mTORC1 inhibition may improve T lymphocytes affected by aging.

BACKGROUND: Due to the increase of the elderly's population and related social and economic problems, it is very important to provide strategies on health. In this regard, induction of T lymphocytes responses, the most important cells of the immune system, may be a good approach. Among different agents considered as antiaging factors, mTORC1 pathway inhibitors are significant. So, the purpose of this study was to evaluate the effect of two mTORC1 inhibitors, Everolimus and Metformin, on age-related features of activated T cells. MATERIALS AND METHODS: Optimum doses of drugs was determined with evaluating the effect of treatments on IL-2 gene expression. T cells isolated from old and young mice were treated with drugs and PHA. IL-2 production was evaluated by ELISA. Also, the expression of CD28, PD-1, and KLRG-1, proliferation, and intracellular oxidative stress were assessed by flow cytometry-based assays, phenotyping, CFSE, and DCF-DA assay respectively. RESULTS: Both drugs increased IL-2 production in the T cells of old mice. Also, using drugs especially Metformin could improve age-related phenotypical markers and increase the proliferation of T cells of old mice significantly. In addition, Metformin and Everolimus reduced intracellular oxidative stress in aged cells. However, the effect of both drugs on the T cells of young mice wasn't significant or was in opposite to the results of old mice T cells. DISCUSSION: In line with studies noting mTOR inhibitors as antiaging drugs, Metformin and Everolimus may improve T cells affected from aging in vitro, and a decrease in intracellular oxidative stress may be one of their mechanism of function.

Tumor suppressor microRNAs: Targeted molecules and signaling pathways in breast cancer.

Breast cancer is the most common type of cancer in women whose prevalence is increasing every year. Common strategies for diagnosis, prognosis and specific treatment of breast cancer need improvements to increase patients' survival. For this reason, there is growing number of efforts world-wide with molecular approaches. With the advent of microRNAs (miRNAs), they have been interested for almost all aspects of tumorgenesis and correlation of breast cancer and microRNAs was discovered for the first time in 2005. MiRNAs form a group of small noncoding RNAs which participate in regulation of gene expression and subsequently several biological processes and pathogenesis of various diseases. As other cancers, miRNAs involved in breast cancer are classified in two groups: the first group is tumor inducing miRNAs (also called oncomirs) that can induce tumor initiation and progression, and their expression is increased in cancerous cells. The second group is tumor suppressor miRNAs. In normal situation, tumor suppressor miRNAs prevent beginning and progression of breast cancer through suppressing the expression of various oncogenes. In this review we will give a general overview about miRNAs and breast cancer, and in the following, more discussion about tumor suppressor miRNAs, with focus on the best known of them and their targeted oncogenes and signaling pathways. Finally, we will point to application of this group of miRNAs in diagnosis, prognosis and treatment of patients.

Preparation and characterization of agarose-nickel nanoporous composite particles customized for liquid expanded bed adsorption.

Agarose-nickel nanoporous composite matrices with a series of densities, named Ag-Ni, were prepared herein for expanded bed adsorption of nanobioproduct/bioproduct by a water-in-oil emulsification method. The optical microscope (OM), scanning electronic microscope (SEM) and particle size analyzer (PSA) were utilized in order to characterize the structure and morphology of the agarose-nickel composite. The results indicated that the matrices prepared had a spherical appearance, appropriate wet density of 1.73-2.56 g/ml, water content of 32.2-58.5% and porosity of 79.4-96.37% and pore size of about 100-150 nm. All the Ag-Ni beads follow logarithmic normal size distribution with the range of 60-230 µm and average diameter of 133.68-148.4 µm. One of the useful properties of the Ag-Ni particles is the high wet density up to 2.56 g/ml, which shows a potential for the operation in an expanded bed at high flow rate. The impact of nickel powder addition on the physical and hydrodynamic properties was also investigated. In addition, the fluidization behavior of the Ag-Ni particles under various conditions was characterized by the measurement of bed expansion and axial dispersion coefficients for the liquid phase when operated in a standard fluidized bed contactor. It was observed that the expansion factors were decreased with the increasing matrix density under the same velocity. The bed expansion and fluid velocity were correlated with Richardson-Zaki equation for all particles prepared and the correlation parameters (the terminal settling velocity U(t) and expansion index n) were investigated. Using measurements of residence time distributions, hydrodynamic properties in the expanded beds were investigated and were compared with reported matrices in other literatures. In addition, the impact of the flow velocity, bed expansion degree and density of adsorbent on hydrodynamic properties in the expanded beds were investigated. The results indicated that the expansion factor showed little effect on the hydrodynamic properties while the fluid velocity was the most essential factor on this regard. Furthermore, the results indicated that the heavy matrices of Ag-Ni-3, Ag-Ni-4 and Ag-Ni-5, were more suited for high operation fluid velocity. In addition, even the light matrices, i.e. Ag-Ni-1 and Ag-Ni-2, seem to be superior to other matrices in hydrodynamic properties, which made them promising adsorbents for further use in EBA processes.

Doctors' views of attitudes towards peer medical error.

BACKGROUND: This study aims at evaluating doctors' attitudes towards handling medical errors made by their peers. MATERIALS: This cross-sectional questionnaire survey was conducted between April and July 2006 and targeted general practitioners attending continuing medical education programmes in Tehran. A total of 474 doctors were approached, 400 of whom completed the questionnaire. The questionnaire contained a clinical vignette with three hypothetical patient outcomes: near-miss, leading to harm, and leading to death. The participants were asked how they would deal with each case. They were also asked how they would prefer their peers to react when they themselves made a medical error. RESULTS: The most common attitude toward peers' medical errors was reporting it to the original doctor and asking them to disclose it to the patient (near-miss: 63.0%; 95% CI 58% to 68%; leading to harm: 70.0%; 95% CI 65.4% to 74.6%; and leading to death: 62.5%; 95% CI 57.5% to 67.5%). In most cases, doctors expected their peers to report their medical errors to them (92.7%; 95% CI 89.7% to 93.0). About 67% of the participating doctors had encountered a peer's medical error in the past 6 months, although 90% of them had received no or very little training in dealing with this issue. DISCUSSION: The most acceptable approach to dealing with a peer's medical error is to report it to the responsible doctor and encourage them to disclose it to the patient.

What do patients expect from their physicians?

BACKGROUND: To identify the most important expectations that patients have from their physicians. METHODS: We collected data from 199 hospitalized and 201 ambulatory patients (response rates 88% and 93% respectively). We used random sampling for selection of hospitalized patients and systematic sampling for the ambulatory ones. The questionnaire consisted of 18 different expectation items categorized in 5 domains. The participants scored each item from 1 to 9 using a VAS scale and ranked domains based on their importance. We analyzed the data using univariate and regression analyses. RESULTS: Among the ambulatory patients, the mean±standard error of the most important expectations was as follows: competency (8.9±0.01), courteousness (8.8±0.04), consultation in case of need (8.8±0.4), clear explanation of the disease (8.8±0.05) and attentiveness (8.8±0.04). In hospitalized patients, the following items were the most important: competency (8.4±0.08), courteousness (8.4±0.09), availability of physician (8.4±0.09), consultation in case of need (8.2±0.11), setting following appointments (8.2±0.1), and disease follow-up (8.2±0.09). In both groups, the most important domain of expectations was "competency and quality of care" followed by "availability" in hospitalized and "giving information and patient autonomy" among ambulatory patients. CONCLUSIONS: Our findings are similar to what reported in the literature from other countries and cultures. In addition to physician expertise and knowledge, patients value giving information and efficient doctor-patient relationship.

Doctors' views of attitudes towards peer medical error.

BACKGROUND: This study aims at evaluating doctors' attitudes towards handling medical errors made by their peers. MATERIALS: This cross-sectional questionnaire survey was conducted between April and July 2006 and targeted general practitioners attending continuing medical education programmes in Tehran. A total of 474 doctors were approached, 400 of whom completed the questionnaire. The questionnaire contained a clinical vignette with three hypothetical patient outcomes: near-miss, leading to harm, and leading to death. The participants were asked how they would deal with each case. They were also asked how they would prefer their peers to react when they themselves made a medical error. RESULTS: The most common attitude toward peers' medical errors was reporting it to the original doctor and asking them to disclose it to the patient (near-miss: 63.0%; 95% CI 58% to 68%; leading to harm: 70.0%; 95% CI 65.4% to 74.6%; and leading to death: 62.5%; 95% CI 57.5% to 67.5%). In most cases, doctors expected their peers to report their medical errors to them (92.7%; 95% CI 89.7% to 93.0). About 67% of the participating doctors had encountered a peer's medical error in the past 6 months, although 90% of them had received no or very little training in dealing with this issue. DISCUSSION: The most acceptable approach to dealing with a peer's medical error is to report it to the responsible doctor and encourage them to disclose it to the patient.

Patients' preferences for receiving clinical information and participating in decision-making in Iran.

INTRODUCTION: This study, the first of its kind in Iran, was to assess Iranian patients' preferences for receiving information and participating in decision-making and to evaluate their satisfaction with how medical information is given to them and with their participation in decision-making at present. METHOD AND MATERIALS: 299 of 312 eligible patients admitted to general internal medicine or surgery wards from May to December 2006 were interviewed according to a structured questionnaire. The questionnaire contained questions about patients' preferences regarding four domains of information and their participation in decision-making. Patients' responses were measured on a visual analogue scale graded from 1 to 10. RESULTS: The mean (SD) score for desire to receive information was 8.88 out of 10 (1.5) and for participation in medical decision-making was 7.75 out of 10 (3). The desire to receive information was greater in women than men (9.0 (1.5) vs 7.8 (1.4), p = 0.025). It was also correlated with their education (r = 0.2, p = 0.001) and their estimation of the severity of their own disease (r = 0.13, p = 0.027). The score for preference to participate in decision-making was higher in women than in men (7.95 (2.8) and 7.0 (3.2), respectively; beta = 0.8, p = 0.022) and was negatively correlated with education (r = -0.14, p = 0.015). DISCUSSION: This study shows that Iranian patients are highly interested in receiving information about their condition and participating in clinical decision-making. No predictive variable for such attitudes was found; therefore, the only way for the physician to recognise patients' desire is to ask them explicitly.

Determination of the pesticide naptalam and its degradation products by positive and negative ion mass spectrometry.

N-1-Naphthylphtalamic acid (naptalam) and its degradation products, 1-naphthylamine and N-(1-naphthyl) phthalimide were simultaneously determined in river water by two independent mass spectrometric (MS) methods. These were negative ion MS (NIMS) and programmable temperature vaporizer gas chromatography mass spectrometry (PTV-GC MS) with electron impact ionization (positive ions). Prior to the NIMS analysis, the samples were preconcentrated by solid phase extraction (SPE) of C18 membrane discs. The PTV-GC MS studies were performed without any preconcentration procedure. Selected ion monitoring (SIM) and internal standardization with naphthalene were applied in both methods. The limits of determination (LOD) of NIMS studies were 230, 270 and 260 ng L-1 for naptalam, 1-naphthylamine and N-(1-naphthyl) phthalimide, respectively, with relative standard deviation (RSD) < 1% (n = 5) and of PTV-GC MS 17, 11 and 15 ng L-1 (RSD < 0.7%, n = 5). The LOD, linearity, RSD and time required for these methods are far better than for HPLC analyses.

Comparison of pyrolysis-mass spectrometry with high performance liquid chromatography for the analysis of vancomycin in serum.

Mass spectrometry coupled with a pyrolysis inlet system (Pyr-ms) is compared with high performance liquid chromatography (HPLC) for the determination of vancomycin and its crystal degradation products (CDP-Is) in human serum. Quantitative analysis of Pyr-ms was performed by selected ion monitoring (SIM) method at 108 mass:charge (m/z) of pyrolysis product of vancomycin. 3-Nitroaniline (138 m/z) was used as an internal standard. A mu-Bondapak C(18) column and the gradient mobile phase of triethylamine buffer (pH 6.2), acetonitrile and tetrahydrofuran and a photometric detection at 205 nm are found to be the optimum conditions for the HPLC determination of vancomycin and CDP-Is. The limit of detection (LOD=1 ng ml(-1)), linearity (1 ng ml(-1)-10 mg ml(-1)), relative standard deviation (R.S.D.=1%), time analysis (1/2 h) and sample volume (50 mul) of Pyr-ms are far better than of the HPLC method. However, the HPLC method can individually determine the concentration of vancomycin and its degradation products.

Cellular regulation of poly ADP-ribosylation of proteins. II. Augmentation of poly(ADP-ribose) polymerase in SV40 3T3 cells following methotrexate-induced G1/S inhibition of cell cycle progression.

SV40-3T3 cells were exposed in monolayer cultures to 5 X 10(-7) M methotrexate (MTX), that inhibited thymidylate synthetase, arrested cell growth without cell killing in 24 h and did not induce single- (ss) or double-strand (ds) breaks in DNA. Following 24, up to 72 h, the poly(ADP-ribose) polymerase content of attached cells was induced by 5 X 10(-7) M MTX and the augmentation of the enzyme increased with the time of exposure to the drug. Inhibition of protein or RNA synthesis abolished augmentation of enzymatic activity; so too did the initiation of maximal cell growth by thymidine + hypoxanthine, by-passing the inhibitory site of MTX. Isolation of the ADP-ribosylated enzyme protein by gel electrophoresis identified poly(ADP-ribose) polymerase protein as the molecule that was induced by 5 X 10(-7) M MTX. Under identical conditions, the poly(ADP-ribose) polymerase induction in 3T3 cells could not be demonstrated. A possible cell-cycle-dependent biosynthesis of the enzyme protein is proposed in SV40 3T3 cells.