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1.
Anim Feed Sci Technol ; 226: 81-87, 2017 Apr.
Article in English | MEDLINE | ID: mdl-32288069

ABSTRACT

Diarrhea, resulting from gastrointestinal infection by pathogens, is a common cause of the high mortality and morbidity of neonatal calves. The objective of this study was to evaluate the effects of supplementing a yeast product in milk replacer (MR) on growth and health of calves, and on fecal populations of some targeted microorganisms related to calf health and growth (i.e., total bacteria, Escherichia coli, Clostridium cluster XIVa, Faecalibacterium prausnitzii and Bifidobacterium spp.). We hypothesized that feeding a Saccharomyces cerevisiae var boulardii (SCB) product would improve gastrointestinal health and growth performance of calves. Forty-two Holstein bull calves (42.6 ± 0.77 kg at birth) were randomly assigned on day 2 of age to either a control or SCB treatment. The SCB was supplemented in MR and fed at 5 g/d per head to supply 10 billion colony-forming units per day. All calves received high quality colostrum (>50 mg/mL of immunoglobulin G) during the first 24 h of life, and were fed with 8 L MR (150 g/L mixed with 40 °C water) daily from day 2-35, and 4 L daily from day 35-42. Calves were also fed calf starter ad libitum from day 7-56. Daily MR and starter offered and refused, daily fecal scores, nasal scores, ear scores, and weekly body weight of calves were recorded. Fecal samples were collected on day 7, 35 and 56 after the first feeding of that day for microbial targets analysis. Overall, there is no serious disease challenge for all the calves during the entire experimental period. No differences were observed in MR intake, starter intake, metabolizable energy (ME) intake, average daily gain, ME intake to gain ratio, fecal score, nasal score, eye score or any targeted microorganisms between treatments throughout the experiment. These results suggest that supplementing SCB in MR has no additive effects on animal growth or fecal biomarkers of gut health when calves do not show deteriorated health status.

2.
J Dairy Sci ; 99(9): 7624-7633, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27344386

ABSTRACT

Recent research suggests that circulating ß-hydroxybutyrate (BHB) levels may be a meaningful indicator of grain intake and rumen development in pre-ruminant calves. As such, BHB levels may be a surrogate measure of rumen function to contribute to minimal weaning stress during the transition from liquid to solid feed. The primary objective of this study was to determine the optimal cut-point of circulating BHB levels that would be predictive of sufficient grain intake and rumen development for a successful transition from liquid to solid feed at the time of weaning. An additional objective was to validate the Precision Xtra (Abbott Diabetes Care, Abingdon, UK) calf-side test for determination of BHB in whole blood in calves around weaning, as compared with the gold standard laboratory method. A total of 20 Holstein female calves were randomly assigned at birth to be weaned at 6 wk (n=10) or 8 wk (n=10) of age. Milk replacer (mixed at 150 g/L) was offered at 1.2kg/calf per d in 2 meals until a 1-wk step down, when milk meals were reduced by 50% 1 wk before weaning. Daily measurements included the intakes of starter grain, chopped straw, and water. Weekly measurements included body weight and blood BHB, until 70 d of life. To assess digestive tract development, rumen fluid samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids. Whole blood was collected by jugular venipuncture, and BHB was determined by the Precision Xtra test at calf-side. In addition, serum was separated from a clotted sample, frozen, and stored until laboratory analysis was performed. Laboratory BHB results were correlated with both the Precision Xtra test (r=0.95) and starter intake over 1 d (r=0.89), a 3-d average (r=0.90), and a 7-d average (r=0.90). Additionally, laboratory BHB results were associated with total ruminal volatile fatty acids (r=0.82), ruminal butyrate (r=0.77), and body weight (r=0.69). A receiver operating characteristic curve was created to plot the true positive rate against the false positive rate at 10µmol/L BHB intervals to determine the optimal cut-point of circulating BHB that is predictive of an average starter intake of 1,000 g/d over a 3-d period. The optimal combination of sensitivity (95.7%) and specificity (96.1%) was at 100µmol of BHB/L of blood. A value of 0.2 mmol/L on the Precision Xtra test yielded a sensitivity and specificity of 84.0 and 97.2%, respectively, over the 3-d average period of starter intake. These results show considerable promise for use of the Precision Xtra whole blood BHB test in the decision-making process of determining sufficient starter grain intake and rumen development for a successful transition from liquid to solid feed, and indicate that this test conducted at calf-side is highly accurate.


Subject(s)
3-Hydroxybutyric Acid/blood , Age Factors , Cattle/physiology , Dairying/methods , Feeding Behavior , Weaning , Animal Feed/analysis , Animals , Diet/veterinary , Female , Random Allocation , Rumen/growth & development
3.
J Dairy Sci ; 98(9): 6315-26, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26142851

ABSTRACT

Recent research has revealed potential advantages of feeding an elevated plane of nutrition to calves during the preweaning period. However, calves fed more nutrients preweaning may be more susceptible to depressed growth and weaning stress during the transition from liquid to solid feed. The objective of this study was to investigate the relationship between the age of weaning and feed intake, and its influence on growth, gastrointestinal development, and behavioral indicators in dairy calves fed an elevated plane of nutrition during the preweaning period. To meet this objective, 20 female Holstein calves were randomly assigned at birth to be weaned at 6 or 8 wk. Milk replacer (mixed at 150 g/L) was offered at 1.2 kg/calf per day in 2 meals until a 1-wk step-down, when meals were reduced by 50% 1 wk before weaning. Daily starter, chopped oat straw, water intake, and weekly body weights were measured until d 70 of life. To assess digestive tract development, rumen fluid, fecal, and blood samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids, blood ß-hydroxybutyrate, and fecal starch, respectively. Behavioral indicators of weaning stress, including vocalizing and non-nutritive oral behavior, were measured by visual observation for 1 h, 3 times per week, before the second feeding of the day during the period from 2 wk before weaning to 2 wk after weaning. The calves weaned at 8 wk compared with 6 wk had higher average daily gain for the week preweaning (0.79±0.09 vs. 0.34±0.10 kg/d) and postweaning (1.05±0.09 vs. 0.35±0.11 kg/d), and were heavier at d 70 (99.9±1.81 vs. 91.0±2.26 kg). From 5 to 8 wk of age, starter and water intakes were lower in calves weaned at 8 wk of age. However, overall starter intake did not differ during the last week of the experiment. Furthermore, calves weaned at 8 wk compared with 6 wk had higher starter intake for 1 wk preweaning (1.36±0.13 vs. 0.40±0.08 kg/d) and postweaning (2.51±0.20 vs. 1.16±0.15 kg/d). In both treatments, weaning increased ruminal short-chain fatty acids, blood ß-hydroxybutyrate, and fecal starch, yet the differences between the week before and after weaning were greater for calves weaned at 6 wk compared with those weaned at 8 wk. Treatment × week relative to weaning interactions indicated that several behaviors varied between early- and later-weaned calves during the week before weaning; calves weaned at 6 wk tended to exhibit 75% more non-nutritive oral behavior and spent 55% less time ruminating, and 36% less time lying compared with calves weaned at 8 wk. Under the conditions of this study, the results suggest that calves fed an elevated plane of nutrition preweaning have higher starter intakes and average daily gain during the weaning period when weaning is extended from 6 to 8 wk of age.


Subject(s)
Animal Feed/analysis , Behavior, Animal , Diet/veterinary , 3-Hydroxybutyric Acid/blood , Animal Nutritional Physiological Phenomena , Animals , Body Weight , Cattle , Fatty Acids, Volatile/metabolism , Gastrointestinal Tract/growth & development , Nutritional Status , Rumen/metabolism , Weaning
4.
Ann Surg Oncol ; 22(6): 1858-65, 2015.
Article in English | MEDLINE | ID: mdl-25476030

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding. METHODS: Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding. RESULTS: Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy. CONCLUSIONS: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.


Subject(s)
Adenocarcinoma/complications , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deglutition Disorders/prevention & control , Enteral Nutrition , Esophageal Neoplasms/complications , Neoadjuvant Therapy/adverse effects , Quality of Life , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Deglutition Disorders/chemically induced , Docetaxel , Epirubicin/administration & dosage , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophagogastric Junction/drug effects , Esophagogastric Junction/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Prospective Studies , Taxoids/administration & dosage
5.
Food Chem ; 151: 500-5, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24423562

ABSTRACT

The aim of this study was to (i) examine how enzymatic hydrolysis with a non-commercially available proteinase of fig-leaf gourd fruit (Cucurbita ficifolia) increased the use value of egg white protein preparations, generated as byproducts in the industrial process of lysozyme and cystatin isolation from egg white, and (ii) evaluate the inhibition of angiotensin I-converting enzyme (ACE) by the obtained hydrolysates. Purification procedures including membrane filtration, gel filtration chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) led to the production of several peptide fractions. Two novel ovalbumin-derived tetrapeptides: SWVE (f 148-151) and DILN (f 86-89) with ACE inhibitory activity were obtained. Study of their inhibitory kinetics revealed a non-competitive binding mode, with an IC50 value against ACE of 33.88 and 73.44 µg for SWVE and DILN, respectively. Synthetic peptides which were designed on the basis of peptide SWVE were examined. A tripeptide sequence of SWV revealed the strongest ACE-inhibitory activity.


Subject(s)
Antihypertensive Agents/therapeutic use , Egg Proteins/chemistry , Peptides/chemistry , Angiotensin-Converting Enzyme Inhibitors/chemistry , Hydrolysis
6.
J Thromb Haemost ; 7(8): 1304-12, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19566550

ABSTRACT

BACKGROUND: Candidate von Willebrand factor (VWF) mutations were identified in 70% of index cases in the European study 'Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand Disease'. The majority of these were missense mutations. OBJECTIVES: To assess whether 14 representative missense mutations are the cause of the phenotype observed in the patients and to examine their mode of pathogenicity. METHODS: Transfection experiments were performed with full-length wild-type or mutant VWF cDNA for these 14 missense mutations. VWF antigen levels were measured, and VWF multimer analysis was performed on secreted and intracellular VWF. RESULTS: For seven of the missense mutations (G160W, N166I, L2207P, C2257S, C2304Y, G2441C, and C2477Y), we found marked intracellular retention and impaired secretion of VWF, major loss of high molecular weight multimers in transfections of mutant constructs alone, and virtually normal multimers in cotransfections with wild-type VWF, establishing the pathogenicity of these mutations. Four of the mutations (R2287W, R2464C, G2518S, and Q2520P) were established as being very probably causative, on the basis of a mild reduction in the secreted VWF or on characteristic faster-running multimeric bands. For three candidate changes (G19R, P2063S, and R2313H), the transfection results were indistinguishable from wild-type recombinant VWF and we could not prove these changes to be pathogenic. Other mechanisms not explored using this in vitro expression system may be responsible for pathogenicity. CONCLUSIONS: The pathogenic nature of 11 of 14 candidate missense mutations identified in patients with type 1 VWD was confirmed. Intracellular retention of mutant VWF is the predominant responsible mechanism.


Subject(s)
Mutation , von Willebrand Factor/genetics , Animals , COS Cells , Chlorocebus aethiops , Humans , Mutant Proteins , Mutation, Missense , Phenotype , Protein Multimerization , Transfection , von Willebrand Diseases/genetics , von Willebrand Factor/metabolism
7.
J Theor Biol ; 252(4): 633-48, 2008 Jun 21.
Article in English | MEDLINE | ID: mdl-18371986

ABSTRACT

Epstein-Barr virus (EBV) is an important human pathogen that establishes a life-long persistent infection and for which no precise animal model exists. In this paper, we describe in detail an agent-based model and computer simulation of EBV infection. Agents representing EBV and sets of B and T lymphocytes move and interact on a three-dimensional grid approximating Waldeyer's ring, together with abstract compartments for lymph and blood. The simulation allows us to explore the development and resolution of virtual infections in a manner not possible in actual human experiments. Specifically, we identify parameters capable of inducing clearance, persistent infection, or death.


Subject(s)
Epstein-Barr Virus Infections/immunology , Models, Immunological , B-Lymphocytes/immunology , B-Lymphocytes/virology , Cell Proliferation , Computer Simulation , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/physiology , Humans , Lymphocyte Activation/immunology , Lymphoid Tissue/microbiology , Virus Latency
8.
Vet Parasitol ; 111(1): 47-57, 2003 Jan 20.
Article in English | MEDLINE | ID: mdl-12523978

ABSTRACT

In order to test various viability assays for Cryptosporidium parvum oocysts were used to infect HCT-8 cells in vitro or baby mice. Infected cells were either stained with fluorescent anti-Cryptosporidium-antibody or lysed and subjected to C. parvum-specific PCR after 48 h. Titrations with infective oocysts were performed and compared to oocysts disinfected with Neopredisan for 2 h at varying concentrations. Caecal smears and histological sections from infected animals were examined in parallel. The number of foci of parasite development in vitro after immunofluorescent staining correlated well with the infection dose. PCR was less quantifiable and the results were not always reproducible, especially when low infection doses were used. Disinfection resulted in a dose-dependent reduction of oocyst infectivity when compared to the controls in all three assays. The infection of cells cultured in vitro with oocysts of C. parvum provides a suitable tool for the estimation of viability after treatment with chemical disinfectants. Immunofluorescence is easy to perform and gives quantitative results, while PCR-based detection of parasite DNA, although possible, requires the use of more sophisticated tools for quantification.


Subject(s)
Cresols/pharmacology , Cryptosporidium parvum/drug effects , Disinfection , Fungicides, Industrial/pharmacology , Oocysts/cytology , Oocysts/drug effects , Animals , Cell Line , Cell Size/drug effects , Cell Survival/drug effects , Cryptosporidium parvum/cytology , Cryptosporidium parvum/genetics , DNA, Protozoan/analysis , Dose-Response Relationship, Drug , Fluorescent Antibody Technique , Mice , Polymerase Chain Reaction
9.
Int J Eat Disord ; 28(3): 293-302, 2000 Nov.
Article in English | MEDLINE | ID: mdl-10942915

ABSTRACT

OBJECTIVE: We previously reported elevated serum levels of the cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients with anorexia nervosa (AN). We investigated the cellular production of these two cytokines and of interferon-gamma (IFN-gamma), interleukin-1alpha (IL-1alpha), and tumor necrosis factor-alpha (TNF-alpha) in subjects with AN, bulimia nervosa (BN), and obesity as well as in normal-weight control subjects. METHODS: Supernatant fluids from isolated peripheral blood mononuclear cells (PBMC) incubated with and without concanavalin A (ConA) were assayed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences across the four groups were found in the stimulated cellular production of IFN-gamma and IL-6. Stimulated IFN-gamma production was elevated in the AN group compared to controls. IL-6 production was significantly elevated in obese subjects relative to the two normal-weight groups, BN and controls, and tended to be higher in the AN group than in the controls, but not significantly so. IL-1alpha production was greater in obese subjects. CONCLUSION: The findings of increased IFN-gamma production and a tendency toward increased IL-6 production (both of which suppress food intake in animals) in individuals who severely restrict food intake suggest a potential role for these cytokines in the pathogenesis of AN. Elevated IL-6 and IL-1alpha production by PBMC in obese individuals requires further investigation to determine if these cytokines contribute to the development or perpetuation of obesity.


Subject(s)
Anorexia Nervosa/immunology , Bulimia/immunology , Cytokines/blood , Obesity/immunology , Adolescent , Adult , Female , Humans , Interferon-gamma/blood , Interleukin-6/blood , Macrophages/immunology , Middle Aged , Reference Values , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/metabolism
10.
Graefes Arch Clin Exp Ophthalmol ; 238(6): 515-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10943677

ABSTRACT

BACKGROUND: The pathogenesis of central serous chorioretinopathy is poorly understood. It is believed to be due to dysfunction of the retinal pigment epithelium and/or choroid and has been associated with elevated levels of epinephrine and administration of corticosteroids. Epinephrine and corticosteroids have previously been shown to induce apoptosis (programmed cell death) in various types of cells. The objective of this study was to investigate whether these agents can induce apoptosis in cultured retinal pigment epithelium cells. This may help elucidate the pathogenesis of central serous chorioretinopathy. METHODS: Third-passage porcine retinal pigment epithelium cells were grown to confluence and incubated for 1-7 days in culture medium containing epinephrine (10(2)-10(9) pg/ml) or a corticosteroid, dexamethasone (4-4x10(4) ng/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. RESULTS: Epinephrine (7x10(7)-10(9) pg/ml) induced apoptosis in a dose- and time-dependent manner. Exposure to lower concentrations of epinephrine (10(2)-6x10(7) pg/ml) and all tested levels of dexamethasone did not result in apoptosis. CONCLUSION: Retinal pigment epithelium cells may undergo apoptosis following exposure to elevated levels of epinephrine. These findings suggest a possible pathophysiologic mechanism for the development of central serous chorioretinopathy.


Subject(s)
Apoptosis/drug effects , Choroid Diseases/etiology , Dexamethasone/pharmacology , Epinephrine/pharmacology , Pigment Epithelium of Eye/pathology , Retinal Diseases/etiology , Animals , Cells, Cultured , Choroid Diseases/pathology , Exudates and Transudates , Glucocorticoids/pharmacology , In Situ Nick-End Labeling , Microscopy, Phase-Contrast , Pigment Epithelium of Eye/drug effects , Retinal Diseases/pathology , Swine , Vasoconstrictor Agents/pharmacology
12.
Int J Eat Disord ; 28(1): 1-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10800008

ABSTRACT

OBJECTIVE: This paper addresses the lack of a standard protocol for pharmacotherapy trials for patients with bulimia nervosa (BN) and anorexia nervosa (AN). METHOD: Twenty-two surveys were sent to established researchers in the field of eating disorders to elicit their opinions regarding medication trials, including baseline laboratory tests, the optimal length/frequency of medication management sessions, and the information that should or should not be included in these sessions. RESULTS: Sixteen of 22 researchers completed and returned the survey. Their answers are the basis of the data presented. DISCUSSION: We propose a battery of screening laboratory tests for both conditions. We suggest 30-45-min initial medication management sessions in both AN and BN trials with 15-min follow-ups to be held weekly for AN subjects, and weekly for 2 weeks, then biweekly for 2 weeks, then monthly, for BN subjects. We also recommend that published trials should include explicit details of medication management.


Subject(s)
Anorexia Nervosa/diagnosis , Anorexia Nervosa/drug therapy , Bulimia/diagnosis , Bulimia/drug therapy , Practice Guidelines as Topic/standards , Randomized Controlled Trials as Topic/standards , Anorexia Nervosa/blood , Attitude of Health Personnel , Bulimia/blood , Clinical Protocols/standards , Drug Monitoring/methods , Drug Monitoring/standards , Humans , Mass Screening/methods , Mass Screening/standards , Patient Education as Topic/methods , Patient Education as Topic/standards , Physician's Role , Research Personnel/psychology , Surveys and Questionnaires
13.
Am J Clin Nutr ; 71(4): 901-7, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10731495

ABSTRACT

BACKGROUND: The concept of a body weight set point, determined predominantly by genetic mechanisms, has been proposed to explain the poor long-term results of conventional energy-restricted diets in the treatment of obesity. OBJECTIVE: The objective of this study was to examine whether dietary composition affects hormonal and metabolic adaptations to energy restriction. DESIGN: A randomized, crossover design was used to compare the effects of a high-glycemic-index (high-GI) and a low-glycemic-index (low-GI) energy-restricted diet. The macronutrient composition of the high-GI diet was (as percent of energy) 67% carbohydrate, 15% protein, and 18% fat and that of the low-GI diet was 43% carbohydrate, 27% protein, and 30% fat; the diets had similar total energy, energy density, and fiber contents. The subjects, 10 moderately overweight young men, were studied for 9 d on 2 separate occasions. On days -1 to 0, they consumed self-selected foods ad libitum. On days 1-6, they received an energy-restricted high- or low-GI diet. On days 7-8, the high- or low-GI diets were consumed ad libitum. RESULTS: Serum leptin decreased to a lesser extent from day 0 to day 6 with the high-GI diet than with the low-GI diet. Resting energy expenditure declined by 10.5% during the high-GI diet but by only 4.6% during the low-GI diet (7.38 +/- 0.39 and 7.78 +/- 0.36 MJ/d, respectively, on days 5-6; P = 0.04). Nitrogen balance tended to be more negative, and energy intake from snacks on days 7-8 was greater, with the high-GI than the low-GI diet. CONCLUSION: Diets with identical energy contents can have different effects on leptin concentrations, energy expenditure, voluntary food intake, and nitrogen balance, suggesting that the physiologic adaptations to energy restriction can be modified by dietary composition.


Subject(s)
Adaptation, Physiological , Diet , Energy Intake , Adolescent , Adult , Blood Glucose/metabolism , Cross-Over Studies , Diet, Reducing , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Humans , Leptin/metabolism , Male , Nitrogen/metabolism
14.
Lancet ; 355(9206): 792-7, 2000 Mar 04.
Article in English | MEDLINE | ID: mdl-10711927

ABSTRACT

BACKGROUND: Several lines of evidence have led us to postulate that afferent vagal hyperactivity could be an important factor in the pathophysiology of the eating disorder bulimia nervosa. Ondansetron is a peripherally active antagonist of the serotonin receptor 5-HT3, and is marketed for prevention of vagally-mediated emesis caused by cancer chemotherapeutic agents. We investigated the effects of ondansetron on bulimic behaviours in patients with severe and chronic bulimia nervosa in a randomised, double-blind, placebo-controlled study. METHODS: We enrolled patients with severe bulimia nervosa (at least seven coupled binge/vomit episodes per week). The patients were otherwise healthy, their weight was normal, and they were not receiving medical or psychiatric treatment. During the first week of the study, patients recorded all eating-behaviour events to establish a baseline. In the second week, all patients received placebo, but were told that they were receiving either placebo or active drug. At the end of this single-blind phase, patients were randomly assigned placebo or ondansetron (24 mg daily) for a further 4 weeks. The primary outcome measure was the number of binge/vomit episodes per week. Data were analysed by intention to treat. FINDINGS: 29 patients met the inclusion criteria, of whom 28 completed the baseline study, and 26 completed the single-blind placebo week. 12 patients were assigned placebo, and 14 ondansetron; one patient in the ondansetron group dropped out owing to accidental injury. During the 4th week of double-blind treatment, mean binge/vomit frequencies were 13.2 per week (SD 11.6) in the placebo group, versus 6.5 per week (3.9) in the ondansetron group (estimated difference 6.8 [95% CI 4.0-9.5]; p<0.0001). The ondansetron group also showed significant improvement, compared with the placebo group, in two secondary indicators of disease severity. The amount of time spent engaging in bulimic behaviours was decreased on average by 7.6 h per week in the ondansetron group, compared with 2.3 h in the placebo group (estimated difference 5.1 [0.6-9.7]). Similarly, the number of normal meals and snacks increased on average by 4.3 normal eating episodes without vomiting per week in the ondansetron group, compared with 0.2 in the placebo group (estimated difference 4.1 [1.0-7.2]). INTERPRETATION: The decrease in binge-eating and vomiting under ondansetron treatment was not achieved by compensatory changes in eating behaviour such as by a smaller number of binges of longer duration, or by not eating, or by binge-eating without vomiting. Instead, our findings indicate a normalisation of the physiological mechanism(s) controlling meal termination and satiation. Since meal termination and satiety are mainly vagally mediated functions, since binge-eating and vomiting produce intense stimulation of vagal afferent fibres, and since ondansetron and other 5-HT3 antagonists decrease afferent vagal activity, the symptom improvement may result from a pharmacological correction of abnormal vagal neurotransmission.


Subject(s)
Antiemetics/therapeutic use , Bulimia/drug therapy , Ondansetron/therapeutic use , Serotonin Antagonists/therapeutic use , Vagus Nerve/drug effects , Adolescent , Adult , Afferent Pathways/drug effects , Afferent Pathways/physiopathology , Antiemetics/adverse effects , Bulimia/physiopathology , Double-Blind Method , Feeding Behavior/drug effects , Feeding Behavior/physiology , Female , Humans , Middle Aged , Ondansetron/adverse effects , Receptors, Serotonin/drug effects , Receptors, Serotonin/physiology , Satiety Response/drug effects , Satiety Response/physiology , Serotonin Antagonists/adverse effects , Vagus Nerve/physiopathology
16.
J Neurosci Methods ; 89(2): 141-9, 1999 Jul 15.
Article in English | MEDLINE | ID: mdl-10491945

ABSTRACT

We have developed an easy and fast method to semiquantify low levels of mRNA from small amounts of brain tissues based on nonradioactive reverse transcription-polymerase chain reaction (RT-PCR). The regulation of mRNA for the growth associated protein GAP-43/B-50 and the homeodomain protein islet-1 was examined in the facial nucleus of the rat after a unilateral transection of the nerve. In both cases a similar sensitivity for radioactive and nonradioactive RT-PCR methods was found. The expression of the housekeeping gene, cyclophilin A was used to normalize total mRNA amounts and PCR conditions. After amplification the PCR products were separated electrophoretically on polyacrylamide gels. For nonradioactive semiquantification gels were stained with ethidium bromide and recorded using a CCD camera and transillumination. The recordings were evaluated with specialized software. Using nonradioactive RT-PCR, the increase in GAP-43/B-50 mRNA in response to axotomy was easily detectable in the small volume of tissue obtained from the facial nucleus. In contrast, the low expression of islet-1 mRNA made it necessary to develop a two-step amplification procedure in order to provide a reliable semiquantitative analysis. The procedure included preamplification of the cDNA and subsequent purification of the cDNA. Using this method, the down-regulation of islet-1 could be demonstrated with a similar sensitivity to that previously shown with radioactive RT-PCR.


Subject(s)
Adaptor Proteins, Signal Transducing , Facial Nerve/metabolism , GAP-43 Protein/metabolism , Nuclear Proteins/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Trans-Activators/metabolism , Animals , Calibration , Male , Peptidylprolyl Isomerase/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction/instrumentation
17.
Biol Psychiatry ; 45(10): 1389-92, 1999 May 15.
Article in English | MEDLINE | ID: mdl-10349046

ABSTRACT

BACKGROUND: Conflicting data have been published regarding pain threshold in subjects with anorexia nervosa (AN), with some studies indicating elevated pain threshold and others indicating normal thresholds. Previous research has indicated the presence of elevated pain threshold in eating disorder subjects with binge-eating behavior. METHODS: In this study pressure pain detection thresholds (PDT) (assessed by a pressure analgesiometer) in binge-eating/purging and restricting subtypes of AN subjects were compared to control subjects. RESULTS: PDT was elevated in AN compared to control subjects at baseline. There was no difference in PDT between the subgroups of AN subjects. CONCLUSIONS: The etiology of elevated PDT in AN subjects is most likely different from the etiology of elevated PDT in bulimia nervosa subjects.


Subject(s)
Anorexia Nervosa/diagnosis , Pain Threshold/physiology , Pain/diagnosis , Adolescent , Adult , Anorexia Nervosa/physiopathology , Body Mass Index , Bulimia/diagnosis , Bulimia/physiopathology , Female , Humans , Pain/physiopathology , Pain Measurement
18.
Compr Psychiatry ; 40(3): 229-33, 1999.
Article in English | MEDLINE | ID: mdl-10360620

ABSTRACT

Subjects with bulimia nervosa (BN) have been shown to exhibit abnormal satiety responses. Short-term satiety is largely mediated by afferent vagal activity. Activation of afferent vagal fibers has also been found to stimulate a descending pain inhibitory pathway that leads to elevation in somatosensory pain thresholds. Therefore, the study of pain thresholds in BN subjects may lead to a better understanding of afferent vagal function in this disorder. In this preliminary study, pressure pain thresholds were assessed in nine subjects with BN on 3 consecutive days during a binge-eating and vomiting (B/V) episode, during a normal meal, and after an overnight fast. A significant time versus condition effect was found with a significant change in the pain threshold in BN subjects under the B/V condition only. These data are consistent with the hypothesis that vagal afferent activation by a B/V episode also activates the descending pain inhibitory pathway.


Subject(s)
Bulimia/complications , Pain/diagnosis , Pain/etiology , Adolescent , Adult , Bulimia/diagnosis , Disease Progression , Female , Humans , Neurons, Afferent/physiology , Pain Measurement/methods , Psychiatric Status Rating Scales , Severity of Illness Index , Time Factors , Vagus Nerve/physiology
19.
Physiol Behav ; 64(5): 629-36, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9817574

ABSTRACT

A sample of 66 monozyogtic twins reared apart (MZA) and 51 dizygotic twins reared apart (DZA), and 101 nontwin individuals (mostly spouses of the twins) who participated in the Minnesota Study of Twins Reared Apart (MISTRA) from 1979 to 1995 completed a self-report food frequency questionnaire. Intraclass-correlations and model-fitting analyses indicated that approximately 30% of the variance in the self-report of diet was attributable to genetic factors, with random environmental factors and measurement error responsible for the remaining variance. Spouse correlations were moderate. To investigate the effects of living together during marriage, the absolute differences between husband and wife on the dietary variables with years of marriage were correlated. None of the correlations were significant. Hierarchical multiple regression analyses also indicated that no convergence occurred during marriage. These results suggest that sharing a current family environment exerts minimal influence on individual differences in self-reported diet.


Subject(s)
Environment , Food Preferences/physiology , Adult , Age Factors , Body Height/physiology , Body Weight/physiology , Eating/genetics , Energy Intake/genetics , Female , Humans , Male , Marriage , Middle Aged , Models, Psychological , Social Class , Twins, Dizygotic/psychology , Twins, Monozygotic/psychology
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