Metabolomic determination of pathogenesis of late-onset preeclampsia

Objective: Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE.

Methods: NMR-based metabolomics analysis was performed on 29 cases of late-PE and 55 unaffected controls. In order to achieve sufficient statistical power to perform the pathway analysis, these cases were combined with a group of previously analyzed specimens, 30 late-PE cases and 60 unaffected controls. Specimens from both groups of cases and controls were collected in the same clinical centers during the same time period. In addition, NMR analyses were performed in the same lab and using the same techniques.

Results: We identified abnormalities in branch chain amino acids (valine, leucine and isoleucine) and propanoate, glycolysis, gluconeogenesis and ketone body metabolic pathways. The results suggest insulin resistance and metabolic syndrome, mitochondrial dysfunction and disturbance of energy metabolism, oxidative stress and lipid dysfunction in the pathogenesis of late PE and suggest a potential role for agents that reduce insulin resistance in PE.

Conclusions: Branched chain amino acids are known markers of insulin resistance and strongly predict future diabetes development. The analysis provides independent evidence linking insulin resistance and late-PE and suggests a potentially important therapeutic role for pharmacologic agents that reduce insulin resistance for late-PE.     

Hypnotic and cardiovascular effects of proprietary and generic propofol formulations do not differ

PURPOSE: The aim of the study was to compare the potency of two different propofol formulations: proprietary and generic propofol using the bispectral index (BIS) monitoring. METHODS: Forty female patients undergoing breast surgery received propofol 3 mg x kg(-1) followed by propofol infusion adjusted to maintain a 40% BIS value, supplemented by 50% nitrous oxide. Proprietary or generic propofol was administered in a randomized double-blind manner. RESULTS: The propofol mg/BIS% ratio obtained after the bolus dose, the cumulative infused propofol mg/BIS% ratio at the end of each five-minute interval and the total dose of propofol administered as bolus + infusion were similar between the two groups. The two groups did not differ with regard to systolic and diastolic blood pressure, heart rate, end-tidal carbon dioxide and arterial oxygen saturation. CONCLUSION: The two propofol formulations are equipotent when hypnotic effect is assessed by BIS monitoring.     

Physicochemical and Toxicological Assay of Leachate from Malt Spent Rootlets Biochar

Bulletin of Environmental Contamination and Toxicology - The aim of this study was to characterize the leachate derived from biochar produced from malt spent rootlets (MSR) and to evaluate the...     

Metastatic bone disease from breast cancer: a review of minimally invasive techniques for diagnosis and treatment

Skeletal-related events in patients with metastatic bone disease include intractable severe pain, pathologic fracture, spinal cord and nerve compression, hypercalcemia and bone marrow aplasia. In patients with breast cancer, the skeleton is the most frequent site for metastases. Treatment options for metastatic bone disease in these patients include bisphosphonates, chemotherapeutic agents, opioids, hormonal therapy, minimally invasive/interventional and surgical techniques. Interventional oncology techniques for breast cancer patients with bone metastases include diagnostic (biopsy) and therapeutic (palliative and curative) approaches. In the latter, percutaneous ablation, augmentation and stabilization are included. The purpose of this article is to describe the basic concepts of biopsy, ablation, embolization and peripheral skeleton augmentation techniques in patients with metastatic bone disease from breast carcinoma. The necessity for a tailored approach applying different techniques for different cases and locations will be addressed.     

Liquid chromatography–mass spectrometry behavior of Girard's reagent T derivatives of oxosteroid intact phase II metabolites for doping control purposes

Intact phase II steroid metabolites have poor product ion mass spectra under collision-induced dissociation (CID) conditions. Therefore, we present herein the liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS/(MS)) behavior of intact phase II metabolites of oxosteroids after derivatization. Based on the fact that Girard's reagent T (GRT), as derivatization reagent, was both convenient and efficient in terms of the enhancement in the ionization efficiency and the production of diagnostic product ions related to the steroid moiety, the latter was preferably selected between methoxamine and hydroxylamine upon the model compounds of androsterone glucuronide and androsterone sulfate. Sixteen different glucuronides and 29 sulfate conjugated metabolites of anabolic androgenic steroids (AASs), available either as pure reference materials or synthesized/extracted from administration studies, were derivatized with GRT, and their product ion spectra are presented. Product ion spectra include in all cases high number of product ions that in some cases are characteristic for certain structures of the steroid backbone. More specifically, preliminary results have shown major differences in fragmentation pattern for 17α/17β-isomers of the sulfate conjugates, but limited differentiation for 17α/17β-isomers of glucuronide conjugates and for 3α/3β- and 5α/5β-stereoisomers of both sulfate and glucuronide conjugates. Further to the suggestion of the current work, application on mesterolone administration studies confirmed—according to the World Anti-Doping Agency (WADA) TD2015IDCR—the presence of seven intact phase II metabolites, one glucuronide and six sulfates with use of LC–ESI–MS/(MS).     

Sedation in digestive endoscopy: the Athens international position statements

Aliment Pharmacol Ther 2010; 32: 425–442

Summary

Background Guidelines and practice standards for sedation in endoscopy have been developed by various national professional societies. No attempt has been made to assess consensus among internationally recognized experts in this field. Aim To identify areas of consensus and dissent among international experts on a broad range of issues pertaining to the practice of sedation in digestive endoscopy. Methods Thirty‐two position statements were reviewed during a 1 ½‐day meeting. Thirty‐two individuals from 12 countries and four continents, representing the fields of gastroenterology, anaesthesiology and medical jurisprudence heard evidence‐based presentations on each statement. Level of agreement among the experts for each statement was determined by an open poll. Results The principle recommendations included the following: (i) sedation improves patient tolerance and compliance for endoscopy, (ii) whenever possible, patients undergoing endoscopy should be offered the option of having the procedure either with or without sedation, (iii) monitoring of vital signs as well as the levels of consciousness and pain/discomfort should be performed routinely during endoscopy, and (iv) endoscopists and nurses with appropriate training can safely and effectively administer propofol to low‐risk patients undergoing endoscopic procedures. Conclusions While the standards of practice vary from country to country, there was broad agreement among participants regarding most issues pertaining to sedation during endoscopy.