Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 104
Filter
1.
Eur Arch Otorhinolaryngol ; 276(11): 3213-3219, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31388759

ABSTRACT

PURPOSE: Total laryngectomy and end tracheal stoma formation are often required to treat advanced laryngeal cancer. Resources on the internet are commonly accessed by patients as a source of healthcare information. YouTube™, the most popular video-hosting website, is one such resource. The aims of this study were to assess the thematic content of the most viewed YouTube™ videos concerning laryngectomy for laryngeal cancer and to evaluate user response to these videos. METHOD: A search of YouTube™ was performed and data were extracted from videos with > 100 views. Upload source, number of views, likes, dislikes and comments were collected and the content of comments was analysed. User response was compared between upload sources using Kruskal-Wallis testing. Inductive thematic analysis of video content was performed to identify overarching themes and subthemes. RESULTS: A total of 96 videos were identified, 16 uploaded by patients, 24 by individual healthcare professionals and 56 by professional healthcare institutions. There were 1214,503 views and no significant differences in the number of views, likes or dislikes between upload sources. Three overarching themes and 17 subthemes were identified. Comments were most frequently characterised as offering praise. CONCLUSION: YouTube™ has been shown to be a popular platform for sharing information about laryngectomy for laryngeal cancer. There is a lack of data concerning the quality of this information, however, and future work should focus on assessing this. Trusted institutions could make use of this medium to disseminate high-quality information to their patients, and to the wider public.


Subject(s)
Information Dissemination/methods , Internet , Laryngeal Neoplasms , Laryngectomy/methods , Social Media , Humans , Information Seeking Behavior , Laryngeal Neoplasms/psychology , Laryngeal Neoplasms/surgery , Video Recording
2.
Neuroscience ; 225: 237-48, 2012 Dec 06.
Article in English | MEDLINE | ID: mdl-22917616

ABSTRACT

Immunological activation may result in the development of depressive-like symptoms in a large percentage of patients treated with cytokine-based therapies. The mechanisms underlying susceptibility to cytokine-induced depression are currently unknown; however activation of the tryptophan catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is associated with the induction of cytokine-induced depression. Peripheral administration of lipopolysaccharide (LPS) is one of the most commonly used immunological challenges in animal models of cytokine-induced depression. Inbred mouse strains are useful tools in the investigation of the neurobiology of psychiatric illnesses. In this study we hypothesised that two strains which differ in stress susceptibility, namely the BALB/c and C57BL/6J mice, would respond differentially to LPS and swim-stress in cytokine profile, corticosterone concentrations and mRNA expression of genes coding for the tryptophan metabolising enzymes, IDO1, IDO2, Tph1 and Tph2. The stress-sensitive BALB/c strain exhibited increased depressive-like behaviour and enhanced corticosterone concentrations in response to LPS. Furthermore, swim-stress attenuated the LPS-induced corticosterone response in BALB/c mice only. LPS significantly increased plasma interleukin (IL)-1ß and tumour necrosis factor α (TNFα) concentrations to a greater extent in BALB/c mice. The LPS-induced increase in IL-1ß mRNA expression was significantly attenuated by swim-stress in the hippocampus of C57BL/6J but not in BALB/c mice. TNFα mRNA expression was significantly increased in BALB/c mice only; this increase was attenuated by swim-stress. Tph1 mRNA expression was upregulated in the brainstem of C57BL/6J mice post-LPS and following the combination of swim-stress and LPS in BALB/c mice. In the hippocampus Tph1 and Tph2 mRNA expression was increased in C57BL/6J but not BALB/c mice in response to LPS challenge and swim-stress. Conversely, IDO2 but not IDO1 mRNA expression was significantly altered following swim-stress and LPS, particularly in the hippocampus of BALB/c mice. These data indicate altered central mRNA expression of tryptophan metabolising enzymes and immune activation in BALB/c mice compared to the normo-sensitive C57BL/6J strain.


Subject(s)
Cytokines/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Lipopolysaccharides/pharmacology , Stress, Psychological/chemically induced , Analysis of Variance , Animals , Brain/drug effects , Brain/enzymology , Corticosterone/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/physiology , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Species Specificity , Stress, Psychological/metabolism , Stress, Psychological/pathology , Swimming/psychology , Time Factors , Tryptophan Hydroxylase/genetics , Tryptophan Hydroxylase/metabolism
3.
Transl Psychiatry ; 2: e88, 2012 Mar 13.
Article in English | MEDLINE | ID: mdl-22832853

ABSTRACT

Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.


Subject(s)
Depressive Disorder, Major/genetics , Gene Expression/genetics , Hippocampus/pathology , Immediate-Early Proteins/genetics , Interleukin-6/blood , Protein Serine-Threonine Kinases/genetics , Transcription Factors/genetics , Adult , Amygdala/pathology , Amygdala/physiopathology , C-Reactive Protein/metabolism , Child , Child Abuse/diagnosis , Child Abuse/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/pathology , Depressive Disorder, Major/physiopathology , Dominance, Cerebral/physiology , Female , Hippocampus/physiopathology , Humans , Male , Middle Aged , Organ Size/genetics , RNA, Messenger/genetics , Receptors, Glucocorticoid/genetics , Reference Values , Statistics as Topic
4.
Neuroscience ; 204: 53-63, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-21952131

ABSTRACT

The endocannabinoid system is an important regulator of the nervous, neuroendocrine, and immune systems, thus representing a novel therapeutic target for stress-related neuroinflammatory and psychiatric disorders. However, there is a paucity of data relating to the effects of endocannabinoids on neuroinflammatory mediators following an immune stress/challenge in vivo. This study investigated the effects of URB597, a selective inhibitor of fatty acid amide hydrolyase (FAAH), the enzyme that preferentially metabolizes anandamide, on lipopolysaccharide (LPS)-induced increases in the expression of immune mediators in the hypothalamus. Systemic administration of URB597 increased the levels of anandamide and the related N-acylethanolamines, N-palmitoylethanolamide, and N-oleoylethanolamide, but not 2-arachidonoyl glycerol, in the hypothalamus and spleen. URB597 attenuated the LPS-induced increase in interleukin (IL)-1ß expression while concurrently augmenting the LPS-induced increase in suppressor of cytokine signalling (SOCS)-3 expression. In addition, URB597 tended to enhance and reduce the LPS-induced increase in IL-6 and IL-10 mRNA expression, respectively. LPS-induced increases in peripheral cytokine levels or plasma corticosterone were not altered by URB597. The present study provides evidence for a role for FAAH in the regulation of LPS-induced expression of inflammatory mediators in the hypothalamus. Improved understanding of endocannabinoid-mediated regulation of neuroimmune function has fundamental physiological and potential therapeutic significance in the context of stress-related disorders.


Subject(s)
Cannabinoid Receptor Modulators/metabolism , Endocannabinoids , Hypothalamus/metabolism , Inflammation Mediators/metabolism , Stress, Physiological/physiology , Animals , Benzamides/pharmacology , Carbamates/pharmacology , Cytokines/metabolism , Hypothalamus/drug effects , Lipopolysaccharides/pharmacology , Male , Rats , Rats, Sprague-Dawley , Stress, Physiological/drug effects
5.
Avian Pathol ; 36(2): 119-26, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17479372

ABSTRACT

FP3 and 612 viruses are enterovirus-like viruses. Antibody to these viruses is widespread in chicken flocks, but nothing is known about their pathogenicity. Seven experiments were carried out to investigate the tissue tropism and associated pathology of these novel fowl enterovirus-like viruses and to compare these with the effects of the previously studied enterovirus-like viruses, ELV-1 and avian nephritis (ANV). ANV is now classified as an astrovirus. Preliminary experiments were carried out with FP3 virus, 612 virus and ELV-1 to determine the distribution of viral antigen. Each preliminary experiment was followed by a larger experiment that included more birds and in which a greater range of tissues was studied. It was shown that all four viruses studied replicated in the intestine and had differing abilities to spread to other tissues. Histological changes were present in most antigen-positive tissues but they were usually relatively mild. ELV-1 was associated with the most severe intestinal lesions, followed by FP3 virus. FP3 virus produced lesions in the kidney that were marginally more severe than those caused by the G-4260 strain of ANV. FP3 virus also caused pancreatic lesions. The 612 virus was found to be only mildly pathogenic in specific pathogen free chickens.


Subject(s)
Chickens/virology , Enterovirus Infections/veterinary , Enterovirus/classification , Enterovirus/pathogenicity , Gastrointestinal Diseases/veterinary , Poultry Diseases/virology , Animals , Antigens, Viral/isolation & purification , Enterovirus/isolation & purification , Enterovirus Infections/virology , Gastrointestinal Diseases/pathology , Gastrointestinal Diseases/virology , Gastrointestinal Tract/pathology , Gastrointestinal Tract/virology , Kidney/pathology , Kidney/virology , Lung/virology , Specific Pathogen-Free Organisms , Spleen/virology
6.
Avian Pathol ; 35(3): 254-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16753618

ABSTRACT

There have been many reports of the severe clinical disease and pathology seen in young chicks that have been vertically infected with chicken anaemia virus (CAV). The disease is characterized by anaemia, and atrophy of the thymus and bone marrow. However, while it has been suggested that horizontally acquired infections of older birds are common, to date there has been no description in the literature of the pathology of this type of infection. In the present study, 3-week-old and 6-week-old chickens were infected by the oral route, as is likely to occur naturally, and a wide range of tissues were examined immunocytochemically for the presence of CAV antigen. Histological examination was carried out on the thymus, spleen and bone marrow of all birds, and on all other tissue samples in which CAV antigen was found. CAV antigen and associated pathological change were detected in the thymus of both 3-week-old and 6-week-old birds. However, CAV antigen was rarely found in other tissues, which is in contrast to what is found in birds infected when 1-day-old. In particular, very few infected cells were found in the bone marrow. Anaemia and bone marrow atrophy, which are typically found in chicks infected vertically or when 1-day-old, did not develop in the 3-week-old or 6-week-old birds. The findings of this study show that CAV is capable of infecting thymocytes of older birds, in contrast to previous belief, and that it is associated with lymphocyte depletion. There was only limited evidence of viral replication in the other tissues examined.


Subject(s)
Aging/immunology , Chicken anemia virus/physiology , Circoviridae Infections/veterinary , Lymphocytes/pathology , Thymus Gland/immunology , Thymus Gland/virology , Administration, Oral , Animals , Chickens , Circoviridae Infections/immunology , Circoviridae Infections/pathology , Lymphocyte Count , Lymphocytes/immunology , Specific Pathogen-Free Organisms , Thymus Gland/pathology , Virus Replication
7.
Epidemiol Infect ; 132(2): 357-68, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15061512

ABSTRACT

In November 1973 Newcastle disease suddenly appeared in Northern Ireland, where the viscerotropic disease had not been seen in 3 1/2 years and the two Irelands had been regarded as largely disease free for 30 years. It was successfully controlled with only 36 confirmed affected layer flocks, plus 10 more slaughtered as 'dangerous contacts'. Contemporary investigations failed to reveal the source of the Irish epidemic. Using archival virus samples from most of the affected flocks, RT PCR was conducted with primers selected for all six NDV genes. Phylogenetic analyses of three genes, HN, M and F, confirmed vaccine as the cause of one of the outbreaks. The other six samples were identical and closely related to previous outbreaks in the United States and western Europe initiated by infected imported Latin American parrots. The probable cause of the epidemic followed from the importation from The Netherlands of bulk feed grains contaminated with infected pigeon faeces.


Subject(s)
Newcastle disease virus/genetics , HN Protein/genetics , Humans , Multigene Family , Newcastle disease virus/classification , Phylogeny , Retrospective Studies
8.
Neuropharmacology ; 44(5): 616-23, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12668047

ABSTRACT

Recent studies indicate that nitric oxide (NO) synthase inhibitors have antidepressant-like potential in various animal models. In the present study the behavioural activity of the NO synthase inhibitors, N(G)-nitro-L-arginine (L-NA) and 7-nitroindazole (7-NI), were assessed in a modified rat forced swimming test (FST). Both L-NA and 7-NI, dose dependently reduced immobility and increased swimming behaviour in the rat FST. This behavioural profile parallels the one previously shown with selective serotonin re-uptake inhibitors and serotonergic agonists. Thus, we examined the role of serotonin mediating the behavioural effects of L-NA and 7-NI in the rat FST. Depletion of endogenous serotonin using para-chlorophenylalanine (pCPA; 3 x 150 mg/kg, i.p.) completely blocked L-NA (20 mg/kg, i.p.) and 7-NI (20 mg/kg, i.p.)-induced reductions in immobility and increases in swimming behaviour during the FST. In conclusion these observations suggest that NO synthase inhibitors elicit their antidepressant-like activity in the modified swimming test through a serotonin dependent mechanism.


Subject(s)
Antidepressive Agents/pharmacology , Enzyme Inhibitors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Serotonin/metabolism , Animals , Antidepressive Agents/therapeutic use , Depression/drug therapy , Depression/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/therapeutic use , Immobilization/physiology , Indazoles/pharmacology , Indazoles/therapeutic use , Male , Motor Activity/drug effects , Motor Activity/physiology , Nitric Oxide Synthase/metabolism , Nitroarginine/pharmacology , Nitroarginine/therapeutic use , Rats , Rats, Sprague-Dawley
9.
Immunol Lett ; 78(2): 67-73, 2001 Sep 03.
Article in English | MEDLINE | ID: mdl-11672589

ABSTRACT

Methylenedioxymethiamphetamine (MDMA; "Ecstasy") is a widely abused amphetamine derivative. In the present study, we examined the effect of acute MDMA administration on an antigen specific immune response. Responsiveness to an in vivo challenge with the soluble protein antigen keyhole limpet haemocyanin (KLH) was examined in rats following MDMA administration (2.5, 5 or 10 mg/kg; i.p.). KLH-specific serum IgM concentrations were measured 7 days following challenge, and serum IgG concentrations were measured 14 days following the KLH challenge. In addition, antigen-specific IFN-gamma and IL-6 production was measured in KLH-stimulated splenocytes. MDMA did not alter the KLH-specific IgM response. In contrast, MDMA (5 and 10 mg/kg) provoked a significant suppression of KLH-specific IgG production. Thus, MDMA administration did not alter the initial generation of the antibody response but rather inhibited antibody class switching from IgM to IgG. Two pathways for the genetic switch from IgM to IgG production were investigated. One pathway requires the Th(1) type cytokine IFN-gamma to stimulate IgM-secreting cells to switch to IgG(2a)-secreting cells. Another pathway requires the Th(2) type cytokines IL-4 and IL-6 to stimulate IgM-secreting cells to switch to IgG(1)-secreting cells. IgG(1) and IgG(2a) levels were measured to determine if these two pathways were differentially affected. The results indicate that only IgG(2a) levels were decreased following MDMA administration. Furthermore, this decrease in IgG(2a) was accompanied by decreased KLH-specific IFN-gamma production 14 days post KLH administration. In conclusion, these data indicate that MDMA alters the ability to switch from IgM to IgG(2a) production, possibly by reducing IFN-gamma. Potential health consequences for MDMA users are discussed.


Subject(s)
Antibody Specificity/drug effects , Epitopes, T-Lymphocyte/immunology , Hemocyanins/immunology , Immunoglobulin G/biosynthesis , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/biosynthesis , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Animals , Female , Immunoglobulin G/blood , Immunoglobulin M/biosynthesis , Immunoglobulin M/blood , Injections, Intraperitoneal , Interferon-gamma/blood , Interleukin-6/biosynthesis , Mollusca/immunology , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , Rats , Rats, Sprague-Dawley , Time Factors
10.
Med Eng Phys ; 23(4): 239-47, 2001 May.
Article in English | MEDLINE | ID: mdl-11427361

ABSTRACT

Hybrid test dummies provide a safe alternative to human subjects when investigating mechanisms of wheelchair tips and falls. The data that researchers acquire from these test dummies are more useful if the test dummy represents the population being studied. The goal of this study was to measure the validity of a 50th percentile Hybrid II test dummy (HTD) as an accurate representation of a wheelchair user. A test pilot with T8 paraplegia due to traumatic spinal cord injury served as a basis for validation. Simple modifications were made to the HTD to approximate the trunk stability characteristics of a person with a spinal cord injury. An HTD, a modified HTD, and a human test pilot were seated in an electric-powered wheelchair and several braking tests performed. The standard HTD underestimated the kinematics when compared to the test pilot. The modified HTD had less trunk stability than the standard HTD during all braking methods. The modified HTD and wheelchair test pilot had similar trunk stability characteristics during kill switch and joystick full-reverse braking conditions. The modified HTD is a satisfactory representation of a wheelchair user with a spinal cord injury; however, the modified test dummy underestimates the trunk dynamics during the less extreme joystick release braking. Work should continue on the development of a low-speed, low-impact test dummy that emulates the wheelchair user population.


Subject(s)
Wheelchairs , Biomechanical Phenomena , Biomedical Engineering , Biophysical Phenomena , Biophysics , Human Experimentation , Humans , Models, Biological , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/rehabilitation , Wheelchairs/adverse effects
11.
Med Eng Phys ; 23(4): 267-73, 2001 May.
Article in English | MEDLINE | ID: mdl-11427364

ABSTRACT

GAME(Wheels) is an interface between a portable roller system and a computer that enables a wheelchair user to play commercially available computer video games. The subject controls the game play with the propulsion of their wheelchair's wheels on the rollers. The purpose of this study was to investigate whether using the GAME(Wheels) System during wheelchair propulsion exercise can help increase the individual's physiological response and aid in the motivation to exercise. Fifteen subjects participated in this study. The subjects propelled their wheelchairs on a portable roller that was equipped with the GAME(Wheels) System. There were two exercise trials consisting of 2 min of warm-up, 16 min of exercise and 2 min of cool-down. Physiological data (ventilation rate, oxygen consumption, heart rate) were collected. A significant difference (P<0.05) was found between exercise with GAME(Wheels) versus without GAME(Wheels) for average ventilation rate and average oxygen consumption. The differences were found during time periods of transition from warm-up to exercise, and before and after the midpoint of exercise. Written questionnaires showed that 87% of the individuals tested reported the system would help them work out on a regular basis. Playing the video game helped these individuals to reach their exercise training zone faster and maintain it for the entire exercise trial.


Subject(s)
Exercise , Motivation , Video Games , Wheelchairs , Adult , Computers , Ergonomics , Female , Heart Rate , Humans , Male , Metabolism , Oxygen Consumption , Respiration , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/psychology , Spinal Cord Injuries/rehabilitation
12.
Life Sci ; 68(12): 1367-82, 2001 Feb 09.
Article in English | MEDLINE | ID: mdl-11388689

ABSTRACT

The substituted amphetamine 3,4 methylenedioxyamphetamine (MDA) is a popular recreational drug of abuse. Administration of MDA to experimental animals has been shown to induce damage to serotonergic axons and nerve terminals. However, there is a lack of information on whether these treatments can produce any long-term changes in behavioural performance particularly under stressful conditions. In the present study, MDA (7.5 mg/kg; i.p.) was administered twice daily to adult male Sprague Dawley rats for four days. Four weeks following the last dose, spontaneous behaviors of these animals were tracked and scored in a novel "open field" environment using an automated video registration and computer interpretation system. Changes in behavior were observed in MDA treated animals including reductions in exploratory oriented behaviors (locomotion and rearing) and increases in grooming behavior when compared to vehicle treated controls. MDA-treated animals also displayed an enhanced locomotor and stereotyped response to d-amphetamine (12 mg/kg; i.p.). Significant reductions in 5-HT concentrations (20-30%) were observed in the frontal cortex, amygdala, striatum, and hypothalamus as a result of MDA treatment. In addition, [3H] paroxetine binding was reduced by (40%) in the cortex of MDA treated rats indicating that the decrease in 5-HT concentrations were accompanied by a reduction in intact presynaptic 5-HT nerve terminals. Changes in behavioural performance in a novel "open field" environment and following d-amphetamine challenge might be considered as a behavioural model of serotonergic deficit induced by MDA. The findings of this study also suggest that MDA use may increase both the abuse potential, and the propensity to develop psychosis as a result of abusing other psychostimulants such as d-amphetamine.


Subject(s)
Dextroamphetamine/pharmacology , Exploratory Behavior/drug effects , Hallucinogens/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Presynaptic Terminals/drug effects , Serotonin/metabolism , Animals , Brain/metabolism , Disease Models, Animal , Hallucinogens/administration & dosage , Injections, Intraperitoneal , Male , Maze Learning/drug effects , Motor Activity/drug effects , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , Paroxetine/metabolism , Presynaptic Terminals/metabolism , Rats , Rats, Sprague-Dawley , Video Recording
13.
Arch Phys Med Rehabil ; 82(5): 702-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11346854

ABSTRACT

OBJECTIVE: To evaluate a novel pushrim-activated, power-assisted wheelchair (PAPAW) for compliance with wheelchair standards, metabolic energy cost during propulsion, and ergonomics during selected activities of daily living (ADLs). DESIGN: A 3-phase study, the second and third of which were repeated-measures designs. SETTING: A rehabilitation engineering center within a Veterans Affairs medical center. PATIENTS: Eleven full-time, community-dwelling, manual wheelchair users (4 women, 6 men) with spinal cord injuries or multiple sclerosis. INTERVENTIONS: Phase 1: Compliance testing, with a test dummy, in accordance with the wheelchair standards of the American National Standards Institute and the Rehabilitation Engineering and Assistive Technology Society of North America. Phase 2: Metabolic energy consumption testing-at 2 speeds and 3 resistance levels-in subjects' manual wheelchair and the PAPAW. Phase 3: Evaluation of ability to perform ADLs and ergonomics of the PAPAW compared with the subjects personal wheelchair. MAIN OUTCOME MEASURES: Phase 1: The PAPAW's static stability, static strength, impact strength, fatigue strength, environmental response, obstacle climbing ability, range, maximum speed, and braking distance. Phase 2: Subjects' oxygen consumption per minute, minute ventilation, and heart rate during different speeds and workloads with a PAPAW and their own wheelchairs. Phase 3: Subject ratings of perceived comfort and basic ergonomics while performing selected ADLs. Completion time, stroke frequency, and heart rate during each ADL. RESULTS: Phase 1: The PAPAW was found to be in compliance with wheelchair standards. Phase 2: With the PAPAW, the user had a significantly lower oxygen consumption (&Vdot;O(2)mL/min: p <.0001; &Vdot;O(2)mL/kg x min: p <.0001) and heart rate (p <.0001) when compared with a manual wheelchair at different speeds. Phase 3: The PAPAW had a significantly higher mean ergonomic evaluation (p <.01) than the subjects' personal wheelchairs. The results of comparing the ratings of the car transfer between the PAPAW and the subjects' personal wheelchair showed a significant difference in the task of taking the wheels off (p <.001) and putting the wheels back on (p =.001), with the PAPAW receiving lower ratings. CONCLUSION: This study indicated that the PAPAW is compliant with wheelchair standards, reduces the energy demand placed on the user during propulsion, and that subjects rated its ergonomics favorably when compared with their personal wheelchair. PAPAWs may provide manual wheelchairs with a less physiologically stressful means of mobility with few adaptations to the vehicle or home environment.


Subject(s)
Wheelchairs/standards , Adult , Durable Medical Equipment/standards , Energy Metabolism , Equipment Design , Equipment Safety/standards , Female , Humans , Male , Multiple Sclerosis/metabolism , Multiple Sclerosis/rehabilitation , Pilot Projects , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/rehabilitation
14.
Eur J Pharmacol ; 418(1-2): 147-52, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11334877

ABSTRACT

The purpose of the present study was to examine the role of serotonin release in methylenedioxymethamphetamine (MDMA)-induced immunosuppression in rats. We examined the effect of pretreatment with the selective serotonin reuptake inhibitor paroxetine, and the tryptophan hydroxylase inhibitor para-chlorophenylalanine on MDMA-induced suppression of interleukin-1beta and tumour necrosis factor (TNF)-alpha secretion following an in vivo lipopolysaccharide challenge. Although paroxetine blocked MDMA-induced serotonin depletion in the cortex and hypothalamus, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced TNF-alpha secretion. Similarly, although para-chlorophenylalanine caused a 90% depletion in cortical and hypothalamic serotonin content, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced interleukin-1beta or TNF-alpha secretion. In conclusion, although MDMA is a potent releaser of serotonin, the suppressive effects of MDMA on lipopolysaccharide-induced proinflammatory cytokine secretion cannot be attributed to its serotonin-releasing properties.


Subject(s)
Frontal Lobe/drug effects , Hypothalamus/drug effects , Interleukin-1/metabolism , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Serotonin/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Fenclonine/pharmacology , Frontal Lobe/metabolism , Hypothalamus/metabolism , Immunosuppression Therapy , Interleukin-1/blood , Lipopolysaccharides/pharmacology , Male , N-Methyl-3,4-methylenedioxyamphetamine/immunology , Paroxetine/pharmacology , Rats , Rats, Sprague-Dawley , Serotonin Antagonists/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology
15.
Life Sci ; 67(13): 1601-12, 2000 Aug 18.
Article in English | MEDLINE | ID: mdl-10983854

ABSTRACT

In this study we examined the effects of methylenedioxymethamphetamine (MDMA) administration on responsiveness to an in vivo immune challenge with lipopolysaccharide (LPS; 100 microg/kg; i.p.). LPS produced an increase in circulating IL-1beta and TNF-alpha in control animals. MDMA (20 mg/kg; i.p.) significantly impaired LPS-induced IL-1beta and TNF-alpha secretion. The suppressive effect of MDMA on IL-1beta secretion was transient and returned to control levels within 3 hours of administration. In contrast, the MDMA-induced suppression of TNF-alpha secretion was evident for up to 12 hours following administration. In a second study we examined the effect of co-administration of MDMA (5, 10 and 20 mg/kg; i.p.) on LPS-induced IL-1beta and TNF-alpha secretion, and demonstrated that all three doses potently suppressed LPS-induced TNF-alpha secretion, but only MDMA 10 and 20 mg/kg suppressed LPS-induced IL-1beta secretion. In addition, serum MDMA concentrations displayed a dose-dependent increase, with the concentrations achieved following administration of 5 and 10 mg/kg being in the range reported in human MDMA abusers. In order to examine the possibility that the suppressive effect of MDMA on IL-1beta and TNF-alpha could be due to a direct effect of the drug on immune cells, the effect of in vitro exposure to MDMA on IL-1beta and TNF-alpha production in LPS-stimulated diluted whole blood was evaluated. However IL-1beta or TNF-alpha production were not altered by in vitro exposure to MDMA. In conclusion, these data demonstrate that acute MDMA administration impairs IL-1beta and TNF-alpha secretion following an in vivo LPS challenge, and that TNF-alpha is more sensitive to the suppressive effects of MDMA than is IL-1beta. However the suppressive effect of MDMA on IL-1beta and TNF-alpha could not be attributed to a direct effect on immune cells. The relevance of these findings to MDMA-induced immunomodulation is discussed.


Subject(s)
Hallucinogens/toxicity , Immunosuppressive Agents/toxicity , Interleukin-1/metabolism , Lipopolysaccharides/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Tumor Necrosis Factor-alpha/metabolism , Animals , Dose-Response Relationship, Immunologic , Female , Hallucinogens/blood , Immunity, Cellular/drug effects , Immunosuppressive Agents/blood , Interleukin-1/blood , Lipopolysaccharides/antagonists & inhibitors , N-Methyl-3,4-methylenedioxyamphetamine/blood , Rats , Rats, Sprague-Dawley
16.
Physiol Behav ; 69(4-5): 531-9, 2000.
Article in English | MEDLINE | ID: mdl-10913793

ABSTRACT

The paradox that experiments in behavioural pharmacology employing nocturnal rodent species are carried out almost exclusively in the resting phase of the animals' circadian cycle has remained largely unexamined and unquestioned. This is despite the fact that all major physiological systems in the body are intrinsically aligned with its natural circadian rhythm. The forced-swim test (FST) is a rodent model that is used extensively as a screening test for antidepressant activity. The objectives of the present study were to examine the behaviour of rats in the FST under diurnal and nocturnal conditions and, in addition, to profile the response of neurochemical, neuroendocrine, and cellular indices of stress at time points up to 120 min following exposure to the FST. The time spent in escape-oriented activity was significantly less when animals were tested in the dark phase. The profile of serum corticosterone and adrenal ascorbic acid concentrations indicates that the animals were less stressed by the test situation during the active (i.e., dark) phase of their circadian cycle. Similarly, increases in blood enzymatic markers of stress-induced cellular damage were less marked following FST exposure in the nocturnal period. Characteristic stress-induced increases in 5-HT turnover in the frontal cortex and amygdala observed in the diurnal phase were reversed in the nocturnal period. In conclusion, circadian differences in behaviour in the FST may be related to parallel alterations in the ability of animals to adapt to exposure to stress.


Subject(s)
Behavior, Animal/physiology , Circadian Rhythm/physiology , Darkness , Light , Swimming/physiology , Adrenal Glands/metabolism , Alanine Transaminase/blood , Amygdala/metabolism , Analysis of Variance , Animals , Ascorbic Acid/metabolism , Aspartate Aminotransferases/blood , Blood Glucose , Brain Chemistry/physiology , Corticosterone/blood , Exercise Test , Frontal Lobe/metabolism , Hydroxyindoleacetic Acid/metabolism , Male , Phosphates/blood , Photoperiod , Rats , Rats, Sprague-Dawley , Serotonin/metabolism
17.
Pharmacol Biochem Behav ; 65(4): 591-7, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10764911

ABSTRACT

The purpose of the present study was to examine the effect of subchronic treatment (24 days) with antidepressants displaying differential effects on noradrenaline and serotonin reuptake, on behavior, neurochemistry, and hypothalamic-pituitary-adrenal (HPA) axis activity following FST exposure in the rat. Desipramine (7.5 mg/kg, IP) significantly decreased immobility in the FST, whilst paroxetine (7.5 mg/kg IP) and venlafaxine (10 mg/kg, IP) were without effect. Nonetheless, treatment with all three antidepressants significantly attenuated stress-related increases in amygdaloid and cortical serotonin turnover. Of the three antidepressants examined, only desipramine attenuated the stress-associated elevation in serum corticosterone. In conclusion, although FST-induced increases in serotonin turnover in the frontal cortex and amygdala were attenuated following treatment with all three antidepressants, FST-induced behavioral changes and increased HPA axis activity were normalized only following desipramine treatment. In addition, these results suggest that neurochemical mechanisms independent of increased serotonergic activity subserve the normalization of behavior and HPA axis responses in the FST. These data also add to our understanding of the interactions between antidepressants and stress-induced behavioral, neurochemical, and endocrine alterations, and illustrates important differences between classes of antidepressants.


Subject(s)
Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Brain Chemistry/drug effects , Depressive Disorder/psychology , Hormones/blood , Swimming/psychology , Amygdala/drug effects , Amygdala/metabolism , Animals , Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Biogenic Amines/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Corticosterone/blood , Cyclohexanols/pharmacology , Desipramine/pharmacology , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/physiology , Male , Motor Activity/drug effects , Paroxetine/pharmacology , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Venlafaxine Hydrochloride
18.
Article in English | MEDLINE | ID: mdl-10763376

ABSTRACT

The sequential tissue distribution of virus was investigated using virus isolation and immunofluorescence tests in 1-day-old piglets inoculated with porcine circovirus 2 (PCV2) and/or porcine parvovirus (PPV). Enlarged mesenteric lymph nodes were seen in the pig inoculated with PCV2 alone and killed at 26 days post-inoculation (PI). One of the pigs inoculated with PCV2 and PPV and killed at 21 days PI had an enlarged liver. The pig killed at 26 days PI in this group had enlarged liver, kidneys and heart. Histopathological changes were seen in lymphoid tissues of the pigs inoculated with PCV2 alone and killed at 14 and 26 days PI. Similar, but more severe, lesions were observed in the pigs infected with PCV2 and PPV and killed from 10 days PI onwards. Histological lesions of nephritis, pneumonia and hepatitis were also apparent in these animals. Mild nephritis was also seen in the pigs infected with PPV alone and killed at 14 and 26 days PI. Moderate amounts of PPV antigen were detected in tissues from the pigs inoculated with PPV alone and killed at 14 days PI. Low levels of PCV antigen were detected, mainly in lymphoid tissues, in the pigs inoculated with PCV alone and killed at 14 days PI. Low to moderate amounts of PCV antigen were detected in a wider range of tissues in the pig in this group killed at 26 days PI. In the pigs inoculated with both viruses, PPV antigen was detected in tissues of pigs killed from 3 to 26 days PI with maximal amounts detected between 6 and 14 days PI. PCV2 antigen was detected in low to moderate amounts in the tissues of pigs killed at 14 days PI. Large amounts of PCV2 antigen were detected in most of the tissues from pigs in this group killed between 17 and 26 days PI. Virus isolation results for PCV2 generally correlated well with the results for immunofluorescent staining. PPV was isolated from almost all tissues from pigs inoculated with PCV2 and PPV, a much higher incidence of positive tissues than observed for immunofluorescent staining.


Subject(s)
Circoviridae Infections/veterinary , Circovirus/isolation & purification , Parvoviridae Infections/veterinary , Parvovirus/isolation & purification , Swine Diseases/virology , Animals , Animals, Newborn , Antibodies, Monoclonal , Antibodies, Viral/blood , Antigens, Viral/analysis , Circoviridae Infections/pathology , Circoviridae Infections/virology , Circovirus/immunology , Fluorescent Antibody Technique, Indirect/veterinary , Hemagglutination Tests/veterinary , Hepatitis, Animal/virology , Lymph Nodes/virology , Nephritis/veterinary , Nephritis/virology , Parvoviridae Infections/pathology , Parvoviridae Infections/virology , Parvovirus/immunology , Pneumonia/veterinary , Pneumonia/virology , Random Allocation , Swine , Swine Diseases/pathology
19.
Immunopharmacology ; 46(3): 223-35, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10741902

ABSTRACT

The purpose of the present study was to examine the effect of the serotonin releasing amphetamine derivatives methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA) and fenfluramine (FEN) on immunity in rats. Similar to MDA and MDMA, FEN reduced the number of circulating lymphocytes, provoked a suppression of Con A-stimulated lymphocyte proliferation and total IFN-gamma and IL-10 production in diluted whole blood cultures. Thus the non-psychostimulant amphetamine derivative FEN, shares the ability of the psychostimulant methylenedioxy-substituted amphetamine derivatives to alter these indices of immune function in the rat. However, when Con A-stimulated cytokine production was normalised for the number of lymphocytes in culture in order to examine cytokine production at a cellular level, the effect of the amphetamine derivatives begins to diverge. FEN shares with MDMA and MDA the ability to suppress production of the Th2 type cytokine IL-10. However the effect of these drugs on Th1 type cytokine secretion was much more complex. While the methylendioxy-substituted amphetamines increases the secretion of the Th1 type cytokine IL-2 without altering the related Th1 type cytokine IFN-gamma, FEN did not alter IL-2 secretion, but suppressed IFN-gamma secretion. In addition to these effects on T-cell responses, all three drugs inhibited LPS-induced TNF-alpha secretion from diluted whole blood cultures suggesting that macrophage activity is impaired following treatment. In all, these data extend our previous findings concerning the effects of MDMA on the immune system and demonstrate that the related serotonin releasers MDA and FEN also provoke immunological changes in rats.


Subject(s)
3,4-Methylenedioxyamphetamine/pharmacology , Fenfluramine/pharmacology , Immunity/drug effects , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Serotonin Agents/pharmacology , Animals , Concanavalin A/pharmacology , Cytokines/biosynthesis , Female , Leukocyte Count , Lipopolysaccharides/pharmacology , Lymphocyte Activation/drug effects , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley
20.
Neurorehabil Neural Repair ; 14(1): 21-31, 2000.
Article in English | MEDLINE | ID: mdl-11228946

ABSTRACT

The sedentary lifestyle of many people with spinal cord injury (SCI) has lead to cardiovascular diseases being a major health concern. A suitable exercise program may help improve the SCI individual's cardiovascular fitness level. GAMEWheels is an interface between a custom wheelchair roller system and a computer that enables an individual to control computer video games by driving his or her wheelchair. The purpose of Phase 1 was to evaluate the design of the GAMEWheels system and to determine the type of computer video game that is likely to motivate wheelchair users to exercise. Phase 2 included physiologic testing of wheelchair users and the GAMEWheels system to investigate whether the system elicits an exercise training response. Thirty-five subjects were recruited to evaluate the GAMEWheels by playing three commercial computer games (Phase 1) and to identify the computer game that they would prefer to use when exercising. The feedback from Phase 1 was used with test subjects to verify that the GAMEWheels system elicits an exercise training effect (Phase 2). Phase 2 included 10 subjects using the GAMEWheels system to play Need for Speed II. During game play, physiologic data were collected and the subjects' oxygen consumption and heart rate were analyzed. Analysis showed that the GAMEWheels system induced nine subjects to reach their training zone, defined as 50% and 60% of their maximum oxygen consumption and heart rate, respectively. This study demonstrates that the GAMEWheels system elicits an exercise training response.


Subject(s)
Exercise Therapy , Spinal Cord Injuries/rehabilitation , User-Computer Interface , Video Games , Wheelchairs , Adult , Equipment Design , Humans , Male , Middle Aged , Motivation
SELECTION OF CITATIONS
SEARCH DETAIL
...