Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents. The mechanisms underlying nitrate tolerance remain incompletely defined and are likely multifactorial. One mechanism seems to be a diminished bioconversion of nitroglycerin, another seems to be the induction of vascular oxidative stress, and a third may include neurohumoral adaptations. Recent studies have revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role in the development of nitrate and crosstolerance. The present review focus first on the role of oxidative stress and second on the role of ALDH-2 in organic nitrate bioactivation leading to the development of tolerance and cross-tolerance (endothelial dysfunction) in response to nitroglycerin treatment. Recently, the role of mitochondrial oxidative stress in the development of nitrate tolerance was demonstrated in a mouse model with a heterozygous deletion of manganese superoxide dismutase (MnSOD^+/?), which is the mitochondrial isoform of this enzyme. Studies from our own laboratory have provided evidence for cross-talk between mitochondrial and cytosolic (Nox-dependent) sources of ROS. We close this review by focusing on the protective properties of the organic nitrate pentaerithrityl tetranitrate, which upregulates enzymes that have strong antioxidative activity, such as heme oxygenase-1 and ferritin, thereby preventing the development of tolerance and endothelial dysfunction.     

气相色谱法测定硝酸布康唑有机溶剂残留

目的建立气相色谱法测定硝酸布康唑中有机溶剂丙酮、乙酸乙酯、二氯甲烷的含量。方法采用毛细管气相色谱法,SE-54色谱柱,程序升温,氮气为载气,氢火焰离子化(FID)检测器,内标法(甲醇为内标)计算含量。结果在该色谱条件下,测得丙酮、乙酸乙酯、二氯甲烷残留溶剂均有良好的线性关系(r=0.9948～0.9998);RSD分别为0.297%,2.23%,0.392%;最低检测限分别为2.04,1.42,1.84ng·mL-1;三批样品中上述有机溶剂残留量均符合要求。结论该方法灵敏、准确、可靠,适合于硝酸布康唑中残留有机溶剂的测定。     

Negative pressure wound therapy with instillation: a pilot study describing a new method for treating infected wounds

This data review reports the results of 15 patients who were treated with Vacuum-Assisted Closure (VAC) negative pressure therapy system in addition to the timed, intermittent delivery of an instilled topical solution for management of their complex, infected wounds. Prospective data for 15 patients treated with negative pressure wound therapy (NPWT)-instillation was recorded and analysed. Primary endpoints were compared to a retrospective control group of 15 patients treated with our institution's standard moist wound-care therapy. Culture-specific systemic antibiotics were prescribed as per specific patient need in both groups. All data were checked for normality of distribution and equality of variance and appropriate parametric and non parametric analyses were conducted. Compared with the standard moist wound-care therapy control group, patients in the NPWT-instillation group required fewer days of treatment (36.5 +/- 13.1 versus 9.9 +/- 4.3 days, P < 0.001), cleared of clinical infection earlier (25.9 +/- 6.6 versus 6.0 +/- 1.5 days, P < 0.001), had wounds close earlier (29.6 +/- 6.5 versus 13.2 +/- 6.8 days, P < 0.001) and had fewer in-hospital stay days (39.2 +/- 12.1 versus 14.7 +/- 9.2 days, P < 0.001). In this pilot study, NPWT instillation showed a significant decrease in the mean time to bioburden reduction, wound closure and hospital discharge compared with traditional wet-to-moist wound care. Outcomes from this study analysis suggest that the use of NPWT instillation may reduce cost and decrease inpatient care requirements for these complex, infected wounds.     

Systemic plasma levels of nitrite/nitrate (NOx) reflect brachial flow-mediated dilation responses in young men and women

1. The aim of the present study was to determine the relationship between plasma levels of nitrite/nitrite (NO(x)) and brachial flow-mediated dilation (FMD) in healthy young men and women. 2. Brachial artery FMD was assessed non-invasively using high-resolution ultrasound in 36 young men and women (21 +/- 3 years; 18 men and 18 women). Blood samples for NO(x) assays were collected from an indwelling venous catheter in the forearm following an overnight fast and a 36 h low-nitrate diet. 3. Plasma levels of NO(x) were related to peak brachial FMD% (r = 0.53; P = 0.001). The relationship was maintained when the brachial dilation was expressed as absolute diameter change (Deltamm; r = 0.51; P = 0.002) and when it was normalized (/s) to the mean shear rate (r = 0.50; P = 0.002). 4. The present study demonstrates a relationship between peak FMD in the brachial artery and plasma levels of NO(x) in young men and women. This relationship suggests that brachial FMD and/or plasma NO(x) may be used as markers of peripheral endothelial function.     

Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanism of action and relevance to psychiatric disorders

Dehydroepiandrosterone (DHEA) is synthesized in the brain and several studies have shown that this steroid is a modulator of synaptic transmission. The effect of DHEA, and its sulfate ester DHEAS, on glutamate and GABA neurotransmission has been extensively studied but some effects on other neurotransmitter systems, such as dopamine, serotonin and nitric oxide, have also been reported. This review summarizes studies showing the effect of DHEA and DHEAS on neurotransmitter systems at different levels (metabolism, release, reuptake, receptor activation), as well as the activation of voltage-gated ion channels and calcium homeostasis, showing the variety of effects that these steroids exert on those systems, allowing the discussion of its mechanisms of action and its relevance to psychiatric disorders.     

Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits

In this study we aimed to evaluate the in vivo effects of myrtle oil (myrtii oleum) on the antioxidant enzymes such as superoxide dismutase and catalase, the levels of malondialdehyde in liver tissues as an index of lipid peroxidation and nitrite–nitrate levels in normoglycaemic and alloxan-induced diabetic and MO-treated rabbits. In our previous study, we assumed that MO with a dose of 50 mg/kg, possesses a hypoglycemic activity and this activity was independent from the effects of insulin. Myrtle oil exerts its hypoglycemic activity by enhanced glycolysis, glycogenesis and decreased glycogenolysis. What is more glucose load data strongly suggest that MO treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose, so MO could be an -glycosidase enzyme inhibitor which had a hypoglycaemic effect only on alloxan-induced diabetic rabbits on the fourth hour and on orally glucose loaded group. The major finding of this new study is that, MO may not offer any protection against oxidative stress during acute studies in normoglycemic and diabetic groups. Although the levels of superoxide dismutase and catalase enzyme activities did not change during acute studies in diabetes + MO group, there was a significant change at the end of 21 days. There is a very limited knowledge about MO and its effects on diabetes. Therefore, we tried to explain the mechanism that might underlie the protective effects of MO with this paper.     

Chemical closure of chronic tympanic membrane perforations

BACKGROUND: The purposes of closing chronic dry perforations of the tympanic membrane are to improve hearing and prevent middle ear infections. Before the use of the operating microscope and improved instrumentation, tympanic membrane perforations were closed by application of chemicals or with a temporary patch. Today, although surgery is the treatment of choice, small dry perforations may be successfully closed by chemical means in an office setting. METHODS: Twenty-eight of the 69 patients with chronic dry tympanic membrane perforations on the surgical waiting list at Hawke's Bay Regional Hospital, Hastings, New Zealand, underwent attempts at chemical myringoplasty. Two techniques were used: (i) cautery of the rim of the perforation with a silver nitrate bead on a metal probe and (ii) application of a urea ointment patch covering and overlapping the perforation. RESULTS: Eighteen of the 28 patients (64%) treated by chemical means experienced closure of their tympanic membrane perforations. Successful closure was achieved in 26% of the patients on the waiting list during the 6-month period. CONCLUSION: Chemical myringoplasty is not only of historical interest. It is an effective means of tympanic membrane closure in selected patients, thereby reducing the surgical waiting list and saving time and money for the patient, surgeon and hospital.     

Immunogold-Silver Staining Overview

Abstract

Silver stains are commonly used in histology laboratories to demonstrate a variety of tissue substances. With the passage of time. it has become evident that several of the chemicals used in silver stains, as well as silver compounds themselves, pose hazards to laboratory workers. Disposal of these chemicals also poses a problem.

This article briefly outlines some of the hazards of working with the chemicals used in silver stains. A comprehensive chemical hygiene plan, which must be developed for each laboratory, provides a standard operating procedure for working safely with chemicals. Material safety data sheets provide information on each chemical used in the laboratory and must be available. The use of several of the chemicals employed in silver stains is covered by Federal, state, and local laws. The state and local laws may be more stringent than the Federal laws. (The J Histotechnol 19:197, 1996)     

Nitrate and bacterial contamination in well waters in Vinh Phuc province, Vietnam

Measurements were made of the nitrate concentration and bacterial contamination of groundwater samples taken from both dug wells and bores in the commune of Hop Thinh', in the administrative district of Vinh Phuc, Vietnam. A significant number (18%) of samples had nitrate concentrations in excess of the WHO Guideline value for drinking water of 50 mg L^-1, with a higher proportion in the dug wells (29%) than the bores (3.8%). High concentrations of thermotolerant coliforms were found in many of the dug wells and even in the deeper drilled bores. At the time of the study no Shigella or other infectious organisms were found. There was no correlation between nitrate concentration and bacterial content and it is concluded that nitrate concentration is not a good indicator for bacterial contamination.