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INTRODUCTION: Oxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC n-3 PUFA supplementation. MATERIALS AND METHODS: This exploratory study investigated the baseline correlations between LC n-3, n-6 and n-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (nâ¯=â¯49). After examining the baseline relationship, the potential effect of supplementation (LC n-3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined. RESULTS: At baseline, the hydroxy product of mead acid (n-9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (pâ¯=â¯0.003, r=-0.41), skeletal muscle mass index (SMMI) (pâ¯=â¯0.001, r=-0.46), handgrip strength (HGS) (p<0.001, râ¯=â¯0.48) and isometric knee extension (p<0.001, r=-0.48). Likewise, LC n-6 PUFA hydroxyPUFA were negatively correlated to HGS (i.e., 12-HETrE, pâ¯=â¯0.002, r=-0.42, and 5- and 11-HETE, pâ¯=â¯0.006, r=-0.47 and p<0.001, r=-0.50 respectively), single leg stand time (i.e., 12-HETrE, pâ¯=â¯0.006, r=-0.39 and 16-HETE, pâ¯=â¯0.002, r=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, pâ¯=â¯0.006, râ¯=â¯0.39), and positively correlated to gait speed (i.e., 12-HETrE, pâ¯=â¯0.007, râ¯=â¯0.38 and 16-HETE, pâ¯=â¯0.006, râ¯=â¯0.39). LC n-3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced n-6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC n-3 PUFA or placebo groups. Changes in plasma oxylipins concentrations were closely related to changes in their parent PUFA, assessed in the erythrocyte membrane, but were not associated with any changes in skeletal muscle parameters. DISCUSSION AND CONCLUSION: At baseline, the status n-9 (5-HETrE) and n-6 PUFA derivates [12-HETrE, and 5-, 11- and 16-HETE], but not n-3 PUFA derived oxylipins, were associated with poor skeletal muscle health parameters (i.e., mass and strength). However, these correlations were no longer present when correlating relative changes from pre to post timepoints. An independent cohort validation is needed to explore baseline correlations further. Further research is warranted to assess other biological mechanisms by which LC n-3 PUFA might affect muscle biology.
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Ácidos Grasos Omega-3 , Sarcopenia , Humanos , Anciano , Oxilipinas , Fuerza de la Mano , Estudios Retrospectivos , Ácidos Grasos , Ácidos Docosahexaenoicos , Suplementos Dietéticos , Músculo Esquelético/metabolismo , BiologíaRESUMEN
PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n = 5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p = 0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.
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Ácido Ascórbico/farmacología , Suplementos Dietéticos , Nefrolitiasis/orina , Oxalatos/orina , Preparaciones de Plantas/farmacología , Eliminación Renal/efectos de los fármacos , Vaccinium macrocarpon , Vitaminas/farmacología , Adulto , Femenino , Humanos , Masculino , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear. METHODS: We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices. RESULTS: Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05-0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents. CONCLUSIONS: Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.
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Anestésicos Generales/farmacología , Anestésicos por Inhalación/farmacología , Corteza Cerebral/efectos de los fármacos , Electrodiagnóstico/métodos , Isoflurano/farmacología , Tálamo/efectos de los fármacos , Animales , Corteza Cerebral/fisiología , Estado de Conciencia/efectos de los fármacos , Femenino , Masculino , Modelos Animales , Tálamo/fisiologíaRESUMEN
The objective of this study was to assess the effects of dietary supplementation of a commercial algal product rich in docosahexaenoic acid (DHA) on boar fertility as assessed in vitro and in vivo. Boars were fed one of three experimental diets for 19 weeks: (i) Control (Ctl) diet (n = 31), (ii) Ctl diet plus 75g All-G-Rich per day (n = 31) or (iii) Ctl diet plus 150g All-G-Rich per day (n = 30). Parameters assessed were (i) raw semen quality; volume, sperm concentration, total motility and morphology (ii) liquid semen quality; progressive motility, viability, hypotonic resistance and acrosomal integrity (iii) frozen-thawed semen quality; motility, thermal stress, viability, membrane fluidity and mitochondrial activity (iv) sperm and seminal plasma (SP) fatty acid composition (FAC) (v) total antioxidant capacity (TAC) of SP and (vi) farrowing rates and litter sizes of sows (n = 1158) inseminated with liquid semen. Boars consuming 75g All-G-Rich had a larger semen volume (P < 0.05) and a higher total sperm number (P < 0.01) than the Ctl treatment, however, there was no effect of treatment on any other semen quality parameter (P > 0.05). There was no effect of dietary treatment on the FAC and TAC of SP or on farrowing rate and litter size (P > 0.05). There was an effect of dietary treatment on the FAC of sperm, represented by an 1.72 and 1.60 fold increase in the DHA content for 75 and 150g treatments, respectively, compared to the Ctl treatment. In conclusion, a significant increase in semen volume and total sperm number in boars supplemented 75g All-G-Rich daily, resulted in an increase in production of 3 to 4 more doses per ejaculate, thus, indicating that the feeding regime described within this study has the potential for increasing the output of boar studs.
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Alimentación Animal , Dieta/veterinaria , Ácidos Docosahexaenoicos/administración & dosificación , Microalgas/química , Porcinos/fisiología , Alimentación Animal/análisis , Animales , Criopreservación/veterinaria , Femenino , Fertilidad , Tamaño de la Camada , Masculino , Semen/química , Análisis de Semen/veterinaria , Preservación de Semen/veterinaria , Motilidad EspermáticaRESUMEN
UNLABELLED: Controlling spread of human pathogens on fresh produce is a top priority for public health reasons. Isolation of compounds from agricultural waste that would control spread of human pathogens was explored using Salmonella enterica serovar Typhimurium as a model organism. In the environment, micro-organisms migrate as a 'community' especially when they move on moist surfaces. This type of motility is characterized as swarming motility. We examined extracts from agricultural waste such as soya bean husk, peels of orange, pineapple, avocado and pomegranate for antiswarming activity. Avocado and pineapple peels showed moderate (~40%) inhibition of swarming motility while pomegranate peel extract had high antiswarming activity (~85% inhibition) and was examined in further detail. Although the pomegranate peel extract was acidic, swarm-inhibitory activity was not due to low pH and the peel extract did not inhibit growth of Salmonella. Among the key swarm motility regulatory genes, class II (fliF, fliA, fliT and fliZ) and class III (fliC and fliM) regulators were downregulated upon exposure to pomegranate peel extract. Pomegranate peels offer great potential as a bioactive repellent for pathogenic micro-organisms on moist surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: Controlling the spread of food-borne pathogens in moist environments is an important microbial food safety issue. Isolation of compounds from agricultural waste (such as fruit peels) that would control spread of human pathogens was explored using Salmonella enterica serovar Typhimurium as a model organism. Pomegranate peels offer great potential as a bioactive repellent for pathogenic micro-organisms.
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Antibacterianos/química , Lythraceae/química , Lythraceae/microbiología , Extractos Vegetales/química , Salmonella typhimurium/metabolismo , Ananas/química , Ananas/microbiología , Citrus sinensis/química , Citrus sinensis/microbiología , Flagelos/genética , Flagelos/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Persea/química , Persea/microbiología , Salmonella typhimurium/genética , Glycine max/química , Glycine max/microbiología , Residuos/análisisRESUMEN
OBJECTIVE: To compare early home biofeedback physiotherapy with pelvic floor exercises (PFEs) for the initial management of women sustaining a primary third-degree tear. DESIGN: Single centre, randomised trial. SETTING: National Maternity Hospital, Dublin, Ireland. POPULATION: A total of 120 women sustaining a primary third-degree tear. METHODS: Women were randomised in a one to three ratio: 30 to early postpartum home biofeedback physiotherapy and 90 to PFEs. MAIN OUTCOME MEASURES: Differences in anorectal manometry results, Cleveland Clinic continence scores and Rockwood faecal incontinence quality of life scale scores after 3 months of postpartum treatment. RESULTS: The mean anal resting pressure was 39 ± 13 mmHg in the early biofeedback physiotherapy group and 43 ± 17 mmHg in the PFE group. The mean anal squeeze pressure was 64 ± 17 mmHg in the biofeedback group and 62 ± 23 mmHg in the PFE group. There was no significant difference in anal resting and squeeze pressure values between the groups (P = 0.123 and P = 0.68, respectively). There were no differences in symptom score and quality of life measurements between the groups. CONCLUSIONS: This study demonstrates no added value in using early home biofeedback physiotherapy in the management of women sustaining third-degree tears. Poor compliance may have contributed because women found it difficult to designate time to using biofeedback.
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Canal Anal/lesiones , Biorretroalimentación Psicológica , Parto Obstétrico/efectos adversos , Terapia por Ejercicio/métodos , Laceraciones/terapia , Perineo/lesiones , Canal Anal/fisiología , Episiotomía , Incontinencia Fecal/prevención & control , Femenino , Humanos , Laceraciones/etiología , Manometría , Parto , Diafragma Pélvico/fisiología , Periodo Posparto , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.
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Vacuna BCG/administración & dosificación , Programas de Inmunización/organización & administración , Tuberculosis/prevención & control , Femenino , Humanos , Recién Nacido , Irlanda/epidemiología , Masculino , Estudios Prospectivos , Tuberculosis/epidemiologíaRESUMEN
Studies have shown that dyslexic children present a deficiency in the temporal processing of auditory stimuli applied in rapid succession. However, discussion continues concerning the way this deficiency can be influenced by temporal variables of auditory processing tests. Therefore, the purpose of the present study was to analyze by auditory temporal processing tests the effect of temporal variables such as interstimulus intervals, stimulus duration and type of task on dyslexic children compared to a control group. Of the 60 children evaluated, 33 were dyslexic (mean age = 10.5 years) and 27 were normal controls (mean age = 10.8 years). Auditory processing tests assess the abilities of discrimination and ordering of stimuli in relation to their duration and frequency. Results showed a significant difference in the average accuracy of control and dyslexic groups considering each variable (interstimulus intervals: 47.9 +/- 5.5 vs 37.18 +/- 6.0; stimulus duration: 61.4 +/- 7.6 vs 50.9 +/- 9.0; type of task: 59.9 +/- 7.9 vs 46.5 +/- 9.0) and the dyslexic group demonstrated significantly lower performance in all situations. Moreover, there was an interactive effect between the group and the duration of stimulus variables for the frequency-pattern tests, with the dyslexic group demonstrating significantly lower results for short durations (53.4 +/- 8.2 vs 48.4 +/- 11.1), as opposed to no difference in performance for the control group (62.2 +/- 7.1 vs 60.6 +/- 7.9). These results support the hypothesis that associates dyslexia with auditory temporal processing, identifying the stimulus-duration variable as the only one that unequally influenced the performance of the two groups.
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Estimulación Acústica/métodos , Trastornos de la Percepción Auditiva/etiología , Dislexia/complicaciones , Trastornos de la Percepción Auditiva/diagnóstico , Trastornos de la Percepción Auditiva/fisiopatología , Estudios de Casos y Controles , Niño , Dislexia/fisiopatología , Femenino , Humanos , Masculino , Factores de TiempoRESUMEN
Studies have shown that dyslexic children present a deficiency in the temporal processing of auditory stimuli applied in rapid succession. However, discussion continues concerning the way this deficiency can be influenced by temporal variables of auditory processing tests. Therefore, the purpose of the present study was to analyze by auditory temporal processing tests the effect of temporal variables such as interstimulus intervals, stimulus duration and type of task on dyslexic children compared to a control group. Of the 60 children evaluated, 33 were dyslexic (mean age = 10.5 years) and 27 were normal controls (mean age = 10.8 years). Auditory processing tests assess the abilities of discrimination and ordering of stimuli in relation to their duration and frequency. Results showed a significant difference in the average accuracy of control and dyslexic groups considering each variable (interstimulus intervals: 47.9 ± 5.5 vs 37.18 ± 6.0; stimulus duration: 61.4 ± 7.6 vs 50.9 ± 9.0; type of task: 59.9 ± 7.9 vs 46.5 ± 9.0) and the dyslexic group demonstrated significantly lower performance in all situations. Moreover, there was an interactive effect between the group and the duration of stimulus variables for the frequency-pattern tests, with the dyslexic group demonstrating significantly lower results for short durations (53.4 ± 8.2 vs 48.4 ± 11.1), as opposed to no difference in performance for the control group (62.2 ± 7.1 vs 60.6 ± 7.9). These results support the hypothesis that associates dyslexia with auditory temporal processing, identifying the stimulus-duration variable as the only one that unequally influenced the performance of the two groups.
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Niño , Femenino , Humanos , Masculino , Estimulación Acústica/métodos , Trastornos de la Percepción Auditiva/etiología , Dislexia/complicaciones , Trastornos de la Percepción Auditiva/diagnóstico , Trastornos de la Percepción Auditiva/fisiopatología , Estudios de Casos y Controles , Dislexia/fisiopatología , Factores de TiempoRESUMEN
Methanolic extracts (25 microug/ml) of species belonging to the genera of Combretum, Terminalia and Pteleopsis, collected during a field expedition in Tanzania in 1999, were screened for their antiproliferative and cytotoxic effects against three human cancer cell lines (HeLa, cervical carcinoma; T 24, bladder carcinoma; and MCF 7, breast carcinoma). A leaf extract of Combretum fragrans and a fruit extract of C. zeyheri gave the strongest antiproliferative and cytotoxic effects of all the twenty-four extracts screened in this investigation. In contrast to the highly powerful leaf extract of C. fragrans, the root extract of this species gave no cytotoxic effects against the investigated cancer cell lines at a concentration of 25 microg/ml. The other investigated species of Combretum and Terminalia differed greatly in their cytotoxic potential. Root extracts of Terminalia sambesiaca and T. sericea gave the strongest cytotoxic effects of the five species of Terminalia used in this study. Eight of the twenty-four investigated plant extracts showed pronounced cytotoxic effects (<30% proliferation compared to the control) against the T 24 bladder cancer cells, seven against the HeLa cells and four against the MCF 7 cells.
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Antineoplásicos Fitogénicos/análisis , Combretaceae/química , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Humanos , Extractos Vegetales/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVE: Transurethral prostatectomy is routinely performed under spinal anaesthesia. This technique can cause hypotension, which is particularly undesirable in the elderly. The objective was to compare spinal anaesthesia for transurethral prostatectomy using hyperbaric bupivacaine 15 mg (control group) and hyperbaric bupivacaine 10 mg (limiting spread by maintaining the upright position for 15 min) and fentanyl 25 microg (fentanyl group) in terms of haemodynamic and pulmonary function. METHODS: Thirty ASA I-III patients were randomly selected and underwent spinal anaesthesia with either hyperbaric bupivacaine 15 mg (immediately positioned supine) or hyperbaric bupivacaine 10 mg (upright for 15 min) and fentanyl 25 microg. RESULTS: The greatest changes in mean arterial pressure (P = 0.9), ephedrine requirements (P = 0.8) and mean maximum change in forced vital capacity (P = 0.5) were similar in both groups. CONCLUSIONS: The addition of fentanyl 25 microg to bupivacaine 10 mg and limiting the spread of the block does not improve either haemodynamic or pulmonary function compared with bupivacaine 15 mg in patients undergoing transurethral prostatectomy.
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Anestesia Raquidea/métodos , Resección Transuretral de la Próstata , Adyuvantes Anestésicos/administración & dosificación , Anciano , Analgésicos Opioides/administración & dosificación , Anestesia Raquidea/efectos adversos , Anestésicos Locales/administración & dosificación , Presión Sanguínea , Bupivacaína/administración & dosificación , Fentanilo/administración & dosificación , Frecuencia Cardíaca , Humanos , Hipotensión/etiología , Inyecciones Espinales/métodos , Masculino , Dimensión del Dolor , Postura , Estudios Prospectivos , Capacidad VitalRESUMEN
RATIONALE: Chronic intermittent administration of amphetamine and cocaine can precipitate psychotic episodes in humans and produce persistent behavioral changes (i.e. increased locomotion, stereotypy) in the rat. The psychostimulant sensitization model of psychosis holds that the repeated administration of drugs such as amphetamine and cocaine induces long-lasting neuroadaptations and behavioral outcomes in animals that parallel aspects of the schizophrenic condition. OBJECTIVES: In the present study, we attempted to validate this model further by examining the effects of short-term withdrawal from repeated administration of cocaine and amphetamine on performance in two animal behavioral models of cognitive deficits found in schizophrenia: latent inhibition and prepulse inhibition. Reductions in both of these behavioral phenomena have been reported in schizophrenic patients and in acutely amphetamine-treated rats. METHODS: Animals were tested after 4 days of withdrawal from 5 days of daily systemic 20 mg/kg cocaine or 1.5 mg/kg amphetamine injections for either latent inhibition of two-way active avoidance acquisition or prepulse inhibition of an acoustic startle response. RESULTS: Our results indicate that, rather than reducing the expression of these behaviors, withdrawal from either cocaine or amphetamine enhanced the expression of latent inhibition of the active avoidance response while having no effect on prepulse inhibition of acoustic startle. CONCLUSIONS: These data indicate that although the sensitized response to amphetamine and cocaine administration may model some aspects of schizophrenic psychosis, behaviors exhibited by sensitized animals in the absence of an acute drug challenge are not consistent with models of the positive symptoms of schizophrenia.
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Reacción de Prevención/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/efectos adversos , Reflejo de Sobresalto/fisiología , Síndrome de Abstinencia a Sustancias/psicología , Estimulación Acústica , Anfetamina , Animales , Conducta Animal/efectos de los fármacos , Cocaína , Generalización Psicológica , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar , Reflejo de Sobresalto/efectos de los fármacosRESUMEN
Psychostimulant-induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non-preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine-sensitized animals exhibited markedly enhanced LI compared to saline-treated animals, due to the fact that NPE-cocaine animals spent more time freezing during the tone CS than NPE-saline animals, whereas PE-cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine-withdrawn NPE animals, the absence of this effect in cocaine-withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.
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Cocaína/efectos adversos , Inhibidores de Captación de Dopamina/efectos adversos , Miedo/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Síndrome de Abstinencia a Sustancias/psicología , Estimulación Acústica , Animales , Condicionamiento Psicológico/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Activated protein C (APC) is a natural anticoagulant that plays a pivotal role in coagulation homeostasis. Severe inherited or acquired deficiency results in a clinical syndrome called purpura fulminans. In addition, APC also appears to have potent cytokine-modifying properties and is protective in animal models of sepsis. The dual functional properties of APC are particularly relevant to severe meningococcemia, where acquired PC deficiency is accompanied by multiorgan failure and purpura fulminans. The authors conducted an open-label prospective study assessing the efficacy of PC replacement therapy in patients with severe meningococcal septicemia, purpura fulminans, and multiorgan failure. The morbidity and mortality were compared with predicted morbidity using the Glasgow Meningococcal Septicemia Prognostic Score. Thirty-six patients with a mean age of 12 years (range 3 months to 72 years) were enrolled in the study. The mean +/- SD for plasma PC was 18 +/- 7 IU/mL. PC was significantly lower than antithrombin or protein S and was also significantly lower than PC levels in a cohort of patients who developed meningococcemia without multiorgan failure and purpura fulminans. A total of 3 of 36 (8%) patients died, which compares favorably with predicted mortality of 18 of 36 (50%). Amputations were required in 4 of 33 (12%) survivors and in 2 of 31 (6.5%) patients who received PC within 24 hours of admission into the hospital, in comparison with the predicted amputation rate of 11 of 33 (30%). In conclusion, PC replacement therapy in severe meningococcal septicemia was associated with a reduction in predicted morbidity and mortality. The beneficial effect of PC replacement may reflect both the anticoagulant and anti-inflammatory properties of the PC pathway. (Blood. 2000;96:3719-3724)
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Vasculitis por IgA/tratamiento farmacológico , Infecciones Meningocócicas/complicaciones , Proteína C/farmacocinética , Adolescente , Adulto , Anciano , Amputación Quirúrgica , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapéutico , Antifibrinolíticos/metabolismo , Niño , Preescolar , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Vasculitis por IgA/sangre , Vasculitis por IgA/etiología , Lactante , Masculino , Infecciones Meningocócicas/sangre , Infecciones Meningocócicas/tratamiento farmacológico , Persona de Mediana Edad , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/tratamiento farmacológico , Insuficiencia Multiorgánica/etiología , Neisseria meningitidis , Inhibidor 1 de Activador Plasminogénico/sangre , Pronóstico , Proteína C/uso terapéutico , Deficiencia de Proteína C/complicaciones , Deficiencia de Proteína C/tratamiento farmacológico , Deficiencia de Proteína C/etiología , Proteína S/metabolismo , Choque Séptico/sangre , Choque Séptico/tratamiento farmacológico , Tasa de SupervivenciaRESUMEN
OBJECTIVES/HYPOTHESIS: Nasal disease, including chronic rhinosinusitis and allergic rhinitis, is a significant source of morbidity. Nasal irrigation has been used as an adjunctive treatment of sinonasal disease. However, despite an abundance of anecdotal reports, there has been little statistical evidence to support its efficacy. The objective of this study was to determine the efficacy of the use of pulsatile hypertonic saline nasal irrigation in the treatment of sinonasal disease. STUDY DESIGN: A prospective controlled clinical study. METHODS: Two hundred eleven patients from the University of California, San Diego (San Diego, CA) Nasal Dysfunction Clinic with sinonasal disease (including allergic rhinitis, aging rhinitis, atrophic rhinitis, and postnasal drip) and 20 disease-free control subjects were enrolled. Patients irrigated their nasal cavities using hypertonic saline delivered by a Water Pik device using a commercially available nasal adapter twice daily for 3 to 6 weeks. Patients rated nasal disease-specific symptoms and completed a self-administered quality of well-being questionnaire before intervention and at follow-up. RESULTS: Patients who used nasal irrigation for the treatment of sinonasal disease experienced statistically significant improvements in 23 of the 30 nasal symptoms queried. Improvement was also measured in the global assessment of health status using the Quality of Well-Being scale. CONCLUSIONS: Nasal irrigation is effective in improving symptoms and the health status of patients with sinonasal disease.
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Cavidad Nasal , Enfermedades Nasales/terapia , Solución Salina Hipertónica/administración & dosificación , Humanos , Estudios Prospectivos , Rinitis/terapia , Sinusitis/terapia , Encuestas y Cuestionarios , Irrigación Terapéutica/métodos , Resultado del TratamientoRESUMEN
Structural plasticity of nerve cells is a requirement for activity-dependent changes in the brain. The growth-associated protein GAP-43 is thought to be one determinant of such plasticity, although the molecular mechanism by which it mediates dynamic structural alterations at the synapse is not known. GAP-43 is bound by calmodulin when Ca2+ levels are low, and releases the calmodulin when Ca2+ levels rise, suggesting that calmodulin may act as a negative regulator of GAP-43 during periods of low activity in the neurons. To identify the function of GAP-43 during activity-dependent increases in Ca2+ levels, when it is not bound to calmodulin, we sought proteins with which GAP-43 interacts in the presence of Ca2+. We show here that rabaptin-5, an effector of the small GTPase Rab5 that mediates membrane fusion in endocytosis, is one such protein. We demonstrate that GAP-43 regulates endocytosis and synaptic vesicle recycling. Modulation of endocytosis by GAP-43, in association with rabaptin-5, may constitute a common molecular mechanism by which GAP-43 regulates membrane dynamics during its known roles in activity-dependent neurotransmitter release and neurite outgrowth.
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Endocitosis/fisiología , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Transporte Vesicular , Química Encefálica/genética , Calmodulina/metabolismo , ADN Complementario/aislamiento & purificación , Endosomas/fisiología , Feto , Técnica del Anticuerpo Fluorescente , Proteína GAP-43/aislamiento & purificación , Expresión Génica/fisiología , Biblioteca de Genes , Humanos , Proteínas de la Membrana/aislamiento & purificación , Microscopía Electrónica , Neuronas/química , Neuronas/metabolismo , Neuronas/ultraestructura , ARN Mensajero/análisis , Vesículas Sinápticas/química , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/ultraestructuraRESUMEN
STUDY OBJECTIVE: To evaluate selective aortic arch perfusion (SAAP) with an oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during cardiac arrest. METHODS: This randomized, controlled study, undertaken at a university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes. Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE) in the same fashion as the control group but were also subjected to SAAP with 275 mL of oxygenated 60% wt/vol perflubron emulsion over 30 seconds. Group 3 dogs (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the first epinephrine dose was given intraaortically. RESULTS: Coronary perfusion pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly greater in the AoE-SAAP group than in the control group. Return of spontaneous circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1 +/- 1.9 minutes in the AoE-SAAP group, compared with 11.0 +/- 5.8 minutes in the IVE-SAAP group. CONCLUSION: SAAP with oxygenated perflubron emulsion improved ROSC, both with and without aortic arch epinephrine. The combination of SAAP with perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more rapid ROSC.
Asunto(s)
Aorta Torácica , Epinefrina/uso terapéutico , Fluorocarburos/uso terapéutico , Paro Cardíaco/terapia , Infusiones Intraarteriales/métodos , Resucitación/métodos , Vasoconstrictores/uso terapéutico , Animales , Modelos Animales de Enfermedad , Perros , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Hemodinámica/efectos de los fármacos , Hidrocarburos Bromados , Infusiones Intravenosas , Distribución AleatoriaRESUMEN
Olfactory threshold was investigated in patients with verified allergic rhinitis to birch pollen. In 20 patients the olfactory threshold was measured before and after challenge with topically applied birch pollen allergen during a non-symptomatic period. After provocation a statistically significant impaired detection sensitivity was found. The change in olfactory threshold was correlated with the measured amount of nasal secretions but not with subjectively or objectively registered nasal obstruction. A pronounced allergic reaction after allergen challenge is accompanied by an elevated olfactory threshold.
Asunto(s)
Alérgenos , Polen , Rinitis Alérgica Estacional/fisiopatología , Umbral Sensorial/fisiología , Olfato/fisiología , 1-Butanol , Administración Intranasal , Adolescente , Adulto , Butanoles/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/metabolismo , Obstrucción Nasal/fisiopatología , Pruebas de Provocación Nasal , Nariz/patología , Nariz/fisiopatología , Odorantes , Rinitis Alérgica Estacional/patología , ÁrbolesRESUMEN
We have determined the nucleotide sequence of the nuclear gene encoding small-subunit ribosomal ribonucleic acid of the ciliate Anophryoides haemophila, a parasite of the American lobster Homarus americanus. The gene is 1763 bp in length, and has a guanosine-plus-cytosine content of 43.9%. Inferred phylogenetic frameworks strongly support the monophyly of the scuticociliates, and suggest that order Scuticociliatida should be elevated to at least subclass rank. Oligonucleotide probes based on A. haemophila ssurDNA can discriminate between DNAs of A. haemophila and other investigated hymenostome ciliates, and effectively prime polymerase chain reaction-based detection of A. haemophila deoxyribonucleic acid against at least a 1600-fold excess of total deoxyribonucleic acid from H. americanus. GENBANK/U51554