Blockade of Inflammatory Markers Attenuates Cardiac Remodeling and Fibrosis in Rats with Supravalvular Aortic Stenosis.

Since cardiac inflammation has been considered an important mechanism involved in heart failure, an anti-inflammatory treatment could control cardiac inflammation and mitigate the worsening of cardiac remodeling. This study evaluated the effects of dexamethasone (DEX) and ramipril treatment on inflammation and cardiac fibrosis in an experimental model of heart failure induced by supravalvular aortic stenosis. Wistar rats (21d) were submitted to an aortic stenosis (AS) protocol. After 21 weeks, an echocardiogram and a maximal exercise test were performed, and after 24 weeks, rats were treated with DEX, ramipril or saline for 14d. The left ventricle (LV) was removed for histological and inflammatory marker analyses. The AS group showed exercise intolerance (-32% vs. Sham), higher relative wall thickness (+63%), collagen deposition and capillary rarefaction, followed by cardiac disfunction. Both treatments were effective in reducing cardiac inflammation, but only DEX attenuated the increased relative wall thickness (-17%) and only ramipril reduced LV fibrosis. In conclusion, both DEX and ramipril decreased cardiac inflammatory markers, which probably contributed to the reduced cardiac fibrosis and relative wall thickness; however, treated AS rats did not show any improvement in cardiac function. Despite the complex pharmacological treatment of heart failure, treatment with an anti-inflammatory could delay the patient's poor prognosis.

Exercise-induced angiogenesis is attenuated by captopril but maintained under perindopril treatment in hypertensive rats.

Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some antihypertensive drugs attenuate this effect. This study compared the effects of captopril and perindopril on exercise-induced cardiac and skeletal muscle angiogenesis. Forty-eight Wistar rats and 48 SHR underwent 60 days of aerobic training or were kept sedentary. During the last 45 days, rats were treated with captopril, perindopril or water (Control). Blood pressure (BP) measurements were taken and histological samples from the tibialis anterior (TA) and left ventricle (LV) muscles were analyzed for capillary density (CD) and vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS) protein level. Exercise increased vessel density in Wistar rats due to higher VEGFR-2 (+17%) and eNOS (+31%) protein level. Captopril and perindopril attenuated exercise-induced angiogenesis in Wistar rats, but the attenuation was small in the perindopril group, and this response was mediated by higher eNOS levels in the Per group compared to the Cap group. Exercise increased myocardial CD in Wistar rats in all groups and treatment did not attenuate it. Both exercise and pharmacological treatment reduced BP of SHR similarly. Rarefaction was found in TA of SHR compared to Wistar, due to lower levels of VEGF (-26%) and eNOS (-27%) and treatment did not avoid this response. Exercise prevented these reductions in control SHR. While rats treated with perindopril showed angiogenesis in the TA muscle after training, those rats treated with captopril showed attenuated angiogenesis (-18%). This response was also mediated by lower eNOS levels in Cap group compared with Per and control group. Myocardial CD was reduced in all sedentary hypertensive compared with Wistar and training restored the number of vessels compared with sedentary SHR. In conclusion, taken into account only the aspect of vessel growth, since both pharmacological treatments reduced BP in SHR, the result of the present study suggests that perindopril could be a drug of choice over captopril for hypertensive practitioners of aerobic physical exercises, especially considering that it does not attenuate angiogenesis induced by aerobic physical training in skeletal and cardiac muscles.

Dexamethasone and Training-Induced Cardiac Remodeling Improve Cardiac Function and Arterial Pressure in Spontaneously Hypertensive Rats.

INTRODUCTION: Dexamethasone (DEX)-induced hypertension and cardiac remodeling are still unclear, especially in spontaneously hypertensive rats (SHR). On the other side, exercise training is a good strategy to control hypertension. Therefore, this study investigated the effects of DEX treatment and physical training on arterial pressure and cardiac remodeling in SHR. MATERIAL AND METHODS: SHR underwent treadmill training (5 days/week, 1h/session, at 50-60% of maximal capacity, 0% degree, 75 days) and received low-dose of DEX (50µg/kg, s.c.) during the last 15 days. Sedentary Wistar rats (W) were used as control. Echocardiography and artery catheterization were performed for cardiac remodeling and function, arterial pressure and autonomic nervous system analyses. In addition, left ventricle (LV) capillary density, myocyte diameter and collagen deposition area were analyzed using specific histological staining. RESULTS: Low-dose of DEX treatment did not exacerbate arterial pressure of SHR and trained groups had lower values, regardless of DEX. DEX and training decreased relative left ventricle wall thickness (RWT) and determined LV angiogenesis (+19%) and lower collagen deposition area (-22%). In addition, it determined increased left ventricular diastolic diameter. These changes were followed by improvements on systolic and diastolic function, since it was observed increased posterior wall shortening velocity (PWSV) and reduced isovolumetric relaxation time (IVRT). CONCLUSION: In conclusion, this study is unique to indicate that low-dose of DEX treatment does not exacerbate arterial pressure in SHR and, when associated with training, it improves LV systolic and diastolic function, which may be due to LV angiogenesis and reduction of wall collagen deposition area.

CYP450 polymorphisms and clinical pharmacogenetics of ibuprofen after lower third molar extraction.

PURPOSE: This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 200 volunteers after dental extraction. In addition, surgical outcomes can determine pain, edema, and trismus and indicate inflammatory reactions after oral surgeries. METHODS: Genetic sequencing was performed to identify CYP450 polymorphisms and the surgical parameters evaluated: pre and postoperative swelling, trismus, and temperature; self-reported postoperative pain with visual analog scale (VAS); rescue medication consumed; and severity of adverse reactions. RESULTS: A multiple linear regression model with independent variables [single nucleotide polymorphisms (SNPs), BMI (body mass index), duration, and difficulty of surgery] and dependent variables [postoperative pain by sum of pain intensity difference (SPID), trismus, and swelling] was used for analysis. The duration of surgery was a predictor for pain at 8 h and 96 h after surgery, and BMI was a predictor for both swelling and trismus on the 2nd postoperative day. When evaluating CYP2C8 and C9 genotyped SNPs, it was observed that normal metabolizers showed higher pain levels than the intermediate/poor metabolizers on the postoperative periods as compared with time 0 h. In another analysis, the poor metabolizers for CYP2C8 and C9 presented lower levels of postoperative pain after 8 h and used rescue medication earlier than normal metabolizers. CONCLUSION: Ibuprofen 600 mg was very effective in controlling inflammatory pain after lower third molar surgeries, without relevant adverse reactions; although in a very subtle way, patients with poor metabolism had higher levels of pain in the first hours, and no longer after 8 h, and used pain relief medication earlier. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ID (NCT03169127), on March 16th, 2017.

Dexamethasone Does Not Inhibit Treadmill Training-Induced Angiogenesis in Myocardium: Role of MicroRNA-126 Pathway.

Dexamethasone (DEX) has important anti-inflammatory activities; however, it induces hypertension and skeletal muscle microcirculation rarefaction. Nevertheless, nothing is known about DEX outcomes on cardiac microcirculation. By contrast, exercise training prevents skeletal and cardiac microvessel loss because of microRNA expression and a better balance between their related angiogenic and apoptotic proteins in spontaneously hypertensive rats. The purpose of this study was to investigate whether DEX and/or exercise training could induce microRNA alterations leading to cardiac angiogenesis or microvascular rarefaction. Animals performed 8 weeks of exercise training and were treated with DEX (50 µg/kg per day, subcutaneously) for 14 days. Cardiovascular parameters were measured, and the left ventricle muscle was collected for analyses. DEX treatment increased arterial pressure and did not cause cardiac microcirculation rarefaction. Treadmill training prevented the DEX-induced increase in arterial pressure. In addition, training, regardless of DEX treatment, increased microRNA-126 expression, phospho-protein kinase B/protein kinase B, and endothelial nitric oxide synthase levels associated with cardiac angiogenesis. In conclusion, this study suggests, for the first time, that treadmill training induces myocardial angiogenesis because of angiogenic pathway improvement associated with an increase in microRNA-126. Furthermore, DEX, per se, did not cause capillary density alterations and did not attenuate cardiac angiogenesis induced by training.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol.

BACKGROUND: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. OBJECTIVE: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. METHOD: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. RESULTS: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. CONCLUSIONS: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol / Impacto do Tabagismo Passivo na Resposta Pressórica à Epinefrina e Felipressina em Ratos Hipertensos 1K1C Tratados ou não com Atenolol

Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Resumo Fundamento: O tabagismo geralmente está associado à hipertensão e pode modificar a resposta vasoconstritora. Objetivo: O presente estudo teve como objetivo analisar e comparar a interação do tabagismo passivo e hipertensão sobre os efeitos da epinefrina e felipressina na pressão arterial após injeção intravascular. Métodos: Ratos Wistar machos de 45 dias tiveram a artéria renal principal esquerda parcialmente obstruída e o rim direito removido (modelo 1K1C). Os ratos foram colocados na câmara para exposição ao tabagismo passivo (10 cigarros) durante 10 minutos (6 dias por semana). Ratos hipertensos receberam atenolol (90 mg/kg/dia) por gavagem durante duas semanas. A resposta hipotensora e hipertensiva, a duração da resposta e a frequência cardíaca foram registradas a partir da medida dos valores diretos da pressão arterial. O nível de significância foi de 5%. Resultados: O tabagismo passivo aumentou a resposta hipertensiva máxima à epinefrina em ratos normotensos e ratos 1K1C tratados com atenolol e à felipressina apenas em ratos 1K1C tratados com atenolol; também reduziu a resposta hipotensiva à epinefrina. A epinefrina aumentou a frequência cardíaca em ratos fumantes passivos ou não-fumantes, normotensos e hipertensos. Comparando os dois vasoconstritores, a epinefrina apresentou maior resposta hipertensiva em fumantes normotensos, ratos 1K1C fumantes e não fumantes tratados com atenolol. No entanto, em ratos normotensos e não fumantes, a felipressina apresentou um efeito hipertensivo maior e mais prolongado. Conclusões: Nossos resultados sugerem que o tabagismo passivo pode reduzir a vasodilatação da epinefrina e aumentar a resposta hipertensiva quando comparado à felipressina. Portanto, a felipressina pode ser segura para pacientes hipertensos, com o objetivo de evitar a interação entre taquicardia e atenolol, mas para pacientes normotensos e não-fumantes, a epinefrina pode ser mais segura que a felipressina.

MicroRNA-126 upregulation, induced by training, plays a role in controlling microcirculation in dexamethasone treated rats.

Microcirculation maintenance is associated with microRNAs. Nevertheless, the role of microRNAs induced by training in preventing dexamethasone (DEX)-induced microvascular rarefaction remains unknown. The study aim was to investigate if training-induced microRNAs are able to improve microcirculation proteins and prevent DEX-induced microvascular rarefaction. Rats underwent training for 8 weeks and then were treated with DEX (50 µg/kg per day, s.c.) for 14 days. Arterial pressure was measured and tibialis anterior (TA) muscle was collected for analyses. DEX induced hypertension concomitantly with capillary density loss (CD, -23.9%) and decrease of VEGF (-43.0%), p-AKT/AKT (-39.6%) and Bcl-2 (-23.0%) and an increase in caspase-3-cleaved protein level (+34.0%) in TA muscle. Training upregulated microRNA-126 expression (+13.1%), prevented VEGF (+61.4%), p-AKT/AKT (+37.7%), Bcl-2 (+7.7%) decrease and caspase-3-cleaved (-23.1%) increase associated with CD (+54.7%) reduction and hypertension prevention. MiRNA-126 upregulation, induced by training, plays a role in controlling microcirculation, which may be a potential target against DEX-induced microvascular rarefaction.

Training counteracts DEX-induced microvascular rarefaction by improving the balance between apoptotic and angiogenic proteins.

This work investigated the mechanisms induced by exercise training that may contribute to attenuate dexamethasone (DEX)-induced microvascular rarefaction and hypertension. Wistar rats underwent training protocol or were kept sedentary for 8 weeks. Dexamethasone was administered during the following 14-days and hemodynamic parameters were recorded at the end. Capillary density (CD) and capillary-to-fiber ratio (C:F ratio) were obtained in soleus muscle (SOL). Also, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), endothelial nitric oxide synthase (eNOS), B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax), p-BAX and caspase-3 cleaved protein levels were analyzed. DEX treatment significantly increased blood pressure (+14%), which was associated with reduced C:F ratio (-41.0%) and CD (-43.1%). Reduction of vessel density was associated with decreased VEGF (-15.6%), VEGFR-2 (-14.6%), Bcl-2 (-18.4%), Bcl-2/Bax ratio (-29.0%) and p-Bax/Bax (-25.4%), and also with increased caspase-3 cleaved protein level (25%). Training, on the other hand, prevented microvessels loss by mitigating all proteins changes induced by DEX. In addition, angiogenic and apoptotic proteins were significantly correlated with CD, which, in turn, was associated with blood pressure. Therefore, we may point out that exercise training is a good strategy to attenuate DEX-induced microvascular rarefaction in soleus muscle and this response involves a better balance between apoptotic and angiogenic proteins, which may contribute for the attenuation of hypertension.

AT1 receptor antagonism promotes bone loss attenuation in experimental periodontitis, blocks inflammatory mediators, and upregulates antioxidant enzymes and bone formation markers.

BACKGROUND: The initiation and progression of periodontitis might involve a local renin-angiotensin system in periodontal tissue. This study hypothesized that Losartan treatment could promote protection to rats submitted to experimental periodontitis (EP) by attenuating alveolar bone loss due to reduction in inflammatory cytokines, better reactive oxidant species regulation and maintenance of the balance between bone formation and resorption factors. METHODS: One hundred and thirty rats were submitted to EP with a silk suture thread (4.0) placed around the lower right first molar for 1, 3, 7, and 14 consecutive days. The study comprised four groups: G1-control without EP; G2-animals with EP treated with water; G3-Losartan-treated animals (treatment started at the same day of EP induction), and G4-animals previously treated with Losartan for 30 days followed by induction of EP and continuity of treatment. RESULTS: G2 rats had greater bone loss volume, increased number, and thickness and decreased separation of trabeculae. On the other hand, G4 animals showed significant improvements in these parameters. Histological analysis revealed that EP favors inflammatory cell infiltration and junctional epithelium, cementum with alveolar bone crest destruction, but animals pretreated with Losartan (G4) did not show these features. Although the G3 animals did not demonstrate the improvements detected in G4, mRNA expression results were similar. In mandibular tissue, EP promoted mRNA increases for ACE, AT1 receptor, and inflammatory mediators as well as decreases for antioxidant enzymes. However, Losartan treatments attenuated these responses in addition to promoting an increase in bone formation markers and transcription factors. CONCLUSION: AT1 receptor modulates EP progression.

Novel rare variations in IRF6 in subjects with non-syndromic cleft lip and palate and dental agenesis.

OBJECTIVE: Subjects with cleft lip and palate (CLP) present high prevalence of dental agenesis. Among candidate genes for these phenotypes is IRF6. However, genetic studies do not analyze dental agenesis as a phenotype associated with cleft. Therefore, we investigated the frequency of rare and novel variations in IRF6 in subjects with non-syndromic unilateral cleft lip and palate (NSUCLP), with and without dental agenesis. SUBJECTS AND METHODS: Genomic DNA samples of 100 subjects with NSUCLP with and without dental agenesis and 50 controls were sequenced. IRF6 mutational screening was conducted by direct sequencing. RESULTS: Ten new and rare missense variations were identified, two in the group cleft with agenesis and eight in the group cleft without agenesis, and none were found in control group. In silico analysis revealed four variations as potentially deleterious, being two in the group with cleft and agenesis and two in the group with cleft without agenesis. CONCLUSION: The study identified novel IFR6 variations in subjects with NSUCLP with or without associated dental agenesis. The hypothesis of a higher frequency of deleterious variations in the subjects with cleft associated with dental agenesis, when compared to the group of cleft without agenesis and control without cleft, was not supported.

Short-term exposure to dexamethasone promotes autonomic imbalance to the heart before hypertension.

Hypertension is one of the chronic side effects of dexamethasone (DEX) treatment; however, almost nothing is known about its acute effects. Therefore, the aim of this study was to investigate the possible mechanisms involved in blood pressure control after acute or short-term DEX treatment in adult animals. Eighty Wistar rats were divided into four groups: C1 and C5, for rats treated with saline for 1 or 5 days, respectively; D1 and D5, for rats treated with DEX for 1 or 5 days, respectively (decadron, 1 mg/kg, i.p.). Heart rate was increased in DEX treatment, but arterial pressure and cardiac muscle mass were not altered. Only few and isolated changes on gene expression and protein level of renin-angiotensin system components were observed. Five days of DEX treatment, but not one day, determined an increase in sympathetic component of spectral analysis (+75.93%, P < .05) and a significant reduction of parasympathetic component (-18.02%, P < .05), which contributed to the autonomic imbalance to the heart (LF/HF, +863.69%). The results of this present study demonstrated, for the first time, that short-term exposure to DEX treatment impairs the autonomic balance to the heart before hypertension, which was independent of renin-angiotensin system.

CCR5Δ32 (rs333) polymorphism is associated with decreased risk of chronic and aggressive periodontitis: A case-control analysis based in disease resistance and susceptibility phenotypes.

Chronic and aggressive periodontitis are infectious diseases characterized by the irreversible destruction of periodontal tissues, which is mediated by the host inflammatory immune response triggered by periodontal infection. The chemokine receptor CCR5 play an important role in disease pathogenesis, contributing to pro-inflammatory response and osteoclastogenesis. CCR5Δ32 (rs333) is a loss-of-function mutation in the CCR5 gene, which can potentially modulate the host response and, consequently periodontitis outcome. Thus, we investigated the effect of the CCR5Δ32 mutation over the risk to suffer periodontitis in a cohort of Brazilian patients (total N=699), representative of disease susceptibility (chronic periodontitis, N=197; and aggressive periodontitis, N=91) or resistance (chronic gingivitis, N=193) phenotypes, and healthy subjects (N=218). Additionally, we assayed the influence of CCR5Δ32 in the expression of the biomarkers TNFα, IL-1ß, IL-10, IL-6, IFN-γ and T-bet, and key periodontal pathogens P. gingivalis, T. forsythia, and T. denticola. In the association analysis of resistant versus susceptible subjects, CCR5Δ32 mutant allele-carriers proved significantly protected against chronic (OR 0.49; 95% CI 0.29-0.83; p-value 0.01) and aggressive (OR 0.46; 95% CI 0.22-0.94; p-value 0.03) periodontitis. Further, heterozygous subjects exhibited significantly decreased expression of TNFα in periodontal tissues, pointing to a functional effect of the mutation in periodontal tissues during the progression of the disease. Conversely, no significant changes were observed in the presence or quantity of the periodontal pathogens P. gingivalis, T. forsythia, and T. denticola in the subgingival biofilm that could be attributable to the mutant genotype.

Exercise attenuates dexamethasone-induced hypertension through an improvement of baroreflex activity independently of the renin-angiotensin system.

Dexamethasone-induced hypertension may be caused by baroreflex alterations or renin-angiotensin system (RAS) exacerbation. Aerobic training has been recommended for hypertension treatment, but the mechanisms responsible for reduction of arterial pressure (AP) in dexamethasone (DEX) treated rats are still inconclusive.This study evaluated whether mechanisms responsible for training-induced attenuation of hypertension involve changes in autonomic nervous system and in RAS components. Rats underwent aerobic training protocol on treadmill or were kept sedentary for 8 weeks. Additionally, animals were treated with DEX during the last 10 days of exercise. Body weight (BW), AP and baroreflex activity were analyzed. Tibialis anterior (TA), soleus (SOL) and left ventricle (LV) were collected for evaluation of RAS components gene expression and protein levels. Dexamethasone decreased BW (20%), caused TA atrophy (16%) and increased systolic AP (SAP, 16%) as well as decreased baroreflex activity. Training attenuated SAP increase and improved baroreflex activity, although it did not prevent DEX-induced BW reduction and muscle atrophy. Neither DEX nor training caused expressive changes in RAS components. In conclusion, exercise training was effective in attenuating hypertension induced by DEX and this response may be mediated by a better autonomic balance through an improvement of baroreflex activity rather than changes in RAS components.

Exercise Training Prevents Dexamethasone-induced Rarefaction.

Dexamethasone (DEX) causes rarefaction. In contrast, training (T) prevents rarefaction and stimulates angiogenesis. This study investigated the mechanisms responsible for the preventive role of T in DEX-induced rarefaction. Rats underwent T or were kept sedentary (8 weeks) and were treated with DEX or saline during the following 14 days. Tibialis anterior muscle was used for measurements of capillary density (CD), capillary-to-fiber ratio (C:F ratio), superoxide dismutase CuZn (SOD-1), superoxide dismutase MnSOD (SOD-2), catalase (CAT) mRNA as well as SOD-1, SOD-2, CAT, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGF-R2), cyclooxygenase-2 (COX-2), B-cell lymphoma 2 (Bcl-2), Bd-2-like protein 4 (Bax), p-Bax, and caspase-3 cleaved protein levels. DEX decreased CD (-38.1%), C:F ratio (-30.0%), VEGF (-19.0%), VEGFR-2 (-20.1%), COX-2 (-22.8%), Bcl-2 (-20.5%), Bcl-2/Bax ratio (-13.7%), p-Bax/Bax (-20.0%) and increased SOD-2 (+41.6%) and caspase-3 cleaved (+24.1%). Conversely, T prevented reductions in CD (+54.2%), C:F ratio (+32.9%), VEGF (+25.3%), VEGFR-2 (+22.2%), COX-2 (+31.5%), Bcl-2 (+35.5%), Bcl-2/Bax ratio (+19.9%), p-Bax/Bax (+32.1%), and caspase-3 cleaved increase (-7.8%). T increased CAT mRNA (+21.5%) in the DEX-treated group. In conclusion, T prevented the DEX-induced rarefaction by increasing antioxidant enzymes resulting in a better balance between apoptotic and anti-apoptotic protein levels.

Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study

BACKGROUND: Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. MATERIAL AND METHODS: Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. RESULTS: Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. CONCLUSIONS: In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE

Role of epigenetics in modulation of immune response at the junction of host-pathogen interaction and danger molecule signaling.

Epigenetic mechanisms have rapidly and controversially emerged as silent modulators of host defenses that can lead to a more prominent immune response and shape the course of inflammation in the host. Thus, the epigenetics can both drive the production of specific inflammatory mediators and control the magnitude of the host response. The epigenetic actions that are predominantly shown to modulate the host defense against microbial pathogens are DNA methylation, histone modification and the activity of non-coding RNAs. There is also growing evidence that opportunistic chronic pathogens, such as Porphyromonas gingivalis, as a microbial host subversion strategy, can epigenetically interfere with the host DNA machinery for successful colonization. Similarly, the novel involvement of small molecule 'danger signals', which are released by stressed or infected cells, at the center of host-pathogen interplay and epigenetics is developing. In this review, we systematically examine the latest knowledge within the field of epigenetics in the context of host-derived danger molecule and purinergic signaling, with a particular focus on host microbial defenses and infection-driven chronic inflammation.

Exercise training attenuates dexamethasone-induced hypertension by improving autonomic balance to the heart, sympathetic vascular modulation and skeletal muscle microcirculation.

OBJECTIVE: Although aerobic exercise training has been recommended as nonpharmacological treatment of high blood pressure, the mechanisms of training-induced blood pressure lowering effects in dexamethasone (DEX)-induced hypertension remain unclear. Therefore, the aim of this study was to investigate the preventive role of exercise training in counteracting DEX-induced hypertension. METHODS: Rats were submitted to aerobic exercise training for 8 weeks or kept sedentary and then treated with DEX (50 µg/kg/day, s.c.) or saline injections for 14 days. Thereafter, all rats underwent carotid artery catheterization, and cardiovascular autonomic modulation was evaluated by spectral analysis. In addition, soleus muscle was collected for morphometric and protein level analysis. RESULTS: DEX treatment increased arterial pressure concomitantly with an increase in low-frequency spectral power of systolic arterial pressure and low frequency in pulse interval (94.11 and 58.58%, respectively), and a decrease in high-frequency spectral power of pulse interval (-12.05%). Capillary density (-25.87%), capillary-to-fibers ratio (-21.22%), vascular endothelial growth factor level (-15.10%), B-cell lymphoma 2 (Bcl-2) level (-16.40%) and Bcl-2/Bcl-2 associated X protein ratio (-27.14%) were all decreased after DEX treatment. Exercise training attenuated DEX-induced increase in arterial pressure accompanied by an attenuation of low-frequency spectral power of systolic arterial pressure, low frequency in pulse interval increases and high-frequency spectral power of pulse interval decrease. Training also prevented the decrease in capillary density (+44.43%), capillary-to-fibers ratio (+36.97%), vascular endothelial growth factor (+16.46%), Bcl-2 (+15.21%) protein level and Bcl-2/Bcl-2-associated X protein ratio (+30.93%). CONCLUSION: These results demonstrate that exercise training improves cardiovascular autonomic balance to the heart associated with an improvement in sympathetic modulation of vascular tone and microcirculatory function in the skeletal muscle of DEX-induced hypertensive rats.