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.

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.

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