RESUMO
Introduced species represent a threat to native wildlife worldwide, due to predation, competition, and disease transmission. Concurrent introduction of parasites may also add a new dimension of competition, i.e. parasite-mediated competition, through spillover and spillback dynamics. Urban areas are major hotspots of introduced species, but little is known about the effects of urban habitat structure on the parasite load and diversity of introduced species. Here, we investigated such environmental effects on the ectoparasite load, richness, and occurrence of spillback in two widespread invasive parakeets, Psittacula krameri and Myiopsitta monachus, in the metropolitan area of Rome, central Italy. We tested 231 parakeets and found that in both species parasite load was positively influenced by host abundance at local scale, while environmental features such as the amount of natural or urban habitats, as well as richness of native birds, influenced parasite occurrence, load, and richness differently in the two host species. Therefore, we highlight the importance of host population density and habitat composition in shaping the role of introduced parakeets in the spread of both native and introduced parasites, recommending the monitoring of urban populations of birds and their parasites to assess and manage the potential occurrence of parasite-mediated competition dynamics as well as potential spread of vector-borne diseases.
Assuntos
Doenças das Aves/parasitologia , Doenças das Aves/transmissão , Espécies Introduzidas , Carga Parasitária , Psittacula/parasitologia , Animais , Ecossistema , Especificidade de Hospedeiro , Itália , Parasitos/classificação , Parasitos/isolamento & purificação , Densidade DemográficaRESUMO
BACKGROUND: Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course. OBJECTIVE: To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation. METHODS: One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded. RESULTS: High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8. CONCLUSION: IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.
Assuntos
Doenças Desmielinizantes/líquido cefalorraquidiano , Progressão da Doença , Inflamação/líquido cefalorraquidiano , Interleucina-8/líquido cefalorraquidiano , Adulto , Biomarcadores/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Masculino , Esclerose Múltipla Crônica Progressiva/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidianoRESUMO
BACKGROUND: Predictive markers of cardiac side effects would be helpful for the stratification and individualized monitoring of multiple sclerosis (MS) patients prescribed with fingolimod. OBJECTIVE: To test whether the autonomic balance predicts a cardiac response after the first dose of fingolimod. METHODS: A total of 55 consecutive relapsing-remitting MS (RRMS) patients underwent 'head-up tilt', Valsalva maneuver, deep breathing and handgrip tests before their first dose of fingolimod. The normalized unit of the high frequency (HF) component (HF normalized units; HFnu), reflecting mostly vagal activity; and the low frequency (LF) component (LF normalized units; LFnu) reflecting mostly sympathetic activity, were considered for the analysis of heart rate (HR) variability. The patients' HR and electrocardiographic parameters ((the interval between P wave and ventricular depolarization (PR); the interval between Q and T waves (QT)) were recorded during 6-hour post-dose monitoring. RESULTS: We found significant correlations between measures of parasympathetic function and fingolimod-induced bradycardia. Subjects with higher Valsalva ratio and HR variation during deep breathing had, in fact, nadir HR ≤ 50 beats/minute (bpm) after the first fingolimod dose. Conversely, significant negative correlations were found between measures of sympathetic function and fingolimod-induced PR interval increase. Subjects with lower LFnu at rest and less increase of blood pressure on the handgrip test showed a PR interval increase > 20 ms after fingolimod. CONCLUSIONS: Assessing autonomic control of cardiovascular functions can be useful to predict cardiac effects after the first fingolimod dose.
Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Cloridrato de Fingolimode/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Sistema Nervoso Autônomo/fisiologia , Bradicardia/induzido quimicamente , Feminino , Cloridrato de Fingolimode/administração & dosagem , Testes de Função Cardíaca , Frequência Cardíaca/fisiologia , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologiaRESUMO
BACKGROUND: Acute optic neuritis is often in association with multiple sclerosis (MS). Proinflammatory cytokines trigger neuronal damage in neuroinflammatory disorders but their role in optic neuritis is poorly investigated. OBJECTIVE: The objective of this work is to investigate the associations of intrathecal contents of proinflammatory cytokines with transient and persistent dysfunctions after optic neuritis. METHODS: In 50 MS patients followed for up to six months, cerebrospinal fluid (CSF) levels of IL-1ß, TNF and IL-8 were determined, along with clinical, neurophysiological and morphological measures of optic neuritis severity. RESULTS: Visual impairment, measured by high- and low-contrast visual acuity, and delayed visual-evoked potential (VEP) latencies were significantly correlated to IL-8 levels during optic neuritis. IL-8 at the time of optic neuritis was also associated with persistent demyelination and final axonal loss, inferred by VEP and optical coherence tomography measures, respectively. Contents of IL-8 were correlated to functional visual outcomes, being higher among patients with incomplete recovery. Multivariate analysis confirmed that IL-8 significantly predicted final visual acuity, at equal values of demographics and baseline visual scores. CONCLUSION: Our study points to IL-8 as the main inflammatory cytokine associated with demyelination and secondary neurodegeneration in the optic nerve after optic neuritis.
Assuntos
Interleucina-1beta/líquido cefalorraquidiano , Interleucina-8/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Neurite Óptica/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adulto , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/fisiopatologia , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Nervo Óptico/patologia , Neurite Óptica/complicações , Neurite Óptica/fisiopatologia , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity. METHODS: In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers. Forty active relapsing-remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12-18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. RESULTS: 62.5% of patients were relapse-free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post-natalizumab-GA therapy is not associated with clinical deterioration. CONCLUSIONS: Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting.
Assuntos
Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Peptídeos/uso terapêutico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Córtex Cerebral/patologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Acetato de Glatiramer , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Natalizumab , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Estudos Prospectivos , Recidiva , Medula Espinal/patologia , Estatísticas não Paramétricas , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Inflammation triggers secondary neurodegeneration in multiple sclerosis (MS). OBJECTIVES: It is unclear whether classical anti-inflammatory cytokines have the potential to interfere with synaptic transmission and neuronal survival in MS. METHODS: Correlation analyses between cerebrospinal fluid (CSF) contents of anti-inflammatory cytokines and molecular, imaging, clinical, and neurophysiological measures of neuronal alterations were performed. RESULTS: Our data suggest that interleukin-13 (IL-13) plays a neuroprotective role in MS brains. We found, in fact, that the levels of IL-13 in the CSF of MS patients were correlated with the contents of amyloid-ß(1-42). Correlations were also found between IL-13 and imaging indexes of axonal and neuronal integrity, such as the retinal nerve fibre layer thickness and the macular volume evaluated by optical coherence tomography. Furthermore, the levels of IL-13 were related to better performance in the low-contrast acuity test and Multiple Sclerosis Functional Composite scoring. Finally, by means of transcranial magnetic stimulation, we have shown that GABAA-mediated cortical inhibition was more pronounced in patients with high IL-13 levels in the CSF, as expected for a neuroprotective, anti-excitotoxic effect. CONCLUSIONS: The present correlation study provides some evidence for the involvement of IL-13 in the modulation of neuronal integrity and synaptic function in patients with MS.
Assuntos
Interleucina-13/líquido cefalorraquidiano , Córtex Motor/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Degeneração Neural/imunologia , Neurônios/imunologia , Adulto , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Sensibilidades de Contraste , Avaliação da Deficiência , Potencial Evocado Motor , Feminino , Humanos , Itália , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Córtex Motor/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Degeneração Neural/líquido cefalorraquidiano , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Degeneração Neural/prevenção & controle , Neurônios/patologia , Fragmentos de Peptídeos/líquido cefalorraquidiano , Transmissão Sináptica , Tomografia de Coerência Óptica , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
To correlate gene expression profiles to fundamental biological processes such as cell growth, differentiation and migration, it is essential to work at the single cell level. Gene expression analysis always starts with the relatively low efficient reverse transcription (RT) of RNA into complementary DNA (cDNA), an essential step as unprocessed RNAs will not be analysed further. In this paper, we present a novel method for RT that uses microfluidics to manipulate nanolitre volumes. We compare our method to conventional protocols performed in microlitre volumes. More specifically, reverse transcription was performed either in a polydimethylsiloxane (PDMS) rotary mixer or in a tube, using a single cell amount of mouse brain RNA (10 pg), and was followed by a template-switching PCR (TS-PCR) amplification step. We demonstrate that, using the microfluidic protocol, 74% of the genes expressed in mouse brain were detected, while only 4% were found with the conventional approach. We next profiled single neuronal progenitors. Using our microfluidic approach, i.e. performing cell capture, lysis and reverse transcription on-chip followed by TS-PCR amplification in tube, a mean of 5000 genes were detected in each neuron, which corresponds to the expected number of genes expressed in a single cell. This demonstrates the outstanding sensitivity of the microfluidic method.
Assuntos
Perfilação da Expressão Gênica , RNA Mensageiro/genética , Animais , Sequência de Bases , Encéfalo/metabolismo , Primers do DNA , Camundongos , Miniaturização , Reação em Cadeia da PolimeraseRESUMO
Proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß (IL1ß) regulate both excitatory and inhibitory synaptic transmission in the central nervous system. The interaction between IL1ß and endocannabinoid system (ECS) is also emerging, based on the evidence that IL1ß effects on striatal spontaneous excitatory and inhibitory postsynaptic currents are regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members of the ECS. Furthermore, IL1ß has also been shown to control the sensitivity of cannabinoid CB1 receptors controlling GABA transmission (CB1Rs(GABA)) in the striatum. To better detail the synaptic action of IL1ß, and to clarify its complex interaction with the ECS, here we investigated the possible interplay between IL1ß and CB1Rs controlling glutamate transmission (CB1Rs(glu)), other critical elements of the ECS. Our results show that the sensitivity of CB1Rs(glu) is fully blocked in the presence of IL1ß in corticostriatal brain slices, and that the protein kinase C/TRPV1 pathway is involved in this effect. IL1ß failed to modulate the sensitivity of glutamate synapses to the stimulation of GABAB receptors. We also provided evidence that IL1ß-CB1Rs(GABA) but not IL1ß-CB1Rs(glu) interaction is under the control of the brain-derived neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because BDNF gene partial deletion, pharmacological blockade of trkB and membrane cholesterol removal with methyl-ß-cyclodextrin all blocked IL1ß-mediated inhibition of CB1Rs(GABA) but left unaltered the sensitivity of CB1Rs(glu) to this cytokine. Our results provide further evidence that synaptic transmission and the ECS are regulated by IL1ß in the striatum.
Assuntos
Ácido Glutâmico/fisiologia , Interleucina-1beta/farmacologia , Neostriado/efeitos dos fármacos , Receptor CB1 de Canabinoide/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Dronabinol/análogos & derivados , Dronabinol/farmacologia , Fenômenos Eletrofisiológicos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Microdomínios da Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neostriado/metabolismo , Proteína Quinase C/genética , Proteína Quinase C/fisiologia , Receptores de GABA-B/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/fisiologiaRESUMO
BACKGROUND AND PURPOSE Alterations of glutamate-mediated synaptic transmission occur early during neuroinflammatory insults, and lead to degenerative neuronal damage in multiple sclerosis (MS) and also in experimental autoimmune encephalomyelitis (EAE), which is a murine model of MS. Fingolimod is an effective orally active agent for the treatment of MS, affecting lymphocyte invasion of the brain. However, it is still unclear if fingolimod can be neuroprotective in this disorder. EXPERIMENTAL APPROACH Using neurophysiological recordings and morphological evaluation of dendritic integrity, we evaluated the effects of oral fingolimod on the clinical score of EAE mice in order to determine whether the compound was associated with preservation of synaptic transmission. KEY RESULTS Oral fingolimod prevented and reversed the pre- and postsynaptic alterations of glutamate transmission in EAE mice. These effects were associated with a clear amelioration of the clinical deterioration seen in EAE mice, and with a significant inhibition of neuronal dendritic pathology. Fingolimod did not alter the spontaneous excitatory postsynaptic currents in control animals, suggesting that only the pathological processes behind the inflammation-induced defects in glutamate transmission were modulated by this compound. CONCLUSIONS AND IMPLICATIONS The beneficial effects of fingolimod on the clinical, synaptic and dendritic abnormalities of murine EAE might correlate with the neuroprotective actions of this agent, as observed in MS patients. LINKED ARTICLE This article is commented on by Gillingwater, pp. 858-860 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01612.x.
Assuntos
Encefalomielite Autoimune Experimental/fisiopatologia , Imunossupressores/farmacologia , Esclerose Múltipla/fisiopatologia , Propilenoglicóis/farmacologia , Esfingosina/análogos & derivados , Sinapses/efeitos dos fármacos , Animais , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Cloridrato de Fingolimode , Ácido Glutâmico/fisiologia , Glicoproteínas , Imunossupressores/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Peptídeos , Propilenoglicóis/uso terapêutico , Esfingosina/farmacologia , Esfingosina/uso terapêutico , Sinapses/fisiologia , Transmissão Sináptica/efeitos dos fármacosRESUMO
Different doses of propylene glycol were compared for lowering plasma NEFA concentration during restricted feed intake. Eight Holstein heifers, averaging 90 d prior to calving at initiation of the trial, were in a 4 x 4 Latin square design with 12-d periods. Heifers consumed alfalfa silage on an ad libitum basis during d 1 to 7 of each period. During d 8 to 12, heifers were gradually restricted to 50% of ad libitum intake. Heifers received an oral drench of 0, 296, 592, or 887 ml of propylene glycol once daily at 6 h prior to feeding on d 8 to 12. Propylene glycol linearly increased glucose and insulin and decreased BHBA and NEFA in blood. Quadratic effects of propylene glycol on plasma glucose, BHBA, and NEFA also occurred; response per milliliter of propylene glycol was greatest at the lowest dose. The highest dose of propylene glycol returned blood glucose, insulin, and NEFA concentrations to those prior to feed restriction. Ruminal acetate to propionate ratio decreased as propylene glycol dose was increased, indicating ruminal conversion of propylene glycol to propionate. A dose of 296 ml of propylene glycol was almost as effective as a dose of 887 ml in reducing lipid mobilization during restricted feed intake.
Assuntos
Bovinos/sangue , Privação de Alimentos , Propilenoglicóis/administração & dosagem , Ácido 3-Hidroxibutírico , Animais , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados/sangue , Feminino , Hidroxibutiratos/sangue , Insulina/sangue , Fígado/metabolismo , Gravidez , Propilenoglicol , Propilenoglicóis/farmacologia , Triglicerídeos/metabolismoRESUMO
Plasma glucose concentration during late gestation was thought to be important for the development of fatty liver near parturition. Thirteen multiparous cows were given a 1-L oral drench of propylene glycol once daily beginning 10 +/- 3.6 d prepartum until parturition. Eleven control cows received a 1-L water drench. Plasma glucose increased following propylene glycol administration. Plasma NEFA concentration was 403 and 234 microM, and plasma insulin concentrations were .354 and .679 ng/ml, for control cows and cows treated with propylene glycol measured from 1 to 7 d prepartum. Plasma NEFA tended to be lower in cows treated with propylene glycol from 1 to 21 d postpartum. Prepartum propylene glycol administration reduced hepatic triglyceride accumulation by 32 and 42% at 1 and 21 d postpartum, respectively. Prepartum plasma BHBA was reduced during propylene glycol administration. Prepartum plasma glucose, NEFA, BHBA, and insulin were strongly correlated with liver triglyceride at 1 d postpartum (r = -.49, .45, .36, and -.49, respectively). Pre- and postpartum DMI were not affected by treatment. Milk production and composition measured through 21 d postpartum were not different between groups.