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Introduction: Recent research highlights the need for a correct instrument for monitoring the individual health status, especially in the elderly. Different definitions of biological aging have been proposed, with a consistent positive association of physical activity and physical fitness with decelerated aging trajectories. The six-minute walking test is considered the current gold standard for estimating the individual fitness status in the elderly. Methods: In this study, we investigated the possibility of overcoming the main limitations of assessing fitness status based on a single measure. As a result, we developed a novel measure of fitness status based on multiple fitness tests. In 176 Sardinian individuals aged 51-80 years we collected the results of eight fitness tests to measure participants' functional mobility, gait, aerobic condition, endurance, upper and lower limb strength, and static and dynamic balance. In addition, the participants' state of health was estimated through validated risk scores for cardiovascular diseases, diabetes, mortality, and a comorbidity index. Results: Six measures contributing to fitness age were extracted, with TUG showing the largest contribution (beta = 2.23 SDs), followed by handgrip strength (beta = -1.98 SDs) and 6MWT distance (beta = -1.11 SDs). Based on fitness age estimates, we developed a biological aging measure using an elastic net model regression as a linear combination of the results of the fitness tests described above. Our newly developed biomarker was significantly associated with risk scores for cardiovascular events (ACC-AHA: r = 0.61; p = 0.0006; MESA: r = 0.21; p = 0.002) and mortality (Levine mortality score: r = 0.90; p = 0.0002) and outperformed the previous definition of fitness status based on the six-minute walking test in predicting an individual health status. Discussion: Our results indicate that a composite measure of biological age based on multiple fitness tests may be helpful for screening and monitoring strategies in clinical practice. However, additional studies are needed to test standardisation and to calibrate and validate the present results.
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OBJECTIVE: Osteomyelitis is a relatively understudied disease with no standardized and evidence-based approach to treatment. We aimed to evaluate a cohort of patients with osteomyelitis, comparing the outcomes between intravenous (IV) and oral treatment. PATIENTS AND METHODS: We performed an observational retrospective study on osteomyelitis cases in adult patients seen for care between 2017 and 2019. We collected information on patient characteristics, microbiological etiology, infection treatment, and outcome. In addition, we divided osteomyelitis cases by antibiotic regimens [oral (OTG) vs. intravenous±oral (ITG)] and therapy durations to evaluate outcomes differences. RESULTS: A total of 235 episodes of osteomyelitis were evaluated, with a higher prevalence in male gender. Staphylococci, especially S. aureus, were the most common strains. Out of the 235 evaluated episodes, we selected 142 cases. Of these, 75 were treated with OTG and 67 with ITG. Gram-positive bacteria were the most frequent aetiological agents, with 81 isolates (61.8%). Full recovery was observed in 79 (55.6%) cases; of these, 36 (53.7%) were in the ITG and 43 (57.3%) in the OTG (p = 0.666). At the logistic regression, a polymicrobial infection [OR 4.16 (95%CI 1.28-13.4), p = 0.017] and a less than six weeks treatment duration [OR 4.24 (95%CI 1.38-5.43) p = 0.004] were significantly associated with a higher risk of treatment failure. CONCLUSIONS: Our study suggests that oral treatment efficacy is comparable to ITG therapy for osteomyelitis, confirming the most recent evidence suggesting that oral therapy is non-inferior to intravenous therapy to treat osteomyelitis.
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Infecções Bacterianas , Osteomielite , Administração Oral , Adulto , Antibacterianos , Infecções Bacterianas/tratamento farmacológico , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Estudos Retrospectivos , Staphylococcus aureusRESUMO
OBJECTIVE: To provide normative data for the Vestibulo-Masseteric Reflex (VMR) and Acoustic-Masseteric Reflex (AMR) in healthy subjects, stratified for age and gender. METHODS: A total of 82 healthy subjects (M:F 43:39, mean age 39.3⯱â¯18.4â¯years, range 13-79â¯years) underwent recording of click-evoked VMR and AMR (0.1â¯ms duration, 5â¯Hz frequency) from active masseter muscles. Masseter responses to uni- and bilateral stimulation were recorded in a zygomatic and a mandibular configuration, according to the position of the reference electrode. Stimulation intensity curves were recorded for each reflex in ten subjects (mean age 20.7⯱â¯8.1â¯years). Gender effect was investigated in 62 subjects and age effect was analyzed in six 10-subject groups aged from <25 to >65â¯years. Onset and peak latencies, interpeak intervals, raw and corrected amplitudes, latency and amplitude asymmetries were analyzed. RESULTS: VMR had a higher elicitation rate than AMR. For both reflexes, rates of elicitation, and corrected amplitudes were higher in the zygomatic configuration, and bilateral stimulation elicited larger responses. Best acoustic ranges of elicitation were 98-113â¯dB for AMR and 128-138â¯dB for VMR. Reflex latencies were shorter in females than males. Frequency and amplitude of VMR and AMR decreased substantially over 55â¯year olds. CONCLUSIONS: VMR and AMR can be easily performed in any clinical neurophysiology laboratory. SIGNIFICANCE: These reflexes can find application in the investigation of brainstem function in central neurological disorders.
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Fatores Etários , Músculo Masseter/fisiologia , Reflexo Acústico/fisiologia , Fatores Sexuais , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adolescente , Adulto , Idoso , Tronco Encefálico/fisiologia , Eletrodos Implantados , Eletromiografia/métodos , Feminino , Humanos , Masculino , Mandíbula , Pessoa de Meia-Idade , Adulto Jovem , ZigomaRESUMO
BACKGROUND: Sinonasal pathology in adults with Cystic Fibrosis (CF) is common but the extent of CT-abnormalities and symptoms of sinonasal disease in children with CF and the age of onset are less frequently studied. METHODS: In this observational, cross-sectional study 58 children with CF from two CF centres were included. All subjects completed a questionnaire regarding sinonasal symptoms, underwent a CT scan of the paranasal sinuses, and in each subject a culture of the upper airways was performed. Subjects were divided in 6 age cohorts (0-2, 3-5, 6-8, 9-11, 12-14 and 15-17years) and were divided into severe and mild CF based on their CFTR mutation. Opacification of the sinonasal system of the subjects was compared with opacification on MRI-scans of an age-matched control group without CF. RESULTS: Most frequently reported symptoms were nasal obstruction and posterior/anterior nasal discharge. Opacification was abundant in every age cohort of the study group and was significantly more compared to the control group. In patients with severe CF the opacification was higher than subjects with mild CF. Upper airway cultures showed predominantly Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. CONCLUSION: CT-abnormalities indicating sinonasal disease and symptoms are present from shortly after birth which may argue for a thorough examination of the upper airways in children with CF.
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Fibrose Cística , Haemophilus influenzae/isolamento & purificação , Obstrução Nasal , Seios Paranasais , Pseudomonas aeruginosa/isolamento & purificação , Sinusite , Staphylococcus aureus/isolamento & purificação , Tomografia Computadorizada por Raios X/métodos , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos Transversais , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Obstrução Nasal/diagnóstico , Obstrução Nasal/etiologia , Países Baixos/epidemiologia , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/microbiologia , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/microbiologia , Sinusite/fisiopatologia , Estatística como Assunto , Avaliação de Sintomas/métodosRESUMO
OBJECTIVE: For hip complaints in the paediatric population, it is common practice to acquire both anteroposterior (AP) and frog-leg lateral (FL) radiographs. This combination of views provides a high diagnostic yield, but also doubles radiation exposure. We investigated the diagnostic accuracy of obtaining a solitary FL view as compared to a combination of the AP and FL view. METHODS: Hip radiographs of 524 children (aged 2-15 years) referred for acute hip pain were retrospectively assessed by two independent radiologists. Cases of trauma, neuromuscular disorders or a history of known hip disease were excluded. Radiologists were blinded to the AP radiograph while assessing the solitary FL radiograph. We used Cohen's kappa test to calculate agreement between the assessment of both views and the solitary FL view. RESULTS: Agreement between the assessment of the solitary FL view and the combination of the AP and FL view was very high with a kappa value of 0.989. CONCLUSION: The diagnostic accuracy of the FL radiograph in cases of hip complaints in children is as high as the current standard employing both AP and FL views. Therefore a solitary FL radiograph appears sufficient. This practice would substantially reduce radiation exposure. KEY POINTS: ⢠Radiation exposure in children should be kept to a minimum. ⢠In paediatric hip radiography a solitary frog-leg lateral view suffices. ⢠This reduces radiation exposure and costs of imaging.
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Artralgia/diagnóstico por imagem , Artrografia/métodos , Articulação do Quadril/diagnóstico por imagem , Perna (Membro)/diagnóstico por imagem , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Adolescente , Artrografia/estatística & dados numéricos , Criança , Pré-Escolar , Epífises/diagnóstico por imagem , Feminino , Fêmur/diagnóstico por imagem , Humanos , Masculino , Variações Dependentes do Observador , Posicionamento do Paciente/métodos , Doses de Radiação , Estudos RetrospectivosRESUMO
Empirical literature has yielded a positive association between psychopathy levels and suicide attempts. This association is centred around impulsivity and disinhibitory facets of psychopathy, whereas suicide and emotional poverty remain independent. Evidence about the relation between suicide and psychopathy in mentally disordered offenders is not conclusive. The present work explores the relation between several measures of antisocial personality, suicide attempt and deliberate self mutilation in a sample of inmates from a forensic psychiatric hospital. Results support the association between disinhibitory aspects of personality and suicide in this population.
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Transtorno da Personalidade Antissocial/psicologia , Prisioneiros/psicologia , Automutilação/psicologia , Tentativa de Suicídio/psicologia , Adulto , Idoso , Transtorno da Personalidade Antissocial/complicações , Transtorno da Personalidade Antissocial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prisioneiros/estatística & dados numéricos , Testes Psicológicos , Automutilação/diagnóstico , Automutilação/epidemiologia , Automutilação/etiologia , Espanha , Tentativa de Suicídio/estatística & dados numéricosRESUMO
BACKGROUND AND AIMS: Ectopic artery calcification has been documented in women with postmenopausal osteoporosis, in whom an imbalance in the number of circulating osteoprogenitor cells (OPCs) has been identified. Circulating OPCs form calcified nodules in vitro; however, it remains unknown whether an association exists between the number of circulating OPCs and aortic calcifications. We investigated the relationship between OPCs and aortic calcifications in women with postmenopausal osteoporosis. METHODS AND RESULTS: The number of circulating OPCs was quantified by FACS analysis in 50 osteoporotic postmenopausal women. OPCs were defined as CD15-/alkaline-phosphatase(AP)+ cells coexpressing or not CD34. Participants underwent measurement of markers of bone metabolism, bone mineral density and abdominal aortic calcium (AAC) by 64-slice computed tomography. Patients with AAC were older, had lower 25(OH)vitamin D levels and higher circulating CD15-/AP+/CD34- cells than those without AAC. Significant correlates of AAC included age (rho = 0.38 p = 0.006), calcium (rho = 0.35 p = 0.01), 25(OH)vitamin D (rho = -0.31, p = 0.03) and the number of CD15-/AP+/CD34- cells (rho = 0.55 p < 0.001). In regression analyses, the log-transformed number of CD15-/AP+/CD34- cells was associated with the presence (OR = 6.45, 95% CI 1.03-40.1, p = 0.04) and severity (ß = 0.43, p < 0.001) of AAC, independent of age, 25(OH)vitamin D, calcium and other potential confounders. Patients with low 25(OH)vitamin D and high CD15-/AP+/CD34- cells had higher median AAC than other patients (1927/µL, 862-2714/µL vs 147/µL, 0-1665/µL, p = 0.003). CONCLUSION: In women with postmenopausal osteoporosis, the number of circulating CD15-/AP+/CD34- cells is significantly associated with increased aortic calcifications, that appear to be correlated also with reduced 25(OH)vitamin D levels.
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Estenose da Valva Aórtica/fisiopatologia , Valva Aórtica/patologia , Calcinose/fisiopatologia , Osteoblastos/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Células-Tronco/metabolismo , Idoso , Fosfatase Alcalina/sangue , Antígenos CD34/sangue , Aorta Abdominal/metabolismo , Aorta Abdominal/fisiopatologia , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Calcinose/complicações , Cálcio/sangue , Estudos Transversais , Feminino , Fucosiltransferases/sangue , Humanos , Antígenos CD15/sangue , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Pós-Menopausa , Análise de Regressão , Células-Tronco/citologia , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/fisiopatologiaRESUMO
The aim of this study was to quantify the error associated with the assessment of oxygen uptake (VO2) by heart rate (HR) monitoring in 15 athletes freely performing their training session. A laboratory-derived equation was used on the running track to calculate VO2 (VO2est) from HR. Oxygen uptake was also assessed by means of a portable gas analyzer (VO2real). Bland and Altman statistics were carried out in order to evaluate agreement between VO2real and VO2est. The excess in carbon dioxide production (CO2excess) was measured to test the hypothesis that the subject with the highest CO2excess had the highest VO2est - VO2real difference. VO 2real was on average 0.14 l x min (-1) below VO2est. The limits of agreement of this difference were between + 0.77 and - 0.48 l x min (-1). Thus, on average VO2real was overestimated by VO2est. Spearman non-parametric statistics found a significant correlation between CO2excess and VO2est - VO2real difference (R = 0.55, p = 0.031). This study demonstrates that the use of HR monitoring to assess VO2 during field training overestimates VO2real, especially when a substantial increase in CO2excess occurs. Therefore, this method should be used with care when an excessive amount of CO2 is produced as occurs in activities that involve the lactic acid anaerobic source of energy production.
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Exercício Físico/fisiologia , Frequência Cardíaca , Monitorização Ambulatorial , Consumo de Oxigênio , Adulto , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
Prolactin blood levels are modulated directly by CNS via the known tubero-infundibular dopaminergic neurons which exert an inhibitory action on lactotrope cells in the hypophysis. Prolactin is devoid of peripheral negative feedback and via lesser known central pathways (e.g., mesolimbic and mesocortical) might be further tuned by means of appropriate stimuli (e.g., addictive drugs, gambling, exercise and so forth). Therefore, a prolactin test can be utilised to obtain an objective index to assess the compliance to exercise in men. This index may be used to identify the most suitable athlete for a given sport and mainly to survey exercise as rewarding behaviour in trained people. Prolactin was assessed in male top world windsurfers (WS) and in a control group of non-windsurfer trained subjects (CS) during an exercise simulating marine windsurfing. The result was that prolactin levels decreased significantly in WS with respect to CS when compared with pre-test levels (WS: -22.7%; P<0.05).
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Dopamina/fisiologia , Exercício Físico , Neurônios/fisiologia , Prolactina/sangue , Esportes , Feminino , Humanos , Masculino , Educação Física e Treinamento , Recompensa , Fatores de TempoRESUMO
BACKGROUND: MxA is an antiviral protein exclusively induced by type I interferons (IFN) and some viruses, and MxA gene expression is one of the most appropriate markers for measuring the biologic activity of exogenous IFNbeta. METHODS: A new quantitative-competitive PCR method was used to quantify MxA mRNA in peripheral blood mononuclear cells of 99 treatment-naïve and 92 IFNbeta-treated patients with MS (22 Avonex, 17 Betaferon, and 53 Rebif-22). Every 3 months, IFNbeta-induced neutralizing antibodies (NAb) were evaluated in sera using a cytopathic effect assay. Three categories of patients were identified: NAb negative (NAb-), persistent NAb positive (NAb+, >or=2 consecutive positive samples), and isolated NAb+ (one positive sample). RESULTS: Treatment-naïve patients expressed detectable MxA mRNA levels (mean = 36 +/- 32 fg MxA/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH); range 1 to 160) and an upper normal threshold was established (mean + 3 SD = 132 fg MxA/pg GAPDH). IFNbeta-treated patients exhibited more than 11-fold higher levels (mean = 412 +/- 282 fg MxA/pg GAPDH; range 16 to 1,172). However, 17 patients did not exhibit an increase in MxA mRNA level; 15 of these 17 patients showed a concurrent Nab+ titer. Moreover, 13 were persistent NAb+. Isolated NAb+ patients did not show a decrease in bioavailability of IFNbeta (n = 9; mean = 567 +/- 366 fg MxA/pg GAPDH; range 83 to 1,120). In NAb- patients, bioavailability was comparable among the three different IFNbeta preparations 12 hours after injection. CONCLUSION: During IFNbeta therapy, the presence of NAb reduced or abolished bioavailability in a relevant percentage of patients. These data could be important for the early detection of patients with MS who are not responsive to IFNbeta therapy.
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Anticorpos/sangue , Interferon beta/imunologia , Esclerose Múltipla/imunologia , Disponibilidade Biológica , Proteínas de Ligação ao GTP/genética , Humanos , Interferon beta-1a , Interferon beta-1b , Interferon beta/farmacocinética , Interferon beta/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Proteínas de Resistência a Myxovirus , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/metabolismo , Valores de ReferênciaRESUMO
BACKGROUND: A field test consisting of 5 continuous runs at the maximum speed possible, playing the ball, starting from the centre line to the basket with a final shot, was studied in order to obtain an index of mechanical work efficiency in basketball players (micro-index=Jmec/Joxy) and evaluate the correlation between micro-index and velocity, acceleration, mechanical power and lactacid anaerobic capacity, respectively. METHODS: Eight male basketball players were studied; Jmec was the external mechanical work output obtained by means of a video image analysis software which gave the potential and the kinetic translational energies of athletes running and jumping and their velocity, acceleration and mechanical power. By means of a telemetric device (Kosmed K4), for measuring O2 consumption ( VO2), we obtained oxidative work (Joxy). By using this device we also assessed the excess of CO2, which was considered an index of lactacid anaerobic capacity. RESULTS: Non-parametric Spearman statistics revealed a significant correlation between mu index and mean velocity (p<0.01, r=0.90), acceleration (p<0.05, r=0.78), mechanical power (p<0.05 r=0.76) and CO2 excess (p<0.01, r=0.95). Consequently athletes who had the best index of mechanical efficiency also had the best biomechanical quality and the greatest lactacid anaerobic capacity. CONCLUSIONS: This study strongly supports the hypothesis that in basketball anaerobic capacity is important in achieving high values of speed, acceleration, mechanical power and endurance velocity.
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Limiar Anaeróbio/fisiologia , Basquetebol/fisiologia , Consumo de Oxigênio/fisiologia , Resistência Física/fisiologia , Aceleração , Adulto , Metabolismo Energético/fisiologia , Humanos , Cinética , Ácido Láctico/sangue , Masculino , Esforço Físico/fisiologia , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNbeta) products in patients with multiple sclerosis (MS). METHODS: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNbeta-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNbeta-1a (Avonex, n = 44) 30 microg intramuscularly once weekly, or IFNbeta-1a (Rebif, n = 36) 22 microg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 microg intramuscularly once or twice weekly. NABs were assessed using the cytopathic effect assay before treatment and every three months during treatment. Patients with two or more consecutive positive samples were considered to be persistent NAB positive (NAB+). RESULTS: At baseline, no patients were NAB+. NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex. Numbers of NAB+ patients observed were similar with intramuscular Rebif and with subcutaneous Rebif. CONCLUSION: The three IFNbeta preparations have different degrees of immunogenicity, with Betaferon producing the highest incidence of NABs and Avonex the lowest. These differences should be considered by neurologists when selecting treatment for their patients with MS because NABs can reduce both bioavailability and clinical efficacy of IFNbeta.
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Anticorpos/sangue , Interferon beta/imunologia , Esclerose Múltipla/imunologia , Testes de Neutralização , Adulto , Especificidade de Anticorpos/imunologia , Esquema de Medicação , Feminino , Humanos , Injeções Intramusculares , Injeções Subcutâneas , Interferon beta-1a , Interferon beta-1b , Interferon beta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológicoRESUMO
The case is reported of an athlete who, during an exercise test, had a complete atrioventricular block without symptoms of cardiac output failure. Heart rate, stroke index, cardiac index, and myocardial contractility were monitored during the episode by an impedance cardiograph. The most important findings of this report are the continuous increase in stroke index, which compensated for the lack of heart rate response, and the normal cardiac index values achieved during the exercise. This stroke index response was mainly due to an increase in myocardial contractility.
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Exercício Físico/fisiologia , Bloqueio Cardíaco/fisiopatologia , Hemodinâmica , Adulto , Teste de Esforço , Futebol Americano/fisiologia , Bloqueio Cardíaco/diagnóstico , Frequência Cardíaca , Humanos , Masculino , Contração Miocárdica/fisiologia , Volume SistólicoRESUMO
Synaptic plasticity was studied in the lateral vestibular nuclei (LVN) of the guinea pig in vivo. High frequency stimulation (HFS) of increasing or decreasing frequencies was applied to the ipsilateral vestibular nerve. Vestibular field potentials (VFPs) and extracellular single unit activity evoked in the LVN by electrical stimulation of the ipsilateral vestibular nerve, were analyzed before and after the application of different protocols of HFS. Results show that the monosynaptic component of the VFPs undergo long-term potentiation (LTP) with stimulation of 100 Hz applied for 20 s lower frequencies, applied for shorter periods, induce only a transient post-tetanic potentiation. This potentiation, although long lasting, is not permanent since it is susceptible of a reversal or cancellation by opposite patterns of HFS that determine a depression or depotentiation of the previously acquired potentiation. The results demonstrate that the plasticity phenomena that take place at the level of the LVN neurons are not steady but undergo continuous adjustment of their sign and gain depending on the variable flow of vestibular information that reach the nuclei from the labyrinthine receptors.
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Potenciação de Longa Duração/fisiologia , Inibição Neural/fisiologia , Núcleo Vestibular Lateral/fisiologia , Animais , Estimulação Elétrica , Potenciais Evocados Auditivos/fisiologia , Feminino , Cobaias , Masculino , Plasticidade Neuronal/fisiologia , Nervo Vestibulococlear/fisiologiaRESUMO
Intracellular expression of human myxovirus protein A (MxA) is exclusively induced by type I IFNs (IFNalpha,beta,omega) or by some viruses and it is strongly increased under IFN treatment. We set up an internally controlled quantitative-competitive polymerase chain reaction (qc-PCR) that quantifies MxA mRNA expressed in human peripheral blood mononuclear cells (PBMC). Our qc-PCR is accurate because the mean ratio of copy number estimated by qc-PCR to that quantified spectrophotometrically is 1.08+/-0.03, moreover it is repeatable with high sensitivity (1 fg MxA/pg GAPDH). MxA mRNA was tested in 47 Relapsing-Remitting Multiple Sclerosis (RR-MS) untreated patients and in 48 patients treated with one of the 3 IFNbeta licensed for MS (24 with Rebif, 14 with Avonex and 10 with Betaferon). All the 48 treated patients were negative to IFNbeta neutralising antibodies (NABs) as tested in our laboratory using a cytopathic assay (CPE). MxA mRNA levels were detectable in all untreated patients (mean 24+/-18 fg MxA/pg GAPDH) and significantly higher levels were found in all the treated patients 12 h after IFNbeta administration (mean 499+/-325 fg MxA/pg GAPDH); furthermore, the three types of IFNbeta showed comparable bioavailability. Our data indicate that the bioavailability of the three available types of IFNbeta can be evaluated by MxA qc-PCR.
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Proteínas de Ligação ao GTP , Interferon beta/farmacologia , Esclerose Múltipla/tratamento farmacológico , Reação em Cadeia da Polimerase/métodos , Proteínas/genética , Humanos , Leucócitos Mononucleares/imunologia , Esclerose Múltipla/imunologia , Proteínas de Resistência a Myxovirus , Biossíntese de Proteínas , RNA Mensageiro/biossíntese , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
The effects of lead exposure at low concentrations were evaluated by studying the post-rotatory nystagmus (PRN) in two groups of rats exposed for 3 months to 50 parts per million (ppm) of sodium acetate and 50 ppm of lead acetate, respectively, in the drinking water. Only animals treated with lead acetate showed changes of the PRN parameters which were significantly related to the concentration of lead in the blood and in brain structures. The patterns of PRN responses were characterized and classified into four types: progressively inhibitory (40%), prematurely inhibitory (25%), late inhibitory (25%), and excitatory-inhibitory (10%). No alterations of the PRN parameters were observed in the animals treated with sodium acetate. The results show that exposure to lead, even at low concentrations, impairs both sensory and motor functions. The findings also point out that the vestibular system and brain stem structures which generate and control the PRN represent targets of the action of this heavy metal. Finally, the results indicate that the evaluation of the vestibulo-ocular-reflex can provide a test suited for the screening of the neurotoxic effects of lead even in the absence of clinical signs typical of lead intoxication.
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Intoxicação do Sistema Nervoso por Chumbo/fisiopatologia , Chumbo/toxicidade , Neurotoxinas/toxicidade , Nistagmo Fisiológico/efeitos dos fármacos , Reflexo Vestíbulo-Ocular/efeitos dos fármacos , Núcleos Vestibulares/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Feminino , Intoxicação do Sistema Nervoso por Chumbo/patologia , Masculino , Nistagmo Fisiológico/fisiologia , Ratos , Ratos Long-Evans , Reflexo Vestíbulo-Ocular/fisiologia , Núcleos Vestibulares/patologia , Núcleos Vestibulares/fisiopatologia , Poluentes Químicos da Água/toxicidadeRESUMO
In the present study the possible derangement of the autonomic system and its influence in life threatening arrhythmias were analysed during paroxysmal activity. In hemispherectomized rats a paroxysmal activation of the hypothalamic and mesencephalic cardioarrhythmogenic triggers was performed by topical application of penicillin-G. Blood gas parameters and electrical activity of the thalamus, hypothalamus, vagal nerve fibre, ECG and arterial blood pressure were simultaneously monitored in basal conditions and repeated after the appearance of paroxysmal activity. Temporal correlation analysis was carried out. Results showed that during activation of these triggers, the spontaneous vagal nerve fibre activity significantly increased and triggered the appearance of cardiac arrhythmias which could become life threatening and induce animal death when blood gas and electrolytic parameters were simultaneously impaired. These experiments suggest that fatal evolution of the heart impairment is related not only to an autonomic cardiac trigger, but also to a concomitant metabolic derangement, which most likely shares the same autonomic origin.
Assuntos
Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Epilepsia/complicações , Epilepsia/fisiopatologia , Animais , Gasometria , Pressão Sanguínea , Eletrocardiografia , Eletroencefalografia , Eletrólitos/sangue , Feminino , Hipotálamo/fisiopatologia , Masculino , Mesencéfalo/fisiopatologia , Fibras Nervosas/fisiologia , Ratos , Ratos Wistar , Tálamo/fisiopatologia , Nervo Vago/fisiopatologiaRESUMO
Hemodynamic events leading to spontaneous postexertional vasovagal syncope are not completely understood because of the lack of beat-to-beat data. We report a case study of a young athlete who undergoes a syncopal episode during the recovery period following a maximal cycle-ergometer test. The episode was monitored by an impedance cardiograph which can gather noninvasively beat-to-beat the flow of heart rate (HR), stroke volume (SV), cardiac output (CO), diastolic filling rate (SV/DT), and myocardial contractility index (PEP/LVET). The most important findings of this report are the dramatic reduction of SV/DT preceding the syncope, the increment of SV together with the reduction of HR preceding and following the syncope, the prompt recovery of CO values after the syncopal episode despite the bradycardia, and the reduction of PEP/LVET after the syncope. This report confirms the importance of active recovery immediately after strenuous exercise and supports the hypothesis that the reduction of SV/DT in the presence of an inotropic stimulation can trigger the vasovagal reaction.
Assuntos
Parada Cardíaca/fisiopatologia , Hemodinâmica/fisiologia , Hóquei/fisiologia , Esforço Físico/fisiologia , Adolescente , Análise de Variância , Bradicardia/etiologia , Bradicardia/fisiopatologia , Débito Cardíaco/fisiologia , Volume Cardíaco/fisiologia , Cardiografia de Impedância , Diástole , Eletrocardiografia , Teste de Esforço , Frequência Cardíaca/fisiologia , Humanos , Masculino , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Síncope Vasovagal/etiologia , Síncope Vasovagal/fisiopatologia , Fatores de TempoRESUMO
The sensitivity and electrophysiological patterns of paroxysmal activity induced in different brain structures by topical application of penicillin-G were evaluated in the rat. Recordings were carried out in five groups of animals, in telencephalon, diencephalon, mesencephalon, rombencephalon and spinal cords. The following analysis were carried out: frequency distribution histograms, latency and time course duration of paroxysmal activity, duration and amplitude of epileptic bursts. The results obtained showed that the nervous structures tested with penicillin-G had a different epileptogenic sensitivity and response pattern which significantly changed along the cerebral cortex-spinal cord axis. The highest epileptic sensitivity was observed in somatosensory cortex (SI) at 500-600 microns depth; in the other cortical layers, a significant lenghtening in latency was observed. Among the other structures, the spinal cord seemed to be the most sensitive target to the epileptogenic action of penicillin-G, whereas in the remaining structures, sensitivity significantly decreased in rostro-caudal direction. As far as the features of the paroxysmal activity are concerned, significant differences among tested structures were observed. In particular, within the SI cortex, the main differences were represented by the gradual increase in burst frequency and voltage from the surface to the IVth layer and by their subsequent decrease in deeper layers (V-VI). In the diencephalon, the paroxysmal activity was similar to that observed in more superficial and deeper cortical layers even though epileptic bursts showed a lower amplitude. Mesencephalon and rombencephalon displayed a paroxysmal activity with a distinctive feature, characterized by long lasting bursts of low amplitude, although bulbar outbursts showed a shorter duration than the mesencephalic ones. In the spinal cord, the epileptiform activity displayed a different paroxysmal pattern, characterized by the longest duration and the highest amplitude. The different sensitivities of the investigated brain structures to penicillin-G and the characteristics of the induced paroxysmal activity have been extensively discussed.
Assuntos
Ventrículos Cerebrais/fisiopatologia , Convulsivantes/toxicidade , Epilepsias Parciais/fisiopatologia , Colículos Inferiores/fisiopatologia , Neurônios/fisiologia , Penicilina G/toxicidade , Córtex Somatossensorial/fisiopatologia , Medula Espinal/fisiopatologia , Teto do Mesencéfalo/fisiopatologia , Tálamo/fisiopatologia , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Epilepsias Parciais/induzido quimicamente , Colículos Inferiores/efeitos dos fármacos , Especificidade de Órgãos , Penicilina G/administração & dosagem , Ratos , Ratos Wistar , Córtex Somatossensorial/efeitos dos fármacos , Teto do Mesencéfalo/efeitos dos fármacos , Tálamo/efeitos dos fármacos , Ácido gama-Aminobutírico/fisiologiaRESUMO
Field tests were performed in 10 volleyball (VB) players (4 females and 6 males) in order to obtain an index of mechanical work efficiency (mu' = Wmec/Woxy) while athletes played a game. Wmec was the mechanical work output, obtained by means of home made video image analysis software, by summing potential, kinetic translational and kinetic rotational energies of running and jumping athletes. Woxy was the oxidative energy consumption obtained from O2 consumption (VO2) by a telemetry device (Cosmed K2) that also gave values of pulmonary ventilation (VE) and heart rate (HR). VB were studied at rest before a game (R), during attacking phases (A) and during defensive phases (D). At R were found: VE = 11 +/- 1 l x min(-1), HR = 78 +/- 7b x min(-1), VO2 = 3.71 +/- 1.1 ml x kg(-1) x min(-1), Woxy = 75.1 +/- 22.3 J x kg(-1) x min(-1). During A all variables increased: VE = 49 +/- 6l x min(-1), HR = 149 +/- 15 b x min(-1), VO2 = 23.1 +/- 3.3ml x kg(-1) x min(-1), Woxy = 482.8 +/- 69.0 J x kg(-1) x min(-1), and Wmec 275.5 +/- 57.0 J x kg(-1) x min(-1) with mu'=0.57 +/- 0.09. In D HR (-9%), VE, VO2 and Woxy (-18%) were reduced when compared to A, decreasing mu' to 0.21 +/- 0.05. On the other hand mu' was found higher than 0.25 during A indicating an anaerobic contribution to energy expenditure; in D the mu' lower than 0.25 indicated a restoration of anaerobic energy sources. It might be proposed that a greater difference in mu' values between A and D also means a higher anaerobic energy contribution to the volleyball game.