Osteryoung square wave stripping voltammetry at mercury film electrode for monitoring ultra trace levels of Tarabine PFS and its interaction with ssDNA

The electrochemical oxidation and reduction behaviour of adsorbed species of antimetabolic antineoplastic agent Tarabine PFS (Cytosar-U) in Sorensen buffer solution of different pH values at an in situ-mercury film electrode (MFE) is studied using cyclic voltammetry (CV) and Osteryoung square-wave stripping voltammetry (OSWSV). Optimal experimental and operational parameters have been selected for the drug preconcentration and determination in aqueous medium. Based on the adsorption and accumulation of Tarabine PFS using Osteryoung square-wave anodic stripping voltammetry (OSWASV) at MFE, the drug is easily detected as 0.134 ng/ml (5.51×10⁻¹⁰ M). Calibration plots have been constructed at different accumulation times. The standard deviation (n=10) at a concentration level of 6×10⁻⁸ M Tarabine PFS is 0.062. The interaction of ssDNA with the drug under the optimal conditions at pH 7.7 has been studied. The formal potentials E° and E°^′ and the equilibrium constants K₁ and K₂ have been calculated for the free form of Tarabine PFS and the bonded form with ssDNA, respectively. It was found that K₂ value for the bonded oxidized form is 298 times than that of K₁ for the bonded reduced form. Therefore, ssDNA has been found to interact strongly with the oxidized form of the drug. The method has been used for the nanogram determination of ssDNA with 1.9% variation coefficient. Detection limit of 3 ng/ml ssDNA has been achieved. Possible interfering organic compounds, cations and anions have been tested. The method has been applied for the drug determination in urine samples, down to 0.23 ng/ml could be easily achieved in such samples.     

Targeting cancer stem cells for more effective therapies: Taking out cancer's locomotive engine

Novel therapies for the treatment of solid tumors have generally failed to improve patient overall survival. These therapeutic approaches are typically focused on targeting signaling pathways implicated in cell growth and/or survival in order to shrink the malignant mass and achieve an objective clinical response; however, too often these responses are followed by eventual regrowth of the tumor. This clinical conundrum could be explained by the existence of a tumorigenic cell population that is relatively resistant to these therapies and retains pluripotent status in order to repopulate the original tumor and/or contribute to distant metastasis following treatment. Compelling data from liquid tumors, and more recently from studies focused on solid tumors, now support the existence of such tumorigenic cells (i.e., cancer stem cells) as a distinct subpopulation within the total tumor cell mass. These cancer stem cells (CSCs), as compared to the non-CSC population, have the ability to reconstitute the primary tumor phenotype when transplanted into recipient animals. In addition, data are beginning to emerge demonstrating that many standard-of-care chemotherapeutics are less effective in promoting cell death or cytostasis in these putative cancer stem cells as compared to effects in the non-stem cell cancerous cells. Therefore, targeting these locomotive drivers of tumors, the cancer stem cell population, should be considered a high priority in the continued pursuit of more effective cancer therapies.     

Subjective Memory Complaints in healthy older adults: Fewer complaints associated with depression and perceived health,more complaints also associated with lower memory performance

Objectives(i) To analyze if general cognitive performance, perceived health and depression are predictors of Subjective Memory Complaints (SMC) contrasting their effect sizes; (ii) to analyze the relationship between SMC and objective memory by comparing a test that measures memory in daily life and a classical test of associated pairs; (iii) to examine if different subgroups, formed according to the MFE score, might have different behaviors regarding the studied variables.MethodsSample: 3921 community-dwelling people (mean age 70.41 ± 4.70) without cognitive impairment. Consecutive non-probabilistic recruitment. Assessment: Mini Cognitive Exam (MCE), daily memory Rivermead Behavioural Memory Test (RBMT), Paired Associates Learning (PAL), Geriatric Depression Scale (GDS), Nottingham Health Profile (NHP). Dependent variable: Memory Failures Everyday Questionnaire (MFE).ResultsTwo different dimensions to explain SMC were found: One subjective (MFE, GDS, NHP) and other objective (RBMT, PAL, MCE), the first more strongly associated with SMC. SMC predictors were NHP, GDS, RBMT and PAL, in this order according to effect size. Considering MFE scores we subdivided the sample into three groups (low, medium, higher scores): low MFE group was associated with GDS; medium, with GDS, NPH and RBMT, and higher, with age as well. Effect size for every variable tended to grow as the MFE score was higher.ConclusionSMC were associated with both health profile and depressive symptoms and, in a lesser degree, with memory and overall cognitive performance. In people with fewer SMC, these are only associated with depressive symptomatology. More SMC are associated with depression, poor health perception and lower memory.     

Pharmacokinetic characterization of mangosteen (Garcinia mangostana) fruit extract standardized to α-mangostin in C57BL/6 mice

Previously, we have reported the pharmacokinetic (PK) properties of α-mangostin in mice. For this study, we evaluated the PK profile of α-mangostin using a standardized mangosteen extract in C57BL/6 mice. The primary objective was to determine the PK properties of α-mangostin when administered as an extract. This experiment was designed to test our primary hypothesis that α-mangostin in an extract should achieve a desirable PK profile. This is especially relevant as dietary supplements of mangosteen fruit are regularly standardized to α-mangostin. Mice received 100 mg/kg of mangosteen fruit extract orally, equivalent to 36 mg/kg of α-mangostin, and plasma samples were analyzed over a 24-hour period. Concentrations of α-mangostin were determined by liquid chromatography–tandem mass spectrometry. In addition, we evaluated the stability in the presence of phase I and phase II enzymes in liver and gastrointestinal microsomes. Furthermore, we identified evidence of phase II metabolism of α-mangostin. Further research will be required to determine if less abundant xanthones present in the mangosteen may modulate the PK parameters of α-mangostin.     

原发性恒磨牙萌出障碍1例的治疗体会

原发性牙齿萌出障碍是一种十分罕见的疾病,临床上很难与机械性牙齿萌出障碍相鉴别,容易误诊、误治[1],该文报道一例原发性牙齿萌出障碍的治疗体会.