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Aims Individuals with intellectual disability (ID) have special health care needs. Teaching self-care behaviors like toothbrushing helps reduce their dependence on adult caregivers. We present a bio-behavioral intervention combining task analysis with skill-based teaching of toothbrushing behavior aimed to promote autonomy in children with various types of ID. Methods One hundred twenty children with ID enrolled at a special school in the State were included in the study. After baseline measurements using task analysis, four methods were used to train the children - instruction, three-phase modeling, physical guidance, and descriptive praise. The caregiver was trained and given instructional videos for reinforcement. After 4 weeks, the children were asked to brush their teeth and performance was evaluated. Results There was increased independence in the performance of toothbrushing behavior, the mild and moderate ID groups showing the most improvement. Steps like oral manipulation of the toothbrush showed the greatest improvement in these groups. The severe ID group showed improvement in certain skills, while requiring assistance for others that demanded dexterity. Conclusion This intervention can be implemented by special schools and special care dentistry centers to foster autonomy in oral self-care skills in the mild and moderate ID children, and complemented with other methods for severe ID children.

Background: This study compared conventional-resin-sealant versus nanofilled-sealant retention at different intervals. Methods: A double-blinded split-mouth randomized control trial was performed on sixty-two children aged from six to nine years. Participants with one pair of contralateral permanent first molars with deep fissures or noncavitated carious lesions were randomly selected for sealant application. Conventional resin sealant was applied on one molar and nanofilled sealant on the contralateral molar. Evaluations were performed at one, three, six, twelve and eighteen months to check for retention. The chi-squared test, McNemar test, Wilcoxon signed-rank test and Friedman test were used for statistical analysis. Results: Conventional resin sealant showed complete retention in 91.4%, 86.2%, 74.1%, 62.1% and 55.2% of the teeth, and nanofilled sealant showed complete retention in 89.7%, 81%, 77.6%, 69% and 67.2% of the teeth, at the end of 1 month, 3 months, 6 months, 12 months and 18 months evaluation, respectively. Each sealant exhibited a statistically significant change (p < 0.05) in the retention rate during the evaluation period. However, when both the sealants were compared with each other, there was no statistically significant difference in any phase. At the end of 18 months, caries development was observed in 13.8% of the teeth sealed with conventional sealant, and in 10.3% of the teeth sealed with nanofilled sealant. Conclusion: At eighteen months, the nanofilled resin sealant exhibited complete retention in 12% more teeth than the conventional sealant. However, the difference was not statistically significant. The nanofilled resin sealant yielded an acceptable performance in sealing the occlusal pits and fissures of mandibular permanent first molars, compared to conventional pit-and-fissure sealants.

Objectives The use of herbal dentifrices has grown exponentially over the years. They are categorically referred to as ethnomedicines. Various agents have been tried with contradicting findings based on phytopharmacological analysis. Miswak is one agent which has been used over the years. A novel Moringa oleifera-based dentifrice has shown promising results in terms of its cytotoxicity, biocompatibility, and as a potent anti-inflammatory agent. Therefore, the present study aims to compare the efficacy of two commercially available miswak- and moringa-based herbal dentifrices on the reduction of plaque and gingivitis scores. Materials and Methods This randomized clinical crossover study included 20 subjects with mild to moderate gingivitis. The study was conducted over a total examination period of 20 days with a wash-out period of 2 weeks between the use of both the toothpastes. The plaque index and gingival index of the study subjects were recorded at the designated time intervals throughout the study period. Statistical Analysis The data collected were entered on Microsoft Excel, and statistical analysis using SPSS software (SPSS version 28, IBM Corp, Armonk, New York, United States) was done. The statistical test used was the Wilcoxon signed-rank test. Moreover, p ≤0.05 was considered significant. Results The results showed that the reduction in mean gingival index scores from baseline to day 3 was more statistically significant in the moringa-based dentifrice. Similarly, the plaque index scores showed statistically significant reduction following the use of the moringa-based dentifrice when compared with the miswak dentifrice. This study reveals that the moringa dentifrice is a safe and effective agent in reducing plaque accumulation and treating gingival inflammation. Conclusion The current study aims to provide an insight into the possible role of moringa dentifrice as a possible adjunctive oral hygiene aid.

The volume of the inferior turbinates (IT) and the lining of the maxillary sinuses are important parameters when assessing sino-nasal diseases. However, no radiographic studies have investigated the correlation between these parameters. The present study was conducted to analyze the association between IT volumes and thickness of maxillary sinus mucosal lining.A retrospective evaluation of the cone-beam computed tomography (CBCT) scans of 100 adult subjects was carried out by two radiologists. The scans were assigned to two groups (Group 12) based on the radiographic evidence of maxillary sinus lining in the CBCT scans. Group 1 consisted of 50 CBCT scans of subjects with no evidence of maxillary sinus mucosal lining, whereas Group 2 consisted of 50 subjects with evidence of maxillary sinus mucosal lining. The scans in the Group 2 were further sub-classified into five categories, based on the thickness of the maxillary sinus mucosal lining. Vesalius 3D software was used to evaluate the total volume of inferior nasal turbinates by the two radiologists and a mean volume was obtained for each study subject.The intraclass correlation coefficient (ICC) between the volumetric estimations performed by the two radiologist was 0.87. Analysis of the results revealed that there was no significant gender-based difference (Group 1, P = 0.67 and Group 2, P = 0.95) in the total turbinate volume in either of the study groups. The total turbinate volume did not show any significant correlation (Group 1, r = 0.24 and Group 2, r = 0.12) with the age. There was a significant increase (P = 0.001) in the total turbinate volume of the subjects in Group 2 compared to Group 1. Regression analysis revealed that the thickness of sinus lining correlated significantly (P = 0.001) with the total turbinate volume.An increase in the total turbinate volume has been associated with an increase in the thickness of the maxillary sinus mucosal lining. The data from this study will be useful for post-operative follow-up of inferior turbinates and maxillary sinus lining after the turbinate volume reduction procedures.

Objective: This study aims to assess the correlation of exhaled CO and nicotine dependence with the occurrence of oral mucosal lesions while also taking into consideration socio-demographic, clinical and anthropometrical characteristics of participants. Methods: An observational cross-sectional study was carried out among smokers who visited the tobacco cessation center at Tertiary Care Dental Hospital in Goa, India. An intra-oral soft tissue examination for detecting presence of oral mucosal lesions followed by a questionnaire-based interview for the measurement of exposure, sociodemographic factors, body mass index, cooking habits and nicotine dependence was conducted. The exhaled CO levels were measured with a CO breath analyzer. Statistical analysis was performed using IBM SPSS version 20.0 Descriptive statistics were calculated and multivariable analysis was done to assess the association of different variables with oral mucosal lesions and carbon monoxide levels. p-value ≤ 0.05 was considered as statistically significant. Results: Of the 173 subjects enrolled in the study, 69.36% were without any lesions while 30.63% were diagnosed with some lesion. In the regression analysis, the variables of physical activity (present vs absent OR: 5.808), exhaled CO levels (OR: 1.098) and nicotine dependence (mild vs moderate OR: 6.518) were significant risk factors influencing the presence of oral mucosal lesions. Usage of both cigarettes and bidis by smokers exhibited highest mean exhaled CO values of 19.67±1.506 ppm. Exhaled CO levels were significantly higher in smokers who were overweight (14.96±9.14 ppm), physically inactive (13.98±8.26 ppm), highly nicotine dependent (20.67±8.30) and used coal for cooking (12.55±8.17). Conclusion: A robust correlation between exhaled CO levels, nicotine dependence and incidence of oral mucosal lesions was established. The multifactorial tenacity of exhaled CO which is affected by smoked tobacco as well as variables such as physical activity, BMI, cooking habits and type of smoking habit should be noted.

Aim To evaluate caries spectrum among 12- and 15-year-old Indian children using the Caries Assessment Spectrum and Treatment (CAST) index. Materials and methods An epidemiological survey of the schoolchildren was carried out in a district in India. A stratified cluster random sampling method was used to select the sample. The caries prevalence of the surveyed population was obtained by using this CAST tool. Chi-square test was used to verify the association between dental fluorosis, socioeconomic status, and age and caries experience. Mann-Whitney U-test was used to compare the caries experience between the two age groups. Results A total of 2,610 children were examined. The majority of the schoolchildren (12 years: 74.2%, 15 years: 75.5%) were healthy concerning their caries experience and the prevalence of the other codes was minimal. The prevalence of dentin carious lesions and the percent of restorable teeth was greater among the 15-year-olds. The mean decayed, missing, and filled teeth (DMFT) of 12- and 15-year-old subjects was calculated to be 0.22 and 0.29 respectively. Conclusion The currently surveyed population showed a low caries prevalence and the use of the tool highlighted the caries spectrum in an impressive way. Clinical significance A well-designed tool to assess the carious spectrum of an individual or a community, thus enabling the responsible stakeholders to plan an appropriate care that is necessary.

Objectives The phytochemical composition of Ocimum tenuiflorum is highly complex and enriched with nutrients and other biologically active compounds. The aim of this randomized clinical trial was to explore the antimicrobial and anti-gingivitis property of 2 % O. tenuiflorum extract gel with 0.2 % chlorhexidine gel on patients diagnosed with dental plaque induced gingival inflammation as an adjunct to oral prophylaxis. Materials and methods 60 patients diagnosed with moderate to severe form of gingivitis, fulfilling the inclusion criteria participated in this randomized double-blind placebo-controlled trial. Following oral prophylaxis, the subjects were randomly dispensed with one of the test gels i.e., Group A – 0.2 % Chlorhexidine gel (n = 20), Group B – placebo gel (n = 20), Group C –2% O. tenuiflorum gel (n = 20) for 15 days. Clinical indices (Plaque index (PI), gingival index (GI) and modified Sulcus Bleeding index (mSBI)) and microbiological parameters were recorded at baseline, 15 days, and 3 months. Results All 3 groups exhibited a reduction in clinical (PI, GI, mSBI) and microbiological parameters (p Conclusion O. tenuiflorum gel has shown enhanced effects on gingival health due to its therapeutic properties and may be considered an alternative adjunct to mechanical plaque control therapy.

Objective: To investigate the total oxidant levels in healthy, chronic periodontitis (CP), and ischemic heart disease (IHD) and to check for any correlation among them. Materials and Methods: A sample of 80 were split into four groups of healthy subjects (Group I), CP subjects (Group II), IHD subjects (Group III), and IHD subjects having periodontitis (Group IV). The serum and saliva samples collected were analyzed for levels of hydrogen peroxide (H2O2), hydroxyl radical (OH-), nitric oxide (NO), and superoxide radical (O2-). Results: There were significant (P < 0.05) variances in the mean serum and salivary levels of hydrogen peroxide, hydroxyl radical, NO, and superoxide within the 4 groups. Oxidant levels of both serum and saliva were lower in disease groups of Group II, III, and IV as compared to healthy controls, with different patterns. Conclusion: The oxidant levels (H2O2, OH-, NO, and O2-) are significantly hampered in periodontitis and IHD subjects as compared to healthy subjects. The oxidants, whether serum or salivary, did not always show the proportional change as a result of change in oxidant stress due to disease as positive correlation was observed only in the serum H2O2 and salivary NO radical levels and between serum superoxide dismutase radical and salivary H2O2 in Group I. In Group III, there was a positive correlation between serum NO radical and salivary H2O2.

Context The purpose of this study was to assess the Oral Hygiene Periodontal Status Dentition Status and Treatment Needs among the detainees in juvenile detention centres of Madhya Pradesh Settings and design Cross sectional survey nbsp Methods and material A survey was scheduled to spread over a period of months from February to July All the children present in the detention centres on the day of survey will be examined Data will be collected using a self administered proforma which will be further divided into two parts First part will record the demographic details oral hygiene practices length of stay first offenders or repeat offenders educational level Dental care utilization and tobacco usage Second part includes Clinical examination which will be performed on the seated patients by a single trained and calibrated examiner under adequate illumination Statistical analysis used All the collected data of the study will be coded and analysed using the latest version of a statistical package for social sciences SPSS Various tests for statistical analysis include Arithmetic mean standard deviation Analysis of variance ANOVA Student t test Chi square test Multiple stepwise linear and logistic regression analysis will be used to determine the predictors of oral hygiene periodontal status and dental caries Results Mean DMFT values in all the age groups were quite low An important finding of our study was that most of the detainees were smokeless tobacco users Difference in OHI S scores among the different age groups was statistically significant p Significant statistical difference was found between education and oral hygiene status p CPI scores and education was found to be significant in present study p Conclusion This study has confirmed that there is a need for organized preventive and curative care for the juvenile detainees of Madhya Pradesh

Use of temporary epicardial pacing (TEP) leads remains a routine perioperative strategy in congenital heart surgery. Selective use of TEP in neonates and infants undergoing cardiac intervention within the first 6 months of life has, yet, to be assessed. Outcome analysis was undertaken. From August 2014 to December 2016, 112 consecutive neonates and infants underwent cardiac intervention within the first 6 months of life. Patients with STS/EACTS Congenital Heart Surgery Mortality (STAT categories) 1–5 were prospectively followed from the index cardiac operation until hospital discharge and included in the study. Patients on permanent pacemaker (PPM) prior to the definitive cardiac intervention were excluded. Selective TEP placement was pursued if specific intraoperative indications were met. Determinants associated with the postoperative use of TEP were assessed. TEP leads were placed in 11 (9.8%) (GroupA). Nine was used for diagnostic and/or therapeutic purposes; two had no use (18%). From 101 patients without TEP (GroupB), one required treatment for postoperative dysrhythmia amenable to pacing. Vasoactive-inotrope score, ICU length of stay and time-to-negative balance was not statistically different between groups (p > 0.05). None of 112 patients required PPM insertion during hospital stay. Intraoperative need for cardioversion, attenuated ventricular function, and sustained sinus/AV node dysfunction or non-resolved elevated serum lactate at the time of operating room discharge were found to be predictors for TEP postoperative use. Selective placement of TEP leads is justified during early infancy for congenital heart surgery. Nearly 20% of those with TEP leads in place, even after its selective use, will not be required following surgery. Specific intraoperative parameters can guide the necessity and potential TEP postoperative use.

To evaluate caries spectrum among 12- and 15-year-old Indian children using the Caries Assessment Spectrum and Treatment (CAST) index.An epidemiological survey of the schoolchildren was carried out in a district in India. A stratified cluster random sampling method was used to select the sample. The caries prevalence of the surveyed population was obtained by using this CAST tool. Chi-square test was used to verify the association between dental fluorosis, socioeconomic status, and age and caries experience. Mann-Whitney U-test was used to compare the caries experience between the two age groups.A total of 2,610 children were examined. The majority of the schoolchildren (12 years: 74.2%, 15 years: 75.5%) were healthy concerning their caries experience and the prevalence of the other codes was minimal. The prevalence of dentin carious lesions and the percent of restorable teeth was greater among the 15-year-olds. The mean decayed, missing, and filled teeth (DMFT) of 12- and 15-year-old subjects was calculated to be 0.22 and 0.29 respectively.The currently surveyed population showed a low caries prevalence and the use of the tool highlighted the caries spectrum in an impressive way.A well-designed tool to assess the carious spectrum of an individual or a community, thus enabling the responsible stakeholders to plan an appropriate care that is necessary.

An increase in lipid peroxidation and a decrease in antioxidant activity have been reported in patients with cancer in comparison with normal subjects. Objective: To estimate the status of serum and saliva by assessing the serum and salivary vitamin E levels in patients with oral potentially malignant disorders and oral cancer. Methods: A total of 90 participants were enrolled in this study. 30 subjects with oral potentially malignant disorders, 30 sub¬jects with oral cancer, and 30 healthy subjects (controls). Serum and saliva samples were collected and vitamin E levels were assessed. The data were analyzed using ANOVA for between-group comparison. Post hoc Tukey analysis was used for comparing the two study groups with the control group. Pearson correlation coefficient was used to determine concordance between the groups. Results: Mean vitamin E levels in serum and saliva were sig¬nificantly decreased in oral potentially malignant disorders and oral cancer compared with controls. Conclusion: As significant reduction in vitamin E levels was observed in saliva, it was evident that salivary vitamin E levels potentially be used as a reliable, non invasive biomarker for diagnosing and managing oral potentially malignant disorders and oral cancer.

Introduction Dentistry, being one of the healing professions, has a commitment to society that its members will adhere to high ethical standards of conduct. Dental Council of India (DCI), the regulating body for dental professionals in the country, has also given certain guidelines and regulations on advertising issues. But, studies on dentists’ opinion on the issues on advertising for dental professionals in India are very meager. Hence, the aim was to evaluate the opinion on advertising issues among practicing dentists from various dental colleges in Bengaluru, India. Materials and methods A descriptive cross-sectional survey was conducted among 258 practicing dentists attached to various dental colleges in Bengaluru city. Chi-square test was used to determine the association of independent variables with each of the main outcome of interest. Results Out of 258 practicing dentists, nearly three quarters of practitioners (68.2%) agreed that there is a need for some form of advertising. Among those who agreed that there is a need for advertising, more than half of the practitioners (63.6%) said that it is required for popularity, visibility, and good business. When asked about which form of advertising can largely benefit their dental practice, 29.1% agreed on the patient testimonials, and 25.2% thought ads in magazines and newspapers are useful. Conclusion Nearly equal number of practitioners agreed and disagreed on the issue of whether advertising may make dentistry seem more like a trade than a health care service. More than three quarters of them agreed with the use of global advertising and tourism. How to cite this article Nayak PP, Raju VK, Kshetrimayum N, Ramesh L, Nayak SS, Kamath V. Dentists’ Outlook on Advertising in their Line of Work in Bengaluru, India: A Cross-sectional Study. World J Dent 2016;7(3):141-145.

The statistical data of cancer, globally, shows that India has one of the highest incidence rates of oral cancer worldwide. Early detection is extremely important as it results in lower morbidity and death rates. The present study was undertaken to assess awareness of oral cancer and knowledge of its early signs and riskfactors in the general public of rural Karnataka (India). It was also intended to educate the rural population for early detection by increasing their ability to recognize signs and risk factors. A systematic questionnaire was formatted related to oral cancer and cancer patients. A total of 267 people were randomly selected and questionnaires were distributed to 3 different rural areas of Dakshina Kannada district (Karnataka). The results were obtained and the level of oral cancer awareness in the rural population was studied.

Hypoxia is known to promote vasodilation of coronary vessels through several mediators including cardiac-derived adenosine and endothelium-derived prostanoids and nitric oxide. To date, the impact of endogenous glycogen depletion in vascular smooth muscle and the resultant alterations in cellular energy state (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been studied. In the present study, ex vivo exposure of endothelium-denuded human saphenous vein rings to hypoxic and glucose-deprived conditions during KCl-induced contractions for 30 min resulted in a marked depletion of endogenous glycogen by ∼80% (from ∼1.78 μmol/g under normoxia to ∼0.36 μmol/g under hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant increases in basal AMPK phosphorylation (∼6-fold ↑) and 5-HT-induced AMPK phosphorylation (∼19-fold ↑) with an accompanying suppression of 5-HT-induced maximal contractile response (∼68% ↓), compared with respective controls. Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK phosphorylation and restored 5-HT-induced maximal contractile response. In addition, the ability of exogenous D-glucose to rescue cellular stress and impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4-independent mechanisms. Together, the present findings from clinically-relevant human saphenous vein suggest that the loss of endogenous glycogen in vascular smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR agonists may constitute a yet another mechanism of metabolic vasodilation of coronary vessels in ischemic heart disease.

Peroxynitrite (ONOO−) contributes to coronary microvascular dysfunction in diabetes mellitus (DM). We hypothesized that in DM, ONOO− interferes with the function of coronary endothelial caveolae, which plays an important role in nitric oxide (NO)-dependent vasomotor regulation. Flow-mediated dilation (FMD) of coronary arterioles was investigated in DM (n = 41) and non-DM (n = 37) patients undergoing heart surgery. NO-mediated coronary FMD was significantly reduced in DM patients, which was restored by ONOO− scavenger, iron-(III)-tetrakis(N-methyl-4'pyridyl)porphyrin-pentachloride, or uric acid, whereas exogenous ONOO− reduced FMD in non-DM subjects. Immunoelectron microscopy demonstrated an increased 3-nitrotyrosine formation (ONOO−-specific protein nitration) in endothelial plasma membrane in DM, which colocalized with caveolin-1 (Cav-1), the key structural protein of caveolae. The membrane-localized Cav-1 was significantly reduced in DM and also in high glucose–exposed coronary endothelial cells. We also found that DM patients exhibited a decreased number of endothelial caveolae, whereas exogenous ONOO− reduced caveolae number. Correspondingly, pharmacological (methyl-β-cyclodextrin) or genetic disruption of caveolae (Cav-1 knockout mice) abolished coronary FMD, which was rescued by sepiapterin, the stable precursor of NO synthase (NOS) cofactor, tetrahydrobiopterin. Sepiapterin also restored coronary FMD in DM patients. Thus, we propose that ONOO− selectively targets and disrupts endothelial caveolae, which contributes to NOS uncoupling, and, hence, reduced NO-mediated coronary vasodilation in DM patients.

Treatment of periodontitis has been one of the most challenging aspects of periodontal therapy. The role of host immune inflammatory response in periodontal disease forms the basis of modernistic therapeutic approaches. The present study evaluates the efficacy of an indigenously formulated flax seed extract in the form of biodegradable gel, as an adjunct in the treatment of chronic periodontitis. Sixty patients diagnosed with localized periodontal disease having pocket probing depth ≥ 5 mm were selected. All the patients were treated with professional oral prophylaxis and root instrumentation as part of the standard periodontal care protocol. The participants were divided into 3 groups with 20 subjects in each group. One group received the formulated flax seed extract gel and second group received flurbiprofen gel. The third and/or control group did not receive any adjunct therapy. The following measurements were recorded at baseline, first and third month, which included, Gingival crevicular fluid (GCF) and saliva samples for estimation of drug release followed by record of clinical parameters i.e. plaque index, gingival index, pocket probing depth and clinical attachment levels. The results of the study demonstrated that the flax seed extract gel could be equally associated to the effectiveness of flurbiprofen gel, at the end of 90 days (p = 0.001). Hence, this randomized clinical trial sets a route for incorporating herbal constituents as targeted drug therapeutic agents for the management of chronic periodontitis. Also, the use of these phytotherapeutic agents can be further encouraged considering its safety, low risk and economical options.

Introduction: Dental caries is the most prevalent chronic disease affecting mankind and is the primary reason for tooth pain and edentulism. The presence or absence of caries depends on the diagnostic cut-off points selected. Aim: This study evaluated the comparability of two systems i.e., the International Caries Detection and Assessment system (ICDAS II) and the World Health Organization (WHO) criteria for detection of carious lesions among a set of outpatient subjects and was assessed for a equivalency point between the systems. Materials and Methods: A total of 242 subjects were independently inspected by two examiners who were trained and calibrated accordingly for detecting a carious lesion using the WHO and the ICDAS II criteria. Caries prevalence and the mean decayed teeth were calculated using both the systems. Wilcoxon test was employed to compare the mean caries score obtained with the WHO criteria and the ICDAS. Caries prevalence, according to the WHO criteria and ICDAS II criteria was compared using McNemar's test. Results: The equivalency point between these two systems was at score four of the ICDAS II in this particular study. Conclusion: In addition to unearthing a significant number of non-cavitated carious lesions, the ICDAS II can be equated to the WHO criteria at score four of the ICDAS II.

Bradykinin (BK) is continuously produced in the heart by the tissue kinin-kallikrein system,1 and is considered to be a key endogenous regulator of coronary blood flow. In this context, Groves et al demonstrated that intracoronary infusion of the BK B2 receptor antagonist, HOE 140, reduced the diameter of epicardial coronary arteries and decreased coronary blood flow in patients without significant coronary occlusion.2 In patients with no signs of coronary artery disease, intracoronary infusion of BK increased coronary artery diameter and elevated coronary blood flow.3 It is known that the rate of BK production increases in response to ischemic insults,4 aiming to maintain coronary dilation and tissue perfusion.5 However, this mechanism often fails in the diseased heart because of the unresponsiveness of coronary resistance arteries to exogenous or endogenous BK.6 Obesity and metabolic syndrome have been shown to have a detrimental effect on the coronary microcirculation of patients undergoing percutaneous coronary intervention.7 Previously, we have shown that BK-induced coronary arteriolar dilation is reduced in obese-normotensive patients, when compared with lean-normotensive individuals.8 The underlying mechanisms responsible for impaired BK-dependent regulation of coronary vascular resistance in obesity are not fully understood. In the circulation, BK is readily cleaved and inactivated by angiotensin-converting enzyme (ACE). The presence of tissue ACE has been described in cardiac myocytes and coronary vessels.9 In the myocardium, ACE plays a crucial role in various homeostatic pathways, including cell growth, extracellular matrix formation and apoptosis.10 In pathological conditions, such as atherosclerosis, hypertension and obesity, upregulation of tissue ACE is known to contribute to morphological changes in the heart by initiating cardiac and vascular hypertrophy.11 These adverse effects are mainly mediated by an increased ACE-dependent, localized production of angiotensin II (AngII).11 Less is known about the functional changes that may occur in coronary resistance arteries as a consequence of tissue ACE activation. The important ACE end-product, AngII, normally dilates coronary resistance arteries through activation of type 2 AngII receptors (AT2Rs).12,13 However, recent studies revealed that AT2R activation may also lead to constriction of resistance arteries in various disease states.14 In this context, Zhang et al have shown that AngII induces constriction of coronary arteries obtained from dogs fed a high-fat diet (HFD), an experimental model of obesity and metabolic dysfunction.15 These authors concluded that activation of tissue ACE could lead to enhanced production of AngII, thus promoting coronary vasoconstriction in obesity. This mechanism remains unconfirmed in human obesity. In addition, it is possible that the upregulated ACE in coronary microvessels interferes with the dilator effects of endogenously produced BK, a pathological mechanism that may also limit myocardial perfusion. In support of this scenario, Kuga et al demonstrated that the diameter of epicardial coronary arteries is increased after intracoronary infusion of the ACE inhibitor, enalaprilat, in patients without significant coronary stenosis.3 Previous studies have shown that systemic administration of an ACE inhibitor improves vasodilator responses in animal models of obesity.16,17 For instance, Russell et al reported that in ramipril-treated JCR:LA-cp obese rats, coronary blood flow in response to BK was significantly enhanced.17 It is important to note that in those studies only indirect evidence has been provided for the upregulated tissue ACE in coronary microvessels in obesity. Beneficial effects of systemic ACE inhibition could be related to the blood pressure (BP)-lowering effect and/or improved insulin resistance in obesity.16,17 Whether upregulated tissue ACE directly interferes with the dilator function of coronary resistance arteries in obesity remains unknown. Thus, in the current study we set out to elucidate the direct vascular effects of ACE inhibition, with the aims of providing evidence for the upregulation of coronary microvascular ACE in obesity and clinical relevance to obese patients. To this end, BK-induced dilator responses were investigated in isolated coronary arterioles in a rat model of diet-induced obesity.

Objective— A disintegrin and metalloproteinase ADAM17 (tumor necrosis factor-α [TNF]–converting enzyme) regulates soluble TNF levels. We tested the hypothesis that aging-induced activation in adipose tissue (AT)-expressed ADAM17 contributes to the development of remote coronary microvascular dysfunction in obesity. Approach and Results— Coronary arterioles (CAs, ≈90 µm) from right atrial appendages and mediastinal AT were examined in patients (aged: 69±11 years, BMI: 30.2±5.6 kg/m 2 ) who underwent open heart surgery. CA and AT were also studied in 6-month and 24-month lean and obese mice fed a normal or high-fat diet. We found that obesity elicited impaired endothelium-dependent CA dilations only in older patients and in aged high-fat diet mice. Transplantation of AT from aged obese, but not from young or aged, mice increased serum cytokine levels, including TNF, and impaired CA dilation in the young recipient mice. In patients and mice, obesity was accompanied by age-related activation of ADAM17, which was attributed to vascular endothelium–expressed ADAM17. Excess, ADAM17-shed TNF from AT arteries in older obese patients was sufficient to impair CA dilation in a bioassay in which the AT artery was serially connected to a CA. Moreover, we found that the increased activity of endothelial ADAM17 is mediated by a diminished inhibitory interaction with caveolin-1, owing to age-related decline in caveolin-1 expression in obese patients and mice or to genetic deletion of caveolin-1. Conclusions— The present study indicates that aging and obesity cooperatively reduce caveolin-1 expression and increase vascular endothelial ADAM17 activity and soluble TNF release in AT, which may contribute to the development of remote coronary microvascular dysfunction in older obese patients.