Pretreatment synthetic MRI features for triple-negative breast cancer.

AIM: To evaluate the quantitative parameters derived from synthetic magnetic resonance imaging (SyMRI) for predicting triple-negative breast cancer (TNBC). MATERIALS AND METHODS: This prospective study enrolled participants with invasive ductal breast carcinoma (IDBC) and separated them into a TNBC group and a Non-TNBC group. Preoperative breast MRI included both the SyMRI and conventional MRI sequences. The quantitative parameters derived from the SyMRI included T1 and T2 relaxation times, proton density (PD), and their standard deviations (SD). Clinicopathological characteristics, conventional MRI findings, and quantitative synthetic parameters were assessed for all participants. Multivariable logistic regression analysis was performed to determine the potential independent imaging predictors for TNBC preoperatively. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of these parameters. RESULTS: A total of 231 participants with histopathological proven IDBC were included in this study (n=46 in the TNBC group and n=185 in the Non-TNBC group). The TNBC group had significantly larger tumour size (p=0.011) and more frequent intratumoural cystic or necrotic lesions (p<0.001) as compared to the Non-TNBC group. The univariate analysis showed that the TNBC tumours had significantly higher T1 (p=0.006) and T2 (p<0.001) values than Non-TNBC tumours. Subsequent multivariable analysis indicated that T2 values and the presence of cystic or necrotic lesions were the independent predictors for TNBC. CONCLUSION: The T2 from synthetic imaging and the presence of cystic degeneration or necrosis within the breast cancer may serve as potential imaging biomarkers for preoperative differentiation of TNBC from Non-TNBC.

[Identification and preliminary validation of potential biomarkers in the peripheral blood mononuclear cells of atopic dermatitis].

Objective: To explore the difference of peripheral blood mononuclear cells (PBMC) transcripts between atopic dermatitis (AD) and healthy controls, and to screen and preliminarily validate potential biomarkers of AD. Methods: From January 2021 to May 2022, blood samples from 9 AD patients and 10 healthy controls were collected from the Dermatology and Cosmetic Center of the Third Affiliated Hospital of Chongqing Medical University, ribonucleic acid-sequencing (RNA-seq) was used to determine the transcriptome and relative expression of PBMC, the differentially expressed genes (DEGs) were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction networks (PPI) analysis, and the potential biomarkers were identified by quantitative real-time PCR (qRT-PCR). Results: The age of patients in the AD group [M (Q1, Q3)] was 26.50 (22.75, 30.50) years old, and the course of disease [M (Q1, Q3)] was 15 (10, 20) years,and the age of the healthy control group [M (Q1, Q3)] was 37.00 (27.75, 40.25) years old. Compared with healthy controls, 1 044 DEGs were detected in PBMC samples in AD group, including 668 up-regulated genes and 376 down-regulated genes. Differential variable splicing (AS) showed that mutually exclusive exons (46.74%) and skipped exon (31.01%) accounted for a large proportion. GO and KEGG enrichment analysis revealed that AD is closely linked to DEGs implicated in the inflammatory response and cytokine interaction and signal pathway. Comprehensive enrichment analysis and PPI analysis selected the expression of 8 candidate genes (CCL4, CCR3, CXCR5, NFKBIA, CXCL1, IL-1B, CCL20, LY96), which was confirmed by qRT-PCR and were consistent with that of RNA-seq. Conclusions: CCL4, CCR3, CXCR5, NFKBIA, CXCL1, IL-1B, CCL20 and LY96 might be potential biomarkers of AD, participating in the occurrence and development of AD.

Clinical efficacy of enhanced external counter pulsation plus sacubitril/valsartan in the treatment of patients with chronic heart failure and the effect on ankle-arm index and cardiac function.

OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of enhanced external counter pulsation (EECP) plus sacubitril/valsartan in the treatment of patients with chronic heart failure (CHF) and the effect on ankle-arm index and cardiac function. PATIENTS AND METHODS: In this retrospective study, 106 patients with chronic heart failure treated in our hospital from September 2020 to April 2022 were recruited and randomly assigned to receive either sacubitril/valsartan (observation group) or EECP plus sacubitril/valsartan (combination group) alternately at the point of admission, with 53 patients in each group. Outcome measures included clinical efficacy, ankle brachial index (ABI), cardiac function indices [N-terminal brain natriuretic peptide precursor (NT-proBNP), 6 min walking distance (6MWD), left ventricular ejection fraction (LVEF)], and adverse events. RESULTS: EECP plus sacubitril/valsartan resulted in significantly higher treatment efficiency and ABI levels vs. sacubitril/valsartan (p<0.05). Patients receiving combined therapy showed significantly lower NT-proBNP levels than those given monotherapy (p<0.05). EECP plus sacubitril/valsartan resulted in longer 6MWD and higher LVEF than sacubitril/valsartan alone (p<0.05). No significant differences were observed in the adverse events between the two groups (p>0.05). CONCLUSIONS: EECP plus sacubitril/valsartan substantially improves the ABI levels, cardiac functions, and exercise tolerance of patients with chronic heart failure, with a high safety profile. EECP improves blood supply to myocardial ischemic tissues by increasing ventricular diastolic blood return and blood perfusion to ischemic myocardium, raises aortic diastolic pressure, restores pumping function, improves LVEF, and reduces NT-proBNP secretion.

The long non-coding RNA AK001796 contributes to poor prognosis and tumor progression in hepatocellular carcinoma.

OBJECTIVE: Increasing studies have indicated the important functions of long non-coding RNAs (lncRNAs) in tumorigenesis and progression including hepatocellular carcinoma (HCC). The study aims to explore the role of long non-coding RNA AK001796 in HCC progression. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (QRT-PCR) analysis was performed to examine the lncRNA AK001796 expression in 73 cases of human HCC tissue samples and matched adjacent normal tissues. Besides, the relationship between lncRNA AK001796 expression and clinicopathologic characteristics was analyzed. Overall survival (OS) curves of patients were constructed by the Kaplan-Meier methods. Multivariate Cox regression analysis was used to evaluate independent risk factors affecting HCC prognosis. Cell proliferation and invasion abilities are analyzed by cell counting kit-8 (CCK-8) and transwell invasion assays. RESULTS: We showed that the lncRNA AK001796 expression was significantly up-regulated in HCC tissues and cell lines, compared to their controls, respectively. Higher lncRNA AK001796 expression closely correlated with tumor size (p<0.05), TNM stage (p<0.05) and the poor overall survival (OS) rate of HCC patients (p<0.05). Besides, multivariate Cox regression analysis found that lncRNA AK001796 expression was identified as an independent risk factor for HCC prognosis. In vitro, we showed that lncRNA AK001796 knockdown markedly suppressed cell proliferation and cell invasion abilities. CONCLUSIONS: Our results suggested that lncRNA AK001796 acts as a predictor of HCC prognosis and may provide an important clinical value for HCC treatment.

[Safety and efficacy of off-pump coronary artery bypass grafting in octogenarians].

Objective: To discuss the clinical safety and efficacy about off-pump coronary artery bypass grafting (OPCABG) in octogenarians. Methods: From June 2005 to July 2014, 252 patients (male 208, female 44, with a mean age of 81.7 years old) underwent OPCABG in Beijing Anzhen Hospital who were aged 80 years or older were enrolled. Results: Eight (3.2%) patients were diagnosed as single vessel coronary artery disease (CAD), 29 cases (11.5%) were diagnosed as bifurcation vessel CAD, and 215 cases (85.3%) were multivessel CAD. One hundred and one cases (40.1%) were diagnosed as left main artery disease, among which 51 cases (20.2%) had old myocardial infarction. Two hundred and forty-eight patients belonged to Canadian Cardiovascular Society (CCS) classⅠ-Ⅲ and 4 cases to CCS class Ⅳ. One hundred and forty-five cases belonged to New York Heart Association (NYHA) classⅠ-Ⅱ and 107 cases to NYHA class Ⅲ-Ⅳ. Mean graft number was 3. Two hundred and six patients (81.7%) received total vein graft operation. Intra-aortic balloon pump (IABP) was used in 43 patients (17.1%). In-hospital death occurred in 15 cases (6.0%). Major in-hospital complications included reoperation (16 cases), re-intubation (16 cases), dialysis (11 cases), sternum infection (2 cases), atrial fibrillation (63 cases). The follow-up time was from 1 to 11 years (with a mean time of 6 years). All-cause mortality was 18.1% (43 cases). The major out-of-hospital complications included recurrent myocardial infarction (3 cases), stroke (3 cases), re-admission (27 cases) and recurrent angina pectoris (20 cases). Conclusion: OPCABG is safe and effective for myocardial revascularization in patients aged 80 years and over.

Evolution of Welding-Fume Aerosols with Time and Distance from the Source: A study was conducted on the spatiotemporal variability in welding-fume concentrations for the characterization of first- and second-hand exposure to welding fumes.

Gas metal arc welding fumes were generated from mild-steel plates and measured near the arc (30 cm), representing first-hand exposure of the welder, and farther away from the source (200 cm), representing second-hand exposure of adjacent workers. Measurements were taken during 1-min welding runs and at subsequent 5-min intervals after the welding process was stopped. Number size distributions were measured in real time. Particle mass distributions were measured using a micro-orifice uniform deposition impactor, and total mass concentrations were measured with polytetrafluorothylene filters. Membrane filters were used for collecting morphology samples for electron microscopy. Average mass concentrations measured near the arc were 45 mg/m3 and 9 mg/m3 at the farther distance. The discrepancy in concentrations at the two distances was attributed to the presence of spatter particles, which were observed only in the morphology samples near the source. As fumes aged over time, mass concentrations at the farther distance decreased by 31% (6.2 mg/m3) after 5 min and an additional 13% (5.4 mg/m3) after 10 min. Particle number and mass distributions during active welding were similar at both distances, indicating similar exposure patterns for welders and adjacent workers. Exceptions were recorded for particles smaller than 50 nm and larger than 3 µm, where concentrations were higher near the arc, indicating higher exposures of welders. These results were confirmed by microscopy analysis. As residence time increased, number concentrations decreased dramatically. In terms of particle number concentrations, second-hand exposures to welding fumes during active welding may be as high as first-hand exposures.

Effect of p53 gene polymorphism on functions of prostate cancer cells.

Prostate cancer cells were transfected with plasmids [empty plasmids, wild-type pcDNA3.1-p53 (V/V), mutant type pcDNA3.1- p53 (G/G)] to analyze the effect of p53 gene polymorphisms on the proliferation, cycle, and apoptosis of prostatic cancer cells. Empty plasmids containing wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1- p53 (G/G) were used to transfect PC3 and LNCaP cells, respectively. Cell proliferation was detected at 0, 24, 48, and 72 h using the MTT method. Cells were collected at 24 and 72 h. The distribution of cell cycles in various groups was detected using flow cytometry (propidium iodide staining method) and the apoptosis rate was detected using annexin V + propidium iodide double staining. Compared with the control group, wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G) showed a significant inhibitory effect on cell proliferation (P < 0.05); the inhibitory effect of the mutant type was stronger than that of the wild-type. There was no significant difference between PC3 cells and LNCaP cells. After transfection with wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G), PC3 and LNCaP cells were arrested in the G0/G1 stage. Transfection with pcDNA3.1-p53 (G/G) showed a more significant effect than transfection with pcDNA3.1-p53 (V/V). Both the wild-type pcDNA3.1-p53 (V/V) and mutant-type pcDNA3.1-p53 (G/G) led to an increased apoptosis rate of PC3 and LNCaP cells. The p53 gene polymorphism affects the proliferation, apoptosis, and cycle of prostate cancer cells and may serve as a reliable index for the diagnosis and treatment of prostate cancer.

Simulation of thermal ablation by high-intensity focused ultrasound with temperature-dependent properties.

An integrated computational framework was developed in this study for modeling high-intensity focused ultrasound (HIFU) thermal ablation. The temperature field was obtained by solving the bioheat transfer equation (BHTE) through the finite element method; while, the thermal lesion was considered as a denatured material experiencing phase transformation and modeled with the latent heat. An equivalent attenuation coefficient, which considers the temperature-dependent properties of the target material and the ultrasound diffraction due to bubbles, was proposed in the nonlinear thermal transient analysis. Finally, a modified thermal dose formulation was proposed to predict the lesion size, shape and location. In-vitro thermal ablation experiments on transparent tissue phantoms at different energy levels were carried out to validate this computational framework. The temperature histories and lesion areas from the proposed model show good correlation with those from the in-vitro experiments.

A Field Study on the Respiratory Deposition of the Nano-Sized Fraction of Mild and Stainless Steel Welding Fume Metals.

A field study was conducted to estimate the amount of Cr, Mn, and Ni deposited in the respiratory system of 44 welders in two facilities. Each worker wore a nanoparticle respiratory deposition (NRD) sampler during gas metal arc welding (GMAW) of mild and stainless steel and flux-cored arc welding (FCAW) of mild steel. Several welders also wore side-by-side NRD samplers and closed-face filter cassettes for total particulate samples. The NRD sampler estimates the aerosol's nano-fraction deposited in the respiratory system. Mn concentrations for both welding processes ranged 2.8-199 µg/m3; Ni concentrations ranged 10-51 µg/m3; and Cr concentrations ranged 40-105 µg/m3. Cr(VI) concentrations ranged between 0.5-1.3 µg/m3. For the FCAW process the largest concentrations were reported for welders working in pairs. As a consequence this often resulted in workers being exposed to their own welding fumes and to those generated from the welding partner. Overall no correlation was found between air velocity and exposure (R2 = 0.002). The estimated percentage of the nano-fraction of Mn deposited in a mild-steel-welder's respiratory system ranged between 10 and 56%. For stainless steel welding, the NRD samplers collected 59% of the total Mn, 90% of the total Cr, and 64% of the total Ni. These results indicate that most of the Cr and more than half of the Ni and Mn in the fumes were in the fraction smaller than 300 nm.

A novel method for assessing respiratory deposition of welding fume nanoparticles.

Welders are exposed to high concentrations of nanoparticles. Compared to larger particles, nanoparticles have been associated with more toxic effects at the cellular level, including the generation of more reactive oxygen species activity. Current methods for welding-fume aerosol exposures do not differentiate between the nano-fraction and the larger particles. The objectives of this work are to establish a method to estimate the respiratory deposition of the nano-fraction of selected metals in welding fumes and test this method in a laboratory setting. Manganese (Mn), Nickel (Ni), Chromium (Cr), and hexavalent chromium (Cr(VI)) are commonly found in welding fume aerosols and have been linked with severe adverse health outcomes. Inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography (IC) were evaluated as methods for analyzing the content of Mn, Ni, Cr, and Cr(VI) nanoparticles in welding fumes collected with nanoparticle respiratory deposition (NRD) samplers. NRD samplers collect nanoparticles at deposition efficiencies that closely resemble physiological deposition in the respiratory tract. The limits of detection (LODs) and quantitation (LOQs) for ICP-MS and IC were determined analytically. Mild and stainless steel welding fumes generated with a robotic welder were collected with NRD samplers inside a chamber. LODs (LOQs) for Mn, Ni, Cr, and Cr(VI) were 1.3 µg (4.43 µg), 0.4 µg (1.14 µg), 1.1 µg (3.33 µg), and 0.4 µg (1.42 µg), respectively. Recovery of spiked samples and certified welding fume reference material was greater than 95%. When testing the method, the average percentage of total mass concentrations collected by the NRD samplers was ~30% for Mn, ~50% for Cr, and ~60% for Ni, indicating that a large fraction of the metals may lie in the nanoparticle fraction. This knowledge is critical to the development of toxicological studies aimed at finding links between exposure to welding fume nanoparticles and adverse health effects. Future work will involve the validation of the method in workplace settings. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: Digestion, extraction, and analysis procedures for nylon mesh screens.].

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles.

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO(2)) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO(2) particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose), and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62 mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.

Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism.

We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO(2) nanoparticles via inhalation to produce a pulmonary deposition of 10 microg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with N(G)-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO(2) exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated ACh-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO(2). Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO(2), but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range.

Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles.

Exposure to fine particulate matter (PM, mean aerodynamic diameter

Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis.

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.

Preliminary study of immunomagnetic quantification of circulating tumor cells in patients with advanced disease.

OBJECTIVES: To enumerate the amount of circulating tumor cells (CTCs) in patients with advanced prostate cancer and to investigate the relationship between these numbers, prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) expression, and clinical parameters. METHODS: Whole blood was collected in proprietary CellSave tubes. Mononuclear cell fractions were isolated using epithelial cell antibody-coated magnetic nanoparticles. On one half of each immunomagnetically enriched cell fraction, automated fluorescent microscopy was used to identify the epithelial tumor cells. From the remainder of each sample, RNA extraction, cDNA synthesis, and polymerase chain reaction amplification of PSA and PSM were performed. RESULTS: Eighty-four patients with advanced prostate cancer submitted 130 samples for analysis. Intact CTCs were identified in 62% of samples; 83.3% of CTC-positive and 0% of CTC-negative samples were reverse transcriptase-polymerase chain reaction positive for PSA and PSM (P = 0.001). A significant positive correlation was found between the CTC number and PSA (r = 0.49), alkaline phosphatase (r = 0.47), and lactate dehydrogenase (r = 0.55) levels, and a significant negative correlation with hemoglobin (r = -0.35). The initial Gleason grade, prior therapy, current therapy, and type of metastasis (bone, soft tissue) did not correlate significantly with the CTC number. CONCLUSIONS: The presence of intact CTCs and the expression of PSA and PSM demonstrated robust agreement. The tumor cell numbers reflected current disease status and correlated significantly with the clinical disease indicators of PSA, hemoglobin, and liver function tests. These findings warrant further investigation of the diagnostic and prognostic value of enumerating intact CTCs.

Brain antioxidant regulation in mammals and anoxia-tolerant reptiles: balanced for neuroprotection and neuromodulation.

Reactive oxygen species (ROS) generated by mitochondrial respiration and other processes are often viewed as hazardous substances. Indeed, oxidative stress, defined as an imbalance between oxidant production and antioxidant protection, has been linked to several neurological disorders, including cerebral ischemia-reperfusion and Parkinson's disease. Consequently, cells and organisms have evolved specialized antioxidant defenses to balance ROS production and prevent oxidative damage. Research in our laboratory has shown that neuronal levels of ascorbate, a low molecular weight antioxidant, are ten-fold higher than those in much less metabolically active glial cells. Ascorbate levels are also selectively elevated in the CNS of anoxia-tolerant reptiles compared to mammals; moreover, plasma and CSF ascorbate concentrations increase markedly in cold-adapted turtles and in hibernating squirrels. Levels of the related antioxidant, glutathione, vary much less between neurons and glia or among species. An added dimension to the role of the antioxidant network comes from recent evidence that ROS can act as neuromodulators. One example is modulation of dopamine release by endogenous hydrogen peroxide, which we describe here for several mammalian species. Together, these data indicate adaptations that prevent oxidative stress and suggest a particularly important role for ascorbate. Moreover, they show that the antioxidant network must be balanced precisely to provide functional levels of ROS, as well as neuroprotection.

Estimating historical respirable crystalline silica exposures for Chinese pottery workers and iron/copper, tin, and tungsten miners.

Collaborative studies of Chinese workers, using over four decades of dust monitoring data, are being conducted by the National Institute for Occupational Safety and Health (NIOSH) and Tongji Medical University in China. The goal of these projects is to establish exposure-response relationships for the development of diseases such as silicosis or lung cancer in cohorts of pottery and mine workers. It is necessary to convert Chinese dust measurements to respirable silica measurements in order to make results from the Chinese data comparable to other results in the literature. This article describes the development of conversion factors and estimates of historical respirable crystalline silica exposure for Chinese workers. Ambient total dust concentrations (n>17000) and crystalline silica concentrations (n=347) in bulk dust were first gathered from historical industrial hygiene records. Analysis of the silica content in historical bulk samples revealed no trend from 1950 up to the present. During 1988-1989, side-by-side airborne dust samples (n=143 pairs) were collected using nylon cyclones and traditional Chinese samplers in 20 metal mines and nine pottery factories in China. These data were used to establish conversion factors between respirable crystalline silica concentrations and Chinese total dust concentrations. Based on the analysis of the available evidence, conversion factors derived from the 1988-1989 sampling campaign are assumed to apply to other time periods in this paper. The conversion factors were estimated to be 0.0143 for iron/copper, 0.0355 for pottery factories, 0.0429 for tin mines, and 0.0861 for tungsten mines. Conversion factors for individual facilities within each industry were also calculated. Analysis of variance revealed that mean conversion factors are significantly different among facilities within the iron/copper industry and within the pottery industry. The relative merits of using facility-specific conversion factors, industry-wide conversion factors, or a weighted average of the two are discussed. The exposure matrix of the historical Chinese total dust concentrations was multiplied by these conversion factors to obtain an exposure matrix of historical respirable crystalline silica concentrations.

Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum.

Somatodendritic release of dopamine (DA) in midbrain represents a novel form of intercellular signaling that inherently differs from classic axon-terminal release. Here we report marked differences in the Ca(2+) dependence and time course of stimulated increases in extracellular DA concentration ([DA](o)) between the substantia nigra pars compacta (SNc) and striatum. Evoked [DA](o) was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry in brain slices. In striatum, pulse-train stimulation (10 Hz, 30 pulses) failed to evoke detectable [DA](o) in 0 or 0.5 mm Ca(2+) but elicited robust release in 1.5 mm Ca(2+). Release increased progressively in 2.0 and 2.4 mm Ca(2+). In sharp contrast, evoked [DA](o) in SNc was nearly half-maximal in 0 mm Ca(2+) and increased significantly in 0.5 mm Ca(2+). Surprisingly, somatodendritic release was maximal in 1.5 mm Ca(2+), with no change in 2.0 or 2.4 mm Ca(2+). Additionally, after single-pulse stimulation, evoked [DA](o) in striatum reached a maximum (t(max)) in <200 msec, whereas in SNc, [DA](o) continued to rise for 2-3 sec. Similarly, the time for [DA](o) to decay to 50% of maximum (t(50)) was 12-fold longer in SNc than striatum. A delayed t(max) in SNc compared with striatum persisted when DA uptake was inhibited by GBR-12909 and D(2) autoreceptors were blocked by sulpiride, although these agents eliminated the difference in t(50). Together, these data implicate different release mechanisms in striatum and SNc, with minimal Ca(2+) required to trigger prolonged DA release in SNc. Coupled with limited uptake, prolonged somatodendritic release would facilitate DA-mediated volume transmission in midbrain.

H(2)O(2) is a novel, endogenous modulator of synaptic dopamine release.

Recent evidence suggests that reactive oxygen species (ROS) might act as modulators of neuronal processes, including synaptic transmission. Here we report that synaptic dopamine (DA) release can be modulated by an endogenous ROS, H(2)O(2). Electrically stimulated DA release was monitored in guinea pig striatal slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenously applied H(2)O(2) reversibly inhibited evoked release in the presence of 1.5 mM Ca(2+). The effectiveness of exogenous H(2)O(2), however, was abolished or decreased by conditions that enhance Ca(2+) entry, including increased extracellular Ca(2+) concentration ([Ca(2+)](o); to 2.4 mM), brief, high-frequency stimulation, and blockade of inhibitory D(2) autoreceptors. To test whether DA release could be modulated by endogenous H(2)O(2), release was evoked in the presence of the H(2)O(2)-scavenging enzyme, catalase. In the presence of catalase, evoked [DA](o) was 60% higher than after catalase washout, demonstrating that endogenously generated H(2)O(2) can also inhibit DA release. Importantly, the Ca(2+) dependence of the catalase-mediated effect was opposite to that of H(2)O(2): catalase had a greater enhancing effect in 2.4 mM Ca(2+) than in 1.5 mM, consistent with enhanced H(2)O(2) generation in higher [Ca(2+)](o). Together these data suggest that H(2)O(2) production is Ca(2+) dependent and that the inhibitory mechanism can be saturated, thus preventing further effects from exogenous H(2)O(2). These findings show for the first time that endogenous H(2)O(2) can modulate vesicular neurotransmitter release, thus revealing an important new signaling role for ROS in synaptic transmission.