Exploring Seaweed and Glycine Betaine Biostimulants for Enhanced Phenolic Content, Antioxidant Properties, and Gene Expression of Vitis vinifera cv. "Touriga Franca" Berries.

Climate change will pose a challenge for the winemaking sector worldwide, bringing progressively drier and warmer conditions and increasing the frequency and intensity of weather extremes. The short-term adaptation strategy of applying biostimulants through foliar application serves as a crucial measure in mitigating the detrimental effects of environmental stresses on grapevine yield and berry quality. The aim of this study was to evaluate the effect of foliar application of a seaweed-based biostimulant (A. nodosum-ANE) and glycine betaine (GB) on berry quality, phenolic compounds, and antioxidant activity and to elucidate their action on the secondary metabolism. A trial was installed in a commercial vineyard (cv. "Touriga Franca") in the Cima Corgo (Upper Corgo) sub-region of the Douro Demarcated Region, Portugal. A total of four foliar sprayings were performed during the growing season: at flowering, pea size, bunch closer, and veraison. There was a positive effect of GB in the berry quality traits. Both ANE and GB increased the synthesis of anthocyanins and other phenolics in berries and influenced the expression of genes related to the synthesis and transport of anthocyanins (CHS, F3H, UFGT, and GST). So, they have the potential to act as elicitors of the secondary metabolism, leading to improved grape quality, and also to set the foundation for sustainable agricultural practices in the long run.

Overexpression of TGF-ß1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous fluid-filled cysts, extensive fibrosis, and the progressive decline in kidney function. Transforming growth factor-ß1 (TGF-ß1), an important mediator for renal fibrosis and chronic kidney disease, is overexpressed by cystic cells compared with normal kidney cells; however, its role in PKD pathogenesis remains undefined. To investigate the effect of TGF-ß1 on cyst growth, fibrosis, and disease progression, we overexpressed active TGF-ß1 specifically in collecting ducts (CDs) of phenotypic normal (Pkd1RC/+) and Pkd1RC/RC mice. In normal mice, CD-specific TGF-ß1 overexpression caused tubule dilations by 5 wk of age that were accompanied by increased levels of phosphorylated SMAD3, α-smooth muscle actin, vimentin, and periostin; however, it did not induce overt cyst formation by 20 wk. In Pkd1RC/RC mice, CD overexpression of TGF-ß1 increased cyst epithelial cell proliferation. However, extensive fibrosis limited cyst enlargement and caused contraction of the kidneys, leading to a loss of renal function and a shortened lifespan of the mice. These data demonstrate that TGF-ß1-induced fibrosis constrains cyst growth and kidney enlargement and accelerates the decline of renal function, supporting the hypothesis that a combined therapy that inhibits renal cyst growth and fibrosis will be required to effectively treat ADPKD.

Photographic comparison: a method for qualitative outdoor thermal perception surveys.

This article addresses the use of photographic comparison as a complementary visual appraisal method in an outdoor thermal perception survey. This survey was carried out during a Ph.D. research exploring how materials and vegetation influence thermal comfort in outdoor public spaces. Objective and subjective thermal perception parameters were combined and quantitative and qualitative research methods were used. The quantitative methods included microclimatic measurements, whilst the qualitative methods comprised observations and spatially localised interviews based on a questionnaire and the photographic comparison. This article explores how such visual research method allowed triangulating findings of this field survey. Three non-edited photographs of outdoor public spaces, under similar summer meteorological conditions but with contrasting spatial features, were shown to respondents to the questionnaire. The photographs depicted undisclosed locations for preventing biased emotional appreciations. Respondents were asked to select the potentially most comfortable and uncomfortable environments depicted. The choice of photographs matched the previous answers on the thermal sensation and evaluation judgement scales. Hence, we discuss the way the visual interpretations by respondents allowed the triangulation of in situ thermal perception data. The extent to which thermal comfort can be interpreted from thermal environments depicted in photographs containing clear visual signs is further discussed. The article concludes on how such a visual appraisal method can be valuable for enriching future qualitative outdoor thermal perception surveys with subjective interpretation of visual data.

Chemical Space Exploration of Oxetanes.

This paper focuses on new derivatives bearing an oxetane group to extend accessible chemical space for further identification of kinase inhibitors. The ability to modulate kinase activity represents an important therapeutic strategy for the treatment of human illnesses. Known as a nonclassical isoster of the carbonyl group, due to its high polarity and great ability to function as an acceptor of hydrogen bond, oxetane seems to be an attractive and underexplored structural motif in medicinal chemistry.

Hippocampal subareas arranged in the dorsoventral axis modulate cardiac baroreflex function in a site-dependent manner in rats.

NEW FINDINGS: What is the central question of this study? Classically, areas of the brainstem are involved in the cardiac baroreceptor reflex. However, forebrain areas, such as the hippocampus, may also modulate the cardiac baroreflex function. What is the main finding and its importance? According to the hippocampal subarea recruited dorsoventrally, the baroreflex function can be either facilitated or inhibited. These results are according to the new topographical division proposed for the hippocampus, i.e. it can be divided into functionally and anatomically different regions along its dorsoventral axis. From a neuroanatomical point of view, we may split the hippocampal formation into the dorsal (DH) and ventral hippocampus (VH). Although the basic intrinsic circuitry of the hippocampus seems to be maintained throughout its longitudinal axis, dorsal and ventral portions connect differently with cortical and subcortical areas and express different gene patterns, being functionally distinct. Differential stimulation of the DH or VH can evoke either an increase or a decrease in blood pressure, heart rate and sympathetic activity. However, to the best of our knowledge, specific involvement of the hippocampus and its different subareas in the baroreflex function remains to be investigated. In the present work, therefore, we evaluated the involvement of hippocampal subareas arranged on the dorsoventral axis in cardiac baroreflex modulation. Our results suggest that inhibition of hippocampal subareas by CoCl2 , a calcium-dependent synaptic neurotransmission blocker, differentially affects baroreflex sensitivity; administration of CoCl2 into the DH increased cardiac baroreflex function, whereas it diminished cardiac baroreflex function when administered into the VH. In contrast, administration of CoCl2 into intermediate portions of the hippocampus did not affect the baroreflex response. Our findings suggest that the hippocampus influences baroreflex function according to the hippocampal subarea recruited dorsoventrally.

Factors associated with non-pathogenic antibodies against desmoglein-3 in pemphigus foliaceus.

BACKGROUND: Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. OBJECTIVES: To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. METHODS: Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. RESULTS: In the PF-anti-Dsg3+ group: age range similar to that of the PV group (p > 0.9999); predominance of the generalized form of PF (p = 0.002); anti-Dsg3 titers lower than those of PV (p < 0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. STUDY LIMITATIONS: Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. CONCLUSION: The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.

The Use of Diets to Improve the Quality of Life of Women With Breast Cancer.

INTRODUCTION: There has been an increase in the incidence of breast cancer cases in the last decade, and despite the treatment increasing the chances of survival, it reduces the quality of life. In this context, diets could decrease the adverse effects of treatment and improve quality of life. METHODOLOGY: A form with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, which contains specific scores for physical, cognitive, emotional, symptomatic, and functional performance, was made available in a Facebook support group. Afterward, the data were analyzed using linear regression and a t-test of independent samples using Jamovi version 2.3.24 (retrieved from https://www.jamovi.org). RESULTS: There was a low number of participants who followed the ketogenic diet or intermittent fasting. In general, adherence to the diets was good. In the t-test, diets showed improvement in physical performance. Linear regression correlated treatment with chemotherapy, metastases, and bad diet adherence with worse symptomatic scores. CONCLUSION: There is evidence that diets can improve the symptoms of these patients; however, there is no consensus about which diet produces the best effect, requiring further studies on this subject.

ENDOCANNABINOID SYSTEM IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS MODULATES AUTONOMIC AND CARDIOVASCULAR CHANGES BUT NOT VASOPRESSIN RESPONSE IN A RAT HEMORRHAGIC SHOCK MODEL.

ABSTRACT: We evaluated the participation of the endocannabinoid system in the paraventricular nucleus of the hypothalamus (PVN) on the cardiovascular, autonomic, and plasma vasopressin (AVP) responses evoked by hemorrhagic shock in rats. For this, the PVN was bilaterally treated with either vehicle, the selective cannabinoid receptor type 1 antagonist AM251, the selective fatty acid amide hydrolase amide enzyme inhibitor URB597, the selective monoacylglycerol-lipase enzyme inhibitor JZL184, or the selective transient receptor potential vanilloid type 1 antagonist capsazepine. We evaluated changes on arterial pressure, heart rate, tail skin temperature (ST), and plasma AVP responses induced by bleeding, which started 10 min after PVN treatment. We observed that bilateral microinjection of AM251 into the PVN reduced the hypotension during the hemorrhage and prevented the return of blood pressure to baseline values in the posthemorrhagic period. Inhibition of local 2-arachidonoylglycerol metabolism by PVN treatment with JZL184 induced similar effects in relation to those observed in AM251-treated animals. Inhibition of local anandamide metabolism via PVN treatment with URB597 decreased the depressor effect and ST drop induced by the hemorrhagic stimulus. Bilateral microinjection of capsazepine mitigated the fall in blood pressure and ST. None of the PVN treatments altered the increased plasma concentration of AVP and tachycardia induced by hemorrhage. Taken together, present results suggest that endocannabinoid neurotransmission within the PVN plays a prominent role in cardiovascular and autonomic, but not neuroendocrine, responses evoked by hemorrhage.

The interplay between climate change and ageing: A systematic review of health indicators.

Climate change and rapid population ageing pose challenges for communities and public policies. This systematic review aims to gather data from studies that present health indicators establishing the connection between climate change and the physical and mental health of the older population (≥ 65 years), who experience a heightened vulnerability to the impacts of climate change when compared to other age cohorts. This review was conducted according to the PICO strategy and following Cochrane and PRISMA guidelines. Three databases (PubMed, Scopus and Greenfile) were searched for articles from 2015 to 2022. After applying inclusion and exclusion criteria,nineteen studies were included. The findings indicated that various climate change phenomena are associated with an elevated risk of mortality and morbidity outcomes in older adults. These included cardiovascular, respiratory, renal, and mental diseases, along with physical injuries. Notably, the impact of climate change was influenced by gender, socioeconomic status, education level, and age-vulnerability factors. Climate change directly affected the health of older adults through ambient temperature variability, extreme and abnormal temperatures, strong winds, sea temperature variability, extreme El Niño-southern Oscillation (ENSO) conditions and droughts, and indirectly by air pollution resulting from wildfires. This review presents further evidence confirming that climate change significantly impacts the health and well-being of older adults. It highlights the urgency for implementing effective strategies to facilitate adaptation and mitigation, enhancing the overall quality of life for all individuals.

Transforming growth factor-ß1 impairs CFTR-mediated anion secretion across cultured porcine vas deferens epithelial monolayer via the p38 MAPK pathway.

The goal of this study was to determine whether transforming growth factor-ß1 (TGF-ß1) affects epithelial cells lining the vas deferens, an organ that is universally affected in cystic fibrosis male patients. In PVD9902 cells, which are derived from porcine vas deferens epithelium, TGF-ß1 exposure significantly reduced short-circuit current (Isc) stimulated by forskolin or a cell membrane-permeant cAMP analog, 8-pCPT-cAMP, suggesting that TGF-ß1 affects targets of the cAMP signaling pathway. Electrophysiological results indicated that TGF-ß1 reduces the magnitude of current inhibited by cystic fibrosis transmembrane conductance regulator (CFTR) channel blockers. Real-time RT-PCR revealed that TGF-ß1 downregulates the abundance of mRNA coding for CFTR, while biotinylation and Western blot showed that TGF-ß1 reduces both total CFTR and apical cell surface CFTR abundance. These results suggest that TGF-ß1 causes a reduction in CFTR expression, which limits CFTR-mediated anion secretion. TGF-ß1-associated attenuation of anion secretion was abrogated by SB431542, a TGF-ß1 receptor I inhibitor. Signaling pathway studies showed that the effect of TGF-ß1 on Isc was reduced by SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK). TGF-ß1 exposure also increased the amount of phospho-p38 MAPK substantially. In addition, anisomycin, a p38 MAPK activator, mimicked the effect of TGF-ß1, which further suggests that TGF-ß1 affects PVD9902 cells through a p38 MAPK pathway. These observations suggest that TGF-ß1, via TGF-ß1 receptor I and p38 MAPK signaling, reduces CFTR expression to impair CFTR-mediated anion secretion, which would likely compound the effects associated with mild CFTR mutations and ultimately would compromise male fertility.

Involvement of the insular cortex in the consolidation and expression of contextual fear conditioning.

The insular cortex (IC) has been reported to be involved in the modulation of memory and autonomic and defensive responses. However, there is conflicting evidence about the role of the IC in fear conditioning. To explore the IC involvement in both behavioral and autonomic responses induced by contextual fear conditioning, we evaluated the effects of the reversible inhibition of the IC neurotransmission through bilateral microinjections of the non-selective synapse blocker CoCl2 (1 mm) 10 min before or immediately after the conditioning session or 10 min before re-exposure to the aversive context. In the conditioning session, rats were exposed to a footshock chamber (context) and footshocks were used as the unconditioned stimulus. Forty-eight hours later, the animals were re-exposed to the aversive context for 10 min, but no shock was given. Behavioral (freezing) as well as cardiovascular (arterial pressure and heart rate increases) responses induced by re-exposure to the aversive context were analysed. It was observed that the local IC neurotransmission inhibition attenuated freezing and the mean arterial pressure and heart rate increase of the groups that received the CoCl2 either immediately after conditioning or 10 min before re-exposure to the aversive context, but not when the CoCl2 was injected before the conditioning session. These findings suggest the involvement of the IC in the consolidation and expression of contextual aversive memory. However, the IC does not seem to be essential for the acquisition of memory associated with aversive context.

Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses.

Neural reflex mechanisms, such as the baroreflex, are involved in regulating cardiovascular system activity. Previous results showed that the ventral portion of the medial prefrontal cortex (vMPFC) is involved in modulation only of the cardiac baroreflex bradycardic component. Moreover, vMPFC N-methyl-D-aspartate (NMDA) receptors modulate the bradycardia baroreflex, but the baroreflex tachycardic component has not been investigated. Furthermore, glutamatergic neurotransmission into the vMPFC is involved in activation of the cardiac sympathetic and parasympathetic nervous system. Finally, it has been demonstrated that glutamatergic neurotransmission into the vMPFC can be modulated by the endocannabinoid system and that activation of the CB1 cannabinoid receptor by anandamide, an endocannabinoid, can decrease both cardiac baroreflex bradycardic and tachycardic responses. Thus, there is the possibility that glutamatergic neurotransmission into the vMPFC does not modulate only the cardiac bradycardic component of the baroreflex. Therefore, the present study investigated whether glutamatergic neurotransmission into the vMPFC modulates both cardiac baroreflex bradycardic and tachycardic responses. We found that vMPFC bilateral microinjection of the NMDA receptor antagonist AP7 (4 nmol/200 nl), of a selective inhibitor of neuronal nitric oxide (NO) synthase N-propyl (0.08 nmol/200 nl), of the NO scavenger carboxy-PTIO (2 nmol/200 nl), or of the NO-sensitive guanylate cyclase ODQ (2 nmol/200 nl) decreased the baroreflex activity in unanesthetized rats. Therefore, our results demonstrate the participation of NMDA receptors, production of NO, and activation of guanylate cyclase in the vMPFC in the modulation of both cardiac baroreflex bradycardic and tachycardic responses.

High resolution melting analysis of KRAS, BRAF and PIK3CA in KRAS exon 2 wild-type metastatic colorectal cancer.

BACKGROUND: KRAS is an EGFR effector in the RAS/RAF/ERK cascade that is mutated in about 40% of metastatic colorectal cancer (mCRC). Activating mutations in codons 12 and 13 of the KRAS gene are the only established negative predictors of response to anti-EGFR therapy and patients whose tumors harbor such mutations are not candidates for therapy. However, 40 to 60% of wild-type cases do not respond to anti-EGFR therapy, suggesting the involvement of other genes that act downstream of EGFR in the RAS-RAF-MAPK and PI3K-AKT pathways or activating KRAS mutations at other locations of the gene. METHODS: DNA was obtained from a consecutive series of 201 mCRC cases (FFPE tissue), wild-type for KRAS exon 2 (codons 12 and 13). Mutational analysis of KRAS (exons 3 and 4), BRAF (exons 11 and 15), and PIK3CA (exons 9 and 20) was performed by high resolution melting (HRM) and positive cases were then sequenced. RESULTS: One mutation was present in 23.4% (47/201) of the cases and 3.0% additional cases (6/201) had two concomitant mutations. A total of 53 cases showed 59 mutations, with the following distribution: 44.1% (26/59) in KRAS (13 in exon 3 and 13 in exon 4), 18.6% (11/59) in BRAF (two in exon 11 and nine in exon 15) and 37.3% (22/59) in PIK3CA (16 in exon 9 and six in exon 20). In total, 26.4% (53/201) of the cases had at least one mutation and the remaining 73.6% (148/201) were wild-type for all regions studied. Five of the mutations we report, four in KRAS and one in BRAF, have not previously been described in CRC. BRAF and PIK3CA mutations were more frequent in the colon than in the sigmoid or rectum: 20.8% vs. 1.6% vs. 0.0% (P=0.000) for BRAF and 23.4% vs. 12.1% vs. 5.4% (P=0.011) for PIK3CA mutations. CONCLUSIONS: About one fourth of mCRC cases wild-type for KRAS codons 12 and 13 present other mutations either in KRAS, BRAF, or PIK3CA, many of which may explain the lack of response to anti-EGFR therapy observed in a significant proportion of these patients.

Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: a review.

The bed nucleus of the stria terminalis (BNST) is a heterogeneous and complex limbic forebrain structure, which plays an important role in controlling autonomic, neuroendocrine and behavioral responses. The BNST is thought to serve as a key relay connecting limbic forebrain structures to hypothalamic and brainstem regions associated with autonomic and neuroendocrine functions. Its control of physiological and behavioral activity is mediated by local action of numerous neurotransmitters. In the present review we discuss the role of the BNST in control of both autonomic and neuroendocrine function. A description of BNST control of cardiovascular and hypothalamus-pituitary-adrenal axisactivity at rest and during physiological challenges (stress and physical exercise) is presented. Moreover, evidence for modulation of hypothalamic magnocellular neurons activity is also discussed. We attempt to focus on the discussion of BNST neurochemical mechanisms. Therefore, the source and targets of neurochemical inputs to BNST subregions and their role in control of autonomic and neuroendocrine function is discussed in details.

Volatile Composition of Fortification Grape Spirit and Port Wine: Where Do We Stand?

Port wine's prominence worldwide is unequivocal and the grape spirit, which comprises roughly one fifth of the total volume of this fortified wine, is also a contributor to the recognized quality of this beverage. Nonetheless, information about the influence of the grape spirit on the final aroma of Port wine, as well as its volatile composition, is extremely limited. Moreover, the aroma characteristics of Port wines are modulated mainly by their volatile profiles. Hence, this review presents a detailed overview of the volatile composition of the fortification spirit and Port wine, along with the methodologies employed for their characterization. Moreover, it gives a general overview of the Douro Demarcated Region (Portugal) and the relevance of fortification spirit to the production of Port wine. As far as we know, this review contains the most extensive database on the volatile composition of grape spirit and Port wine, corresponding to 23 and 208 compounds, respectively. To conclude, the global outlook and future challenges are addressed, with the position of the analytical coverage of the chemical data on volatile components discussed as crucial for the innovation centered on consumer preferences.

Ascophyllum nodosum Extract and Glycine Betaine Preharvest Application in Grapevine: Enhancement of Berry Quality, Phytochemical Content and Antioxidant Properties.

The Douro Demarcated Region (DDR) has peculiar edaphoclimatic characteristics that provide a suitable terroir for premium wine production. As climate change effects continue to emerge, ensuring productivity and quality becomes increasingly important for viticulturists, as those directly determine their profits. Cultural approaches, such as the use of biostimulants, are actively being developed to mitigate abiotic stress. The main objective of this work was to assess the effect of foliar sprays of a seaweed (Ascophyllum nodosum)-based extract (ANE) and glycine betaine (GB) on grape berry quality, bioactive compounds, and antioxidant activity. A trial was installed in a commercial vineyard (cv. 'Touriga Franca') in the Douro Superior (Upper Douro) sub-region of the Douro Demarcated Region. In 2020 and 2021, three foliar sprayings were performed during the growing season, namely at pea size, bunch closure, and veraison. There was a positive effect of both biostimulants (ANE and GB) on the physiological and biochemical performance of cv. 'Touriga Franca' exposed to summer stress. In general, the GB 0.2% spraying was the most promising treatment for this grape cultivar, as it increased berry quality, the concentration of bioactive compounds (total phenolics, flavonoids, and ortho-diphenols), and the antioxidant activity. These results revealed the efficacy of biostimulant sprayings as a sustainable viticultural practice, improving berry quality under summer stress conditions.

COVID-19 in the nervous system: physiopathology and neurological manifestations.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory manifestations have received greater visibility during the pandemic caused by this virus, numerous neurological complaints related to coronavirus 2 infection have been documented in several countries. These records suggest that this pathogen presents neurotropism, and it can cause different neurological conditions of varying intensity. OBJECTIVE: To investigate the ability of coronavirus 2 to invade the central nervous system (CNS) and its neurological clinical outcomes. METHODS: The present study consists in a comprehensive literature review of the records available in the PubMed, SciELO, and Google Scholar databases. The descriptors COVID-19, brain and physiopathology, associated with the Boolean operator AND, were used in the search. Regarding the inclusion and exclusion criteria, we selected the papers published since 2020 with the highest number of citations. RESULTS: We selected 41 articles, most of them in English. The main clinical manifestation associated with COVID-19 patients was headache, but cases of anosmia, hyposmia, Guillain-Barré syndrome, and encephalopathies were also described with considerable frequency. CONCLUSION: Coronavirus-2 presents neurotropism, and it can reach the CNS by hematogenous dissemination and by direct infection of the nerve endings. It causes brain injuries through several mechanisms, such as cytokine storm, microglial activation, and an increase in thrombotic factors.

ANTECEDENTES: A doença do coronavírus 2019 (coronavirus disease 2019, Covid-19, em inglês) é uma infecção viral provocada pelo coronavírus 2 da síndrome respiratória aguda grave (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, em inglês). Embora as manifestações respiratórias tenham recebido maior visibilidade ao longo da pandemia provocada por esse vírus, inúmeras queixas neurológicas relacionadas à infecção pelo coronavírus 2 foram documentadas em diversos países. Tais registros sugerem que esse patógeno apresenta neurotropismo, e é capaz de provocar quadros neurológicos diversos e de intensidade variáveis. OBJETIVO: Investigar a capacidade de invasão do sistema nervoso central (SNC) pelo coronavírus 2 e seus principais desfechos clínicos neurológicos. MéTODOS: O presente estudo consiste em uma ampla revisão de literatura a partir dos registros das bases de dados PubMed, SciELO e Google Acadêmico. Nesse contexto, os descritores COVID-19, cérebro e fisiopatologia, associados com o operador booleano AND, foram utilizados na busca. Quanto aos critérios de inclusão e exclusão, selecionou-se os trabalhos publicados a partir de 2020 com o maior número de citações. RESULTADOS: Foram selecionados 41 artigos, a maioria na língua inglesa. A principal manifestação clínica associada a pacientes acometidos pela COVID-19 foi a cefaleia, mas casos de anosmia, hiposmia, síndrome de Guillain-Barré e encefalopatias também foram descritos com frequência considerável. CONCLUSãO: O coronavírus 2 apresenta neurotropismo, e é capaz de alcançar o SNC por disseminação hematogênica e por infecção direta das terminações nervosas. Ele provoca injúria cerebral por meio de variados mecanismos, como tempestade de citocinas, ativação da micróglia e aumento dos fatores trombóticos.

Transforming growth factor beta 1 induces tight junction disruptions and loss of transepithelial resistance across porcine vas deferens epithelial cells.

Epithelial cells lining the male excurrent duct contribute to male fertility by employing a number of physiological mechanisms that generate a luminal microenvironment conducive to spermatozoa maturation and storage. Among these mechanisms, male duct epithelia establish intercellular tight junctions that constitute a barrier to paracellular diffusion of water, solutes, large molecules, and cells. Mechanisms regulating the male duct epithelial barrier remain unidentified. Transforming growth factor beta (TGFB) is a regulatory cytokine present in high concentrations in human semen. This study examined whether TGFB has any effects on epithelial function exhibited by primary cultures of porcine vas deferens epithelia. TGFB1 exposure caused a 70%-99% decrease in basal transepithelial electrical resistance (R(TE), a sensitive indicator of barrier integrity), while a significant decrease in anion secretory response to forskolin was detected at the highest levels of TGFB1 exposure employed. SB431542, a selective TGFB receptor I (TGFBR1) inhibitor, prevented decreases in barrier function. Results also demonstrated that TGFB1 exposure modifies the distribution pattern of tight junction proteins occludin and claudin 7. TGFBR1 is localized at the apical border of the native porcine vas deferens epithelium. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) 11 (also known as p38-MAPK) did not alter the effect of TGFB1 on R(TE) significantly. These data suggest that epithelia lining the vas deferens are subject to disruptions in the physical barrier if active TGFB becomes bioavailable in the luminal fluid, which might be expected to compromise fertility.

Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB(1) receptors.

Neural reflex mechanisms, such as the baroreflex, are involved in the regulation of cardiovascular system activity. Previous results from our group (Resstel LB, Correa FM. Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex. Eur J Neurosci 23: 481-488, 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB(1) receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB(1) receptors modulate baroreflex activity. We found that bilateral microinjection of the CB(1) receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB(1) receptors, which modulate local glutamate release.

Lateral septal area α1- and α2-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats.

The lateral septal area (LSA) is a limbic structure involved in autonomic, neuroendocrine and behavioural responses. An inhibitory influence of the LSA on baroreflex activity has been reported; however, the local neurotransmitter involved in this modulation is still unclear. In the present study, we verified the involvement of local LSA adrenoceptors in modulating cardiac baroreflex activity in unanaesthetized rats. Bilateral microinjection of the selective α(1)-adrenoceptor antagonist WB4101 (10 nmol in a volume of 100 nl) into the LSA decreased baroreflex bradycardia evoked by blood pressure increases, but had no effect on reflex tachycardia evoked by blood pressure decreases. Nevertheless, bilateral administration of the selective α(2)-adrenoceptor antagonist RX821002 (10 nmol in 100 nl) increased baroreflex tachycardia without affecting reflex bradycardia. Treatment of the LSA with a cocktail containing WB4101 and RX821002 decreased baroreflex bradycardia and increased reflex tachycardia. The non-selective ß-adrenoceptor antagonist propranolol (10 nmol in 100 nl) did not affect either reflex bradycardia or tachycardia. Microinjection of noradrenaline into the LSA increased reflex bradycardia and decreased the baroreflex tachycardic response, an opposite effect compared with those observed after double blockade of α(1)- and α(2)-adrenoceptors, and this effect of noradrenaline was blocked by local LSA pretreatment with the cocktail containing WB4101 and RX821002. The present results provide advances in our understanding of the baroreflex neural circuitry. Taken together, data suggest that local LSA α(1)- and α(2)-adrenoceptors modulate baroreflex control of heart rate differently. Data indicate that LSA α(1)-adrenoceptors exert a facilitatory modulation on baroreflex bradycardia, whereas local α(2)-adrenoceptors exert an inhibitory modulation on reflex tachycardia.