Inpatient Burden and Mortality of Methanol Intoxication in the United States

BackgroundThis study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilization of hospitalization for methanol intoxication in the United States.Materials and MethodsA total of 603 hospitalized patients with a primary diagnosis of methanol intoxication from 2003 to 2014 were identified in the National Inpatient Sample database. The inpatient prevalence, clinical characteristics, treatments, outcomes, resource utilization, were investigated. Multivariable logistic regression was performed to identify factors independently associated with in-hospital mortality.ResultsThe overall inpatient prevalence of methanol intoxication among hospitalized patients was 6.4 cases per 1,000,000 admissions in the United States. The mean age was 38±18 (range 0–86) years. 44% used methanol for suicidal attempts. 20% of admissions required mechanical ventilation, and 40% required renal replacement therapy. The three most common complications were metabolic acidosis (44%), hypokalemia (18%), and visual impairment or optic neuritis (8%). The three most common end-organ failures were renal failure (22%), respiratory failure (21%), and neurological failure (17%). 6.5% died in the hospital. Factors associated with increased in-hospital mortality included alcohol drinking, hypernatremia, renal failure, respiratory failure, circulatory failure, and neurological failure. The mean length of hospital stay was 4.0 days. The mean hospitalization cost per patient was $43,222ConclusionThe inpatient prevalence of methanol intoxication in the United States was 6.4 cases per 1,000,000 admissions. The risk of in-hospital mortality mainly depended on the number of end-organ failures.     

Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster.

Propolis is a substance produced by honeybees (Apis mellifera L.). Its components are strong antioxidants and free radical scavengers. The aim of this study was to evaluate the protective effects of a water extract of Brazilian green propolis (WEP) combined with the antitumor agent doxorubicin (DXR) on Drosophila melanogaster wing cells through the somatic mutation and recombination test (SMART). Two different crosses were used: The standard (ST) cross and the high bioactivation (HB) cross. The HB cross is characterized by a constitutively enhanced level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Larvae obtained from these two crosses were chronically treated with different concentrations of WEP (12.5,25.0 and 50.0 mg/mL) alone or combined with DXR (0.125 mg/mL). The results obtained with the two different crosses were rather similar. Neither toxicity nor genotoxicity were observed in WEP treated series. Simultaneous treatment with different concentrations of WEP and DXR led to a reduction in the frequency of recombination compared to the treatment with DXR alone. This anti-recombinogenic effect was proportional to the concentrations applied, indicating a dose-response correlation and can be attributed to the powerful scavenger ability of WEP.     

Indications for a threshold of chemically-induced aneuploidy in vitro in human lymphocytes

The possible existence of a threshold for compounds inducing chromosomal loss was investigated for four known aneugens (colchicine, COL; carben-dazim, MBC; mebendazole, MEB; nocodazole, NOC) and two clastogens (methyl methanesulfo-nate, MMS; mitomycin C, MMC) using the micronu-cleus (MN) test in human lymphocytes. The presence of a whole chromosome in the MN was studied by fluorescent in situ hybridization (FISH) using a synthetic pancentromeric oligonucleotide probe. FISH was applied on two different MN preparations: cytokinesis-blocked MN (MNCB) assay, and MN sorted by flow cytometry. At subtoxic concentrations analyzed by MNCB and FISH, COL, MEB, MBC, and NOC induced a concentration-dependent increase in centromere-positive MN (MNCen+), MMC seemed to induce an increase in both types of MN (MNCen- and MNCen+), while MMS induced only MNCen-. On the sorted micronuclei (in a wide range of low to subtoxic concentrations), the concentration-effect profile for MNCen+, with the four aneugens tested, showed a statistically nonsignificant increase over a range of concentrations, followed by a second range of high concentrations with a statistically significant increase. To analyze the existence of a threshold, a piecewise linear regression was applied to the data. The first concentration that showed a statistically significant increase in MNCen+ was chosen as a breakpoint (0.037 μM for COL, 2.62 μM for MBC, 0.27 μM for MEB, and 0.066 μM for NOC). The statistical correlation between observed and predicted values showed a high correlation (r = 0.99), indicating a clear threshold for aneuploidy induction. However, for MMS the concentration-effect profile for MNCen+ showed a continuous concentration-dependent decrease with no threshold. With the two cytotoxicity assays used (Bio-Rad and MTT), no significant reduction was detected either in the protein content or in mitochondrial succinate dehydrogenase activity with all chemicals tested for MN induction. Therefore, our data suggest that the observed thresholds were not due to indirect toxic effects but to real aneugenic effects. © 1995 Wiley-Liss, Inc.     

In vivo imaging of a diabetogenic CD8+ T cell response during type 1 diabetes progression

Type 1 diabetes is preceded by a long, protracted period of pancreatic islet inflammation by autoreactive lymphocytes. Noninvasive imaging of islet inflammation prior to the onset of hyperglycemia might have diagnostic and therapeutic implications, but this is not currently possible. Here, MRI is used to track, noninvasively, the accumulation diabetogenic CD8+ T-cells during type 1 diabetes progression in nonobese diabetic (NOD) mice. The contrast agent is an MRI probe (MN-NRP-V7) that specifically labels CD8+ T-cells recognizing residues 206-214 of islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP(206-214)) in the context of the major histocompatibility complex (MHC) class I molecule H-2K(d). This probe consists of superparamagnetic iron oxide nanoparticles (MN) coated with K(d) molecules presenting NRP-V7, a high-avidity mimotope of IGRP(206-214). NOD mice of different ages (5, 8, 15, and 24 weeks) were imaged by MRI before and after a single intravenous injection of MN-NRP-V7 or unmodified MN nanoparticles. MN-NRP-V7 accumulation, as determined by semiquantitative MRI analysis of pancreas-associated T(2) relaxation time, was antigen-specific, age-dependent, and well correlated with the numbers of MN-NRP-V7-labeled CD8+ T-cells recovered from the pancreata of the treated mice. Antigen/MHC-coupled nanoparticles represent a promising new avenue for noninvasive imaging of lymphocyte inflammation in organ-specific autoimmunity and transplantation.     

Nurr1在MN9D细胞中的过表达及其对酪氨酸羟化酶的影响

目的 :观察MN9D细胞中Nurr1的表达和分布及Nurr1过表达对酪氨酸羟化酶的影响。 方法 :应用高压液相色谱、免疫细胞化学、转基因、Westernblot和Northernblot等方法检测了MN9D细胞中多巴胺及其代谢物的水平和Nurr1蛋白在细胞中的分布 ,建立了过表达Nurr1的细胞株并观察了Nurr1过表达对TH基因的影响。结果 :MN9D细胞裂解液中含有大量多巴胺及其代谢物 ;Nurr1蛋白主要分布在MN9D细胞的胞质中 ,尤以核周最多 ;MN9D细胞中有Nurr1的mRNA存在和蛋白质的表达 ;过表达Nurr1的MN9D细胞A1株酪氨酸羟化酶表达增高。结论 :Nurr1与多巴胺能神经元发育有关 ,有可能用于帕金森病的基因治疗。