Daniel Moura

A crise climática afeta desproporcionalmente crianças e jovens, ampliando desigualdades existentes. Apesar de terem contribuído minimamente para o aquecimento global, as novas gerações enfrentarão seus impactos mais severos, incluindo riscos à saúde, à segurança alimentar e às oportunidades de desenvolvimento. Esta obra aborda o tema "Juventudes, educação climática e ação local para enfrentar a crise climática". Juventudes são altamente engajadas na ação climática, mas ainda sub-representadas nos processos de decisão. Embora jovens demonstrem forte interesse em participar da agenda climática, barreiras institucionais e falta de financiamento limitam sua participação efetiva na formulação de políticas públicas. A educação climática é uma ferramenta estratégica para proteger direitos e fortalecer o protagonismo juvenil. Ao integrar conhecimento científico, valores socioambientais e competências para ação coletiva, a educação ambiental prepara crianças e jovens para atuar como agentes de transformação em seus territórios. Escolas, programas de formação e experiências práticas podem transformar juventudes em lideranças climáticas. Iniciativas como certificação de escolas sustentáveis, academias de justiça climática e programas de voluntariado mostram como educação, participação e ação local podem gerar impactos concretos. Governos locais têm papel central em criar oportunidades para o engajamento juvenil na agenda climática. Ao apoiar programas educacionais, mecanismos participativos e iniciativas comunitárias, municípios podem fortalecer a liderança jovem e acelerar a implementação de soluções sustentáveis. Esta obra integra a coleção Agenda Política Pública.

It has been suggested that there is a link between epinephrine synthesis and the development of β2-adrenoceptor-mediated effects, but it remains to be determined whether this development is triggered by epinephrine. The aim of this study was to characterize β-adrenoceptor-mediated relaxation and facilitation of norepinephrine release in the aorta of phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice. Catecholamines were quantified by reverse-phase high-performance liquid chromatography-electrochemical detection. Aortic rings were mounted in a myograph to determine concentration-response curves to selective β1- or β2-adrenoceptor agonists in the absence or presence of selective β1- or β2-adrenoceptor antagonists. Aortic rings were also preincubated with [(3)H]norepinephrine to measure tritium overflow elicited by electrical stimulation in the presence of increasing concentrations of nonselective β- or selective β2-adrenoceptor agonists. β2-Adrenoceptor protein density was evaluated by Western blotting and β2-adrenoceptor localization by immunohistochemistry. Epinephrine is absent in Pnmt-KO mice. The potency and the maximal effect of the β2-adrenoceptor agonist terbutaline were lower in Pnmt-KO than in wild-type (WT) mice. The selective β2-adrenoceptor antagonist ICI 118,551 [(±)-erythro-(S*,S*)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride] antagonized the relaxation caused by terbutaline in WT but not in Pnmt-KO mice. Isoproterenol and terbutaline induced concentration-dependent increases in tritium overflow in WT mice only. β2-Adrenoceptor protein density was decreased in membrane aorta homogenates of Pnmt-KO mice, and this finding was supported by immunofluorescence confocal microscopy. In conclusion, epinephrine is crucial for β2-adrenoceptor-mediated vasodilation and facilitation of norepinephrine release. In the absence of epinephrine, β2-adrenoceptor protein density was decreased in aorta cell membranes, thus potentially hindering its functional activity.

Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options.

Narrowband ultraviolet B (nbUVB) phototherapy is widely used in psoriasis treatment. UVB irradiation decreases catechol-O-methyltransferase (COMT) activity in human keratinocytes and melanoma cells. COMT activity is higher in psoriatic lesions than in normal skin but the effect of nbUVB on COMT activity in psoriasis patients is unknown. To evaluate COMT activity in patients with psoriasis and determine whether nbUVB modifies this activity. An open observational study was conducted with 20 psoriasis patients and 15 healthy volunteers. Patients were treated with nbUVB thrice weekly during six weeks and evaluated at baseline, three and six weeks after phototherapy and four weeks after stopping. In each evaluation body mass index (BMI), Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were calculated and blood samples for erythrocytes soluble (S-) COMT activity assessment were taken. Before phototherapy (baseline), using a single concentration of substrate adreneline (1,000 μM), S-COMT activity levels (pmol/mg protein/h) were significantly higher in psoriasis patients than in controls. After nbUVB treatment, S-COMT activity significantly decreased. This decrease correlated positively with baseline activity. Four weeks after stopping phototherapy, S-COMT activity returned to baseline levels. After phototherapy, PASI score improved significantly but no correlation to baseline S-COMT values or decrease in S-COMT activity was found. This study shows that baseline S-COMT activity is higher in psoriasis patients than in controls and that this activity is significantly decreased by nbUVB treatment for psoriasis. This decrease is more evident in patients with higher baseline S-COMT activity.

Diet has a high relevance in health. Hypertension is a major risk factor for cardiovascular diseases and has an important impact on public health, and consequently on countries economy. Scientific research gathered strong evidence about the role of several dietary factors either in etiology or in treatment/prevention of these diseases. Peptides from different food matrices have been studied, and indicated as compounds with particular interest in the context of hypertension. The classical approach involves the identification of peptides with an in vitro ACE inhibitory activity and the assumption that the observed in vivo effects are due to this enzyme blockade. However, in some cases the potency of ACE blockade does not correlate with the antihypertensive activity in vivo. This paper reviews the current literature that identifies mechanisms of action, other than ACE inhibition, that might explain antihypertensive effects of biologically active peptides from different food sources.

Summary: Background: Catechol‐O‐methyltransferase (COMT) is a ubiquitous enzyme inactivating catecholic compounds. COMT is expressed also in human skin samples, and in melanoma cells it may be cytoprotective. A role of COMT in keratinocytes (HaCat) is unknown.Objective: The objective of this study is: to investigate whether ultraviolet‐B (UVB) radiation modifies COMT activity in melanocytes and HaCat and whether COMT inhibition plays a role in UVB‐induced cell death.Methods: Human cell lines of melanotic melanoma (SK‐mel‐1) and HaCat were used. COMT activity was evaluated under basal conditions and after UVB irradiation (311 nm) at a low (8 mJ/cm²) and a high dose (60 mJ/cm²). Tolcapone 1 μM was used to inhibit COMT.Results: Both SK‐mel‐1 and Ha‐Cat cells express COMT activity. In SK‐mel‐1, COMT activity is reduced nearly 50% both 24 h and 48 h after a high dose UVB. In Ha‐Cat cells, COMT activity increased 24 h after a high dose UVB but decreased at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. High concentrations of tolcapone reduced melanin levels in melanoma cells parallel to reduced cell numbers.Conclusions: Ultraviolet radiation differentially modifies COMT activity in melanoma cells and HaCat. Furthermore, tolcapone increased death of HaCat after irradiation but did not affect melanoma cells.

The urinary levels of catecholamines [adrenaline (AD), noradrenaline (NA), and dopamine (DA)] and their metabolites [L-3,4-dihydroxyphenylalanine (L-DOPA), and 3,4-dihydroxyphenylacetic acid (DOPAC)], as indicators of physiological stress, were assessed in 40 patients with Down syndrome (DS). The analysis was performed by an optical fiber (OF) bioanalyzer; which was constituted by two main components: a miniaturized chromatographic system and a detection system based on an OF coated with an enzymatic matrix. In this study some working conditions such as, number of fibers in the miniaturized chromatographic column, number of dips for sensitive coating deposition, temperature and time of cure of the sensitive matrix, were optimized in order to achieve higher analytical performance. After tested for calibration the bioanalyzer was applied to urine samples analysis of catecholamines and their metabolites, comparing the results with those obtained by both, a classical analytical method, namely high performance liquid chromatography coupled to an electrochemical detector (HPLC-ED), and an OF biosensor based on a sensitive cladding of laccase (LacOF biosensor). The results of catecholamines in patients with DS revealed that 15% and 22.5% of the analyzed subjects showed DA and AD concentrations, respectively, above the pathological levels. In the determinations of NA, the 40 samples showed concentration values below the normal levels, while in the determination of catecholamines metabolites 5% of the urine samples showed values above 118 and 1681 for L-DOPA and DOPAC, respectively.

Ultraviolet radiation is the major environmental insult to the skin and stimulates the synthesis of melanin in melanocytes, which then distribute it to the neighboring keratinocytes where it confers photo-protection. Skin color results from the paracrine interaction between these two cell types. Recent studies suggest that endocannabinoids are potential mediators in the skin. Here, we investigated whether cannabinoid drugs play a role in melanogenesis and if ultraviolet radiation modifies the cutaneous endocannabinoid system. We used human melanotic melanoma cell line (SK-mel-1) in monoculture or co-culture with human keratinocytes (HaCat). Endocannabinoid levels, cannabinoid receptors expression, and melanin content were evaluated under basal conditions and after ultraviolet-B irradiation (311 nm). We provide evidence that human melanoma cells (SK-mel-1) express CB₁ receptors, and when in co-culture with keratinocytes (HaCat), the selective CB₁ receptor agonist arachidonyl-2-chloroethylamide (ACEA 1 and 10 μM) inhibited (by 33.4 and 37.3%, respectively) basal melanogenesis. In addition, ultraviolet-B-induced melanogenesis in co-cultures was abolished by ACEA 10 μM. Both ACEA inhibitory effects were reversed by AM251 (1 μM), a selective CB₁ antagonist. Furthermore, ultraviolet-B radiation increased endocannabinoids levels only in keratinocytes, whereas CB₁ cannabinoid receptor expression was up-regulated only in melanoma cells. Our results collectively suggest that ultraviolet radiation activates paracrine CB₁-mediated endocannabinoid signaling to negatively regulate melanin synthesis. The endocannabinoid system in the skin may be a possible target for future therapies in pigmentary disorders.