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INTRODUCTION: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. METHODS: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). RESULTS: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. CONCLUSIONS: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.
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Disfunción Cognitiva , Fragilidad , Torque teno virus , Femenino , Anciano , Humanos , Anciano de 80 o más Años , Fragilidad/epidemiología , Torque teno virus/fisiología , Viremia/complicaciones , Anciano Frágil/psicología , Evaluación Geriátrica , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/epidemiologíaRESUMEN
Formaldehyde (FA) is a high-volume production chemical manufactured worldwide to which many people are exposed to both environmentally and occupationally. FA was recently reclassified as a human carcinogen. Several epidemiological studies have revealed an increased risk of cancer development among workers exposed to FA. Although FA genotoxicity was confirmed in a variety of experimental systems, data from human studies are conflicting. The aim of the present study was to evaluate the occupational exposure to FA in a multistage approach relating the exposure with different biomarkers (dose and effect) and individual susceptibility. Air monitoring was performed to estimate the level of exposure to FA during shift work. Eighty-five workers from hospital anatomy-pathology laboratories exposed to FA and 87 controls were tested for cytogenetic alterations in lymphocytes (micronucleus, MN; sister-chromatid exchange, SCE) and T-cell receptor (TCR) mutation assay. The frequency of MN in exfoliated buccal cells, a first contact tissue was also assessed. Percentages of different lymphocyte subpopulations were selected as immunotoxicity biomarkers. The level of formic acid in urine was investigated as a potential biomarker of internal dose. The effects of polymorphic genes of xenobiotic metabolising enzymes and DNA repair enzymes on the endpoints studied were determined. The mean level of FA exposure was 0.38⯱â¯0.03â¯ppm. MN (in lymphocytes and buccal cells) and SCE were significantly increased in FA-exposed workers compared to controls. MN frequency positively correlated with FA levels of exposure and duration. Significant alterations in the percentage of T cytotoxic lymphocytes, NK cells and B lymphocytes were found between groups. Polymorphisms in CYP2E1, GSTP1 and FANCA genes were associated with increased genetic damage in FA-exposed subjects. The obtained information may provide new important data to be used by health and safety care programs and by governmental agencies responsible for setting the acceptable levels for occupational exposure to FA.
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Contaminantes Ocupacionales del Aire/análisis , Formaldehído/análisis , Mucosa Bucal , Neoplasias/epidemiología , Exposición Profesional/estadística & datos numéricos , Contaminantes Ocupacionales del Aire/toxicidad , Biomarcadores/metabolismo , Daño del ADN , Formaldehído/toxicidad , Humanos , Linfocitos , Pruebas de MicronúcleosRESUMEN
Amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric, emphathogenic, entactogenic, and hallucinogenic properties. Although most amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine ("ecstasy") represent well-recognized examples, the use of natural related compounds, namely cathinone and ephedrine, has been part of the history of humankind for thousands of years. Resulting from their amphiphilic nature, these drugs can easily cross the blood-brain barrier and elicit their well-known psychotropic effects. In the field of amphetamines' research, there is a general consensus that mitochondrial-dependent pathways can provide a major understanding concerning pathological processes underlying the neurotoxicity of these drugs. These events include alterations on tricarboxylic acid cycle's enzymes functioning, inhibition of mitochondrial electron transport chain's complexes, perturbations of mitochondrial clearance mechanisms, interference with mitochondrial dynamics, as well as oxidative modifications in mitochondrial macromolecules. Additionally, other studies indicate that amphetamines-induced neuronal toxicity is closely regulated by B cell lymphoma 2 superfamily of proteins with consequent activation of caspase-mediated downstream cell death pathway. Understanding the molecular mechanisms at mitochondrial level involved in amphetamines' neurotoxicity can help in defining target pathways or molecules mediating these effects, as well as in developing putative therapeutic approaches to prevent or treat the acute- or long-lasting neuropsychiatric complications seen in human abusers.
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Trastornos Relacionados con Anfetaminas/complicaciones , Mitocondrias/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Anfetaminas/administración & dosificación , Anfetaminas/farmacocinética , Anfetaminas/toxicidad , Animales , Barrera Hematoencefálica/metabolismo , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/farmacocinética , Estimulantes del Sistema Nervioso Central/toxicidad , Transporte de Electrón/efectos de los fármacos , Humanos , Síndromes de Neurotoxicidad/fisiopatologíaRESUMEN
OBJECTIVES: Studies on the use of intrathecal perfusion devices (IPD) are still limited and therefore the aim of this study is to access the infectious complications associated to these devices. MATERIALS AND METHODS: A retrospective analysis of 145 patients who had an IPD implanted at the Chronic Pain Unit of Hospital de São João over the last 20 years. Mean follow-up time was 7.24 years (range: 0.47-17.41 years). Intrathecal antispastic drug perfusion was used in 123 patients (84.8%) and intrathecal analgesia in 22 patients. RESULTS: A total of 19 (8.71%) infections involving the IPD were identified of which, 14 (6.4%) were surgical site infections (SSIs). Methicillin-sensitive Staphylococcus aureus was the most commonly isolated bacteria in this group. Superficial SSIs were treated with oral antibiotic treatment or local wound care, while in deep SSI the pump was removed. Meningitis was identified in 5 (2.3%) patients and was always preceded by deep surgical site infections, some of which were already being treated with intravenous antibiotics. Median time to meningitis development was 2.2 months (IQR 82.58 months), after the introduction of the pump. Pump removal with anti-biotherapy were the treatment of choice. One patient died of a septic shock with associated meningitis and urinary tract infection. CONCLUSIONS: As seen in this study, infectious complications following implantation of IPD are not uncommon and include a variety of microorganisms. Antibiotic therapy without pump removal may be enough for superficial surgical site infections, but our data suggests that pump removal is the treatment of choice for deep infections as the infection may proceed to meningitis.
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Analgésicos/efectos adversos , Baclofeno/efectos adversos , Inyecciones Espinales/efectos adversos , Espasticidad Muscular/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Infección de la Herida Quirúrgica/etiología , Adolescente , Adulto , Anciano , Niño , Dolor Crónico/complicaciones , Dolor Crónico/tratamiento farmacológico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Espasticidad Muscular/etiología , Manejo del Dolor , Infecciones Estafilocócicas/tratamiento farmacológico , Centros de Atención Terciaria , Adulto JovenRESUMEN
Postherpetic neuralgia is one of the most severe complications after herpes zoster infection. Patients who experience persistent pain despite conservative treatment may benefit from interventional therapies, such as spinal cord stimulation. We present the case of a patient with severe refractory postherpetic neuralgia in the right T8 to L1 distribution who responded effectively to spinal cord stimulation. After its implantation, the patient had improvements in pain intensity, pain-related interference, quality of life, and satisfaction, with a simultaneous reduction of previous medications. This case report highlights the role of spinal cord stimulation in refractory neuropathic pain secondary to herpes zoster.
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Neuralgia Posherpética , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Neuralgia Posherpética/terapia , Portugal , Masculino , Anciano , FemeninoRESUMEN
BACKGROUND: Persistent inflammation related to aging ("inflammaging") is exacerbated by chronic infections and contributes to frailty in older adults. We hypothesized associations between Toxoplasma gondii (T. gondii), a common parasite causing an oligosymptomatic unremitting infection, and frailty, and secondarily between T. gondii and previously reported markers of immune activation in frailty. METHODS: We analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) serointensity was measured with an enzyme-linked immunosorbent assay. The Fried criteria were used to define frailty status. Validated translations of Mini-Mental State Examination, Geriatric Depression Scale, and the Charlson Comorbidity Index were used to evaluate confounders. Previously analyzed biomarkers that were significantly associated with frailty in both prior reports and the current study, and also related to T. gondii serointensity, were further accounted for in multivariable logistic models with frailty as outcome. RESULTS: In T. gondii-seropositives, there was a significant positive association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for multiple successive confounders. Among biomarkers linked with frailty, kynurenine/tryptophan and soluble tumor necrosis factor receptor II were positively associated with T. gondii serointensity in seropositives (p < .05). Associations with other biomarkers were not significant. CONCLUSIONS: This first reported association between T. gondii and frailty is limited by a cross-sectional design and warrants replication. While certain biomarkers of inflammaging were associated with both T. gondii IgG serointensity and frailty, they did not fully mediate the T. gondii-frailty association.
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Fragilidad , Toxoplasma , Toxoplasmosis , Humanos , Femenino , Anciano , Masculino , Estudios Transversales , Inmunoglobulina G , Anticuerpos Antiprotozoarios , Biomarcadores , Inmunoglobulina M , Factores de RiesgoRESUMEN
Spontaneous intracranial hypotension (SIH) is a syndrome characterized by disabling orthostatic headache, due to reduced cerebrospinal fluid (CSF) volume probably caused by a CSF fistula. It affects mostly women of working-age, although it is probably underdiagnosed. The aim of this article is to present a practical approach to the diagnosis and treatment of SIH. After a description of its symptoms and signs, we present a step-by-step approach to the confirmation of the diagnosis and treatment, considering different clinical scenarios. This is intended to guide clinical decision making, through a systematized and individualized management, aimed at the best interest of the patient.
A hipotensão intracraniana espontânea (HIE) é uma síndrome caracterizada por cefaleia ortostática incapacitante, fruto de uma redução do volume de líquido cefalorraquidiano (LCR) provavelmente causada por uma fístula de LCR. Afeta sobretudo mulheres em idade ativa, estando provavelmente subdiagnosticada. Este protocolo visa apresentar uma proposta de abordagem prática ao diagnóstico e tratamento da HIE. Após uma secção descritiva das manifestações clínicas da HIE, apresentamos um modelo de atuação passo-a-passo para a confirmação do seu diagnóstico e tratamento, considerando diferentes cenários clínicos. Pretende-se, assim, facilitar a decisão clínica através de uma conduta sistematizada e individualizada, visando o melhor interesse do doente.
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Hipotensión Intracraneal , Humanos , Femenino , Masculino , Hipotensión Intracraneal/diagnóstico , Hipotensión Intracraneal/terapia , Hipotensión Intracraneal/etiología , Pérdida de Líquido Cefalorraquídeo/complicaciones , Cefalea/diagnóstico , Cefalea/etiología , Cefalea/terapia , Síndrome , Toma de Decisiones Clínicas , Imagen por Resonancia MagnéticaRESUMEN
Ageing is accompanied with a decline in several physiological systems. Frailty is an age-related syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalisation, and death in older adults. The aim of this study was to understand the relationship between frailty syndrome, immune activation, and oxidative stress. Serum concentrations of vitamins A and E were also evaluated, as well as inflammatory biomarkers (CRP and IL-6) and oxidative DNA levels. A group of Portuguese older adults (≥65 years old) was engaged in this study and classified according to Fried's frailty phenotype. Significant increases in the inflammatory mediators (CRP and IL-6), neopterin levels, kynurenine to tryptophan ratio (Kyn/Trp), and phenylalanine to tyrosine ratio (Phe/Tyr), and significant decreases in Trp and Tyr concentrations were observed in the presence of frailty. IL-6, neopterin, and Kyn/Trp showed potential as predictable biomarkers of frailty syndrome. Several clinical parameters such as nutrition, dependency scales, and polypharmacy were related to frailty and, consequently, may influence the associations observed. Results obtained show a progressive immune activation and production of pro-inflammatory molecules in the presence of frailty, agreeing with the inflammageing model. Future research should include different dimensions of frailty, including psychological, social, biological, and environmental factors.
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BACKGROUND: Neuropathic pain is a complex condition that is difficult to control and has a high impact on quality of life. 8% Capsaicin patch can be a therapeutic strategy in the treatment of peripheral neuropathic pain. OBJECTIVES: This study aims to (1) evaluate clinical efficacy and (2) tolerability of 8% capsaicin patch in a Pain Unit. STUDY DESIGN: Retrospective observational study. SETTING: Portuguese Pain Unit. METHODS: A sample of 120 patients diagnosed with peripheral neuropathic pain, underwent treatment with the 8% capsaicin patch between February 2011 and February 2019 in a Portuguese Pain Unit. Patients were included in one of the following groups according to the etiology of pain: postherpetic neuralgia (PHN), chronic post-surgical pain (CPSP), post traumatic neuropathic pain (PTNP), diabetic neuropathy (DN), regional pain syndrome. complex I and II (CRPS I / II), HIV-associated neuropathy (HIVN), lumbar neuropathic pain (LNP), trigeminal neuralgia (TN) and other neuropathies (O). The evaluated parameters were: pain intensity according to unit protocol (numerical rating scale), pain characteristics, location, size of the painful area. The evolution of pain intensity after treatment (patients were considered as responders to therapy if the decrease in NRS was equal to or greater than 30%; patients with a decrease in NRS of 50% or more were also analyzed), the area of pain and the need for adjuvant analgesic therapy, as well as the tolerability to treatment and the identification of eventual predictors of its efficacy were evaluated, at 15 days, 8 weeks and 12 weeks after 8% capsaicin patch. RESULTS: Of the 120 patients in the sample, 40.8% had a >= 30% decrease in basal pain intensity 15 days after treatment, 43.3% after 8 weeks and 45.0% after 12 weeks. 30.8% of patients had >= 50% decreased basal pain intensity 15 days after treatment, 27.5% after 8 weeks and 30.0% after 12 weeks. Pain area decreased in 36.7% of patients and 18.3% reduced chronic analgesic therapy within 12 weeks after 8% capsaicin patch application. There was only one case of intolerance to the treatment. LIMITATIONS: This study has the limitations inherent to a retrospective study. The study period was only 12 weeks and some diagnostic groups included a small number of patients. CONCLUSION: Treatment of peripheral neuropathic pain with 8% capsaicin patch seem to be effective in the short and medium term, both in decreasing pain intensity and in reducing the painful area. Its application is tolerated by most patients.
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Capsaicina/administración & dosificación , Neuralgia/tratamiento farmacológico , Manejo del Dolor/métodos , Parche Transdérmico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Dolor Crónico/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Frailty is an age-related syndrome expected to increase over the next decades. This syndrome has been identified to be the most common condition leading to disability, institutionalisation and death in the elderly. The aim of this pilot study is to investigate a possible link between frailty status, biomarkers and environmental exposures. A group of 71 older adults (≥65 years old) was engaged in this study. The study population was classified as 45.1% robust, 45.1% pre-frail and 9.8% frail. A significant higher prevalence of second-hand smokers was found in the pre-frail group when compared to robust. Furthermore, a higher prevalence of robust individuals was found among those consuming home-produced vegetables and water from well/springs. Significant differences were found between data collected in a lifetime exposure questionnaire (LTEQ) and the levels of genotoxicity endpoints and the mercury levels analysed regarding some exposure-related parameters, namely, smoking habits, intake of home-produced vegetables and the use of pesticides in agriculture. Understanding if the way we live(d) or worked can impact the way we age are important questions to be explored. Data obtained in this pilot study encourage further studies on this matter, exploring the role of exposures history and its impact on health.
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INTRODUCTION: Spasticity is a complex problem in patients with neurological disorders and may distress their quality of life. Intrathecal baclofen infusion pumps reduce spasticity with low doses and minimal side effects but are not free from complications. We aimed to evaluate the efficacy and safety of intrathecal baclofen infusion pumps as well as patients' satisfaction. MATERIAL AND METHODS: Retrospective cohort study including all intrathecal baclofen infusion pumps placed up to December 2015. Demographic characteristics, clinical diagnoses, date of placement or withdrawal/replacement of intrathecal baclofen infusion pumps, baclofen dosage and complications of intrathecal baclofen infusion pumps were collected. Assessments from the Ashworth and Penn's scales, Katz index and patients' global satisfaction were analysed. RESULTS: In 19 years we placed 251 intrathecal baclofen infusion pumps in 155 patients. The mean age was 41.1 ± 15.8 years. The most frequent conditions were: trauma (34%), cerebral palsy (14%), multiple sclerosis (12%) and stroke (12%). Eighty-five patients (55%) required a second pump, and eleven (7%) a third one. The lifetime of the first pump was 72 (36 - 89) and the total follow-up time was 96 (9 - 132) months. The causes of withdrawal/replacement were: battery failure (57%), catheter migration/kinking (24%), infection (14%) and pump displacement/exteriorization (7%). The complication rate was 0.21 events/month. There was a significant improvement in the Ashworth and Penn's scales after the placemen of intrathecal baclofen infusion pumps (p < 0.001 for all diagnoses) and the patients were satisfied with the treatment. DISCUSSION: The incidence of complications was within range of other international studies despite our long follow-up time. Events per month, loss to follow-up, re-intervention rate, incidence of infection and mortality were similar to other studies. CONCLUSION: Intrathecal baclofen infusion pumps are safe and effective in the treatment of spasticity. Infusion pumps provide a high level of satisfaction regarding treatment and quality of life.
Introdução: A espasticidade é um problema complexo em doentes com distúrbios neurológicos influenciando a sua qualidade de vida. As bombas perfusoras intratecais de baclofeno reduzem a espasticidade com doses baixas e efeitos laterais mínimos, mas não estão livres de complicações. Pretendemos avaliar a eficácia, segurança e satisfação dos doentes com bombas perfusoras intratecais de baclofeno. Material e Métodos: Estudo de coorte retrospetivo, incluindo todas as bombas perfusoras intratecais de baclofeno colocadas até dezembro de 2015. Foram avaliadas as características demográficas, diagnósticos, data de colocação ou retirada/substituição e complicações das bombas perfusoras intratecais de baclofeno. Analisaram-se as escalas Ashworth, Penn, Katz e satisfação dos doentes. Resultados: Durante 19 anos colocaram-se 251 bombas perfusoras intratecais de baclofeno em 155 doentes. A idade média foi 41,1 ± 15,8 anos. As patologias mais freqüentes foram: traumatismo (34%), paralisia cerebral (14%), esclerose múltipla (12%) e acidente vascular cerebral (12%). Oitenta e cinco doentes (55%) precisaram de uma segunda e onze (7%) de uma terceira bomba. A semi-vida da primeira bomba foi 72 (36 89) e o tempo total de seguimento 96 (9 132) meses. As causas de retirada/substituição foram: falha de bateria (57%), migração/kinking do cateter (24%), infeção (14%) e deslocamento/exteriorização da bomba (7%). A taxa de complicações foi 0,21 eventos/mês. Houve uma melhoria significativa nas escalas de Ashworth e Penn após colocação das bombas perfusoras intratecais de baclofeno (p < 0,001 para todos os diagnósticos) e os doentes ficaram satisfeitos com o tratamento. Discussão: A incidência de complicações situou-se dentro do intervalo reportado por outros estudos internacionais, apesar do longo tempo de seguimento. Número de eventos por mês, perda de seguimento, taxas de re-intervenção ou infecção e mortalidade foram semelhantes a outros estudos. Conclusão: As bombas perfusoras intratecais de baclofeno são seguras e eficazes no tratamento da espasticidade e oferecem um alto nível de satisfação quanto ao tratamento e qualidade de vida.
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Baclofeno/administración & dosificación , Bombas de Infusión , Relajantes Musculares Centrales/administración & dosificación , Espasticidad Muscular/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Remoción de Dispositivos , Falla de Equipo , Femenino , Estudios de Seguimiento , Humanos , Bombas de Infusión/efectos adversos , Bombas de Infusión/estadística & datos numéricos , Infusión Espinal/efectos adversos , Infusión Espinal/instrumentación , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Portugal , Estudios RetrospectivosRESUMEN
HIGHLIGHTS: Chronic anal fissure is a common condition associated with intense pain.Local botulinum toxin injection is a valid option in its management.Pain intensity scores significantly improved after BoNT injection.Side effects were rare and mild.Our results support the inclusion of BoNT in the management algorithm of chronic anal fissure. INTRODUCTION: Chronic anal fissure is a common condition associated with intense pain. Local botulinum toxin injection is a valid option in its management. The purpose of this study was to evaluate the efficacy of botulinum toxin on pain relief in chronic anal fissure patients. METHODS: We conducted a retrospective cohort study, involving 81 consecutive patients referred to a chronic pain management unit due to a chronic anal fissure for treatment with botulinum toxin, during a 4 year period. Data were collected from hospital records regarding pre-treatment and post-treatment pain (numeric rating scale), side effects, need for botulinum toxin reinjection and need for surgical treatment. We used standard statistical methods for inter (t-test and qui2) and intra-group (paired sample t-test) comparisons, according to variables distribution. RESULTS: Pain intensity rest score significantly improved after BoNT injection [variation: -4.2 ± 2.9 (p < 0.001)], as did pain post-defecation score [variation: -5.1 ± 3.0 (p < 0.001)]. 8.6% needed botulinum toxin reinjection and 23.5% were submitted to surgery. Side effects were reported in 8.6%. DISCUSSION: The efficacy of botulinum toxin use on pain reduction along with its non-permanent and minor side effects support its role in the resolution of chronic anal fissure. However, treatment failure in the long term is still significant. CONCLUSION: Botulinum toxin is effective on pain relief in patients with chronic anal fissure, which supports its inclusion in the management algorithm of this condition.
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BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a worldwide drug of abuse commonly used by adolescents. Most reports focus on MDMA's neurotoxicity and use high doses in adult animals, meanwhile studies in adolescents are scarce. We aimed to assess in rats the acute MDMA toxicity to the brain and peripheral organs using a binge dose scheme that tries to simulate human adolescent abuse. METHODS: Adolescent rats (postnatal day 40) received three 5 mg/kg doses of MDMA (estimated equivalent to two/three pills in a 50 kg adolescent), intraperitoneally, every 2 h, while controls received saline. After 24 h animal sacrifice took place and collection of brain areas (cerebellum, hippocampus, frontal cortex and striatum) and peripheral organs (liver, heart and kidneys) occurred. RESULTS: Significant hyperthermia was observed after the second and third MDMA doses, with mean increases of 1 °C as it occurs in the human scenario. MDMA promoted ATP levels fall in the frontal cortex. No brain oxidative stress-related changes were observed after MDMA. MDMA-treated rat organs revealed significant histological tissue alterations including vascular congestion, but no signs of apoptosis or necrosis were found, which was corroborated by the lack of changes in plasma biomarkers and tissue caspases. In peripheral organs, MDMA did not affect significantly protein carbonylation, glutathione, or ATP levels, but liver presented a higher vulnerability as MDMA promoted an increase in quinoprotein levels. CONCLUSIONS: Adolescent rats exposed to a moderate MDMA dose, presented hyperthermia and acute tissue damage to peripheral organs without signs of brain oxidative stress.
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Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , N-Metil-3,4-metilenodioxianfetamina/administración & dosificación , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Adenosina Trifosfato/sangre , Adenosina Trifosfato/metabolismo , Factores de Edad , Animales , Relación Dosis-Respuesta a Droga , Fiebre/sangre , Fiebre/inducido químicamente , Alucinógenos/administración & dosificación , Alucinógenos/toxicidad , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Amphetamine-type psychostimulants (ATS), such as amphetamine (AMPH), 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) are psychoactive substances widely abused, due to their powerful central nervous system (CNS) stimulation ability. Young people particularly use ATS as recreational drugs. Moreover, AMPH is used clinically, particularly for attention deficit hyperactivity disorder, and has the ability to cause structural and functional brain alterations. ATS are known to interact with monoamine transporter sites and easily diffuse across cellular membranes, attaining high levels in several tissues, particularly the brain. Strong evidence suggests that ATS induce neurotoxic effects, raising concerns about the consequences of drug abuse. Considering that many teenagers and young adults commonly use ATS, our main aim was to review the neurotoxic effects of amphetamines, namely AMPH, MDMA, and METH, in the adolescence period of experimental animals. Reports agree that adolescent animals are less susceptible than adult animals to the neurotoxic effects of amphetamines. The susceptibility to the neurotoxic effects of ATS seems roughly located in the early adolescent period of animals. Many authors report that the age of exposure to ATS is crucial for the neurotoxic outcome, showing that the stage of brain maturity has a strong importance. Moreover, recent studies have been undertaken in young adults and/or consumers during adolescence that clearly indicate brain or behavioural damage, arguing for long-term neurotoxic effects in humans. There is an urgent need for more studies during the adolescence period, in order to unveil the mechanisms and the brain dysfunctions promoted by ATS.
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Trastornos Relacionados con Anfetaminas/complicaciones , Anfetaminas/toxicidad , Estimulantes del Sistema Nervioso Central/toxicidad , Sistema Nervioso/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Adolescente , HumanosRESUMEN
Tetanus remains a serious problem in public health, particularly in developing countries, despite efficient prevention programs. A retrospective study was conducted at an infectious diseases intensive care unit during 1998-2003 involving patients admitted with grade III tetanus. The aim of the study was to evaluate the efficacy and safety of intrathecal baclofen for the treatment of tetanus. Lumbar puncture was performed, and a subarachnoid catheter was inserted for drug administration. An intrathecal bolus of baclofen was followed by a continuous infusion of 20 microg/h, until a maximum daily dose of 2 mg was provided. Twenty-two patients were treated overall. Control of the symptoms was achieved in all patients but one. Seven patients had colonization of the catheter, and 1 patient developed meningitis. All patients except one recovered. In our study, this means of treatment was efficacious and well tolerated.