PJ. Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat. Am J Physiol Heart Circ Physiol 296: H524 -H533, 2009. First published December 12, 2008 doi:10.1152/ajpheart.00543.2008.-Recent studies show that pulmonary vasodilator responses to nitrite are enhanced by hypoxia. However, the mechanism by which nitrite is converted to vasoactive nitric oxide (NO) is uncertain. In the present study, intravenous injections of sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure were enhanced when tone in the pulmonary vascular bed was increased with U-46619. Under elevated tone conditions, decreases in pulmonary and systemic arterial pressures in response to nitrite were attenuated by allopurinol in a dose that did not alter responses to the NO donors, sodium nitroprusside and diethylamine/NO, suggesting that xanthine oxidoreductase is the major enzyme-reducing nitrite to NO. Ventilation with a 10% O 2 gas mixture increased pulmonary arterial pressure, and the response to hypoxia was enhanced by N G -nitro-L-arginine methyl ester and not altered by allopurinol. This suggests that NO formed by the endothelium and not from the reduction of plasma nitrite modulates the hypoxic pulmonary vasoconstrictor response. Although intravenous injections of sodium nitrite reversed pulmonary hypertensive responses to U-46619, hypoxia, and N G -nitro-L-arginine methyl ester, the pulmonary vasodilator response to nitrite was not altered by ventilation with 10% O2 when baseline pulmonary arterial pressure was increased to similar values in animals breathing room air or the hypoxic gas. These data provide evidence that xanthine oxidoreductase is the major enzyme-reducing nitrite to vasoactive NO, and that this mechanism is not modified by hypoxia. nitric oxide; xanthine oxidoreductase; pulmonary hypertension; nitric oxide synthase ENDOTHELIAL NITRIC OXIDE (NO) formation plays an important role in the regulation of the pulmonary and systemic vascular beds (15, 28). The importance of NO has been demonstrated in experimental animals and in human subjects by the use of NO synthase (NOS) inhibitors (2,15,28). Although NO synthesis is important in the regulation of baseline tone in most vascular beds, the role of NO in the regulation of tone in the pulmonary vascular bed of the rat has been questioned (15). NO once released from the endothelium into the blood reacts rapidly with red cell hemoglobin (14, 21a, 26). Furthermore, NO that escapes hemoglobin scavenging can be oxidized to nitrite (21a). NO formed from nitrite that escapes inactivation relaxes vascular smooth muscle by a cGMP-dependent mechanism (7, 26). It has been reported that plasma nitrite concentrations reflect constitutive NOS activity and correlate with endothelial function (21a). In addition, recent research speculates that nitrite anion represents a storage form of NO that can have important pharmacological actions (13,22). This is...

Background: High incidence of treatable oral conditions has been reported among palliative patients. However, a large proportion of palliative patients lose their ability to communicate their sufferings. Therefore, it may lead to under-reporting of oral conditions among these patients. This review systematically synthesized the published evidence on the presence of oral conditions among palliative patients, the impact, management, and challenges in treating these conditions. Methods: An integrative review was undertaken with defined search strategy from five databases and manual search through key journals and reference list. Studies which focused on oral conditions of palliative patients and published between years 2000 to 2017 were included. Results: Xerostomia, oral candidiasis and dysphagia were the three most common oral conditions among palliative patients, followed by mucositis, orofacial pain, taste change and ulceration. We also found social and functional impact of having certain oral conditions among these patients. In terms of management, complementary therapies such as acupuncture has been used but not well explored. The lack of knowledge among healthcare providers also posed as a challenge in treating oral conditions among palliative patients. Conclusions: This review is first in its kind to systematically synthesize the published evidence regarding the impact, management and challenges in managing oral conditions among palliative patients. Although there is still lack of study investigating palliative oral care among specific group of patients such as patients with dementia, geriatric or pediatric advanced cancer patients, this review has however provided baseline knowledge that may guide health care professionals in palliative settings.

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) continues to spread globally. It has become a major cause of concern for health care professionals all over the world. Objective. The aim of this study was to assess knowledge, awareness and hygiene practices regarding COVID-19 among private dental practitioners practicing in Tricity (Chandigarh, Panchkula and Mohali) in India during these critical times. Materials and Methods. A total of 245 private dentists participated in this cross-sectional survey and finally 215 constituted the final sample size. A self-administered, multiple choice type questionnaire (verified by a specialist) was administered to obtain information from the subjects. The questionnaire was divided into two parts and included 15 questions on knowledge and awareness regarding COVID-19. Statistical analysis was done using ANOVA and Student’s t-test. Results. Percentage of subjects who answered correctly regarding main symptoms of COVID-19 and primary mode of transmission was 87% and 82.5% respectively. One-third of the subjects were not aware regarding Personal Protective Equipment (PPE) to be used while rendering dental treatment. 75% of subjects were of the opinion that supportive care is the current treatment regime for COVID-19. Less than one-third of subjects (30.2%) reported high scores. Education level (p=0.018) and health sector profile (p=0.024) of the subjects were significantly associated with mean knowledge scores. Conclusion. The findings of the present study showed that some notable deficiencies in knowledge existed among dental professionals regarding some vital aspects of COVID-19. Therefore, there is an urgent need for improving dentists’ knowledge via health education and training programs. Further studies on the subject are also warranted once the situation normalizes.

PJ. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat. Am J Physiol Heart Circ Physiol 299: H819 -H826, 2010. First published June 11, 2010; doi:10.1152/ajpheart.00959.2009.-It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was ϳ1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat. mitochondrial aldehyde dehydrogenase; xanthine oxidoreductase; nitric oxide; glyceryl trinitrate; sodium nitrite; sodium nitroprusside; allopurinol; cyanamide; U-46619; N G -nitro-L-arginine methyl ester GLYCERYL TRINITRATE (GTN) and, to a lesser extent, amyl nitrite have been used in the treatment of angina and heart failure for more than a century (4, 5, 38). However, the molecular mechanism by which GTN relaxes vascular smooth muscle is still the subject of current investigation and remains unknown. Although it is well established that nitric oxide (NO) activates soluble guanylyl cyclase, increases cGMP formation, and relaxes vascular smooth muscle, the role of NO release in mediating the vasorelaxant response to GTN is uncertain (11,17,21,26,30,37,39). Although studies in the literature provide evidence that NO is released from GTN, other studies show that NO is not released and suggest that the activation of guanylyl cyclase is mediated by a closely related but not currently identified chemical species with NO-guanylyl cyclase stimulating properties (2, 11, 16, 23, 25, 29 -31, 36, 39). There is substantial evidence in the literature that mitochondrial aldehyde dehydrogenase (ALDH2) plays an i...

Badejo AM Jr, Dhaliwal JS, Casey DB, Gallen TB, Greco AJ, Kadowitz PJ. Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat. Am J Physiol Lung Cell Mol Physiol 295: L828 -L836, 2008. First published August 8, 2008 doi:10.1152/ajplung.00042.2008.-The small GTP-binding protein Rho and its downstream effector, Rho-kinase, are important regulators of vasoconstrictor tone. Rho-kinase is upregulated in experimental models of pulmonary hypertension, and Rho-kinase inhibitors decrease pulmonary arterial pressure in rodents with monocrotaline and chronic hypoxia-induced pulmonary hypertension. However, less is known about responses to fasudil when pulmonary vascular resistance is elevated on an acute basis by vasoconstrictor agents and ventilatory hypoxia. In the present study, intravenous injections of fasudil reversed pulmonary hypertensive responses to intravenous infusion of the thromboxane receptor agonist, U-46619 and ventilation with a 10% O2 gas mixture and inhibited pulmonary vasoconstrictor responses to intravenous injections of angiotensin II, BAY K 8644, and U-46619 without prior exposure to agonists, which can upregulate Rho-kinase activity. The calcium channel blocker isradipine and fasudil had similar effects and in small doses had additive effects in blunting vasoconstrictor responses, suggesting parallel and series mechanisms in the lung. When pulmonary vascular resistance was increased with U-46619, fasudil produced similar decreases in pulmonary and systemic arterial pressure, whereas isradipine produced greater decreases in systemic arterial pressure. The hypoxic pressor response was enhanced by 5-10 mg/kg iv nitro-Larginine methyl ester (L-NAME), and fasudil or isradipine reversed the pulmonary hypertensive response to hypoxia in control and in L-NAME-treated animals, suggesting that the response is mediated by Rho-kinase and L-type Ca 2ϩ channels. These results suggest that Rho-kinase is constitutively active in regulating baseline tone and vasoconstrictor responses in the lung under physiological conditions and that Rho-kinase inhibition attenuates pulmonary vasoconstrictor responses to agents that act by different mechanisms without prior exposure to the agonist.Rho-kinase pathway; Ca 2ϩ sensitization; pulmonary vascular bed; U-46619; isradipine; hypoxia; nitro-L-arginine methyl ester THE SMALL GTP-binding protein Rho and its downstream effector Rho-kinase play an important role in the regulation of vascular smooth muscle tone (3,4,6,18,20,28,34,36). It has been hypothesized that the Rho-kinase system is constitutively active in regulating vasoconstrictor tone and that upregulation of this pathway occurs in a variety of cardiovascular diseases (8,19,21,22,32,33,35). Rho-kinase has been shown to be a potential therapeutic target in a number of cardiovascular diseases including pulmonary hypertension (1,2,10,12,15,16,26,27,29,38). It has been reported that Rho-kinase is upregulated in monocrotaline and chronic hypoxia-induced pulmonary hypertensio...

Aims and Objectives:To study the prevalence of dentine hypersensitivity and related risk factors in rural population of Punjab, India.Materials and Methods:A total of 650 subjects reporting dentine sensitivity were included in the study comprising of 270 males and 380 females. All the subjects completed an interview and the subjects reporting dentine hypersensitivity were examined further using air syringe to put a blast of air to confirm the diagnosis of dentine hypersensitivity. Periodontal attachment loss and gingival recession of all the sensitive teeth were examined and recorded.Results:The prevalence of dentine hypersensitivity was 25% in the oral test. The subjects receiving the treatment of hypersensitivity were only 15.1%. The older group in the 50-59 years had the highest number (98%) of subjects with dentine hypersensitivity. Most commonly affected teeth were mandibular incisors. The other factors related to dentine hypersensitivity were the socioeconomic status, lower education level, and access to dental care. The periodontal factors related to hypersensitivity were gingival recession and poor oral hygiene.Conclusions:The prevalence of dentine hypersensitivity was 25% in the rural population of Punjab.

Topical tacrolimus 0.03% ointment seems to be a promising second-line immunosuppressant in management of high-risk grafts.

The small GTP-binding protein and its downstream effector Rho kinase play an important role in the regulation of vasoconstrictor tone. Rho kinase activation maintains increased pulmonary vascular tone and mediates the vasoconstrictor response to nitric oxide (NO) synthesis inhibition in chronically hypoxic rats and in the ovine fetal lung. However, the role of Rho kinase in mediating pulmonary vasoconstriction after NO synthesis inhibition has not been examined in the intact rat. To address this question, cardiovascular responses to the Rho kinase inhibitor fasudil were studied at baseline and after administration of an NO synthesis inhibitor. In the intact rat, intravenous injections of fasudil cause dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and increases in cardiac output. L-NAME caused a significant increase in pulmonary and systemic arterial pressures and a decrease in cardiac output. The intravenous injections of fasudil after L-NAME caused dose-dependent decreases in pulmonary and systemic arterial pressure and increases in cardiac output, and the percent decreases in pulmonary arterial pressure in response to the lower doses of fasudil were greater than decreases in systemic arterial pressure. The Ca(++) entry blocker isradipine also decreased pulmonary and systemic arterial pressure in L-NAME-treated rats. Infusion of sodium nitroprusside restored pulmonary arterial pressure to baseline values after administration of L-NAME. These data provide evidence in support of the hypothesis that increases in pulmonary and systemic vascular resistance following L-NAME treatment are mediated by Rho kinase and Ca(++) entry through L-type channels, and that responses to L-NAME can be reversed by an NO donor.