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1.
J Dairy Sci ; 105(5): 4272-4288, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35221068

RESUMEN

This research explores possible options to reduce greenhouse gas (GHG) emissions in the Australian dairy industry by (1) including an environmental component in the national breeding program and (2) estimating the economic and environmental impacts of implementation of the subsequent indexes. A total of 12 possible selection indexes were considered. These indexes were developed to predict changes in gross per-animal methane production (using 3 scenarios depending on availability and efficacy of a direct methane trait breeding value prediction) with 4 different carbon prices, integrating them into an augmentation of the current conventional national selection index. Although some economic response is lost with inclusion of the GHG subindexes in the Balanced Performance Index, options do exist where this loss is marginal and, even in scenarios where all selection pressure is based on the environmental weighting, economic progress is still made in all cases. When including environmental traits within an index, if a relatively low percentage of economic gain or index progression is sacrificed, then approximately 40 to 50% of the maximum possible reductions in emissions may be achieved. This concurrent selection of estimated breeding values that have a correlated favorable response in emissions in addition to direct selection on a residual methane trait allows a high level of methane reduction to be achieved with a realized cost to farmers that is far lower than the economic value placed on carbon. By implementing a GHG subindex in the national breeding program, we can achieve up to a 7.9% decrease in residual methane and 9 times the reduction in gross emissions in 10 yr, compared with the current breeding program, with little to no cost to farmers. By 2050, selection based on one of the more moderate index scenarios at a carbon price of AUD$250/t (AUD$1 = US$0.71), or opportunity cost to farmers of AUD$87.22, will reduce gross emissions by 8.23% and emissions intensity by 21.25%, therefore offering a mitigation strategy that will be effective at reducing emissions with little compromise to profit.


Asunto(s)
Industria Lechera , Gases de Efecto Invernadero , Animales , Australia , Carbono , Metano , Leche , Selección Genética
2.
J Dairy Sci ; 104(10): 10979-10990, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34334195

RESUMEN

The dairy industry has been scrutinized for the environmental impact associated with rearing and maintaining cattle for dairy production. There are 3 possible opportunities to reduce emissions through genetic selection: (1) a direct methane trait, (2) a reduction in replacements, and (3) an increase in productivity. Our aim was to estimate the independent effects of traits in the Australian National Breeding Objective on the gross methane production and methane intensity (EI) of the Australian dairy herd of average genetic potential. Based on similar published research, the traits determined to have an effect on emissions include production, fertility, survival, health, and feed efficiency. The independent effect of each trait on the gross emissions produced per animal due to genetic improvement and change in EI due to genetic improvement (intensity value, IV) were estimated and compared. Based on an average Australian dairy herd, the gross emissions emitted per cow per year were 4,297.86 kg of carbon dioxide equivalents (CO2-eq). The annual product output, expressed in protein equivalents (protein-eq), and EI per cow were 339.39 kg of protein-eq and 12.67 kg of CO2-eq/kg of protein-eq, respectively. Of the traits included in the National Breeding Objective, genetic progress in survival and feed saved were consistently shown to result in a favorable environmental impact. Conversely, production traits had an unfavorable environmental impact when considering gross emissions, and favorable when considering EI. Fertility had minimal impact as its effects were primarily accounted for through survival. Mastitis resistance only affected IV coefficients and to a very limited extent. These coefficients may be used in selection indexes to apply emphasis on traits based on their environmental impact, as well as applied by governments and stakeholders to track trends in industry emissions. Although initiatives are underway to develop breeding values to reduce methane by combining small methane data sets internationally, alternative options to reduce emissions by utilizing selection indexes should be further explored.


Asunto(s)
Metano , Leche , Animales , Australia , Bovinos/genética , Industria Lechera , Ambiente , Femenino
3.
J Dairy Sci ; 104(8): 8983-9001, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34001361

RESUMEN

Selecting for lower methane (CH4) emitting animals is one of the best approaches to reduce CH4 given that genetic progress is permanent and cumulative over generations. As genetic selection requires a large number of animals with records and few countries actively record CH4, combining data from different countries could help to expedite accurate genetic parameters for CH4 traits and build a future genomic reference population. Additionally, if we want to include CH4 in the breeding goal, it is important to know the genetic correlations of CH4 traits with other economically important traits. Therefore, the aim of this study was first to estimate genetic parameters of 7 suggested methane traits, as well as genetic correlations between methane traits and production, maintenance, and efficiency traits using a multicountry database. The second aim was to estimate genetic correlations within parities and stages of lactation for CH4. The third aim was to evaluate the expected response of economically important traits by including CH4 traits in the breeding goal. A total of 15,320 methane production (MeP, g/d) records from 2,990 cows belonging to 4 countries (Canada, Australia, Switzerland, and Denmark) were analyzed. Records on dry matter intake (DMI), body weight (BW), body condition score, and milk yield (MY) were also available. Additional traits such as methane yield (MeY; g/kg DMI), methane intensity (MeI; g/kg energy-corrected milk), a genetic standardized methane production, and 3 definitions of residual methane production (g/d), residual feed intake, metabolic BW (MBW), BW change, and energy-corrected milk were calculated. The estimated heritability of MeP was 0.21, whereas heritability estimates for MeY and MeI were 0.30 and 0.38, and for the residual methane traits heritability ranged from 0.13 to 0.16. Genetic correlations between different methane traits were moderate to high (0.41 to 0.97). Genetic correlations between MeP and economically important traits ranged from 0.29 (MY) to 0.65 (BW and MBW), being 0.41 for DMI. Selection index calculations showed that residual methane had the most potential for inclusion in the breeding goal when compared with MeP, MeY, and MeI, as residual methane allows for selection of low methane emitting animals without compromising other economically important traits. Inclusion of residual feed intake in the breeding goal could further reduce methane, as the correlation with residual methane is moderate and elicits a favorable correlated response. Adding a negative economic value for methane could facilitate a substantial reduction in methane emissions while maintaining an increase in milk production.


Asunto(s)
Lactancia , Metano , Animales , Australia , Canadá , Bovinos/genética , Dieta , Femenino , Lactancia/genética , Leche , Suiza
4.
J Dairy Sci ; 104(1): 539-549, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33131823

RESUMEN

Methane is a greenhouse gas of high interest to the dairy industry, with 57% of Australia's dairy emissions attributed to enteric methane. Enteric methane emissions also constitute a loss of approximately 6.5% of ingested energy. Genetic selection offers a unique mitigation strategy to decrease the methane emissions of dairy cattle, while simultaneously improving their energy efficiency. Breeding objectives should focus on improving the overall sustainability of dairy cattle by reducing methane emissions without negatively affecting important economic traits. Common definitions for methane production, methane yield, and methane intensity are widely accepted, but there is not yet consensus for the most appropriate method to calculate residual methane production, as the different methods have not been compared. In this study, we examined 9 definitions of residual methane production. Records of individual cow methane, dry matter intake (DMI), and energy corrected milk (ECM) were obtained from 379 animals and measured over a 5-d period from 12 batches across 5 yr using the SF6 tracer method and an electronic feed recording system, respectively. The 9 methods of calculating residual methane involved genetic and phenotypic regression of methane production on a combination of DMI and ECM corrected for days in milk, parity, and experimental batch using phenotypes or direct genomic values. As direct genomic values (DGV) for DMI are not routinely evaluated in Australia at this time, DGV for FeedSaved, which is derived from DGV for residual feed intake and estimated breeding value for bodyweight, were used. Heritability estimates were calculated using univariate models, and correlations were estimated using bivariate models corrected for the fixed effects of year-batch, days in milk, and lactation number, and fitted using a genomic relationship matrix. Residual methane production candidate traits had low to moderate heritability (0.10 ± 0.09 to 0.21 ± 0.10), with residual methane production corrected for ECM being the highest. All definitions of residual methane were highly correlated phenotypically (>0.87) and genetically (>0.79) with one another and moderately to highly with other methane candidate traits (>0.59), with high standard errors. The results suggest that direct selection for a residual methane production trait would result in indirect, favorable improvement in all other methane traits. The high standard errors highlight the importance of expanding data sets by measuring more animals for their methane emissions and DMI, or through exploration of proxy traits and combining data via international collaboration.


Asunto(s)
Bovinos/metabolismo , Metano/metabolismo , Animales , Australia , Peso Corporal/genética , Bovinos/genética , Industria Lechera , Dieta/veterinaria , Femenino , Genoma , Gases de Efecto Invernadero , Lactancia , Leche , Fenotipo , Embarazo , Selección Artificial
5.
J Dairy Sci ; 102(12): 11142-11152, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31587909

RESUMEN

In this study, we estimated genetic parameters and genomic prediction accuracies of serum biomarkers of health in early-lactation dairy cows. A single serum sample was taken from 1,393 cows, located on 14 farms in southeastern Australia, within 30 d after calving. Sera were analyzed for biomarkers of energy balance (ß-hydroxybutyrate and fatty acids), macromineral status (Ca and Mg), protein nutritional status (urea and albumin), and immune status (globulins, albumin-to-globulin ratio, and haptoglobin). After editing, 47,162 SNP marker genotypes were used to estimate genomic heritabilities and breeding values (GEBV) for these traits in ASReml. Heritabilities were low for ß-hydroxybutyrate, fatty acids, Ca, Mg, and urea (0.09 ± 0.04, 0.18 ± 0.05, 0.07 ± 0.04, 0.19 ± 0.06, and 0.18 ± 0.05, respectively), and moderate for albumin, globulins, and albumin-to-globulin ratio (0.27 ± 0.06, 0.46 ± 0.06, and 0.41 ± 0.06, respectively). The heritability of haptoglobin concentration was close to 0. The magnitude of genetic correlations between traits (estimated using bivariate models) varied considerably (0.01 to 0.96), and standard errors of these correlations were high (0.02 to 0.44). Interestingly, the direction of most genetic correlations was favorable, suggesting that selecting for more optimal concentrations of one biomarker may result in more optimal concentrations of other biomarkers. Correlations between biomarker GEBV and existing breeding values for survival, somatic cell count, and daughter fertility were small to moderate (0.07 to 0.45) and favorable, whereas correlations with breeding values for milk production traits were small (≤0.15). Accuracies of GEBV were evaluated by using 5-fold cross validation, and by calculating accuracies from prediction error variances associated with the GEBV. Accuracies of GEBV predicted using 5-fold cross validation were low (0.05 to 0.27), whereas the means of individual accuracies were greater, ranging from 0.31 to 0.51. Although increasing the size of the reference population should theoretically improve accuracies, our results suggest that genomic prediction of health biomarkers may allow identification of cows that are less susceptible to diseases in early lactation.


Asunto(s)
Biomarcadores/sangre , Bovinos/sangre , Genómica , Indicadores de Salud , Lactancia/genética , Ácido 3-Hidroxibutírico/sangre , Animales , Cruzamiento , Bovinos/genética , Ácidos Grasos/sangre , Femenino , Fertilidad , Genotipo , Fenotipo
6.
Animal ; 15(1): 100005, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33573960

RESUMEN

A recently developed methodological approach for determining the greenhouse gas emissions impact of national breeding programs was applied to measure the effects of current and future breeding goals on the emission intensity (EI) of the Canadian dairy industry. Emission intensity is the ratio of greenhouse gas outputted in comparison to the product generated. Traits under investigation affected EI by either decreasing the direct emissions yield (i.e. increasing feed performance), changing herd structure (i.e. prolonging herd life) or through the dilution effect of increased production (i.e. increasing fat yield). The intensity value (IV) of each trait, defined as the change in emissions' intensity per unit change in each trait, was calculated for each of the investigated traits. The IV trend of these traits was compared for the current and prospective selection index, as well as for a system with and without quota (the supply management policy designed to prevent overproduction). The overall EI of the average genetic merit Canadian dairy herd per breeding female was 5.07 kg CO2eq/kg protein equivalent output. The annual reduction in EI due to the improvement of production traits was -0.027, -0.018 and -0.006 for fat, protein and milk other solids, respectively. The functional traits, herd life and mastitis resistance, had more modest effects (-0.008 and -0.001, respectively). These results are consistent with international studies that identified traits related to production, survival, health and fertility as having the largest impact on the environmental footprint of dairy cattle. Overall, the dairy industry is becoming more efficient by reducing its EI through selection of environmentally favorable traits, with a 1% annual reduction of EI in Canada.


Asunto(s)
Industria Lechera , Leche , Animales , Canadá , Bovinos/genética , Ambiente , Femenino , Estudios Prospectivos
7.
Animal ; 14(1): 171-179, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31327334

RESUMEN

Feed represents a substantial proportion of production costs in the dairy industry and is a useful target for improving overall system efficiency and sustainability. The objective of this study was to develop methodology to estimate the economic value for a feed efficiency trait and the associated methane production relevant to Canada. The approach quantifies the level of economic savings achieved by selecting animals that convert consumed feed into product while minimizing the feed energy used for inefficient metabolism, maintenance and digestion. We define a selection criterion trait called Feed Performance (FP) as a 1 kg increase in more efficiently used feed in a first parity lactating cow. The impact of a change in this trait on the total lifetime value of more efficiently used feed via correlated selection responses in other life stages is then quantified. The resulting improved conversion of feed was also applied to determine the resulting reduction in output of emissions (and their relative value based on a national emissions value) under an assumption of constant methane yield, where methane yield is defined as kg methane/kg dry matter intake (DMI). Overall, increasing the FP estimated breeding value by one unit (i.e. 1 kg of more efficiently converted DMI during the cow's first lactation) translates to a total lifetime saving of 3.23 kg in DMI and 0.055 kg in methane with the economic values of CAD $0.82 and CAD $0.07, respectively. Therefore, the estimated total economic value for FP is CAD $0.89/unit. The proposed model is robust and could also be applied to determine the economic value for feed efficiency traits within a selection index in other production systems and countries.


Asunto(s)
Contaminación del Aire/economía , Industria Lechera/economía , Ingestión de Alimentos , Metano/economía , Animales , Canadá , Bovinos , Dieta/veterinaria , Metano/metabolismo
8.
Science ; 220(4596): 527-30, 1983 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-6836298

RESUMEN

Brief deprivation of vision after unilateral lesions of the frontal eye field prevents the appearance of contralateral inattention to visual, auditory, and somatosensory stimuli. The forced circling that accompanies inattention, however, is not affected. An equivalent preoperative period in the dark only partly reduces inattention symptoms. Visual deprivation does not reduce or prevent inattention resulting from lesions of the superior colliculus.


Asunto(s)
Atención/fisiología , Lóbulo Frontal/fisiología , Privación Sensorial/fisiología , Colículos Superiores/fisiología , Percepción Visual/fisiología , Animales , Oscuridad , Masculino , Movimiento , Ratas
9.
Lung Cancer ; 48(1): 47-57, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15777970

RESUMEN

UNLABELLED: Both cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) are thought to play important roles in the pathogenesis of non-small cell lung cancer (NSCLC). A number of in vitro studies have postulated a link between EGFR activation and subsequent COX-2 upregulation. The relationship between these factors has not been established in patients with NSCLC. COX-2 and EGFR expression were studied in 172 NSCLC specimens using standard immunohistochemical techniques. Western blotting was used to determine COX-2 and EGFR levels in five NSCLC cell lines. The effect of treatment with EGF on COX-2 expression in A549 cells was assessed. RESULTS: Both EGFR and COX-2 are overexpressed in NSCLC. The predominant pattern of COX-2 and EGFR staining was cytoplasmic. Membranous EGFR staining was seen in 23.3% of cases. There was no relationship between COX-2 and EGFR expression and survival or any clinicopathological features. No correlation was seen between EGFR expression and COX-2 expression in the immunohistochemical series or in the cell lines. Treatment with EGF did not upregulate COX-2 levels in A549 cells, either in serum free or serum-supplemented conditions. CONCLUSIONS: Although COX-2 and EGFR are over-expressed in NSCLC neither was of prognostic significance in this series of cases. There is no correlation between these two factors in either tumour samples or cell lines. Although these factors show no correlation in NSCLC, they remain potential, though independent targets for treatment.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/biosíntesis , Perfilación de la Expresión Génica , Neoplasias Pulmonares/genética , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Anciano , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Ciclooxigenasa 2 , Citoplasma , Receptores ErbB/análisis , Receptores ErbB/genética , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Proteínas de la Membrana , Pronóstico , Prostaglandina-Endoperóxido Sintasas/análisis , Prostaglandina-Endoperóxido Sintasas/genética , Análisis de Supervivencia , Células Tumorales Cultivadas , Regulación hacia Arriba
10.
Biol Psychiatry ; 46(1): 73-7, 1999 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-10394475

RESUMEN

BACKGROUND: Treatment-resistance in schizophrenia remains a public health problem. Clozapine has been shown to be effective in about one third of this population, but carries with it medical risks and weekly blood draws. As olanzapine is a drug with a very similar biochemical profile to clozapine, it is important to evaluate whether non-response to olanzapine predicts clozapine non-response. METHODS: Forty-four treatment-resistant patients received eight weeks of olanzapine, either in a double-blind trial or subsequent open treatment at a mean daily dose of 25 mg/day. Two of 44 patients (5%) responded to olanzapine treatment. Patients who did not respond could then receive clozapine. Twenty-seven subsequently received an 8-week open trial of clozapine. RESULTS: Patients who did and did not receive clozapine did not differ demographically or in psychopathology. Eleven of 27 (41%) met a priori response criteria during clozapine treatment (mean dose 693 mg/day) after failing to respond to olanzapine. CONCLUSIONS: This study demonstrates that failure to respond to olanzapine treatment does not predict failure to clozapine. Treatment-resistant patients who fail on olanzapine may benefit from a subsequent trial of clozapine.


Asunto(s)
Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Pirenzepina/análogos & derivados , Esquizofrenia/tratamiento farmacológico , Adulto , Benzodiazepinas , Método Doble Ciego , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Olanzapina , Pirenzepina/uso terapéutico , Resultado del Tratamiento
11.
Neuropsychologia ; 27(9): 1119-27, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2812296

RESUMEN

Monkeys were trained on a conditional position discrimination in which the conditional cue was a light blinking at two distinct rates and the discriminanda (illuminated buttons) appeared in varying symmetrical positions of eccentricity. Unilateral arcuate, posterior parietal, or principal sulcus lesions were performed at criterion. The monkeys were tested to recovery when a homologous lesion was made contralaterally. The first of two analyses examined a period of 4 weeks following each lesion; the unit of analysis was lesions. The arcuate and parietal lesions produced impairments on both widely eccentric and central discriminanda locations; initially, virtually all responses were deflected to the ipsilateral side. There was significant improvement after the arcuate and parietal lesions from weeks 1 to 4. An analysis of total trials to criterion showed major deficits from the second arcuate and parietal lesions, with the arcuate lesion impairment being particularly severe. These results establish that a spatial concept of left vs right is seriously deranged by unilateral lesions of cortical association areas involved in spatial orientation and discrimination.


Asunto(s)
Núcleo Arqueado del Hipotálamo/fisiología , Condicionamiento Operante/fisiología , Aprendizaje Discriminativo/fisiología , Dominancia Cerebral/fisiología , Orientación/fisiología , Lóbulo Parietal/fisiología , Percepción Visual/fisiología , Animales , Atención/fisiología , Mapeo Encefálico , Femenino , Lóbulo Frontal/fisiología , Macaca , Masculino , Desempeño Psicomotor/fisiología
12.
Neuropharmacology ; 35(11): 1537-46, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-9025101

RESUMEN

Release of acetylcholine (ACh) from the presynaptic terminals in skate electric organ was tested for its sensitivity to calcium channel antagonists. A pharmacological profile was established by measuring inhibition of K(+)-stimulated release of [3H]ACh from prelabelled tissue slices. Peptide antagonists of N-type (omega-conotoxins GVIA and MVIIA) and P-type (omega-agatoxin-IVA) channels had no effect, whereas both omega-conotoxins MVIIC and SVIB produced concentration-dependent inhibition and could completely block ACh release. omega-Conotoxin GVIA and omega-agatoxin IVA did not attenuate the block by omega-conotoxin MVIIC. The inorganic ions, Cd2+ and Ni2+, also produced a full inhibition of release (Cd2+ > > Ni2+) and Gd3+ a partial one. Drugs targeting L-type channels (diltiazem, nifedipine and verapamil) at low microM concentrations and a synthetic analogue of the polyamine toxin from funnel web spider venom (sFTX) at 1 mM were all non-inhibitory. Inhibition by omega-conotoxins MVIIC (IC50 25 nM) and SVIB (IC50 500 nM) was reversible and modulated by external concentrations of Ca2+. Inhibitory potency was increased by lowering and decreased by elevating external Ca2+. This "antagonistic" effect of Ca2+ was also seen with Cd2+ inhibition. The inhibitory potency of omega-conotoxin MVIIC was unaffected by predepolarisation. End plate potentials generated by release of endogenous ACh in electrically-stimulated slices were also reversibly blocked by Cd2+ and omega-conotoxins MVIIC and SVIB but were unaffected by omega-conotoxin GVIA and omega-agatoxin IVA. It is concluded that ACh release in skate electric organ depends on presynaptic calcium channels which have different pharmacological properties from established sub-types.


Asunto(s)
Acetilcolina/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Órgano Eléctrico/metabolismo , Receptores Presinapticos/metabolismo , Rajidae/metabolismo , Animales , Órgano Eléctrico/efectos de los fármacos , Estimulación Eléctrica , Electrofisiología , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Técnicas In Vitro , Cinética , Potasio/farmacología , Receptores Presinapticos/efectos de los fármacos
13.
Neuroscience ; 80(2): 635-51, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9284364

RESUMEN

Schwann cells are integral cellular components of the dense cholinergic presynaptic plexus (nerve plate) which innervates each electrocyte in skate electric organ. Using the Ca2+-sensitive dye fura-2, we have followed the response in these cells to various chemical challenges. In K+ depolarized nerve plates nerve terminals consistently responded with a rapid and sustained Ca2+ signal. Schwann cell responses to depolarization were rarely seen but, when observed, were always delayed in onset when compared to nerve terminal response (6-10 s later). The possibility that these responses were triggered by mediators released from nerve terminals was tested by direct application of candidate substances. Schwann cells were found to respond to adenosine triphosphate and adenosine diphosphate with a biphasic increase of intracellular Ca2+ concentration, a rapid peak response being followed in the majority of cells by a sustained plateau phase. In the absence of external Ca2+ only the transient peak response was observed. Depletion of internal Ca2+ stores with thapsigargin completely inhibited the adenosine triphosphate-stimulated rise in Schwann cell Ca2+. The response to adenosine triphosphate was concentration-dependent (EC50 2.8 microM) and was reversibly blocked by two antagonists of P2 purinoceptors: suramin and reactive blue 2. Adenosine diphosphate and 2-methylthio-adenosine triphosphate were equipotent with adenosine triphosphate and at high concentrations (100 microM) diadenosine tetraphosphate produced responses comparable to low concentrations of adenosine triphosphate. Adenosine, adenosine monophosphate, the alpha beta-methylene analogues of adenosine triphosphate and adenosine diphosphate, uridine triphosphate, cytidine triphosphate and guanosine triphosphate were without significant effect. These results show that, in skate electric organ Schwann cells, the release of Ca2+ from intracellular stores is triggered by adenosine triphosphate acting on P(2gamma) receptors and suggest that Schwann cells may be targets for synaptically-released adenosine triphosphate in the electric organ model of the neuromuscular junction.


Asunto(s)
Adenosina Trifosfato/farmacología , Calcio/metabolismo , Órgano Eléctrico/metabolismo , Terminaciones Nerviosas/fisiología , Receptores Purinérgicos P2/efectos de los fármacos , Células de Schwann/metabolismo , Rajidae/fisiología , Acetilcolina/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Órgano Eléctrico/efectos de los fármacos , Órgano Eléctrico/ultraestructura , Técnicas In Vitro , Microscopía Electrónica , Microscopía Fluorescente , Terminaciones Nerviosas/efectos de los fármacos , Terminaciones Nerviosas/metabolismo , Agonistas del Receptor Purinérgico P2 , Antagonistas del Receptor Purinérgico P2 , Células de Schwann/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología
14.
Lung Cancer ; 39(1): 1-13, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12499088

RESUMEN

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1beta, Tumour Necrosis Factor (TNF)-alpha and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Receptores ErbB/metabolismo , Isoenzimas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos Clínicos como Asunto , Ciclooxigenasa 2 , Humanos , Neoplasias Pulmonares/patología , Proteínas de la Membrana
15.
J Neuroendocrinol ; 10(11): 829-37, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9831259

RESUMEN

The neurosteroid pregnenolone sulphate (PS) interacts allosterically with ionotropic glutamate receptors and thereby could be an important modulator of activity within the hypothalamic magnocellular nuclei. The present in-vitro study therefore examined the effect of perifusion of PS (100 microM) on activity of supraoptic oxytocin (OT) and vasopressin (VP) neurones, in which firing was stimulated by local application of glutamate, NMDA or AMPA. In the presence of locally applied glutamate, PS significantly potentiated firing in putative VP neurones, but had little effect on putative OT neurones. In both cell types, PS increased firing in the presence of NMDA and depressed firing in the presence of AMPA. The action of PS on glutamate- and NMDA-stimulated firing was unaffected by addition of the GABA(A) receptor antagonist, picrotoxin (50 microM). The suppressive action of PS on AMPA-stimulated firing was, however, reversed by picrotoxin and therefore probably requires intact GABAergic transmission for its expression. When putative VP neurones were stimulated by local application of K+, in the presence of picrotoxin, PS evoked a small increase in the ongoing activity, although this did not reach significance. When the glutamate receptor antagonists, NBQX (20 microM) and AP5 (40 microM), were included in the medium, no change in K+ -stimulated firing was observed. Hence PS has no effect on activity of putative VP neurones in the absence of exogenous and endogenous glutamate excitation. In conclusion, PS selectively potentiates glutamate-stimulated activity in putative VP neurones, probably via NMDA receptors, thus providing a mechanism whereby this neurosteroid might exert rapid non-genomic effects on VP secretion. The lack of effect of PS in putative OT neurones probably relates to the relatively small involvement of NMDA receptors in mediating glutamate excitation in this cell type.


Asunto(s)
Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oxitocina/metabolismo , Pregnenolona/farmacología , Núcleo Supraóptico/metabolismo , Vasopresinas/metabolismo , Animales , Electrofisiología , Agonistas de Aminoácidos Excitadores/farmacología , Femenino , Ácido Glutámico/farmacología , N-Metilaspartato/farmacología , Neuronas/fisiología , Ratas , Ratas Wistar , Núcleo Supraóptico/citología , Núcleo Supraóptico/efectos de los fármacos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacología
16.
J Neuroendocrinol ; 12(9): 843-52, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10971809

RESUMEN

The mesencephalic ventral tegmentum has been implicated in the milk-ejection reflex and modulation of inputs from this region could provide a mechanism whereby central oxytocin facilitates synchronous bursting of oxytocin neurones during suckling. Experiments were therefore undertaken to investigate the effect of intracerebroventricular (i.c.v.) oxytocin on the response of oxytocin neurones to ventral tegmental stimulation. Oxytocin neurones were recorded in the supraoptic nucleus of urethane-anaesthetized lactating rats during suckling, and their response to single shock stimulation of the ventral tegmentum was monitored using peri-stimulus time-interval histograms. Before i.c.v. oxytocin, oxytocin neurones were either unresponsive to ventral tegmental stimulation, or displayed a small inhibition. However, after administration of oxytocin (2.2 ng i.c.v.), seven out of eight neurones tested displayed a pronounced excitatory response (onset latency 78.4 +/- 4.8 ms, duration 73.4 +/- 8.3 ms). This permissive effect on the excitatory response was only observed in the presence of suckling, and followed the same time course as facilitation of the milk-ejection reflex, being maximal immediately before each facilitated bursting response in the oxytocin neurones. The response to ventral tegmental stimulation remained unaltered after intraperitoneal administration of hypertonic saline to cause a generalized increase in the excitability of the oxytocin neurones. Moreover, i.c.v. oxytocin had no effect on the response of oxytocin neurones to stimulation of a descending input from the medial septum. In conclusion, administration of i.c.v. oxytocin has a selective permissive effect on the excitation of oxytocin neurones from the ventral tegmentum, and this supports previous in vitro studies suggesting that centrally released oxytocin may act as a modulator of afferent transmission to the magnocellular nuclei. This effect on the afferent excitation of oxytocin neurones may provide a mechanism whereby i.c.v. oxytocin facilitates suckling-evoked bursting activity.


Asunto(s)
Lactancia/fisiología , Neuronas/fisiología , Oxitocina/administración & dosificación , Oxitocina/fisiología , Potenciales de Acción , Animales , Estimulación Eléctrica , Electrodos , Femenino , Inyecciones Intraventriculares , Cinética , Eyección Láctea/fisiología , Oxitocina/farmacología , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Conducta en la Lactancia
17.
Behav Neurosci ; 101(1): 134-8, 1987 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3828052

RESUMEN

Lesions of right parietal cortex in the rat increase activity in the open field compared with left parietal lesions, especially after section of the corpus callosum. Left or right motor or medial frontal cortex lesions do not have a lateralized effect. This evidence of a localized asymmetry between the cerebral hemispheres strongly implies that right parietal cortex has a role in emotionality in this species. Our findings suggest a functional similarity to right parietal cortex in man.


Asunto(s)
Dominancia Cerebral/fisiología , Emociones/fisiología , Lóbulo Parietal/fisiología , Animales , Nivel de Alerta/fisiología , Mapeo Encefálico , Cuerpo Calloso/fisiología , Lóbulo Frontal/fisiología , Masculino , Actividad Motora/fisiología , Ratas , Ratas Endogámicas
18.
Behav Brain Res ; 22(3): 227-31, 1986 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-3790245

RESUMEN

Rats were given unilateral aspiration lesions of parietal, medial frontal, or dorsolateral frontal (motor) cortex and then tested for visual, auditory and tactile neglect, and for circling. All medial frontal lesion animals showed contralateral neglect in each modality and circled ipsiversively. The parietal lesion rats initially displayed contralateral visual and auditory neglect as severe as that in the medial frontal group. Three weeks after the lesions, the parietal group had a smaller residual deficit on the visual test than the medial frontal group. In the first week, parietal animals responded less than the medial frontals to stroking the vibrissae but were more responsive to mild pinching of a toe contralateral to the lesion side. In striking contrast to the medial frontal animals, the parietal group circled strongly to the contralateral side. No rat with a motor cortex lesion neglected or circled preferentially. Like medial frontal cortex, unilateral parietal lesions also produce neglect and circling, but there are important features distinguishing unilateral lesion effects in these two regions.


Asunto(s)
Lóbulo Frontal/fisiología , Orientación/fisiología , Lóbulo Parietal/fisiología , Sensación/fisiología , Estimulación Acústica , Animales , Masculino , Estimulación Luminosa , Estimulación Física , Ratas , Conducta Estereotipada/fisiología , Campos Visuales
19.
Behav Brain Res ; 19(2): 187-90, 1986 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3964408

RESUMEN

Unilateral lesions in such brain regions as medial frontal cortex and superior colliculus produce polysensory neglect contralateral to the lesion. Since the pineal gland is an unpaired brain structure, both electrophysiologically and hormonally responsive to visual and auditory stimulation, it may modulate bilateral sensory attention mechanisms. Long-Evans male rats were given pineal or sham lesions and were tested behaviourally. Sensory assessment revealed that in comparison to sham animals rats with pineal lesion exhibited unilateral visual and auditory neglect to stimuli presented on either side of the body. Animals with pineal lesions were more likely than sham-lesioned animals to demonstrate visual allesthesis and, compared to sham-lesioned rats, showed extinction on the left side to bilateral simultaneous visual stimulation. This is the first report that midline neuroendocrine damage can produce bilateral sensory inattention.


Asunto(s)
Atención/fisiología , Percepción Auditiva/fisiología , Glándula Pineal/fisiología , Percepción Visual/fisiología , Animales , Mapeo Encefálico , Masculino , Orientación/fisiología , Ratas , Reflejo/fisiología , Campos Visuales
20.
Brain Res ; 767(1): 158-61, 1997 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-9365030

RESUMEN

Experiments were undertaken to compare effects of the NMDA and non-NMDA receptor antagonists, AP5 (40 microM) and NBQX (10 microM), on glutamate-induced firing in supraoptic oxytocin (OT) and vasopressin (VP) neurones in vitro. In putative OT neurones NBQX caused a significantly greater reduction in firing than AP5, whilst in putative VP neurones both antagonists reduced activity powerfully and to a similar extent. The relatively small effect of AP5 in putative OT neurones was unaffected by the removal of extracellular magnesium. These results suggest that glutamate-induced firing in putative OT neurones is predominantly controlled by non-NMDA receptors.


Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/farmacología , Neuronas/efectos de los fármacos , Oxitocina/análisis , 2-Amino-5-fosfonovalerato/farmacología , Animales , Leucina Encefalina-2-Alanina/farmacología , Femenino , Técnicas In Vitro , Neuronas/química , Quinoxalinas/farmacología , Ratas , Ratas Wistar
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