Periodontal disease metabolomics signatures from different biofluids: a systematic review.

BACKGROUND: Periodontitis is resulted from a complex interaction between genetics and epigenetics, microbial factors, and the host response. Metabolomics analyses reflect both the steady-state physiological equilibrium of cells or organisms as well as their dynamic metabolic responses to environmental stimuli. AIM OF REVIEW: This systematic review of the literature aimed to assess which low molecular weight metabolites are more often found in biological fluids of individuals with periodontitis compared to individuals with gingivitis or periodontal health. KEY SCIENTIFIC CONCEPTS OF REVIEW: All the included studies employed untargeted analysis. One or more biological fluids were analyzed, including saliva (n = 14), gingival crevicular fluid (n = 6), mouthwash (n = 1), serum (n = 3) and plasma (n = 1). Fifty-six main metabolites related to periodontitis have been identified in at least two independent studies by NMR spectroscopy or MS-based metabolomics. Saliva was the main biological fluid sampled. It is noteworthy that 14 metabolites of the 56 detected were identified as main metabolites in all studies that sampled the saliva. The majority of metabolites found consistently among studies were amino acids, organic acids and derivates: acetate, alanine, butyrate, formate, GABA, lactate, propionate, phenylalanine and valine. They were either up- or down-regulated in the studies or this information was not mentioned. The main metabolic pathway was related to phenylalanine, tyrosine and tryptophan biosynthesis. Metabolites more frequently found in individuals with periodontitis were related to both the host and to microorganism responses. Future studies are needed, and they should follow some methodological standards to facilitate their comparison.

Impact of chronic gingivitis management on the cytokine and anti-PPAD expressions in juvenile systemic lupus erythematosus: A six-month follow-up.

OBJECTIVE: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment. BACKGROUND: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1. MATERIALS AND METHODS: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment. RESULTS: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1ß, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed. CONCLUSION: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term.

Efficacy of Minoxidil Combined With Photobiomodulation for the Treatment of Male Androgenetic Alopecia. A Double-Blind Half-Head Controlled Trial.

BACKGROUND: Androgenetic alopecia (AGA) is a hair loss disorder that frequently affects the male population. Conventional treatment modalities are limited to minoxidil, 5α reductase inhibitors, and hair transplantation procedures. The efficacy of low-level laser therapy (LLLT), also known as photobiomodulation, in the treatment of AGA has been reported, yet little is known about the outcomes of combining photobiomodulation with other conventional therapies. OBJECTIVE: To evaluate hair growth improvement in males with AGA, during the administration of minoxidil with and without photobiomodulation, using a half-head model. STUDY DESIGN/MATERIALS AND METHODS: Twenty-one men with AGA agreed to undergo 12 minutes of low-level laser irradiation (using a modified Capellux®), followed by topical minoxidil application (1 ml of 5% solution), to the affected scalp two times per day for 6 months. The photobiomodulation devices were modified such that the left half emitted light, and the right half did not. Efficacy was assessed by blinded analyses of clinical photos and automated phototrichograms (Trichoscan®) taken before treatment and after 3 and 6 months of therapy. RESULTS: None of the study participants experienced any adverse events. All patients showed improvements in hair coverage on both sides of the scalp at 3 and 6 months. On the side with combined treatments, the number of total hairs was significantly increased after 3 (P < 0.001) and 6 months (P = 0.001). A similar increase was also observed on the minoxidil-only side, at both 3 (P < 0.001) and 6 months (P < 0.001). No statistically significant differences were detected between sides (P > 0.05). CONCLUSION: Additional improvement was not observed with the association of photobiomodulation to topical minoxidil in male AGA. Differences from previous studies that might have influenced our result include non-collimated light source, higher dosimetry, and a cohort with darker skin phototype and more severe alopecia. Lasers Surg. Med. 2021. © 2021 Wiley Periodicals LLC.

Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis can corroborate with development and progression of atherosclerosis and a possible bidirectional interaction between both pathologies has been hypothesized. The aim of this work was to study the interactions between diet-induced hypercholesterolemia and ligature-induced periodontitis in Wistar rats submitted to both conditions. MATERIAL AND METHODS: Animals were divided into four experimental groups: C (control: standard diet without periodontitis), Perio (periodontitis plus standard diet), HC (high cholesterol diet without periodontitis), and HC + Perio (high cholesterol diet plus periodontitis). The diets were offered for 45 days and a silk ligature was applied in the lower first molars of Perio and HC-Perio animals on day 34 and maintained for 11 days until euthanasia. The mandibles were excised, and alveolar bone loss was determined by macroscopic and micro-tomographic (µ-CT) imaging. Blood samples were obtained, and platelet aggregation was induced in plasma rich in platelets by adenosine diphosphate (ADP) and collagen. Endothelium-dependent vascular reactivity and protein expression of endothelial (eNOS), phosphorylated endothelial (peNOS), and inducible (iNOS) nitric oxide synthases were evaluated in aorta samples. RESULTS: The HC diet combined with periodontitis (HC + Perio group) was associated with an increased alveolar bone loss, when compared to the other groups. Both in Perio and HC groups, platelet aggregation induced by ADP or collagen was increased, while maximum aortic relaxation induced by acetylcholine was decreased. Periodontitis or HC diet alone decreased the expression of peNOS and HC diet increased the expression of iNOS. In contrast, no additive or synergistic effects were found in vascular reactivity or in platelet aggregation when the two conditions were associated (HC + Perio group). CONCLUSION: Hypercholesterolemia accelerated the process of bone loss induced by periodontitis while a high cholesterol diet or periodontitis individually increased platelet aggregation and vascular reactivity in rats without additive or synergistic effects, when associated.

Arginine and aerobic training prevent endothelial and metabolic alterations in rats at high risk for the development of the metabolic syndrome.

Endothelial function is a key mechanism in the development of CVD. Arginine and exercise are important non-pharmacological strategies for mitigating the impact of metabolic changes in the metabolic syndrome, but the effect of their combined administration is unknown. Thus, the aim of this study was to investigate the isolated and combined effects of aerobic training and arginine supplementation on metabolic variables and vascular reactivity in rats at high risk for developing the metabolic syndrome. Wistar rats were divided into two groups: control and fructose (F - water with 10 % fructose). After 2 weeks, the F group was divided into four groups: F, fructose+arginine (FA, 880 mg/kg per d of l-arginine), fructose+training (FT) and fructose+arginine+training (FTA); treatments lasted for 8 weeks, and no difference was observed in body mass gain. Arginine did not improve the body protein content, and both the FA and FT groups show a reversal of the increase in adipose tissue. Insulin increase was prevented by training and arginine, without additive effect, and the increase in serum TAG was prevented only by training. The F group showed impaired endothelium-dependent vasodilation and hyperreactivity to phenylephrine, but arginine and training were capable of preventing these effects, even separately. Higher nitric oxide level was observed in the FA and FT groups, and no potentiating effect was detected. Thus, only training was able to prevent the increase in TAG and improve the protein mass, and training and arginine exert similar effects on fat content, insulin and endothelial function, but these effects are not additive.

Anti-atherogenic effects of a new thienylacylhydrazone derivative, LASSBio-788, in rats fed a hypercholesterolemic diet.

The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4-methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to have antiplatelet, vasodilatory, and anti-inflammatory properties in vitro. We hypothesize that LASSBio-788 may exert beneficial effects on atherosclerosis. Male wistar rats were divided into 4 groups: Control group received standard rat chow, hypercholesterolemic group (HC) and HC+788 (compound LASSBio-788 group) received hypercholesterolemic diet for 45 days. HC+788 group received compound LASSBio-788 (100 µmol/kg) once daily in the last 15 days. LASSBio-788 reduced the levels of total cholesterol (109.1 ± 4.3 vs. 361.0 ± 12.8 mg/dl), triglycerides (66.1 ± 1.1 vs. 186.9 ± 17.7 mg/dl), LDLc (63.2 ± 6.1 vs. 330.9 ± 9.7 mg/dl), VLDLc (9.8 ± 1.1 vs. 45.0 ± 4.6 mg/dl) and malondialdehyde (4.8 ± 0.3 vs. 9.4 ± 0.5 nmol/ml) compared to the HC group. LASSBio-788 presented antiplatelet properties and decreased inflammatory markers levels. LASSBio-788 promoted a decrease in contractile response to phenylephrine and an improvement in endothelium-dependent vasorelaxant response by increasing two-fold the expression of nitric oxide synthase (eNOS). Our results suggest that the compound LASSBio-788 represents a new multi-targeted drug candidate for the treatment of atherosclerosis.

Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System.

Atrial fibrillation (AF) is the most common type of sustained arrhythmia. The numerous gaps concerning the knowledge of its mechanism make improving clinical management difficult. As omics technologies allow more comprehensive insight into biology and disease at a molecular level, bioinformatics encompasses valuable tools for studying systems biology, as well as combining and modeling multi-omics data and networks. Network medicine is a subarea of network biology where disease traits are considered perturbations within the interactome. With this approach, potential disease drivers can be revealed, and the effect of drugs, novel or repurposed, used alone or in combination, may be studied. Thus, this work aims to review AF pathology from a network medicine perspective, helping researchers to comprehend the disease more deeply. Essential concepts involved in network medicine are highlighted, and specific research applying network medicine to study AF is discussed. Additionally, data integration through literature mining and bioinformatics tools, with network building, is exemplified. Together, all of the data show the substantial role of structural remodeling, the immune system, and inflammation in this disease etiology. Despite this, there are still gaps to be filled about AF.

Subacute administration of cilostazol modulates PLC-γ/PKC-α/p38/NF-kB pathway and plays vascular protective effects through eNOS activation in early stages of atherosclerosis development.

AIMS: Hypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 clinically prescribed for intermittent claudication treatment. Due to its pleiotropic properties, such as lipid lowering, anti-inflammatory, and antioxidant effects, the therapeutic repurposing of cilostazol has become a strategic approach for atherosclerosis treatment. This study aimed to investigate the effects of subacute administration of cilostazol on the aortas of hypercholesterolemic rats, focusing on the signaling pathways involved in these actions. MAIN METHODS: A murine model of hypercholesterolemia was employed to mimic the early stages of atherosclerosis development. Vascular reactivity assays were performed on thoracic aorta rings to assess the vascular response, as well as the non-invasive blood pressure was evaluated by plethysmography method. Pro-inflammatory markers and malondialdehyde (MDA) levels were measured to investigate the anti-inflammatory and antioxidant effects of cilostazol. Western Blot analysis was performed in aortas homogenates to evaluate the role of cilostazol on PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB and PKA/eNOS/PKG pathways. KEY FINDINGS: The hypercholesterolemic diet induced the production of pro-inflammatory mediators such as TNF-α, TXB2, VCAM, and worsened vascular function, marked by increased contractile response, decreased maximum relaxation, and elevated systolic and diastolic blood pressure. Cilostazol seems to counteract the deleterious effects promoted by hypercholesterolemic diet, showing important anti-inflammatory and vasculoprotective properties possibly through the inhibition of the PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB pathway and activation of the PKA/eNOS/PKG pathway. SIGNIFICANCE: Cilostazol suppressed hypercholesterolemia-induced vascular dysfunction and inflammation. Our data suggest the potential repurposing of cilostazol as a pharmacological treatment for atherosclerosis.

Auras in temporal lobe epilepsy with hippocampal sclerosis: relation to seizure focus laterality and post surgical outcome.

We examined the relationship between presence and frequency of different types of auras and side of lesion and post surgical outcomes in 205 patients with medically intractable mesial temporal lobe epilepsy (MTLE) with unilateral hippocampal sclerosis (HS). With respect to the number of auras, multiple auras were not associated with side of lesion (p=0.551). The side of HS was not associated with the type of auras reported. One hundred fifty-seven patients were operated. The occurrence of multiple auras was not associated with post-surgical outcome (p=0.740). The presence of extratemporal auras was significantly higher in patients with poor outcome. In conclusion, this study suggests that the presence of extratemporal auras in patients with MTLE-HS possibly reflects extratemporal epileptogenicity in these patients, who otherwise showed features suggestive of TLE. Therefore, TLE-HS patients undergoing pre-surgical evaluation and presenting clinical symptoms suggestive of extratemporal involvement should be more extensively evaluated to avoid incomplete resection of the epileptogenic zone.

Cilostazol attenuates cardiac oxidative stress and inflammation in hypercholesterolemic rats.

Atherosclerosis is a multifactorial chronic disease associated with pro-inflammatory and pro-oxidative cardiovascular states. Cilostazol, a selective phosphodiesterase 3 inhibitor (PDE3), is clinically used in the treatment of intermittent claudication and secondary prevention of cerebral infarction. The aim of this study was to evaluate the cardioprotective effects of cilostazol and the molecular mechanisms involved in hypercholesterolemic rats. Male Wistar rats were divided into four groups: control group (C) and control + cilostazol group (C+CILO), that were fed a standard chow diet, and hypercholesterolemic diet group (HCD) and HCD + cilostazol (HCD+CILO) that were fed a hypercholesterolemic diet. Cilostazol treatment started after 30 days for C+CILO and HCD+CILO groups. Animals were administered cilostazol once a day for 15 days. Subsequently, serum and left ventricles were extracted for evaluation of lipid profile, inflammatory, and oxidative biomarkers. The HCD group displayed increased serum lipid levels, inflammatory cytokines production, and cardiac NF-kB protein expression and decreased cardiac Nrf2-mediated antioxidant activity. Conversely, the cilostazol treatment improved all these cardiac deleterious effects, inhibiting NF-kB activation and subsequently decreasing inflammatory mediators, reestablishing the antioxidant properties through Nrf2-mediated pathway, including increased SOD, GPx, and catalase expression. Taken together, our results indicated that cilostazol protects hypercholesterolemia-induced cardiac damage by molecular mechanisms targeting the crosstalk between Nrf2 induction and NF-kB inhibition in the heart.

Evaluation of the effects produced by subacute tributyltin administration on vascular reactivity of male wistar rats.

Tributyltin chloride (TBT) is an organotin compound widely used in several high biocides for agroindustrial applications, such as fungicides, and marine antifouling paints leading to endocrine disrupting actions, such as imposex development in mollusks. In female rats, TBT has been shown to promote ovarian dysfunction, reduction of estrogen protective effect in the vascular morphophysiology, at least in part by oxidative stress consequences. Estrogen causes coronary endothelium-dependent and independent vasodilation. However, the TBT effects on cardiovascular system of male rats are not fully understood. The aim of this study was to evaluate the effects of subacute TBT exposure in aorta vascular reactivity from male wistar rats. Rats were randomly divided into three groups: control (C), TBT 500 ng/kg/day and TBT 1000 ng/kg/day. TBT was administered daily for 30 days by oral gavage. We found that TBT exposure enhanced testosterone serum levels and it was also observed obesogenic properties. TBT exposure evoked an increase in endothelium-dependent and independent phenylephrine-induced contraction, associated to an inhibition in eNOS activity. On the other hand, it was observed an enhancement of iNOS and NF-kB protein expression. We also observed an increase in oxidative stress parameters, such as superoxide dismutase (SOD) and catalase expression, and also an increase in malondialdehyde production. Finally, TBT exposure produced aortic intima-media thickness. Taken together, these data suggest a potential cardiovascular toxicological effect after subacute TBT exposure in male rats.

Impact of Brazil Nut (Bertholletia excelsa, H.B.K.) Supplementation on Body Composition, Blood Pressure, and the Vascular Reactivity of Wistar Rats When Submitted to a Hypersodium Diet.

Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascular homeostasis.Objective: The aim of this study was to investigate the impact of Brazil nut (Bertholletia excelsa, H.B.K.) (BN) supplementation (10% in chow, wt/wt) on the vascular reactivity of Wistar rats during chronic exposure to a sodium overload (1% in water).Methods: First, male Wistar rats were allocated into two groups: Control Group (CG) and the Hypersodic Group (HG) for 4 weeks. Afterward, the CG was divided into the Brazil Nut Group (BNG) and the HG Group into the Hypersodic Brazil Nut Group (HBNG) for a further 8 weeks, totaling 4 groups. Blood pressure was measured during the protocol. At the end of the protocol, the vascular reactivity procedure was performed. Glucose, lipid profile, lipid peroxidation, and platelet aggregation were analyzed in the serum. Body composition was determined by the carcass technique.Results: The groups that were supplemented with the BN chow presented less body mass gain and body fat mass, together with lower serum glucose levels. The HG Group presented an increase in blood pressure and a higher platelet aggregation, while the BN supplementation was able to blunt this effect. The HG Group also showed an increase in contractile response that was phenylephrine-induced and a decrease in maximum relaxation that was acetylcholine-induced when compared to the other groups.Conclusion: The BN supplementation was able to prevent an impaired vascular function in the early stages of arterial hypertension, while also improving body composition, serum glucose, and platelet aggregation.

Accuracy of genomic selection in simulated populations mimicking the extent of linkage disequilibrium in beef cattle.

BACKGROUND: The success of genomic selection depends mainly on the extent of linkage disequilibrium (LD) between markers and quantitative trait loci (QTL), the number of animals in the training set (TS) and the heritability (h2) of the trait. The extent of LD depends on the genetic structure of the population and the density of markers. The aim of this study was to calculate accuracy of direct genomic estimated breeding values (DGEBV) using best linear unbiased genomic prediction (GBLUP) for different marker densities, heritabilities and sizes of the TS in simulated populations that mimicked previously reported extent and pattern of LD in beef cattle. RESULTS: The accuracy of DGEBV increased significantly (p < 0.05) with the increase in the number of bulls in the TS (480, 960 or 1920), trait h2 (0.10, 0.25 or 0.40) and marker densities (40 k or 800 k). Increasing the number of animals in the TS by 4-fold and using their phenotypes to estimate marker effects was not sufficient to maintain or increase the accuracy of DGEBV obtained using estimated breeding values (EBVs) when the trait h2 was lower than 0.40 for both marker densities. Comparing to expected accuracies of parent average (PA), the gains by using DGEBV would be of 27%, 13% and 10% for trait h2 equal to 0.10, 0.25 and 0.40, respectively, considering the scenario with 40 k markers and 1920 bulls in TS. CONCLUSIONS: As reported in dairy cattle, the size of the TS and the extent of LD have major impact on the accuracy of DGEBV. Based on the findings of this simulation study, large TS, as well as dense marker panels, aiming to increase the level of LD between markers and QTL, will likely be needed in beef cattle for successful implementation of genomic selection.

[Meanings and uses of hunger in Brazil's political debate: recurrence and presence]. / Sentidos e usos da fome no debate político brasileiro: recorrência e atualidade.

Hunger is a persistent and structural issue in Brazil, occupying space intermittently on the political agenda, especially in times of political crisis. But when does it become interesting to denounce hunger? Who enunciates the problem and how? The article discusses the different discursive uses and meanings associated with hunger in Brazil's political debate from 1986 to 2015 and sheds light for updating the debate since 2016. This is a policy analysis study that aims to back reflection on the strategies and objectives of recent public policies to fight hunger in Brazil. The study analyzed government policy documents related to hunger from 1986 to 2015, revealing different meanings of hunger that were mobilized politically at different moments in the Brazilian context. Hunger was viewed variably as nutritional deficiency, poverty, destitution, social injustice, inequality, and food insecurity. As for political uses, hunger was mobilized discursively by different actors, according to the scenario of political dispute, until it practically disappeared from the debate, only to return during a new crisis in 2016. The return to the debate also reflects the failure to deal with structural inequalities. When hunger lost space on the political agenda, food and nutritional security policy was also undermined, and many gains were lost. The article concludes that the political discourse on hunger mobilizes audiences and is important to keep the fight against hunger in the political debate so long as there are people going hungry in the country. This should be a central item on the agenda to guarantee food and nutritional security.

A fome é uma questão persistente e estrutural no Brasil, ocupando espaço na agenda política de tempos em tempos, em especial em momentos de crise política. Mas quando se torna interessante denunciar a fome? Quem enuncia o problema e de que modo? O artigo discute os diferentes usos retóricos e sentidos associados à fome no debate político brasileiro no período de 1986 a 2015 e lança luz sobre a reatualização do debate a partir de 2016. Trata-se de um estudo de análise de políticas que visa subsidiar a reflexão sobre as estratégias e objetivos das políticas públicas recentes de combate à fome no Brasil. A pesquisa analisou documentos relacionados à fome referidos à política governamental de 1986 a 2015, revelando diferentes sentidos de fome acionados politicamente em momentos distintos do contexto brasileiro: a fome vista como carência nutricional, pobreza, miséria, injustiça social, desigualdade, insegurança alimentar grave. Quanto aos usos políticos, a fome foi mobilizada retoricamente por diferentes atores, conforme o cenário de disputa política, até praticamente sumir do debate, retornando a partir de uma nova crise no ano de 2016. Esse retorno também diz respeito ao não enfrentamento de desigualdades estruturais. Quando a fome perdeu espaço na agenda política, fragilizou-se também a política de segurança alimentar e nutricional e muitas conquistas retrocederam. Conclui-se que a retórica política mobiliza auditórios, sendo importante manter a pauta de combate à fome no debate político enquanto existirem pessoas passando fome no país, e que essa deve ser uma agenda central para garantia da segurança alimentar e nutricional.

El hambre es una cuestión persistente y estructural en Brasil, ocupando espacio en la agenda política cada cierto tiempo, en especial en momentos de crisis política. Sin embargo, ¿cuándo se hace interesante denunciar el hambre? ¿Quién enuncia el problema y de qué modo? El artículo discute los diferentes usos retóricos y sentidos asociados al hambre en el debate político brasileño, durante el período de 1986 a 2015, y proyecta luz hacia la reactualización del debate a partir de 2016. Se trata de un estudio de análisis de políticas que tiene por objetivo apoyar la reflexión sobre las estrategias y objetivos de las políticas públicas de combate al hambre en Brasil recientemente. La investigación analizó documentos relacionados con el hambre, referidos a la política gubernamental de 1986 a 2015, revelando diferentes sentidos del hambre activados políticamente en momentos distintos del contexto brasileño. El hambre vista como carencia nutricional, pobreza, miseria, injusticia social, desigualdad e inseguridad alimentaria grave. En cuanto a los usos políticos, el hambre fue movilizada retóricamente por diferentes actores conforme el escenario de disputa política, hasta prácticamente desaparecer del debate, volviendo otra vez a partir de una nueva crisis en el año de 2016. Este regreso también se refiere al no enfrentamiento de las desigualdades estructurales. Cuando el hambre perdió su espacio en la agenda política, se fragilizó también la política de seguridad alimentaria y nutricional y muchas conquistas conseguidas retrocedieron. Se concluye que la retórica política moviliza auditorios, siendo importante mantener la pauta de combate al hambre en el debate político, mientras existan personas pasando hambre en el país, debiendo ser esta una agenda central para la garantía de la seguridad alimentaria y nutricional.

Could cilostazol be beneficial in COVID-19 treatment? Thinking about phosphodiesterase-3 as a therapeutic target.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that has emerged and rapidly spread across the world. The COVID-19 severity is associated to viral pneumonia with additional extrapulmonary complications. Hyperinflammation, dysfunctional immune response and hypercoagulability state are associated to poor prognosis. Therefore, the repositioning of multi-target drugs to control the hyperinflammation represents an important challenge for the scientific community. Cilostazol, a selective phosphodiesterase type-3 inhibitor (PDE-3), is an antiplatelet and vasodilator drug, that presents a range of pleiotropic effects, such as antiapoptotic, anti-inflammatory, antioxidant, and cardioprotective activities. Cilostazol also can inhibit the adenosine uptake, which enhances intracellular cAMP levels. In the lungs, elevated cAMP promotes anti-fibrotic, vasodilator, antiproliferative effects, as well as mitigating inflammatory events. Interestingly, a recent study evaluated antiplatelet FDA-approved drugs through molecular docking-based virtual screening on viral target proteins. This study revealed that cilostazol is a promising drug against COVID-19 by inhibiting both main protease (Mpro) and Spike glycoprotein, reinforcing its use as a promising therapeutic approach for COVID-19. Considering the complexity associated to COVID-19 pathophysiology and observing its main mechanisms, this article raises the hypothesis that cilostazol may act on important targets in development of the disease. This review highlights the importance of drug repurposing to address such an urgent clinical demand safely, effectively and at low cost, reinforcing the main pharmacological actions, to support the hypothesis that a multi-target drug such as cilostazol could play an important role in the treatment of COVID-19.

Biometric, nutritional, biochemical, and cardiovascular outcomes in male rats submitted to an experimental model of early weaning that mimics mother abandoning.

Literature describes breast milk as the best food for the newborn, recommending exclusive breastfeeding for up to 6 months of age. However, it is not available for more than 40% of children worldwide. Pharmacological and non-pharmacological models of 3-day early weaning were developed in rodents to investigate later outcomes related solely to this nutritional insult. Thus, the present work aimed to describe biometric, nutritional, biochemical, and cardiovascular outcomes in adult male rats submitted to 3-day early weaning achieved by maternal deprivation. This experimental model comprises not only nutritional insult but also emotional stress, simulating mother abandoning. Male offspring were physically separated from their mothers at 21st (control) or 18th (early weaning) postnatal day, receiving water/food ad libitum. Analysis performed at postnatal days 30, 90, 150, and 365 encompassed body mass and food intake monitoring and serum biochemistry determination. Further assessments included hemodynamic, echocardiographic, and cardiorespiratory evaluation. Early-weaned males presented higher body weight when compared to control as well as dyslipidemia, higher blood pressure, diastolic dysfunction, and cardiac hypertrophy in adult life. Animals early deprived of their mothers have also presented a worse performance on the maximal effort ergometer test. This work shows that 3-day early maternal deprivation favors the development of cardiovascular disease in male rats.

Overweight during lactation and its implications for biometric, nutritional and cardiovascular parameters of young and adult male and female rats.

Litter size reduction can induce early overnourishment, being an attractive experimental model to study short- and long-term consequences of childhood obesity. Epidemiological data indicate sex differences regarding cardiometabolic disorders and hypertrophic cardiomyopathy. The present study aimed to describe biometric, nutritional and cardiovascular changes related to neonatal overweight promoted by litter size reduction in young and adult Wistar rats of both sexes. Litter adjustment to eight or four pups/mother (1:1 male-to-female ratio) gave, respectively, control and overweight groups. Body mass, food intake, haemodynamic and echocardiographic parameters and cardiorespiratory capacity were evaluated at postnatal days 30 and 150. Diminished litters were correlated with higher body mass and weight gain (12 %) during lactation, validating the experimental model of neonatal overweight. Soon after weaning male (16 %) and female (25 %) offspring of these litters presented a lower food intake than their respective control, without differences in body mass. Adult males from reduced litters presented higher abdominal circumference (7 %), systolic blood pressure (10 %), interventricular septum thickness (15 %) and relative wall thickness (15 %) compared with their respective control. Rats' performance on the maximal effort ergometer test was not affected by neonatal overweight. Data suggest the occurrence of catch-down growth and hypophagia in male and female rats submitted to neonatal overweight. However, only male rats presented haemodynamic and cardiac structural changes. These findings are crucial to personalised/gender medicine.

Inosine, an endogenous purine nucleoside, avoids early stages of atherosclerosis development associated to eNOS activation and p38 MAPK/NF-kB inhibition in rats.

Atherosclerosis is a multifactorial chronic disease, initiated by an endothelial dysfunction. Adenosine and its analogs can change a variety of inflammatory diseases and has shown important effects at different disease models. Inosine is a stable analogous of adenosine, but its effects in inflammatory diseases, like atherosclerosis, have not yet been studied. The aim of this study was to evaluate the pharmacological properties of inosine, administered sub chronically in a hypercholesterolemic model. Male Wistar rats were divided into four groups: control group (C) and control + inosine (C + INO) received standard chow, hypercholesterolemic diet group (HCD) and HCD + inosine (HCD + INO) were fed a hypercholesterolemic diet. At 31st experimentation day, the treatment with inosine was performed for C + INO and HCD + INO groups once daily in the last 15 days. We observed that the hypercholesterolemic diet promoted an increase in lipid levels and inflammatory cytokines production, while inosine treatment strongly decreased these effects. Additionally, HCD group presented a decrease in maximum relaxation acetylcholine induced and an increase in contractile response phenylephrine induced when compared to the control group, as well as it has presented an enhancement in collagen and ADP-induced platelet aggregation. On the other hand, inosine treatment promoted a decrease in contractile response to phenylephrine, evoked an improvement in endothelium-dependent vasorelaxant response and presented antiplatelet properties. Moreover, inosine activated eNOS and reduced p38 MAPK/NF-κB pathway in aortic tissues. Taken together, the present results indicate inosine as a potential drug for the treatment of cardiovascular disorders such as atherosclerosis.

Aerobic Training Associated with Arginine Supplementation Reduces Collagen-Induced Platelet Hyperaggregability in Rats under High Risk to Develop Metabolic Syndrome.

BACKGROUND: Increased platelet response is seen in individuals with metabolic syndrome. Previous reports have shown that arginine supplementation and aerobic exercise training enhance vascular nitric oxide (NO) activity and inhibit platelet hyperaggregability; however, the effects of their association remain unknown. AIM: To investigate whether arginine supplementation and aerobic exercise association may exert beneficial effects, reducing platelet hyperaggregability in rats under high risk to develop metabolic syndrome. METHODS: Wistar rats were divided into two groups: control (C) and fructose (F - water with 10% of fructose). After two weeks, the F group was subdivided into four groups: F, the same as before; fructose + arginine (FA - 880 mg/kg/day of L-arginine by gavage); fructose + training (FT); and fructose + arginine + training (FTA). Treatment lasted for eight weeks. RESULTS: The fructose administration was able to increase the collagen-induced platelet aggregation (27.4 ± 2.7%) when compared to the C group (8.0 ± 3.4%). Although the arginine supplementation (32.2 ± 6.3%) or aerobic training (23.8 ± 6.5%) did not promote any change in platelet collagen-induced hyperaggregability, the association of arginine supplementation and aerobic exercise promoted an inhibition of the platelet hyperaggregability induced by fructose administration (13.9 ± 4.4%) (P < 0.05). These effects were not observed when ADP was employed as an agonist. In addition, arginine supplementation associated with aerobic exercise promoted a decrease in interleukin-6 (IL-6) and interleukin-8 (IL-8) serum levels when compared to the fructose group, demonstrating an anti-inflammatory effect. CONCLUSIONS: Our data indicate an important role of arginine supplementation associated with aerobic exercise, reducing platelet hyperaggregability and inflammatory biomarker levels in rats under high risk to develop metabolic syndrome.