Cerebral glucose utilisation in hepatitis C virus infection-associated encephalopathy

Patients with hepatitis C virus (HCV) infection frequently show neuropsychiatric symptoms. This study aims to help clarify the neurochemical mechanisms behind these symptoms and to add further proof to the hypothesis that HCV may affect brain function. Therefore, 15 patients who reported increasing chronic fatigue, mood alterations, and/or cognitive decline since their HCV infection underwent neurologic and neuropsychological examination, magnetic resonance imaging, ¹⁸F-fluoro-deoxy-glucose positron emission tomography of the brain, and single photon emission tomography of striatal dopamine and midbrain serotonin transporter (SERT) availability. None of the patients had liver cirrhosis. Patients'' data were compared with data of age-matched controls. In addition, regression analysis was performed between cognitive deficits, and mood and fatigue scores as dependent variables, and cerebral glucose metabolism, dopamine, or SERT availability as predictors. Patients showed significant cognitive deficits, significantly decreased striatal dopamine and midbrain SERT availability, and significantly reduced glucose metabolism in the limbic association cortex, and in the frontal, parietal, and superior temporal cortices, all of which correlated with dopamine transporter availability and psychometric results. Thus, the study provides further evidence of central nervous system affection in HCV-afflicted patients with neuropsychiatric symptoms. Data indicate alteration of dopaminergic neurotransmission as a possible mechanism of cognitive decline.     

LC-MS/(MS) confirmatory doping control analysis of intact phase II metabolites of methenolone and mesterolone after Girard's Reagent T derivatization

In the present study, the application and evaluation of Girard's Reagent T (GRT) derivatization for the simultaneous detection and significantly important identification of different phase II methenolone and mesterolone metabolites by LC-MS/(MS) are presented. For the LC-MS analysis of target analytes two complementary isolation methods were developed; a derivatization and shoot method in which native urine is diluted with derivatization reagent and is injected directly to LC-MS and a liquid–liquid extraction method, using ethyl acetate at pH 4.5, for the effective isolation of both sulfate and glucuronide metabolites of the named steroids as well as of their free counterparts. For the evaluation of the proposed protocols, urine samples from methenolone and mesterolone excretion studies were analyzed against at least one sample from a different excretion study. Retention times, along with product ion ratios, were evaluated according to the WADA TD2021IDCR requirements, in order to determine maximum detection and identification time windows for each metabolite. Established identification windows obtained after LC-MS/(MS) analysis were further compared with those obtained after GC-MS/(MS) analysis of the same samples from the same excretion studies, for the most common analytes monitored by GC-MS/(MS). Full validation was performed for the developed derivatization and shoot method for the identification of methenolone metabolite, 3α-hydroxy-1-methylen-5α-androstan-17-one-3-glucuronide (mth3). Overall, the GRT derivatization presented herein offers a tool for the simultaneous sensitive detection of free, intact glucuronide and sulfate metabolites by LC-MS/(MS) that enhance significantly the detection and identification time windows of specific methenolone and mesterolone metabolites for doping control analysis.     

Metallurgical and electrochemical characterization of contemporary silver-based soldering alloys

Objective:To investigate the microstructure, hardness, and electrochemical behavior of four contemporary Ag-based soldering alloys used for manufacturing orthodontic appliances.Materials and Methods:The Ag-based alloys tested were Dentaurum Universal Silver Solder (DEN), Orthodontic Solders (LEO), Ortho Dental Universal Solder (NOB), and Silver Solder (ORT). Five disk-shaped specimens were produced for each alloy, and after metallographic preparation their microstructural features, elemental composition, and hardness were determined by scanning electron microscopy with energy-dispersive X-ray (EDX) microanalysis, X-ray diffraction (XRD) analysis, and Vickers hardness testing. The electrochemical properties were evaluated by anodic potentiodynamic scanning in 0.9% NaCl and Ringer''s solutions. Hardness, corrosion current (I_corr), and corrosion potential (E_corr) were statistically analyzed by one-way analysis of variance and Tukey test (α  =  .05).Results:EDX analysis showed that all materials belong to the Ag-Zn-Cu ternary system. Three different mean atomic contrast phases were identified for LEO and ORT and two for DEN and NOB. According to XRD analysis, all materials consisted of Ag-rich and Cu-rich face-centered cubic phases. Hardness testing classified the materials in descending order as follows: DEN, 155 ± 3; NOB, 149 ± 3; ORT, 141 ± 4; and LEO, 136 ± 8. Significant differences were found for I_corr of NOB in Ringer''s solution and E_corr of DEN in 0.9% NaCl solution.Conclusion:Ag-based soldering alloys demonstrate great diversity in their elemental composition, phase size and distribution, hardness, and electrochemical properties. These differences may anticipate variations in their clinical performance.     

Skin application of isoflurane attenuates the responses to a mechanical and an electrical stimulation

PURPOSE: This prospective randomized crossover study was performed to test the potential of an analgesic effect of isoflurane after its local application to the skin. METHODS: We evaluated the local analgesic effect of isoflurane solution in 31 healthy volunteers. The right or left forearm of each subject was exposed to isoflurane and the contralateral forearm to water for 30 min. Then, the response of both forearms to a mechanical stimulus of 650 gr and an electrical stimulus of 2 Hz was tested. The procedure was repeated the next day with the forearms exposed to anaesthetic or water in an inverse way. The averaged responses to the mechanical and electrical stimuli obtained from both forearms after exposure to isoflurane were expressed on a VAS scale and compared with the averaged responses obtained after exposure to water, using the Wilcoxon signed-ranks matched-pairs test. RESULTS: The average VAS scores obtained from both forearms after the mechanical stimulus were decreased after isoflurane compared with water (3.5 +/- 2.1 cm vs 4.3 +/- 2.2 cm, P < 0.0001). After the electrical stimulus local application of isoflurane was associated with a decrease in the VAS scores obtained from both the right and left forearms (3.6 +/- 2.0 cm) when compared with water, (5.2 +/- 2.1 cm, P < 0.0001). CONCLUSION: These data suggest that isoflurane may have an analgesic effect in the peripheral tissues, which may interfere with the MAC determination as well with decreased responses to other nociceptive stimuli.     

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway

BACKGROUND: Somatic activating mutations of the thyrotropin (thyroid-stimulating hormone (TSH)) receptor (TSHR) and G(alphas) protein have been detected in solitary toxic adenomas and toxic multinodular goiters, but their role in the pathogenesis of autonomous nodules is debated. The frequency of mutations is highly variable among populations and is inversely proportional to iodine intake. DESIGN AND PATIENTS: We screened 28 clinically and histologically heterogeneous autonomous nodules from 24 Greek patients for the presence of TSHR and G(alphas) mutations. RESULTS: By direct sequencing of genomic DNA, we detected 11 somatic heterozygous gain-of-function mutations in TSHR and one in G(alphas). Forty-three percent (12 of 28) of all nodules and 57% (four of seven) of solitary toxic adenomas harbored an activating mutation. Typical adenomas and hyperplastic nodules did not differ in mutation frequency. Substitutions I568T and T632I were detected in both histological types of nodules. CONCLUSIONS: Our findings indicate that activating somatic mutations in the TSH signaling pathway are frequent in autonomous nodules in Greece. This may be due to earlier exposure of the population to iodine deficiency, which was corrected in Greece only over the past two decades. Gain-of-function mutations are shared by nodules with varying histological and clinical presentations. Thus, they may represent a common molecular mechanism underlying the pathogenesis of non-autoimmune thyroid autonomy.     

Kidney transplantation outcomes from expanded criteria donors,standard criteria donors or living donors older than 60 years

Objectives: To evaluate outcomes in kidney allograft recipients from donors with expanded criteria (ECD) versus standard criteria (SCD) or living donors (LD) >60 years. Methods: We studied all patients who received a kidney between 2005 and 2011, focusing in recipients of kidneys from deceased ECD, SCD and LD >60 years. ECD was any deceased donor >60 years or >50 years with two of the following: hypertension (HTN), stroke as the cause of death, or serum creatinine >1.5?mg/dL. We recorded characteristics of the transplant procedure, patient, graft survival and renal function 1 year after transplantation and at the end of follow-up. Results: Six-hundred and five patients were transplanted between 2005 and 2011 in our department. There were 142 (25.1%) transplantations from ECD, 192 (33.98%) from SCD and 96 (16.99%) from LDs older than 60 years. In a mean follow-up time of 36.4 months, graft survival rates were similar for all groups. Calculated GFR was found statistically different between the ECD and SCD groups, but still satisfactory at first year, and at end of follow-up time. Comparison of the patients, who received transplants from ECD, even older than 70 years, and those from LD >60 years revealed equivalent renal function in short and long term. Conclusions: Utilization of marginal kidneys effectively doubled our deceased transplant volume in the period 2005–2011. Patients’ and graft survival were shown similar at the end of follow-up for all groups. Renal outcomes were shown equivalent between the ECD and LD >60 years groups, and although significantly lower between the ECD and the SCD group, were still very satisfactory.