Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Denture-related stomatitis is associated with endothelial dysfunction. [Journal Article]
- Biomed Res Int 2014.:474016.
Oral inflammation, such as periodontitis, can lead to endothelial dysfunction, accelerated atherosclerosis, and vascular dysfunction. The relationship between vascular dysfunction and other common forms of oral infections such as denture-related stomatitis (DRS) is unknown. Similar risk factors predispose to both conditions including smoking, diabetes, age, and obesity. Accordingly, we aimed to investigate endothelial function and major vascular disease risk factors in 44 consecutive patients with dentures with clinical and microbiological features of DRS (n = 20) and without DRS (n = 24). While there was a tendency for higher occurrence of diabetes and smoking, groups did not differ significantly in respect to major vascular disease risk factors. Groups did not differ in main ambulatory blood pressure, total cholesterol, or even CRP. Importantly, flow mediated dilatation (FMD) was significantly lower in DRS than in non-DRS subjects, while nitroglycerin induced vasorelaxation (NMD) or intima-media thickness (IMT) was similar. Interestingly, while triglyceride levels were normal in both groups, they were higher in DRS subjects, although they did not correlate with either FMD or NMD.
Conclusions.Denture related stomatitis is associated with endothelial dysfunction in elderly patients with dentures. This is in part related to the fact that diabetes and smoking increase risk of both DRS and cardiovascular disease.
- Enhanced Bacterial Tumor Delivery by Modulating the EPR Effect and Therapeutic Potential of Lactobacillus casei. [JOURNAL ARTICLE]
- J Pharm Sci 2014 Jul 16.
Bacteria of micrometer size could accumulate in tumor based on enhanced permeability and retention (EPR) effect. We report here Lactobacillus casei (L. casei), a nonpathogenic facultatively anaerobic bacterium, preferentially accumulated in tumor tissues after intravenously (i.v.) injection; at 24 h, live bacteria were found more in the tumor, whereas the bacteria in normal tissues including the liver and spleen were cleared rapidly. The tumor-selective accumulation and growth of L. casei is probably due to the EPR effect and the hypoxic tumor environment. Moreover, the bacterial tumor delivery was significantly increased by a nitric oxide (NO) donor nitroglycerin (NG, 10-70 times) and an angiotensin II converting enzyme inhibitor, enalapril (6-18 times). Consequently significant suppression of tumor growth was found in a colon cancer C26 model, and more remarkable antitumor effect was achieved when L. casei was combined with NG, probably by modulating the host nonspecific immune responses; tumor necrosis factor-α significantly increased in tumor after the treatment, as well as NO synthase activity and myleoperoxidase activity. These findings suggest the potential of L. casei as a candidate for targeted bacterial antitumor therapy, especially in combine with NG or other vascular mediators. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
- Testing a conceptual model on early opening of the microcirculation in severe sepsis and septic shock: A randomised, controlled pilot study. [JOURNAL ARTICLE]
- Eur J Anaesthesiol 2014 Jul 16.
Organ failure in severe sepsis and septic shock may be caused by microcirculatory failure.The objective of this study is to test a conceptual model of microcirculatory failure by using a resuscitation strategy targeting early opening of the constricted microcirculation with active vasodilatation.A prospective, randomised controlled pilot study.Single-centre mixed medical and surgical tertiary ICU.Ninety severe sepsis and septic shock patients randomised to early opening microcirculation resuscitation group or standard resuscitation group.Standard resuscitation group: fluids, noradrenaline, dobutamine and hydrocortisone were given to achieve a mean arterial pressure (MAP) of more than 60 mmHg, cardiac index more than 2.5 l min m and ScvO2 more than 70%. Microcirculation resuscitation group: nitroglycerin, enoximone, dopamine and dexamethasone targeting a microvascular flow index (MFI), measured by sublingual side-stream dark field imaging, more than 2.5.A decrease in organ failure score (SOFA) on day four of ICU treatment.Data from 37 microcirculation resuscitation and 28 standard resuscitation patients were analysed. In the microcirculation resuscitation group, MFI of more than 2.5 was achieved after a mean ± SD of 7.0 ± 4.6 h. The microcirculation resuscitation group received more fluids, and noradrenaline was equally prescribed in both groups. Per protocol, the decrease in SOFA score at day 4 was not different between groups (P = 0.64). There was a significant reduction in SOFA score in both groups compared with admission (1.2 and 1.6 in microcirculation resuscitation and standard resuscitation groups, respectively; P = 0.028 and P = 0.045).Early opening of the microcirculation in patients with severe sepsis and septic shock using nitroglycerin, enoximone, dopamine and corticosteroids did not result in a faster reduction in organ failure than standard resuscitation.Clinicaltrials.gov identifier NCT00484133.
- P183Arginase inhibition protecs from ischemia-reperfusion injury in patients with coronary artery disease. [Journal Article]
- Cardiovasc Res 2014 Jul 15.:S32.
Arginase is an important regulator of nitric oxide production by competing with nitric oxide synthase for their common substrate L-arginine. Up-regulation of arginase in patients with coronary artery disease (CAD) and diabetes mellitus (DM) may thereby be of major importance for the development of endothelial dysfunction and ischemia-reperfusion (IR) injury by reducing the bioavailability of nitric oxide. Accordingly, arginase inhibition reduces infarct size and improves endothelial function by nitric oxide synthase-dependent processes in animal models. Purpose: To investigate if arginase inhibition protects from endothelial dysfunction induced by IR in patients with CAD with and without DM. Methods: Male patients with CAD (n=12) or CAD + DM (n=12), were included in this cross-over study with blinded evaluation. Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and 20 min after a 20 min period of arm ischemia. The patients were given an intra-arterial infusion of the arginase inhibitor Nω-hydroxy-nor-arginine (nor-NOHA, 0.1 mg/min) or saline on the two occasions. The infusions were given for 20 min starting 5 min before reperfusion. Endothelium-independent vasodilatation was assessed by sublingual nitroglycerin. Results: IR decreased FMD in patients with CAD from 12.7±1.5% to 7.9±1.2% during saline administration. Nor-NOHA administration prevented the decrease in FMD in the CAD group (11.5±1.0% FMD at reperfusion, P<0.0.5 vs. saline). Baseline endothelium-dependent vasodilatation was significantly lower in the CAD+DM group (8.3±0.6%) than in the CAD group (P<0.05). IR induced a non-significant decrease in FMD in patients with CAD+DM. FMD at reperfusion was higher following nor-NOHA (11.2±1.0%) than following saline (7.2±1.0%) administration in the CAD + DM group (P<0.01). Endothelium-independent vasodilatation did not differ between the occasions in either group.Inhibition of arginase protects against endothelial dysfunction caused by IR in patients with CAD. Arginase may thereby be a promising therapeutic target in the treatment of IR injury.
- Evaluation of Statin Therapy on Endothelial Function in Hypercholesterolemic Rabbits by Automatic Measurement of Arterial Wall Movement Using Ultrasound Images. [JOURNAL ARTICLE]
- Ultrasound Med Biol 2014 Jul 10.
The aim of this study was to evaluate arterial endothelial function, assessed as acetylcholine-mediated dilation (AMD), in a hypercholesterolemic atherosclerotic rabbit model to investigate the effects of atorvastatin in the atherosclerotic process, using a new computerized analysis model and ultrasound images. Twenty-seven rabbits were fed a high-cholesterol (2%) diet for 6 wk and then divided into three groups for an additional 9 wk: Group A received regular chow food, group B received a 2% cholesterol-rich diet plus atorvastatin drug, and group C received regular chow food plus atorvastatin. Ultrasound examinations of endothelial function of the rabbit abdominal aorta artery were performed immediately after the 6 weeks (0 wk) and then 3, 6 and 9 wk after that. For off-line analysis, a computerized analysis method for evaluating instantaneous changes in the wall of the rabbit abdominal aorta was used. As parameters of improvement resulting from treatment, endothelium-dependent acetylcholine-induced dilation and endothelium-independent nitroglycerin-induced dilation were evaluated in treated rabbits. Differences among groups were tested using analysis of variance. On histopathology, intima-media thickness decreased after treatment in all groups. There were no significant differences in arterial diameter and blood velocity changes among treated rabbits at 0, 3, 6 and 9 wk of treatment in all groups, except in end-diastolic velocity, radial strain percentage, pulse index and resistance index in group C. In group A, AMD did not significantly improve after 3, 6 and 9 wk, as compared with 0 wk. Atorvastatin treatment significantly increased AMD (18%) at 3 wk in group B, compared with week 0. AMD significantly increased after 3 (26%), 6 (124%) and 9 (182%) wk in group C, compared with 0 wk. It is concluded that the new automatic method enables accurate and repeated evaluation of endothelial function during the progression and regression of atherosclerosis. Also, the results obtained in this study indicate that short-term administration of atorvastatin can improve endothelial function in cholesterol-fed rabbits.
- sGC-cGMP Signaling: Target for Anticancer Therapy. [JOURNAL ARTICLE]
- Adv Exp Med Biol 2014.:5-13.
The biologic endogenous production of cGMP was reported in the 1960s and followed by the demonstration of guanylyl cyclase activity and the isoforms of soluble and membrane-bound guanylyl cyclases. During the same period, cGMP specific phosphodiesterases also was discovered. Murad's lab established link between the endothelium derived relaxation factor (EDRF) and elevated cGMP concentration in the vascular system. October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning nitric oxide (NO) as a signaling molecule in the cardiovascular system. In contrast with the short research history of the enzymatic synthesis of NO, the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin; GTN) is the first compound of this category. Alfred Nobel (the founder of the Nobel Prize) himself had suffered from angina pectoris and was prescribed nitroglycerin for his chest pain while he refused to take due to the induction of headaches. Almost a century after its first chemical use, research in the nitric oxide and 3',5'-cyclic guanosine monophosphate (NO/cGMP) pathway has dramatically expanded and the role of NO/cGMP in physiology and pathology has been extensively studied. Soluble guanylyl cyclase (sGC) is the receptor for NO. The α1β1 heterodimer is the predominant isoform of sGC that is obligatory for catalytic activity. NO binds to the ferrous (Fe(2+)) heme at histidine 105 of the β1 subunit and leads to an increase in sGC activity and cGMP production of at least 200-fold. In this chapter, we reviewed the studies of sGC-cGMP signaling in cell proliferation; introduced our work of targeting sGC-cGMP signaling for cancer therapy; and explored the role of sGC-cGMP signaling in the chromatin-microenvironment.
- Correlation between algogenic effects of calcitonin-gene-related peptide (CGRP) and activation of trigeminal vascular system, in an in vivo experimental model of nitroglycerin-induced sensitization. [JOURNAL ARTICLE]
- Eur J Pharmacol 2014 Jul 3.
The neural mechanism(s) underlying migraine remain poorly defined at present; preclinical and clinical studies shows an involvement of CGRP in this disorder. However current evidence pointed out that CGRP does not exert an algogenic action per se, but it is able to mediate migraine pain only if the trigeminal-vascular system is sensitized. The present study was addressed to investigate CGRP-evoked behavior in nitric oxide (NO) sensitized rats, using an experimental model of nitroglycerin induced sensitization of trigeminal system, looking at neuropeptide release from different cerebral areas after the intra-peritoneal (i.p.) administration of NO-donors. CGRP injected into the rat whisker pad did not induce significant changes in face rubbing behavior compared to controls. On the contrary, CGRP injected in animals pre-treated with 10mg/kg nitroglycerin significantly increased the time spent in face rubbing. Nitroglycerin pre-treated animals did not show any rubbing behavior after locally injected saline. Furthermore, the i.p. treatment with nitroglycerin produced an increase of CGRP levels in brainstem and trigeminal ganglia, but not in the hypothalamus and hippocampus. The absolute amounts of CGRP produced in the brainstem were lower compared to those in the trigeminal ganglion; however, after nitroglycerin stimulation the percentage increase was higher in the brainstem. In conclusion, findings presented in this study suggest that CGRP induces a painful behavior in rats only after sensitization of trigeminal system; thus supporting the concept that a genetic as well as acquired predisposition to trigemino- vascular activation represents the neurobiological basis of CGRP nociceptive effects in migraineurs.
- Intraoperative "Kounis syndrome" that improved electrocardiography changes and hemodynamic situation after administering nitroglycerine. [JOURNAL ARTICLE]
- Braz J Anesthesiol 2014 July - August; 64(4):281-285.
A 58-year-old female without cardiovascular risk factors, was going to be operated to repair the rotator cuff. Induction and interscalene brachial plexus block were uneventful, but after her placement for surgery the patient started with severe bronchospasm, hypotension, cutaneous allergic reaction and ST elevation on the electrocardiogram. An anaphylactic shock was suspected and treated but until the perfusion of nitroglycerina was started no electrocardiographic changes resolved. After necessary diagnostic test the final diagnosis was variant I of Kounis syndrome due to cefazolin and rocuronium. Ephinephrine is the cornerstone of treatment for anaphylaxis but should we use it if the anaphylactic reaction is also accompanied by myocardial ischemia? The answer is that we should not use it because myocardial ischemia in this syndrome is caused by vasospasm, so it would be more useful drugs such as nitroglycerin. But what if we do not know if it is a Kounis syndrome or not? In this article we report our experience that maybe could help you in a similar situation.
- Nitroglycerin-induced myocardial protection and tolerance: role for CGRP. [LETTER]
- Trends Pharmacol Sci 2014 Jul 2.
- Coronary vasodilation by the use of sublingual nitroglycerin using 64-slice dual-source coronary computed tomography angiography. [JOURNAL ARTICLE]
- J Cardiol 2014 Jun 30.
Sublingual nitroglycerin capsules or spray is routinely used to treat anginal attacks and to maximally dilate the epicardial coronary arteries during coronary angiography. These dilated coronary vessels have an advantage, but increased heart rates were disadvantageous for coronary computed tomography angiography (CTA).The influence of applying nitroglycerin was analyzed regarding the coronary diameter, coronary luminal attenuation, evaluable number of coronary segments, heart rate (HR), HR variability, the optimal reconstruction phase, and image scoring of CTA in the same patients using a 64-slice dual-source CT.Fifty-two patients with atypical chest pain underwent coronary CTA before and after the administration of sublingual nitroglycerin without heart rate control. The coronary diameter and luminal attenuation were measured on short-axial images in each coronary segment. The coronary vasodilation ratios (VRs) were calculated from the coronary diameters at the same location before and after the use of nitroglycerin. The local institutional review board approved this study and written informed consent was obtained from all the patients.No significant differences were noted in the HR variability or optimal reconstruction phase, despite an increase in HR after the use of nitroglycerin. Nitroglycerin significantly enlarged the coronary artery diameter, and VRs of each coronary segment ranged from 7.54% to 22.26%. As compared with baseline coronary diameter, VRs of minor segments (16.91%) were significantly larger than those of major segments (11.35%), and the magnitude of VR correlated with the baseline coronary diameter (r=-0.48, p<0.001). Coronary luminal attenuation significantly increased due to additional administration of contrast material after the use of nitroglycerin (p<0.01), but no significant difference was noted in the image quality after the use of nitroglycerin.Sublingual nitroglycerin significantly enlarged the coronary diameters, especially in peripheral small coronary arteries, and increased the evaluable number of coronary segments on coronary CTA.