the process of validating the 23 preliminary candidate genes found from this study among independent yet comparable cases.


Asunto(s)
Algoritmos , Marcadores Genéticos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Adulto , Anciano , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
12.
Am J Hum Biol ; 4(3): 285-290, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-28524296

RESUMEN

The concept of harmony in a set of anthropometric dimensions is identified with the notion of minimum variance associated with a function of several variables in those dimensions. When the chosen function is linear in the natural logarithms of the variables, the resulting model is the well-known multivariate allometry and the notion of minimum variance corresponds to the eigenvector associated with the smallest eigenvalue of the covariance matrix. This multivariate allometry model was fitted to four skinfolds in a sample of 250 newborns. The existence of a harmonic relationship among the skinfolds which is independent of weight, total body fat, body mass index, and several other maternal variables is indicated. There is, however, some evidence suggesting a possible correlation with the nutritional condition of the mother. © 1992 Wiley-Liss, Inc.

13.
Domest Anim Endocrinol ; 20(2): 89-100, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11311847

RESUMEN

The objective was to test the hypothesis that dopamine regulates prolactin (PRL) secretion by determining acute changes in catecholamine concentrations in hypophyseal portal blood of cattle, and their relation to peripheral blood concentration of PRL in hypophyseal stalk-transected (HST) and sham-operated controls (SOC). Holstein heifers (606 +/- 21 kg BW; mean +/- SE) were subjected to neurosurgery for 8 h to collect hypophyseal portal blood with a stainless steel cannula designed with a cuff placed under the pituitary stalk and peripheral blood via a jugular vein catheter. PRL plasma concentration was measured by radioimmunoassay, and dopamine and norepinephrine in portal plasma by radioenzymatic assay. During anesthesia before HST or SOC, PRL plasma concentration ranged from 20-40 ng/ml throughout 255 min. PRL abruptly increased and remained above 90 ng/ml after HST compared with a steady decrease to <20 ng/ml in SOC heifers throughout 440 min. Within 5 min after severing the hypophyseal stalk, dopamine in portal blood (>8 ng/ml) was significantly increased (P < 0.05) compared with peripheral blood (<2 ng/ml). Norepinephrine concentration in portal blood was significantly greater (P < 0.05) than in peripheral blood during the first 60 min. The sustained high PRL level in peripheral plasma after severing the hypophyseal stalk stimulated hypothalamic dopamine secretion from hypophyseal portal vessels during the prolonged period of blood collection. Norepinephrine concentration in these cattle was greater in hypophyseal portal than in peripheral blood, implicating both an important hypothalamic source of the catecholamine as well as an adrenal gland contribution during anesthesia.


Asunto(s)
Bovinos/fisiología , Dopamina/metabolismo , Norepinefrina/metabolismo , Hipófisis/irrigación sanguínea , Prolactina/sangre , Animales , Dopamina/sangre , Femenino , Cinética , Norepinefrina/sangre , Hipófisis/fisiología , Hipófisis/cirugía , Sistema Porta
14.
Acta Vet Scand ; 38(1): 1-7, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9129341

RESUMEN

Four zebu cows were bilaterally ovariectomized through lateral laparotomy. Three months after ovariectomy, blood samples were collected by jugular venipuncture daily for 5 consecutive days prior to a single injection of ACTH to establish baseline concentrations of cortisol and progesterone. Baseline concentrations of cortisol and progesterone were 31 +/- 5 nmol/L and 0.3 +/- 0.01 nmol/L, respectively. On the day of ACTH treatment the cows were allowed to rest for 2 h to reduce the stress of cannulation before the sampling period started. Blood samples were collected every 30 min from 2 h before until 2 h after the injection of 6 micrograms ACTH and hourly between 2-6 h after ACTH injection. A significant increase was observed in cortisol secretion from 90 min before until 120 min after ACTH injection. No significant increase was observed in progesterone secretion before ACTH injection. After ACTH injection progesterone was significantly elevated for 120 min. Four weeks after the ACTH treatment the cows were cannulated again and blood samples were collected following the same bleeding schedule used during the ACTH experiment. Instead of ACTH a saline injection was given via the catheter. A significant increase in cortisol concentration was recorded 90 min before saline injection. This increase was not accompanied by an elevation in progesterone concentration. No significant changes were observed in cortisol and progesterone levels after saline injection. When cortisol was added to a plasma pool having a progesterone concentration of 0.3 nmol/L and a cortisol concentration of 25.4 nmol/L and assayed for progesterone in 2 different assays no increase in progesterone concentration was observed. We conclude that the adrenal glands can be an extra-ovarian source of progesterone during stress in Zebu cows.


Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Hidrocortisona/sangre , Ovariectomía/veterinaria , Progesterona/sangre , Animales , Recolección de Muestras de Sangre/métodos , Recolección de Muestras de Sangre/veterinaria , Bovinos , Costa Rica , Femenino , Clima Tropical
15.
Acta Vet Scand ; 34(3): 255-62, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8310898

RESUMEN

A radioimmunoassay for bovine (bLH), ovine (oLH) and porcine (pLH) luteinizing hormone was developed using a human 125ILH tracer from a commercial kit and a monoclonal antibody (518B7) specific for LH but with low species specificity. Standard curves demonstrated similar binding kinetics when bLH, oLH and pLH were incubated with tracer and antibody for 2 h at room temperature. A 30-min delay in the addition of the tracer gave sufficient sensitivity when analysing pLH. Separation of antibody-bound LH from free hormone was achieved by using second antibody-coated micro Sepharose beads. The assay was validated and the performance compared with that of an RIA currently in use for determination of bLH and oLH (coefficient of correlation: 0.99 and 0.98). Regardless of the standards used, intra-assay coefficients of variation were < 10% for LH concentrations exceeding 1 microgram/L. The inter-assay coefficients of variation were < 15%. The assay was used for clinical evaluation demonstrating the pre-ovulatory LH surge in two cyclic cows, LH pulsatility in an oophorectomized ewe and LH response to GnRH injection in a boar.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Bovinos/inmunología , Hormona Luteinizante/inmunología , Radioinmunoensayo/veterinaria , Ovinos/inmunología , Porcinos/inmunología , Animales , Especificidad de Anticuerpos , Biomarcadores , Femenino , Humanos , Masculino , Estándares de Referencia
16.
Acta Vet Scand ; 36(3): 343-52, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7502951

RESUMEN

To assess endocrine and morphological responses of ovaries to total weaning at parturition, 6 Zebu (Bos indicus) cows 5 years or older were investigated. Following parturition, blood samples were collected daily during the first month and twice weekly thereafter until day 60 to determine concentrations of progesterone (P4) and prostaglandin F2 alpha metabolite. It took between 25 to 32 days to complete uterine involution. The prostaglandin metabolite remained elevated for a mean period of 14.2 days (range, 4-21) postpartum. Five of the animals resumed cyclicity with a short estrous cycle starting between days 7 to 34 and lasting between 7 and 14 days. No estrous behavior was recorded prior to the short estrous cycles, but subsequent normal-length estrous cycles were all preceded by signs of estrus. In the 1 animal that resumed cyclicity with an estrous cycle of normal length on day 37 (length 20 days), the cycle was preceded by estrous behavior. Progesterone concentrations reached a mean maximum of 4.8 nmol liter-1 during the short estrous cycles, and prostaglandin metabolite concentrations peaked while P4 concentrations were decreasing. P4 concentrations reached a mean maximum of 12.2 nmol liter-1 during the estrous cycles of normal length. The interval from parturition to the first estrous cycle of normal length varied between 16 and 48 days, and the length of the cycle was 18 to 22 days. Starting 2 days postpartum, ovaries from 5 of the cows were scanned by ultrasonography every second day until day 30 postpartum. Medium-sized follicles were detected between days 4 to 7 postpartum in 4 of the scanned cows that later had short estrous cycles. The time between parturition and the appearance of the first dominant follicle was 7.6 days (range 6-10 days). The interval between parturition and the appearance of the first ovulatory-sized follicle was 10.2 days (range 8-13 days). In 3 of the scanned cows this ovulatory-sized follicle ovulated. We conclude that cyclic ovarian activity in Zebu cows can start early in the postpartum period in the absence of offspring, and that short luteal phases, not preceded by estrous behavior, may play an important role in establishing normal postpartum ovarian activity.


Asunto(s)
Bovinos/fisiología , Lactancia/fisiología , Ovario/fisiología , Periodo Posparto , Animales , Estro/fisiología , Femenino , Ovulación/fisiología , Progesterona/sangre , Factores de Tiempo
17.
Acta Vet Scand ; 36(2): 161-73, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7484544

RESUMEN

The present study was undertaken to estimate the time for the attainment of spermatogenesis in springborn Corriedale ram lambs under conditions of extensive grazing systems in Uruguay. Clinical (live weight, scrotal circumference, penile/preputial separation), morphological (light and electron microscopy) and endocrinological (testosterone levels) parameters were examined. Two experiments in 2 consecutive years were carried out. In Exp. I, 40 ram lambs were clinically examined, weighed, and blood-sampled at 2 week-intervals between 78 and 216 days of age. Sixteen were castrated in 3 selected periods: 132-162 (n:2), 145-175 (n:6) and 186-216 days (n:8). In Exp. II, 40 ram lambs appertaining to the next generation of the same flock were examined as above at 180-210 days of age, and castrated for morphological studies. The time for attainment of complete spermatogenesis correlated significantly with most corporal parameters (i.e. scrotal circumference (r = 0.52); testicular weight (r = 0.61), epididymal weight (r = 0.60), penile/preputial separation (r = 0.75). The age of castrated ram lambs correlated with the degree of spermatogenesis (r = 0.83), although no significant correlations were found with live weight or with levels of circulating testosterone. The histology showed major variations in the degree of development of the seminiferous epithelium. Cells undergoing degeneration were a common finding through the initial stages of spermatogenesis, coincident to the presence of sperm abnormalities and foreign cells in semen. By day 180 and onwards, both histology and seminal picture normalized. It is concluded that, under these rearing conditions, the onset of puberty (expressed as morphologically established spermatogenesis) in Corriedale ram lambs is attained at 180-216 days of age when they reach 23 cm of scrotal circumference and 191 g of testis weight. The finding of a high correlation between these parameters (r: 0.93) confirms the usefulness of the measurement of scrotal circumference during clinical examination of ram lambs in this breed.


Asunto(s)
Crianza de Animales Domésticos , Ovinos/fisiología , Espermatogénesis/fisiología , Análisis de Varianza , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Clima , Masculino , Poaceae , Radioinmunoensayo/veterinaria , Estaciones del Año , Testosterona/sangre , Factores de Tiempo , Uruguay
18.
An Med Interna ; 16(9): 461-2, 1999 Sep.
Artículo en Español | MEDLINE | ID: mdl-10609359

RESUMEN

A case of acute oliguric renal failure secondary to poisoning by acetic acid (AA) is described. The patient presents caustic damage in the mucous digestive, myoglobinuria, thrombopaenia, elevation of the enzymes of damage tissular and acute hepatic affectation. To the entrance, the patient show a good hemodynamic state and the hematologic study discarded the hemolysis presence, what allowed to establish the direct action of the AA on the kidney like cause of the oliguric failure renal next to the tubular toxic effect of the myoglobin. The oral ingesta of AA is an unusual fact and its relationship with the acute renal failure it has not been communicated previously in our country.


Asunto(s)
Ácido Acético/envenenamiento , Lesión Renal Aguda/inducido químicamente , Oliguria/inducido químicamente , Lesión Renal Aguda/diagnóstico , Adulto , Estenosis Esofágica/inducido químicamente , Estenosis Esofágica/diagnóstico , Esofagitis/inducido químicamente , Gastritis/inducido químicamente , Humanos , Masculino , Oliguria/diagnóstico , Intoxicación/complicaciones , Intoxicación/diagnóstico , Intento de Suicidio
19.
Cell Death Dis ; 5: e1413, 2014 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-25210796

RESUMEN

The deregulation of miR-101 and DNMT3a has been implicated in the pathogenesis of multiple tumor types, but whether and how miR-101 silencing and DNMT3a overexpression contribute to lung tumorigenesis remain elusive. Here we show that miR-101 downregulation associates with DNMT3a overexpression in lung cancer cell lines and patient tissues. Ectopic miR-101 expression remarkably abrogated the DNMT3a 3'-UTR luciferase activity corresponding to the miR-101 binding site and caused an attenuated expression of endogenous DNMT3a, which led to a reduction of global DNA methylation and the re-expression of tumor suppressor CDH1 via its promoter DNA hypomethylation. Functionally, restoration of miR-101 expression suppressed lung cancer cell clonability and migration, which recapitulated the DNMT3a knockdown effects. Interestingly, miR-101 synergized with decitabine to downregulate DNMT3a and to reduce DNA methylation. Importantly, ectopic miR-101 expression was sufficient to trigger in vivo lung tumor regression and the blockage of metastasis. Consistent with these phenotypes, examination of xenograft tumors disclosed an increase of miR-101, a decrease of DNMT3a and the subsequent DNA demethylation. These findings support that the loss or suppression of miR-101 function accelerates lung tumorigenesis through DNMT3a-dependent DNA methylation, and suggest that miR-101-DNMT3a axis may have therapeutic value in treating refractory lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Animales , Carcinogénesis , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética
20.
Oncogene ; 31(10): 1264-74, 2012 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-21804599

RESUMEN

The phosphatidylinositol-3-OH kinase (PI3K)-Akt pathway is activated in cancer by genetic or epigenetic events and efforts are under way to develop targeted therapies. phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is the major brake of the pathway and a common target for inactivation in glioblastoma, one of the most aggressive and therapy-resistant cancers. To achieve potent inhibition of the PI3K-Akt pathway in glioblastoma, we need to understand its mechanism of activation by investigating the interplay between its regulators. We show here that PTEN modulates the PI3K-Akt pathway in glioblastoma within a tumor suppressor network that includes Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) and pleckstrin-homology domain leucine-rich repeat protein phosphatases 1 (PHLPP1). The NHERF1 adaptor, previously characterized by our group as a PTEN ligand and regulator, shows also PTEN-independent Akt-modulating effects that led us to identify the PHLPP1/PHLPP2 Akt phosphatases as NHERF1 ligands. NHERF1 interacts via its PDZ domains with PHLPP1/PHLPP2 and scaffolds heterotrimeric complexes with PTEN. Functionally, PHLPP1 requires NHERF1 for membrane localization and growth-suppressive effects. PHLPP1 loss boosts Akt phosphorylation only in PTEN-negative cells and cooperates with PTEN loss for tumor growth. In a panel of low-grade and high-grade glioma patient samples, we show for the first time a significant disruption of all three members of the PTEN-NHERF1-PHLPP1 tumor suppressor network in high-grade tumors, correlating with Akt activation and patient's abysmal survival. We thus propose a PTEN-NHERF1-PHLPP PI3K-Akt pathway inhibitory network that relies on molecular interactions and can undergo parallel synergistic hits in glioblastoma.


Asunto(s)
Neoplasias Encefálicas/etiología , Glioblastoma/etiología , Proteínas Nucleares/fisiología , Fosfohidrolasa PTEN/fisiología , Fosfoproteínas Fosfatasas/fisiología , Fosfoproteínas/fisiología , Intercambiadores de Sodio-Hidrógeno/fisiología , Proteínas Supresoras de Tumor/fisiología , Anciano , Humanos , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Transducción de Señal
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