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Control of algal blooms and associated biologically-induced water quality risks in drinking reservoirs is problematic. Copper sulphate (CuSO4) treatment is one intervention that has been utilised for >100 years. Evidence indicates a favourable short-term reduction in Cyanobacterial biomass (e.g. bloom termination), but here we indicate that it may also increase longer-term water quality risk. In 2022, we investigated the impacts of CuSO4 spraying on Cyanobacterial communities and nutrient levels within a drinking water supply reservoir using environmental DNA (eDNA) to assess community shifts, alongside monitoring nutrient fractions, orthophosphate (OP) and total phosphate (TP), post-treatment. CuSO4 application successfully reduced Cyanobacterial abundance, however elimination of Cyanobacteria resulted in a shift in bacterial dominance favouring Planctomycetota throughout the summer and a combination of Actinobacteriota and Verrucomicrobiota, throughout autumn. As Cyanobacterial abundance recovered post-treatment, Cyanobacterial genera demonstrated greater diversity compared to only three Cyanobacterial genera present across samples pre-treatment, and included taxa associated with water quality risk (e.g. taste and odour (T&O) metabolite and toxin producers). The increase in Cyanobacteria post-treatment was attributed to an increase in biologically available nutrients, primarily a significant increase in OP. Overall, findings suggest that the significant shift in biodiversity likely induces a less stable ecosystem with greater plasticity of response to changing environmental and biogeochemical variables. Legacy implications of CuSO4 spraying, in terms of shifts in ecosystem and nutrient balance over time, may have implications for drinking water quality, but importantly also for reservoir management options. As such, the effects of CuSO4 spraying should be considered carefully before consideration as a contender for in-reservoir biological control.
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Sulfato de Cobre , Cianobacterias , Calidad del Agua , Cianobacterias/efectos de los fármacos , EutrofizaciónRESUMEN
There is growing evidence that anaesthetic trainees experience, and may be particularly susceptible to, high levels of work stress, burnout and depression. This is concern for the safety and wellbeing of these doctors and for the patients they treat. To date, there has been no in-depth evaluation of these issues among UK anaesthetic trainees to examine which groups may be most affected, and to identify the professional and personal factors with which they are associated. We conducted an anonymous electronic survey to determine the prevalence of perceived stress, risk of burnout/depression and work satisfaction among anaesthetic trainees within South-West England and Wales, and explored in detail the influence of key baseline characteristics, lifestyle and anaesthetic training variables. We identified a denominator of 619 eligible participants and received 397 responses, a response rate of 64%. We observed a high prevalence of perceived stress; 37% (95%CI 32-42%), burnout risk 25% (21-29%) and depression risk 18% (15-23%), and found that these issues frequently co-exist. Having no children, > 3 days sickness absence in the previous year, ≤ 1 h.week-1 of exercise and > 7.5 h.week-1 of additional non-clinical work were independant predictors of negative psychological outcomes. Although female respondents reported higher stress, burnout risk was more likely in male respondents. This information could help in the identification of at-risk groups as well as informing ways to support these groups and to influence resource and intervention design. Targeted interventions, such as modification of exercise behaviour and methods of reducing stressors relating to non-clinical workloads, warrant further research.
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Anestesiólogos/psicología , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Depresión/epidemiología , Depresión/psicología , Satisfacción en el Trabajo , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Adulto , Familia , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Satisfacción Personal , Factores de Riesgo , Factores Sexuales , Ausencia por Enfermedad/estadística & datos numéricos , Reino Unido/epidemiología , Carga de Trabajo/psicología , Adulto JovenRESUMEN
BACKGROUND: Paranoia involves thoughts and beliefs about the harmful intent of others but the social consequences have been much less studied. We investigated whether paranoia predicts maladaptive social behaviour in terms of cooperative and punitive behaviour using experimental game theory paradigms, and examined whether reduced cooperation is best explained in terms of distrust as previous studies have claimed. METHODS: We recruited a large population sample (N = 2132) online. All participants completed the Green et al. Paranoid Thoughts Scale and (i) a Dictator Game and (ii) an Ultimatum Game, the former with an option for costly punishment. Following distrust-based accounts, we predicted highly paranoid people would make higher offers when the outcome depended on receiving a positive response from their partner (Ultimatum Game) but no difference when the partner's response was irrelevant (Dictator Game). We also predicted paranoia would increase punitive responses. Predictions were pre-registered in advance of data collection. Data and materials are open access. RESULTS: Highly paranoid participants actually made lower offers than non-paranoid participants both in the Dictator Game and in the Ultimatum Game. Paranoia positively predicted punitive responses. CONCLUSIONS: These findings suggest that distrust is not the best explanation for reduced cooperation in paranoia and alternative explanations, such as increased self-interest, may apply. However, the tendency to attribute harmful intent to partners was important in motivating punitive responses. These results highlight differing motivations underlying adverse social behaviour in paranoia and suggest that accounts based solely on the presenting features of paranoia may need to be rethought.
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Conflicto Psicológico , Conducta Cooperativa , Teoría del Juego , Trastornos Paranoides/psicología , Conducta Social , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The prevalence of overweight and obesity in reproductive-age adults is increasing worldwide. While the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/obese on fecundity and offspring health has received minimal attention. Using a 2 × 2 study design in rodents we established the relative contributions of paternal and maternal obesity on fetal and embryo development and whether combined paternal and maternal obesity had an additive effect. Here, we show that parental obesity reduces fetal and placental weights without altering pregnancy establishment and is not dependent on an in utero exposure to a high-fat diet. Interestingly combined parental obesity seemed to accumulate both the negative influences of paternal and maternal obesity had alone on embryo and fetal health rather than an amplification, manifested as reduced embryo developmental competency, reduced blastocyst cell numbers, impaired mitochondrial function, and alterations to active and repressive embryonic chromatin marks, resulting in aberrant placental gene expression and reduced fetal liver mtDNA copy numbers. Further understanding both the maternal cytoplasmic and paternal genetic interactions during this early developmental time frame will be vital for understanding how developmental programming is regulated and for the proposition of interventions to mitigate their effects.
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Desarrollo Embrionario , Desarrollo Fetal , Regulación del Desarrollo de la Expresión Génica , Exposición Materna , Obesidad , Exposición Paterna , Animales , Blastocisto , Recuento de Células , Dieta Alta en Grasa , Femenino , Peso Fetal , Masculino , Ratones , Mitocondrias , Tamaño de los Órganos , Placenta , EmbarazoRESUMEN
Paranoia is associated with variation in social behaviour, such as lower inclination to trust others or to behave generously in economic game settings. Such variation may stem, in part, from a reduced tendency to socially identify with others, although previous studies have reported mixed results. We tested whether paranoia involves altered social identification in a pre-registered online study investigating the relationship between a measure of social identification, paranoia, and social behaviours in economic games. We successfully manipulated social identification, but paranoia was associated with slightly increased social identification overall. Neither paranoia nor social identification predicted behaviour in the economic games, and there was no interaction between paranoia and social identification regarding trusting and cooperative behaviours. Our results converge with recent work suggesting that more paranoid individuals may harbour a higher tendency to perceive themselves as having similar beliefs to others. We discuss some key areas for future research to progress understanding in this area.
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Striatal dopamine is important in paranoid attributions, although its computational role in social inference remains elusive. We employed a simple game-theoretic paradigm and computational model of intentional attributions to investigate the effects of dopamine D2/D3 antagonism on ongoing mental state inference following social outcomes. Haloperidol, compared with the placebo, enhanced the impact of partner behaviour on beliefs about the harmful intent of partners, and increased learning from recent encounters. These alterations caused substantial changes to model covariation and negative correlations between self-interest and harmful intent attributions. Our findings suggest that haloperidol improves belief flexibility about others and simultaneously reduces the self-relevance of social observations. Our results may reflect the role of D2/D3 dopamine in supporting self-relevant mentalising. Our data and model bridge theory between general and social accounts of value representation. We demonstrate initial evidence for the sensitivity of our model and short social paradigm to drug intervention and clinical dimensions, allowing distinctions between mechanisms that operate across traits and states.
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Paranoia is a common symptom of psychotic disorders but is also present on a spectrum of severity in the general population. Although paranoia is associated with an increased tendency to perceive cohesion and conspiracy within groups, the mechanistic basis of this variation remains unclear. One potential avenue involves the brain's dopaminergic system, which is known to be altered in psychosis. In this study, we used large-N online samples to establish the association between trait paranoia and perceptions of cohesion and conspiracy. We further evaluated the role of dopamine on perceptions of cohesion and conspiracy using a double-blind, placebo-controlled laboratory experiment where participants received levodopa or a placebo control. Our results were mixed: group perceptions and perceptions of cohesion were higher among more paranoid individuals but were not altered under dopamine administration. We outline the potential reasons for these discrepancies and the broader implications for understanding paranoia in terms of dopamine dysregulation.
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Trastornos Paranoides , Trastornos Psicóticos , Humanos , Dopamina , Trastornos Paranoides/tratamiento farmacológico , Percepción , Método Doble CiegoRESUMEN
Paranoia and conspiracy thinking are known to be distinct but correlated constructs, but it is unknown whether certain types of conspiracy thinking are more common in paranoia than others. In a large (n = 1000), pre-registered online study we tested if endorsement of items on a new Components of Conspiracy Ideation Questionnaire varied according to whether harm was described as being (a) intentional and (b) self-referential. Our predictions were supported: paranoia was positively associated with endorsement of items on this questionnaire overall and more paranoid individuals were more likely to endorse items describing intentional and self-referential harm. Belief in any item on the Components of Conspiracy Ideation Questionnaire was associated with belief in others and items describing incidental harm and harm to others were found to be more believable overall. Individuals who endorsed conspiracy theory items on the questionnaire were more likely to state that people similar to them would as well, although this effect was not reduced in paranoia, counter to our expectations.
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The potential of edible mushrooms as an unexploited treasure trove, although rarely included in known food guidelines, is highlighted. Their role in shielding people against the side effects of an unhealthy stylish diet is reviewed. Mushrooms complement the human diet with various bioactive molecules not identified or deficient in foodstuffs of plant and animal sources, being considered a functional food for the prevention of several human diseases. Mushrooms have been widely used as medicinal products for more than 2,000 years, but globally the potential field of use of wild mushrooms has been untapped. There is a broad range of edible mushrooms which remain poorly identified or even unreported which is a valuable pool as sources of bioactive compounds for biopharma utilization and new dietary supplements. Some unique elements of mushrooms and their role in preventative healthcare are emphasized, through their positive impact on the immune system. The potential of mushrooms as antiviral, anti-inflammatory, anti-neoplastic, and other health concerns is discussed. Mushrooms incorporate top sources of non-digestible oligosaccharides, and ergothioneine, which humans are unable to synthesize, the later a unique antioxidant, cytoprotective, and anti-inflammatory element, with therapeutic potential, approved by world food agencies. The prebiotic activity of mushrooms beneficially affects gut homeostasis performance and the balance of gut microbiota is enhanced. Several recent studies on neurological impact and contribution to the growth of nerve and brain cells are mentioned. Indeed, mushrooms as functional foods' nutraceuticals are presently regarded as next-generation foods, supporting health and wellness, and are promising prophylactic or therapeutic agents.
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Alteration in land use is likely to be a major driver of changes in the distribution of ecosystem services before 2050. In Europe, urbanization will probably be the main cause of land-use change. This increase in urbanization will result in spatial shifts in both supplies of ecosystem services and the beneficiaries of those services; the net outcome of such shifts remains to be determined. Here, we model changes in urban land cover in Britain based on large (16%) projected increases in the human population by 2031, and the consequences for three different services--flood mitigation, agricultural production and carbon storage. We show that under a scenario of densification of urban areas, the combined effect of increasing population and loss of permeable surfaces is likely to result in 1.7 million people living within 1 km of rivers with at least 10 per cent increases in projected peak flows, but that increasing suburban 'sprawl' will have little effect on flood mitigation services. Conversely, losses of stored carbon and agricultural production are over three times as high under the sprawl as under the 'densification' urban growth scenarios. Our results illustrate the challenges of meeting, but also of predicting, future demands and patterns of ecosystem services in the face of increasing urbanization.
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Ecosistema , Modelos Biológicos , Urbanización/tendencias , Agricultura/estadística & datos numéricos , Carbono/análisis , Simulación por Computador , Inundaciones/estadística & datos numéricos , Humanos , Densidad de Población , Reino UnidoRESUMEN
Altered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. Twenty seven healthy male participants received 150mg L-DOPA, 3 mg haloperidol, or placebo in a double-blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect (i) attributions of harmful intent and (ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest about opponents' decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals.
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Dopamina , Trastornos Paranoides , Afecto , Deluciones , Método Doble Ciego , Humanos , Masculino , Percepción SocialRESUMEN
The sensitization model suggests that paranoia is explained by over-sensitivity to social threat. However, this has been difficult to test experimentally. We report two preregistered social interaction studies that tested (i) whether paranoia predicted overall attribution and peak attribution of harmful intent and (ii) whether anxiety, interpersonal sensitivity and worry predicted the attribution of harmful intent. In Study 1, we recruited a large general population sample (N = 987) who serially interacted with other participants in multi-round dictator games and matched to fair, partially fair or unfair partners. Participants rated attributions of harmful intent and self-interest after each interaction. In Study 2 (N = 1011), a new sample of participants completed the same procedure and additionally completed measures of anxiety, worry and interpersonal sensitivity. As predicted, prior paranoid ideation was associated with higher and faster overall harmful intent attributions, whereas attributions of self-interest were unaffected, supporting the sensitization model. Contrary to predictions, neither worry, interpersonal sensitivity nor anxiety was associated with harmful intent attributions. In a third exploratory internal meta-analysis, we combined datasets to examine the effect of paranoia on trial-by-trial attributional changes when playing fair and unfair dictators. Paranoia was associated with a greater reduction in harmful intent attributions when playing a fair but not unfair dictator, suggesting that paranoia may also exaggerate the volatility of beliefs about the harmful intent of others.
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The tolerance and beta-adrenergic blocking activity of flestolol, a short-acting beta-blocker, was investigated in 30 subjects. Flestolol infused intravenously at doses up to 100 micrograms/kg/min was found to be well tolerated. A dose-dependent attenuation of isoproterenol-induced tachycardia and increase in systolic blood pressure occurred with flestolol at doses ranging from 0.5 to 15.0 micrograms/kg/min. The average percent reduction in isoproterenol-induced tachycardia (beta-blockade) at each dose of flestolol, 0.5, 2.5, 5.0, 15.0, and 50.0 micrograms/kg/min, was 15.1%, 45.9%, 67.0%, 85.9%, and 90.3%, respectively. The onset of beta-blockade occurred within 30 minutes. After the end of flestolol infusion there was a marked reduction in beta-blockade within 6 minutes, with complete recovery from beta-blockade within 30 to 45 minutes. There was a statistically significant (P less than 0.01) positive correlation between flestolol dosage and its blood levels (r = 0.91) as well as between the flestolol-induced beta-blockade and its dosage (r = 0.62).
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Fluorobencenos , Propanolaminas/farmacología , Adulto , Análisis de Varianza , Presión Sanguínea/efectos de los fármacos , Evaluación de Medicamentos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Parenterales , Isoproterenol/efectos adversos , Masculino , Propanolaminas/efectos adversos , Propanolaminas/sangre , Propanolaminas/uso terapéutico , Taquicardia/inducido químicamente , Taquicardia/tratamiento farmacológicoRESUMEN
This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Ceftriaxona/uso terapéutico , Ácidos Clavulánicos/uso terapéutico , Administración Oral , Amoxicilina/administración & dosificación , Combinación Amoxicilina-Clavulanato de Potasio , Antibacterianos/administración & dosificación , Ceftriaxona/administración & dosificación , Preescolar , Ácidos Clavulánicos/administración & dosificación , Quimioterapia Combinada/administración & dosificación , Quimioterapia Combinada/uso terapéutico , Femenino , Fiebre , Estudios de Seguimiento , Infecciones por Haemophilus/tratamiento farmacológico , Humanos , Lactante , Inyecciones Intramusculares , Leucocitosis , Masculino , Infecciones Meningocócicas/tratamiento farmacológico , Análisis Multivariante , Infecciones Neumocócicas/tratamiento farmacológico , Estudios Prospectivos , Análisis de Regresión , Resultado del TratamientoRESUMEN
BACKGROUND: Although symptoms of heart failure abate after heart transplantation, other symptoms caused by the surgery, immunosuppressant drugs, and complications can be new sources of symptom distress for patients after operation. METHODS: This two-site National Institutes of Health study compared symptom distress in 173 adult heart transplant recipients from before operation to 3 months after operation. The Heart Transplant Symptom Scale was used to measure 92 symptoms related to heart disease and heart failure, transplantation, medication side effects, and complications commonly found in this population. Analysis was via paired t tests with Bonferroni correction. Most patients (93%) were receiving a triple immunosuppressant regimen of cyclosporine, azathioprine, and prednisone. RESULTS: Total symptom distress decreased significantly (p = 0.013) from before operation to 3 months after heart transplantation. The 23 symptoms that decreased the most (p = 0.000) after operation accounted for a cumulative total reduction of 583% less symptom distress. These symptoms were primarily cardiopulmonary, neuromuscular, and emotional. The 10 symptoms that worsened the most (p = 0.000) after operation accounted for a cumulative total increase of 284% more symptom distress. These symptoms were primarily dermatologic, neurologic, and gastrointestinal and were all side effects of prednisone and cyclosporine. CONCLUSIONS: The net change in symptom distress resulted in 299% less symptom distress in this cohort at 3 months after heart transplantation. This significant improvement in symptom outcomes scientifically documents the effectiveness of heart transplantation in reducing symptoms of heart failure, along with accompanying emotional symptoms. These research findings therefore reinforce and support the positive symptom outcomes often reported anecdotally in clinical practice.
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Cardiopatías/cirugía , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Cardiopatías/etiología , Insuficiencia Cardíaca/etiología , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del TratamientoRESUMEN
In a double-blind, randomized, crossover study in ten patients with asthma, the effects on specific airway resistance of esmolol, a new ultra-short-acting beta 1-selective adrenoceptor blocker, were compared with those of placebo. Specific airway resistance was measured during increasing doses of esmolol infusion, during dry air provocation tests, and following isoproterenol inhalation. These same studies were later carried out on six of ten patients following intravenous propranolol infusion. All patients were able to tolerate the maximum dose of esmolol (300 micrograms/kg/min); treatment differences between esmolol and placebo were not found. In contrast, intravenous propranolol produced marked symptomatic bronchoconstriction after the lowest dose (1 mg) in two of six patients. Esmolol produced slight but statistically significant enhancement of patients' sensitivity to dry air provocation. Similarly, a slight but significant inhibition of bronchomotor sensitivity to isoproterenol was noted during esmolol infusion. After infusion of 5 mg of intravenous propranolol, one of four patients had a clinically significant increase in sensitivity to dry air. It is concluded that esmolol, because of its short duration of action and relative lack of effect on airway resistance, may be preferred over propranolol in patients with asthma who require treatment with an intravenous beta-blocking agent.
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Antagonistas Adrenérgicos beta/uso terapéutico , Asma/tratamiento farmacológico , Propanolaminas/uso terapéutico , Adulto , Resistencia de las Vías Respiratorias/efectos de los fármacos , Asma/fisiopatología , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Volumen Espiratorio Forzado , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Placebos , Propanolaminas/efectos adversos , Propranolol/uso terapéutico , Pulso Arterial/efectos de los fármacos , Distribución Aleatoria , Capacidad Vital/efectos de los fármacosRESUMEN
The pharmacokinetics and pharmacodynamics of flestolol, a new short-acting, beta-adrenergic receptor antagonist, were examined in nine healthy subjects after a constant intravenous infusion of 5 micrograms/kg/min for 72 hours. Flestolol blood levels were determined by high-performance liquid chromatography. In all subjects, flestolol blood concentration attained steady state 30 minutes after initiation of infusion. The mean +/- standard deviation steady-state concentration of flestolol was 31.1 +/- 12.0 ng/mL. The elimination half-life averaged 7.2 minutes. The mean +/- standard deviation total body clearance was 181 +/- 66 mL/min/kg. The apparent volume of distribution and the area under the curve averaged 1.89 L/kg and 2.23 micrograms-hr/mL, respectively. Flestolol did not cause any significant change (P greater than .05) in the heart rate or systolic or diastolic blood pressure from the baseline. Flestolol significantly (P less than .05) attenuated the isoproterenol-induced increase in heart rate and systolic blood pressure and decrease in diastolic blood pressure in comparison with baseline. The average maximum reduction in isoproterenol tachycardia was in the range of 63% to 79% during flestolol infusion. There was a rapid recovery from beta blockade after termination of flestolol infusion; the recovery averaged 96% 20 minutes after the infusion was stopped. We conclude that flestolol exhibits a very short half-life and is cleared mainly by extrahepatic routes. It is an effective beta blocker and possesses a short duration of action.
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Antagonistas Adrenérgicos beta/farmacología , Fluorobencenos , Hemodinámica/efectos de los fármacos , Propanolaminas/farmacología , Antagonistas Adrenérgicos beta/sangre , Antagonistas Adrenérgicos beta/farmacocinética , Adulto , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Isoproterenol/farmacología , Masculino , Propanolaminas/sangre , Propanolaminas/farmacocinéticaRESUMEN
The hemodynamic effects of flestolol were evaluated in 30 patients undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to flestolol), at steady state during IV flestolol infusion (1, 5, and 10 micrograms/kg/min) and at 20 to 30 minutes after discontinuation (postinfusion). Flestolol-induced hemodynamic changes were similar to those induced by other beta blockers without intrinsic sympathomimetic activity. Significant dose-dependent reduction in heart rate, rate pressure product, and increase in peripheral vascular resistance were seen. Flestolol produced clinically insignificant decrease in myocardial contractility as shown by slight decrease in LVdp/dt, CI, and LVEF. Hemodynamic data from patients with paced heart rate, further confirms a direct mild cardiac depressant effect of flestolol, a finding common to other beta blockers. Consistent with the short elimination half-life of flestolol (t1/2 = 6.5 minutes), most of the hemodynamic changes rapidly returned to preinfusion level within 20 to 30 minutes following its discontinuation. Thus flestolol, with its unique pharmacokinetic profile and titrability, may be beneficial in the treatment of critically ill patients.
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Antagonistas Adrenérgicos beta/farmacología , Fluorobencenos , Hemodinámica/efectos de los fármacos , Propanolaminas/farmacología , Antagonistas Adrenérgicos beta/sangre , Adulto , Anciano , Enfermedad Coronaria/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Propanolaminas/sangreRESUMEN
One group of 12 rats received discrete 6-hydroxydopamine (6-OHDA) injections into the caudate nucleus on one side of the brain and sham infusions on the other. Following chronic daily injections of cocaine (20 mg/kg, i.p.) or saline (1 ml/kg, i.p.) for 15 days, the caudate nuclei were separately dissected, and the number of benzodiazepine receptors labeled with [3H]Ro 15-1788 were assessed using individual homogenate receptor binding assays. A second group of 24 rats received bilateral infusions of 6-hydroxydopamine or sham infusions into the lateral ventricles followed by chronic cocaine or saline administration as described above. The animals were sacrificed by cardiac perfusion, and the brains were sectioned and prepared for light microscopic quantitative autoradiography. The extent of the lesion was assessed by measuring dopaminergic and noradrenergic uptake sites visualized with [3H]mazindol, while [3H]Ro 15-1788 was used to estimate the number of benzodiazepine receptors. Chronic cocaine administration resulted in significant increases in benzodiazepine receptors in the caudate nucleus, and these effects were attenuated following dopamine depletion. These data suggest that the effects of cocaine on benzodiazepine receptors may be mediated, in part, through the effects of the drug on dopaminergic neuronal activity.
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Núcleo Caudado/metabolismo , Cocaína/farmacología , Dopamina/fisiología , Flumazenil/metabolismo , Receptores de GABA-A/metabolismo , Animales , Núcleo Caudado/efectos de los fármacos , Hidroxidopaminas , Masculino , Neurotoxinas , Oxidopamina , Ratas , Ratas Endogámicas F344 , Receptores de GABA-A/efectos de los fármacosRESUMEN
Rabbit lenses were incubated in organ culture with 14C-galactose for 6, 12 and 20 hours. Gangliosides were extracted using the Folch-Suzuki method, purified by dialysis and analyzed by thin-layer chromatography. Six radioactive bands, including the origin, were observed. Tentative identification of these bands as N-acetylneuraminylgalactosylglucosylceramide (GM3), N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM2), galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)- galactosylglucosylceramide (GM1), N-acetylneuraminylgalactosyl-N- acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GD1a), N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-(N- acetylneuraminyl-N-acetylneuraminyl)-galactosylglucosylceramide (GT) was made by comparison with authentic standard gangliosides. Galactose incorporation into GM3 and GM2 increased during the first 12 hours but decreased during the period from 12 to 20 hours. GD1a and GT incorporated the greatest amount of label during the period from 12 to 20 hours. Incorporation of labeled galactose into GM1 was nearly constant during this time period. Specific activities for GM1, GM3 and GT were nearly the same at 6 hours and were about half those of GM2 and GD1a for the same time period.