Combined deletion of Mct8 and Dio2 impairs SVZ neurogliogenesis and olfactory function in adult mice.

Within the adult mouse subventricular zone (SVZ), neural stem cells (NSCs) produce neuroblasts and oligodendrocyte precursor cells (OPCs). T3, the active thyroid hormone, influences renewal and commitment of SVZ progenitors. However, how regulators of T3 availability affect these processes is less understood. Using Mct8/Dio2 knockout mice, we investigated the role of MCT8, a TH transporter, and DIO2, the T3-generating enzyme, in regulating adult SVZ-neurogliogenesis. Single-cell RNA-Seq revealed Mct8 expression in various SVZ cell types in WT mice, while Dio2 was enriched in neurons, astrocytes, and quiescent NSCs. The absence of both regulators in the knockout model dysregulated gene expression, increased the neuroblast/OPC ratio and hindered OPC differentiation. Immunostainings demonstrated compromised neuroblast migration reducing their supply to the olfactory bulbs, impairing interneuron differentiation and odor discrimination. These findings underscore the pivotal roles of MCT8 and DIO2 in neuro- and oligodendrogenesis, offering targets for therapeutic avenues in neurodegenerative and demyelinating diseases.

Parental burnout during COVID-19: The moderating role of anxiety and family functioning.

Parental burnout (PB) is characterised by parental exhaustion resulting from exposure to chronic parental stress. Due to the social and economic changes resulting from the COVID-19 pandemic that impacted families, there is a significant scientific interest in identifying factors related to PB within the pandemic context. This study aimed to analyse the relationships between parental stress (parental concerns, parental satisfaction, lack of control, and fears and anxieties), family functioning, psychological morbidity (anxiety and depression), and burnout in parents. The sample consisted of 253 parents, legal guardians or primary caregivers of children aged between 0 and 6 years. Results revealed that the child's age, psychological morbidity (depression), and parental stress were significant predictors of PB. Anxiety and family functioning played a moderating role in the relationship between parental satisfaction and PB. According to the results, intervention programs should focus on anxiety symptoms and family functioning to mitigate the effects of parental stress on PB.

Thyroid hormone action in adult neurogliogenic niches: the known and unknown.

Over the last decades, thyroid hormones (THs) signaling has been established as a key signaling cue for the proper maintenance of brain functions in adult mammals, including humans. One of the most fascinating roles of THs in the mature mammalian brain is their ability to regulate adult neurogliogenic processes. In this respect, THs control the generation of new neuronal and glial progenitors from neural stem cells (NSCs) as well as their final differentiation and maturation programs. In this review, we summarize current knowledge on the cellular organization of adult rodent neurogliogenic niches encompassing well-established niches in the subventricular zone (SVZ) lining the lateral ventricles, the hippocampal subgranular zone (SGZ), and the hypothalamus, but also less characterized niches in the striatum and the cerebral cortex. We then discuss critical questions regarding how THs availability is regulated in the respective niches in rodents and larger mammals as well as how modulating THs availability in those niches interferes with lineage decision and progression at the molecular, cellular, and functional levels. Based on those alterations, we explore the novel therapeutic avenues aiming at harnessing THs regulatory influences on neurogliogenic output to stimulate repair processes by influencing the generation of either new neurons (i.e. Alzheimer's, Parkinson's diseases), oligodendrocytes (multiple sclerosis) or both (stroke). Finally, we point out future challenges, which will shape research in this exciting field in the upcoming years.

Perceptions and Experiences of Parents of Burn-Injured Children during Hospital Stay: A Need for Integrated Care.

Pediatric burn injuries are a critical medical condition that triggers a series of ongoing multifactorial stressors that affect both children and their families. To inform healthcare research and clinical practice, this study aimed to understand and describe the perceptions and experiences of the parents of burn-injured children during hospital stay. Forty-six parents (thirty-eight mothers) of forty-six children (eighteen girls) with a mean age of 2.28 years (SD = 1.52) answered ten open-ended questions. This qualitative study was conducted in a referral hospital in the northern region of Portugal. Qualitative data were analyzed using an inductive content analysis. Five key themes emerged from the data analysis: diving into the crisis of the child burn injury, being together and in good hands, becoming aware of an uncertain future, enhancing supportive care and environment, and finding ways to guide parents. Qualitative findings underlined the pressing need for integrated care within this context. Parents were significantly burdened and distressed during the inpatient phase. These parents should be included in the integrated care plan starting from admission. Understanding and addressing parents' healthcare needs and psychosocial adjustment difficulties is paramount to the development of future intervention programs and the delivery of suitable integrated healthcare.

Insights on the role of thyroid hormone transport in neurosensory organs and implication for the Allan-Herndon-Dudley syndrome.

Thyroid hormones play an important role during the development and functioning of the different sensory systems. In order to exert their actions, thyroid hormones need to access their target cells through transmembrane transporter proteins, among which the monocarboxylate transporter 8 (MCT8) stands out for its pathophysiological relevance. Mutations in the gene encoding for MCT8 lead to the Allan-Herndon-Dudley syndrome (AHDS), a rare disease characterised by severe neuromotor and cognitive impairments. The impact of MCT8 deficiency in the neurosensory capacity of AHDS patients is less clear, with only a few patients displaying visual and auditory impairments. In this review we aim to gather data from different animal models regarding thyroid hormone transport and action in the different neurosensory systems that could aid to identify potential neurosensorial alterations in MCT8-deficient patients.

Portuguese Validation of the TAPQoL: A Health-Related Quality of Life Instrument for Children Aged 0-6 Years.

In Portugal, there are few generic and specific instruments to assess health-related quality of life (HRQoL) in children, especially those of preschool age. This study aimed to adapt and validate the Portuguese version of the Preschool Children Quality of Life Questionnaire (TAPQoL) in a community and clinical sample of children aged 0-6 years. The parents of 409 healthy children and 137 children undergoing treatment for burns and acute lymphoblastic leukemia completed the TAPQoL and were assessed on psychological morbidity and family functioning. Exploratory and confirmatory factor analyses were performed, as well as analysis of the psychometric properties as shown by internal consistency measures, convergent validity, and average variance extracted. Confirmatory factor analysis confirmed an 11-factor structure with good psychometric properties. The current version of the TAPQoL is a valid and reliable instrument for assessing HRQoL in Portuguese preschool children in community and clinical settings.

Parental distress in childhood acute lymphoblastic leukemia: A systematic review of the literature.

The present study is a systematic review of factors and consequences of parental distress following their children's acute lymphoblastic leukemia (ALL) diagnosis. PubMed, Web of Science, and APA PsycInfo databases were searched. Twenty-eight papers were included, with only three longitudinal studies. Fifteen studies explored factors of parental distress, including sociodemographic, psychosocial, psychological, family, health, and ALL-specific variables. Correlations were found between social support, illness cognitions, coping strategies, and parental distress, as well as contradictory results regarding sociodemographic variables. Family cohesion and the overall impact of illness were associated with parental distress. Resilience factors contributed negatively to parental distress symptoms, and perceived caregiver strain and negative child's emotional functioning contributed positively. Thirteen papers explored the consequences of parental distress, including psychological, family, health, and social/education factors. Distress was correlated with care burden and contributed to family strain, child's symptom burden, and parental protective behavior. Significant correlations were found between parental distress, at diagnosis, and further adjustment of parents and children. Most papers reported correlations between parental distress and psychological condition and quality of life; few studies reported no association. Correlations between maternal depression and child's participation in education and social life were found. Differences on distress were found regarding parents' gender, age, children's group risk, and treatment phases. Longitudinal studies are needed to better understand the phenomenon and its consequences. Future interventions should address parents' mental health needs in an early and ongoing assessment in order to promote healthier outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neurovascular unit disruption and blood-brain barrier leakage in MCT8 deficiency.

BACKGROUND: The monocarboxylate transporter 8 (MCT8) plays a vital role in maintaining brain thyroid hormone homeostasis. This transmembrane transporter is expressed at the brain barriers, as the blood-brain barrier (BBB), and in neural cells, being the sole known thyroid hormone-specific transporter to date. Inactivating mutations in the MCT8 gene (SLC16A2) cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8 deficiency, a rare X-linked disease characterized by delayed neurodevelopment and severe psychomotor disorders. The underlying pathophysiological mechanisms of AHDS remain unclear, and no effective treatments are available for the neurological symptoms of the disease. METHODS: Neurovascular unit ultrastructure was studied by means of transmission electron microscopy. BBB permeability and integrity were evaluated by immunohistochemistry, non-permeable dye infiltration assays and histological staining techniques. Brain blood-vessel density was evaluated by immunofluorescence and magnetic resonance angiography. Finally, angiogenic-related factors expression was evaluated by qRT-PCR. The studies were carried out both in an MCT8 deficient subject and Mct8/Dio2KO mice, an AHDS murine model, and their respective controls. RESULTS: Ultrastructural analysis of the BBB of Mct8/Dio2KO mice revealed significant alterations in neurovascular unit integrity and increased transcytotic flux. We also found functional alterations in the BBB permeability, as shown by an increased presence of peripheral IgG, Sodium Fluorescein and Evans Blue, along with increased brain microhemorrhages. We also observed alterations in the angiogenic process, with reduced blood vessel density in adult mice brain and altered expression of angiogenesis-related factors during brain development. Similarly, AHDS human brain samples showed increased BBB permeability to IgG and decreased blood vessel density. CONCLUSIONS: These findings identify for the first time neurovascular alterations in the MCT8-deficient brain, including a disruption of the integrity of the BBB and alterations in the neurovascular unit ultrastructure as a new pathophysiological mechanism for AHDS. These results open a new field for potential therapeutic targets for the neurological symptoms of these patients and unveils magnetic resonance angiography as a new non-invasive in vivo technique for evaluating the progression of the disease.

Thyroid Hormone Transporters MCT8 and OATP1C1 Are Expressed in Projection Neurons and Interneurons of Basal Ganglia and Motor Thalamus in the Adult Human and Macaque Brains.

Monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1) are thyroid hormone (TH) transmembrane transporters relevant for the availability of TH in neural cells, crucial for their proper development and function. Mutations in MCT8 or OATP1C1 result in severe disorders with dramatic movement disability related to alterations in basal ganglia motor circuits. Mapping the expression of MCT8/OATP1C1 in those circuits is necessary to explain their involvement in motor control. We studied the distribution of both transporters in the neuronal subpopulations that configure the direct and indirect basal ganglia motor circuits using immunohistochemistry and double/multiple labeling immunofluorescence for TH transporters and neuronal biomarkers. We found their expression in the medium-sized spiny neurons of the striatum (the receptor neurons of the corticostriatal pathway) and in various types of its local microcircuitry interneurons, including the cholinergic. We also demonstrate the presence of both transporters in projection neurons of intrinsic and output nuclei of the basal ganglia, motor thalamus and nucleus basalis of Meynert, suggesting an important role of MCT8/OATP1C1 for modulating the motor system. Our findings suggest that a lack of function of these transporters in the basal ganglia circuits would significantly impact motor system modulation, leading to clinically severe movement impairment.

Novel, Edible Melanin-Protein-Based Bioactive Films for Cheeses: Antimicrobial, Mechanical and Chemical Characteristics.

The cheese rind is the natural food packaging of cheese and is subject to a wide range of external factors that compromise the appearance of the cheese, including color defects caused by spoilage microorganisms. First, eight films based on whey protein isolate (WPI) coatings were studied, of which IS3CA (WPI 5% + sorbitol 3% + citric acid 3%) was selected for presenting better properties. From the IS3CA film, novel films containing melanin M1 (74 µg/mL) and M2 (500 µg/mL) were developed and applied to cheese under proof-of-concept and industrial conditions. After 40 days of maturation, M2 presented the lowest microorganism count for all the microbial parameters analyzed. The cheese with M2 showed the lowest lightness, which indicates that it is the darkest cheese due to the melanin concentration. It was found that the mechanical and colorimetric properties are the ones that contribute the most to the distinction of the M2 film in cheese from the others. Using FTIR-ATR, it was possible to distinguish the rinds of M2 cheeses because they contained the highest concentrations of melanin. Thus, this study shows that the film with M2 showed the best mechanical, chemical and antimicrobial properties for application in cheese.

Family Functioning in a Portuguese Sample of Adults during COVID-19: Does Hope Matter? / Funcionamiento familiar en una muestra portuguesa de adultos durante el COVID-19: ¿importa la esperanza?

The purpose of this study was to explore the relationships between sociodemographic, clinical, and psychological variables and their contribution towards family functioning during the first wave of COVID-19 in Portugal. The COVID-19 pandemic was an overwhelming and stressful life event with social consequences that impacted family functioning and contributed to multilevel disruptions. The study used a cross-sectional design and included 110 participants (94 women), with a mean age of 35.71 (SD = 13.53). Participants answered self-report measures assessing family satisfaction, hope, psychological well-being, risk perception, and family functioning. Hope (pathways subscale) played a moderating role in the relationship between family satisfaction and family functioning. Family satisfaction and psychological well-being partially mediated the relationship between hope and family functioning. Clinical relevance and implications for further research are addressed. Intervention should focus on increasing psychological well-being and hope together with family satisfaction in order to promote family functioning. For those individuals struggling with COVID-19 issues, mental health interventions are paramount. (AU)

Este estudio ha tenido como objetivo explorar la relación entre las variables sociodemográficas, clínicas y psicológicas y el funcionamiento familiar en la primera oleada de COVID-19 en Portugal. La pandemia de COVID-19 fue una situación de vida abrumadora y estresante con consecuencias sociales que afectaron en el funcionamiento familiar. El estudio utilizó un diseño transversal e incluyó 110 participantes (94 mujeres), con una edad media de 35.71 años (SD = 13.53). Los participantes respondieron a medidas que evaluaban la satisfacción familiar, la esperanza, el bienestar psicológico, la percepción del riesgo y el funcionamiento familiar. La esperanza (subescala “caminos”) desempeñó un papel moderador en la relación entre la satisfacción familiar y el funcionamiento familiar. La satisfacción familiar y el bienestar psicológico mediaron parcialmente en la relación entre la esperanza y el funcionamiento familiar. Se abordan la importancia clínica y las implicaciones para futuras investigaciones. La intervención deberá centrarse en aumentar el bienestar psicológico y la esperanza junto con la satisfacción familiar para promover el funcionamiento familiar. Para los individuos que luchan con problemas de COVID-19 son primordiales las intervenciones de salud mental. (AU)

Thyroid Hormone Transporters MCT8 and OATP1C1 Are Expressed in Pyramidal Neurons and Interneurons in the Adult Motor Cortex of Human and Macaque Brain.

Monocarboxylate transporter 8 (MCT8) and organic anion transporter polypeptide 1C1 (OATP1C1) are thyroid hormone (TH) transmembrane transporters that play an important role in the availability of TH for neural cells, allowing their proper development and function. It is important to define which cortical cellular subpopulations express those transporters to explain why MCT8 and OATP1C1 deficiency in humans leads to dramatic alterations in the motor system. By means of immunohistochemistry and double/multiple labeling immunofluorescence in adult human and monkey motor cortices, we demonstrate the presence of both transporters in long-projection pyramidal neurons and in several types of short-projection GABAergic interneurons in both species, suggesting a critical position of these transporters for modulating the efferent motor system. MCT8 is present at the neurovascular unit, but OATP1C1 is only present in some of the large vessels. Both transporters are expressed in astrocytes. OATP1C1 was unexpectedly found, only in the human motor cortex, inside the Corpora amylacea complexes, aggregates linked to substance evacuation towards the subpial system. On the basis of our findings, we propose an etiopathogenic model that emphasizes these transporters' role in controlling excitatory/inhibitory motor cortex circuits in order to understand some of the severe motor disturbances observed in TH transporter deficiency syndromes.

Maternal Administration of the CNS-Selective Sobetirome Prodrug Sob-AM2 Exerts Thyromimetic Effects in Murine MCT8-Deficient Fetuses.

Background: Monocarboxylate transporter 8 (MCT8) deficiency is a rare X-linked disease where patients exhibit peripheral hyperthyroidism and cerebral hypothyroidism, which results in severe neurological impairments. These brain defects arise from a lack of thyroid hormones (TH) during critical stages of human brain development. Treatment options for MCT8-deficient patients are limited and none have been able to prevent or ameliorate effectively the neurological impairments. This study explored the effects of the TH agonist sobetirome and its CNS-selective amide prodrug, Sob-AM2, in the treatment of pregnant dams carrying fetuses lacking Mct8 and deiodinase type 2 (Mct8/Dio2 KO), as a murine model for MCT8 deficiency. Methods: Pregnant dams carrying Mct8/Dio2 KO fetuses were treated with 1 mg of sobetirome/kg body weight/day, or 0.3 mg of Sob-AM2/kg body weight/day for 7 days, starting at embryonic day 12.5 (E12.5). As controls, pregnant dams carrying wild-type and pregnant dams carrying Mct8/Dio2 KO fetuses were treated with daily subcutaneous injections of vehicle. Dams TH levels were measured by enzyme-linked immunosorbent assay (ELISA). Samples were extracted at E18.5 and the effect of treatments on the expression of triiodothyronine (T3)-dependent genes was measured in the placenta, fetal liver, and fetal cerebral cortex by real-time polymerase chain reaction. Results: Maternal sobetirome treatment led to spontaneous abortions. Sob-AM2 treatment, however, was able to cross the placental as well as the brain barriers and exert thyromimetic effects in Mct8/Dio2 KO fetal tissues. Sob-AM2 treatment did not affect the expression of the T3-target genes analyzed in the placenta, but it mediated thyromimetic effects in the fetal liver by increasing the expression of Dio1 and Dio3 genes. Interestingly, Sob-AM2 treatment increased the expression of several T3-dependent genes in the brain such as Hr, Shh, Dio3, Kcnj10, Klf9, and Faah in Mct8/Dio2 KO fetuses. Conclusions: Maternal administration of Sob-AM2 can cross the placental barrier and access the fetal tissues, including the brain, in the absence of MCT8, to exert thyromimetic actions by modulating the expression of T3-dependent genes. Therefore, Sob-AM2 has the potential to address the cerebral hypothyroidism characteristic of MCT8 deficiency from fetal stages and to prevent neurodevelopmental alterations in the MCT8-deficient fetal brain.

Intracerebroventricular High Doses of 3,3',5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency.

Introduction: Patients lacking functional monocarboxylate transporter 8 (MCT8), a highly specific thyroid hormone (TH) transporter, present severe psychomotor disabilities. MCT8 deficiency leads to peripheral hyperthyroidism and brain hypothyroidism, the latter due to impaired transport of TH across brain barriers. Available treatments for patients are limited and aim to overcome the limited TH transport across brain barriers. The use of TH analogues such as 3,3',5-triiodothyroacetic acid (TRIAC) that do not require MCT8 to cross the cellular membranes is considered a potential therapy for MCT8 deficiency. Previous studies have shown that systemic administration of TRIAC at therapeutic doses does not increase TRIAC content in the brain, while intracerebroventricular (ICV) administration of therapeutic doses of TRIAC increases TRIAC content in the brain but does not mediate thyromimetic effects. In view of this, we hypothesize that ICV administration of high doses of TRIAC can mediate thyromimetic effects in the brain without worsening the brain hypothyroidism or peripheral hyperthyroidism of patients. Methods: We administered 400 ng/g of body weight per day of ICV TRIAC in a mouse model of MCT8 deficiency: Mct8-/y and deiodinase 2 (Dio2)-/- double knockout mice. The effects of this treatment on TH and TRIAC levels/content in blood and tissues were determined by radioimmunoassay and effects on TH-regulated genes were assessed by real time-quantitative polymerase chain reaction in peripheral and central tissues. Results: ICV administration of high doses of TRIAC ameliorated the peripheral hyperthyroidism. In the brain, this treatment did not further aggravate brain hypothyroidism and increased TRIAC content in several brain regions; however, only moderate thyromimetic activity was observed in restricted brain areas. Conclusion: Administration of high doses of TRIAC by ICV delivery at juvenile stages in a mouse model of MCT8 deficiency is effective in normalizing peripheral hyperthyroidism but exerts minimal thyromimetic activity in the brain.

The orphan G protein-coupled receptor, GPR139, is expressed in the hypothalamus and is involved in the regulation of body mass, blood glucose, and insulin.

GPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system, including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its involvement in the regulation of body mass, blood insulin, and glycemia.

A CRISPR/Cas9-engineered avatar mouse model of monocarboxylate transporter 8 deficiency displays distinct neurological alterations.

Inactivating mutations in the specific thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to an X-linked rare disease named MCT8 deficiency or Allan-Herndon-Dudley Syndrome. Patients exhibit a plethora of severe endocrine and neurological alterations, with no effective treatment for the neurological symptoms. An optimal mammalian model is essential to explore the pathological mechanisms and potential therapeutic approaches. Here we have generated by CRISPR/Cas9 an avatar mouse model for MCT8 deficiency with a point mutation found in two MCT8-deficient patients (P253L mice). We have predicted by in silico studies that this mutation alters the substrate binding pocket being the probable cause for impairing thyroid hormone transport. We have characterized the phenotype of MCT8-P253L mice and found endocrine alterations similar to those described in patients and in MCT8-deficient mice. Importantly, we detected brain hypothyroidism, structural and functional neurological alterations resembling the patient's neurological impairments. Thus, the P253L mouse provides a valuable model for studying the pathophysiology of MCT8 deficiency and in the future will allow to test therapeutic alternatives such as in vivo gene therapy and pharmacological chaperone therapy to improve the neurological impairments in MCT8 deficiency.

Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development.

Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to profound brain alterations, including myelination impairments, in humans. We aimed to further explore the pathophysiological mechanisms underlying the MCT8 deficiency-associated myelination impairments to unravel new biomarkers and therapeutic targets. We have performed brain histological analysis on an MCT8-deficient subject and histological, ultrastructural, and magnetic resonance imaging (MRI) analysis in the brain of a mouse model of the syndrome, lacking MCT8 and enzyme deiodinase type 2 (DIO2, Mct8/Dio2 KO). We have found that the MCT8-deficient subject presents severely reduced myelin lipid and protein staining and increased proportion of small-caliber myelinated axons in detriment of large-caliber ones. Mct8/Dio2 KO mice present myelination impairments and abnormal oligodendroglial development. We conclude that the greater proportion of small-caliber axons and impairments in the oligodendroglia lineage progression arise as potential mechanisms underlying the permanent myelination defects in MCT8-deficiency. Moreover, we present the Mct8/Dio2 KO mouse model, and MRI as a non-invasive biomarker, as highly valuable tools for preclinical studies involving MCT8 deficiency. These findings contribute to the understanding of the pathological mechanisms in MCT8 deficiency and suggest new biomarkers and therapeutic targets to consider therapeutic options for the neurological defects in patients.

Melanin: Production from Cheese Bacteria, Chemical Characterization, and Biological Activities.

Pigments are compounds of importance to several industries, for instance, the food industry, where they can be used as additives, color intensifiers, and antioxidants. As the current trend around the world is shifting to the use of eco-friendly commodities, demand for natural dyes is increasing. Melanins are pigments that are produced by several microorganisms. Pseudomonas putida ESACB 191, isolated from goat cheese rind, was described as a brown pigment producer. This strain produces a brown pigment via the synthetic Müeller-Hinton Broth. This brown compound was extracted, purified, analyzed by FTIR and mass spectrometry, and identified as eumelanin. The maximum productivity was 1.57 mg/L/h. The bioactivity of eumelanin was evaluated as the capacity for scavenging free radicals (antioxidant activity), EC50 74.0 ± 0.2 µg/mL, and as an acetylcholinesterase inhibitor, with IC50 575 ± 4 µg/mL. This bacterial eumelanin did not show cytotoxicity towards A375, HeLa Kyoto, HepG2, or Caco2 cell lines. The effect of melanin on cholesterol absorption and drug interaction was evaluated in order to understand the interaction of melanin present in the cheese rind when ingested by consumers. However, it had no effect either on cholesterol absorption through an intestinal simulated barrier formed by the Caco2 cell line or with the drug ezetimibe.

Repercussão da COVID-19 em crianças e adolescentes: nova inflamação multissistêmica ou desencadeamento da doença de Kawasaki? / COVID-19 repercussion in children and adolescents: a new multisystem inflammation or a Kawasaki disease trigger?

A doença causada pelo novo coronavírus (COVID-19) teve início em dezembro de 2019 na China e rapidamente adquiriu grande importância epidemiológica, com um crescente número de casos e mortes no Brasil e no mundo. Entre os diversos estudos sobre a doença causada pelo SARS-CoV-2, foram relatados casos de crianças infectadas que apresentaram inflamação multissistêmica, mimetizando a doença de Kawasaki, o que instigou a possibilidade de uma associação entre esta e a COVID-19. O presente artigo de revisão visa destacar esta nova possibilidade diagnóstica, discutindo principalmente os sintomas, exames laboratoriais e a epidemiologia que podem diferenciar a síndrome inflamatória multissistêmica em crianças (MIS-C) como decorrente da COVID- 19 ou desencadeante da doença de Kawasaki. O banco de dados eletrônico PubMed foi utilizado para a pesquisa de artigos originais e de revisão de 2020 e 2021, selecionados de acordo com critérios de atualidade e menção a descritores científicos como infecções por coronavírus, síndrome de linfonodos mucocutâneos e inflamação. A revisão dos sintomas da MIS-C e achados de exames laboratoriais relacionados à COVID-19 foi feita por meio de artigos com estudos realizados com mais de 10 pacientes. Entre os principais resultados obtidos tem-se a diferença entre a faixa etária e etnia acometidas, presença de sintomas gastrointestinais, mecanismos de lesão cardíaca envolvidos e alterações de exames laboratoriais na doença de Kawasaki e na MIS-C. Assim, a conclusão é que a MIS-C está relacionada à infecção prévia pelo SARS-CoV-2, compartilhando dos sintomas da doença de Kawasaki, sem atuar como um desencadeante desta doença.

Coronavirus disease 2019 (COVID-19) arose in December 2019 in China and quickly assumed great epidemiological importance, with an increasing number of cases and deaths in Brazil and worldwide. Among the several studies on this disease, cases of children infected with SARS-CoV-2 who had multisystem inflammation, mimicking Kawasaki disease, were reported, which raised the possibility of an association between Kawasaki disease and COVID-19. This review article aims to highlight this new diagnostic possibility and mainly discusses the symptoms, laboratory tests, and epidemiology that may differentiate multisystem inflammatory syndrome in children (MIS-C) as a result of COVID-19 or as a Kawasaki disease trigger. Original and review articles from 2020 and 2021 that were current and mentioned keywords such as coronavirus infections, mucocutaneous lymph node syndrome, and inflammation were selected from the electronic database PubMed. The review of MIS-C symptoms and laboratory findings related to COVID-19 was based on articles of studies that included more than 10 patients. The main results obtained were differences between the affected age group and ethnicity, presence of gastrointestinal tract symptoms, different mechanisms of cardiac injury involved, and changes in laboratory tests in Kawasaki disease and MIS-C. In conclusion, MIS-C is related to previous SARS-CoV-2 infection and leads to the same symptoms of Kawasaki disease, without acting as a trigger for this disease.

BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats.

PURPOSE: In the present study, the therapeutic efficacy of a selective BKCa channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) was investigated. METHODS: PAH was induced in male Wistar rats by a single injection of MCT. After two weeks, the MCT-treated group was divided into two groups that were either treated with compound X or vehicle. Compound X was administered daily at 28 mg/kg. Electrocardiographic, echocardiographic, and haemodynamic analyses were performed; ex vivo evaluations of pulmonary artery reactivity, right ventricle (RV) and lung histology as well as expression levels of α and ß myosin heavy chain, brain natriuretic peptide, and cytokines (TNFα and IL10) in heart tissue were performed. RESULTS: Pulmonary artery rings of the PAH group showed a lower vasodilatation response to acetylcholine, suggesting endothelial dysfunction. Compound X promoted strong vasodilation in pulmonary artery rings of both control and MCT-induced PAH rats. The untreated hypertensive rats presented remodelling of pulmonary arterioles associated with increased resistance to pulmonary flow; increased systolic pressure, hypertrophy and fibrosis of the RV; prolongation of the QT and Tpeak-Tend intervals (evaluated during electrocardiogram); increased lung and liver weights; and autonomic imbalance with predominance of sympathetic activity. On the other hand, treatment with compound X reduced pulmonary vascular remodelling, pulmonary flow resistance and RV hypertrophy and afterload. CONCLUSION: The use of a selective and potent opener to activate the BKCa channels promoted improvement of haemodynamic parameters and consequent prevention of RV maladaptive remodelling in rats with MCT-induced PAH.