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At least 415 records · Page 23Linked to original sources
PubMed1993

Nitrate therapy and the development of tolerance.

The efficacy of organic nitrates in the treatment of acute episodes of angina pectoris is unquestioned. However, long-term use of these agents is associated with the development of tolerance or of reduced efficacy over time when given in doses or formulations that maintain therapeutic blood levels for 24-hour periods. Thus, the role of long-term use of nitrates in prophylactic treatment of stable angina has been questioned. The purpose of this brief review is to evaluate nitrate tolerance, a key issue in the prophylactic use of nitrates, as well as to review what is known about clinical rebound. These issues are discussed, and ways of preventing tolerance development are explored. Intermittent therapy involving a dose-free interval during each 24-hour period helps prevent tolerance.

Angina Pectoris↗
PubMed2000

Lens opacifications detected by slitlamp biomicroscopy are associated with exposure to organic nitrate explosives.

CONTEXT: Unusual cataracts (flecks) have been reported to occur at very low levels of trinitrotoluene exposure, but prevalence estimates vary widely. Cataracts have not been reported among workers in the United States exposed to organic nitrate explosives. OBJECTIVES: To determine the prevalence of unusual cataracts in a population of workers in the United States exposed to organic nitrate explosives, to determine whether associations exist with reported cataract risk factors, and to determine if other eye effects (eg, retinal hemorrhage) are associated with exposure. DESIGN: Cohort prevalence study. SETTING: A university-based ophthalmologic clinic. SUBJECTS: Sixty-one workers from an explosives plant comprised the exposed group. The comparison group consisted of 56 workers using chemicals other than organic nitrate explosives. OUTCOME MEASURES: The primary outcome measure was opacifications (flecks) of the crystalline lens, graded clinically on a scale of 0 to 4 +. Additional measures included visual acuity, applanation tonometry, and clinical evaluation using standard examination techniques. RESULTS: Sixty-three percent of the workers had anterior cortical lens opacifications in a pattern of peripheral flecks. Exposed subjects were 18 times more likely to exhibit changes than those not exposed, a statistically significant association (95% confidence interval [CI], 5.0-65.0; P<.001). A statistically significant association with the duration of exposure was also found. CONCLUSIONS: Asymptomatic, low-grade cataracts (flecks) were identified in 63% of the workers exposed to pentolite. No other eye effects were found to be associated with exposure. Cataracts were not associated with other known risk factors, but were associated with the duration of exposure. Biomicroscopy is widely available and useful for detecting changes in the asymptomatic stages.

Adult↗
PubMed1999

The antioxidant defense protein ferritin is a novel and specific target for pentaerithrityl tetranitrate in endothelial cells.

The organic nitrate pentaerithrityl tetranitrate (PETN) is known to exert long-term antioxidant and antiatherogenic effects by as yet unidentified mechanisms. In porcine aortic endothelial cells, a 24 h incubation with PETN (1-100 microM) or its metabolite pentaerithrityl trinitrate (PETriN) increased levels of the antioxidant protein ferritin up to three-fold over basal, whereas isosorbide dinitrate and isosorbide-5-mononitrate were without significant effect under these conditions. PETriN-induced ferritin expression was blocked by the NO scavenger PTIO but remained unaltered in the presence of ODQ, an inhibitor of soluble guanylyl cyclase. 8-Bromo cyclic GMP and dibutyryl cyclic GMP did not influence basal ferritin synthesis. The iron chelator desferrioxamine abolished ferritin induction by PETriN. Our results show that PETN or its active metabolite PETriN induce ferritin synthesis through NO- and iron-dependent but cyclic GMP-independent pathways. Increased activity of ferritin may contribute to, and at least in part explain, the specific antiatherogenic and antioxidant action of PETN.

Animals↗
PubMed2002

Heme oxygenase-1 induction may explain the antioxidant profile of pentaerythrityl trinitrate.

The organic nitrate pentaerythrityl tetranitrate (PETN) is known to exert long-term antioxidant and antiatherogenic effects by as yet unidentified mechanisms. In cultured endothelial cells derived from human umbilical vein, the active PETN metabolite PETriN (0.01-1 mM) increased heme oxygenase (HO)-1 mRNA and protein levels in a concentration-dependent fashion. HO-1 induction was accompanied by a marked increase in catalytic activity of the enzyme as reflected by enhanced formation of carbon monoxide and bilirubin. Pretreatment with PETriN or bilirubin at low micromolar concentrations protected endothelial cells from hydrogen peroxide-mediated toxicity. HO-1 induction and endothelial protection by PETriN were not mimicked by isosorbide dinitrate, another long-acting nitrate. The present study demonstrates that PETriN stimulates mRNA and protein expression as well as enzymatic activity of the antioxidant defense protein HO-1 in endothelial cells. Increased HO-1 expression and ensuing formation of cytoprotective bilirubin may contribute to and explain the specific antioxidant and antiatherogenic actions of PETN.

Animals↗
PubMed1995

Effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate in experimental atherosclerosis.

This study was performed to determine whether long-term treatment with organic nitrovasodilators exhibit pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in the cholesterol fed rabbit. The major finding of this study is that PETN, but not ISMN, decreases the extent of aortic intimal lesions and the development of endothelial dysfunction. In addition, 15 weeks of feeding a diet enriched with either PETN or ISMN did not induce a measurable extent of vascular in-vitro tolerance to the vasodilator activity of these drugs.

Animals↗
PubMed1995

The exercise-induced increase in plasma levels of endothelin-1 is enhanced in patients with atherosclerotic coronary artery disease. Modulation by pentaerithrityltetranitrat (PETN).

BACKGROUND AND OBJECTIVE: Previous studies have suggested that endothelin (ET)-1 with its marked vasoconstrictive potency may play a role in the induction of coronary artery spasms. Furthermore, it was demonstrated using in-vitro vessel preparations that the secretion of ET-1 by the vascular endothelium is enhanced in the presence of atherosclerotic alterations. The objective of the present study was to investigate a) the effects of ergometric exercise on ET-1 plasma concentrations in 10 patients with coronary artery disease (CAD) as compared to an age and sex matched control group and b) the modulatory role of the orally administered organic nitrate, pentaerithrityltetranitrat (PETN), in patients with CAD. PATIENTS AND METHODS: 10 male patients with CAD confirmed by coronarography and 10 male healthy controls underwent a bicycle ergometry according to the WHO-standards upt to 125 watts. Venous blood samples for determination of ANP and ET-1 plasma concentrations were drawn in supine position directly before and 5 min after ergometric exercise. Subsequently, patients were randomized and treated for 3 days in a crossover design either with placebo or PETN (150 mg b.i.d.). RESULTS: Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls), resp. (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the placebo-treated patient group, whereas they remained constant (5.5 +/- 0.7 pg/ml) in the PETN-treated patient group. Blood pressure and heart rate were not modified by the PETN-treatment. ET-1 plasma levels remained unaffected by ergometric exercise in controls. DISCUSSION: In contrast to healthy controls ergometric exercise induced an increase in ET-1 plasma concentrations in patients with CAD that may be potentially harmful by promoting coronary vasospasms. The almost complete blunting of the ET-1-increase in the presence of PETN-therapy may result from local-hemodynamic effects of the organic nitrate; it may be hypothesized that the nitrate-induced rise in local NO-concentrations counteracts ET-secretion. The findings of the present study are in accordance with the beneficial clinical effects of organic nitrates in patients with CAD.

Administration, Oral↗
PubMed2005

[Silica-containing urinary stones--clinical issues to keep in mind].

Formation of calculi in efferent urinary passages is always due to supersaturation of urinary calculi substances and associated increased crystallization. Apart from the typical calculi, consisting of calcium oxalate, inorganic phosphates, uric acid or cystine, there are occasional signs of rare substance classes. Although more than 50 silicate stones have already been reported internationally, this stone entity remains relatively unknown. In particular, the occurrence of silicate stones in the absence of magnesium trisilicate abuse is extremely rare. A medium-sized left-sided ureterolith was removed from a 54-year-old male patient using a ureteroscope. X-ray diffraction showed it to be a compound stone consisting of 40% silicate. The patient, who in 1986 was living close to the nuclear reactor accident in Chernobyl, showed no signs of a constant uptake of magnesium trisilicate. However, he had undergone partial (2/3) gastrectomy 4 months before for a drug-refractory gastric ulcer, which had been diagnosed at the end of the 1980s and treated with excessive dosages of a magnesium trisilicate antacid preparation until the time of the operation. The patient had also been suffering from unstable angina pectoris since 1986 and treated with Pentalong (pentaerythrityltetranitrate) for 17 years. We were also able to detect silicium dioxide in components of this drug using X-ray diffraction. Silicate uroliths are extremely rare but they can be clearly identified by X-ray diffraction or infrared spectroscopy and distinguished from artifacts or quartz pebbles. Formation of calculi can be prevented by increasing diuresis as well as switching to a different drug and reducing the dosage.

Angina, Unstable↗