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1.
Am J Surg ; 226(4): 524-530, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37156679

RESUMEN

BACKGROUND: Hospital consolidation into health systems has mixed effects on surgical quality, potentially related to degree of surgical centralization at high-volume (hub) sites. We developed a novel measure of centralization and evaluated a hub and spoke framework. METHODS: Surgical centralization within health systems was measured using hospital surgical volumes (American Hospital Association) and health system data (Agency for Healthcare Research and Quality). Hub and spoke hospitals were compared using mixed effects logistic regression and system characteristics associated with surgical centralization were identified using a linear model. RESULTS: Within 382 health systems containing 3022 hospitals, system hubs perform 63% of cases (IQR 40-84%). Hubs are larger, in metropolitan and urban areas, and more often academically affiliated. Degree of surgical centralization varies ten-fold. Larger, multistate, and investor-owned systems are less centralized. Adjusting for these factors, there is less centralization among teaching systems (p â€‹< â€‹0.001). CONCLUSIONS: A hub-spoke framework applies to most health systems but centralization varies significantly. Future studies of health system surgical care should assess the contributions of surgical centralization and teaching status on differential quality.


Asunto(s)
Atención a la Salud , Hospitales , Humanos , Estados Unidos , Programas de Gobierno
2.
Aust Vet J ; 101(6): 219-224, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36967588

RESUMEN

OBJECTIVE: To report the clinical presentations, treatments and outcomes of toad toxicity in domestic cats in Southeastern Queensland, Australia. METHODS: This report describes a retrospective study of 190 cases of cane toad (Rhinella marina) toxicity in cats in south-eastern Queensland, Australia. All cases were presented for veterinary treatment between 2011 and 2020 at four specialist veterinary emergency centres in Southeast Queensland, Australia. Cane toad toxicity was diagnosed based on a history of exposure and clinical signs. RESULTS: Domestic short-hair breeds accounted for 53.6% of the cases. Presentation was seasonal with the highest incidence over the warmer months of the year (November - March). Hypersalivation was described in 96.3% (183/190), tachypnoea in 34.2% (65/190) and altered behaviour in 18.4% (35/190) of cases. Seizures occurred in 1% of cases. Of the 190 cases, 6.3% (12/190) were hospitalised and 0.5% (1/190) were euthanised and overall 99.5% (189/190) survived hospital discharge. CLINICAL SIGNIFICANCE: Cane toad toxicity is relatively common in cats in Southeast Queensland and following buccal lavage the prognosis for recovery was excellent.


Asunto(s)
Especies Introducidas , Animales , Gatos , Queensland/epidemiología , Bufo marinus , Estudios Retrospectivos , Australia , Pronóstico
3.
Neurobiol Dis ; 179: 106034, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36775043

RESUMEN

The endocannabinoid system plays an important role in multiple behavioral responses due to its wide distribution in the central nervous system. The cannabinoid CB1 receptor was associated to the loss of behavioral control over food intake occurring during food addiction. The cannabinoid CB2 receptor (CB2R) is expressed in brain areas canonically associated with addictive-like behavior and was linked to drug-addictive properties. In this study, we evaluated for the first time the specific role of the CB2R in food addiction by using a well-validated operant mouse model of long-term training to obtain highly palatable food. We have compared in this model the behavioral responses of wild-type mice, mutant mice constitutively lacking CB2R, and transgenic mice overexpressing CB2R. The lack of CB2R constitutes a protective factor for the development of food addiction and the impulsive and depressive-like behavior associated. In contrast, the overexpression of CB2R induces a vulnerable phenotype toward food addiction after long-term exposure to highly palatable chocolate pellets. Relevant transcriptomic changes were associated to resilience and vulnerability to food addiction depending on the genotype, which provides a mechanistic explanation for these behavioral changes. Therefore, CB2R may constitute a potential therapeutic target for the loss of eating control and the comorbid emotional effects associated to food addiction.


Asunto(s)
Cannabinoides , Adicción a la Comida , Ratones , Masculino , Animales , Receptor Cannabinoide CB2/genética , Encéfalo , Endocannabinoides , Receptor Cannabinoide CB1/genética
4.
Mult Scler Relat Disord ; 56: 103266, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34555758

RESUMEN

BACKGROUND: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. OBJECTIVE: To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index. METHODS: Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples. RESULTS: In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G â†’ C), leading to an amino acid change (Lys â†’ Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection. CONCLUSIONS: . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.


Asunto(s)
Virus JC , Leucoencefalopatía Multifocal Progresiva , Esclerosis Múltiple , Infecciones por VIH , Humanos , Virus JC/genética , Leucocitos Mononucleares , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/genética , Mutación , Natalizumab/uso terapéutico
5.
Neuropharmacology ; 186: 108466, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33482225

RESUMEN

Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.


Asunto(s)
Conducta Adictiva/fisiopatología , Encéfalo/fisiopatología , Susceptibilidad a Enfermedades/fisiopatología , Red Nerviosa/fisiopatología , Animales , Conducta Adictiva/diagnóstico , Conducta Adictiva/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Susceptibilidad a Enfermedades/diagnóstico , Susceptibilidad a Enfermedades/metabolismo , Electroencefalografía/efectos de los fármacos , Electroencefalografía/métodos , Fenómenos Electrofisiológicos/efectos de los fármacos , Fenómenos Electrofisiológicos/fisiología , Humanos , Drogas Ilícitas/efectos adversos , Red Nerviosa/efectos de los fármacos , Red Nerviosa/metabolismo , Piperazinas/metabolismo
6.
Eur Rev Med Pharmacol Sci ; 25(24): 7654-7667, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34982427

RESUMEN

Cervical cancer is characterized by the cellular transformation caused by Human Papillomavirus (HPV), favoring cell proliferation, migration, invasion, and metastasis. Cervical cancer is conventionally treated with radiation therapy, and chemotherapy focused on the destruction of tumor cells. However, chemoresistance and low selectivity between tumor and non-tumor cells have been reported, causing side effects in patients. Metabolites of natural origin have shown selectivity against tumor cells, suggesting their use for reducing the side effects caused by drugs used in conventional therapy. Among these compounds, several natural coumarins stand out, such as auraptene, scopoletin, osthole, and praeruptorin, of which antiproliferative, anti-migratory, and anti-invasive activity have been reported. Auraptene, scopoletin, osthole, and praeruptorin show a cytotoxic or antiproliferative effect on cervical tumor cells, arresting the cell cycle by inducing the overexpression of negative regulators of the cell cycle, or inducing cell death by increasing the expression of pro-apoptotic proteins and decreasing that of anti-apoptotic proteins. On the other hand, auraptene, scopoletin, and praeruptorin inhibit the capacity for migration, invasion, and metastasis of cervical tumor cells, mainly by inhibiting the expression and activity of matrix metalloproteinase-2 and -9. The PI3K/Akt signal pathway appears to be central to the anti-tumor activity of the coumarins analyzed in this review. In addition, auraptene, osthole, and praeruptorin are useful in sensitizing tumor cells to radiotherapy or chemotherapeutic molecules, such as FOLFOX, cisplatin, or DOX. Coumarins offer an excellent possibility for developing new drugs as complementary medicine with an integrative approach against cervical cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Cumarinas/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Terapias Complementarias , Cumarinas/farmacología , Femenino , Humanos
7.
Poult Sci ; 99(12): 6954-6963, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33248611

RESUMEN

A total of 945 male Ross 308 broiler chicks were used in a growth study to explore the interaction between dietary crude protein concentration and available phosphorus. Nine experimental treatments were constructed factorially by offering low, medium, or standard protein concentrations without or with low, standard, or high available phosphorus. Diets were based on corn, wheat, and soybean meal and all nutrients other than protein/amino acids and available phosphorus were maintained at or above breeder guidelines. Additional synthetic amino acids were used in the diets with low protein concentration in attempt to maintain digestible amino acid supply. Diets were offered to 7 replicate pens of 15 chicks per pen from day 8 to 35. Growth performance was measured during the grower (day 8-24) and finisher (day 25-35) periods. On day 35 carcass composition was determined, blood was drawn for various biochemical measurements and the tibia was excised for mechanical and compositional analyses. Birds that received the low-protein diet had lower terminal body weight and higher feed conversion ratio compared with those that received diets with adequate crude protein content. However, addition of available phosphorus to the low-protein diet resulted in significant reductions in weight-corrected feed conversion that were not evident in the diet with adequate protein content. Bone architecture was only moderately influenced by dietary treatment but birds that ingested the diets containing low and medium protein concentrations had relatively heavier abdominal fat pad weight. Blood biochemistry, especially ammonia, uric acid, and phosphorus, was influenced by both dietary protein and available phosphorus and trends suggested that both axes are involved in protein accretion and catabolism. It can be concluded that performance losses associated with feeding low protein diets to broiler chickens may be partially restored by additional available phosphorus. The implications for use of exogenous enzymes such as protease and phytase and protein nutrition per se warrants further examination.


Asunto(s)
Composición Corporal , Pollos , Dieta con Restricción de Proteínas , Crecimiento , Fósforo , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Composición Corporal/efectos de los fármacos , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Dieta con Restricción de Proteínas/veterinaria , Crecimiento/efectos de los fármacos , Masculino , Fósforo/farmacología , Distribución Aleatoria
8.
Rev. med. vet. zoot ; 67(1): 17-32, ene.-abr. 2020. tab, graf
Artículo en Español | LILACS, COLNAL | ID: biblio-1127010

RESUMEN

RESUMEN Los lagomorfos y los histricomorfos, como los cuyos y las chinchillas, comparten características dentales como: dentadura elodonta e hipsodonta. Estas peculiaridades predisponen la presentación de maloclusión debido al consumo de dietas inadecuadas, poco abrasivas. El propósito de este trabajo es identificar la prevalencia de maloclusión en cada una de las especies mencionadas, de acuerdo con su sexo y grupo etario. Además, tiene como objetivo hacer una evaluación objetiva de los estudios radiográficos de los ejemplares, basada en líneas de referencia anatómica, para determinar los principales hallazgos radiográficos según el grado de maloclusión diagnosticado de forma clínica. El 30% de todos los individuos evaluados presentaron problemas de maloclusión, 42,86% de ellos conejos, 16,6% cuyos y 23% chinchillas. No se evidenciaron diferencias significativas en la presentación por sexo. En conejos fue más común el diagnóstico de ejemplares del grupo etario I y II, mientras que en cuyos lo fue en los grupos II y III. El grado I y II fueron los más diagnosticados en conejos y cuyos. En las radiografías las lesiones más comunes fueron el sobrecrecimiento de las raíces maxilares y mandibulares, elongación de incisivos, pérdida de la superficie de oclusión y deformación de las raíces mandibulares. Se propone un método de corrección para las proyecciones radiográficas LL con rotación evidente para mantener la objetividad de la evaluación radiográfica.


ABSTRACT Lagomorphs and histricomorphs, as guinea pigs and chinchillas, have common dental characteristics, such as the elodont and hypsodont teeth. These peculiarities predispose to the presentation of malocclusion due to the consumption of inadequate, non-abrasive diets. The purpose of this work is to identify the prevalence of malocclusion in each case. In addition, it aims to make an objective evaluation of the radiological studies of the specimens, based on anatomical reference lines, to determine the main radiographic findings according to the degree of malocclusion clinically diagnosed. 30% of the individuals evaluated presented malocclusion problems being 42.86% rabbits, 16.6% guinea pigs and 23% chinchillas. There is no evidence of significant differences in the presentation by sex. In rabbits, the diagnosis of the specimens from the group I and II were more common, while in guinea pigs they were II and Ill. Grade I and II were the most diagnosed in rabbits and guinea pigs. In the radiographs, the most common lesions are the overgrowth of the maxillary and mandibular roots, elongation of the incisors, loss of the occlusal surface and deformation of the mandibular roots. A method of correction for LL radiographic projections with evident rotation is proposed to maintain the objectivity of the radiographic evaluation.


Asunto(s)
Animales , Conejos , Chinchilla , Prevalencia , Dentición , Diagnóstico , Etología , Animales Exóticos , Cobayas , Maloclusión , Sexo , Diagnóstico por Imagen , Fauna , Otoscopía , Absceso , Endoscopía , Inflamación , Maxilares , Lagomorpha
9.
Eur Neuropsychopharmacol ; 33: 1-35, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32165103

RESUMEN

Cannabis is the third most used psychoactive substance worldwide. The legal status of cannabis is changing in many Western countries, while we have very limited knowledge of the public health impact of cannabis-related harms. There is a need for a summary of the evidence of harms and risks attributed to cannabis use, in order to inform the definition of cannabis risky use. We have conducted a systematic review of systematic reviews, aiming to define cannabis-related harms. We included systematic reviews published until July 2018 from six different databases and following the PRISMA guidelines. To assess study quality we applied the AMSTAR 2 tool. A total of 44 systematic reviews, including 1,053 different studies, were eligible for inclusion. Harm was categorized in three dimensions: mental health, somatic harm and physical injury (including mortality). Evidence shows a clear association between cannabis use and psychosis, affective disorders, anxiety, sleep disorders, cognitive failures, respiratory adverse events, cancer, cardiovascular outcomes, and gastrointestinal disorders. Moreover, cannabis use is a risk factor for motor vehicle collision, suicidal behavior and partner and child violence. Cannabis use is a risk factor for several medical conditions and negative social consequences. There is still little data on the dose-dependency of these effects; evidence that is essential in order to define, from a public health perspective, what can be considered risky use of cannabis. This definition should be based on quantitative and qualitative criteria that informs and permits the evaluation of current approaches to a regulated cannabis market.


Asunto(s)
Cannabis/efectos adversos , Fumar Marihuana/efectos adversos , Accidentes/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Revisiones Sistemáticas como Asunto , Adulto Joven
10.
Clin Rheumatol ; 38(10): 2819-2824, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31222573

RESUMEN

INTRODUCTION: The complement system has an important role in the pathogenesis of vasculitis associated with antineutrophilic cytoplasmic antibody (AAV) mainly at the level of the kidneys because patients with complement deposits on the glomerular basal membrane present more aggressive disease compared with those with pauci-immune vasculitis. AIM: To analyze the association of hypocomplementemia with the clinical manifestations, laboratory data, renal histology, progress to renal insufficiency, and mortality of patients with AAV. METHODS: Retrospective cohort study (2000-2007) included 93 patients with AAV. Hypocomplementemia is defined as having C3 values lower than 80 mg/dL or C4 values below 15 mg/dL. Demographic, statistical, clinical, hematological, serological, and histopathological characteristics of all the patients with and without diagnosis of hypocomplementemia were compared. In order to evaluate variable independence, a logistic regression analysis was used. RESULTS: Ninety-three patients were studied of whom 63 (67.7%) had complement dosage at the moment of AAV diagnosis. Seven patients (11.1%) presented hypocomplementemia and a greater kidney involvement compared with normocomplementemic patients. Thirty renal biopsies were analyzed and 4 (13.3%) showed immunocomplex (IC) or complement deposits by an immunofluorescence test (IFT). Patients with "non-pauci-immune" AAV also presented terminal chronic renal disease (TCRD). CONCLUSION: There is an association between low complement and the degree of renal damage in patients with AAV. Patients with renal biopsies confirming IC and/or complement deposits showed more aggressive renal disease. Key Points • The complement system has an important role in the pathogenesis of vasculitis associated to antineutrophilic cytoplasmic antibody. • The studies in murine models confirming the complement activation by alternative pathway and particularly the receptor C5a (C5aR) is necessary for the development of glomerulonefritis. • Complement deposit observed in the renal biopsies of patients diagnosed with AAV was correlated to greater kidney damage, greater proteinuria and major disease activity compared to patients diagnosed with typical pauci-immune vasculitis. • The presence of hypocomplementemia at the onset of the disease was also associated with a greater organ involvement, poor prognosis and greater mortality.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Activación de Complemento , Complemento C3/análisis , Complemento C4/análisis , Enfermedades Renales/inmunología , Adulto , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Biopsia , Complemento C3/inmunología , Complemento C4/inmunología , Femenino , Estudios de Seguimiento , Granulomatosis con Poliangitis/sangre , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/inmunología , Humanos , Riñón/inmunología , Riñón/patología , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/inmunología , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos
11.
Neuropharmacology ; 148: 291-304, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30668942

RESUMEN

Neuropathic pain is a complex disorder associated with emotional and cognitive deficits that may impair nociceptive manifestations. There is high inter-individual variability in the manifestations of human neuropathic pain, which largely depends on personality traits. We aim to identify the influence of different behavioral traits in the inter-individual vulnerability to neuropathic pain manifestations using behavioral, electrophysiological and genetic approaches. We first selected mice with extreme social and emotional traits and look for correlation with the spontaneous neuronal activity in the central amygdala. Neuropathic pain was induced to these mice to evaluate the influence of behavioral traits on nociceptive manifestations and gene expression profiles in the amygdala. Our results show an association of the spontaneous central amygdala neuronal activity with the sociability behavior. We demonstrate that low sociable, high anxious and low depressive phenotypes develop enhanced nociceptive hypersensitivity after nerve injury. However, greater emotional alterations and cognitive impairment are observed in high sociable, anxious-like and depressive-like mice, indicating that nociceptive, emotional and cognitive manifestations of neuropathic pain do not correlate with each other. Gene analyses identify high Pdyn and Il6 levels in the amygdala as indicative of enhanced nociceptive hypersensitivity and reveal an association between high Gadd45 expression and attenuated emotional and cognitive manifestations of neuropathic pain.


Asunto(s)
Cognición/fisiología , Emociones/fisiología , Individualidad , Neuralgia/fisiopatología , Neuralgia/psicología , Dolor Nociceptivo/psicología , Animales , Conducta Animal , Proteínas de Ciclo Celular/biosíntesis , Núcleo Amigdalino Central/metabolismo , Núcleo Amigdalino Central/fisiología , Encefalinas/metabolismo , Expresión Génica , Interleucina-6/metabolismo , Masculino , Ratones , Neuralgia/complicaciones , Dolor Nociceptivo/complicaciones , Precursores de Proteínas/metabolismo , Conducta Social
12.
Psychopharmacology (Berl) ; 236(4): 1187-1197, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30470859

RESUMEN

RATIONALE: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are. OBJECTIVES: To study the interaction between hypothyroidism and ethanol consumption. METHODS: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety. RESULTS: We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation. CONCLUSIONS: Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.


Asunto(s)
Consumo de Bebidas Alcohólicas/sangre , Etanol/administración & dosificación , Hipotiroidismo/sangre , Factores de Edad , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/psicología , Aldehído Deshidrogenasa Mitocondrial/sangre , Animales , Ansiedad/sangre , Ansiedad/psicología , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/psicología , Masculino , Ratas , Ratas Wistar , Hormonas Tiroideas/sangre , Tiroxina/sangre , Triyodotironina/sangre
13.
Sci Rep ; 8(1): 15690, 2018 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-30356074

RESUMEN

GRASPs are proteins involved in cell processes that seem paradoxical: responsible for shaping the Golgi cisternae and involved in unconventional secretion mechanisms that bypass the Golgi. Despite its physiological relevance, there is still a considerable lack of studies on full-length GRASPs. Our group has previously reported an unexpected behavior of the full-length GRASP from the fungus C. neoformans: its intrinsically-disordered characteristic. Here, we generalize this finding by showing that it is also observed in the GRASP from S. cerevisae (Grh1), which strongly suggests it might be a general property within the GRASP family. Furthermore, Grh1 is also able to form amyloid-like fibrils either upon heating or when submitted to changes in the dielectric constant of its surroundings, a condition that is experienced by the protein when in close contact with membranes of cell compartments, such as the Golgi apparatus. Intrinsic disorder and fibril formation can thus be two structural properties exploited by GRASP during its functional cycle.


Asunto(s)
Proteínas Amiloidogénicas/química , Proteínas Intrínsecamente Desordenadas/química , Péptidos/química , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Transporte Vesicular/química , Secuencia de Aminoácidos , Amiloide/química , Benzotiazoles/química , Dicroismo Circular , Rojo Congo/química , Aparato de Golgi/metabolismo , Proteínas de la Matriz de Golgi/química , Imagen Óptica , Conformación Proteica en Lámina beta , Desnaturalización Proteica , Saccharomyces cerevisiae/metabolismo , Solventes/química , Espectrometría de Fluorescencia , Temperatura , Red trans-Golgi/metabolismo
14.
Biochem Pharmacol ; 157: 159-168, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30134192

RESUMEN

Cannabis is the most consumed illicit drug worldwide. Its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), affects multiple brain functions, including cognitive performance, by modulating cannabinoid type-1 (CB1) receptors. These receptors are strongly enriched in presynaptic terminals, where they modulate neurotransmitter release. We analyzed, through a proteomic screening of hippocampal synaptosomal fractions, those proteins and pathways modulated 3 h after a single administration of an amnesic dose of THC (10 mg/kg, i.p.). Using an isobaric labeling approach, we identified 2040 proteins, 1911 of them previously reported in synaptic proteomes, confirming the synaptic content enrichment of the samples. Initial analysis revealed a significant alteration of 122 proteins, where 42 increased and 80 decreased their expression. Gene set enrichment analysis indicated an over-representation of mitochondrial associated functions and cellular metabolic processes. A second analysis focusing on extreme changes revealed 28 proteins with altered expression after THC treatment, 15 of them up-regulated and 13 down-regulated. Using a network topology-based scoring algorithm we identified those proteins in the mouse proteome with the greatest association to the 28 modulated proteins. This analysis pinpointed a significant alteration of the proteasome function, since top scoring proteins were related to the proteasome system (PS), a protein complex involved in ATP-dependent protein degradation. In this regard, we observed that THC decreases 20S proteasome chymotrypsin-like protease activity in the hippocampus. Our data describe for the first time the modulation of the PS in the hippocampus following THC administration under amnesic conditions that may contribute to an aberrant plasticity at synapses.


Asunto(s)
Dronabinol/farmacología , Hipocampo/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Animales , Hipocampo/enzimología , Hipocampo/metabolismo , Masculino , Ratones Endogámicos C57BL , Proteoma/efectos de los fármacos , Proteómica , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo
15.
J Anim Physiol Anim Nutr (Berl) ; 102(3): 755-768, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29473221

RESUMEN

A 3 × 3 + 1 factorial, involving three levels of protease (0, 15,000 or 30,000 PROT/kg) and three levels of phytase (1,000, 2,000 or 3,000 FYT/kg), was used to evaluate the effect of replacing commercial soybean meal (SBM) with raw, full-fat soybean (RFSB) at 75 g/kg of diet for broilers. A control diet was used for comparison. Each treatment was replicated six times, with nine birds per replicate. The concentration of trypsin inhibitors (TIs) in the test diets was approximately 10,193.4 TIU/kg. Regardless of enzyme supplementation, feed intake (FI) and body weight gain (BWG) of birds in the control group were superior to those on the test diets. Birds that received the protease-free test diets had reduced FI and BWG, but when supplemented with protease, were similar to the control diet in BWG, FI (except 0-35 days) and feed conversion ratio (FCR). When the test diet was supplemented with elevated levels (extradose) of protease and phytase, the BWG was improved during 0-10 days (p = .05) and 0-24 days (p < .01). Regardless of protease supplementation, the weight of thighs was lower for birds fed the test diets. Birds that received the control diet had smaller weight of pancreas. Increasing the level of phytase supplementation reduced (p < .05) the weight of the pancreas. The apparent ileal digestibility (AID) of CP and AA was higher in birds on the control diets, but this was also improved in test diets by protease supplementation. The activities of trypsin (7%), general proteolytic (11%) and lipase (12%) were slightly increased because of protease supplementation. Mucosal depth and apparent villus surface areas were increased by about 2.9% and 20%, respectively, due to supplementation of elevated level of phytase. It can be concluded that RFSB could partially replace SBM in broiler diets, provided the diets are supplemented with elevated levels of protease and phytase.


Asunto(s)
6-Fitasa/administración & dosificación , Pollos , Grasas de la Dieta/administración & dosificación , Glycine max/química , Péptido Hidrolasas/administración & dosificación , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga
16.
Br Poult Sci ; 59(2): 180-189, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29130331

RESUMEN

1. The objective of this study was to investigate the effect of range type, multi-enzyme applications, and a combination of benzoic acid (BA) and essential oils (EO) on the productive performance, organ weight and egg quality of free-range laying hens. 2. Three hundred laying hens were evaluated for the short-term (6 weeks) and long-term (12 weeks) effects of range type (G = no pasture, P = pasture) and feed additives (T1 = control; T2 = betaglucanase/pectinase/protease; T3 = BA/EO). Body weight, feed intake (FI), feed conversion ratio (FCR), egg production (EP), digestive organ weight, and egg quality (EQ) were evaluated. Data were analysed using SPSS 2.2 in a 2×2×3 factorial arrangement. 3. Hens that ranged on pasture were significantly heavier (2043 g vs. 1996 g; p < 0.001), laid heavier eggs (61.9 g vs. 60.3 g; p < 0.001) and produced darker yolk colour (4.3 vs. 7.0; p < 0.001) compared to hens ranged on gravel. Hens fed T2 were significantly heavier (2050 g) compared to hens fed T1 (2005 g) or T3 (2008 g). Organ weights (gizzard, liver and pancreas) were significantly heavier in hens ranged on pasture (16.8 g/kg BW, 22.3 g/kg BW and 1.89 g/kg BW, respectively) compared to hens ranged on gravel (14.2 g/kg BW, 21.7 g/kg BW and 1.83 g/kg BW, respectively). Over time, body weight (1970-2070 g; p < 0.001) and egg weight (59.5-62.8 g; p < 0.001) increased, FI (123-120 g; p = 0.024) was reduced and FCR (2.36-2.10; p = 0.002) improved 4. In conclusion, hens housed on pasture and fed multi-enzyme supplemented diets had significantly heavier body weight and produced heavier eggs with darker yolk colour. Pasture intake and enzyme supplementation increased digestive organ weight significantly.


Asunto(s)
Crianza de Animales Domésticos/métodos , Ácido Benzoico/metabolismo , Pollos/fisiología , Complejos Multienzimáticos/metabolismo , Aceites Volátiles/metabolismo , Alimentación Animal/análisis , Animales , Ácido Benzoico/administración & dosificación , Dieta/veterinaria , Suplementos Dietéticos/análisis , Femenino , Intestinos/efectos de los fármacos , Complejos Multienzimáticos/administración & dosificación , Aceites Volátiles/administración & dosificación , Tamaño de los Órganos/efectos de los fármacos , Óvulo/efectos de los fármacos , Reproducción/efectos de los fármacos
17.
J Anim Physiol Anim Nutr (Berl) ; 102(2): 533-544, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29024064

RESUMEN

A 2 × 3 factorial study (protease: 0 or 1,5000 PROT/kg and raw full-fat soya bean meal [RSBM] replacing the commercial SBM at 0, 45 and 75 g/kg of diet) was conducted to examine the performance of broilers. Phytase (2000 FYT/kg) was uniformly added to each diet, each also replicated six times, with eight birds per replicate. Birds were raised in climate-controlled rooms using sawdust as the bedding material and offered starter, grower and finisher diets. Feed intake (FI) and body weight gain (BWG) were reduced (p < .05) due to increasing levels of RSBM, but feed conversion ratio (FCR; 0-35 days) was unaffected. Over the first 24 days, neither RSBM nor protease supplementation affected (p > .05) mortality, footpad dermatitis or intestinal lesions in birds. At day 24, the weight, length, width and strength of tibia bone were reduced in chickens that received an elevated level of RSBM (75 g/kg of diet), but this was not significant at day 35. At day 24 (p < .05) and 35 (p < .01), Ca concentration in the litter was reduced when the RSBM level was increased in the diet, but P content was not affected. On days 24 (p < .05) and 35 (p < .01), the N content in litter was also increased with increase in dietary RSBM. Protease supplementation increased (p < .05) the uric acid concentration in the litter (at day 35), but the reverse was the case for ammonia concentration. Overall, the results of this study indicate that there are no major health-related risks, associated with the replacement of commercial SBM with RSBM (≤25%) in broiler diets.


Asunto(s)
Alimentación Animal/análisis , Pollos , Dieta/veterinaria , Grasas de la Dieta/administración & dosificación , Glycine max/química , Péptido Hidrolasas/administración & dosificación , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Densidad Ósea/efectos de los fármacos , Dermatitis/veterinaria , Suplementos Dietéticos , Pisos y Cubiertas de Piso , Enfermedades del Pie/veterinaria , Enfermedades de las Aves de Corral
18.
Eur J Pain ; 22(4): 763-773, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29280233

RESUMEN

BACKGROUND: Pregabalin is a first-line agent for neuropathic pain treatment whose abuse liability remains controversial. Surprisingly, studies exploring the reinforcing properties of pregabalin in operant mouse models are missing. METHODS: We evaluated the acquisition of operant pregabalin self-administration in mice exposed to a partial sciatic nerve ligation (PSNL) or a sham operation. After surgery, mice were trained in operant boxes to intravenously self-administer pregabalin at 1.5 or 3 mg/kg/inf or saline during 10 days. Thermal and mechanical sensitivity were assessed before and after self-medication, and depressive-like behaviour was evaluated after discontinuation of the treatment. RESULTS: Partial sciatic nerve ligation and sham-operated mice exposed to pregabalin at 3 mg/kg/inf showed higher active responding compared to mice exposed to saline. The differences in active responding were more robust in nerve-injured than in sham-operated mice. Self-medication at either dose of pregabalin partially inhibited thermal hypersensitivity, whereas only self-medication at 3 mg/kg/inf reduced mechanical sensitivity. Finally, a depressive-like behaviour was revealed after saline treatment in nerve-injured mice, and this emotional manifestation was abolished after pregabalin treatment at the high dose. CONCLUSIONS: Pregabalin showed reinforcing effects both in PSNL and sham-operated mice and attenuated the nociceptive and emotional manifestations of neuropathic pain in mice self-administering this drug. Therefore, pregabalin self-administration was related to neuropathic pain relief, but also to reinforcing properties related to psychotropic drug effects. This study reveals the improvement in nociceptive and emotional manifestations of neuropathic pain after operant pregabalin self-medication in mice and suggests the reinforcing effects of this drug in an operant paradigm. SIGNIFICANCE: This study shows that mice with a nerve injury self-administer pregabalin at doses effective reducing nociceptive hypersensitivity and depressive-like behaviour associated with the neuropathic pain model. Interestingly, mice without neuropathy also develop operant self-administration behaviour, suggesting potential abuse liability of this first-line drug for neuropathic pain treatment.


Asunto(s)
Analgésicos/uso terapéutico , Condicionamiento Operante/efectos de los fármacos , Hiperalgesia/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/complicaciones , Pregabalina/uso terapéutico , Analgésicos/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Hiperalgesia/etiología , Masculino , Ratones , Neuralgia/etiología , Pregabalina/administración & dosificación , Nervio Ciático/efectos de los fármacos , Autoadministración
19.
VozAndes ; 29(1): 5-6, 2018.
Artículo en Español | LILACS | ID: biblio-988425

RESUMEN

La salud es un estado de bienestar físico, mental y social. La percepción de la salud que tienen las personas, guarda una relación directa con sus condiciones de vida y varios factores socio-culturales. A su vez, la forma en que una persona enfrenta un quebranto en su salud, sea éste un malestar simple, un síntoma más serio o una enfermedad declarada, depende primero del conocimiento que tenga sobre el problema y, posteriormente, de sus actitudes y prácticas destinadas a recuperar o mantener la condición de bienestar.


Asunto(s)
Humanos , Masculino , Femenino , Autocuidado , Automedicación , Conocimientos, Actitudes y Práctica en Salud
20.
Poult Sci ; 96(11): 3960-3972, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-29050421

RESUMEN

Two broiler chicken experiments were conducted to investigate the effects of canola meal (CM) replacing soybean meal (SBM) in diets supplemented with carbohydrase and protease on performance and partitioning of energy. First, a 2 × 2 × 2 factorial arrangement of treatments was employed to evaluate: protein meals (CM vs. SBM), carbohydrase (none or 300 mg/kg), protease (none or 200 mg/kg), and their interactions. Each treatment was fed to 6 replicated pens of 16 male broilers (Ross 308) from d 10 to 35. In the second experiment, 32 broiler chicks were used in a 2 × 2 factorial arrangement to investigate CM and carbohydrase effects on energy partitioning. Birds were transferred into 16 closed-circuit calorimeter chambers (4 chambers/diet; 2 birds/chamber) to measure heat production (HP), metabolizable and net energy (NE) by gaseous exchange, and total excreta collection from d 25 to 28. There were no 3-way interactions among experimental factors for any of the performance parameters measured. Birds given CM diets consumed less feed, had lower BW, and exhibited higher FCR compared to the control birds (P < 0.01). Both enzymes, alone or in combination, improved final BW and FCR (P < 0.05). There was an interaction between carbohydrase and protease for FCR over the grower period (P < 0.01), in which the combination of the enzymes resulted in further improvement of FCR. Energy, DM, and crude protein digestibility values were higher in control birds (P < 0.05). There was an interaction of protein meal and carbohydrase for HP, respiratory quotient (P < 0.05), and NE:ME ratio of the diets (P = 0.06). Inclusion of CM without carbohydrase increased HP and decreased NE and NE:ME ratio of the diets (P < 0.05). Carbohydrase decreased HP and increased retained energy (P = 0.06) and NE and NE:ME ratio (P < 0.05). In conclusion, high CM in the diet negatively affects growth performance through reduction in feed consumption, nutrient digestibility, and NE of the diet, which could partly be restored by enzyme supplementation.


Asunto(s)
Brassica/química , Pollos/fisiología , Digestión/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Glicósido Hidrolasas/metabolismo , Serina Proteasas/metabolismo , Actinomycetales/química , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Aspergillus/química , Bacillus licheniformis/genética , Pollos/crecimiento & desarrollo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Proteínas Fúngicas/administración & dosificación , Proteínas Fúngicas/metabolismo , Glicósido Hidrolasas/administración & dosificación , Masculino , Microorganismos Modificados Genéticamente/genética , Distribución Aleatoria , Serina Proteasas/administración & dosificación
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