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Background: Soft tissue preservation using a hydroxyapatite-coated abutment in bone conduction hearing implant surgery may lead to improved clinical outcomes over the short (1 year) and long term (3 years). Methods: In this open multi-center, randomized (1:1), controlled clinical trial, subjects with conductive, mixed hearing loss or single-sided sensorineural deafness were randomly assigned to receive the conventional intervention, a titanium abutment with soft tissue reduction surgery (control), or a new intervention, a hydroxyapatite-coated abutment with soft tissue preservation surgery (test). The primary efficacy outcome was the combined endpoint of numbness, pain, peri-abutment dermatitis, and soft tissue thickening/overgrowth after 1 and 3 years. Results: The Intention-to-treat (ITT) population consisted of 52 control subjects and 51 test subjects. The difference between the groups after 1 year of follow-up as measured by the primary efficacy outcome was not statistically significant (p = 0.12) in the ITT population (n = 103), but did reach statistical significance (p = 0.03) in the per-protocol (PP) population (n = 96). It showed an advantage for the test group, with over twice as many subjects (29%) without these medical events during the first year compared to the control group (13%). After 3 years, the difference between the two groups had declined and did not reach statistical significance (24 vs. 10%, ITT p = 0.45). Secondary outcome measures which showed a statistical significant difference during the first year, such as surgical time (15 vs. 25 minutes, p < 0.0001), numbness (90 vs. 69% of subjects experienced no numbness at 1 year, p < 0.01), neuropathic pain at 3 months (p = 0.0087) and the overall opinion of the esthetic outcome (observer POSAS scale at 3 months, p < 0.01) were favorable for the test group. More soft tissue thickening/overgrowth was observed at 3 weeks for the test group (p = 0.016). Similar results were achieved for the long term follow up. Conclusions: Soft tissue preservation with a hydroxyapatite-coated abutment leads to a reduction in the combined occurrence of complications over the first year which is not statistically significant in the ITT population but is in the PP population. This effect decreased for the long-term study follow up of 3 years and did also not reach statistical significance.
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AIM: To investigate the incidence of persisting auditory and vestibular sequelae in a group of 30 young adults recovering from Traumatic Brain Injury (TBI). METHODS: 30 participants, aged 21-45 years, with TBI suffered 19 months to 27 years previously, underwent a semi-structured interview and pure-tone hearing test in their home. Participants who failed the hearing screen then undertook a more comprehensive audiological evaluation. RESULTS: A variety of sequelae to TBI were reported. These were interpreted as tinnitus (53%), vestibular dysfunction (83%), abnormal facial sensory symptoms (27%) and intolerance to loud/sudden noises (87%). Ten (33%) participants demonstrated significant sensorineural hearing impairment in addition to speech recognition performance significantly worse than would have been predicted from their hearing impairment. CONCLUSIONS: Findings from this study will be of benefit to health professionals working in this area of rehabilitation as they seek to provide functional assessments and devise programmes to treat the often devastating auditory processing problems of people recovering from TBI.
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Lesiones Encefálicas/complicaciones , Trastornos de la Audición/etiología , Enfermedades Vestibulares/etiología , Adulto , Audiometría de Tonos Puros , Mareo/etiología , Femenino , Trastornos de la Audición/diagnóstico , Trastornos de la Audición/epidemiología , Humanos , Incidencia , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Índice de Severidad de la Enfermedad , Percepción del Habla , Encuestas y Cuestionarios , Factores de Tiempo , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/epidemiología , Vómitos/etiologíaRESUMEN
Detection of fluorescent signals in living cells is a common and powerful technique used to monitor gene expression for multiple biomedical applications. A disadvantage of this approach in vivo, is the limited accessibility for long-term monitoring of the fluorescent signals within organs in living animals. Because of the multiple applications of gene expression monitoring through fluorescent signals, innovative methods for readout are required. We developed a strategy combining gene transfer, fiber-optic or endoscope monitoring, and confocal microscopy for the brain interstitial or cavitary endoscopic visualization of the efficacy of gene delivery and expression in vivo. The approach is also effective in vitro and can be applied to multiple organs in vivo. We show an example of the detection of green fluorescent protein (GFP)-emitted fluorescence following the administration of recombinant GFP-expressing adenovirus or implantation of rat C6 glioblastoma cells infected with the recombinant GFP adenovirus into the rat hippocampus of chronically cannulated rats. The results show that fiber-optic monitoring coupled with confocal microscopy in gene transfer studies is a practical approach that results in a direct, efficient, rapid, and sensitive visualization of fluorescent signals in the brain. This allows for the continuous real-time in vitro or in vivo brain monitoring of gene expression, accurate anatomical localization, multiple experimental manipulations in the same subject or preparation, while no sacrifice of the animal is required to monitor the efficacy of gene transfer and/or expression.
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Tecnología de Fibra Óptica/métodos , Expresión Génica/fisiología , Técnicas de Transferencia de Gen/instrumentación , Microscopía Confocal/métodos , Animales , Tecnología de Fibra Óptica/instrumentación , Vectores Genéticos , Glioblastoma , Proteínas Fluorescentes Verdes , Indicadores y Reactivos/análisis , Proteínas Luminiscentes/análisis , Masculino , Microscopía Confocal/instrumentación , Microscopía Fluorescente/instrumentación , Microscopía Fluorescente/métodos , Fibras Ópticas , Ratas , Ratas Wistar , Células Tumorales Cultivadas/virologíaRESUMEN
Gram-negative bacteria-derived lipopolysaccharide (LPS or endotoxin) is known to play an important role in immune and neurological manifestations during bacterial infections. LPS exerts its effects through cytokines, and peripheral or brain administration of LPS activates cytokine production in the brain. In this study, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions and peripheral organs, as well as serum tumor necrosis factor (TNF)-alpha protein levels, in response to the intraperitoneal administration of LPS. For the first time, the simultaneous analysis of interleukin (IL)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, transforming growth factor (TGF)-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, and pro-opiomelanocortin (opioid peptide precursor) mRNAs was done in samples from specific brain regions in response to peripherally administered LPS. The same brain region/organ sample was assayed for all cytokine mRNA components. Peripherally administered LPS up-regulated pro-inflammatory cytokine (IL-1beta and/or TNF-alpha) mRNAs within the cerebral cortex, cerebellum, hippocampus, spleen, liver, and adipose tissue. LPS also increased plasma levels of TNF-alpha protein. LPS did not up-regulate inhibitory (anti-inflammatory) cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs in most brain regions (except for IL-1 receptor antagonist in the cerebral cortex and for TGF-beta1 in the hippocampus), while they were increased in the liver, and IL-1 receptor antagonist was up-regulated in the spleen and adipose tissue. Overall, peripherally administered LPS modulated the levels of IL-1beta system components within the brain and periphery, but did not affect the neuropeptide-related components studied. The data suggest specificity of transcriptional changes induced by LPS and that cytokine component up-regulation in specific brain regions is relevant to the neurological and neuropsychiatric manifestations associated with peripheral LPS challenge.
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Receptores de Activinas Tipo I , Encéfalo/metabolismo , Citocinas/metabolismo , ARN Mensajero/metabolismo , Receptores de Interleucina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Interleucina-1/metabolismo , Interleucinas/metabolismo , Lipopolisacáridos , Masculino , Neuropéptido Y/metabolismo , Proopiomelanocortina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Wistar , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Bazo/metabolismoRESUMEN
Physical (neurogenic) stressors may influence immune functioning and interleukin-1beta (IL-1beta) mRNA levels within several brain regions. The present study assessed the effects of an acute or repeated naturalistic, psychogenic stressor (predator exposure) on brain cytokine and neuropeptide mRNAs. Acute predator (ferret) exposure induced stress-like behavioral effects, including elicitation of a startle response and reduced exploratory behaviors; these responses diminished after 30 sessions. Moreover, acute and repeated predator exposure, like acute restraint stress, increased plasma corticosterone levels measured 5 min later, but not 2 h after stressor exposure. In contrast, none of the stressors used influenced IL-1beta, IL-1 receptor antagonist, IL-1 receptor type I, IL-1 receptor accessory proteins I and II, or tumor necrosis factor-alpha mRNA levels in the prefrontal cortex, amygdala, hippocampus, or hypothalamus. Likewise, there were no stressor effects on transforming growth factor-beta1, neuropeptide Y, glycoprotein 130, or leptin receptor mRNAs in brain regions. Thus, the naturalistic/psychogenic stressor used does not affect any of the brain cytokine component mRNAs studied. It is suggested that this type of stressor activates homeostatic mechanisms (e.g., glucocorticoid release), which act to preclude brain cytokine alterations that would otherwise favor neuroinflammatory/neuroimmunological responses and the consequent increase of brain sensitivity to neurotoxic and neurodegenerative processes.
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Encéfalo/metabolismo , Interleucina-1/metabolismo , Neuropéptidos/metabolismo , ARN Mensajero/análisis , Receptores de Superficie Celular , Estrés Psicológico/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Análisis de Varianza , Animales , Proteínas Portadoras/metabolismo , Interleucina-1/genética , Masculino , Morfolinas/metabolismo , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Neuropéptidos/genética , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Leptina , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Cytokines and neuropeptides may be involved in seizure-associated processes. Following amygdala kindling in rats, we determined alterations of IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory proteins (IL-1R AcPs) I and II, TNF-alpha, TGF-beta1, neuropeptide Y (NPY), glycoprotein 130 (gp 130) and pro-opiomelanocortin (POMC) mRNA levels in the parietal, prefrontal and piriform cortices, amygdala, hippocampus and hypothalamus. Messenger RNAs expression in all brain regions was determined 2 h or 3 weeks following the last generalized convulsive seizure triggered from the ipsilateral kindled amygdala. The same brain region sample was used to assay for changes of all mRNA components. The results show that the 2 h-kindled group exhibited a significant up-regulation of IL-1beta, IL-1RI, TNF-alpha and TGF-beta1 mRNAs in all three cortical brain regions, amygdala and hippocampus. The largest up-regulation occurred in the prefrontal cortex (about 30-fold induction for IL-1beta and TNF-alpha mRNAs). IL-1R AcP I and II mRNA levels were also up-regulated in the cortical regions. No changes in IL-1beta, IL-1RI or TNF-alpha mRNA levels occurred in the 3 week-kindled group. NPY mRNA levels increased in the hippocampus, prefrontal and piriform cortices in the 2 h-kindled group, while IL-1Ra, gp 130, or POMC mRNA levels did not change in any group. The overall profile of mRNA changes shows specificity of transcriptional modulation induced by amygdala kindling. The data support a role of cytokines and NPY in the adaptive mechanisms associated with generalized seizure activity, with implications for neuroprotection, neuronal dysfunction and vulnerability associated with epileptic activity.
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Encéfalo/metabolismo , Interleucina-1/metabolismo , Excitación Neurológica/fisiología , Neuropéptidos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Amígdala del Cerebelo/metabolismo , Animales , Contactinas , Corticosterona/sangre , Electrofisiología , Interleucina-1/genética , Proteína Accesoria del Receptor de Interleucina-1 , Excitación Neurológica/genética , Masculino , Moléculas de Adhesión de Célula Nerviosa/genética , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Neuropéptidos/genética , Isomerasa de Peptidilprolil/genética , Isomerasa de Peptidilprolil/metabolismo , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Long-Evans , Receptores de Interleucina-1/genética , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Interferon-alpha (IFN-alpha) immunotherapy is associated with significant adverse neurological effects, including anorexia, which can be a limiting factor in immunotherapy. Thus, it is important to develop strategies that could ameliorate IFN-alpha-induced neurological manifestations without significantly affecting its immunomodulating properties. In this study, we tested the hypothesis that an endogenous feeding-enhancing peptide, neuropeptide Y (NPY), could inhibit IFN-alpha-induced anorexia in rats. The results show that IFN-alpha induced significant anorexia when administered centrally into the third cerebral ventricle at an immunotherapeutically relevant dose (1,350 IU/rat). Heat-inactivated IFN-alpha had no effect. NPY (5.0 microg/rat) counteracted the IFN-alpha-induced anorexia when administered 3 or 10 h following IFN-alpha, or when it was concomitantly administered with IFN-alpha. The data suggest that NPY and its agonists could represent a potential novel intervention for IFN-alpha immunotherapy-associated anorexia.
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Anorexia/inducido químicamente , Interferón-alfa , Neuropéptido Y/farmacología , Animales , Ritmo Circadiano , Interacciones Farmacológicas , Ingestión de Energía/efectos de los fármacos , Masculino , Ratas , Ratas WistarRESUMEN
By diminishing the role of communicative context, traditional tests of speech perception may underestimate or misrepresent the actual speech perception abilities of adults with a hearing impairment. This study investigates this contention by devising an assessment that may better simulate some aspects of "real-life" speech perception. A group of 31 participants with a severe-to-profound hearing impairment took part in a series of speech perception tests while wearing their hearing aids. The tests used question/answer or adjacency pairs, where the stimulus sentence was preceded by a question spoken by the participant. Four conditions were included: (a) where there was no initiating sentence, as in a traditional open-set speech perception test; (b) where the initiating question was neutral (e.g. "Why?"); (c) where there was a disruptive semantic relationship between the question and answer; and (d) where there was a strong contextual relationship between the question and answer. The time delay between the question and answer was also varied. Results demonstrated that in all conditions where there was a preceding question speech perception improved, and increasing the cohesion between the question and the reply improved speech perception scores. Additionally, time delay and the relatedness of the reply interacted. The effects of semantic context appeared to diminish over a 10-s period while other linguistic effects remained more constant. These results indicate the utility of simulating communicative environments within speech perception tests.
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Comunicación , Percepción del Habla/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Neuropeptide Y (NPY), NPY 3-36 and pancreatic polypeptide (PP) increase short-term (2-h) food intake to varying degrees when given intracerebroventricularly (i.c.v.). Various Y receptor subtypes are proposed to participate in Y receptor ligand-induced stimulation of food intake. Here, we used an antisense phosphothio-oligodeoxynucleotide sequence (-5 relative to the initiating ATG) to the Y5 receptor subtype, which has been suggested to mediate NPY-induced feeding. Rats were treated with i.c.v. antisense or sense phosphothio-oligodeoxynucleotide for 3.5 days before NPY, NPY 3-36, or PP i.c.v. administration. The results show that antisense to the Y5 receptor had no effect on either spontaneous 2-h or NPY-, NPY 3-36-, or PP-stimulated 2-h food intake. However, there was a significant decrease relative to the sense control group in 10-h food intake following the initial 2-h feeding response to NPY (n = 10, p < 0.0001) or NPY 3-36 (n = 10, p < 0.05). The data suggest that the Y5 receptor has a modulatory role in the maintenance of feeding, but not as the critical receptor to confer for NPY and NPY 3-36 action on food intake.
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Regulación del Apetito/fisiología , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Receptores de Neuropéptido Y/fisiología , Animales , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Neuropéptido Y/farmacología , Oligonucleótidos Antisentido , Polipéptido Pancreático/farmacología , Ratas , Ratas Wistar , Receptores de Neuropéptido Y/efectos de los fármacos , TionucleótidosAsunto(s)
Dieta , Ingestión de Alimentos , Proteínas/fisiología , Humanos , Leptina , Saciedad/fisiologíaRESUMEN
Neuropeptide Y (NPY) and related compounds increase short-term feeding. Previous studies have used different animal models, feeding schedules, sources of the compounds, and time and routes of administration. These differences in methodology are important in the variability reported on the potency of NPY-related compounds. To obtain reliable data on the relative efficacy, we tested NPY, NPY 3-36, and pancreatic polypeptide (PP) using an identical protocol and the same commercial source. These three NPY-related compounds were tested using the intracerebroventricular (i.c.v., into the third ventricle) administration, and the profile of the feeding enhancement including the dose response and potency was determined. Compounds were tested in parallel on at least 2 successive days. NPY, NPY 3-36, and PP exhibited different potencies in enhancing 2-h food intake. Comparison of their dose responses (using 0.1, 0.25, 0.5, 1.0, 2.5, and 5.0 microg/rat) demonstrated an overall potency of NPY 3-36 > NPY > PP for the high doses. To study ligand interactions, we examined the effects of various combinations of NPY-related compounds administered concomitantly. These combinations were justified based on the data obtained from the individual dose responses. The data show that the effects of NPY plus NPY 3-36 or NPY 3-36 plus PP were less than additive. When compared to the individual responses, the effects of NPY 3-36 were almost identical to those induced by the combinations using low doses of NPY plus NPY 3-36, or low and high doses of PP plus NPY 3-36. The results support the notion that NPY and its analogues induce a short-term feeding response by activating multiple receptor subtypes.
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Estimulantes del Apetito/farmacología , Conducta Alimentaria/efectos de los fármacos , Neuropéptido Y/análogos & derivados , Neuropéptido Y/farmacología , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intraventriculares , Masculino , Polipéptido Pancreático/farmacología , Fragmentos de Péptidos/farmacología , Ratas , Ratas WistarRESUMEN
Bacterial-derived products [e.g., lipopolysaccharide (LPS) from Gram-negative and muramyl dipeptide (MDP) from Gram-positive bacteria] are proposed to play a pivotal role in the generation of neurological and neuroinflammatory/immunological responses during bacterial infections of the nervous system. LPS and MDP may act through cytokines; cytokine-neuropeptide interactions may also be involved. Here, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions in response to the intracerebroventricular administration of LPS and MDP. IL-beta1 system components (ligand, signalling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, TGF-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, Y5 receptor, and pro-opiomelanocortin (opioid peptide precursor) mRNAs were analyzed. The same brain region sample was assayed for all components. LPS and MDP administration induced significantly different behavioral and molecular profiles. LPS was significantly more potent than MDP in inducing anorexia and in up-regulating pro-inflammatory cytokines (IL- beta1 and TNF-alpha mRNAs in the cerebellum, hippocampus and hypothalamus; MDP was more potent in up-regulating anti-inflammatory cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs. LPS and MDP also modulated hypothalamic IL-1 receptor mRNA components, but did not affect any of the neuropeptide-related components examined. The results suggest that the magnitude of neurological manifestations induced by LPS and MDP may involve the ratio between stimulatory and inhibitory cytokines, and this ratio may have implications for the neuroinflammatory/neurotoxic events associated with bacterial infections of the central nervous system.
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Acetilmuramil-Alanil-Isoglutamina/inmunología , Encéfalo/inmunología , Citocinas/biosíntesis , Lipopolisacáridos/inmunología , Receptores de Superficie Celular , Animales , Antígenos CD/biosíntesis , Antígenos CD/genética , Encéfalo/microbiología , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Receptor gp130 de Citocinas , Citocinas/genética , Ingestión de Alimentos , Bacterias Gramnegativas/inmunología , Bacterias Grampositivas/inmunología , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/genética , Proteína Accesoria del Receptor de Interleucina-1 , Masculino , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Neuropéptido Y/biosíntesis , Neuropéptido Y/genética , Proopiomelanocortina/biosíntesis , Proopiomelanocortina/genética , Biosíntesis de Proteínas , Proteínas/genética , ARN Mensajero , Ratas , Ratas Wistar , Receptores de Interleucina-1/biosíntesis , Receptores de Interleucina-1/genética , Receptores de Leptina , Receptores de Neuropéptido Y/biosíntesis , Receptores de Neuropéptido Y/genética , Sialoglicoproteínas/biosíntesis , Sialoglicoproteínas/genética , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56-3.5 microg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 microg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 microg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.
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Ventrículos Cerebrales/fisiología , Ritmo Circadiano , Ingestión de Energía/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Proteínas/farmacología , Animales , Ventrículos Cerebrales/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Infusiones Parenterales , Leptina , Masculino , Obesidad , Proteínas/administración & dosificación , Ratas , Ratas Wistar , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiologíaRESUMEN
We investigated the effectiveness of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted Wistar rats allowed to refeed. We also assayed for changes in mRNA levels of IL-1 system components, TNF-alpha, TGF-beta1, glycoprotein 130 (gp 130), leptin receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NPY), glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions. The data show that LPS and MDP induced anorexia differentially during refeeding. LPS-induced anorexia was of a stronger magnitude and duration than that of MDP. RNase protection assays showed that LPS and MDP significantly increased the expression of IL-1beta, IL-1 receptor type I, and TNF-alpha mRNAs in the cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP treatment, on the other hand, induced a stronger increase in hypothalamic levels of IL-1 receptor antagonist (IL-1Ra) and TGF-beta1 mRNAs relative to LPS. In addition, competitive RT-PCR analysis showed that LPS induced an eleven-fold increase in IL-1alpha mRNA in the hypothalamus relative to vehicle. These findings suggest that LPS and MDP mediate anorexia through different cytokine mechanisms. A stronger up-regulation of anti-inflammatory cytokines (IL-1Ra and TGF-beta1) mRNA expression by MDP may be involved in the weaker MDP-induced anorexia relative to LPS. No significant changes were observed in the peptide components examined except for an up-regulation in cerebellar gp 130 mRNA and down-regulation of hypothalamic GR mRNA expression in response to LPS or MDP. This study shows that LPS and MDP induce anorexia in fasted rats allowed to refeed, and suggests an important role for endogenous cytokine-cytokine interactions.
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Anorexia/fisiopatología , Química Encefálica/fisiología , Citocinas/genética , Ayuno/fisiología , Neuropéptidos/genética , Receptores de Superficie Celular , Acetilmuramil-Alanil-Isoglutamina/farmacología , Adyuvantes Inmunológicos/farmacología , Hormona Adrenocorticotrópica/metabolismo , Animales , Anorexia/inducido químicamente , Conducta Animal/fisiología , Proteínas Portadoras/genética , Cerebelo/química , Ingestión de Alimentos/fisiología , Hipocampo/química , Hipotálamo/química , Interleucina-1/genética , Lipopolisacáridos/farmacología , Proteínas de Membrana de los Lisosomas , Masculino , Glicoproteínas de Membrana/genética , Neuropéptido Y/genética , Péptidos Opioides/genética , Reacción en Cadena de la Polimerasa , Proopiomelanocortina/genética , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Glucocorticoides/genética , Receptores de Leptina , Ribonucleasas , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Adults with severe or severe-to-profound hearing losses constitute between 11% and 13.5% of the hearing-impaired population. A detailed investigation of the speech recognition of adults with severe (n = 20) or severe-to-profound (n = 14) hearing loss was conducted at The University of Melbourne. Each participant took part in a series of speech recognition tasks while wearing his or her currently fitted hearing aid(s). The assessments included closed-set tests of consonant recognition and vowel recognition, combined with open-set tests of monosyllabic word recognition and sentence recognition. Sentences were presented in quiet and in noise at +10 dB SNR to replicate an environment more typical of everyday listening conditions. Although the results demonstrated wide variability in performance, some general trends were observed. As expected vowels were generally well perceived compared with consonants. Monosyllabic word recognition scores for both the adults with a severe hearing impairment (M = 67.2%) and the adults with a severe-to-profound hearing impairment (M = 38.6%) could be predicted from the segmental tests, with an allowance for lexical effects. Scores for sentences presented in quiet showed additional linguistic effects and a significant decrease in performance with the addition of background noise (from 82.9% to 74.1% for adults with a severe hearing loss and from 55.8% to 34.2% for adults with a severe-to-profound hearing loss). Comparisons were made between the participants and a group of adults using a multiple-channel cochlear implant. This comparison indicated that some adults with a severe or severe-to-profound hearing loss may benefit from the use of a cochlear implant. The results of this study support the contention that cochlear implant candidacy should not rely solely on audiometric thresholds.
Asunto(s)
Implantación Coclear , Audífonos , Pérdida Auditiva Sensorineural/rehabilitación , Percepción del Habla , Adolescente , Adulto , Niño , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Fonética , Ajuste de Prótesis , Índice de Severidad de la EnfermedadRESUMEN
Bacterial lipopolysaccharide (LPS) or endotoxin induces neurological manifestations including anorexia. It is proposed that LPS-induced cytokine production is involved in the generation of neurological manifestations and in neuroinflammatory/immunological responses during gram-negative infections. For example, LPS-induced effects can be blocked or ameliorated by the interleukin-1 receptor antagonist (IL-1Ra). Here, sensitive and specific RNase protection assays were used to investigate the effects of the intracerebroventricular (i.c.v.) administration of LPS on mRNA levels of interleukin-1beta (IL-1beta) system components, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and neuropeptide Y (NPY) in the cerebellum, hippocampus, and hypothalamus. The same brain region sample was analyzed with all of the antisense probes. The data show simultaneous local induction of multiple cytokine components messenger ribonucleic acids (mRNAs) within specific brain regions in anorectic rats responding to i.c.v. administered LPS (500 ng/rat). Interleukin-1beta and IL-1Ra had a similar mRNA induction profile (hypothalamus > cerebellum > hippocampus). Interleukin-1 receptor type I (IL-1RI) mRNA also increased in all three brain regions examined, and the soluble form of IL-1 receptor accessory protein (IL-1R AcP II) mRNA was induced in the hypothalamus. Tumor necrosis factor-alpha mRNA levels increased in the hypothalamus > hippocampus > cerebellum. Levels of membrane bound IL-1R AcP, TGF-beta1, and NPY mRNAs did not change significantly in any brain region. The results suggest that: (1) endogenous up-regulation of IL-1beta and TNF-alpha in the hypothalamus contribute to LPS-induced anorexia; and (2) the ratio IL-1Ra/IL-1beta, and IL-1beta <--> TNF-alpha interactions may have implications for gram-negative infections associated with high levels of LPS in the brain-cerebrospinal fluid.
Asunto(s)
Anorexia/metabolismo , Encéfalo/metabolismo , Ventrículos Cerebrales/fisiología , Interleucina-1/biosíntesis , Lipopolisacáridos/toxicidad , Neuropéptido Y/biosíntesis , Biosíntesis de Proteínas , Proteínas , Receptores de Interleucina-1/biosíntesis , Sialoglicoproteínas/biosíntesis , Transcripción Genética/efectos de los fármacos , Animales , Anorexia/inducido químicamente , Anorexia/inmunología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Ventrículos Cerebrales/efectos de los fármacos , Ventrículos Cerebrales/fisiopatología , Escherichia coli , Infusiones Parenterales , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/antagonistas & inhibidores , Proteína Accesoria del Receptor de Interleucina-1 , Lipopolisacáridos/administración & dosificación , Especificidad de Órganos , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Factor de Crecimiento Transformador beta/biosíntesisRESUMEN
IL-1beta induces anorexia and adipsia. Here, we report that intracerebroventricular (ICV) pretreatment with an antisense (but not sense) phosphothio-oligodeoxynucleotide to the IL-1 receptor type I (IL-1RI, 1.28 microg or 239 pmol twice daily for 3.5 days before IL-1beta plus antisense) inhibits the anorexia, but not the adipsia induced by the ICV administration of 2.0 ng IL-1beta/rat (a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). The mean 2 h food intake decrease in response to IL-1beta was 5.6% (n = 10) in the antisense- and 43% in the sense (n = 9)-treated groups; the mean 2 h water intake decrease was 40% in the antisense- and 39% in the sense-treated groups. The intraperitoneal administration of IL-1RI antisense, in doses equivalent to those administered centrally, had no effect on the anorexic effect induced by ICV administered IL-1beta; this indicates a direct action in the central nervous system. The results suggest that: i) IL-1RI is involved in the short-term anorexigenic, but not the adipsogenic effect induced by centrally administered IL-1beta; and ii) the approach presented using antisense strategies is applicable to study the molecular basis of IL-1 mediated behaviors.
Asunto(s)
Apetito/fisiología , Ingestión de Líquidos/fisiología , Ingestión de Alimentos/fisiología , Hambre/fisiología , Interleucina-1/farmacología , Receptores de Interleucina-1/fisiología , Animales , Apetito/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hambre/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Wistar , Receptores de Interleucina-1/efectos de los fármacosRESUMEN
This paper has arisen from an investigation of the lives and circumstances of 88 people who are mentally handicapped and living in their own homes or tenancies. This study is funded by the Economic and Social Research Council. The difficulties inherent in interviewing people who are mentally handicapped are outlined. This is followed by a consideration of the findings of previous research and a listing of guidelines for interviewing. The paper also explores consent procedures and issues pertaining to the measurement of satisfaction.
Asunto(s)
Discapacidad Intelectual/psicología , Entrevistas como Asunto/métodos , Comportamiento del Consumidor , Vivienda , Humanos , Consentimiento Informado , Discapacidad Intelectual/rehabilitación , Proyectos PilotoRESUMEN
This study describes the circumstances of 12 adults who are mentally handicapped who are residing with their parents. The results are derived from a content analysis of interviews. The analysis explores the reliability of a procedure for rating people's satisfaction. It also investigates people's views regarding the following: money, cooking, laundry, shopping, cleaning, home, neighbours, friends, support, interests and the ATC.
Asunto(s)
Discapacidad Intelectual/psicología , Satisfacción Personal , Actividades Cotidianas , Adulto , Empleo , Femenino , Vivienda , Humanos , Discapacidad Intelectual/rehabilitación , Relaciones Interpersonales , Masculino , PadresRESUMEN
This paper reports an investigation to determine whether staff in an Adult Training Centre could estimate the performance of adults who are mentally handicapped on a test of moral knowledge. It also sought to discover whether estimations are more accurate in instances where staff claim to have a closer knowledge of the subjects. Not only do the results indicate that training staff are unable to estimate accurately, but they overestimate knowledge in this subject area. The degree of knowledge of the subjects made no difference to the accuracy of staff estimations. The implications of these results are considered in terms of the training needs of staff in Adult Training Centre and the use of assessment criteria prior to the entry of students into specific training programmes.