Melatonin as a regulatory hub of plant hormone levels and action in stress situations.

Melatonin, a molecule first discovered in animal tissues, plays an important role in multiple physiological responses as a possible plant master regulator. It mediates responses to different types of stress, both biotic and abiotic. Melatonin reduces the negative effects associated with stressors, improving the plant response by increasing plant stress tolerance. When plants respond to stress situations, they use up a large amount of plant resources through a set of perfectly synchronized actions. Responses mediated by melatonin use the plant's hormones to, after adequate modulation, counteract and overcome the negative action of the stressor. In this paper, we review melatonin-plant hormone relationships. Factors that trigger the stress response and the central role of melatonin are analysed. An extensive analysis of current studies shows that melatonin modulates the metabolism of plant hormones (biosynthesis and catabolism), the rise or fall in their endogenous levels, the regulation of signalling elements and how melatonin affects the final response of auxin, gibberellins, cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates, brassinosteroids, polyamines and strigolactones. Lastly, a general overview of melatonin's actions and its regulatory role at a global level is provided and proposals for future research are made.

Melatonin in flowering, fruit set and fruit ripening.

KEY MESSAGE: Melatonin induces a delay in flowering stabilizing DELLA proteins and also promotes the transcription of FLC. In fruit set, melatonin is able to induce parthenocarpy. Melatonin promotes ripening and retards senescence of fruits. Melatonin is an animal hormone involved in many regulatory processes such as those related to sleep. Melatonin was discovered in plants in 1995 and is called phytomelatonin. Also in plants, a great variety of physiological processes have been described in which melatonin plays a role. In plants, melatonin is mainly involved in stress situations but also in germination, plant growth, rhizogenesis, senescence and as a protector agent improving important processes such as photosynthesis, CO2 uptake, cell water economy and primary and secondary metabolism. Melatonin has been related to changes in the majority of plant hormones. Many revisions of stress situations have been published. However, melatonin and plant reproductive development have been poorly studied. The aim of this review is to provide an overview of works related to flowering, fruit set and development, including parthenocarpy and fruit ripening/senescence, and the role played by melatonin in the same.

The Potential of Cryotherapy to Remove Sugarcane Mosaic Virus from Sugarcane (Saccharum spp. hybrids) Shoot Tips.

BACKGROUND: Virus-free sugarcane is difficult to achieve due to the multiple vegetative propagation cycles employed commercially. In vitro culture using small (1 mm) meristematic shoot tips has eliminated viruses but survival is low with small explants. OBJECTIVE: Droplet-Vitrification (D-V) and V-Cryoplate protocols were investigated for the elimination of Sugarcane mosaic virus (SCMV) from large (c. 3 mm) in vitro-derived shoot tips. MATERIALS AND METHODS: Shoot tips excised from NCo376 and N19 cultivars were exposed to both cryogenic procedures. Virus indexing by RT-qPCR was performed 16 weeks after recovery. RESULTS: Explants exposed to cryo-treatments that recovered and multiplied was 30-92%, while at least 90% of control explants regenerated. No virus was detected in multiplied shoots from either cultivar after D-V and liquid nitrogen immersion. In NCo376, virus was eliminated after D-V without cooling. CONCLUSION: The preliminary findings suggest that cryotherapy and/or osmotherapy are viable options for SCMV removal from infected plants.

Sustained attention in school-age children with congenital hypothyroidism: Influence of episodes of overtreatment in the first three years of life. / Atención sostenida en niños con hipotiroidismo congénito en edad escolar. Influencia de los episodios de sobretratamiento en los primeros 3 años de vida.

INTRODUCTION: Children with congenital hypothyroidism (CH) are at risk of developing mild cognitive impairment despite normal overall intellectual performance. These deficits may be caused by disease-related and treatment-related factors. This study explores the impact of abnormal thyroid function during the first 3 years of life on attention performance at school age. METHODS: We included 49 children diagnosed with CH and receiving treatment for the condition: 14 boys (mean age 9.5±2.8 years) and 35 girls (9.6±2.6 years). The number of episodes of normal, under-, and overtreatment were estimated based on TSH levels during their first 3 years of life (at 12, 18, 24, 30, and 36 months). Children were assessed using a computerised version of a Sustained attention test. General linear models were calculated with the attention index as the dependent variable and sex, aetiology, and number of episodes of normal, under-, and overtreatment as independent variables. RESULTS: Higher numbers of episodes of overtreatment (low TSH level) were associated with poorer attention performance at school age (P=.005, r=-0.45). CONCLUSIONS: Children with CH should be monitored closely during the first 3 years of life in order to prevent not only hypothyroidism but also any adverse effects of overtreatment that may affect attentional function at school age.

Melatonin and its relationship to plant hormones.

BACKGROUND: Plant melatonin appears to be a multi-regulatory molecule, similar to those observed in animals, with many specific functions in plant physiology. In recent years, the number of studies on melatonin in plants has increased significantly. One of the most studied actions of melatonin in plants is its effect on biotic and abiotic stress, such as that produced by drought, extreme temperatures, salinity, chemical pollution and UV radiation, among others. SCOPE: This review looks at studies in which some aspects of the relationship between melatonin and the plant hormones auxin, cytokinin, gibberellins, abscisic acid, ethylene, jasmonic acid and salicylic acid are presented. The effects that some melatonin treatments have on endogenous plant hormone levels, their related genes (biosynthesis, catabolism, receptors and transcription factors) and the physiological actions induced by melatonin, mainly in stress conditions, are discussed. CONCLUSIONS: Melatonin is an important modulator of gene expression related to plant hormones, e.g. in auxin carrier proteins, as well as in metabolism of indole-3-acetic acid (IAA), gibberellins, cytokinins, abscisic acid and ethylene. Most of the studies performed have dealt with the auxin-like activity of melatonin which, in a similar way to IAA, is able to induce growth in shoots and roots and stimulate root generation, giving rise to new lateral and adventitious roots. Melatonin is also able to delay senescence, protecting photosynthetic systems and related sub-cellular structures and processes. Also, its role in fruit ripening and post-harvest processes as a gene regulator of ethylene-related factors is relevant. Another decisive aspect is its role in the pathogen-plant interaction. Melatonin appears to act as a key molecule in the plant immune response, together with other well-known molecules such as nitric oxide and hormones, such as jasmonic acid and salicylic acid. In this sense, the discovery of elevated levels of melatonin in endophytic organisms associated with plants has thrown light on a possible novel form of communication between beneficial endophytes and host plants via melatonin.

Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale.

OBJECTIVES: The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. MATERIALS AND METHODS: The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. RESULTS: Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928). CONCLUSION: Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies.

Molecular mechanisms by which white tea prevents oxidative stress.

The flavonoid content of tea (Camellia sinensis) has beneficial properties in the prevention of diseases. However, the mechanisms by which white tea can protect against oxidative stress remain unclear. To shed light on this issue, rats were given distilled water (controls), 0.15 mg/day (dose 1) or 0.45 mg/day (dose 2) of solid tea extract/kg body weight for 12 months. All the animals received an injection of adriamycin (ADR; 10 mg/kg body weight), except half of the control group, which were given an injection of saline solution. The expression of the nuclear factor, E2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (Nqo1), glutathione S-transferase (Gst), haem oxygenase-1 (Ho1), catalase (Cat), superoxide dismutase (Sod) and glutathione reductase (Gr) in liver was analysed by real-time PCR, and the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) was measured spectrophotometrically. ADR significantly increased the expression of Nrf2, Gst, Nqo1, Ho1, Cat, Sod and Gr with respect to the control levels and also increased the activity of CAT, SOD and GR. The intake of white tea increased in a higher degree the expression of Nrf2, Gst, Nqo1 and Ho1 in the tea + ADR group compared with the control group and C + ADR group. In addition, tea + ADR groups decreased the expression and activity of CAT, SOD and GR in a dose-dependent manner.

Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome.

Individual responses to growth hormone (GH) treatment are variable. Short-term generation of insulin-like growth factor-I (IGF-I) is recognized as a potential marker of sensitivity to GH treatment. This prospective, phase IV study used an integrated genomic analysis to identify markers associated with 1-month change in IGF-I (ΔIGF-I) following initiation of recombinant human (r-h)GH therapy in treatment-naïve children with GH deficiency (GHD) (n=166) or Turner syndrome (TS) (n=147). In both GHD and TS, polymorphisms in the cell-cycle regulator CDK4 were associated with 1-month ΔIGF-I (P<0.05). Baseline gene expression was also correlated with 1-month ΔIGF-I in both GHD and TS (r=0.3; P<0.01). In patients with low IGF-I responses, carriage of specific CDK4 alleles was associated with MAPK and glucocorticoid receptor signaling in GHD, and with p53 and Wnt signaling pathways in TS. Understanding the relationship between genomic markers and early changes in IGF-I may allow development of strategies to rapidly individualize r-hGH dose.

[Addison's disease: forms of presentation in paediatrics]. / Enfermedad de Addison. Formas de presentación en pediatría.

Addison's disease or primary adrenal insufficiency is a rare disease in children. The signs and symptoms at diagnosis are frequently non-specific and insidious. Since adrenal crisis represents an emergency, it is important to be aware and to have a high degree of suspicion of the disorder in order to achieve an early diagnosis and treatment. We present a retrospective study describing the epidemiological, clinical and etiological data at diagnosis of five patients with Addison's disease followed up in our hospital. Dehydration, hyponatremia and skin hyperpigmentation were the most prevalent signs and symptoms at onset of the disease. The patients had low serum cortisol levels and positive adrenal antibodies. One patient with negative antibodies presented with a polyglandular syndrome.

Timo intratiroideo ectópico como causa de nódulo tiroideo solitario / Ectopic intrathyroidal thymus as cause of a solitary thyroid nodule

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Pubertad precoz central: secuela poco frecuente tras traumatismo craneoencefálico severo / True precocious puberty: a rare sequel after severe head trauma

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Consejo genético en la hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa / Prenatal counselling of 21-hydroxylase deficiency

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Enfermedad de Cushing en la edad pediátrica. Tratamiento y evolución / Cushing’s syndrome in pediatric age. Treatment and evolution

El síndrome de Cushing endógeno es infrecuente en pediatría. La causa principal son los tumores hipofisarios productores de corticotropina (enfermedad de Cushing). Debe sospecharse en todo niño con una ganancia ponderal injustificada asociada a una disminución de la velocidad de crecimiento. La primera opción terapéutica en la enfermedad de Cushing es la adenomectomía transesfenoidal, seguida de la radioterapia si persiste el hipercortisolismo. Tras el tratamiento pueden asociarse alteraciones hipofisarias que precisen terapia sustitutiva; el déficit de hormona del crecimiento en niños puede originar un crecimiento recuperador insuficiente. Presentamos el caso de una niña de casi 11 años de edad, con ganancia ponderal injustificada, estancamiento del crecimiento, virilización y miopatía proximal. Mediante las determinaciones hormonales se confirmó un hipercortisolismo dependiente de corticotropina. La resonancia magnética craneal puso de manifiesto un microadenoma hipofisario, que se resecó mediante adenomectomía transesfenoidal, con remisión clínica y analítica. Previamente se había instaurado tratamiento con ketoconazol para controlar el hipercortisolismo. Al cabo de 4 años no había signos de recidiva (AU)

Endogenous Cushing’s syndrome is rare endocrine disorders in pediatric age whose most common cause are the pituitary tumors producers of adrenocorticotropin (ACTH) (Cushing’s syndrome, CS). This disease must be suspected in any children with unjustified weight gain associated with a decrease in the speed of growth. The first therapeutic option in the CS is the transsphenoidal adenomectomy, followed by radiotherapy if CS persists. After the treatment pituitary disorders can be associated which will need a substitutive therapy, growth hormone deficit can cause an inadequate catch-up growth in children. We report the case of a nearly 11 years-old girl with unjustified weight gain, growth stagnation, signs of virilization and proximalmyopathy. Through hormonal determinations was confirmed an ACTH-dependent hypercortisolism was confirmed. The cranial MRI showed a pituitary micro adenoma that was removed through transsphenoidal adenomectomy with clinical and analytic remission. Before surgery, ketoconazole was used in order to control hypercortisolism. There were no signs of relapse four years later (AU)

Episodes of overtreatment during the first six months in children with congenital hypothyroidism and their relationships with sustained attention and inhibitory control at school age.

BACKGROUND/AIMS: Contradictory results regarding the optimal initial dose of levothyroxine in children with congenital hypothyroidism (CH) hamper the clinical management of these children during their early infancy. We explore the relationships between the initial dose of levothyroxine and endocrine control during the first 6 months and cognition at school age. SUBJECTS AND METHODS: Fifty children with CH, 14 boys (10+/-3.1 years) and 36 girls (9.7+/-2.6 years), at the Pediatric Endocrine Unit of the Hospital Gregorio Marañón in Madrid were studied. Neurocognitive evaluation was carried out exploring alertness and inhibitory control. The number of episodes of overtreatment during the first 6 months, the initial dose of levothyroxine, etiology and sex were the predictor variables. RESULTS: Inhibitory control was significantly lower in children with CH than in controls. An interaction with gender and etiology was obtained. Alertness had an inverse relationship with the number of episodes of overtreatment with no interaction with gender or etiology. CONCLUSION: Episodes of overtreatment and not the initial dose of levothyroxine are a risk factor for deficit in alertness whereas subtle inhibitory control deficit seems to be a permanent problem with the current therapeutic approach.

Enfermedad tiroidea autoinmunitaria: posibilidad de asociación a gastritis autoinmunitaria / Autoimmune thyroid disease: Autoimmune gastritis association's possibility

Introducción: Se ha descrito una elevada prevalencia de anticuerpos anticélula parietal gástrica (ACPG) en niños con enfermedad tiroidea autoinmunitaria (ETAI). El objetivo de este trabajo fue determinar la prevalencia de marcadores de gastritis autoinmunitaria en niños con ETAI. Sujetos y métodos: Se incluyó a 26 pacientes con ETAI. Se realizaron hemograma, valores plasmáticos de vitamina B12, ácido fólico, gastrina y ACPG. Se estudió también la comorbilidad de otras enfermedades autoinmunitarias. Resultados: Los valores de tiroxina libre y tirotropina fueron normales con tratamiento hormonal sustitutivo. Los valores de hemoglobina, volumen corpuscular medio, hemoglobina corpuscular media, vitamina B12, ácido fólico y gastrina estaban en rango de normalidad en todos los niños. Se detectaron 6 casos de diabetes mellitus de tipo 1 (DM1) y 2 de ellos también tenían enfermedad celíaca (EC). Se halló ACPG en una niña hipertiroidea de 14 años sin comorbilidad autoinmune. Conclusiones: La ETAI se asocia a otras enfermedades de similar etiología, principalmente DM1 y EC. La presencia de ACPG es un marcador precoz y sensible de gastritis autoinmunitaria (AU)

Introduction: A high prevalence of parietal cell antibodies (PCA) has been reported in children with autoimmune thyroid disease (AITD). The aim of this study was to determine the prevalence of autoimmune gastritis markers among children diagnosed as AITD. Patients and methods: We studied 26 patients with AITD. Basal samples were taken to determine: hemogram, vitamin B12 and folic acid plasmatic levels, gastrin plasmatic levels, and PCA’s determination. Other autoimmune disease comorbility were also studied. Results: Free T4 and TSH values were normal, with hormonal substitutive treatment. Hb, MCV, HCM, vitamine B12, folic acid and gastrin were in normal range for all 26 patients. We reported 6 cases diabetes mellitus type 1 and 2 of celiac disease. A single patient was PCA positive. It was a 14-year-old hyperthyroid girl without any other autoimmune disease. Conclusions: AITD in childhood and adolescence is associated with other autoimmune diseases, specially DM1 and CD. PCA becomes an early and sensitive marker to detect autoinmune gastritis (AU)