Parallel Metabolomics and Lipidomics of a PSMA/GCPII Deficient Mouse Model Reveal Alteration of NAAG Levels and Brain Lipid Composition.

Glutamate carboxypeptidase II (GCPII, also known as PSMA or FOLH1) is responsible for the cleavage of N-acetyl-aspartyl-glutamate (NAAG) to N-acetyl-aspartate and glutamate in the central nervous system and facilitates the intestinal absorption of folate by processing dietary folyl-poly-γ-glutamate in the small intestine. The physiological function of GCPII in other organs like kidneys is still not known. GCPII inhibitors are neuroprotective in various conditions (e.g., ischemic brain injury) in vivo; however, their utilization as potential drug candidates has not been investigated in regard to not yet known GCPII activities. To explore the GCPII role and possible side effects of GCPII inhibitors, we performed parallel metabolomic and lipidomic analysis of the cerebrospinal fluid (CSF), urine, plasma, and brain tissue of mice with varying degrees of GCPII deficiency (fully deficient in Folh1, -/-; one allele deficient in Folh1, +/-; and wild type, +/+). Multivariate analysis of metabolites showed no significant differences between wild-type and GCPII-deficient mice (except for NAAG), although changes were observed between the sex and age. NAAG levels were statistically significantly increased in the CSF, urine, and plasma of GCPII-deficient mice. However, no difference in NAAG concentrations was found in the whole brain lysate likely because GCPII, as an extracellular enzyme, can affect only extracellular and not intracellular NAAG concentrations. Regarding the lipidome, the most pronounced genotype-linked changes were found in the brain tissue. In brains of GCPII-deficient mice, we observed statistically significant enrichment in phosphatidylcholine-based lipids and reduction of sphingolipids and phosphatidylethanolamine plasmalogens. We hypothesize that the alteration of the NAA-NAAG axis by absent GCPII activity affected myelin composition. In summary, the absence of GCPII and thus similarly its inhibition do not have detrimental effects on metabolism, with just minor changes in the brain lipidome.

Nanofibrous material from hyaluronan derivatives preserving fibrous structure in aqueous environment.

Nanofibrous materials produced from natural polymers have wide range of potential uses in regenerative medicine. This paper focuses on preparation of nanofibrous layers produced from intentionally hydrophobized derivatives of hyaluronan, which is known for its ability to promote wound healing. This structural modification of hyaluronan expands the range of potential uses of this promising material, which is otherwise limited due to the hydrophilic nature of hyaluronic acid. The aim of this research was preparation of nanofibrous material that would retain its fibrous structure and dimensional stability even after getting into contact with an aqueous medium, which is impossible to achieve with layers composed solely of native hyaluronan. As a result, such material would be able to retain its breathability and good mechanical properties when both dry and wet. Furthermore, all prepared materials were proved non-toxic for cells. This self-supporting nanofibrous matrix can be used as a scaffold, or porous wound dressing.

The pentafluorophenyl stationary phase shows a unique separation efficiency for performing fast chromatography determination of highbush blueberry anthocyanins.

A high-performance liquid chromatography method using an alternative pentafluorophenyl (PFP) core-shell stationary phase has been developed and used for rapid separation of 23 anthocyanins in a highbush blueberry Bluehaven cultivar. A high efficiency of separation of anthocyanins was achieved in the core-shell column Kinetex PFP, 150×4.6mm (particle size 2.6µm) with a 5×4.6mm precolumn, using a simple linear gradient elution with a mobile phase of acetonitrile and a water solution of 2% formic acid at a flow rate of 1.0ml/min and at a temperature of 50°C. The detection wavelength was set at 520nm for detection of all anthocyanins. The homogenized blueberry sample (Bluehaven cultivar) was extracted using pure methanol with 1.3% formic acid using an ultrasound bath for 20min and then filtrated. A 5-µL sample volume was directly injected into the HPLC system. The developed method showed an efficient separation of 23 anthocyanins in a total runtime of 21min. The potential of the pentafluorophenyl phase for efficient separation was demonstrated on a wide range of anthocyanins varying in glycosylation and acylation patterns found in highbush blueberries. The fluorinated stationary phase showed an alternative and complementary separation approach providing unique aromatic and polar selectivity in comparison with common C-18 phases.

Can difficult intubation be easily and rapidly predicted?

AIM: Failed endotracheal intubation and inadequate ventilation with subsequent insufficient oxygenation can result in serious complications potentially leading to permanent health damage. Difficult intubation may occur not only in patients with apparent pathologies in the orofacial region but also, unexpectedly, in those without abnormalities. This study aimed at finding anthropometric parameters that are easy to examine and that would aid in predicting difficult intubation. METHOD: A case-control study was undertaken. Based on defined criteria, 15 parameters were examined in patients with unanticipated difficult intubation. The parameters included a previous history of difficult intubation, pathologies associated with difficult intubation, clinical symptoms of airway pathology, the Mallampati score, upper lip bite test, receding mandible, and cervical spine and temporomandibular joint movement. Thyromental, hyomental and sternomental distances and inter-incisor gap were measured. The methods were precisely defined and the measurements were carried out by a trained anesthesiologist. Statistical analysis was performed on data from 74 patients with difficult intubation and 74 control patients with easy intubation. RESULTS: Significant predictors of difficult intubation were inter-incisor gap (IIG), thyromental distance (TMD) and class 3 limited movement of the temporomandibular joint. The IIG and TMD cut-offs were set at 42 mm and 93 mm, respectively. CONCLUSION: The results will be used to confirm these predictors in an anesthesiology clinic along with the aid of the laryngoscopic findings to improve the prediction of unanticipated difficult intubation.

Incidence of postoperative nausea and vomiting in patients at a university hospital. Where are we today?

AIM: To determine the incidence of postoperative nausea and vomiting (PONV), identify risk factors, assess treatment and its effectiveness. DESIGN: A prospective, observational, questionnaire- and interview-based study. SETTING: Standard and intensive care units of the following university hospital departments: abdominal, thoracic and vascular surgery; gynecology; plastic and esthetic surgery; urology; and traumatology. MATERIAL AND METHODS: Adult patients scheduled for elective surgery who gave informed consent were enrolled. A questionnaire-based study was performed on the first postoperative day. The collected data relevant to PONV were statistically analyzed. CONCLUSION: The incidence of PONV was significantly lower than generally presumed and was related to the patient gender, type of surgery and overall health status. PONV was more frequent in obese patients and when drugs antagonizing opioids or muscle relaxants were used. Early administration of antiemetic agents led to considerably less discomfort.