Methylphenidate ameliorates the homeostatic balance between levels of kynurenines in ADHD children.

The kynurenine pathway of tryptophan metabolism has been involved in ADHD We quantified basal levels and daily fluctuations of tryptophan and several kynurenine metabolites, as well as their changes after treatment with methylphenidate (MPH). A total of 179 children were recruited, grouped into ADHD (n = 130) and healthy controls (CG,n = 49). Blood samples were drawn at 20:00 and 09:00 h and only in the ADHD group after 4.63±2.3 months of treatment. Nocturnal urine was collected between both draws. Factorial analysis (Stata12.0) was performed with Groups, Time, Hour of Day and Depressive Symptoms (DS) as factors. MPH significantly increased plasma Kynurenic acid (2.4 ± 1.03/2.78±1.3 ng/mL; baseline/post-treatment, morning; z = 1.96,p<0.05) and Xanthurenic acid (2.39±0.95/2.88±1.19 ng/mL; baseline/post, morning; z = 2.7,p<0.007) levels, both with higher values in the evening. In DS+ patients, MPH caused a pronounced decrease in evening Anthranilic acid [3.08±5.02/ 1.82±1.46 ng/mL, z = 2.68,p = 0.0074] until matching values to other subgroups. In urine, MPH decreased the excretion of both Nicotinamide and Quinolinic acids, but only in the DS- subgroup. The kynurenine pathway may participate in the highly clinical favorable response to MPH. The observed changes could be considered as protective (i.e. increased plasma kynurenic acid vs. decreased quinolinic acid excretion) based on the knowledge of its physiological homeostatic functions.

Indole Tryptophan Metabolism and Cytokine S100B in Children with Attention-Deficit/Hyperactivity Disorder: Daily Fluctuations, Responses to Methylphenidate, and Interrelationship with Depressive Symptomatology.

Background: Indole tryptophan metabolites (ITMs), mainly produced at the gastrointestinal level, participate in bidirectional gut-brain communication and have been implicated in neuropsychiatric pathologies, including attention-deficit/hyperactivity disorder (ADHD). Method: A total of 179 children, 5-14 years of age, including a healthy control group (CG, n = 49), and 107 patients with ADHD participated in the study. The ADHD group was further subdivided into predominantly attention deficit (PAD) and predominantly hyperactive impulsive (PHI) subgroups. Blood samples were drawn at 20:00 and 09:00 hours, and urine was collected between blood draws, at baseline and after 4.63 ± 2.3 months of methylphenidate treatment in the ADHD group. Levels and daily fluctuations of ITM were measured by tandem mass spectrometer, and S100B (as a glial inflammatory marker) by enzyme-linked immunosorbent assay. Factorial analysis of variance (Stata 12.0) was performed with groups/subgroups, time (baseline/after treatment), hour of day (morning/evening), and presence of depressive symptoms (DS; no/yes) as factors. Results: Tryptamine and indoleacetic acid (IAA) showed no differences between the CG and ADHD groups. Tryptamine exhibited higher evening values (p < 0.0001) in both groups. No changes were associated with methylphenidate or DS. At baseline, in comparison with the rest of study sample, PHI with DS+ group showed among them much greater morning than evening IAA (p < 0.0001), with treatment causing a 50% decrease (p = 0.002). Concerning indolepropionic acid (IPA) MPH was associated with a morning IPA decrease and restored the daily profile observed in the CG. S100B protein showed greater morning than evening concentrations (p = 0.001) in both groups. Conclusion: Variations in ITM may reflect changes associated with the presence of DS, including improvement, among ADHD patients.

BDNF concentrations and daily fluctuations differ among ADHD children and respond differently to methylphenidate with no relationship with depressive symptomatology.

RATIONALE: Brain-derived neurotrophic factor (BDNF) enhances the growth and maintenance of several monoamine neuronal systems, serves as a neurotransmitter modulator and participates in the mechanisms of neuronal plasticity. Therefore, BDNF is a good candidate for interventions in the pathogenesis and/or treatment response of attention deficit hyperactivity disorder (ADHD). OBJECTIVE: We quantified the basal concentration and daily fluctuation of serum BDNF, as well as changes after methylphenidate treatment. METHOD: A total of 148 children, 4-5 years old, were classified into groups as follows: ADHD group (n = 107, DSM-IV-TR criteria) and a control group (CG, n = 41). Blood samples were drawn at 2000 and 0900 hours from both groups, and after 4.63 ± 2.3 months of treatment, blood was drawn only from the ADHD group for BDNF measurements. Factorial analysis was performed (Stata software, version 12.0). RESULTS: Morning BDNF (36.36 ± 11.62 ng/ml) in the CG was very similar to that in the predominantly inattentive children (PAD), although the evening concentration in the CG was higher (CG 31.78 ± 11.92 vs PAD 26.41 ± 11.55 ng/ml). The hyperactive-impulsive group, including patients with comorbid conduct disorder (PHI/CD), had lower concentrations. Methylphenidate (MPH) did not modify the concentration or the absence of daily BDNF fluctuations in the PHI/CD children; however, MPH induced a significant decrease in BDNF in PAD and basal day/night fluctuations disappeared in this ADHD subtype. This profile was not altered by the presence of depressive symptoms. CONCLUSIONS: Our data support a reduction in BDNF in untreated ADHD due to the lower concentrations in PHI/CD children, which is similar to other psychopathologic and cognitive disorders. MPH decreased BDNF only in the PAD group, which might indicate that BDNF is not directly implicated in the methylphenidate-induced amelioration of the neuropsychological and organic immaturity of ADHD patients.

Methylphenidate ameliorates depressive comorbidity in ADHD children without any modification on differences in serum melatonin concentration between ADHD subtypes.

UNLABELLED: The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria) were divided into subgroups using the "Children's Depression Inventory" (CDI). Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD) of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. CONCLUSIONS: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.

Programa de intervención mixta sobre el cumplimiento y calidad de vida en pacientes hipertensos / Mixed intervention programme on compliance and quality of life in hypertensive patients

El 70% de los pacientes en tratamiento antihipertensivo no controla adecuadamente sus cifras tensionales. El objetivo del estudio es comparar el impacto de diferentes intervenciones de formación de pacientes hipertensos esenciales, respecto a un grupo control sin intervención, sobre el cumplimiento terapéutico autorreferido, la presión arterial, el peso y la calidad de vida. Ensayo clínico aleatorizado multicéntrico, con tres ramas de intervención (intervención educativa, información escrita y control) incluyendo 520 pacientes hipertensos esenciales. Las variables de estudio fueron: TA, peso, cumplimiento fármacodietético, grado de conocimiento sobre la enfermedad y calidad de vida. Completaron el estudio 428 pacientes. Analizando los resultados, los pacientes del grupo de intervención tuvieron un descenso de la PAS/PAD superior al resto de los grupos. Así mismo, se aprecia un elevado nivel de cumplimiento farmacológico, menor cumplimiento higiénico dietético y mayor nivel de conocimientos en pacientes de centros hospitalarios. La mayoría de los pacientes, mostraron niveles muy altos de satisfacción hacia personal sanitario en los diferentes aspectos analizados (AU)

70% of patients on treatment for hypertension do not control their blood pressure levels adequately. The aim of the study is to compare the impact of different training interventions for essential hypertensive patients, compared to a control group with no intervention, on self-referred therapeutic compliance, blood pressure, weight and quality of life. Multi-centre randomized clinical trail with three branches of intervention (educational intervention, written information and check-up) including 520 essential hypertensive patients. The variables in the study were BP, weight, medication and diet compliance, level of knowledge of the illness and quality of life. 428 patients completed the study. Analysing the results, patients in the group with intervention had a higher reduction in systolic/diastolic BP than the other groups. The results also showed a high level of medication compliance, lower health and diet compliance, and greater knowledge in patients in hospitals. Most of the patients showed very high levels of satisfaction towards healthcare staff in the different aspects analysed (AU)

Eficacia de un programa de intervención sobre el control del peso en pacientes obesos hipertensos / Efficacy of a weight control intervention programme in obese hypertensive patients

La obesidad supone un importante riesgo añadido en la población de pacientes hipertensos, por su prevalencia y por su agregación a otros factores de riesgo. Nuestro objetivo fue cuantificar las diferencias en la reducción de peso de dos tipos de intervención educacional conducidos por enfermería: intensiva frente a información escrita. Para ello se diseñó un estudio clínico prospectivo, comparativo entre dos ramas de intervención no farmacológica, en la que se realizan dos tipos distintos de intervenciones que se asignarán de forma aleatoria por el investigador: 1) programa de intervención intensiva de 6 meses de duración con 6 visitas educativas individuales basado en el programa "FORMA" (grupo intervención) y 2) Aporte de información verbal y material escrito, en una única ocasión, para recomendar la pérdida de peso, sin que se realicen visitas de seguimiento, hasta los 6meses (grupo control).Se reclutaron pacientes, hipertensos esenciales, obesos, no diabéticos y sin complicaciones cardiovasculares, atendidos de forma consecutiva y que cumplían los criterios de selección: edad 18-70 años, IMC: 28-40 kg/m2. Completaron el estudio 145 pacientes (53.7±12 años de edad, 58.8% mujeres), reclutados en 16 centros. El programa de intervención intensiva indujo una reducción promedio de peso significativa frente al grupo 2 (3.7± 3.4 vs. 0.66± 2.9 kg, p=0.001). Los factores que influían significativamente en la reducción, según un modelo de regresión lineal múltiple, fueron el sexo (mayor en los hombres) y el centro. Los niveles de presión al inicio (146±17/88±13mmHg) eran similares en ambos grupos, siendo la reducción de presión mayor en el grupo de intervención intensiva, sin alcanzar la significación (9.0±19.5 vs4.5±12.9 mmHg), aunque en los hombres, la diferencia si fue significativa (15.1±19.3 vs. 6.48±11.4mmHg)...(AU)

Obesity is an important added risk factor in the population of hypertensive patients, because of its prevalence and its aggregation to other risk factors. Our aim was to quantify the differences in weight loss of two types of nursing-led educational intervention: intensive compared to written information. For this purpose a prospective clinical study was designed comparing two branches of non-pharmacological intervention, in which two different types of intervention were conducted, which were assigned at random by the researcher: 1) 6-month intensive intervention programme with 6 individual educational visits, based on the “FITNESS” programme (intervention group) and 2) Distribution of verbal information and written material, on a single occasion, to recommend losing weight, but without any follow-up visits until 6 months later (control group).Essential hypertensive, obese non-diabetic patients without cardiovascular complications were recruited and were attended consecutively, in line with the following selection criteria: age 18-70, BMI: 28-40kg/m2. A total of 145 patients completed the study (aged 53.7±12 years, 58.8% women), recruited in16 centres. The intensive intervention programmeled to significant average weight loss compared to group 2 (3.7± 3.4 v. 0.66± 2.9 kg, p=0.001). The factors that had a significant influence on the weight loss, according to a multiple linear regression model, were sex (greater in men) and the centre. Blood pressure levels at the start (146±17/88±13mmHg) were similar in both groups, with the biggest reduction in blood pressure occurring in the intensive intervention group, without achieving a significant level(9.0±19.5 v 4.5±12.9 mmHg), although in men the difference was significant (15.1±19.3 v. 6.48±11.4mmHg). In the multivariant model, the fall in blood pressure depended on the weight loss obtained, the sex and the centre...(AU)