Vitamin C and vitamin C plus E improve the immune function in the elderly.

With aging the immune response is impaired. This immunosenescence, in which an alteration of the redox state of the immune cells appears, is involved in the rate of aging. Since leukocyte function is a good marker of health and predictor of longevity, the effects of daily oral administration of the antioxidant vitamin C (500 mg), or both vitamin C (500 mg) and vitamin E (200 mg) on several blood neutrophil (adherence, chemotaxis, phagocytosis, and superoxide anion levels) and lymphocyte (adherence, chemotaxis, proliferation, interleukin-2 secretion and natural killer activity) functions were studied in healthy elderly men and women. These parameters were analysed before supplementation, after 3 months of supplementation, and 6 months after the end of supplementation. The results showed that vitamin C, in elderly participants, improved the immune functions studied which achieved values close to those of young adults. These effects were maintained in several functions after 6 months without supplementation. Similar effects were found in the elderly supplemented with both vitamin C and E. Thus, a short period of vitamin C or vitamin C and E ingestion, with the doses used, improves the immune function in elderly men and women and could contribute to a healthy longevity.

Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial.

RATIONALE: Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes. OBJECTIVES: To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. METHODS: In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (n = 26) or no CPAP (control; n = 24), while their usual medication for diabetes remained unchanged. MEASUREMENTS AND MAIN RESULTS: HbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1ß, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1ß were independently related to the 6-month change in HbA1c levels (r(2) = 0.510, P = 0.002). CONCLUSIONS: Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).

Systemic inflammation and higher perception of dyspnea mimicking asthma in obese subjects.

BACKGROUND: There are a variable number of obese subjects with self-reported diagnosis of asthma but without current or previous evidence of airflow limitation, bronchial reversibility, or airway hyperresponsiveness (misdiagnosed asthma). However, the mechanisms of asthma-like symptoms in obesity remain unclear. OBJECTIVES: We sought to evaluate the perception of dyspnea during bronchial challenge and exercise testing in obese patients with asthma and misdiagnosed asthma compared with obese control subjects to identify the mechanisms of asthma-like symptoms in obesity. METHODS: In a cross-sectional study we included obese subjects with asthma (n = 25), misdiagnosed asthma (n = 23), and no asthma or respiratory symptoms (n = 27). Spirometry, lung volumes, exhaled nitric oxide levels, and systemic biomarker levels were measured. Dyspnea scores during adenosine bronchial challenge and incremental exercise testing were obtained. RESULTS: During bronchial challenge, patients with asthma or misdiagnosed asthma reached a higher Borg-FEV1 slope than control subjects. Moreover, maximum dyspnea and the Borg-oxygen uptake (V'O2) slope were significantly greater during exercise in subjects with asthma or misdiagnosed asthma than in control subjects. The maximum dyspnea achieved during bronchial challenge correlated with IL-1ß levels, whereas peak respiratory frequency, ventilatory equivalent for CO2, and IL-6 and IL-1ß levels were independent predictors of the Borg-V'O2 slope during exercise (r(2) = 0.853, P < .001). CONCLUSIONS: A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.

A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders.

BACKGROUND & AIMS: Several authors have reported low folate intake in patients with eating disorders (ED). This vitamin plays an essential role in synthesis reactions for neurotransmitters and structural elements of neurons, and therefore its deficiency has been associated with the presence of different disorders linked to mental function. The aim of this study was to determine the effect of folic acid supplementation on homocysteine levels and the cognitive and depressive status of a group of patients with eating disorders with low folate intake. SUBJECTS/METHODS: The study was designed as a randomised, prospective clinical trial, which included 24 participants assigned to two treatment groups for six months: supplemented group (SG) (10 mg/day of folic acid [ACFOL]) and a placebo group (PG). Both groups maintained their medical, dietary and psychological treatment. At baseline and end of the intervention, anthropometric, dietary and biochemical parameters (plasma homocysteine [Hcy], serum and red blood cell folate) were recorded. Cognitive and depressive status questionnaires were administered (Stroop Test, Trail Making Test and Beck Depression Inventory). RESULTS: Twenty-two patients completed the study (SG: 12, PG: 10, mean age: 24.2 ± 8.8 years, BMI 18.9 ± 3.5 kg/m2). The SG significantly increased their serum and red blood cell folate levels and lowered Hcy levels (9.4 ± 2.4 µmol/l vs. 7.5 ± 1.7 µmol/l, P < 0.01). The SG also significantly improved most of their test scores for cognitive and depressive status. The PG showed no significant changes in any of the evaluated variables. CONCLUSIONS: The results show that folic acid supplementation may be used as another tool within the comprehensive and multidisciplinary treatment applied to patients with ED.

Introducción y objetivo: Diferentes autores han reportado una baja ingesta de ácido fólico en pacientes con Trastornos de la Conducta Alimentaria (TCA). Esta vitamina desempeña un papel esencial en las reacciones de síntesis de neurotransmisores y elementos estructurales de las neuronas y, por lo tanto, su deficiencia se ha asociado con la presencia de diferentes trastornos relacionados con la función mental. El objetivo de este estudio fue determinar el efecto de la suplementación con ácido fólico sobre los niveles de homocisteína y sobre marcadores de función cognitiva y depresión en un grupo de pacientes con TCA con baja ingesta de ácido fólico. Sujetos y métodos: Estudio clínico randomizado y prospectivo en el que se incluyeron 24 pacientes asignados a dos grupos de tratamiento durante un período de 6 meses: grupo suplementado (SG) (10 mg/día de ácido fólico [ACFOL®]) y grupo placebo (PG). Ambos grupos mantuvieron su tratamiento médico, dietético y psicológico. Al inicio del estudio y tras la intervención se evaluaron parámetros antropométricos, dietéticos y bioquímicos (homocisteína plasmática [Hcy], folato sérico y eritrocitario). Como marcadores de función cognitiva y depresión se administraron diferentes cuestionarios (Test de Stroop, Trail Making Test, BDI: Cuestionario de percepción de función cognitiva). Resultados: Completaron el estudio 22 pacientes (SG: 12, PG: 10, edad media: 24,2 ± 8,8 años, IMC 18,9 ± 3,5 kg/m2). El grupo SG incrementó de forma significativa sus niveles de folato sérico y eritrocitario y redujo el de homocisteína (9,4 ± 2,4 µmol/l vs. 7,5 ± 1,7 µmol/l, P < 0,01). Además, el grupo SG también mejoró significativamente las puntuaciones de los test de función cognitiva y depresión. En el grupo PG, en cambio, no se observaron cambios significativos en ninguna de las variables evaluadas. Conclusiones: Los resultados obtenidos demuestran que la suplementación con ácido fólico podría emplearse como una herramienta más dentro del complejo y multidisciplinario tratamiento que requieren estos pacientes.

A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders / Estudio piloto sobre el efecto de la suplementación con ácido fólico en la mejora de los niveles de homocisteína, función cognitiva y estado depresivo en trastornos de la conducta alimentaria

BACKGROUND & AIMS: Several authors have reported low folate intake in patients with eating disorders (ED). This vitamin plays an essential role in synthesis reactions for neurotransmitters and structural elements of neurons, and therefore its deficiency has been associated with the presence of different disorders linked to mental function. The aim of this study was to determine the effect of folic acid supplementation on homocysteine levels and the cognitive and depressive status of a group of patients with eating disorders with low folate intake.SUBJECTS/METHODS: The study was designed as a randomised, prospective clinical trial, which included 24 participants assigned to two treatment groups for six months: supplemented group (SG) (10 mg/day of folic acid [ACFOL]) and a placebo group (PG). Both groups maintained their medical, dietary and psychological treatment. At baseline and end of the intervention, anthropometric, dietary and biochemical parameters (plasma homocysteine [Hcy], serum and red blood cell folate) were recorded. Cognitive and depressive status questionnaires were administered (Stroop Test, Trail Making Test and Beck Depression Inventory).RESULTS: Twenty-two patients completed the study (SG: 12, PG: 10, mean age: 24.2 ± 8.8 years, BMI 18.9 ± 3.5 kg/m2). The SG significantly increased their serum and red blood cell folate levels and lowered Hcy levels (9.4 ± 2.4 μmol/l vs. 7.5 ± 1.7 μmol/l, P < 0.01). The SG also significantly improved most of their test scores for cognitive and depressive status. The PG showed no significant changes in any of the evaluated variables. CONCLUSIONS: The results show that folic acid supplementation may be used as another tool within the comprehensive and multidisciplinary treatment applied to patients with ED (AU)

Introducción y objetivo: Diferentes autores han reportado una baja ingesta de ácido fólico en pacientes con Trastornos de la Conducta Alimentaria (TCA). Esta vitamina desempeña un papel esencial en las reacciones de síntesis de neurotransmisores y elementos estructurales de las neuronas y, por lo tanto, su deficiencia se ha asociado con la presencia de diferentes trastornos relacionados con la función mental. El objetivo de este estudio fue determinar el efecto de la suplementación con ácido fólico sobre los niveles de homocisteína y sobre marcadores de función cognitiva y depresión en un grupo de pacientes con TCA con baja ingesta de ácido fólico. Sujetos y métodos: Estudio clínico randomizado y prospectivo en el que se incluyeron 24 pacientes asignados a dos grupos de tratamiento durante un período de 6 meses: grupo suplementado (SG) (10 mg/día de ácido fólico [ACFOL®]) y grupo placebo (PG). Ambos grupos mantuvieron su tratamiento médico, dietético y psicológico. Al inicio del estudio y tras la intervención se evaluaron parámetros antropométricos, dietéticos y bioquímicos (homocisteína plasmática [Hcy], folato sérico y eritrocitario). Como marcadores de función cognitiva y depresión se administraron diferentes cuestionarios (Test de Stroop, Trail Making Test, BDI: Cuestionario de percepción de función cognitiva). Resultados: Completaron el estudio 22 pacientes (SG: 12, PG: 10, edad media: 24,2 ± 8,8 años, IMC 18, ± 3,5 kg/m2). El grupo SG incrementó de forma significativa sus niveles de folato sérico y eritrocitario y redujo el de homocisteína (9,4 ± 2,4 /µmol/l vs. 7,5 ± 1,7 µmol/l, P < 0,01). Además, el grupo SG también mejoró significativamente las puntuaciones de los test de función cognitiva y depresión. En el grupo PG, en cambio, no se observaron cambios significativos en ninguna de las variables evaluadas. Conclusiones: Los resultados obtenidos demuestran que la suplementación con ácido fólico podría emplearse como una herramienta más dentro del complejo y multidisciplinario tratamiento que requieren estos pacientes (AU)

Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV). STUDY DESIGN: The study cohort comprised 26 patients with symptomatic congenital CMV born between 1993 and 2009 in a single center. Absolute and weight deficit-adjusted head circumference were considered. Cerebrospinal fluid (CSF) investigations included standard cytochemical analysis, determination of beta2-microglobulin (ß2-m), neuron-specific enolase, and CMV DNA detection. Neuroimaging was classified according to a validated scoring system comprising calcifications, ventriculomegaly, and atrophy, with findings graded from 0 to 3. Systematic long-term neurodevelopmental assessment included motor function, cognition, behavior, hearing, vision, and epilepsy. Sequelae were graded as mild/absent, moderate, or severe; adverse outcome was defined as death or moderate to severe disability. RESULTS: Three children died. The mean age at follow-up of the survivors was 8.7 ± 5.3 years (range, 19 months to 18.0 years). Neonatal findings showing a significant association with adverse outcome were relative microcephaly, CSF ß2-m concentrations, and grade 2-3 neuroimaging abnormalities (P < .05). Receiver operator characteristic curve analysis indicated that the most accurate single factor for predicting unfavorable outcome was CSF ß2-m >7.9 mg/L (area under the curve, 0.84 ± 0.08; sensitivity, 69%; specificity, 100%). The combination of CSF ß2-m >7.9 mg/L and moderate-severe neuroimaging alterations improved predictive ability (area under the curve, 0.92 ± 0.06; sensitivity, 87%; specificity, 100%). CONCLUSION: Adjusted head circumference, CSF ß2-m level, and neuroimaging studies have prognostic significance for neurodevelopmental outcome in newborns with congenital CMV. A combination of early findings improves the predictive value.

Dynamic hyperinflation, arterial blood oxygen, and airway oxidative stress in stable patients with COPD.

BACKGROUND: There is considerable evidence that oxidative stress is increased in patients with COPD, although little information is available about its relationship with the structural and functional alterations produced by COPD. In this study, we evaluated the relationship between 8-isoprostane in exhaled breath condensate (EBC) of stable patients with COPD and the main parameters of the disease (such as dyspnea), stages of severity, lung parenchyma densities, lung function impairment, and exercise tolerance in order to identify the predictors of airway oxidative stress. METHODS: In a cross-sectional study, we included 76 men with moderate to very severe COPD. 8-Isoprostane levels in EBC were measured by enzyme immunoassay. Regional lung densities were measured by lung densitometry with high-resolution CT scanning. Arterial blood gas levels, lung volumes, and diffusing capacity were determined. Patients performed a 6-min walk test and an incremental exercise test with measurement of breathing pattern and operating lung volumes. RESULTS: Significant severity-related differences in 8-isoprostane were identified according to the BMI, obstruction, dyspnea, and exercise (BODE) index. 8-Isoprostane levels were related to smoking intensity, lung densities in expiration, static lung volumes, PaO(2), diffusion capacity, distance walked in 6 min, peak oxygen uptake, and anaerobic threshold. Concentration of 8-isoprostane was higher in the 60 patients (79%) who developed dynamic hyperinflation than in the remaining 16 (21%) who did not. In a multivariate linear regression analysis using 8-isoprostane as a dependent variable, end-expiratory lung volume change and PaO(2) were retained in the prediction model (r(2) = 0.734, P < .001). CONCLUSIONS: In stable patients with COPD, oxygen level and dynamic hyperinflation are related to airway oxidative stress.

Sulfur-containing antioxidants increase in vitro several functions of lymphocytes from mice.

The in vitro effects of several sulfur-containing antioxidants, such as glutathione (GSH), N-acetylcysteine (NAC), thioproline (TP) and taurine (TAU), at different concentrations, on key functions of lymphocytes from axillary nodes, spleen, thymus and peritoneum from young-adult BALB/c mice have been investigated. The functions studied have been proliferation, both spontaneous and in response to the mitogen Concanavalin A, mobility both spontaneous and directed to a chemical attractant (chemotaxis) and adherence to substrate. The effect of these antioxidants on the viability of leukocytes was also investigated. The results show an antioxidant-induced stimulation of all the functions studied. The highest concentrations used of each antioxidant were the most effective in proliferation (5mM for GSH, 1mM for TP and NAC and 40 mM for TAU). These concentrations increase mobility significantly. The presence of TP+NAC enhances the chemotaxis of peritoneal lymphocytes more than each antioxidant separately. The adherence capacity of peritoneal lymphocytes also increased at 10 min of incubation with GSH, TP and NAC. All these antioxidants increase the viability of leukocytes in culture, especially in cells from spleen. In conclusion, the sulfur-containing antioxidants studied in vitro improve the functional capacity of lymphocytes from young-adult mice and these results showing that the improvement of the immune response, and specifically of the lymphocyte functions, found after ingesting diet supplemented with the antioxidants studied, are due to a direct action of these compounds in the immune cells.

Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation.

RATIONALE: Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity. OBJECTIVES: To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD. METHODS: In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate. MEASUREMENTS AND MAIN RESULTS: Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), Vo(2) (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = -0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = -0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r(2) = 0.84; P = 0.001). CONCLUSIONS: Daily physical activity of patients with COPD is mainly associated with dynamic hyperinflation, regardless of severity classification.

Vitamin E ingestion improves several immune functions in elderly men and women.

The effects of diet supplementation with the antioxidant vitamin E (200 mg daily) on several blood neutrophil, lymphocyte and natural killer cell functions have been investigated in healthy elderly men and women before supplementation, after 3 months of supplementation and 6 months after the end of supplementation (post-supplementation). In parallel, samples of healthy adult men and women were used as age controls. In elderly men and women, an impairment of immune functions was observed in comparison with the respective adult controls and the intake of vitamin E resulted in a significant enhancement of immune parameters in both elderly men and women, bringing their values close to those in the adults. These effects were not found in post-supplementation samples in several but not in all functions. The present findings suggest that supplementation with vitamin E can produce an improvement of immune functions and therefore of health in aged people.

A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence.

The intensity of behavioral and neuroendocrine responses to stressful stimuli in rodent strains seems to be inversely related to their life span. We have previously shown that interindividual differences in members of outbred Swiss and inbred BALB/c mouse populations, both male and female, may be related to their behavior in a simple T-maze test. The animals that explore the maze slowly show impaired neuromuscular vigor and coordination, decreased locomotor activity, increased level of emotionality/anxiety, decreased levels of brain biogenic amines as well as immunosenescence and decreased life span, when compared to their control counterparts, which quickly explore the maze. These traits are similar to some of the alterations previously observed in aging animals and therefore we proposed that those 'slow mice' are biologically older than the fast animals and may be a model of prematurely aging mice (PAM). Although most of our work on this model has been performed on chronologically adult-mature animals, we have also shown that certain characteristics of PAM, such as increased anxiety and deficient immune response, are already present in chronologically young animals. Thus, it is tempting to hypothesize that chronic hyperreactivity to stress (trait anxiety) leading to immune dysfunction may have a causal relationship with impaired health and premature aging. In view of the link between oxidative stress and the aging process, the redox state of peritoneal leukocytes from PAM has been studied, showing an oxidative stress situation. In the present work we have determined the levels of a key antioxidant, reduced glutathione (GSH), and the oxidant malondialdehyde (MDA), a marker of lipid peroxidation, both in the spleen and brain of male and female PAM and non-PAM (NPAM). We found that GSH and MDA are decreased and increased, respectively, in PAM with respect to NPAM. Moreover, diet supplementation with antioxidants showed to be an effective strategy for protection against early immune and behavioral decline, altered redox state of leukocytes and premature mortality in PAM, which supports the validity of this model of premature aging as well as its link with oxidative stress.

Plasma aminothiol compounds, but not serum tumor necrosis factor receptor II and soluble receptor for advanced glycation end products, are related to the cognitive impairment in Alzheimer's disease and mild cognitive impairment patients.

Increasing evidence indicates that factors such as oxidative stress, plasma homocysteine increase and glutathione depletion, elevated pro-inflammatory cytokines and advanced glycation end products can play a role in Alzheimer's disease (AD) pathogenesis. The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in neurodegeneration, and a soluble isoform of RAGE (sRAGE) has the ability to prevent the adverse effects of RAGE signaling by acting as a decoy. Twenty-five patients with AD, 26 with mild cognitive impairment (MCI) and 44 age-matched control subjects were studied. All subjects were classified according to their clinical, cognitive and positron emission tomography study. Serum levels of sRAGE and TNF-alpha receptor II were not significantly different in AD or MCI patients compared to controls. Total plasma levels of glutathione and its metabolite cysteinglycine were decreased in AD and MCI patients compared to the control group. In addition, AD patients presented significantly increased plasma homocysteine compared to those in MCI patients and controls. We found significant positive correlations between sRAGE and glutathione, cysteinglycine and cysteine levels. Moreover, a significant negative correlation between the total score of cognitive impairment and homocysteine levels, and significant positive correlations with glutathione, cysteinglycine and cysteine levels were observed. These findings indicate that plasma aminothiol compounds are associated with AD and MCI patients and with their cognitive status.

[Increased homocysteine levels in polycystic ovary syndrome]. / Concentraciones elevadas de homocisteína en el síndrome de ovario poliquístico.

BACKGROUND AND OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit frequently risk factors that predispose to cardiovascular disease. Hyperhomocysteinemia is an independent risk factor for this disease. The aim of this study was to know whether young women with PCOS have increased homocysteine levels. We also analyzed their possible relation with folate and vitamin B12 levels. PATIENTS AND METHOD: Thirty nine patients with PCOS were studied; (age: mean [standard deviation] 28.9 [5.8] years), and 39 healthy women similar in age. We evaluated in all of them: smoking, menstrual cycles, hirsutism, body mass index, metabolic syndrome and levels of homocysteine, lipids, glucose, creatinine, folate, vitamin B12, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and androstendione. RESULTS: Menstrual cycles, hirsutism, androstendione, LH levels and LH/FSH were higher, as we expected, in patients with PCOS. Moreover, patients had increased homocysteine (9.1 [2.1] vs 6.4 [1.8] micromol/L; p < 0.001) and glucose levels (99 [13] vs 88 [10] mg/dl; p < 0.001), a higher frequency of abnormal fasting glycemia (> 110 mg/dl) (23% vs 2.5%; p =.01) and lower folate levels (7.6 [3.7] vs 10.2 [3.6] ng/ml; p = 0.02). A multiple linear regression showed a negative association between homocysteine and folate levels (r2 = 0.05; p =.02). CONCLUSIONS: Homocysteinemia is increased in women with PCOS, and it is negatively associated with folate levels.

Beta2-microglobulin concentrations in cerebrospinal fluid correlate with neuroimaging findings in newborns with symptomatic congenital cytomegalovirus infection.

OVERVIEW: In newborns with symptomatic congenital cytomegalovirus (CMV) infection, neuroimaging is the best available predictor of neurodevelopmental outcome. Cerebrospinal fluid (CSF) findings in congenital CMV infection have seldom been described. Neonates with central nervous system infections present high CSF Beta(2)-microglobulin (beta(2)-m) levels. OBJECTIVES: The objectives of this study were: (1) to determine whether CSF beta(2)-m is increased in newborns with symptomatic congenital CMV infection, and (2) to examine its correlation with neuroimaging findings. MATERIALS AND METHODS: Fourteen newborns with symptomatic congenital CMV infection admitted to La Paz Hospital from 1990 through 2004 underwent determination of CSF beta(2)-m. Ninety-three newborns, constituting the comparison group, underwent CSF beta(2)-m determination as part of a sepsis or meningo/encephalitis work-up, and at discharge had sterile cultures and normal neurological status. Neuroimaging findings were scored according to a semiquantitative system: (0) no abnormalities; (1) single punctate periventricular (PV) calcification and/or hyperechogenic areas in the thalamus and basal ganglia; (2) multiple discrete PV calcifications and/or ventriculomegaly; and (3) extensive PV calcifications and/or brain atrophy. DISCUSSION AND CONCLUSION: CSF beta(2)-m was increased in newborns with CMV infection (median 6.21 mg/L) compared with controls (1.68 mg/L) (P<.001). beta(2)-m showed a correlation with neuroimaging scores (r (s)=0.753, P=.002). beta(2)-m was higher in patients who scored 2-3 (12.83 mg/L) than in patients who scored 0-1 (5.52 mg/L) (P=.028). CSF beta(2)-m is increased in newborns with symptomatic congenital CMV infection and correlates with neuroimaging abnormalities. beta(2)-m appears to be an indicator of the severity of brain involvement in congenital CMV infection.

Nitric oxide released by accessory cells mediates the gastrin-releasing peptide effect on murine lymphocyte chemotaxis.

Several neuropeptides, including gastrin-releasing peptide (GRP), modulate the immune response, specifically lymphocyte chemotaxis. In the present work the effect of GRP on the chemotaxis of murine lymphocytes from different immune locations in both, total leukocyte populations and populations depleted of adherent cells have been studied. Specificity of the GRP effect on chemotaxis using an antagonist of the GRP receptor, as well as the implication of nitric oxide (NO), using inhibitors of NO synthase and donors of NO, were investigated. The effects of GRP stimulating the chemotaxis of lymphocytes from peritoneum, axillary nodes and spleen and decreasing the chemotaxis from thymus were receptor-specific and disappeared in lymphocytes from populations depleted of adherent cells. NO synthase inhibitors blocked the GRP effect on lymphocyte chemotaxis, and this action was reversed in the presence of l-arginine. Thus, the effect of GRP on murine lymphocyte chemotaxis appears to be mediated by NO secreted by adherent cells.

Congenital syphilis: beta2-microglobulin in cerebrospinal fluid and diagnosis of neurosyphilis in an affected newborn.

Meningoencephalitis in neonatal congenital syphilis (CS) is a difficult diagnosis because of the limitation of standard cerebrospinal fluid (CSF) tests. This limitation means that new markers in CSF tests are needed to establish whether meningitis is present in presumptive cases of CS. beta2-Microglobulin (beta2-m) is raised in CSF recovered from neonates with central nervous system (CNS) infections, but it does not correlate with cellular count or proteins in the CSF. We present a preterm newborn with symptomatic CS. First-day CSF showed 50 cells/mm3, protein of 220 mg/dL and a beta2-m concentration of 16.9 mg/dL (normal <2.25 mg/dL). Serial determinations of beta2-m showed a marked reduction (76%) after 10 days of appropriate treatment. At 30 days of life, beta2-m was already within the normal range (1.8 mg/dL). Cerebral ultrasonography showed ventricular dilatation, moderate periventricular echogenicity, subependimal hemorrhages, and linear hyperechoic areas in the thalamus and basal ganglia. We suggest that beta2-microglobulin is very useful in the diagnosis of CNS involvement and in monitoring the response to treatment. In addition, infants with CS may exhibit CNS imaging findings similar to those observed in other intrauterine CNS infections.

Effect of calcitonin gene-related peptide, neuropeptide Y, substance P, and vasoactive intestinal peptide on interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha production by peripheral whole blood cells from rheumatoid arthritis and osteoarthritis patients.

In the present study, we have investigated the in vitro effect of calcitonin-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal peptide (VIP) at concentrations of 10(-8), 10(-9) and 10(-10) M on the production of different proinflammatory cytokines or chemokines such as IL-1beta, IL-6 and TNFalpha by peripheral whole blood cells from patients with rheumatoid arthritis, as well as from osteoarthritis patients studied as a control group without immunoinflammatory background. We have found that CGRP, NPY, SP and VIP stimulated significantly the production of those cytokines and chemokines in rheumatoid arthritis patients. In general, the stimulation was higher at the 10(-9) M concentration, with SP and VIP, and in rheumatoid arthritis patients compared to osteoarthritis ones. Neuropeptides did not significantly modify the LPS-induced cytokine production by whole blood cells. The results indicate that physiological concentrations of the neuropeptides studied can modulate the inflammatory and immunological response, stimulating significantly the production of inflammatory cytokines by human whole blood cells in rheumatoid arthritis patients, as well as, in a minor way, in osteoarthritis patients.

Characterization of monoaminergic systems in brain regions of prematurely ageing mice.

We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration ("slow mice") being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

Folate status and a new repletion cut-off value in a group of healthy Majorcan women.

BACKGROUND AND AIMS: Folate status is complex, complicated to assess and we lack consensus for laboratory determination. Total plasma homocysteine (Hcy) is a sensitive marker of folate status. The aim of this study was choosing a plasma total homocysteine (tHcy) measurement method and folate repletion level; assess the mutation C677T frequency for methylenetetrahydrofolate reductase (MTHFR) and the prevalence of hyperhomocysteinemia in healthy Majorcan women. METHODS: The measurement methods were compared using 219 women. Folate status assessment was determined by plasma tHcy, serum and erythrocyte folate and C677T for MTHFR in 342 healthy women. The mutation frequency is established with 146 of them. RESULTS: The measurement method comparison is summarized by Y = 1.013 (IC 95% 0.959, 1.069) X +0.829 (IC 95% 0.485, 1.170). The folate repletion level was set at Hcy < or = 8.6 micromol/l. Women (67.1%) are heterozygotic and do not carry the mutation. Homozygotic frequency is 18.5%, significantly higher in women under 40 years (P = 0.033). Hyperhomocysteinemia prevalence is 19.3%, and 51.7% in the younger group. CONCLUSIONS: Hcy determination by polarized fluorescence immunoassay reflects folate status. Levels < or = 8.6 micromol/l suggest folate repletion, which is less frequent in homozygotes. Population frequency for homozygotic-TT alleles for C677T-MTHFR reductase and hyperhomocysteinemia is significantly higher in women under 40 years.

Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-alpha have been demonstrated in thyroid follicular cells and TNF-alpha and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-alpha have been reported to be elevated and administration of TNF-alpha to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome. OBJECTIVE: To evaluate serum concentrations of TNF-alpha and the soluble receptor for TNF-alpha (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. DESIGN: We studied 20 patients with hypothyroidism (18 women and 2 men, mean age +/- SD, 48.8 +/- 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 +/- 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 +/- 15.1 years) were also studied as a control group. SETTING: All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic. MEASUREMENTS: Serum concentrations of free T4 (FT4), total T3, TSH, TNF-alpha and sTNFR-I were measured in all subjects. TNF-alpha and sTNFR-I were measured using a quantitative enzyme immunoassay. RESULTS: In patients with hypothyroidism serum concentrations of TNF-alpha (3.17 +/- 1.18 pg/ml) and sTNFR-I (1273 +/- 364 pg/ml) were significantly higher than those found in controls (2.42 +/- 0.76 pg/ml, P < 0.05, and 971 +/- 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with l-thyroxine therapy did not significantly modify TNF-alpha or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-alpha and sTNFR-I in patients with autoimmune (n = 14) or nonautoimmune (n = 6) hypothyroidism. Before therapy, patients with hyperthyroidism showed elevated serum concentrations of TNF-alpha (3.36 +/- 1.21 pg/ml; P < 0.01) and sTNFR-I (2274 +/- 579 pg/ml; P < 0.001) in relation to the control group. Treatment of hyperthyroidism was accompanied by a normalization of TNF-alpha levels (2.46 +/- 0.89 pg/ml; P < 0.001) and by a significant decrease in sTNFR-I concentrations (1369 +/- 475 pg/ml; P < 0.001). Post-therapy levels of TNF-alpha and sTNFR-I showed a significant correlation with loss of weight (r = 0.674, P < 0.01, and r = 0.629, P < 0.01, respectively) in hypothyroid patients. No correlation between these parameters was found in the group of patients with hyperthyroidism. CONCLUSIONS: In summary, these results confirm the relevance of activation of the TNF-alpha system in patients with thyroid dysfunction, as high plasma concentrations of TNF-alpha and sTNFR-I have been demonstrated in patients with hypothyroidism or hyperthyroidism. Treatment of hyperthyroidism is accompanied by a significant reduction in the previously elevated concentrations of both TNF-alpha and sTNFR-I. However, these changes are not seen when normalizing thyroid function in patients with hypothyroidism.