Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice.

This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole+LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole+LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole+LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1ß, TNF-α, and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole+LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors.

Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice

This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole+LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole+LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole+LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1β, TNF-α, and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole+LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors.

Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke.

BACKGROUND AND OBJECTIVES: Despite a confirmed association between obstructive sleep apnea (OSA) and stroke, the pathogenesis of OSA in stroke has not been hitherto clarified. The aim of this study was to evaluate the relationship between respiratory abnormalities and atherogenic pro-inflammatory markers, interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in acute ischemic stroke patients. METHODS: Nocturnal polygraphy was performed in 50 consecutive patients with acute ischemic stroke in the first week after the event. Levels of inflammatory markers (IL-6, IL-1ß and TNF-α) were determined from morning blood samples and comparatively analyzed between cases with and without severe OSA and with age-matched controls. RESULTS: All patients with acute ischemic stroke, 31 men, mean age (64.3 ± 7.7 years), had apnea-hypopnea index (AHI) > 5 and 35 (70%) had severe OSA (AHI ≥ 30). Hypertension was more frequent in patients with severe OSA (85.7%) when compared to controls (40.0%) (P = 0.002). Stroke outcome, assessed by the Barthel index, tended to be more severe (P = 0.06) in cases with severe OSA. Patients with mild/moderate OSA and with severe OSA showed higher levels of IL-6 when compared to controls (P = 0.01 and P = 0.000, respectively). Among cases with acute stroke and severe OSA, IL-6 levels were correlated with lower oxyhemoglobin desaturation (r=-0.30; P = 0.001) and with the desaturation index (r = 0.15; P = 0.02). CONCLUSIONS: IL-6, an atherogenic marker, shows a commensurate increase in stroke patients with OSA. It is correlated with oxyhemoglobin desaturation and with desaturation index and may be a surrogate measure to evaluate continuous positive airway pressure therapy.

Clinical outcome after acute ischaemic stroke: the influence of restless legs syndrome.

BACKGROUND AND PURPOSE: the objective was to evaluate the presence of Restless Legs Syndrome (RLS) in acute stroke, its association with sleep disturbances and clinical outcome during long-term follow-up. METHODS: this was a longitudinal study (N = 96, 59 men, mean age 64.0 ± 8.9) of cases with acute ischaemic stroke. Patients were asked about the occurrence of RLS symptoms before the cerebrovascular event. RLS was diagnosed using the criteria established by the International RLS Study Group. Stroke outcome was estimated by the Barthel Index and the modified Rankin Scale. Daytime somnolence (Epworth Sleepiness Scale -ESS > 10), poor sleep quality (Pittsburgh Sleep Quality Index -PSQI > 5) and risk of obstructive sleep apnea (OSA) (Berlin questionnaire) were evaluated. RESULTS: twelve patients (12.5%) met the diagnostic criteria for RLS. All cases had symptoms of RLS before stroke. However, none of the cases had a previous medical diagnosis of RLS or were on use of specific medication. In only one case, a family history of RLS was found. In all patients, RLS symptoms started after the age of 40 (mean age 64 ± 6.7). Daytime sleepiness (44.8%) and poor quality sleep (62.8%) were present. Patients with RLS (12.5%) presented greater neck circumference (P = 0.04) and worse sleep quality (P = 0.007). Risk of OSA (56.2%) was associated with hypertension [OR = 0.12; CI=0.03-0.42]. Stroke outcome was significantly worse at three and 12 months (ancova, P < 0.005) in patients with RLS, remaining after adjustment for diabetes and body mass index (P < 0.05). CONCLUSIONS: patients with acute stroke and RLS have worse clinical outcome, at three and 12 months of follow-up.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease.

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients.

We have tested the hypothesis that restless leg syndrome (RLS) is related to quality of sleep, fatigue and clinical disability in multiple sclerosis (MS). The diagnosis of RLS used the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Fatigue was assessed by the Fatigue Severity Scale (FSS >27), quality of sleep by the Pittsburgh Sleep Quality Index (PSQI >6), excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS >10) and clinical disability by the Expanded Disability Status Scale (EDSS). Forty-four patients (32 women) aged 14 to 64 years (43 +/- 14) with disease from 0.4 to 23 years (6.7 +/- 5.9) were evaluated. Thirty-five were classified as relapsing-remitting, 5 as primary progressive and 4 as secondary progressive. EDSS varied from 0 to 8.0 (3.6 +/- 2.0). RLS was detected in 12 cases (27%). Patients with RLS presented greater disability (P = 0.01), poorer sleep (P = 0.02) and greater levels of fatigue (P = 0.03). Impaired sleep was present in 23 (52%) and excessive daytime sleepiness in 3 cases (6.8%). Fatigue was present in 32 subjects (73%) and was associated with clinical disability (P = 0.000) and sleep quality (P = 0.002). Age, gender, disease duration, MS pattern, excessive daytime sleepiness and the presence of upper motor neuron signs were not associated with the presence of RLS. Fatigue was best explained by clinical disability and poor sleep quality. Awareness of RLS among health care professionals may contribute to improvement in MS management.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients

We have tested the hypothesis that restless leg syndrome (RLS) is related to quality of sleep, fatigue and clinical disability in multiple sclerosis (MS). The diagnosis of RLS used the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Fatigue was assessed by the Fatigue Severity Scale (FSS >27), quality of sleep by the Pittsburgh Sleep Quality Index (PSQI >6), excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS >10) and clinical disability by the Expanded Disability Status Scale (EDSS). Forty-four patients (32 women) aged 14 to 64 years (43 ± 14) with disease from 0.4 to 23 years (6.7 ± 5.9) were evaluated. Thirty-five were classified as relapsing-remitting, 5 as primary progressive and 4 as secondary progressive. EDSS varied from 0 to 8.0 (3.6 ± 2.0). RLS was detected in 12 cases (27 percent). Patients with RLS presented greater disability (P = 0.01), poorer sleep (P = 0.02) and greater levels of fatigue (P = 0.03). Impaired sleep was present in 23 (52 percent) and excessive daytime sleepiness in 3 cases (6.8 percent). Fatigue was present in 32 subjects (73 percent) and was associated with clinical disability (P = 0.000) and sleep quality (P = 0.002). Age, gender, disease duration, MS pattern, excessive daytime sleepiness and the presence of upper motor neuron signs were not associated with the presence of RLS. Fatigue was best explained by clinical disability and poor sleep quality. Awareness of RLS among health care professionals may contribute to improvement in MS management.

Swallowing dysfunction in Wilson's disease: a scintigraphic study.

Although dysphagia is a common complaint of patients with Wilson's disease (WD) and pneumonia is an important cause of death in these patients, swallowing function remains an underinvestigated field in this condition. The aim of this study was to characterize swallowing dynamics in WD patients. Eight WD patients and 15 age-matched controls underwent scintigraphic evaluation of oral and pharyngeal deglutition. Patients had significantly slower oral transit (P = 0.008) and a greater percentage of oral residue (P = 0.006) when compared to controls. Two of eight patients were free of neurological symptoms at time of examination. Impaired oropharyngeal function was found in patients without dysphagia and without neurological symptoms. Our findings indicate that WD may present with objective swallowing dysfunction, even in the absence of neurological manifestations. Further studies are necessary to investigate the impact of this dysfunction on morbidity and mortality in WD.

Cortisol and dehydroepiandosterone sulfate plasma levels and their relationship to aging, cognitive function, and dementia.

We have studied the relationship between dehydroepiandrosterone sulfate (DHEAS), cortisol, and cognitive function in a population of demented patients (n=29), age-matched controls (n=46), and younger subjects (n=11). All were submitted to morning collection of blood for determination of plasma cortisol and DHEAS measured by 125I radioimmunoassay. DHEAS levels and cortisol/DHEAS ratios were significantly different among groups with higher DHEAS levels and lower cortisol/DHEAS ratios in younger people (Bonferroni p<.05). Cortisol levels were associated to the presence of dementia (Odds ratio=.93; 95% CI,.86-1.01). There was no difference between DHEAS levels of demented and age-matched controls; however, demented patients showed a trend for higher cortisol/DHEAS ratios than age-matched controls and the latter showed higher ratio values than younger subjects. DHEAS and cortisol plasma values were significantly correlated in all individuals (p<.01). In this study cortisol was independently associated to the presence of dementia.

Aplicação do teste de informação, memória e concentração (IMC) ao estudo epidemiológico de demência senil em Fortaleza

O presente trabalho teve por objetivo verificar a ocorrência de demência senil em amostra de pessoas de 65 e mais anos de idade residentes no Município de Fortaleza. Foram estudados 865 idosos, a partir do teste de Informação, Memória e Concentração, IMC (teste de Hachinski, modificado), que aborda aspectos concernentes à identificação da pessoa, à memória de fatos atuais e remotos e à concentração, determinando os estados demenciais em função do número e grau de respostas numa sequência programada e previamente testada quanto à sensibilidade e especificidade. Analisando-se os resultados quanto a idade, sexo e condição social, evidenciou-se uma prevalência de 8,4de demência senil no conjunto geral, com diferenças n†o significativa na faixa de 75 e mais anos de idade (9,3), comparada ao grupo de 65 a 74 anos (7,5). Os percentuais foram semelhantes para homens e mulheres: 8,7e 8,3, respectivamente. Quanto à condição social, foi verificado um aumento progressivo nas proporções de estados demenciais, desde 4,2para o estrato A/B (abastados), 6,9 para o grupo C (nível intermediário) e 10,3no nível D/E correspondente ao estrato de pessoas economicamente desprivilegiadas. Estes resultados, entretanto, dever†o ser vistos com certa reserva, dado o grau de recusa por ocasião das entrevistas, especialmente nos estratos A/B (19,3) e D/E (9,3)

Muscarinic receptors and acetylcholinesterase activity in brain of patients with dementia

The present paper describes the determination of muscarinic receptor number ([3H]-N-methylscopolamine binding) and acetylcholinesterase activity in six brain areas (pre-central gyrus, post-central gyrus, hippocampus, caudate nucleus,lentiform nucleus and substantia inominata) of demented patients (diagnosed by screening tests and neurological evaluation) and age-matched controls.These was a significant increase in muscarinic receptors in the hippocampus and substanctia inominata (171.2 and 359.4fmol/mg protein, respectively) of the demented group as compared with controls (123.9 and 219.0 fmol/mg protein, respectively). No changes were observed in pre-and post-central gyrus, while a tendency towards decreased binding was detected in the caudate nucleus and lentiform nucleus of the demented group. Lower acetylcholinesterase activity was also detected in the demented group in all areas studied although the differences were significant only in the post-central gyrus, caudate nucleus and substantia inominata which showed a 49.21 and 25% decrease in enzyme activity respectively. The results are discussed in terms of a compensatory mechanism of presynaptic deficiency such as that occurring in Parkinson's disease

Adaptaçäo de um teste de "screening" para a detecçäo de demência / Screening test application for detection of dementia in the elderly

O presente trabalho apresenta os resultados da aplicaçäo do teste IMC, de Informaçäo, Memória e Concentraçäo, em uma amostra de idosos do Lar Torres de Melo em Fortaleza, Ceará. O teste foi adaptado de Hachinski de modo a atender as características sócio-econômicas e culturais da populaçäo testada. Dos 71 pacientes examinados, 37 ou 52,1% foram considerados como dementes pelo exame neurológico. Estas cifras näo indicam risco nem tampouco prevalência, em virtude de se tratar de amostra näo aleatória, em populaçäo de idosos internados. Com a aplicaçäo do IMC-modificado, objetiva-se dispor de um instrumento dotado de razoável sensibilidade-especificidade e que poderá ser útil como método auxiliar na detecçäo de demência em grupos específicos

Adaptacao de um teste de "screening" para a deteccao de demencia

O presente trabalho apresenta os resultados da aplicacao do teste IMC, de Informacao, Memoria e Concentracao, em uma amostra de idosos da Lar Torres de Melo em Fortaleza, Ceara. O teste foi adaptado de Hachinski de modo a atender as caracteristicas socio-economico e culturais da populacao testada. Dos 71 pacientes examinados, 37 ou 52,1 por cento foram considerados como dementes pelo exame neurologico. Estas cifras nao indicam risco nem tampouco prevalencia, em virtude de se tratar de amostra nao aleatoria, em populacao de idoso internados. Com a aplicacao do IMC-modificado, objetiva-se dispor de um instrumento dotado de razoavel sensibilidade-especificidade e que podera ser util como metodo auxiliar na deteccao de demencia em grupos especificos.