Inmunoglobulina G intravenosa como tratamiento adyuvante en epilepsia infantil farmacorresistente / Intravenous immunoglobulin G as adjuvant treatment in drug-resistant childhood epilepsy

INTRODUCCIÓN: La epilepsia es la enfermedad neurológica más común en la infancia; dependiendo de la definición de epilepsia farmacorresistente la incidencia varía del 10 a 23% en la población pediátrica. El objetivo de este estudio fue contabilizar la disminución en la frecuencia y/o duración mensual de crisis epilépticas en pacientes pediátricos con epilepsia farmacorresistente tratados con antiepilépticos, antes y después de la adición de inmunoglobulina G intravenosa (IgG iv). MÉTODOS: Estudio analítico, observacional retrospectivo de casos-controles. Se estudiaron pacientes pediátricos con epilepsia farmacorresistente atendidos en el Centro Médico Nacional 20 de Noviembre de la Ciudad de México durante el período 2003-2013 y que recibieron tratamiento con IgG IV. RESULTADOS: Ciento sesenta y siete pacientes (19,5%) presentaron epilepsia farmacorresistente y 44 (5,1%) iniciaron tratamiento adyuvante con IgG IV. La edad media de los pacientes al inicio del tratamiento fue de 6,12 años (± 5,14); 28 (73,6%) tuvieron una etiología estructural adquirida, 5 (13,1%) genética, uno (2,6%) inmune y 4 (10,5%) desconocida. A los 2 meses de la aplicación de inmunoglobulina la duración de las crisis se redujo al 66,66% y la frecuencia de las crisis alcanzó una reducción del 64% a los 4 meses de iniciado el tratamiento(p < 0,001). CONCLUSIONES: La IgG IV puede ser una terapia eficaz para la disminución en la frecuencia y duración de las convulsiones en pacientes pediátricos con epilepsia farmacorresistente, como lo demuestran los resultados de este estudio

BACKGROUND: Epilepsy is the most common neurological disease in childhood; depending on the definition of drug-resistant epilepsy, incidence varies from 10% to 23% in the paediatric population. The objective of this study was to account for the decrease in the frequency and/or monthly duration of epileptic seizures in paediatric patients with drug-resistant epilepsy treated with antiepileptic drugs, before and after adding intravenous immunoglobulin G (iIV IgG). METHODS: This is an analytic, observational, retrospective case-control study. We studied paediatric patients with drug-resistant epilepsy who were treated with IV IgG at the Centro Médico Nacional 20 de Noviembre, in Mexico City, from 2003 to 2013. RESULTS: One hundred and sixty seven patients (19.5%) had drug-resistant epilepsy and 44 (5.1%) started adjuvant treatment with IV IgG. The mean age of patients at the beginning of treatment was 6.12 years ± 5.14); aetiology was structural acquired in 28 patients (73.6%), genetic in 5 (13.1%), immune in 1 (2.6%), and unknown in 4 (10.5%). At 2 months from starting IV IgG, seizure duration had reduced to 66.66%; the frequency of seizures was reduced by 64% at 4 months after starting treatment (P < .001). CONCLUSIONS: According to the results of this study, intravenous immunoglobulin may be an effective therapy for reducing the frequency and duration of seizures in paediatric patients with drug-resistant epilepsy

Intravenous immunoglobulin G as adjuvant treatment in drug-resistant childhood epilepsy. / Inmunoglobulina G intravenosa como tratamiento adyuvante en epilepsia infantil farmacorresistente.

BACKGROUND: Epilepsy is the most common neurological disease in childhood; depending on the definition of drug-resistant epilepsy, incidence varies from 10% to 23% in the paediatric population. The objective of this study was to account for the decrease in the frequency and/or monthly duration of epileptic seizures in paediatric patients with drug-resistant epilepsy treated with antiepileptic drugs, before and after adding intravenous immunoglobulin G (iIV IgG). METHODS: This is an analytic, observational, retrospective case-control study. We studied paediatric patients with drug-resistant epilepsy who were treated with IV IgG at the Centro Médico Nacional 20 de Noviembre, in Mexico City, from 2003 to 2013. RESULTS: One hundred and sixty seven patients (19.5%) had drug-resistant epilepsy and 44 (5.1%) started adjuvant treatment with IV IgG. The mean age of patients at the beginning of treatment was 6.12 years±5.14); aetiology was structural acquired in 28 patients (73.6%), genetic in 5 (13.1%), immune in 1 (2.6%), and unknown in 4 (10.5%). At 2 months from starting IV IgG, seizure duration had reduced to 66.66%; the frequency of seizures was reduced by 64% at 4 months after starting treatment (P<.001). CONCLUSIONS: According to the results of this study, intravenous immunoglobulin may be an effective therapy for reducing the frequency and duration of seizures in paediatric patients with drug-resistant epilepsy.

The yin/yang of inflammatory status: Blood-brain barrier regulation during sleep.

Sleep loss induces a low-grade inflammatory status characterized by a subtle but sustained increase of pro-inflammatory mediators, which are key regulators of blood-brain barrier function. To investigate the influence of inflammatory status on blood-brain barrier dysfunction induced by sleep restriction we performed an experiment using two strains of mice with different immunological backgrounds, C57BL/6 mice that have a predominant pro-inflammatory response and BALB/c mice that have a predominant anti-inflammatory response. Mice were sleep-restricted during 10 days using the flowerpot technique during 20 h per day with 4 h of daily sleep opportunity. The systemic inflammatory status, blood-brain barrier permeability, and the hippocampal expression of neuroinflammatory markers were characterized at the 10th day. Serum levels of TNF and IFN-γ increased in sleep-restricted C57BL/6 but not in BALB/c mice; no changes in other cytokines were found. Sleep restriction increased blood-brain barrier permeability in C57BL/6 strain but not in BALB/c. The hippocampus of sleep-restricted C57BL/6 mice exhibited an increase in the expression of the neuroinflammatory markers Iba-1, A2A adenosine receptor, and MMP-9; meanwhile in sleep-restricted BALB/c mice the expression of this markers was lesser than the control group. These data suggest that cytokines may be playing a key role in modulating blood-brain barrier function during sleep restriction, and probably the effects are related to Iba-1, MMP-9 and A2A adenosine receptor overexpression.

Chronic sleep restriction disrupts interendothelial junctions in the hippocampus and increases blood-brain barrier permeability.

Chronic sleep loss in the rat increases blood-brain barrier permeability to Evans blue and FITC-dextrans in almost the whole brain and sleep recovery during short periods restores normal blood-brain barrier permeability. Sleep loss increases vesicle density in hippocampal endothelial cells and decreases tight junction protein expression. However, at the ultrastructural level the effect of chronic sleep loss on interendothelial junctions is unknown. In this study we characterised the ultrastructure of interendothelial junctions in the hippocampus, the expression of tight junction proteins, and quantified blood-brain barrier permeability to fluorescein-sodium after chronic sleep restriction. Male Wistar rats were sleep restricted using the modified multiple platform method during 10 days, with a daily schedule of 20-h sleep deprivation plus 4-h sleep recovery at their home-cages. At the 10th day hippocampal samples were obtained immediately at the end of the 20-h sleep deprivation period, and after 40 and 120 min of sleep recovery. Samples were processed for transmission electron microscopy and western blot. Chronic sleep restriction increased blood-brain barrier permeability to fluorescein-sodium, and decreased interendothelial junction complexity by increasing the frequency of less mature end-to-end and simply overlap junctions, even after sleep recovery, as compared to intact controls. Chronic sleep loss also induced the formation of clefts between narrow zones of adjacent endothelial cell membranes in the hippocampus. The expression of claudin-5 and actin decreased after chronic sleep loss as compared to intact animals. Therefore, it seems that chronic sleep loss disrupts interendothelial junctions that leads to blood-brain barrier hyperpermeability in the hippocampus.

Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link.

Sleep is a vital phenomenon related to immunomodulation at the central and peripheral level. Sleep deficient in duration and/or quality is a common problem in the modern society and is considered a risk factor to develop neurodegenerative diseases. Sleep loss in rodents induces blood-brain barrier disruption and the underlying mechanism is still unknown. Several reports indicate that sleep loss induces a systemic low-grade inflammation characterized by the release of several molecules, such as cytokines, chemokines, and acute-phase proteins; all of them may promote changes in cellular components of the blood-brain barrier, particularly on brain endothelial cells. In the present review we discuss the role of inflammatory mediators that increase during sleep loss and their association with general disturbances in peripheral endothelium and epithelium and how those inflammatory mediators may alter the blood-brain barrier. Finally, this manuscript proposes a hypothetical mechanism by which sleep loss may induce blood-brain barrier disruption, emphasizing the regulatory effect of inflammatory molecules on tight junction proteins.

Effect of low-frequency repetitive transcranial magnetic stimulation on sleep pattern and quality of life in patients with focal epilepsy.

OBJECTIVE: In this study we analyzed the effects of transcranial magnetic stimulation (TMS) on sleep and on the self-perceived quality of life in epileptic patients. METHODS: A total of 24 male patients diagnosed with focal epilepsy were included in the study. Pharmacological treatment with levetiracetam was standardized at 2 g daily. Before TMS onset, all-night polysomnographic recording (PSG) was performed, and the Quality of Life in Epilepsy Inventory (QOLIE-31) was administered. Thereafter, patients underwent low-frequency repetitive TMS (1000 pulses/1 Hz) daily for 10 days. After the end of the treatment, a second polysomnographic study was performed, and the QOLIE-31 questionnaire was administered again. RESULTS: TMS induced a significant increase in sleep efficiency and in total sleep time, along with a decrease in sleep latency and the number of awakenings. In addition, the number of interictal discharges during sleep decreased significantly. Concerning the QOLIE-31 scale values, the patients showed great improvement in the self-perceived quality of life. CONCLUSION: The present results indicate that TMS may mediate therapeutic effects in the treatment of patients with focal epilepsy, and that TMS treatment is accompanied by improvement of sleep patterns as well as improvement in self-perceived quality of life. However, a study that includes a control group undergoing sham stimulation is needed to confirm these findings.

Steroid hormones and sleep regulation.

In the search of the sleep substance, many studies have been addressed for different hormones, responsible for sleep-wake cycle regulation. In this article we mentioned the participation of steroid hormones, besides its role regulating sexual behavior, they influence importantly in the sleep process. One of the clearest relationships are that estrogen and progesterone have, that causing changes in sleep patterns associated with the hormonal cycles of women throughout life, from puberty to menopause and specific periods such as pregnancy and the menstrual cycle, including being responsible for some sleep disorders such as hypersomnia and insomnia. Another studied hormone is cortisol, a hormone released in stressful situations, when an individual must react to an extraordinary demand that threatens their survival, but also known as the hormone of awakening because the release peak occurs in the morning, although this may be altered in some sleep disorders like insomnia and mood disorders. Furthermore neurosteroids such as pregnanolone, allopregnanolone and pregnenolone are involved in the generation of slow wave sleep, the effect has been demonstrated in experimental animal studies. Thus we see that the sleep and the endocrine system saved a bidirectional relationship in which depends on each other to regulate different physiological processes including sleep.

Anti-CD43 and anti-galectin-1 autoantibodies in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies and also by T-cell dysfunction. CD43 is expressed by most immune cells, is involved in lymphocyte adhesion and activation, and interacts with galectin-1 (Gal-1). The aim of this work was to evaluate the plasma levels of autoantibodies against CD43 and Gal-1 as well as the levels of soluble Gal-1 in SLE Mexican mestizo patients, with the aim of establishing a correlation between these parameters and the clinical profile. METHODS: Serum levels of immunoglobulin (Ig)G autoantibodies against CD43 and Gal-1 and levels of soluble Gal-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 55 patients with SLE and 71 healthy controls. RESULTS: We found significantly enhanced titres of anti-CD43 and anti-Gal-1 antibodies in sera from SLE patients compared to controls. In addition, the serum levels of Gal-1 were significantly higher in SLE patients than in healthy individuals. However, we could detect no correlation of these parameters with disease activity [using the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI)], age, or a variety of different clinical or laboratory features. Similarly, no significant correlation with immunosuppressive or glucocorticoid therapy was observed. By contrast, a significant association was found between anti-CD43 titres and time of disease evolution, complement levels, and the presence of anti-Gal-1 antibodies. CONCLUSIONS: As CD43 and Gal-1 participate in modulating the immune system, we suggest that the presence of autoantibodies against these molecules may contribute to the immune deregulation observed in SLE.

Polysomnographic features in infants with early diagnosis of congenital hypothyroidism.

Thyroid hormones play a major role in the maturation process of the brain. Currently, congenital hypothyroidism is detected by mass screening. The impact of this early hormonal deficiency on the organization of the sleep pattern is not known. In this study, the polysomnographic features in children diagnosed with congenital hypothyroidism were analyzed. Children were detected by mass population screening and the hormonal replacement therapy starts immediately. Children's age ranged between 1.5 and 18 months of age. The duration of hormonal treatment before sleep recordings varied between 8 days and 17 months. Children were polysomnographically recorded in the morning, for at least 2h, obtaining more than one sleep cycle. Results showed a high prevalence of females (5/1) in the group studied. A high proportion of infants (43%) displayed central apnea in different degrees (mild, moderate and severe) as well as hypopnea (83%), mainly in subjects around 4 and 8 months of age. The proportion of infants displaying central apnea decreases as age increases. In addition, indeterminate (light) sleep increase and quiet (slow wave) sleep decrease significantly regardless of age and treatment. The percentage of REM sleep correlated positively with the age of the child at the beginning of the treatment, and negatively with their age at the time of the study. These data indicate that congenital hypothyroidism facilitates the presence of central sleep apnea. The decrease of these respiratory alterations correlates with the increase of the hormonal replacement therapy. It seems that sleep respiratory alterations in congenital hypothyroidism are linked to brain maturation processes in which thyroid hormones play a major role.

The H1 histamine receptor blocker, chlorpheniramine, completely prevents the increase in REM sleep induced by immobilization stress in rats.

Chlorpheniramine is a selective antagonist of the H1 histaminergic receptor subtype and its effects in humans include somnolence. Chlorpheniramine affects sleep in rats, mainly by decreasing REM sleep. On the other hand, stress by immobilization induces an important increase in the percentage of REM sleep. In this study we analyzed the effects of blocking histaminergic receptors on REM sleep induced by immobilization stress. Adult male Wistar rats were chronically implanted for sleep recording. Immobilization stress was induced by placing the rat in a small cylinder for 2 h. Experimental conditions were: A. Control; B. Stress; C. Stress plus vehicle and D. Stress plus chlorpheniramine. Independent experiments were done both in the dark, as well as the light period. Results showed that the increase in REM sleep observed after immobilization stress was completely abolished by chlorpheniramine, both in the dark and in the light phase. Furthermore, the decrease in REM sleep was significant even when compared to the non-stressed control rats. REM sleep latency was also significantly longer during both light phases. The present results suggest that REM sleep is quite sensitive to histaminergic blockage. It is possible that chlorpheniramine is also blocking the cholinergic mechanisms generating REM sleep.

Sexual behavior of female rats in a multiple-partner preference test.

In this study, sexually experienced female rats were tested in a multiple-partner preference test (MPPT) in which they were allowed to pace their sexual contacts with four sexually active males. Four cylinders, with a small hole through which only the female could move freely from one cylinder to another, were assembled forming in the center an empty compartment. An intact female was placed in the central compartment and a sexually active male in each cylinder. Female sexual behavior was analyzed throughout the estrus cycle in four consecutive days. Each daily test lasted 15 min. The percentage of exits after intromission or ejaculation was significantly higher than the percentage of exits after each mount. The female spent significantly longer time with one of the males. We designated this male as the preferred male (PM). Although in each of the 4 days studied, females spent significantly longer time with the PM, however, the male selected was not the same throughout the estrus cycle. The number of entries into the compartment of the PM was significantly higher and increased around proestrus. Compared to previous studies, pacing behavior was notably lower in the conditions of the MPPT. No significant differences were observed during the estrous cycle concerning the other parameters recorded. The present results suggest that the MPPT could be a good model to study partner preference in the female rat.

Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes.

OBJECTIVES: To measure the effect of metformin on the body composition, insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus (type 2 DM). DESIGN: Placebo-controlled clinical trial. MATERIAL AND METHODS: Twenty-three subjects with risk factors for type 2 DM were randomly assigned to receive 850 mg of metformin or a placebo twice a day for 2 months. Before and after the treatment, the body mass index and waist/hip ratio were calculated, the body composition was measured through bioelectric impedance and the fasting levels of blood glucose, insulin, triglycerides and cholesterol were measured. The level of insulin resistance was calculated by the homeostatic model and the level of sensitivity by the quantitative insulin sensitivity check index method. The Wilcoxon rank test was used. RESULTS: Twenty-one subjects completed the study, 12 of the metformin group and nine of the placebo group. In the metformin group, there was a decrease in fat weight from 25.9 +/- 9.4 to 20.8 +/- 9.2 kg, p < 0.01, an increase in lean weight from 57.05 +/- 13.6 to 61.9 +/- 16.5 kg, p < 0.01, an increase in basal metabolism from 1735 +/- 413 to 1878 +/- 505 calories/day, p < 0.05 and an increase in body water, p < 0.05. There was no significant decrease in insulin resistance. In the placebo group, the blood glucose increased from 84.7 +/- 13 to 96.7 +/- 16 mg/dl, p < 0.05. There were no significant modifications in lipids. CONCLUSIONS: The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM.

[West syndrome as an epileptic presentation in Menkes' disease. Two cases report]. / Síndrome de West como manifestación epiléptica de enfermedad de Menkes. Presentación de dos casos.

INTRODUCTION: Menkes' disease is a neurodegenerative disorder, recessive X chromosome linked (Xp13.3) that normally codify an ATPasa copper transporter. CASE REPORTS: Case 1: patient exhibit failure in the gastrointestinal copper absorption, which is insufficient to cover the needing during the first twelve months of life. The first case was a 5 months male. His developmental skills were normal until he was 5 months old, when he exhibited visual impairment and failure to continue getting normal developmental skills. One month later he had infantile spasms and hypsarrhythmia in the EEG. He had kinky hair, alopecia zones and copper serum level in 0 microg/dL (range 590-1,180 microg/dL) brain CT scan revealed diffuse cortical atrophy. The patient is 5 years old now, he is free of seizures but he has a severe neurological impairment. Case 2: he is a 7 months old male who developed during the two days of life hypotonia and weak suction. He exhibited later hypertonia, delayed neurological development and infantile spasms, microcephaly, kinky hair, blindness and EEG pattern of hypsarrhythmia. The serum copper level was 84 microg/dL (range: 590-1,180 microg/dL). The brain CT scan showed generalized atrophy, including cerebellum, extradural effusion and MRI with multiple infarcts in different stages. Electronic microscopy revealed pili torti. In both cases the diagnosis was suspected because of the hair and eyebrow features. CONCLUSIONS: We suggest a careful hair and eyebrow clinical exam in those patients with delayed milestones and early epilepsy without a documented etiology, and the copper serum level determination in those patients with suspected disease.

Síndrome de West como manifestación epiléptica de enfermedad de Menkes. Presentación de dos casos / West syndrome as an epileptic presentation in menkes'disease. Two cases report

Introducción. La enfermedad de Menkes es una patología neurodegenerativa recesiva ligada al cromosoma X (Xp13.3), que normalmente codifica una ATPasa transportadora de cobre. Casos clínicos. Caso 1: varón de 5 meses de edad que presenta un déficit en la absorción de cobre a través del intestino que le impide cubrir sus necesidades durante los doce primeros meses de vida. Sus habilidades evolutivas fueron normales hasta los 5 meses de edad, cuando manifestó trastornos visuales y se interrumpió la adquisición de las habilidades evolutivas. Un mes después presentó espasmos infantiles e hipsarritmia en el EEG. Tenía el cabello ensortijado, zonas de alopecia y nivel sérico de cobre de 0 µg/dL (intervalo: 590-1.180 µg/dL). Un estudio por tomografía computarizada cerebral mostró atrofia cortical difusa. Ahora el paciente tiene 5 años, está libre de crisis pero tiene un deterioro neurológico grave. Caso 2: varón de 7 meses de edad que desarrolló hipotonía y succión débil durante los dos primeros días de vida. Más adelante manifestó hipertonía, desarrollo neurológico retrasado y espasmos infantiles, microcefalia, cabello ensortijado, ceguera y patrón EEG de hipsarritmia. El nivel sérico de cobre fue de 84 µg/dL (intervalo: 590-1.180 µg/dL). El estudio por tomografía computarizada cerebral reveló atrofia generalizada con afectación del cerebelo, derrame extradural e imágenes de resonancia magnética con múltiples infartos en diferentes etapas de su evolución. Una exploración mediante microscopía electrónica reveló la existencia de pili torti. En ambos casos, las características que presentaban el cabello y las cejas llevaban a sospechar este diagnóstico. Conclusiones. Sugerimos que se realice una exploración meticulosa del cabello y de las cejas ante cualquier paciente con retraso en el desarrollo y epilepsia precoz sin etiología documentada, y la determinación del nivel sérico de cobre ante la sospecha de esta enfermedad (AU)

Introduction. Menkes’ disease is a neurodegenerative disorder, recessive X chromosome linked (Xp13.3) that normally codify an ATPasa cupper transporter. Case reports. Case 1: patient exhibit failure in the gastrointestinal cupper absorption, which is insufficient to cover the needing during the first twelve months of life. The first case was a 5 months male. His developmental skills were normal until he was 5 months old, when he exhibited visual impairment and failure to continue getting normal developmental skills. One month later he had infantile spasms and hypsarrhythmia in the EEG. He had kinky hair, alopecia zones and cupper serum level in 0 µg/dL (range: 590-1,180 µg/dL) Brain CT scan revealed diffuse cortical atrophy. The patient is 5 years old now, he is free of seizures but he has a severe neurological impairment. Case 2: he is a 7 months old male who developed during the two days of life hypotonia and weak suction. He exhibited later hypertonia, delayed neurological development and infantile spasms, microcephaly, kinky hair, blindness and EEG pattern of hypsarrhythmia. The serum cupper level was 84 µg/dL (range: 590-1,180 µg/dL). The brain CT scan showed generalized atrophy, including cerebellum, extradural effusion and MRI with multiple infarcts in different stages. Electronic microscopy revealed pili torti. In both cases the diagnosis was suspected because of the hair and eyebrown features. Conclusions. We suggest a careful hair and eyebrown clinical exam in those patients with delayed milestones and early epilepsy without a documented etiology, and the cupper serum level determination in those patients with suspected disease (AU)

[Spinocerebellar ataxia type 7: clinical and molecular genetic analysis of a Mexican family]. / Ataxia espinocerebelosa tipo 7: descripcion de una familia mexicana.

INTRODUCTION: Spinocerebellar ataxias (SCA) constitute a group of neurodegenerative diseases characterized by cerebellar disfunction alone or associated with other neurological anomalies. The combination of progressive cerebellar ataxia, macular pigment dystrophy, ophtalmoplegia, spasticity and an autosomal dominant pattern of transmission is characteristic of SCA 7. Genome wide linkage analysis mapped the defective gene to 3p12 13. OBJECTIVE: To describe a Mexican family with SCA 7. CASE REPORTS: We present a family pedigree of 13 individuals with ataxia and other neurologic findings in 3 generations. The evaluation consisted of a complete clinical and neurologic examination; neuropsychologic, neurophysiologic, ophthalmologic, neuroradiologic assessments and a molecular genetic study. The first 2 generations had a history of gait disturbance and visual loss. We objectively found a global cerebellar syndrome, pyramidal signs, visual impairment and ophtalmoparesis in variable grades in all members of the third generation All had progressive retinal degeneration, cerebellar, brainstem and hemispheric atrophy. We observed anticipation phenomena. Genetic analysis of the father of the third generation showed expansion of CAG triplet repeats at the SCA 7 gene. CONCLUSION: The clinical and genetic findings confirmed the diagnosis of SCA 7, and this is the first report in a Mexican family.

Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine [correction of flouxetine].

An antidepressant action of nicotine (NIC) has recently been suggested. Flouxetine, a selective serotonin reuptake inhibitor, is currently the most widely used antidepressant. In the present study, we analyzed the effects of the administration of NIC, fluoxetine (FLX), and the combination of both drugs given acutely, subchronically, and chronically as well as 7 days after chronic administration of these drugs on the forced swim test. Results showed that NIC induced a significant reduction of the time in immobility during the forced swim test (antidepressant effect), with a concomitant increase in swimming activity (serotonergic activation), after acute administration. These effects remain the same after subchronic and chronic administration. FLX failed to induce any effect after acute administration but did induce a significant decrease of immobility and an increase of swimming after subchronic administration. The effect of the chronic administration was significantly larger compared to subchronic administration. The combination of both drugs induced a larger effect than that observed after a single administration but only after subchronic treatment. No effect was observed after the end of the 7-day treatments. Data suggest that NIC has an antidepressant action that is expressed faster than FLX but remains the same later. Thus, cholinergic-serotonergic interactions could play an important role in the treatment of depression.

Ataxia espinocerebelosa de tipo 7: descripción de una familia mexicana / Spinocerebellar ataxia type 7: description of a mexican family

Introducción. Las ataxias espinocerebelosas (SCA, del inglés spinocerebellar ataxias) forman un grupo de enfermedades neurodegenerativas que se caracterizan por una disfunción cerebelosa, sola o en combinación con otras anormalidades neurológicas. La asociación de ataxia cerebelosa, distrofia macular pigmentaria progresiva, oftalmoplejía, signos piramidales y un patrón de herencia dominante, es característico de la SCA 7; los estudios de genética molecular han identificado la alteración en el cromosoma 3p12-13.Objetivo. Describir una familia mexicana con SCA 7. Casos clínicos. Se presenta el caso de una familia de 13 individuos de tres generaciones con ataxia y otros signos neurológicos. La evaluación consistió en una historia clínica y un examen neurológico completo, estudios neuropsicológicos, neurofisiológicos, oftalmológico, neurorradiológico y genético molecular. Las primeras dos generaciones tuvieron una historia de alteración en la marcha y disminución de la agudeza visual; en todos los miembros de la última generación se comprobó un síndrome cerebeloso global, piramidalismo, afectación visual y oftalmoparesia en grado variable, maculopatía con degeneración retiniana progresiva, atrofia del cerebelo, el tronco encefálico y los hemisferios cerebrales. Existió un fenómeno clínico de anticipación. El ADN del padre de la última generación mostró una expansión repetida de los tripletes CAG en el gen de SCA 7.Conclusión. Los hallazgos clínicos y genéticos demuestran que se trata de una SCA 7. Es la primera publicación de SCA 7 en una familia mexicana (AU)

Introduction. Spinocerebellar ataxias (SCA) constitute a group of neurodegenerative diseases characterized by cerebellar disfunction alone or associated with other neurological anomalies. The combination of progressive cerebellar ataxia, macular pigment dystrophy, ophtalmoplegia, spasticity and an autosomal-dominant pattern of transmission is characteristic of SCA-7. Genome-wide linkage analysis mapped the defective gene to 3p12-13. Objective. To describe a Mexican family with SCA-7. Case reports. We present a family pedigree of 13 individuals with ataxia and other neurologic findings in 3 generations. The evaluation consisted of a complete clinical and neurologic examination; neuropsychologic, neurophysiologic, ophthalmologic, neuroradiologic assessments and a molecular genetic study. The first 2 generations had a history of gait disturbance and visual loss. We objectively found a global cerebellar syndrome, pyramidal signs, visual impairment and ophtalmoparesis in variable grades in all members of the third generation All had progressive retinal degeneration, cerebellar, brainstem and hemispheric atrophy. We observed anticipation phenomena. Genetic analysis of the father of the third generation showed expansion of CAG triplet repeats at the SCA-7 gene. Conclusion. The clinical and genetic findings confirmed the diagnosis of SCA-7, and this is the first report in a Mexican family (AU)

[Lifestyle and metabolic control in patients with type 2 diabetes mellitus. Construct validation of IMEVID questionnaire]. / Estilo de vida y control metabólico en pacientes con diabetes mellitus tipo 2. Validación por constructo del IMEVID.

OBJECTIVE: To evaluate construct validity of an instrument to measure lifestyle in patients with type 2 diabetes mellitus (IMEVID questionnaire) DESIGN: Comparative cross-sectional study. SETTING: Six family medicine units (primary care). PATIENTS: 412 adults with type 2 diabetes. MEASUREMENTS: The IMEVID was applied by self-administration and the following metabolic control parameters values were measured: body mass index (BMI), waist/hip index (WHI), hemoglobin A1C (HbA1C), total cholesterol (TC), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the average of fasting plasma glucose in the last three months (FG). The test hypothetic construct was that higher total scores in the IMEVID (better lifestyle) would be associated with lower values in the metabolic control parameters. Three groups of subjects were formed based on the total score: group one (quartile 75). Differences on these parameters between groups were researched. RESULTS: 389 subjects completed the study, 69,2% were women. Seven IMEVID domains had weak correlations at least with two of eight parameters (r between 0.22 and 0.16; P<.05). The total score had correlation with six of eight parameter (r between 0.18 and 0.10; P< or =.05). The group three subjects had lower levels of BMI, WHI, HbA1C, FG, TC and TGL than group one subjects (P<.05). CONCLUSIONS: IMEVID has construct validity to measure the lifestyle in subjects with DM2. Its total score discriminates outstanding clinical characteristics in these patients.

Estilo de vida y control metabólico en pacientes con diabetes mellitus tipo 2. Validación por constructo del IMEVID / Lifestyle and metabolic control in patients with type 2 diabetes mellitus. Construct validation of IMEVID questionnaire

Objetivo. Evaluar la validez de constructo de un instrumento para medir el estilo de vida en los pacientes con diabetes mellitus tipo 2 (cuestionario IMEVID).Diseño. Estudio observacional transversal comparativo. Emplazamiento. Seis unidades de medicina familiar (atención primaria).Participantes. Un total de 412 adultos con diabetes mellitus tipo 2.Mediciones principales. Se aplicó el IMEVID por autoadministración y se midió el índice de masa corporal (IMC), índice cintura/cadera (ICC), hemoglobina glucosilada (HbA1C), colesterol total (CT), triglicéridos (TG), presión arterial (PA) y glucemia en ayunas (GA). El constructo hipotético de prueba fue que las mayores calificaciones totales en el IMEVID (mejor estilo de vida) estarían asociadas a valores menores de estas variables clínicas. Se dividió a los sujetos en tres grupos según su calificación total: grupo uno ( cuartil 75) y se buscaron diferencias intergrupo en los valores de los parámetros medidos. Resultados. Completaron el estudio 389 sujetos, y un 69,2 por ciento eran mujeres. Siete dimensiones del IMEVID tuvieron correlaciones débiles al menos con dos de los ocho parámetros (r, -0,22 a 0,16; p 0,05). La calificación total se correlacionó con seis de ocho parámetros (r, -0,18 a 0,10; p 0,05). Los sujetos del grupo tres tuvieron valores menores de IMC, ICC, HbA1C, GA, CT y TGL que los del grupo 1 (p < 0,05).Conclusiones. El IMEVID tiene validez de constructo para medir el estilo de vida en los sujetos con diabetes tipo 2. Su calificación total discrimina las características clínicamente relevantes (AU)

Stress-induced REM sleep increase is antagonized by naltrexone in rats.

RATIONALE: The expression of sleep is influenced by situations that take place during the preceding waking period, giving rise to different patterns of sleep architecture. Immobilization stress (IMB) induces an increase of both rapid eye movement (REM) and slow wave sleep (SWS). It has been suggested that these changes are mediated in part by noradrenaline and by the corticotrophin releasing factor. OBJECTIVE: To determine the participation of mu receptors in the stress-induced increase of REM sleep using naltrexone (NTX). METHODS: Twelve adult male rats were implanted for sleep recordings. Subjects were recorded under control conditions as well as after: a) IMB stress (1 h); b) injection of NTX (1.5 mg/kg); c) NTX plus IMB. To assess corticosterone levels, additional groups ( n=5) were decapitated at 0, 1, 3 and 6 h after vehicle injection and after immobilization. Four groups were decapitated at 0, 1, 3, and 6 h after NTX plus IMB. Corticosterone plasma levels were determined by HPLC. RESULTS: IMB induces an increase in REM and SWS, and a decrease in wakefulness. Administration of NTX before IMB suppresses the effects of stress on sleep. NTX administration is innocuous in non-stressed animals. However, NTX administration does not prevent the rise of corticosterone normally observed after IMB stress. CONCLUSION: These data suggest that NTX prevents the effects of IMB stress on sleep by acting outside of the hypothalamic-pituitary-adrenal axis that partially mediates the stress response.