Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension.

Hypertension is a chronic condition that requires lifelong therapeutic management. Strict adherence to drug administration timing improves efficacy, while poor adherence leads to safety concerns. In light of these challenges, we present a nanofluidic technology that enables long-acting drug delivery with tunable timing of drug administration using buried gate electrodes in nanochannels. We developed a poly(ethylene glycol) methyl ether-block-poly(ε-caprolactone) (PEG-PCL)-based micellar formulation of amlodipine besylate, a calcium channel blocker for hypertension treatment. The electrostatically charged PEG-PCL micellar formulation enhanced drug solubility and rendered amlodipine responsive to electrostatic release gating in nanochannels for sustained release at clinically relevant therapeutic dose. Using a low-power (<3 VDC) gating potential, we demonstrated tunable release of amlodipine-loaded micelles. Additionally, we showed that the released drug maintained biological activity via calcium ion blockade in vitro. This study represents a proof of concept for the potential applicability of our strategy for chronotherapeutic management of hypertension.

Ocular fundus abnormalities in cats affected by systemic hypertension: Prevalence, characterization, and outcome of treatment.

OBJECTIVES: To determine the prevalence of ocular fundus abnormalities in cats with a diagnosis of systemic hypertension, to characterize the abnormalities observed, and to evaluate ophthalmoscopic evolution during treatment with amlodipine besylate. ANIMALS STUDIED: Cats diagnosed as affected by SHP in a 2-year period. PROCEDURES: Systemic hypertension was assessed by oscillometric blood pressure measurement, and its etiology was also established. All the cats received an ophthalmic examination, and ocular lesions were classified with a score from 0 (no abnormalities) to 4 (severe abnormalities). All cats received amlodipine besylate by mouth, and those that showed fundus abnormalities were regularly rechecked from 7 to 365 days after diagnosis. Data were statistically analyzed to compare Psys and Pdia with all the variables and to correlate Psys and Pdia with the fundus score. RESULTS: A total of 225 cats were enrolled in the study, and the prevalence of fundus abnormalities was 58.6% (21.2%: grade 1; 18.2%: grade 2; 36.4%: grade 3; and 24.2%: grade 4). Systemic hypertension was diagnosed concurrently with chronic renal failure (60.4%), hyperthyroidism (28.9%), both chronic renal failure and hyperthyroidism (7.6%), and hypertrophic myocardiopathy (3.1%). A significant effect of Psys values on the fundus score was detected. Amlodipine therapy improved fundus abnormalities in 50% of cases at the 21-day follow-up. CONCLUSIONS: This study showed that fundus abnormalities are common in hypertensive cats at the time of the systemic diagnosis, and most of the abnormalities are moderate to severe. Treatment with amlodipine appeared to improve ophthalmic lesions over time.

Comparative Analysis of the Morphology of Dentition in Normotensive and Hypertensive Rats Exposed to Chronic Stress.

The peculiarities of the histological structure and morphometrical parameters of the dentition in ISIAH rats (inherited stress-induced arterial hypertension) before stress and after modeling of everyday life stress regimen (chronic stress) were compared with those in WAG rats. The area of blood vessels of the periodontium, the thickness of the endothelium in the periodontal and pulp vessels, and the number of fibroblasts were increased, while the level of odontoblasts was reduced in ISIAH rats both before and after exposure to chronic stress, which can reflect more pronounced reaction to stress in hypertensive animals.

Changes in the Periodontium and Pulp in ISIAH Rats Caused by Stress Exposures in Different Modes.

It was shown that the intensity of morphological changes in the dental system tissues (periodontium and pulp) of ISIAH rats depends on the mode of stress exposure. Acute stress was associated with a significant increase in the area of periodontal and pulp vessels, a decrease in the area of connective tissue of these components, and an increase in the thickness of the vascular endothelium. Chronic stress in these animals induced an increase in the thickness of the endothelial layer of the periodontal and pulp vessels, fibromatosis (increase in the number of fibroblasts), and a sharp decrease in the level of odontoblasts.

Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase.

RATIONALE: The function of Nox4, a source of vascular H(2)O(2), is unknown. Other Nox proteins were identified as mediators of endothelial dysfunction. OBJECTIVE: We determined the function of Nox4 in situations of increased stress induced by ischemia or angiotensin II with global and tamoxifen-inducible Nox4(-/-) mice. METHODS AND RESULTS: Nox4 was highly expressed in the endothelium and contributed to H(2)O(2) formation. Nox4(-/-) mice exhibited attenuated angiogenesis (femoral artery ligation) and PEG-catalase treatment in control mice had a similar effect. Tube formation in cultured Nox4(-/-) lung endothelial cells (LECs) was attenuated and restored by low concentrations of H(2)O(2,) whereas PEG-catalase attenuated tube formation in control LECs. Angiotensin II infusion was used as a model of oxidative stress. Compared to wild-type, aortas from inducible Nox4-deficient animals had development of increased inflammation, media hypertrophy, and endothelial dysfunction. Mechanistically, loss of Nox4 resulted in reduction of endothelial nitric oxide synthase expression, nitric oxide production, and heme oxygenase-1 (HO-1) expression, which was associated with apoptosis and inflammatory activation. HO-1 expression is controlled by Nrf-2. Accordingly, Nox4-deficient LECs exhibited reduced Nrf-2 protein level and deletion of Nox4 reduced Nrf-2 reporter gene activity. In vivo treatment with hemin, an inducer of HO-1, blocked the vascular hypertrophy induced by Nox4 deletion in the angiotensin II infusion model and carbon monoxide, the product of HO-1, blocked the Nox4-deletion-induced apoptosis in LECs. CONCLUSION: Endogenous Nox4 protects the vasculature during ischemic or inflammatory stress. Different from Nox1 and Nox2, this particular NADPH oxidase therefore may have a protective vascular function.

Exacerbation of Thrombotic Responses to Silver Nanoparticles in Hypertensive Mouse Model.

With advent of nanotechnology, silver nanoparticles, AgNPs owing majorly to their antibacterial properties, are used widely in food industry and biomedical applications implying human exposure by various routes including inhalation. Several reports have suggested AgNPs induced pathophysiological effects in a cardiovascular system. However, cardiovascular diseases such as hypertension may interfere with AgNPs-induced response, yet majority of them are understudied. The aim of this work was to evaluate the thrombotic complications in response to polyethylene glycol- (PEG-) coated AgNPs using an experimental hypertensive (HT) mouse model. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times, i.e., on days 7, 14, 21, and 28 post-angiotensin II-induced HT, or vehicle (saline) infusion. On day 29, various parameters were assessed including thrombosis in pial arterioles and venules, platelet aggregation in whole blood in vitro, plasma markers of coagulation, and fibrinolysis and systemic oxidative stress. Pulmonary exposure to PEG-AgNPs in HT mice induced an aggravation of in vivo thrombosis in pial arterioles and venules compared to normotensive (NT) mice exposed to PEG-AgNPs or HT mice given saline. The prothrombin time, activated partial thromboplastin time, and platelet aggregation in vitro were exacerbated after exposure to PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Elevated concentrations of fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor were seen after the exposure to PEG-AgNPs in HT mice compared with either PEG-AgNPs exposed NT mice or HT mice given with saline. Likewise, the plasma levels of superoxide dismutase and nitric oxide were augmented by PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Collectively, these results demonstrate that PEG-AgNPs can potentially exacerbate the in vivo and in vitro procoagulatory and oxidative stress effect in HT mice and suggest that population with hypertension are at higher risk of the toxicity of PEG-AgNPs.

Mast cells contribute to alveolar bone loss in Spontaneously Hypertensive Rats with periodontal disease regulating cytokines production.

Mast cells (MCs) play a pivotal role in inflammatory responses and had been studied in inflammatory bone disorders, however, their role in alveolar bone loss induced by periodontal disease (PD) is not yet fully understood. We, therefore, aimed to evaluate the effects of MCs depletion in the PD-induced alveolar bone loss in Wistar (W) and Spontaneously Hypertensive Rats (SHRs). PD was induced by ligating the lower first molars with silk thread one day after the MCs depletion, by the pre-treatment with compound 48/80 for 4 days. After 15 days of PD induction, the hemi-mandibles were surgically collected for qRT-PCR, histological analyses, immunostaining, and ELISA. Systolic blood pressure (SBP) was verified by tail plethysmography to confirm the hypertensive status, and SHR presented SBP >150 mmHg, and previous MC depletion alone or associated with PD did not alter this parameter. SHRs showed a more severe alveolar bone loss compared to W, and MC depletion significantly inhibited this response in both strains, with a more significant response in SHRs. MCs were less abundant in 48/80+PD groups, thus validating the previous MCs depletion in our model. PD increased the number of MC in the gingival tissue of SHR. Cytokine production (TNF-α, IL-6, IL-1ß, and CXCL3) was constitutively higher in SHR and increased further after PD, which was also significantly reduced in the MCs-depleted animals. PD led to an increased expression of Opn, Rankl, Rank, Vtn, Itga5, Itgb5, Trap, and Ctsk in the mandible of W and SHRs, which was reversed in MCs-depleted animals. These results suggest that MCs significantly contributes to the PD-induced alveolar bone resorption, especially in the SHR, which is associated with a more severe PD progression compared to Wistar, partly explained by these cells contribution to the inflammatory status and mediator production, stimulating osteoclast-related response markers, which were reduced after MC depletion in our experimental model.

Sites of blood collection and topical antiseptics associated with contaminated cultures: prospective observational study.

We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. This single-center, prospective observational study of 249 consecutive patients aged ≥ 20 years proceeded in the ED of a university hospital in Japan during 6 months. Pairs of blood samples were collected for aerobic and anaerobic culture from all patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. We found 50 (20.1%) patients with potentially contaminated blood cultures. Fifty-six (22.5%) patients were true bacteremia and 143 (57.4%) patients were true negatives. Multivariate analysis associated more frequent contamination when puncture sites were disinfected with povidone-iodine than with alcohol/chlorhexidine (adjusted risk difference, 12.9%; 95% confidence interval [CI] 8.8-16.9; P < 0.001). Sites of blood collection were also associated with contamination. Femoral and central venous with other sites were associated with contamination more frequently than venous sites (adjusted risk difference), 13.1% (95% CI 8.2-17.9; P < 0.001]) vs. 17.3% (95% CI 3.6-31.0; P = 0.013). Rates of contaminated blood cultures were significantly higher when blood was collected from femoral sites and when povidone-iodine was the topical antiseptic.

Association between oral health and dementia in the elderly: a population-based study in Korea.

We have investigated the association of oral health with development of dementia in elderly Koreans. Data for subjects aged ≥65 years who underwent regular National Health Insurance Service check-ups and received dental care in 2017 were analysed. Those treated for dementia in 2017 served as the dementia group and those with no record of dementia in 2002-2017 as the control group. Explanatory variables were sex, age, household income, place of residence, smoking status, alcohol consumption, and presence of diabetes mellitus and hypertension, periodontitis, and removable dentures. Regression analysis showed that dementia was significantly more common in women than in men and in those aged ≥81 years than in those aged 65-70 years. The risk of dementia was highest in the 'upper-middle' income group and in the rural population. Smokers and those who consumed alcohol were less likely to develop dementia. Subjects with diabetes were more likely to have dementia than those without it, as were those with hypertension. Dementia was less likely in subjects with periodontitis and more likely in those with removable dentures. Therefore, loss of teeth may contribute to development of dementia.

ACE Gene Variant Causing High Blood Pressure May Be Associated With Medication-related Jaw Osteonecrosis.

The association of the high blood pressure D variant of the angiotensin-converting enzyme (ACE) gene with medication-related jaw osteonecrosis (MRONJ) is described in two Greek patients. The first patient, a 73-year-old man, took zolendronate, 4 mg/100 ml IV once per month for two years for prostate cancer and bone metastases. Three months after drug discontinuation, extraction of the first premolar was performed. After the intervention, he suffered from osteonecrosis of the mandible. He presented with hypertension and genetic testing revealed that he was homozygous for the high blood pressure D variant of the ACE gene. The second patient, a 65 years old woman, took denosumab, 120 mg subcutaneously once per month for 6 months for possible bone metastases from breast cancer. Three months after extraction of the first molar, she suffered from MRONJ. He also presented with hypertension and genetic testing revealed that she had the high blood pressure D variant of the ACE gene in a heterozygous state, which moderately predisposes to hypertension. To our knowledge, this is the first report indicating that genetic predisposition to hypertension may increase risk for MRONJ.

Repeated Porphyromonas gingivalis W83 exposure leads to release pro-inflammatory cytokynes and angiotensin II in coronary artery endothelial cells.

The role of Porphyromonas gingivalis (P. gingivalis) or its virulence factors, including lipopolysaccharide (LPS) not only has been related with periodontitis but also with endothelial dysfunction, a key mechanism involved in the genesis of atherosclerosis and hypertension that involving systemic inflammatory markers as angiotensin II (Ang II) and cytokines. This study compares the effect of repeated and unique exposures of P. gingivalis W83 LPS and live bacteria on the production and expression of inflammatory mediators and vasoconstrictor molecules with Ang II. Human coronary artery endothelial cells (HCAEC) were stimulated with purified LPS of P. gingivalis (1.0, 3.5 or 7.0 µg/mL) or serial dilutions of live bacteria (MOI 1: 100 - 1:0,1) at a single or repeated exposure for a time of 24 h. mRNA expression levels of AGTR1, AGTR2, IL-8, IL-1ß and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1ß and GM-CSF levels were measured by flow cytometry, ELISA determined Ang II levels. Live bacteria in a single dose increased mRNA levels of AGTR1, and repeated doses increased mRNA levels of IL-8 and IL-1ß (p < 0.05). Repeated exposure of live-P. gingivalis induced significant production IL-6, MCP-1 and GM-CSF (p < 0.05). Moreover, these MCP-1, IL-6 and GM-CSF levels were greater than in cells treated with single exposure (p < 0.05), The expression of AGTR1 and production of Ang II induced by live-P. gingivalis W83 showed a vasomotor effect of whole bacteria in HCAEC more than LPS. In conclusion, the findings of this study suggest that repeated exposure of P. gingivalis in HCAEC induces the activation of proinflammatory and vasoconstrictor molecules that lead to endothelial dysfunction being a key mechanism of the onset and progression of arterial hypertension and atherosclerosis.

Anandamide-nanoformulation obtained by electrospraying for cardiovascular therapy.

Anandamide (AEA), an endogenous cannabinoid, has a relevant antihypertensive effect. However, its cardioprotective role has been barely explored due to unfavorable physico-chemical properties and, sometimes, undesirable psychoactive effects. In this context, drug encapsulation in nanocarriers could overcome the limitations associated with the administration of AEA in free form. The aim of the present study was to encapsulate AEA in poly-ε-caprolactone/Pluronic® F127 nanoparticles (AEA/PCL/PF127 NPs) by means of electrospraying, to characterize their physico-chemical properties and cytocompatibility and to evaluate their effect in an in vivo model of cardiovascular remodeling caused by hypertension. AEA/PCL/PF127 NPs were characterized in terms of morphology, size, polydispersity, Z-potential, hydrophilicity, thermal and spectroscopic properties. Also, the encapsulation and loading efficiencies and in vitro release of AEA were analyzed. AEA/PCL/PF127 NPs (700-1000 nm) showed adequate cytocompatibility. For the cardiovascular remodeling studies, normotensive (WKY) and hypertensive (SHR) male rats were treated or not with AEA/PCL/PF127 NPs (5 mg/Kg, intraperitoneal injection) weekly for 1 month. Inflammatory markers and hemodynamic, structural and cardiac functional parameters were monitored. In SHR, the treatment with AEA/PCL/PF127 NPs reversed all altered cardiovascular markers and parameters (p < 0.05). Overall, nanoformulated AEA obtained by electrospraying proved to be effective for the treatment of hypertension and its comorbidities, especially cardiovascular remodeling.

Atenolol reduces salivary activity in pups of spontaneously hypertensive and normotensive rats treated during pregnancy and lactation.

The salivary activity in pups of spontaneously hypertensive rats (SHR) and Wistar (W) rats treated with atenolol during pregnancy, and lactation was evaluated. Atenolol's anti-hypertensive effect on the SHR rats was noticed from the beginning of treatment. Atenolol-treated SHR and Wistar rat pups showed a decrease in salivary gland weight, salivary flow, and protein concentration, with no alteration in salivary amylase activity. Atenolol's effect on salivary glands can interfere with oral health maintenance.

Associação entre hipertensão arterial sistêmica e indicadores antropométricos em idosos do estudo brazuca / Association between systemic arterial hypertension and anthropometric indicators in the elderly in the brazuca study / Asociación entre hipertensión arterial sistémica y indicadores antropométricos en adultos mayores del estudio brazuca

Introdução:A Hipertensão Arterial Sistêmica é uma doença crônica que acometea maior parte idosos brasileiros, sendo uma das principais causas de mortes prematuras e incapacidades funcionais que causam complicações cardiovasculares e cerebrais, as quais podem estar associadas a diversos fatores predisponentes como a obesidade.Objetivo:Avaliar a associação entre hipertensão arterial sistêmica e indicadores antropométricos em idosos do estudo BrazucaNatal.Metodologia: Estudo transversal de base populacional com 191 idosos do município Natal-RN. Foram coletados dados sociodemográficos, econômicos e antropométricos (peso, estatura, perímetro da cintura e perímetro do quadril) e cálculo do Índice de Massa Corporal, Razão Cintura-Estatura e Razão Cintura Quadril. A hipertensão arterial foi auto referida. Os dados foram analisados pelo software SPSS versão 20.0. Teste t de Student foi utilizado para avaliar as diferenças entre médias das variáveis de acordo com o sexo e presença de hipertensão arterial. A associação entre a presença da doença e as variáveisfoi realizadapela Regressão de Poisson, comas razões de prevalência brutas e ajustadas e seus intervalos de confiança (95%).Resultados:A maioria dos idosos eram do sexo feminino (55%), com média de idade 69,48 anos (DP=7,38) e índice de massa corporalde 28,46 (DP=5,25), 59,4% possuíamexcesso de peso e 60,1% hipertensão. Ao comparar os sexos, registramos maiores médias de índice de massa corporal, perímetro do quadrile relação cintura estaturanas mulheres (p<0,05). Observamos maiores médias de idadee indicadores antropométricos entre os idosos com hipertensão (p<0,05). Constatamos que a presença de hipertensão estava associada a perímetro da cintura e índice de massa corporal no modelo bruto, mantendo-se apenas o perímetro da cinturano modelo ajustado. Conclusões:Indicadores antropométricos de fácil aplicação e baixo custo como o perímetroda cintura podeser eficientes para a detecção precoce da hipertensão arterial em idosos (AU).

Introduction:SystemicArterial Hypertension is a chronic disease that affects most Brazilian older adults and is one of the main causes of premature deaths and functional disabilities that cause cardiovascular and brain complications. Obesityis among the several predisposing factorsassociatedwithhypertension. Objective:To evaluate the association between SAHand anthropometric indicators in older adultsof the Brazuca Natal study.Methodology: Cross-sectional population-based study with 191 older adults in the city of Natal-RN.Sociodemographic, economic and anthropometric data (weight, height, waist circumference,and hip circumference),Body Mass Index, Waist-Height Ratio and Waist-Hip Ratio were collected. Hypertension was self-reported. Data were analyzed using the SPSS software, version 20.0. The Student's t-test was used to compare themeans of the variables according to sexand presence of hypertension. The association between the presence of the disease and the variables wasperformed by Poisson regression, with crude and adjusted prevalence ratios and respectiveconfidence intervals (95%).Results:The majority of the elderly were female (55%), with a mean age of 69.48 years (SD = 7.38) andBody Mass Indexof 28.46 (SD = 5.25), 59.4% were overweight and 60.1% had hypertension. Mean Body Mass Index, hip circumference and Waist-Height Ratiovalues were higher in women (p<0.05). The age and anthropometric indicators values were higher among the older adults with hypertension (p<0.05). We found that the presence of hypertension was associated with body weight and Body Mass Index,in the crude model and only with body weight in the adjusted model. Conclusions:Anthropometric indicators of easy application and lowcost such as waist circumference can be efficient todetect hypertension in older adults (AU).

Introducción:La Hipertensión Arterial Sistémica es una enfermedad crónica que afecta principalmente ancianos brasileños, siendo una de las principales causas de muertes prematuras ydiscapacidades funcionales que causan complicaciones cardiovasculares y cerebrales, las cuales pueden estar asociadas a diversos factores predisponentes como la obesidad. Objetivo:Evaluar la asociación entre la hipertensión arterial sistémica y los indicadores antropométricos en ancianos del estudio Brazuca Natal. Metodología:Estudio transversal de base poblacional con 191 ancianos del municipio Natal-RN. Se reconpilaron datos sociodemográficos, económicos y antropométricos (peso, estatura, perímetro de la cintura y perímetro de la cadera) y cálculo del Índice de Masa Corporal,Razón Cintura-Estatura y Razón Cintura Cadera. La hipertensión fue auto referida. Los datos fueron analizados por el software SPSSversión 20.0. Test t de Student fue realizado para evaluar las diferencias entre medias de las variables de acuerdo con el sexo y la presencia de hipertensión arterial. La asociación entre la presencia de la enfermedad y las variables fue realizada por la Regresión de Poisson, con las razones de prevalencia brutas y ayustadas y sus intervalos de confianza (95%). Resultados:La mayoría de los ancianos eran mujeres (55%), con una media de 69,48 años (DP= 7,38) y Índice de Masa Corporalde 28,46 (DP= 5,25), 59,4% poseían exceso de peso y 60,1% hipertensión. Observamos mayores medias de edady indicadores antropométricosentre los ancianos con hipertensión (p<0,05).Constatamos que la presencia de hipertensión estaba asociada al perímetro de la cinturae Índice de Masa Corporalen el modelo bruto, manteniendo solo el perímetro de la cinturaen el modelo ayustado. Conclusiones:Indicadores antropométricos de fácil aplicación y bajo costo como el perímetro de la cintura puede ser eficaz para la detección temprana de la hipertensión arterial en los ancianos (AU).

Effects of Diabetes and Hypertension on Oral Mucosa and TGFß1 Salivary Levels.

The aim of this study was to investigate salivary levels of TGFß1 and proliferation/ maturation of epithelial mucosa cells in diabetic and hypertensive patients. DESIGN: in this cross-sectional study, whole stimulated saliva and oral mucosa exfoliative cytology specimens were collected from 39 patients that were healthy (control, n=10) or presented history of arterial hypertension (HAS, n=9), diabetes mellitus (DM, n=10) or both (DM+HAS, n=10). Salivary flow rate (SFR), TGFß1 level in saliva, AgNORs and the epithelial maturation were evaluated. Non-parametric Kruskal-Wallis test, followed by Dunn's multiple comparison post-test and the Spearman test correlation analysis were used. SFR showed a significant decreased in DM and DM+HAS (0.47±0.11 and 0.64±0.43 mL/min) when compared to control (1.4±0.38 mL/min). DM+HAS presented the highest value of TGFß1 concentration (24.72±5.89 pg/mL). It was observed a positive correlation between TGFß1 and glycaemia (R=0.6371; p<0.001) and a negative correlation between TGFß1 and saliva (R=-0.6162; p<0.001) and glycaemia and SFR (R=-0.5654; P=0.001). AgNORs number and status of maturation of mucosa cells were similar for all conditions. DM and DM+HAS presented the lowest SFR, which correlated with increased TGFß1 levels. Despite the higher TGFß1 secretion it was not observed changes in the morphology or proliferation of epithelial cells when diabetes or hypertension was present.

Quercetin attenuates hypertension induced by sodium fluoride via reduction in oxidative stress and modulation of HSP 70/ERK/PPARγ signaling pathways.

Hypertension is one of the silent killers in the world with high mortality and morbidity. The exposure of humans and animals to fluoride and/or fluoride containing compounds is almost inevitable. This study investigated the modulatory effects of quercetin on sodium fluoride (NaF)-induced hypertension and cardiovascular complications. Forty male rats were randomly separated into four groups (n =10). Group A animals served as the control, rats in Group B were exposed to 300 ppm of NaF, Groups C and D animals were exposed to 300 ppm of NaF along with quercetin orally at 50 mg/kg and 100 mg/kg orally by gavage, while NaF was administered in drinking water, respectively, for a week. Administration of NaF caused severe hypertension as indicated with significant increases in the systolic, diastolic, and mean arterial blood pressure, together with prolonged ventricular depolarization (QRS) and the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT) intervals when compared with controls. NaF significantly decreased the activities of antioxidant enzymes, caused increase in markers of oxidative stress and renal damage when compared with controls. Immunohistochemical staining revealed lower expressions of Hsp70, ERK, and PPARγ in the heart, kidney, and aorta of rats-administered NaF relative to the controls. Together, quercetin co-treatment with NaF restored blood pressure, normalized QRS interval, and improved antioxidant defense system. © 2018 BioFactors, 44(5):465-479, 2018.

Inverse association between number of teeth and left ventricular mass in women.

OBJECTIVES: Recently, we have demonstrated a sex-specific inverse association between the number of teeth and hypertension. Left ventricular hypertrophy is a major cardiac sequel of hypertension. With the present study we sought to investigate whether there is also an inverse association between the number of teeth and left ventricular mass (LVM). METHODS: We used data from 1913 subjects (1036 women and 877 men) who were recruited for the population-based Study of Health in Pomerania (SHIP). The number of teeth, with the exception of the third molars, was counted in the full mouth. LVM was determined echocardiographically. Multivariable analyses were adjusted for major confounders. RESULTS: Women with fewer teeth had higher values for LVM than women with more teeth. This association was stable when controlled for major confounders. In the full model, edentulous women had an adjusted LVM of 178.4 g [95% confidence interval (CI) 170.4, 186.3 g] while women with 24-28 teeth had an adjusted LVM of 164.8 g (95% CI 156.8, 172.9 g; P < 0.01). In men, no such differences were observed. CONCLUSIONS: We conclude that there is an association between the number of teeth and LVM in women aged 45 years or older. In women, these findings further explain why poor oral health predicts all-cause and circulatory mortality. Further research in young, low-risk populations is needed to explore this association in men.

Correlation between the state of periodontal tissues and selected risk factors for periodontitis and myocardial infarction.

BACKGROUND: The current level of knowledge indicates a relationship between periodontitis and diabetes and/or cardiovascular diseases (CVD). Periodontitis can be not only a risk factor for these diseases, but also a condition modifying other primary risk factors associated with the occurrence of cardiovascular complications (lipid disorders, arterial hypertension, etc.) or diabetes. OBJECTIVES: The aim of the study was an analysis of the correlation between the state of periodontal tissues and selected risk factors for myocardial infarction (MI) in patients after recent myocardial infarction. MATERIAL AND METHODS: The study included 417 patients (92 women, 325 men) hospitalized due to recent MI. The inclusion criteria were MI history and age below 70 years. The state of periodontal tissues (plaque index, bleeding on probing, pocket depth and clinical attachment loss, CPI index) and selected risk factors for periodontitis and CVD were recorded. RESULTS: An analysis of the results showed no statistically significant correlation between the depth, the number, percentage of periodontal pockets and the average clinical attachment level on one hand and BMI on the other hand. Whereas a statistically significant correlation was observed between tobacco smoking and the degree of severity of periodontal diseases measured by the average pocket depth, the number and percentage of pockets above 4 mm and the average clinical attachment loss, as well as between hypertension and the state of oral hygiene and between diabetes and the number of preserved teeth and the number of pockets above 4 mm. CONCLUSIONS: The degree of severity of periodontal disease can impact hypertension and diabetes, which could potentially influence the occurrence and course of CVD.

Morphometric and histologic characterization of alveolar bone from hypertensive patients.

BACKGROUND: Hypertension is considered a risk factor in implant dentistry but the underlying reasons remain unclear. It may be that hypertension has a negative impact on the local bone quality. PURPOSE: Here we evaluated the structural and histological parameters of bone collected from hypertensive patients treated by antagonists of the renin-angiotensin system, and of bone collected from normotensive patients. MATERIAL AND METHODS: A total of 30 patients were referred for rehabilitation with dental implants to be placed in the posterior mandible. The first group were hypertensive patients treated with RAS antagonists. The second group were normotensive patients not taking medication. Bone biopsies collected during implant installation were subjected to analysis. Micro CT revealed the structural parameters. Histological analyses together with immunohistochemical staining of osteogenic markers were performed. RESULTS: The structural parameters of bone volume, trabecular thickness, trabecular number, separation of the trabecular, and total porosity were similar between the 2 groups (P > .05). The histological appearance of bone derived from hypertensive patients was normal. The staining pattern of Runx-2, osteopontin, and osteocalcin were comparable in both groups. CONCLUSIONS: These observations suggest that hypertensive patients treated with renin-angiotensin system antagonists have regular alveolar bone with respect to bone structure and histological parameters.

Proteomic analysis reveals an impaired Ca2+/AQP5 pathway in the submandibular gland in hypertension.

Hypertension is a systemic disorder that affects numerous physiological processes throughout the body. Improper sodium transport is a common comorbidity of hypertension, and sodium transport is also critical for maintaining the secretion of submandibular glands, whether the function of submandibular glands is affected by hypertension remains unclear. To determine whether hypertension induces changes in the protein expression of submandibular glands, we compared the proteome of submandibular glands from 14-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats using LC-MS/MS. The results revealed that 95 proteins displayed different levels of expression between the submandibular glands from the SHRs and WKYs. Among these, 35 proteins were more abundant, and 60 proteins were less abundant in the SHR compared with the WKY rats. Specifically, aquaporin 5 and parvalbumin, which are correlated with water transport and intracellular Ca2+ signal transduction, were verified to exhibit differences in protein abundance. Impaired Ca2+ response to carbachol was confirmed in the acinar cells from SHRs, and hyposecretion by the submandibular glands was further confirmed by in vivo saliva collection. In conclusion, the proteomic analysis of the submandibular glands of SHRs revealed novel changes in protein abundance that provides possible mechanisms connecting hypertension and hyposecretion in submandibular glands.