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- Estimating screening-level organic chemical half-lives in humans. [JOURNAL ARTICLE]
- Environ Sci Technol 2013 Dec 3.
Relatively few measured data are available for the thousands of chemicals requiring assessment. The whole body, total elimination half-life (HLT) and the whole body, primary biotransformation half-life (HLB) are key parameters determining the extent of bioaccumulation, biological concentration, and risk from chemical exposure. A one-compartment pharmacokinetic (1-CoPK) mass balance model was developed to estimate organic chemical HLB from measured HLT data in mammals. Approximately 1,900 HLs for human adults were collected and reviewed and the 1-CoPK model was parameterized for an adult human to calculate HLB from HLT. Measured renal clearance and whole body total clearance data for 306 chemicals were used to calculate empirical HLB,emp. The HLB,emp values and other measured data were used to corroborate the 1-CoPK HLB model calculations. HLs span approximately 7.5 orders of magnitude from 0.05 h for nitroglycerin to 2×106 h for 2,3,4,5,2',3',5',6'-octachlorobiphenyl with a median of 7.6 h. The automated Iterative Fragment Selection (IFS) method was applied to develop and evaluate various Quantitative Structure-Activity Relationships (QSARs) to predict HLT and HLB from chemical structure and two novel QSARs are detailed. The HLT and HLB QSARs show similar statistical performance, i.e. r2 = 0.89, r2-ext = 0.72 and 0.73 for training and external validation sets, respectively, and root mean square errors for the validation datasets are 0.70 and 0.75, respectively.
- Association between glycemic control and morning blood pressure surge with vascular endothelial dysfunction in type 2 DM patients. [JOURNAL ARTICLE]
- Diabetes Care 2013 Dec 2.
ObjectiveMorning blood pressure surge (MBPS) is an independent predictor of cardiovascular events. However, little is known on the association between glycemic control and MBPS and its effect on vascular injury in patients with type 2 diabetes mellitus (T2DM). The present study examined the association between glycemic control and MBPS and the involvement of MBPS in the development of vascular dysfunction in T2DM patients.Research Design and MethodsWe examined MBPS in T2DM patients (M/F; 25/25, age; 60.1±13.2 years, n=50) by 24-hour ambulatory blood pressure monitoring, and assessed vascular function by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD).ResultsHbA1c (ρ=0.373, p=0.009) and triglyceride (ρ=0.375, p=0.009) correlated significantly and positively with MBPS. In multiple regression analysis including triglyceride and HbA1c in addition to age, 24-hour systolic blood pressure (24h-SBP) as independent variables, HbA1c (β=0.328, p=0.016) and triglyceride (β=0.358, p=0.014) associated significantly in a positive manner with MBPS. In non-insulin user, when HOMA-R was included in place of TG, HOMA-R emerged as a significant factor. MBPS (ρ=-0.289, p=0.043), and HbA1c (ρ=-0.301, p=0.035) correlated significantly and negatively with FMD, while 24h-SBP correlated with both FMD (ρ=-0.359, p=0.012) and NMD (ρ=-0.478, p=0.004). In multiple regression analysis, including age, gender, 24h-SBP, MBPS, LDL-cholesterol, and HbA1c, MBPS (β=-0.284, p=0.044) alone associated significantly in a negative manner with FMD, but not with NMD.ConclusionsThe present study demonstrated that poor glycemic control and insulin resistance are independently associated with the occurrence of MBPS in T2DM patients, which might be significantly associated with endothelial dysfunction.
- Pacemaker-mediated angina. [JOURNAL ARTICLE]
- Exp Clin Cardiol 2013; 18(1):35-37.
Angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back or arm. It is typically aggravated by exertion or emotional stress and relieved by nitroglycerin. Atherosclerotic coronary artery disease is the most common cause of angina. Dual-chamber pacemakers track the atrial electrical activity by pacing the ventricle. The present article reports the first case in the literature involving pacemaker-mediated angina. A 78-year-old man complained of chest pain shortly after the placement of a permanent dual-chamber pacemaker and experienced immediate relief of his pain after the pacemaker mode was switched from tracking the atrium and pacing the ventricle to sensing and pacing the ventricle. The pain was identified as angina pectoris. The comprehensive history-taking performed before pacemaker placement helped to quickly identify the cause of the patient's pain.
- Postoperative management of Dupuytren's disease with topical nitroglycerin. [JOURNAL ARTICLE]
- Can J Plast Surg 2012; 20(4):249-250.
Dupuytren's contracture remains a significant clinical challenge due to associated complications and a recurrence rate of up to 60%. Commonly, the operated skin tends to rebuild scar in the area of surgery. Assuming local ischemia as an etiological factor, two cases in which topical nitroglycerin was used following surgical treatment of Dupuytren's disease are presented. In these patients, no raised scar formation developed during healing. At least six months after surgery, disease recurrence was not noted and the patients and surgeon reported improved skin quality. In the present study, the use of topical nitroglycerin, a local vasodilator, appeared to prevent recurrent scar formation, possibly through prevention of local ischemia. Further study and follow-up is necessary.
- Potent Vasodilatory Effect of Fasudil on Radial Artery Graft in Coronary Artery Bypass Operations. [JOURNAL ARTICLE]
- Ann Thorac Surg 2013 Nov 25.
The radial artery (RA) is a useful conduit for coronary artery bypass grafting (CABG) but is susceptible to vasospasm during harvesting. We evaluated the usefulness of fasudil, a Rho kinase inhibitor, in dilating the RA graft and increasing graft free flow (GFF) compared with the conventional graft-dilating agents papaverine and verapamil-nitroglycerin (VG).Between June 2012 and January 2013, 45 patients with ischemic heart disease who underwent isolated CABG using the RA were enrolled and randomly assigned to fasudil (n = 15), papaverine (n = 15), or VG (n = 15). Fasudil (2.67 mmol/L), papaverine (1.0 mmol/L) mixed with heparinized blood, or VG (30 μmol/L each of verapamil and nitroglycerin) was injected intraluminally into the RA graft after harvesting. Main outcome measures were RA GFF, hemodynamic changes, and histopathologic examination of the RA.In the fasudil group, GFF increased significantly (p < 0.001) from 36.8 ± 20.4 at baseline to 148.0 ± 88.3 mL/min after injection. GFF increased significantly (p < 0.001) from 36.0 ± 19.0 to 72.3 ± 36.7 mL/min in the papaverine group and increased significantly (p < 0.001) from 39.5 ± 23.3 to 64.3 ± 29.9 mL/min in the VG group. The GFF was significantly higher (p = 0.001) in fasudil-treated RA than in papaverine- or VG-treated RA. Histopathologically, RA graft diameter was markedly increased after fasudil injection, and the structure of the multiple elastic lamellae was intact. Blood pressure did not change significantly after drug injection in all groups.Fasudil exhibited a very potent vasodilatory effect on the RA compared with conventional papaverine or VG, resulting in increased GFF. This agent is useful for dilating RA grafts in CABG.
- [Unstable angina pectoris - a combination of an epicardial stenosis and a Prinzmetal spasm]. [English Abstract, Journal Article]
- Dtsch Med Wochenschr 2013 Dec; 138(49):2546-9.
History and admission findings: A 61-year-old man presented with recurrent angina pectoris at rest for 3 days. The medical history revealed hypertension and an elevated cholesterol level as cardiovascular risk factors. Investigations: The physical examination revealed no pathological findings. ECG at admission showed no signs of ischemia, while high-sensitive Troponin T was slightly elevated. Echocardiography showed diastolic dysfunction and biatrial dilatation. Treatment and course: During another episode of angina at rest, ECG showed T-wave inversion in lead aVL. Therefore, coronary angiography was performed. At the beginning of the examination the patient complained of angina at rest and ECG showed ST-elevation in the inferior leads. Coronary angiography revealed a subtotal stenosis in the middle part of the RCA. After intracoronary nitroglycerin injection there was a high-grade stenosis in this region. An intracoronary acetycholin provocation test was performed which reproduced a focal spasm in the area of the RCA stenosis with simultaneous changes in the ECG and reproduction of the patient's unusual angina. After implantation of a bare metal stent a subsequent ACH-test did not elicit any further coronary spasm. Four weeks after the procedure the patient had no further complaints under medical treatment.
Conclusion:This case illustrates a patient with a focal Prinzmetal-type spasm with ST-elevation on top of a high-grade stenosis of the right coronary artery as an explanation for the unstable angina. Coronary spasm of the Prinzmetal-type can occur in vessels with epicardial stenosis as well as in vessels without stenosis. In some cases focal coronary spasm can be prevented by the implantation of a stent.
- Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. [JOURNAL ARTICLE]
- Brain 2013 Nov 25.
Our aim was identify brain areas involved in the premonitory phase of migraine using functional neuroimaging. To this end, we performed positron emission tomography scans with H2(15)O to measure cerebral blood flow as a marker of neuronal activity. We conducted positron emission tomography scans at baseline, in the premonitory phase without pain and during migraine headache in eight patients. We used glyceryl trinitrate (nitroglycerin) to trigger premonitory symptoms and migraine headache in patients with episodic migraine without aura who habitually experienced premonitory symptoms during spontaneous attacks. The main outcome was comparing the first premonitory scans in all patients to baseline scans in all patients. We found activations in the posterolateral hypothalamus, midbrain tegmental area, periaqueductal grey, dorsal pons and various cortical areas including occipital, temporal and prefrontal cortex. Brain activations, in particular of the hypothalamus, seen in the premonitory phase of glyceryl trinitrate-triggered migraine attacks can explain many of the premonitory symptoms and may provide some insight into why migraine is commonly activated by a change in homeostasis.
- Clevidipine for Perioperative Blood Pressure Control in Infants and Children. [JOURNAL ARTICLE]
- Pharmaceuticals (Basel) 2013; 6(1):70-84.
Various pharmacologic agents have been used for perioperative BP control in pediatric patients, including sodium nitroprusside, nitroglycerin, β-adrenergic antagonists, fenoldopam, and calcium channel antagonists. Of the calcium antagonists, the majority of the clinical experience remains with the dihydropyridine nicardipine. Clevidipine is a short-acting, intravenous calcium channel antagonist of the dihydropyridine class. It undergoes rapid metabolism by non-specific blood and tissue esterases with a half-life of less than 1 minute. As a dihydropyridine, its cellular and end-organ effects parallel those of nicardipine. The clevidipine trials in the adult population have demonstrated efficacy in rapidly controlling BP in various clinical scenarios with a favorable adverse effect profile similar to nicardipine. Data from large clinical trials regarding the safety and efficacy of clevidipine in children is lacking. This manuscript aims to review the commonly used pharmacologic agents for perioperative BP control in children, discuss the role of calcium channel antagonists such as nicardipine, and outline the preliminary data regarding clevidipine in the pediatric population.
- Safety of Intranasal Fentanyl in the Out-of-Hospital Setting: A Prospective Observational Study. [JOURNAL ARTICLE]
- Ann Emerg Med 2013 Nov 13.
Initial out-of-hospital analgesia is sometimes hampered by difficulties in achieving intravenous access or lack of skills in administering intravenous opioids. We study the safety profile and apparent analgesic effect of intranasal fentanyl in the out-of-hospital setting.In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses of either 50 or 100 μg, and the ambulance crew recorded adverse effects and numeric rating scale (0 to 10) pain scores before and after treatment.Our 903 evaluable patients received a mean cumulative fentanyl dose of 114 μg (range 50 to 300 μg). There were no serious adverse effects and no use of naloxone. Thirty-six patients (4%) experienced mild adverse effects: mild hypotension, nausea, vomiting, vertigo, abdominal pain, rash, or decrease of Glasgow Coma Scale score to 14. The median reduction in pain score was 3 (interquartile range 2 to 5) after fentanyl administration.The out-of-hospital administration of intranasal fentanyl in doses of 50 to 100 μg is safe and appears effective.
- Optical coherence tomography reveals a non-spasm pseudo-coronary artery stenosis: a case report and review of literature. [JOURNAL ARTICLE]
- Int J Clin Exp Med 2013; 6(10):1001-1005.
We described a case of angiographic stenosis that was highly suitable for stenting and it remained even after repeated intracoronary administration of nitroglycerin. However, optical coherence tomography showed the stenosis disappeared and the artery wall was smooth. It was therefore speculated that this was a just non-spasm pseudo-coronary artery stenosis. We hope that sharing this experience can aid cardiologists to avoid unnecessary implantation of stents.