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Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy.
Tilma, KK, Bek, T
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2020;(3):236-242
Abstract
BACKGROUND Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. METHODS The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. RESULTS Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. CONCLUSIONS The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.
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2.
Rosuvastatin reduces ischemia-reperfusion injury in patients with acute coronary syndrome treated with percutaneous coronary intervention.
Jiang, F, Yang, J, Zhang, L, Li, R, Zhuo, L, Sun, L, Zhao, Q
Clinical cardiology. 2014;(9):530-5
Abstract
BACKGROUND Statins reduce the incidence of cardiovascular events after percutaneous coronary intervention (PCI), but no clinical studies have investigated the role of statins in ischemia-reperfusion injury after PCI. HYPOTHESIS Rosuvastatin could reduce ischemia-reperfusion injury in patients with acute coronary syndrome treated with PCI. OBJECTIVES We investigated the effects of rosuvastatin on ischemia-reperfusion injury in patients with acute coronary syndrome after PCI and evaluated short-term prognosis. METHODS Patients scheduled for emergent PCI were given either rosuvastatin for ≥6 months (10 mg/d, every night; n = 55) or no statins (control group; n = 65). Serum superoxide dismutase activity, malondialdehyde, brain natriuretic peptide (BNP), and high-sensitivity C-reactive protein (hs-CRP) were determined before and after PCI, as well as left ventricular ejection fraction and left ventricular end-diastolic volume. Major adverse cardiac events were observed at follow-ups for 6 months. RESULTS Superoxide dismutase activity in the rosuvastatin-treated group was higher than that of the control group; serum levels of malondialdehyde were lower. BNP and hs-CRP levels in the rosuvastatin-treated group were lower than that of the control group. Four weeks after PCI, the left ventricular ejection fraction in the treatment group was higher than that of the control group, and the left ventricular end-diastolic volume was lower. At the 6-month follow-up, there was no difference in major adverse cardiac events between the 2 groups. CONCLUSIONS Rosuvastatin before PCI reduced ischemia-reperfusion injury in patients with acute coronary syndrome, which suggests the importance of application of rosuvastatin before PCI for early intervention.
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3.
Influence of SLCO1B1 polymorphisms on the drug-drug interaction between darunavir/ritonavir and pravastatin.
Aquilante, CL, Kiser, JJ, Anderson, PL, Christians, U, Kosmiski, LA, Daily, EB, Hoffman, KL, Hopley, CW, Predhomme, JA, Schniedewind, B, et al
Journal of clinical pharmacology. 2012;(11):1725-38
Abstract
The authors investigated whether SLCO1B1 polymorphisms contribute to variability in pravastatin pharmacokinetics when pravastatin is administered alone versus with darunavir/ritonavir. HIV-negative healthy participants were prospectively enrolled on the basis of SLCO1B1 diplotype: group 1 (*1A/*1A, n = 9); group 2 (*1A/*1B, n = 10; or *1B/*1B, n = 2); and group 3 (*1A/*15, n = 1; *1B/*15, n = 5; or *1B/*17, n = 1). Participants received pravastatin (40 mg) daily on days 1 through 4, washout on days 5 through 11, darunavir/ritonavir (600/100 mg) twice daily on days 12 through 18, with pravastatin 40 mg added back on days 15 through 18. Pharmacokinetic studies were conducted on day 4 (pravastatin alone) and day 18 (pravastatin + darunavir/ritonavir). Pravastatin area under the plasma concentration-time curve (AUC(tau)) was 21% higher during administration with darunavir/ritonavir compared with pravastatin alone; however, this difference was not statistically significant (P = .11). Group 3 variants had 96% higher pravastatin AUC(tau) on day 4 and 113% higher pravastatin AUC(tau) on day 18 compared with group 1. The relative change in pravastatin pharmacokinetics was largest in group 3 but did not differ significantly between diplotype groups. In sum, the influence of SLCO1B1*15 and *17 haplotypes on pravastatin pharmacokinetics was maintained in the presence of darunavir/ritonavir. Because OATP1B1 inhibition would be expected to be greater in carriers of normal or high-functioning SLCO1B1 haplotypes, these findings suggest that darunavir/ritonavir is not a potent inhibitor of OATP1B1-mediated pravastatin transport in vivo.
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Optimal period for the prophylactic administration of neutrophil elastase inhibitor for patients with esophageal cancer undergoing esophagectomy.
Iwahashi, M, Nakamori, M, Nakamura, M, Ojima, T, Naka, T, Yamaue, H
World journal of surgery. 2011;(7):1573-9
Abstract
BACKGROUND The present study was designed to determine the optimal period for the prophylactic administration of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing transthoracic esophagectomy. Sivelestat is reported to be effective in patients who undergo esophagectomy by providing an increased oxygenation ability and suppressing the serum inflammatory cytokines in the postoperative period. However, the optimal period for the prophylactic administration of Sivelestat remains to be elucidated. METHODS The 30 patients who underwent esophagectomy for thoracic esophageal cancer were enrolled in one of two groups. The initial 15 patients were assigned to group A and received intravenous infusion of Sivelestat sodium hydrate until postoperative day (POD) 2, and the subsequent 15 patients were assigned to group B and received Sivelestat until POD 5. Historical controls without Sivelestat administration were used. The postoperative courses and serum inflammatory cytokines were evaluated. RESULTS Sivelestat improved oxygenation in the postoperative period; however, there were no differences between the two groups in terms of duration of mechanical ventilation, intensive care unit stay, systemic inflammatory response syndrome, and postoperative change of oxygenation. In addition, there were no differences in the postoperative changes in the serum interleukin (IL)-6 and high mobility group box chromosomal protein 1. Although the serum IL-8 on POD 3 was lower in group B than in group A, the neutrophil elastase showed no difference between these groups. None of the patients in either group suffered respiratory complications. CONCLUSIONS The two-day administration of Sivelestat initiated immediately after intrathoracic manipulation was found to be sufficient for prophylactic use to prevent pulmonary complications by suppressing hypercytokinemia after esophagectomy.
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5.
Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis.
Moura, LM, Ramos, SF, Zamorano, JL, Barros, IM, Azevedo, LF, Rocha-Gonçalves, F, Rajamannan, NM
Journal of the American College of Cardiology. 2007;(5):554-61
Abstract
OBJECTIVES The objective of this study was to test the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor on the progression of moderate to severe aortic stenosis as measured by echocardiography. BACKGROUND Recent retrospective studies support the hypothesis that statins slow the progression of aortic stenosis. METHODS We performed an open-label, prospective study evaluating 121 consecutive patients with asymptomatic moderate to severe aortic stenosis (aortic valve area > or = 1.0 cm2; mean age 73.7 +/- 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months. RESULTS Sixty-one patients (50.4%) with elevated LDL (159.7 +/- 33.4 mg/dl), aortic valve velocity (3.65 +/- 0.64 m/s), and aortic valve area (1.23 +/- 0.42 cm2) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 +/- 37.4 mg/dl), aortic valve velocity (3.62 +/- 0.61 m/s), and aortic valve area (1.20 +/- 0.35 cm2) received no statin. During a mean follow-up of 73 +/- 24 weeks, the change in aortic valve area in the control group was -0.10 +/- 0.09 cm2/year versus -0.05 +/- 0.12 cm2/year in the rosuvastatin group (p = 0.041). The increase in aortic valve velocity was 0.24 +/- 0.30 m/s/year in the control group and 0.04 +/- 0.38 m/s/year in the rosuvastatin group (p = 0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group. CONCLUSIONS Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/NCT00114491?order = 1; NCT0014491).
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6.
Intravenous magnesium sulfate enhances the ability of intravenous ibutilide to successfully convert atrial fibrillation or flutter.
Tercius, AJ, Kluger, J, Coleman, CI, White, CM
Pacing and clinical electrophysiology : PACE. 2007;(11):1331-5
Abstract
BACKGROUND A previous randomized trial found that adjunctive use of intravenous magnesium (a total of 4 grams) can attenuate the corrected QT interval (QTc) prolongation associated with ibutilide, but its impact on ibutilide efficacy has not been elucidated. METHODS This was a cohort evaluation of 229 consecutive patients who received ibutilide in the presence or absence of intravenous magnesium. Multivariate logistic regression analysis was used to determine the impact of magnesium on ibutilide efficacy as well as the impact of magnesium dosing intensity on ibutilide efficacy. RESULTS The overall chemical conversion rate with ibutilide in the presence or absence of magnesium was 59.8%. The concurrent administration of magnesium (n = 141) was associated with a 78% increased odds of successful chemical conversion (adjusted odds ratio, AOR; 1.78 [95% confidence intervals,CI 1.02-3.09]) compared to those who did not receive magnesium (n = 88). Magnesium dosing intensity appeared to be an important determinant of ibutilide efficacy, with the 4 grams dose associated with a threefold increase in the odds of successful chemical conversion (AOR; 2.98 [95% CI 1.46-6.11). The 1 to 3 grams subgroup was associated with only a trend toward an improvement. There was only one case of Torsade de Pointes (TdP) which occurred in the no adjunctive magnesium group. CONCLUSIONS Concurrent use of magnesium enhanced the ability of ibutilide to successfully convert atrial fibrillation (AF) or flutter (AFl). The 4 grams magnesium dose appeared to provide the greatest benefit.
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Efficacy of expulsive therapy using nifedipine or tamsulosin, both associated with ketoprofene, after shock wave lithotripsy of ureteral stones.
Micali, S, Grande, M, Sighinolfi, MC, De Stefani, S, Bianchi, G
Urological research. 2007;(3):133-7
Abstract
Extracorporeal shock wave lithotripsy (ESWL) is currently considered one of the main treatments for ureteral stones. Some studies have reported the effectiveness of pharmacologic therapies (calcium antagonists or alpha-blockers) in facilitating ureteral stone expulsion after ESWL. We prospectively evaluated the efficacy, after ESWL, of nifedipine on upper-middle ureteral stones, and tamsulosin on lower ureteral stones, both associated to ketoprofene as anti-edema agent. From January 2003 to March 2005 we prospectively evaluated 113 patients affected by radiopaque or radiolucent ureteral stones. Average stone size was 10.16 +/- 2.00 mm (range 6-14 mm). Thirty-seven stones were located in the upper ureter, 27 in the middle ureter, and 49 in the lower ureter. All patients received a single session of ESWL (mean number of shock waves: 3,500) by means of a Dornier Lithotripter S (mean energy power for each treatment: 84%). Both ultrasound and X-ray were used for stone scanning. After treatment, 63 of 113 patients were submitted to medical therapy to aid stone expulsion: nifedipine 30 mg/day for 14 days administered to 35 patients with upper-middle ureteral stones (group A1) and tamsulosin 0.4 mg/day for 14 days administered to 28 patients with stones located in the distal ureter (group A2). The remaining 50 patients were used as a control group (29 upper-middle ureteral stones-B1-and 21 lower ureteral stones-B2-), receiving only pain-relieving therapy. No significant difference in stone size between the groups defined was observed. Stone clearance was assessed 1 and 2 months after ESWL by means of KUB, ultrasound scan and/or excretory urography. A stone-free condition was defined as complete stone clearance or the presence of residual fragments smaller than 3 mm in diameter. The stone-free rates in the expulsive medical therapy group were 85.7 and 82.1% for the nifedipine (A1) and tamsulosin (A2) groups respectively; stone-free rates in the control groups were 51.7 and 57.1% (B1 and B2, respectively). Five patients (14.3%) in group A1, 5 (17.8%) in group A2, 14 (48.3%) in group B1 and 9 (42.8%) in group B2 were not stone-free after a single ESWL session and required ESWL re-treatment or an endoscopic treatment. Medical therapy following ESWL to facilitate ureteral stone expulsion results in increased 1- and 2-month stone-free rates and in a lower percentage of those needing re-treatment. The efficacy of nifedipine for the upper-mid ureteral tract associated with ketoprofene makes expulsive medical therapy suitable for improving overall outcomes of ESWL treatment for ureteral stones.
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8.
Dorzolamide and corneal recovery from edema in patients with glaucoma or ocular hypertension.
Giasson, CJ, Nguyen, TQ, Boisjoly, HM, Lesk, MR, Amyot, M, Charest, M
American journal of ophthalmology. 2000;(2):144-50
Abstract
PURPOSE To investigate whether dorzolamide alters corneal hydration control in patients with glaucoma or ocular hypertension. METHODS Pachymetry, tonometry, and endothelial cell density were measured by a masked observer in 19 subjects with bilateral glaucoma or ocular hypertension. They were treated with 2% dorzolamide in one eye, and with saline in the other, before wearing contact lenses under patched eyes. Corneal thickness, measured each 30 minutes up to 4.5 hours after contact lens removal, enabled estimation of percentage recovery per hour and time for 95% of corneal thickness recovery for both eyes. Seven patients repeated this test after 1 year of dorzolamide use, and their results were compared with those of the preceding year. RESULTS After induction of hypoxic corneal edema, there was no significant difference between paired corneas in swelling levels (60.0+/-11.8 and 59.8+/-12.9 microm) (P = .94), time to 95% recovery (440.6+/-255.8 and 445.4+/-186.7 minutes) (P = .93), and percentage recovery per hour (38.1%+/-10.9% and 36.1%+/-9.6%) (P = .40). Subjects followed up after 1 year of dorzolamide use did not differ significantly in values of endothelial cell density, percentage recovery per hour, or time to 95% recovery from those obtained a year before. One subject developed persistent corneal edema after his stress test in the eye treated with dorzolamide. CONCLUSION There is no significant difference in the recovery from induced corneal edema after either a short-term or 1-year use of dorzolamide in patients with glaucoma or ocular hypertension with a normal corneal endothelium. One patient had persistent corneal edema after the stress test was performed on the dorzolamide-treated eye.