Electroacupuncture-induced activation of GABAergic system alleviates airway inflammation in asthma model by suppressing TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Electroacupuncture (EA) has been shown to attenuate airway inflammation in asthmatic mice; however, the underlying mechanism is not fully understood. Studies have shown that EA can significantly increase the inhibitory neurotransmitter γ-aminobutyric acid (GABA) content in mice, and can also increase the expression level of GABA type A receptor (GABAAR). Furthermore, activating GABAAR may relieve inflammation in asthma by suppressing toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Therefore, this study aimed to investigate the role of GABAergic system and TLR4/MyD88/NF-κB signaling pathway in asthmatic mice treated with EA. METHODS: A mouse model of asthma was established, and a series of methods including Western blot and histological staining assessment were employed to detect the level of GABA, and expressions of GABAAR and TLR4/MyD88/NF-κB in lung tissue. In addition, GABAAR antagonist was used to further validate the role and mechanism of GABAergic system in mediating the therapeutic effect of EA in asthma. RESULTS: The mouse model of asthma was established successfully, and EA was verified to alleviate airway inflammation in asthmatic mice. The release of GABA and the expression of GABAAR were significantly increased in asthmatic mice treated with EA compared with untreated asthmatic mice ( P  < 0.01), and the TLR4/MyD88/NF-κB signaling pathway was down-regulated. Moreover, inhibition of GABAAR attenuated the beneficial effects of EA in asthma, including the regulation of airway resistance and inflammation, as well as the inhibitory effects on TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: Our findings suggest that GABAergic system may be involved in mediating the therapeutic effect of EA in asthma, possibly by suppressing the TLR4/MyD88/NF-κB signaling pathway.

Probable mechanisms involved in the antiepileptic activity of Clerodendrum polycephalum Baker (Labiatae) leaf extract in mice exposed to chemical-induced seizures.

The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. This study is aimed at evaluating the effects of Clerodendrum polycephalum (CP) leaf extract on chemical-induced seizures in mice and the possible mechanisms of action. Swiss albino mice were pretreated with CP (50, 100, or 500 mg/kg, p.o.) prior to intraperitoneal injection of picrotoxin (PTX) or pentylenetetrazole (PTZ). However, the most effective dose was used to elucidate the role of GABAergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling mechanisms in mice brains. Accordingly, we evaluated the preventive and reversal effects of CP on kainic acid (KA)-induced temporal lobe epilepsy (TLE), oxidative stress, and neuroinflammatory in mice. The pretreatment of mice with CP delayed the latencies to PTX and PTZ-induced seizures and decrement in the period of tonic-clonic attacks. Interestingly, CP (100 mg/kg) completely prevented PTZ-induced tonic-clonic seizures. Contrastingly, flumazenil (benzodiazepine receptor antagonist), NG -nitro-L-Arginine (L-NNA) (10 mg/kg., neuronal nitric oxide synthase inhibitor), and methylene blue (MB) (2 mg/kg, a soluble guanylyl cyclase inhibitor) but not L-arginine (150 mg/kg., nitric oxide precursor) reversed CP-induced anticonvulsant-like effect in PTZ model. Furthermore, KA-elicited TLE was prevented by CP treatment. CP also attenuated KA-induced oxidative stress, cyooxygenase-2 (COX-2), and nuclear factor kappa-B (NF-κB) elevated expressions in the hippocampus. The study revealed that the ethanolic leaf extract of CP produced anticonvulsant actions through enhancement of antioxidant defense, GABAergic, and NO-cGMP signaling pathways as well as attenuation of inflammatory processes. PRACTICAL APPLICATIONS: The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. For this reason, we believe that supplementation of the Clerodendrum polycephalum leaf extract would prevent epileptic-related disorders in mice induced with epileptic conditions using kainic acid and other behavioral phenotypic models. Here, our findings clearly revealed that Clerodendrum polycephalum leaf extract protects against conditions of epileptic-related disorders and thus might be relevant as a dietary supplement in the prevention or delay of the onset of seizures and epileptic behavior.

Tratamiento del Síndrome Neuropsiquiátrico Diferido por intoxicación con monóxido de carbono con risperidona y oxígeno hiperbárico / Treatment of Delayed Post-Hypoxic Leukoencephalopathy as a complication of carbon monoxide poisoning with risperidone and hyperbaric oxygen therapy

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European guideline for the diagnosis and treatment of insomnia

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Actitudes ante el insomnio de los médicos de AP de Mallorca / Attitudes to insomnia by Primary Care physicians of Majorca (Spain)

OBJETIVOS: Describir la conducta actual en el manejo clínico del insomnio de los médicos de AP (MAP). DISEÑO: Estudio descriptivo transversal. Emplazamiento: Área sanitaria de Mallorca, 2011-2012. PARTICIPANTES: MAP, se excluyó a médicos residentes, de urgencias y pediatras. Mediciones: Cuestionario autoadministrado con variables sociodemográficas, profesionales, formación en insomnio, preferencias de prescripción y su manejo clínico. RESULTADOS: Respondieron 322 de 435 médicos (74%). Un 55% eran mujeres, con una media de edad de 48 años y una media de años de profesión de 21 años. La mayoría considera el insomnio como un problema importante de salud y refiere interrogar sobre hábitos del sueño y su repercusión sobre la vida diaria. Un tercio ha recibido formación los últimos 5 años. Un 0,6% deriva a los pacientes al psiquiatra y un 1,9% al psicólogo. El tratamiento farmacológico más prescrito son benzodiacepinas (33,4%) y fármacos Z (25,7%); el 69,4% declara revisarlo al mes de su inicio. Refieren prescribir higiene del sueño un 85,1%, plantas medicinales un 15,1% y terapia cognitivo-conductual (TCC) un 14,2%. El 70% consideraba esta terapia efectiva y aplicable por médicos y enfermeros. Los de mayor edad prescriben con menor frecuencia benzodiacepinas y las mujeres más medidas de higiene del sueño y plantas medicinales. CONCLUSIONES: La mayoría de los MAP consideran el insomnio como un problema importante de salud que manejan ellos mismos. Los tratamientos más empleados son higiene del sueño, benzodiacepinas y fármacos Z. La TCC es considerada efectiva pero escasamente utilizada

OBJECTIVES: To describe the current clinical management of insomnia by family physicians. DESIGN: Cross-sectional study. SETTING: Majorca Health Area, 2011-2012. PARTICIPANTS: Family physicians (FP). Paediatricians, resident physicians and emergency physicians were excluded. Measurements: Using a self-administered questionnaire, the following variables were collected: social, demographic, professional, training in insomnia, prescription preferences, and its clinical management. RESULTS: A total of 322 of 435 physicians answered (74%), of whom 55% were female. The mean age was 48 years with a mean of 21 years in the profession. Most of them consider insomnia as a major health problem, and refer to asking patients about sleep habits and its impact on daily life. About one third have been trained in insomnia in the last 5 years. Very few (0.6%) refers patients to a psychiatrist, and 1.9% to a psychologist. The most prescribed drugs are benzodiazepines (33.4%) and Z drugs (25.7%), with 69.4% of them claiming to have checked the treatment after month of onset. Most refer to advice about sleep hygiene measures (85.1%), 15.1% prescribe herbal remedies, and 14.2% behavioural cognitive therapy (CBT). Seven out of ten physicians consider CBT as effective and applicable by both physicians and nurses. The older FPs prescribe benzodiazepines with less frequency, while female FPs prescribe more sleep hygiene measures and herbal remedies. CONCLUSIONS: Most FPs consider insomnia as a major health problem, in which they usually get involved. The most commonly used treatments are sleep hygiene advice, followed by benzodiazepines and Z drugs. The CBT is considered effective but not widely used

Estudio epidemiológico multicéntrico de las técnicas anestésicas en la cirugía de la hernia inguinal en España / Multicentre epidemiological study of anaesthetic techniques in inguinal hernia surgery in Spain

Objetivo: Recientemente se ha producido renovado interés sobre la técnica anestésica en la cirugía de la hernia inguinal y las ventajas y los inconvenientes derivados de las diferentes técnicas anestésicas. En nuestro país no hay información acerca de la la técnica anestésica en la hernioplastia. Nuestro objetivo es realizar un estudio epidemiológico sobre las técnicas anestésicas en la cirugía de la hernia inguinal. Pacientes y métodos: Estudio epidemiológico transversal, descriptivo y multicéntrico en 20 hospitales de España. Cada centro incluyó a 12 pacientes sometidos a herniorrafia y registró datos sociodemográficos, antecedentes patológicos, técnica realizada, parámetros de recuperación y complicaciones. Resultados: Se incluyó a 238 pacientes (el 91% ASA I-II), con una media de edad de 57 (25-84) años, 213 varones y 25 mujeres. El régimen de hospitalización fue: cirugía ambulatoria un 47%, corta estancia un 26% y el resto con ingreso. Se realizó anestesia subaracnoidea en un 60%, anestesia general en un 27% y anestesia local con sedación, habitualmente benzodiacepinas, en un 13% de los casos. El alta de los pacientes intervenidos en régimen de cirugía ambulatoria fue entre 1 y 6 h en el 94 y el 100% de los casos de anestesia general y anestesia local respectivamente, frente a un 68% para la anestesia subaracnoidea. No hubo diferencias en las características del dolor, náuseas y vómitos entre las técnicas anestésicas; sin embargo, hubo 10 episodios de retención urinaria, todos ellos en el grupo de anestesia subaracnoidea, en pacientes varones y con una edad media de 68 años. Conclusiones: La anestesia subaracnoidea es la más utilizada en España para la herniorrafia, y se asocia con una elevada incidencia de retención urinaria y retraso en el alta hospitalaria (> 6 h en un 32% de los casos) en comparación con la anestesia local. Esta debería ser promovida activamente en nuestro país(AU)

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Treatment options for insomnia--pharmacodynamics of zolpidem extended-release to benefit next-day performance.

BACKGROUND: Insomnia can manifest as difficulty in falling asleep, in maintaining sleep throughout the night, or waking up too early, with symptoms often unpredictably changing over time. Pharmacologic options for insomnia treatment include prescription hypnotics, such as gamma-amino butyric acid-receptor agonists, sedating antidepressants, over-the-counter antihistamines, melatonin-receptor agonists, and alternative therapies. A concern with insomnia medications is the risk of next-day residual effects, which can impair memory and ability to perform certain tasks, such as driving, and may increase the risk of accidents and falls, especially in the elderly. OBJECTIVES: To describe the impact of current insomnia treatments on next-day performance. RESULTS: The longer-acting benzodiazepines are associated with next-day "hangover" effects and, as a result, have been largely replaced by agents in the nonbenzodiazepine class, which typically have shorter half-lives. The hypnotic, sedative activities of these classes of drugs depend on variations in binding characteristics to the alpha1 subunit of the gamma-amino butyric acidA-receptor, which inhibits neuronal activity in broad areas of the brain and is found in areas of the brain responsible for sleep/wakefulness and sedation. However, nonbenzodiazepines with a rapid onset of action and short half-life have shown limited efficacy for maintaining sleep throughout the night. These properties have contributed to the development of modified-release formulations. Zolpidem extended-release is a bilayer tablet that retains the fast onset of action of its parent compound zolpidem while extending the duration of hypnotic activity, owing to a slower-release portion of the tablet. CONCLUSIONS: Based on clinical evidence, the risk of residual next-day effects of zolpidem extended-release is limited, mainly due to the similarly short half-life in its extended-release formulation.