Oxidative damage in the central nervous system: protection by melatonin.

Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects.

Melatonin (N-acetyl-5-methoxytryptamine), an endogenously produced indole found throughout the animal kingdom, was recently reported, using a variety of techniques, to be a scavenger of a number of reactive oxygen and reactive nitrogen species both in vitro and in vivo. Initially, melatonin was discovered to directly scavenge the high toxic hydroxyl radical (*OH). The methods used to prove the interaction of melatonin with the *OH included the generation of the radical using Fenton reagents or the ultraviolet photolysis of hydrogen peroxide (H202) with the use of spin-trapping agents, followed by electron spin resonance (ESR) spectroscopy, pulse radiolysis followed by ESR, and several spectrofluorometric and chemical (salicylate trapping in vivo) methodologies. One product of the reaction of melatonin with the *OH was identified as cyclic 3-hydroxymelatonin (3-OHM) using high-performance liquid chromatography with electrochemical (HPLC-EC) detection, electron ionization mass spectrometry (EIMS), proton nuclear magnetic resonance (1H NMR) and COSY 1H NMR. Cyclic 3-OHM appears in the urine of humans and other mammals and in rat urine its concentration increases when melatonin is given exogenously or after an imposed oxidative stress (exposure to ionizing radiation). Urinary cyclic 3-OHM levels are believed to be a biomarker (footprint molecule) of in vivo *OH production and its scavenging by melatonin. Although the data are less complete, besides the *OH, melatonin in cell-free systems has been shown to directly scavenge H2O2, singlet oxygen (1O2) and nitric oxide (NO*), with little or no ability to scavenge the superoxide anion radical (O2*-) In vitro, melatonin also directly detoxifies the peroxynitrite anion (ONOO-) and/or peroxynitrous acid (ONOOH), or the activated form of this molecule, ONOOH*; the product of the latter interaction is proposed to be 6-OHM. How these in vitro findings relate to the in vivo antioxidant actions of melatonin remains to be established. The ability of melatonin to scavenge the lipid peroxyl radical (LOO*) is debated. The weight of the evidence is that melatonin is probably not a classic chain-breaking antioxidant, since its ability to scavenge the LOO* seems weak. Its ability to reduce lipid peroxidation may stem from its function as a preventive antioxidant (scavenging initiating radicals), or yet unidentified actions. In sum, in vitro melatonin acts as a direct free radical scavenger with the ability to detoxify both reactive oxygen and reactive nitrogen species; in vivo, it is an effective pharmacological agent in reducing oxidative damage under conditions in which excessive free radical generation is believed to be involved.

Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence

Two antioxidative lactobacilli strains as promising probiotics.

Photoinduced hydroxyl radical and photocatalytic activity of samarium-doped TiO2 nanocrystalline

Terephthalic acid: A dosimeter for the detection of hydroxyl radicals in vitro

Cholecystokinin is a gastrointestinal hormone known to physiologically regulate pancreatic protein secretion and gallbladder contractility. Some evidence suggests that cholecystokinin is also involved in the maintenance of gastrointestinal mucosal integrity. This study was undertaken to ascertain whether cholecystokinin could prevent the gastric mucosal injury induced by acidified ethanol and what role prostaglandins, and type A and type B cholecystokinin receptors might play in this process. Conscious, fasted rats were given subcutaneous saline or cholecystokinin octapeptide (10–100 µg/kg) 30 min before a l-ml oral gastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Five minutes later, rats were sacrificed and the total area of macroscopic injury quantitated (square millimeters). In additional experiments using a similar protocol, 1 ml of either the cyclooxygenase inhibitor, indomethacin (5 mg/kg), a type A cholecystokinin receptor antagonist, L-364,718 (0.01–1 mg/kg), or the type B cholecystokinin receptor antagonist, L-365,260 (12.5–25 mg/kg) was given intraperitoneally 30 min prior to pretreatment with cholecystokinin octapeptide. Cholecystokinin octapeptide dose-dependently prevented mucosal injury from acidified ethanol (corroborated by histology). The protective effect of cholecystokinin octapeptide was completely negated by L-364,718 and partially reversed by indomethacin, while L-365,260 had no discernible effect in this process. In a further study, cholecystokinin was unable to prevent the damaging effects of aspirin and the inhibition of endogenous prostaglandins. Thus, it appears that cholecystokinin is able to maintain mucosal integrity in the face of a damaging insult by activation of type A cholecystokinin receptors, an effect mediated, at least in part, through the release of endogenous prostaglandins.

Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat - Role of endogenous prostaglandins

This study aimed to determine the causes of sudden cardiac arrest (SCA) in apparently healthy children at a single center in the era of primary prevention (screening questionnaire [SQ]) and secondary prevention (automated external defibrillator [AED] and the automated implantable cardioverter defibrillator [AICD]). Any child 0 to 18 years of age without prior known disease, except for attention deficit disorder, who underwent out-of-the hospital cardiopulmonary resuscitation was included in the study as a SCA subject. A retrospective chart review was used to evaluate the efficacy of the SQ, electrocardiogram (ECG), chest roentgenogram (CXR), and echocardiogram. The findings showed that for 44 of 6,656 children admitted to intensive care with SCA, an AED was used for 39%, an AICD was placed in 18%,and survival to hospital discharge was 50%. The etiology for SCA was identified in 57% of the cases, mostly in those older than 1 year, and the majority of these had a cardiac etiology (50%), whereas 7% had rupture of an arteriovenous malformation. Stimulant medication use was seen in 11% of the SCA subjects. In the best-case scenario of hypothesized primary prevention, a prior SQ, CXR, ECG, or echocardiogram may have detected respectively 18, 9, 23 and 16% of the at-risk cases, and 32% of the cases may have been detected with ECG and SQ together. Based on a historical control cohort, a positive ECG was significantly higher in the children with SCA (p = 0.014). An ECG together with a screening SQ may be more effective in identifying children potentially at risk for SCA than an SQ alone.

Sudden Unexplained Cardiac Arrest in Apparently Healthy Children: A Single-Center Experience

Computed tomography (CT) evaluation of the acute polytrauma patient has become well established as a mainstay of ER triage in hemodynamically stable patients. The radiologist plays a pivotal role in directing management by identifying and appropriately categorizing the severity of a patient's injuries. High-grade liver injuries have undergone an increasing trend of nonoperative management over the last several decades, with concurrent decrease in mortality. However, we present a case of a patient with a grade V liver laceration, in whom a rare portacaval shunt was also present. In the setting of this rare injury, the radiologist will likely be the first person to recognize and categorize a severe complication, which may indicate the need for a fundamental change in patient management.

http://www.radiologycases.com/index.php/radiologycases/article/download/1817/pdf

Nathaniel H. P. Strobel

Papers

Terephthalic acid: A dosimeter for the detection of hydroxyl radicals in vitro

Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat - Role of endogenous prostaglandins

Sudden Unexplained Cardiac Arrest in Apparently Healthy Children: A Single-Center Experience

Traumatic Portacaval Shunt: A Case Report and Literature Review