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1.
Sci Rep ; 14(1): 5277, 2024 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-38438389

RESUMEN

Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.


Asunto(s)
Metronidazol , Microbiota , Humanos , Perros , Animales , Metronidazol/farmacología , Metronidazol/uso terapéutico , ARN Ribosómico 16S/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Diarrea
2.
Animals (Basel) ; 13(20)2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37894015

RESUMEN

Senior pets can suffer from a wide range of age-related diseases that can impact the quality of life for the pet and the relationship between a pet and their owner. Dietary fibre plays a key role in shaping the gastrointestinal health in mammalian species. The aim of this study was to investigate the impact of a novel prebiotic fibre blend containing sugar beet pulp, galacto-oligosaccharides, and cellulose on the health of senior dogs when fed on top of a background commercial dry diet. Thirty-two dogs aged >8 years received the prebiotic fibre blend as a dietary topper for 21 days on top of a nutritionally complete diet using a cross-over study design. The prebiotic fibre blend improved the gastrointestinal health of senior dogs as measured through improved faecal quality scores, a reduction in faecal pH, changes to the taxonomic composition of the gut, and a reduction in faecal branched-chain fatty acids, which are markers for proteolytic degradation. Broader systemic measures, such as changes to serum cytokines, were not impacted by the prebiotic fibre blend. In conclusion, a novel prebiotic fibre blend containing sugar beet pulp, galacto-oligosaccharides, and cellulose improved the gastrointestinal health of senior dogs and could have a range of potential future dietary applications.

3.
Am J Surg ; 222(2): 329-333, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33419518

RESUMEN

BACKGROUND: Surgical trainees experience intrinsic stress and anxiety during high-acuity clinical situations which can negatively impact performance. Emerging data suggests that education in mindfulness-based coping techniques may improve performance. We evaluated the effects of a stress recovery intervention on novice trainees' perceived level of anxiety during an intentionally stressful simulation. METHODS: Participants were recruited from surgical intern classes over three consecutive years. All participants completed a simulation intentionally designed to evoke a stress response. Participants then completed a stress recovery intervention or received no additional training. All participants then completed a second novel simulation. RESULTS: Intervention participants had significantly higher self-reported ability to manage stress (intervention 2.4 to 3.6, p < 0.01; control 2.8 to 3.3, p = 0.06), and stop, think, and observe (intervention 2.5 to 3.7, p < 0.01; control 2.6 to 3.3, p = 0.08) during the second simulation. Both groups also had significantly lower levels of state anxiety during the second simulation as compared to the first (intervention 45.1 vs 59.3, p < 0.01; control 49.3 vs 57.4, p < 0.05). During the second simulation, trainees in both groups reported improvements in perceived abilities to: recognize stress (intervention 2.7 to 4.1, p < 0.01; control 2.9 to 3.6, p < 0.05), communicate with and lead their team (intervention 2.4 to 3.3, p < 0.05; control 2.3 to 3.3, p < 0.01), and to prioritize, plan, and prepare (intervention 2.1 to 3.1, p < 0.05; control 2.1 to 3.0, p < 0.01). CONCLUSION: Our research shows that a brief intervention was associated with a significant increase in trainee ability to both recognize internal stress and engage in proactive coping mechanisms. This research also shows that while repeated stress-inducing simulations may themselves decrease perceived anxiety levels in novice surgical trainees, training in coping strategies may potentiate this effect.


Asunto(s)
Ansiedad/prevención & control , Internado y Residencia , Atención Plena , Autoimagen , Procedimientos Quirúrgicos Operativos/educación , Adaptación Psicológica , Ansiedad/etiología , Competencia Clínica , Humanos , Entrenamiento Simulado
4.
Future Healthc J ; 7(3): e85-e87, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33094265

RESUMEN

Service redevelopment has taken place across the NHS in response to the COVID-19 pandemic. At North Bristol NHS Trust, six vulnerable medical staff in non-patient facing roles set up a virtual advice service called 'Ask the Medical Reg'. This service aimed to provide senior medical support to inpatient and community teams for general medical and COVID-19-related queries. Here we outline the structure of our service and present data from the first 4 weeks of operation. We describe how the service has supported both junior doctors working within the hospital and GPs and paramedics, helping with complex decisions to prevent unnecessary admissions.

5.
Am J Surg ; 220(5): 1258-1263, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32680624

RESUMEN

INTRODUCTION: Rectal cancer treatment can lead to sexual dysfunction. METHODS: We designed a retrospective survey-based study to quantify rates of sexual dysfunction in rectal cancer survivors. Patients that underwent surgery for rectal cancer between 2005 and 2016 at our institution were identified, and the following were distributed: Quality of Life measure for oncology (QoL-30), Female Sexual Function Index (FSFI), and International Index of Erectile Function (IIEF). RESULTS: Survey response rate was 21%, 17 females and 30 males (n = 47). 50% of males recalled a physician asking about sexual function during or after treatments, compared to 18% of females (p = 0.034). More than 50% of those surveyed wished one of their physicians had discussed the possibility of sexual dysfunction. In men, the QoL-30 significantly correlated with IIEF orgasmic function (r = 0.50, p = 0.004) and IIEF overall satisfaction (r = 0.60, p < 0.001). CONCLUSIONS: Our findings demonstrate that rectal cancer patients experience posttreatment sexual dysfunction, desire discussion with their physicians on this topic, and that there are gender differences in how providers approach counseling regarding posttreatment sexual dysfunction.


Asunto(s)
Complicaciones Posoperatorias , Proctectomía , Neoplasias del Recto/cirugía , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Adulto , Anciano , Femenino , Indicadores de Salud , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Calidad de Vida , Estudios Retrospectivos , Factores Sexuales , Disfunciones Sexuales Fisiológicas/diagnóstico , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Psicológicas/diagnóstico , Disfunciones Sexuales Psicológicas/epidemiología , Resultado del Tratamiento
6.
R Soc Open Sci ; 6(7): 182158, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31417704

RESUMEN

Previous work has shown a strong correlation between zeolite framework flexibility and the nature of structural symmetry and phase transitions. However, there is little experimental data regarding this relationship, in addition to how flexibility can be connected to the synthesis of these open-framework materials. This is of interest for the synthesis of novel zeolites, which require organic additives to permutate the resulting geometry and symmetry of the framework. Here, we have used high-pressure powder X-ray diffraction to study the three zeolites: Na-X, RHO and ZK-5, which can all be prepared using 18-crown-6 ether as an organic additive. We observe significant differences in how the occluded 18-crown-6 ether influences the framework flexibility-this being dependent on the geometry of the framework. We use these differences as an indicator to define the role of 18-crown-6 ether during zeolite crystallization. Furthermore, in conjunction with previous work, we predict that pressure-induced symmetry transitions are intrinsic to body-centred cubic zeolites. The high symmetry yields fewer degrees of freedom, meaning it is energetically favourable to lower the symmetry to facilitate further compression.

7.
Sci Justice ; 59(3): 268-291, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31054817

RESUMEN

This paper aspires to assist those tasked with data generation and analysis for the purpose of the validation and/or optimisation of trace evidence recovery. It does so via a detailed report of the authors' approach to this problem in the context of target fibre retrieval using self-adhesive tapes. Textile fibres can provide valuable evidence at both source and activity levels. This ability stems from their near ubiquity in the man-made environment, their potential for high levels of discrimination (especially when found in combination) and their reproducible transfer and persistence behaviours. To realise this value for the criminal justice system, it is vital that police forces and forensic providers are collectively able to search for, recover and analyse fibres found at crime scenes and correctly evaluate their evidential value. ISO accreditation provides quality assurance for such activities. The work reported in this paper was part of a study to validate crime scene fibre retrieval processes for the purposes of ISO17020 accreditation. However, it is hoped that it will be of assistance to those wishing to validate and/or optimise forensic fibre recovery whether at the crime scene or in the laboratory. Further, the methods described may be of value to those who need to validate and/or optimise the recovery of other types of trace evidence. This paper outlines a series of experiments that investigated the effect of four factors on the rate at which target fibres could be recovered from surfaces by tape lifting. The factors were tape type (with two levels, namely: J-LAR and Crystal Tabs), tape storage temperature (three levels: -5 °C, room temperature [19 ±â€¯1 °C] and 35 °C), taping method (two levels: zonal and one-to-one) and surface (12 levels: each being a surface type commonly encountered at crime scenes). This resulted in 144 unique experimental conditions. For each of these, five repeat fibre recovery rate determinations were carried out, generating 720 data points. All surfaces were clean and dry prior to target fibres being transferred and recovered. In all cases, the tapes were applied to the surfaces at 19 ±â€¯1 °C. These experiments showed that the surfaces can be divided into three stable clusters based on the median and interquartile range of the fibre retrieval rate achieved from each of them. Also, they showed that, in terms of the proportion of the target fibres retrieved, typically and setting aside interaction effects: However, notably, a good degree of between-condition overlap was also apparent in the data. To understand this, a four-way factorial ANOVA model was built which revealed significant and substantive effects for all four main effects and for 10 of the 11 interactions. Importantly, the four-way interaction term was amongst those found to be significant. The interplay between the effects of the four factors was analysed by means of simple effects tests and pairwise contrasts. Tables and interactive parallel coordinate plots have been created. Using these it can easily be seen which of any given pair of levels of each of the four factors resulted in the higher fibre retrieval rate under any one of the unique conditions of the study, and the effect size and statistical significance of this observation. Qualitative evaluations of the effect of tape storage temperatures on tape pliability and its propensity to tear in use were also made.

8.
Molecules ; 24(3)2019 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-30759754

RESUMEN

The roles of organic additives in the assembly and crystallisation of zeolites are still not fully understood. This is important when attempting to prepare novel frameworks to produce new zeolites. We consider 18-crown-6 ether (18C6) as an additive, which has previously been shown to differentiate between the zeolite EMC-2 (EMT) and faujasite (FAU) frameworks. However, it is unclear whether this distinction is dictated by influences on the metastable free-energy landscape or geometric templating. Using high-pressure synchrotron X-ray diffraction, we have observed that the presence of 18C6 does not impact the EMT framework flexibility-agreeing with our previous geometric simulations and suggesting that 18C6 does not behave as a geometric template. This was further studied by computational modelling using solid-state density-functional theory and lattice dynamics calculations. It is shown that the lattice energy of FAU is lower than EMT, but is strongly impacted by the presence of solvent/guest molecules in the framework. Furthermore, the EMT topology possesses a greater vibrational entropy and is stabilised by free energy at a finite temperature. Overall, these findings demonstrate that the role of the 18C6 additive is to influence the free energy of crystallisation to assemble the EMT framework as opposed to FAU.


Asunto(s)
Zeolitas/química , Éteres Corona/química , Cristalización/métodos , Presión , Temperatura , Difracción de Rayos X/métodos
9.
BMC Microbiol ; 18(1): 15, 2018 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-29482521

RESUMEN

BACKGROUND: Salmonella enterica is a recognised cause of diarrhoea in dogs and humans, yet the potential for transfer of salmonellosis between dogs and their owners is unclear, with reported evidence both for and against Salmonella as a zoonotic pathogen. A collection of 174 S. enterica isolates from clinical infections in humans and dogs were analysed for serotype distribution, carbon source utilisation, chemical and antimicrobial sensitivity profiles. The aim of the study was to understand the degree of conservation in phenotypic characteristics of isolates across host species. RESULTS: Serovar distribution across human and canine isolates demonstrated nine serovars common to both host species, 24 serovars present in only the canine collection and 39 solely represented within the human collection. Significant differences in carbon source utilisation profiles and ampicillin, amoxicillin and chloramphenicol sensitivity profiles were detected in isolates of human and canine origin. Differences between the human and canine Salmonella collections were suggestive of evolutionary separation, with canine isolates better able to utilise several simple sugars than their human counterparts. Generally higher minimum inhibitory concentrations of three broad-spectrum antimicrobials, commonly used in veterinary medicine, were also observed in canine S. enterica isolates. CONCLUSIONS: Differential carbon source utilisation and antimicrobial sensitivity profiles in pathogenic Salmonella isolated from humans and dogs are suggestive of distinct reservoirs of infection for these hosts. Although these findings do not preclude zoonotic or anthroponotic potential in salmonellae, the separation of carbon utilisation and antibiotic profiles with isolate source is indicative that infectious isolates are not part of a common reservoir shared frequently between these host species.


Asunto(s)
Antibacterianos/farmacología , Fermentación , Salmonella/efectos de los fármacos , Salmonella/metabolismo , Animales , Carbono/metabolismo , Perros , Especificidad del Huésped , Humanos , Pruebas de Sensibilidad Microbiana , Salmonella/aislamiento & purificación , Salmonella/patogenicidad , Salmonelosis Animal/microbiología , Salmonella enterica/efectos de los fármacos , Salmonella enterica/aislamiento & purificación , Salmonella enterica/metabolismo , Salmonella enterica/patogenicidad , Serogrupo , Zoonosis/microbiología
10.
J Neurosurg Pediatr ; 20(3): 239-246, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28621574

RESUMEN

The authors demonstrate the use of an endovascular plug in securing a carotid artery pseudoaneurysm in an emergent setting requiring craniotomy for a concurrent subdural empyema. They describe the case of a 14-year-old boy with sinusitis and bifrontal subdural empyema who underwent transsphenoidal exploration at an outside hospital. An injury to the right cavernous segment of the ICA caused torrential epistaxis. Bleeding was successfully controlled by inflating a Foley balloon catheter within the sphenoid sinus, and the patient was transferred to the authors' institution. Emergent angiography showed a dissection of the right cavernous carotid artery, with a large pseudoaneurysm projecting into the sphenoid sinus at the site of arterial injury. The right internal carotid artery was obliterated using pushable coils distally and an endovascular plug proximally. The endovascular plug enabled the authors to successfully exclude the pseudoaneurysm from the circulation. The patient subsequently underwent an emergent bifrontal craniotomy for evacuation of a left frontotemporal subdural empyema and exenteration of both frontal sinuses. He made a complete neurological recovery. Endovascular large-vessel sacrifice, obviating the need for numerous coils and antiplatelet therapy, has a role in the setting of selected acute neurosurgical emergencies necessitating craniotomy. The endovascular plug is a useful adjunct in such circumstances as the device can be deployed rapidly, safely, and effectively.


Asunto(s)
Aneurisma Falso/cirugía , Traumatismos de las Arterias Carótidas/cirugía , Arteria Carótida Interna/cirugía , Embolización Terapéutica , Empiema Subdural/cirugía , Procedimientos Endovasculares/métodos , Infecciones Estafilocócicas/cirugía , Adolescente , Aneurisma Falso/complicaciones , Aneurisma Falso/diagnóstico por imagen , Traumatismos de las Arterias Carótidas/complicaciones , Traumatismos de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Interna/diagnóstico por imagen , Empiema Subdural/complicaciones , Empiema Subdural/diagnóstico por imagen , Humanos , Lactobacillus/aislamiento & purificación , Masculino , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/diagnóstico por imagen
11.
Res Vet Sci ; 111: 99-107, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28222337

RESUMEN

Dietary means of reducing plaque and calculus deposits are frequently sought for the maintenance of oral health in cats and dogs. In the development of such products sensitive, reliable, reproducible methods of measuring plaque and calculus are key. The aim of this study was to assess Quantitative Light-induced Fluorescence (QLF™) for the detection of dental plaque coverage in cats compared to the modified Logan and Boyce technique. The techniques were utilised in a crossover study, which compared two diets for their effect on plaque deposition in a cohort of 24 adult cats. Analysis of the effect of diet on plaque coverage by both the modified Logan and Boyce technique and QLF showed a significant effect of feeding regime (p=0.024 and p≤0.0001, respectively) with good agreement between the techniques in the percentage reduction of plaque accumulation. A within study assessment of QLF demonstrated excellent intra-operator repeatability (coefficient of variation 2.2%). Similarly, inter-operator reproducibility was also good (coefficient of variation 2.3%). A retrospective analysis, using the data to estimate the sample size required for at least 90% power to detect a 15% difference between treatments in a two-way crossover study, established that 10 cats would be sufficient for plaque measurement by QLF, while assessment by the modified Logan and Boyce method required over 30 cats. QLF was determined to be a reliable, reproducible method for the assessment of plaque deposition in cats and requires fewer subjects for the detection of differences between treatment effects compared to the modified Logan and Boyce method.


Asunto(s)
Enfermedades de los Gatos/diagnóstico , Placa Dental/veterinaria , Odontología/veterinaria , Animales , Gatos , Estudios Cruzados , Placa Dental/diagnóstico , Odontología/métodos , Femenino , Fluorescencia , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos
12.
Vet Microbiol ; 175(2-4): 294-303, 2015 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-25523504

RESUMEN

The human oral microbiome is known to play a significant role in human health and disease. While less well studied, the feline oral microbiome is thought to play a similarly important role. To determine roles oral bacteria play in health and disease, one first has to be able to accurately identify bacterial species present. 16S rRNA gene sequence information is widely used for molecular identification of bacteria and is also useful for establishing the taxonomy of novel species. The objective of this research was to obtain full 16S rRNA gene reference sequences for feline oral bacteria, place the sequences in species-level phylotypes, and create a curated 16S rRNA based taxonomy for common feline oral bacteria. Clone libraries were produced using "universal" and phylum-selective PCR primers and DNA from pooled subgingival plaque from healthy and periodontally diseased cats. Bacteria in subgingival samples were also cultivated to obtain isolates. Full-length 16S rDNA sequences were determined for clones and isolates that represent 171 feline oral taxa. A provisional curated taxonomy was developed based on the position of each taxon in 16S rRNA phylogenetic trees. The feline oral microbiome curated taxonomy and 16S rRNA gene reference set will allow investigators to refer to precisely defined bacterial taxa. A provisional name such as "Propionibacterium sp. feline oral taxon FOT-327" is an anchor to which clone, strain or GenBank names or accession numbers can point. Future next-generation-sequencing studies of feline oral bacteria will be able to map reads to taxonomically curated full-length 16S rRNA gene sequences.


Asunto(s)
Bacterias/genética , Gatos/microbiología , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Animales , Secuencia de Bases , ADN Ribosómico/genética , Humanos , Microbiota/genética , Filogenia , Reacción en Cadena de la Polimerasa
13.
PLoS One ; 7(4): e36067, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22558330

RESUMEN

Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S rRNA-gene sequence comparison, shared between humans and dogs, two divergent mammalian species. Second, canine oral bacteria are of interest to veterinary and human medical communities for understanding their roles in health and infectious diseases. The bacteria involved are mostly unnamed and not linked by 16S rRNA-gene sequence identity to a taxonomic scheme. This manuscript describes the analysis of 5,958 16S rRNA-gene sequences from 65 clone libraries. Full length 16S rRNA reference sequences have been obtained for 353 canine bacterial taxa, which were placed in 14 bacterial phyla, 23 classes, 37 orders, 66 families, and 148 genera. Eighty percent of the taxa are currently unnamed. The bacterial taxa identified in dogs are markedly different from those of humans with only 16.4% of oral taxa are shared between dogs and humans based on a 98.5% 16S rRNA sequence similarity cutoff. This indicates that there is a large divergence in the bacteria comprising the oral microbiomes of divergent mammalian species. The historic practice of identifying animal associated bacteria based on phenotypic similarities to human bacteria is generally invalid. This report describes the diversity of the canine oral microbiome and provides a provisional 16S rRNA based taxonomic scheme for naming and identifying unnamed canine bacterial taxa.


Asunto(s)
Perros/microbiología , Metagenoma , Boca/microbiología , Animales , Bacterias/clasificación , Bacterias/genética , Clonación Molecular , Placa Dental/microbiología , Encía/microbiología , Humanos , Datos de Secuencia Molecular , Filogenia
14.
FEMS Microbiol Ecol ; 69(1): 113-24, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19453738

RESUMEN

The surfaces of marine eukaryotes provide a unique habitat for colonizing microorganisms where competition between members of these communities and chemically mediated interactions with their host are thought to influence both microbial diversity and function. For example, it is believed that marine eukaryotes may use their surface-associated bacteria to produce bioactive compounds in defence against competition and to protect the host against further colonization. With the increasing need for novel drug discovery, marine epibiotic bacteria may thus represent a largely underexplored source of new antimicrobial compounds. In the current study, 325 bacterial isolates were obtained from the surfaces of marine algae Delisea pulchra and Ulva australis. Thirty-nine showed to have antimicrobial activity and were identified via 16S rRNA gene sequencing. The majority of those isolates belonged to Alpha- and Gammaproteobacteria. Interestingly, the most commonly isolated bacterial strain, Microbulbifer sp., from the surface of D. pulchra has previously been described as an ecologically significant epibiont of different marine eukaryotes. Other antimicrobial isolates obtained in this study belonged to the phyla Actinobacteria, Firmicutes and Bacteroidetes. Phylogenetically, little overlap was observed among the bacteria obtained from surfaces of D. pulchra and U. australis. The high abundance of cultured isolates that produce antimicrobials suggest that culturing remains a powerful resource for exploring novel bioactives of bacterial origin.


Asunto(s)
Antiinfecciosos/metabolismo , Bacterias/aislamiento & purificación , Descubrimiento de Drogas , Agua de Mar/microbiología , Ulva/microbiología , Microbiología del Agua , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , ADN Bacteriano/genética , Genes de ARNr , Filogenia , ARN Ribosómico 16S/genética
15.
Cell Metab ; 6(5): 398-405, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17983585

RESUMEN

The burden of type 2 diabetes and its associated premature morbidity and mortality is rapidly growing, and the need for novel efficacious treatments is pressing. We report here that serotonin 2C receptor (5-HT(2C)R) agonists, typically investigated for their anorectic properties, significantly improve glucose tolerance and reduce plasma insulin in murine models of obesity and type 2 diabetes. Importantly, 5-HT(2C)R agonist-induced improvements in glucose homeostasis occurred at concentrations of agonist that had no effect on ingestive behavior, energy expenditure, locomotor activity, body weight, or fat mass. We determined that this primary effect on glucose homeostasis requires downstream activation of melanocortin-4 receptors (MC4Rs), but not MC3Rs. These findings suggest that pharmacological targeting of 5-HT(2C)Rs may enhance glucose tolerance independently of alterations in body weight and that this may prove an effective and mechanistically novel strategy in the treatment of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor de Melanocortina Tipo 4/fisiología , Agonistas del Receptor de Serotonina 5-HT2 , Agonistas de Receptores de Serotonina/farmacología , Transducción de Señal/efectos de los fármacos , Absorciometría de Fotón , Animales , Western Blotting , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Homeostasis/efectos de los fármacos , Inmunohistoquímica , Insulina/sangre , Masculino , Ratones , Ratones Noqueados , Ratones Obesos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Piperazinas/farmacología , Reacción en Cadena de la Polimerasa , Proopiomelanocortina/genética , Receptor de Melanocortina Tipo 4/química , Receptor de Melanocortina Tipo 4/metabolismo
16.
Psychopharmacology (Berl) ; 193(1): 1-9, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17372721

RESUMEN

RATIONALE: The cannabinoid CB(1) receptor inverse agonist SR141716A (rimonabant) is known to cause hypophagia and this study uses microstructural data to elucidate the relevant behavioural mechanisms. OBJECTIVES: The aim of these studies was to determine the behavioural changes induced by SR141716A in animals consuming either a fat or carbohydrate solution. These behavioural changes were directly compared with those induced by behavioural manipulations that modify motivational state and palatability. METHODS: Male hooded Lister rats drank a highly palatable fat emulsion (10% Intralipid) or a carbohydrate solution (10% sucrose) during 30-min test sessions. Microstructural analyses of licking patterns were made after either administration of SR141716A (0, 0.3, 1 and 3 mg/kg, ip) or one of the after behavioural manipulations: pre-feeding, addition of quinine to the fat solution or changes in sucrose concentration. RESULTS: Intake of the fat solution was decreased after both the drug treatment and the behavioural manipulations of pre-feeding and addition of quinine. Pre-feeding and SR141716A-induced reductions were mediated via changes in bout number whereas addition of quinine caused a decrease in bout size. Although sucrose drinking was also decreased by pre-feeding, reduced sucrose concentration and SR141716A, the drug did not significantly alter the microstructure of intake. CONCLUSIONS: The effects of SR141716A on consumption of Intralipid solutions are likely to reflect changes in motivational state rather than modified hedonic impact.


Asunto(s)
Ingestión de Alimentos , Conducta Alimentaria/efectos de los fármacos , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidores , Alimentación Animal , Animales , Inyecciones Intraperitoneales , Masculino , Motivación , Piperidinas/administración & dosificación , Pirazoles/administración & dosificación , Ratas , Ratas Endogámicas , Rimonabant , Gusto
17.
Pharmacol Biochem Behav ; 84(2): 353-9, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16814374

RESUMEN

The cannabinoid CB1 receptor inverse agonist rimonabant induces hypophagia and body weight loss. Reduced body weight may potentially be due to decreased food intake or to direct metabolic effects of drug administration on energy expenditure. This study uses a paired-feeding protocol to quantify the contributions of energy intake to rimonabant-induced body weight loss. Diet-induced obese (DIO) rats were dosed with rimonabant (3, 10 mg/kg PO once daily) and matched with pair-fed controls. Food intake and body weight were measured daily. Blood samples and adipose tissue were collected on day 15 for measurement of plasma adiponectin and adiponectin mRNA levels. DIO rats treated with rimonabant and pair-fed controls showed very similar changes in body weight. Although tolerance developed to the anorectic effect of rimonabant, total food intake was significantly decreased over the 14-day study period and fully accounted for the observed reductions in body weight. Adiponectin mRNA and plasma adiponectin were elevated in vehicle-treated chow-fed animals compared to obese controls, and did not differ between rimonabant-treated and pair-fed animals. The similarities between rimonabant-treated and pair-fed animals in body weight loss and the absence of differences in measures of adiponectin activity between drug-treated and pair-fed animals suggest that the outcomes of this experiment were solely mediated by the drug-induced reduction in food intake.


Asunto(s)
Adiponectina/fisiología , Peso Corporal/efectos de los fármacos , Grasas de la Dieta/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Obesidad/fisiopatología , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidores , Adiponectina/biosíntesis , Adiponectina/sangre , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Rimonabant
18.
Neuron ; 51(2): 239-49, 2006 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-16846858

RESUMEN

The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.


Asunto(s)
Ingestión de Alimentos/fisiología , Neuronas/fisiología , Receptor de Melanocortina Tipo 3/fisiología , Receptor de Serotonina 5-HT1B/fisiología , Receptores de Melanocortina/fisiología , Serotonina/fisiología , Animales , Ingestión de Alimentos/efectos de los fármacos , Estimulación Eléctrica , Masculino , Ratones , Ratones Endogámicos A , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Ratones Transgénicos , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Neuronas/efectos de los fármacos , Piridinas/farmacología , Receptor de Melanocortina Tipo 4/agonistas , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Receptor de Melanocortina Tipo 4/fisiología , Receptores de Melanocortina/agonistas , Receptores de Melanocortina/antagonistas & inhibidores , Serotonina/farmacología , Agonistas del Receptor de Serotonina 5-HT1
19.
Am J Vet Res ; 67(6): 1005-12, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16740094

RESUMEN

OBJECTIVE: To evaluate the effect of dietary supplementation with the probiotic strain Lactobacillus acidophilus DSM13241 in healthy adult cats. ANIMALS: 15 adult cats. PROCEDURES: Cats were fed a nutritionally complete dry food for 5 weeks. Fecal character was assessed daily, and a single fecal sample and 3-mL blood sample were collected for bacterial enumeration and hematologic analysis, respectively. Cats were then fed the same diet supplemented with L acidophilus DSM13241 (2 x 10(8) CFU/d) for 4.5 weeks. Repeat fecal and hematologic measurements were taken prior to the return to control diet for a 4-week period. RESULTS: The probiotic species was recovered from feces, demonstrating survival through the feline gastrointestinal tract. Probiotic supplementation was associated with increased numbers of beneficial Lactobacillus and L acidophilus groups in feces and decreased numbers of Clostridium spp and Enterococcus faecalis, indicating an altered bacterial balance in the gastrointestinal tract microflora. Fecal pH was also decreased suggesting a colonic environment selective for the beneficial lactic acid bacterial population. Systemic and immunomodulatory effects were associated with administration of L acidophilus DSM13241 including altered cell numbers within WBC subsets and enhanced phagocytic capacity in the peripheral granulocyte population. In addition, plasma endotoxin concentrations were decreased during probiotic feeding, and RBCs had a decreased susceptibility to osmotic pressure. CONCLUSIONS AND CLINICAL RELEVANCE: Probiotic strain L acidophilus DSM13241 fed at 2 x 10(8) CFU/d can alter the balance of gastrointestinal microflora in healthy cats. Furthermore, administration of this probiotic results in beneficial systemic and immunomodulatory effects in cats.


Asunto(s)
Gatos , Salud , Lactobacillus acidophilus/metabolismo , Probióticos/farmacología , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Estudios Cruzados , Dieta/veterinaria , Suplementos Dietéticos , Heces
20.
Psychopharmacology (Berl) ; 179(2): 452-60, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15821957

RESUMEN

RATIONALE: The CB1 receptor antagonist SR141716A reduces food intake in rats. This effect is likely to depend on modulation of reward related processes. OBJECTIVE: To investigate the effects of SR141716A on responding for food under a second order instrumental task in which responding and consumption of food can be separated, and on Pavlovian responding for a stimulus predictive of food reward. METHODS: Instrumental responding and pellet consumption following administration of SR141716A (0-3 mg/kg) were recorded under an FI5 min FR5(5:S) operant schedule that incorporates both a 5 min initial appetitive phase and a 25 min consummatory phase. We compared the drug-induced change in responding to that recorded following a reduction in motivational state induced by pre-feeding. In a second experiment we assessed the effects of SR141716A (0-3 mg/kg) on Pavlovian approach behaviour for a stimulus (lever) associated with food reward (CS+) and a neutral stimulus (lever) not associated with reward (CS-). RESULTS: SR141716A reduced pellet consumption and instrumental responding during both the appetitive and consummatory phases of the second order schedule. Pre-feeding had a similar effect on responding during the appetitive phase, suggesting an effect on incentive motivation. SR141716A also blocked an enhancement of responding that occurred during the consummatory phase in pre-fed animals. SR141716A and pre-feeding had no effect on responding in the Pavlovian autoshaping paradigm. CONCLUSIONS: SR141716A impacts on motivational processes in both the appetitive and consummatory phases of feeding behaviour.


Asunto(s)
Depresores del Apetito , Conducta Consumatoria/efectos de los fármacos , Alimentos , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidores , Animales , Condicionamiento Clásico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Habituación Psicofisiológica/efectos de los fármacos , Masculino , Ratas , Esquema de Refuerzo , Refuerzo en Psicología , Rimonabant
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