What has a year of social isolation due to the COVID-19 pandemic influenced oral parafunctional habits and temporomandibular disorders? A case-control study.

OBJECTIVE: Few studies investigated the influence of oral parafunctional habits during the COVID-19 pandemic. Since some studies have demonstrated that signs and symptoms of temporomandibular disorder (TMD), as well as psychological alterations, increased during the COVID-19 pandemic lockdown, the aim of this study was to investigate whether social isolation is a situation that increases the prevalence of oral parafunctional habits. METHODS: This was an observational case-control study. An online survey with questions about TMD symptoms (Diagnostic Criteria Symptom Questionnaire) and oral parafunctional habits (Oral Behaviours Checklist [OBC]) was administered to Brazilian residents at two different times (2020 and 2021). The participants were divided according to social isolation practices into study groups (GI: 2020, n = 507; GIII: 2021, n = 282) and control groups (GII: 2020, n = 98; GIV: 2021, n = 202). RESULT: In each group, we evaluated the association of the frequency of oral parafunctional habits with the symptoms of TMD, and we observed that individuals with a greater presence of painful TMD present a greater number of oral parafunctional habits. Despite the literature showing that individuals who practiced social isolation developed more oral parafunctional habits, when analysing the association of the OBC questions in Groups GI × GII and GIII × GIV, only 'sustained talking' (p = .0022) and 'hold telephone between your hand and shoulders' (p = .0124) showed a significant difference in GI × GII. Kendall's coefficient of concordance revealed that there was a very strong concordance (GI × GII 0.9515 (p = .0087) and GIII × GIV 0.9655 (p = .0074)) between the ranks of the analysed oral parafunctional habits in all groups. CONCLUSION: We can state that Individuals who practiced social isolation did not present more oral parafunctional habits than individuals who did not.

Farm specific estimates of forage variability result in larger optimal control limits for forage quality monitoring.

Variation in forage composition decreases the accuracy of diets delivered to dairy cows. However, variability of forages can be managed using a renewal reward model (RRM) and genetic algorithm (GA) to optimize sampling and monitoring practices for farm conditions. Specifically, use of quality-control-charts to monitor forage composition can identify changes in composition for which adjustment in the formulated diet will result in a better match of the nutrients delivered to cows. The objectives of this study were 1) assess the use of a clustering algorithm to estimate the mean time the process is stable or in-control (d) (TStable) and the magnitude of the change in forage composition between stable periods (ΔForage) for corn silage and alfalfa-grass silage which are input parameters for the RRM; 2) compare optimized farm-specific sampling practices (number of samples (n), sampling interval (TSample) and control limits (ΔLimit) using previously proposed defaults and our estimates for the TStable and ΔForage input parameters; and 3) conduct a simulation study to compare the number of recommended diet changes costs of quality control under the proposed sampling and monitoring protocols. We estimated the TStable and ΔForage parameters for corn silage NDF and starch and alfalfa-grass silage NDF and CP using a k-means clustering approach applied to forage samples collected from 8 farms, 3x/week during a 16-week period. We compared 4 sampling and monitoring protocols that resulted from the 2 methods for estimating TStable and ΔForage (default values and our proposed method) and either optimizing only the control limit (Optim1) or optimizing the control limits, the number of samples, and the number of days between sampling (Optim2). We simulated the outcomes of implementing the optimized monitoring protocols using a quality control chart for corn silage and alfalfa-grass silage of each farm. Estimates of T^Stable and Δ^Forage from the k-means clustering analysis were, respectively, shorter and larger than previously proposed default values. In the simulated quality control monitoring, larger Δ^Forage estimates increased the optimized ΔLimit resulting in fewer detected shifts in composition of forages and a lower frequency of false alarms and a lower quality control cost ($/d). Recommended diet reformulation intervals from the simulated quality control analysis were specific for the type of forage and farm management practices. The median of the diet reformulation intervals for all farms using our optimal protocols was 14 d (Q1 = 8, Q3 = 26) for corn silage and 16 d (Q1 = 8, Q3 = 26) for alfalfa-grass silage.

ARE THERE ADVANTAGES IN DOUBLE TRANSIT RECONSTRUCTION AFTER TOTAL GASTRECTOMY IN PATIENTS WITH GASTRIC CANCER? A SYSTEMATIC REVIEW.

BACKGROUND: Curative treatment for gastric cancer involves tumor resection, followed by transit reconstruction, with Roux-en-Y being the main technique employed. To permit food transit to the duodenum, which is absent in Roux-en-Y, double transit reconstruction has been used, whose theoretical advantages seem to surpass the previous technique. AIMS: To compare the clinical evolution of gastric cancer patients who underwent total gastrectomy with Roux-en-Y and double tract reconstruction. METHODS: A systematic review was carried out on Web of Science, Scopus, EmbasE, SciELO, Virtual Health Library, PubMed, Cochrane, and Google Scholar databases. Data were collected until June 11, 2022. Observational studies or clinical trials evaluating patients submitted to double tract (DT) and Roux-en-Y (RY) reconstructions were included. There was no temporal or language restriction. Review articles, case reports, case series, and incomplete texts were excluded. The risk of bias was calculated using the Cochrane tool designed for randomized clinical trials. RESULTS: Four studies of good methodological quality were included, encompassing 209 participants. In the RY group, there was a greater reduction in food intake. In the DT group, the decrease in body mass index was less pronounced compared to preoperative values. CONCLUSIONS: The double tract reconstruction had better outcomes concerning body mass index and the time until starting a light diet; however, it did not present any advantages in relation to nutritional deficits, quality of life, and post-surgical complications.

Partitioning of nutrient variation in alfalfa and corn silage by source on New York dairy farms.

Variation in feed components contributes to variation and uncertainty of diets delivered to dairy cows. Forages often have a high inclusion rate (50% to 70% of DM fed) and variable composition, and thus are an important contributor to nutrient variability of delivered diets. Our objective was to quantify the variation and identify the main sources of variability in corn silage and alfalfa-grass haylage composition at harvest (fresh forage) and feed-out (fermented forage) on New York dairy farms. Corn silage and alfalfa-grass haylage were sampled on 8 New York commercial dairy farms during harvest in the summer and fall of 2020 and during their subsequent feed-out in the winter and spring of 2021. At harvest, a composite sample of fresh chopped forage of every 8-ha section of individual fields was collected from piles delivered for silo filling. During a 16-wk feed-out period, 2 independent samples of each forage were collected 3 times per week. The fields of origin of each forage sample during feed-out were identified and recorded using silo maps created at filling. A mixed-model analysis quantified the variance of corn silage DM, NDF, and starch and haylage DM, NDF, and CP content. Fixed effects included soil type, weather conditions, and management practices during harvest and feed-out, and random effects were farm, silo unit, field, and day. At harvest, between-farm variability was the largest source of variation for both corn silage and haylage, but within-farm sources of variation exceeded farm-to-farm variation for haylage at feed-out. At feed-out, haylage DM and NDF content had higher within-farm variability than corn silage. In contrast, corn silage starch showed higher within-farm variation at feed-out than haylage CP content. For DM content at feed-out, day-to-day variation was the most relevant source of within-farm variation for both forages. However, for the nutrient components at feed-out (NDF and CP for haylage; NDF and starch for corn silage) silo-to-silo variation was the largest source of variability. Weather conditions systematically explained a proportion of the farm-to-farm variability for both forages at harvest and feed-out. We concluded that because of the high farm-to-farm variation, corn silage and haylage must be sampled on individual farms. We also concluded that due to the high silo-to-silo variability, and the still significant day-to-day and field-to-field variability within-farm, corn silage and haylage should be sampled within individual silos to better capture changes in forage components at feed-out.

Long-term effects of photobiomodulation therapy on blood pressure in obese rats induced by a high-fat diet.

The main cardiovascular disease risk associated with obesity is hypertension. The therapeutic use of photobiomodulation therapy (PBM) is suggested for the treatment of wound healing, osteoarthritis, and arterial diseases. However, few studies have measured how red laser (at 660 nm) acts over hypertension, and any of those studies used experimental obesity model. The aim of the study was an attempt to evaluate the long-term effect of PBM on systolic blood pressure in an animal model of obesity, induced by a high-fat diet (HFD). Our results indicate that PBM carried out 3 days a week was able to prevent the increase in blood pressure (133.75 ± 4.82 mmHg, n = 8) induced by a high-fat diet (150.00 ± 4.57 mmHg, n = 8; p < 0.05), restore nitric oxide levels (control: 31.7 ± 5.5 µM, n = 8; HFD + PBM: 29.9 ± 3.7 µM, n = 8 > HFD: 22.2 ± 2.9 µM, n = 8, p < 0.05), decrease lipoperoxidation (control: 1.65 ± 0.25 nM, n = 8; HFD + PBM: 2.05 ± 0.55 nM, n = 8 < HFD: 3.20 ± 0.47 nM, n = 8; p < 0.05), and improve endothelial function (pD2 control: 7.39 ± 0.08, n = 8 > pD2 HFD + PBM: 7.15 ± 0.07, n = 8 > HFD: 6.94 ± 0.07, n = 8; p < 0.05). Our results indicate that PBM prevents the elevation of blood pressure in an obese animal model by a mechanism that involves improvement of endothelial function through an antioxidant effect.

Use of ozone therapy in Implant Dentistry: a systematic review.

PURPOSE: Ozone is a potent antioxidant agent which presents an important antimicrobial action and many other biological effects. Although ozone therapy has been widely described and summarized in several other Dentistry areas recently, the studies concerning Dental Implantology have not been systematically compiled and evaluated. Thus, the present study aimed to evaluate the effectiveness of ozone therapy in dental implant procedures. METHODS: MEDLINE (via PUBMED), Cochrane Central Register of Controlled Trials (CENTRAL), and OpenGrey databases were searched (up to, and including, January 23, 2023) for studies in the English language. In addition, the reference lists of the articles were manually examined. Only interventional studies (controlled clinical trials, randomized or not) were considered eligible for inclusion. The risk of bias in each included study was assessed using the Cochrane tool for assessing risk of bias in randomized trials - version 2. RESULTS: 71 potentially eligible records were retrieved but only 5 articles were evaluated and considered eligible for inclusion. Among the studies, 2 addressed clinical situations related to implant insertion, and 3 involved pathological conditions affecting implants in function. Furthermore, only one randomized clinical trial was categorized as low risk of bias. CONCLUSION: The adjuvant use of ozone therapy may positively affect some outcomes in Implant Dentistry, both in treating pathological conditions and conducting rehabilitation (implant installation, secondary implant stability). However, as most studies have a high risk of bias and high heterogeneity, a definitive conclusion cannot be drawn.

Are there advantages in double transit reconstruction after total gastrectomy in patients with gastric cancer? a systematic review / Há vantagens na reconstrução em duplo trânsito após a gastrectomia total em portadores de câncer gástrico? revisão sistemática

ABSTRACT BACKGROUND: Curative treatment for gastric cancer involves tumor resection, followed by transit reconstruction, with Roux-en-Y being the main technique employed. To permit food transit to the duodenum, which is absent in Roux-en-Y, double transit reconstruction has been used, whose theoretical advantages seem to surpass the previous technique. AIMS: To compare the clinical evolution of gastric cancer patients who underwent total gastrectomy with Roux-en-Y and double tract reconstruction. METHODS: A systematic review was carried out on Web of Science, Scopus, EmbasE, SciELO, Virtual Health Library, PubMed, Cochrane, and Google Scholar databases. Data were collected until June 11, 2022. Observational studies or clinical trials evaluating patients submitted to double tract (DT) and Roux-en-Y (RY) reconstructions were included. There was no temporal or language restriction. Review articles, case reports, case series, and incomplete texts were excluded. The risk of bias was calculated using the Cochrane tool designed for randomized clinical trials. RESULTS: Four studies of good methodological quality were included, encompassing 209 participants. In the RY group, there was a greater reduction in food intake. In the DT group, the decrease in body mass index was less pronounced compared to preoperative values. CONCLUSIONS: The double tract reconstruction had better outcomes concerning body mass index and the time until starting a light diet; however, it did not present any advantages in relation to nutritional deficits, quality of life, and post-surgical complications.

RESUMO RACIONAL: O tratamento curativo do câncer gástrico envolve a ressecção do tumor, seguida de reconstrução do trânsito, sendo o Y-de-Roux a principal técnica empregada. Para permitir o trânsito alimentar para o duodeno, ausente em Y-de-Roux, tem-se utilizado a reconstrução de duplo trânsito, cujas vantagens teóricas parecem superar a técnica anterior. OBJETIVOS: Comparar a evolução clínica de pacientes com câncer gástrico submetidos à gastrectomia total com Y-de-Roux e reconstrução de duplo trânsito. MÉTODOS: Foi realizada uma revisão sistemática nas bases de dados: Web of Science, Scopus, Embase, Scielo, Biblioteca Virtual em Saúde, PubMed e Cochrane. Os dados foram coletados até 11 de junho de 2022. Foram incluídos estudos observacionais ou ensaios clínicos avaliando pacientes que utilizaram reconstruções de duplo trânsito (DT) e Y-de-Roux (RY). Não houve restrição temporal ou de idioma. Foram excluídos artigos de revisão, relatos de casos, séries de casos e aqueles com texto incompleto. O risco de viés foi calculado utilizando a ferramenta Cochrane desenvolvida para ensaios clínicos randomizados. RESULTADOS: Foram incluídos quatro estudos de boa qualidade metodológica, abrangendo 209 participantes. No grupo RY houve maior redução na ingestão alimentar. No grupo DT, a diminuição do índice de massa corporal (IMC) foi menos pronunciada em comparação aos valores pré-operatórios. CONCLUSÕES: A reconstrução de duplo trânsito apresentou melhores resultados em relação ao índice de massa corporal e ao tempo para início de dieta leve, porém não apresentou vantagens em relação aos déficits nutricionais, qualidade de vida e complicações pós-cirúrgicas.

Methane prediction equations including genera of rumen bacteria as predictor variables improve prediction accuracy.

Methane (CH4) emissions from ruminants are of a significant environmental concern, necessitating accurate prediction for emission inventories. Existing models rely solely on dietary and host animal-related data, ignoring the predicting power of rumen microbiota, the source of CH4. To address this limitation, we developed novel CH4 prediction models incorporating rumen microbes as predictors, alongside animal- and feed-related predictors using four statistical/machine learning (ML) methods. These include random forest combined with boosting (RF-B), least absolute shrinkage and selection operator (LASSO), generalized linear mixed model with LASSO (glmmLasso), and smoothly clipped absolute deviation (SCAD) implemented on linear mixed models. With a sheep dataset (218 observations) of both animal data and rumen microbiota data (relative sequence abundance of 330 genera of rumen bacteria, archaea, protozoa, and fungi), we developed linear mixed models to predict CH4 production (g CH4/animal·d, ANIM-B models) and CH4 yield (g CH4/kg of dry matter intake, DMI-B models). We also developed models solely based on animal-related data. Prediction performance was evaluated 200 times with random data splits, while fitting performance was assessed without data splitting. The inclusion of microbial predictors improved the models, as indicated by decreased root mean square prediction error (RMSPE) and mean absolute error (MAE), and increased Lin's concordance correlation coefficient (CCC). Both glmmLasso and SCAD reduced the Akaike information criterion (AIC) and Bayesian information criterion (BIC) for both the ANIM-B and the DMI-B models, while the other two ML methods had mixed outcomes. By balancing prediction performance and fitting performance, we obtained one ANIM-B model (containing 10 genera of bacteria and 3 animal data) fitted using glmmLasso and one DMI-B model (5 genera of bacteria and 1 animal datum) fitted using SCAD. This study highlights the importance of incorporating rumen microbiota data in CH4 prediction models to enhance accuracy and robustness. Additionally, ML methods facilitate the selection of microbial predictors from high-dimensional metataxonomic data of the rumen microbiota without overfitting. Moreover, the identified microbial predictors can serve as biomarkers of CH4 emissions from sheep, providing valuable insights for future research and mitigation strategies.

Chronic red laser treatment induces hypotensive effect in two-kidney one-clip model of renovascular hypertension in rat.

To evaluate whether the chronic effect of photobiomodulation therapy (PBM) on systolic arterial pressure (SAP) from two kidneys one clip (2 K-1C) hypertension animal models can cause a hypotensive effect. Serum levels of nitric oxide were also analyzed and the assessment of lipid peroxidation of the thoracic aorta artery. Male Wistar rats were used. Hypertensive animals (2 K-1C) with Systolic arterial pressure (SAP) greater than or equal to 160 mmHg were used. Systolic arterial pressure (SAP) was determined by the tail plethysmography technique. Normotensive (2 K) and hypertensive (2 K-1C) rats were treated to PBM for 4 weeks using a laser whose irradiation parameters were: red wavelength (λ) = 660 nm: operating continuously; 56 s per point (3 points) spot size = 0.0295 cm2; average optical power of 100 mW; energy of 5.6 J per point; irradiance of 3.40 W/cm2; fluency of 190 J/cm2 per point. The application was on the animals tails, at 3 different points simultaneously, in contact with the skin. To assess serum nitrite and nitrate (NOx) levels, blood collection was performed after chronic PBM treatment, 24 h after the last laser application. The evaluation of the lipid peroxidation of the thoracic aorta artery was performed by measuring the concentration of hydroperoxide by the FOX method. Chronic photobiomodulation therapy (PBM) by red laser (660 nm) can induce a hypotensive effect in 64% of 2 K-1C hypertensive animals, which we say responsive animals. There was no difference in serum NO levels 24 h after the last red laser application, between treated and non-treated groups. Aortic rings from 2 K-1C hypertensive animals present a higher lipid peroxidation. The chronic PBM treatment by red laser decreased aortic rings lipid peroxidation in hypertensive responsive groups, compared to control. our results indicate that chronic PBM made by red laser has an important hypotensive effect in renovascular hypertensive models, by a mechanism that involves decrease in oxidative stress from vascular beds.

Photobiomodulation With a Continuous Wave Red Laser (660 nm) as Monotherapy for Adult Alopecia Areata: A Case Presentation.

Introduction: Alopecia areata (AA) is an autoimmune, inflammatory, non-scarring hair loss in which T-cells target hair follicles. Given that the available therapeutic options generally do not induce and sustain remission of AA effectively and many adverse effects may occur, monochromatic light sources have been recently gaining attention from clinicians. Therefore, the present paper aimed to report the first case in which photobiomodulation therapy (PBMT) with a continuous wave red laser (660 nm) was used as monotherapy for AA. Case Presentation: An isolated round area of complete hair loss was subjected to daily PBMT sessions, resulting in significant regrowth (hair of normal coloration and thickness) within 7 days. On the 21st day, the patient's aesthetic concern was completely resolved. Conclusion: PBMT with a continuous wave red laser seems to be a promising therapeutic option for the treatment of AA; however, additional studies are necessary to obtain more robust evidence.

Photobiomodulation Therapy for Multiple Painful Fixed Drug Eruptions: The First Case Report.

Introduction: Fixed drug eruption (FDE), a very specific adverse drug reaction and one of the most common types of drug eruption, generally resolves spontaneously within 7-10 days upon withdrawal of the causative agent; however, extensive and severe cases may also require systemic drug therapy. The present study aimed to report a case in which a broad spectrum of severe, painful lesions of FDE was managed with photobiomodulation therapy (PBMT). Case Report: A 31-year-old Caucasian woman presented with many extremely painful mucocutaneous lesions of FDE which had arisen 8 days before, following a long period of hospitalization. The lesions were not responsive to either corticosteroids or analgesics within 5 days, and then seven daily sessions of PBMT were proposed. Pain alleviation was achieved on the 1st day of PBMT, and the lesions showed an advanced course of healing on the 3rd day. Within 7 days of PBMT, the lesions were almost completely repaired. In a 3-month follow-up period, no relapse of any FDE lesion was reported. Conclusion: PBMT may be a promising strategy for the management of painful lesions of FDE refractory to conventional medication therapy. However, further studies are needed to confirm this hypothesis.

Impact of different anesthetic approaches on the outcomes of temporomandibular joint arthrocentesis: a systematic review.

PURPOSE: To assess the impact of different types of anesthesia on the outcomes of arthrocentesis of the TMJ. METHODS: Electronic databases were searched to identify peer-reviewed studies, followed by reference list search and further hand-searching. Randomized clinical trials and controlled studies were considered for inclusion when comparing at least two anesthetic approaches. The risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Of a total of 506 potentially eligible studies, only a randomized controlled clinical trial and an observational study were included. The former compared some outcomes of arthrocentesis under local and general anesthesia and the latter under sedation and general anesthesia. Moreover, both studies were judged as "high risk of bias." CONCLUSIONS: In general, there appears to be a slight trend toward better outcomes of arthrocentesis for internal TMJ derangements (Wilkes grades I to III) when performed under general anesthesia; however, given that the available evidence is remarkably limited and a high risk of bias was detected within the included studies, a definitive statement cannot be made.

Protection of dystrophic muscle cells using Idebenone correlates with the interplay between calcium, oxidative stress and inflammation.

There is strong cross-talk between abnormal intracellular calcium concentration, high levels of reactive oxygen species (ROS) and an exacerbated inflammatory process in the dystrophic muscles of mdx mice, the experimental model of Duchenne muscular dystrophy (DMD). In this study, we investigated effects of Idebenone, a potent anti-oxidant, on oxidative stress markers, the anti-oxidant defence system, intracellular calcium concentrations and the inflammatory process in primary dystrophic muscle cells from mdx mice. Dystrophic muscle cells were treated with Idebenone (0.05 µM) for 24 h. The untreated mdx muscle cells were used as controls. The MTT assay showed that Idebenone did not have a cytotoxic effect on the dystrophic muscle cells. The Idebenone treatment was able to reduce the levels of oxidative stress markers, such as H2 O2 and 4-HNE, as well as decreasing intracellular calcium influx in the dystrophic muscle cells. Regarding Idebenone effects on the anti-oxidant defence system, an up-regulation of catalase levels, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity was observed in the dystrophic muscle cells. In addition, the Idebenone treatment was also associated with reduction in inflammatory molecules, such as nuclear factor kappa-B (NF-κB) and tumour necrosis factor (TNF) in mdx muscle cells. These outcomes supported the use of Idebenone as a protective agent against oxidative stress and related signalling mechanisms involved in dystrophinopathies, such as DMD.

Photobiomodulation Therapy for Managing Motor and Sensory Dysfunctions Following Temporomandibular Joint Surgery: A Case Report.

Introduction: Surgical procedures involving the temporomandibular joint (TMJ) are frequently associated with nerve injuries and subsequent dysfunctions. Considering that traumatic peripheral nerve injuries may resolve slowly and their prognosis is generally unpredictable, the current study aimed to report a clinical case in which both motor (affecting the temporal and zygomatic branches of the facial nerve) and sensory dysfunctions (affecting the auriculotemporal nerve of the trigeminal nerve) following TMJ surgery were effectively treated by using photobiomodulation therapy (PBMT). Case Report: PBMT sessions, involving a total of 30 facial points, were administered twice a week for 10 weeks. The following parameters were utilized: wavelength of 808 nm, energy density of 75 J/cm2, power output of 100 mW, total energy of 3 J, and duration of 30 seconds per point. A considerable improvement in both facial asymmetry and muscle function was achieved within 5 weeks, along with a total restoration of cutaneous sensitivity. By the 10th week of PBMT, the facial movement dysfunction was completely resolved. Conclusion: According to the current case, PMBT seems to be an effective intervention to manage motor and sensory nerve dysfunctions following TMJ surgery.

Ancestry estimation in forensic anthropology: accuracy of the AncesTrees software in a Brazilian sample.

The objective of this study is to analyze the accuracy and applicability of the AncesTrees software with respect to a set of cranial measurements of a Brazilian sample consisting of 114 identified skulls from two osteological collections, predominantly composed of European (n = 59), African (n = 35), and admixed individuals (n = 20). Twenty-four different craniometric measurements are performed and input to AncesTrees via two algorithms, one of which is used in three configurations, with different ancestral groups integrated in the model. The software exhibits superior performance in the estimation of European individuals, reaching 73% accuracy, compared with 66% in the African individuals. Those individuals classified as admixed produce a variety of ancestral classifications, mainly European. Overall, the most accurate combination of AncesTrees is obtained using ancestralForest with only the European and African groups integrated into the algorithm, where the accuracy reaches 70%. The applicability of this software to a specific population is fragile because of the high admixing load, making it necessary to create a more representative anthropometric database of the Brazilian people. Key points: Ancestry estimation methods are seldom validated in Brazil.AncesTrees performed poorly on our sample, with a maximum accuracy of 70%.Brazil's highly mixed population hinders ancestry estimation.Mixed individuals (pardos) are predominantly classified as Europeans.The insertion of Brazilian metric data into the AncesTrees database would produce better results.

Vascular Effects of the Fetal Hemoglobin Inducer Agent 3-(1,3-Dioxoisoindolin-2-yl) Benzyl Nitrate.

Vascular endothelium is a protective layer of cells lining the lumen of blood vessels that plays important roles by releasing factors responsible for controlling the vascular tone, regulating the expression of pro-inflammatory cytokines, and expressing adhesion molecules involved in vascular hemostasis. Imbalance of vascular properties leads to endothelial dysfunction (ED) and cardiovascular damage. Some diseases, such as sickle cell anemia, are characterized by ED with reduction in the levels of nitric oxide (NO). Previously, we have shown that the fetal hemoglobin inducer agent 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (Lapdesf-4c) could act as NO donor, inhibiting platelet aggregation and reducing the inflammation associated with SCA. However, the vascular effect of this compound was not yet studied. Herein, we evaluated the effects of Lapdesf-4c in vascular reactivity experiments using aortic rings from male Wistar rats (300 g/90 days). We have found that Lapdesf-4c induced vasodilation in the presence (E+) or absence of endothelium (E-) with an average of EMax values of 101.8 ± 3.33% and 111.8 ± 3.21%. The mechanism of action was studied using 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), L-NG-nitroarginine methyl ester (L-NAME), and hydroxocobalamin. The EMax values for those pathways were hydroxocobalamin (30.6 ± 2.21%), ODQ (4.75 ± 0.51%), and L-NAME (109 ± 3.65), suggesting that Lapdesf-4c exhibits NO-dependent mechanisms. Lapdesf-4c was able to prevent angiotensin-induced ED after incubation of aorta rings for 1 h. We found based on the concentration-effect curve using acetylcholine (ACh) that pEC50 values for the control, Ang II, and combination of (Ang II + Lapdesf-4c) were 6.73, 6.46, and 7.15, respectively. In conclusion, Lapdesf-4c has emerged as a new drug candidate that can promote vasodilation and act as a protective agent against ED, being useful to prevent vascular damage.