Using an UPLC/MS-based untargeted metabolomics approach for assessing the antioxidant capacity and anti-aging potential of selected herbs

Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis, Lavandula officinalis, Matricaria chamomilla, Camellia sinensis and Pelargonium graveolens. The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties.

Aging is an unavoidable fate that afflicts all life, during this process in mammals, reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging.     

Glutathione‐S‐transferase‐oxidative stress relationship in the internal spermatic vein blood of infertile men with varicocele

This study aimed to assess glutathione‐S–transferase (GST) enzyme‐ oxidative stress (OS) relationship in the internal spermatic vein (ISV) of infertile men associated with varicocele (Vx). Ninety five infertile oligoasthenoteratozoospemic (OAT) men associated with Vx were subjected to history taking, clinical examination and semen analysis. During inguinal varicocelectomy, GST, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated in the blood samples drawn from ISV and median cubital veins. The mean levels of GST, GPx were significantly decreased and the mean level of GPx was significantly increased in the ISV compared with the peripheral blood. The mean level of GST and GPx in the ISV was significantly decreased, and the mean level of MDA was significantly increased in Vx grade III compared with Vx grade II cases. There was nonsignificant difference in the mean level of GST in the ISV in unilateral Vx cases compared with bilateral Vx cases. There was significant positive correlation of GST with sperm count, sperm motility, GPx and significant negative correlation with sperm abnormal forms, MDA. It is concluded that ISV of infertile men associated with Vx has decreased levels of GST compared with peripheral venous circulation that is correlated with both OS and Vx grade.     

Adding a custom made pressure release valve during air enema for intussusception: A new technique

Background:

Non-surgical reduction remains the first line treatment of choice for intussusception. The major complication of air enema reduction is bowel perforation. The authors developed a custom made pressure release valve to be added to portable insufflation devices, delivering air at pressures accepted as safe for effective reduction of intussusception in children under fluoroscopic guidance. The aim of this study was to develop a custom made pressure release valve that is suitable for the insufflation devices used for air enema reduction of intussusception and to put this valve into regular clinical practice.

Materials and Methods:

An adjustable, custom made pressure release valve was assembled by the authors using readily available components. The valve was coupled to a simple air enema insufflation device. The device was used for the trial of reduction of intussusception in a prospective study that included 132 patients.

Results:

The success rate for air enema reduction with the new device was 88.2%. The mean pressure required to achieve complete reduction was 100 mmHg. The insufflation pressure never exceeded the preset value (120 mmHg). Of the successful cases, 58.3% were reduced from the first attempt while 36.1% required a second insufflation. Only 5.55% required a third insufflation to complete the reduction. In cases with unsuccessful pneumatic reduction attempt (18.1%), surgical treatment was required. Surgery ranged from simple reduction to resection with a primary end to end anastomosis. No complications from air enema were recorded.

Conclusions:

The authors recommend adding pressure release valves to ensure safety by avoiding pressure overshoot during the procedure.Key words: Air enema, intussusception, pneumatic, pressure release, reduction, safety, valve     

Brain Neuronal Degeneration Caused by Episodic Alcohol Intoxication in Rats: Effects of Nimodipine, 6,7-Dinitro-quinoxaline-2,3-dione, and MK-801

Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a role for excitotoxicity, we have attempted to prevent the degeneration using antagonists that are neuroprotective in this type of brain damage. In an initial study, continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration in several brain regions and severe behavioral intoxication that precluded survival if combined with high blood alcohol levels (～300 mg/dl). Moreover, the lower, nonneurotoxic blood alcohol levels (～150 mg/dl) that were compatible with survival worsened the MK-801-induced brain damage. In a subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801 (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a voltage-gated Ca²⁺ channel blocker, reduced the neuronal damage in the dentate gyrus, but greatly increased it in the piriform cortex when administered intragastrically at 600 mg/kg/day; it provided no protection from alcohol-dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous intracere-broventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro-quinoxa-line-2,3-dione, a glutamate/α-amino-3-hydroxy-5-methyl-4-isoxazole receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any brain region. We conclude that brain damage from episodic “binge” alcohol intoxication is not primarily mediated by excitotoxic mechanisms, implying that other, nonexcrtotoxic pathophysiological mechanisms, are involved. Furthermore, MK-801, far from protecting from the alcohol-induced damage, at high doses causes widespread neuropathology that is significantly potentiated by alcohol.     

Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16–40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.