Indicator Of Early Damage Research Articles

Short-term exposure to ozone and ECG abnormalities in China: A nationwide longitudinal study

Ambient ozone (O3) pollution has been associated with an increased risk of cardiovascular diseases. However, few studies have addressed the effect of O3 exposure on electrocardiogram (ECG) abnormalities, a subclinical indicator of early damage to the cardiovascular system. This study aimed to examine the association between short-term exposure to O3 and ECG abnormalities. We included 102,027 visits of 47,290 participants over 40 years old who had a normal ECG at baseline and then visited again at least once from the China National Stroke Screening Survey (CNSSS). Short-term ozone exposure concentrations were measured as averages of maximum daily 8-h O3 concentrations over the two weeks prior to ECG measurements. The generalized estimation equations models were used to evaluate the association between O3 exposure and ECG abnormalities. For every 10 µg/m3 increment in short-term O3 concentration, the odds ratio of any ECG abnormality was 1.055 (95% confidence interval [CI] 1.045–1.064). For ECG-diagnosed cardiac arrhythmia, the odds ratio was 1.062 (95% CI 1.052–1.072). A nonlinear analysis showed a sublinear relationship between O3 exposure and risk for ECG abnormalities. The association between O3 exposure and ECG abnormalities varied by subpopulation. Our study provided new epidemiological evidence on the association between short-term O3 exposure and ECG abnormalities. There is an urgent need to control ambient O3 pollution to prevent cardiovascular events.

POS-147 URINARY N-ACETYL-BETA-D-GLUCOSAMINIDASE, A MARKER OF LUPUS NEPHRITIS ACTIVITY

Increased activity of urinary N-acetyl-beta-D-glucosaminidase can be used as an early indicator of damage to the tubular epithelium. Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disorder. Lupus nephritis (LN) is a common and serious complication of SLE and the strongest predictor of poor outcome.

Ultrasonic evaluation of early damage of a coating by using second-harmonic generation technique

For an in-service structure with a coating, damage accumulation may develop gradually within the coating or at the interface between the substrate and coating under external loads. By considering the fact that different levels of external load are closely related to the degrees of accumulated early damage which is very difficult to be measured directly, and that the early damage may cause the nonlinearity of Rayleigh surface waves, the acoustic nonlinearity parameter (ANP) is employed as an indicator of early damage of a coating. This research reports on the experimental observation of the monotonic correlation between the ANP measured with nonlinear Rayleigh waves and the applied stress on an AZ31 magnesium alloy plate specimen using ultrasonic second-harmonic generation technique. Rayleigh waves are generated and detected with wedge transducers, and the nonlinearity parameters are measured at different stress levels for the specimens with coatings. The result shows that there is a significant increase in the nonlinearity parameters with the increasing tensile stress although there is no obvious change for the coating when the tensile stress is less than a certain level. The research suggests an effective nondestructive evaluation method to track the coating damage using the higher order harmonic generation technique.

Using Diffusion Tensor Imaging and Mixed-Effects Models to Investigate Primary and Secondary White Matter Degeneration in Alzheimer's Disease and Mild Cognitive Impairment

White matter (WM) degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with mixed-effects models. Four indices of diffusion were assessed in 61 healthy control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of the study was to use advanced mixed-effects models to investigate the retrogenesis hypothesis of AD, which suggests that tracts that are late to myelinate in ontogenetic development are the earliest to be affected in AD. Our results show that a number of late-myelinating pathways, including the parahippocampal region and the inferior longitudinal fasciculus, were predominantly affected by changes in WM volume. Conversely, early-myelinating pathways were found to be affected by a combination of both WM and gray matter (GM) atrophy. A model of the entire WM structure of the brain returned GM models for two indices of diffusion, suggesting that more complex regional landscapes of diffusion lie hidden beneath a global analysis of the entire brain. Our results warn against an explanation of white matter damage that points simply to one of two mechanisms: secondary degeneration or direct damage of myelin. We suggest that tracts may be affected by both mechanisms, with the balance depending on whether tracts are early or late-myelinating. A greater understanding of the pattern of WM changes in AD may prove useful for the early detection of AD.

Mechanical Barkhausen noise during fatigue of iron

In this paper, the potentiality for using the mechanical Barkhausen noise (BN) to monitor fatigue tests of ferrous materials is investigated. The fatigue tests are carried out on iron specimens subjected to rotational bending on a standard fatigue bench. The mechanical BN is detected using an encircling coil. The mechanical BN exhibits three main stages during the fatigue life: it increases at the beginning of the test, then a plateau is reached and finally it decreases before rupture. These successive stages can be associated to the classical stages of the fatigue life of metals and alloys: crystalline microstructure changes, a saturation stage, and microcrack nucleation and growth leading to rupture. An early indicator of damage is derived from the results.

Urinary N‐acetyl‐β‐D‐glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis

Increased activity of urinary N-acetyl-beta-D-glucosaminidase (NAG) can be used as an early indicator of damage to the tubular epithelium. Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease. Nephritis is known as the most serious complication of SLE and the strongest predictor of poor outcome. In this study urinary NAG excretion was investigated in 24 SLE patients with normal renal function (serum creatinine < or =1.2 mg/dL) and the results were compared with those from 26 untreated patients with rheumatoid arthritis (RA) and 27 healthy controls. The SLE patients were divided into two groups according to their urinary total protein levels: group A consisted of 16 patients with < or =3.5 g/day proteinuria, and group B consisted of eight patients with nephrotic-range proteinuria (>3.5 g/day). Serum and urinary creatinine, total urinary protein levels, and urinary NAG excretion were measured in patients with SLE and RA. In addition, serum C3 and C4 levels were determined in the SLE patients. Renal biopsies were performed in all of the SLE patients. Glomerular lesions were classified according to WHO criteria for lupus nephritis (LN) I-V. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used to assess disease activity. Urinary NAG excretion was significantly higher in the SLE groups than in the healthy controls (P<0.001). In urinary NAG excretion there was also significant difference between SLE groups and RA patients (P<0.001). However, there was no significant difference in NAG excretion between the RA and control groups (P=0.062). Urinary NAG excretion was significantly higher (P<0.05) in group B compared to group A. There were no differences in SLEDAI scores, ages, and serum creatinine levels between study groups (P=0.601, P=0.285, P=0.669, respectively). Elevated SLEDAI values and hypocomplementemia were detected more often in younger patients (P<0.010, r=-0.529 and P<0.010, r=-0.569, respectively). There was a strong positive correlation between proteinuria and urinary NAG activity (P<0.001, r=0.759). These results suggest that the determination of urinary NAG activity may be a useful supplement to the routine biochemical analysis performed on the urine in cases of SLE.

Analysis of VMAT2 binding after methamphetamine or MPTP treatment: disparity between homogenates and vesicle preparations.

[3H]Dihydrotetrabenazine ([3H]DTBZ), a specific ligand for the vesicular monoamine transporter (VMAT2), has been used to characterize the integrity of monoaminergic nerve terminals in experimental animals and humans. The purpose of the present studies was to compare the loss of VMAT2 binding with the loss of other neurochemical markers of the dopamine (DA) nerve terminals in mice treated with neurotoxic doses of methamphetamine (METH) or MPTP. Profound decreases (> or =70%) in DA content, tyrosine hydroxylase activity, and PH]carbomethoxy-3-(4-fluorophenyl)tropane binding to the DA transporter were observed in striatal homogenates at both 1 and 6 days after exposure to the neurotoxins. It is surprising that no significant loss of [3H]DTBZ binding in the homogenates was observed at 1 day after exposure, although a significant loss (-50%) was apparent 6 days later. However, in isolated vesicle preparations, [3H]DTBZ binding and active [3H]DA uptake were markedly reduced (>70%) at 1 day. These observations indicate that vesicle function is compromised at an early time point after exposure to neurotoxic insult. Furthermore, the changes in [H]DTBZ binding in homogenates may not be a sensitive indicator of early damage to synaptic vesicles, although homogenate binding reliably identifies a loss of VMAT2 at later times.

Loss of tyrosine hydroxylase immunoreactivity in dendrites is a sensitive index of kainic acid-induced damage in rat substantia nigra neurons in vivo

An early indicator of damage to substantia nigra dopamine neurons in vitro is loss of dendrites that precedes loss of the cell body. To investigate dendritic damage in vivo, rats were treated for 1 day or 1 week with kainic acid (KA; 5 or 10 mg/kg i.p.), the brain fixed and substantia nigra (SN) dopamine neurons and their dendrites labeled using an antibody to tyrosine hydroxylase (TH). KA (10 mg/kg) produced seizures initially and resulted in significant loss of TH immunoreactivity in dendrites of dopamine neurons 1 week, but not 1 day, after a single injection. Daily injections of 5 mg/kg KA, which did not produce seizures, resulted in more extensive dendritic damage. The findings indicate that loss of dendritic staining is a sensitive index of damage to SN dopamine neurons in vivo.

PLASMA GLUTATHIONE PEROXIDASE AND ITS RELATIONSHIP TO RENAL PROXIMAL TUBULE FUNCTION. • 2215

Extracellular glutathione peroxidase (EGPx) is a unique seleno-enzyme found in plasma and other extracellular fluids. Based on the disappearance of plasma EGPx activity in nephrectomized animals and the high level of EGPx mRNA in renal tissue, it was previously concluded that the kidney was the major source of plasma EGPx activity. We have previously shown that humans with renal failure receiving chronic dialysis treatment possess 42% plasma GPx activity. We examined the effect of nephrectomy and renal transplantation on plasma GPx activity. Nephrectomized patients have 22% plasma GPx activity, which increases to ≥ 100% of normal within 2 weeks following transplantation.In situ hybridization studies have shown that EGPx message is predominantly localized to the proximal convoluted tubules. We have determined that the EGPx mRNA is localized specifically to the S1 and S2 segments of the proximal tubules. We therefore examined the effect of nephrotoxic agents known to affect proximal tubule function. In rabbits, a nephrotoxic dose of cephaloglycin (300 mg/kg) caused a 52% decrease in plasma GPx activity within 24 hours. This effect was prevented by concomitant treatment with probenecid. Patients receiving ifosfamide chemotherapy were found to have lower levels of plasma GPx activity. Three patients with Fanconi syndrome associated with ifosfamide therapy had 50, 56, and 23% of control plasma GPx activity. After resolution of the Fanconi syndrome in one patient, plasma GPx activity returned to normal within one month. We speculate that plasma GPx activity may be a sensitive and early indicator of damage to renal proximal tubules.

Diagnostic value of short-wavelength automated perimetry.

Short-wavelength automated perimetry (SWAP) uses a bright yellow background and a large blue stimulus to isolate and measure the sensitivity of short-wavelength-sensitive mechanisms throughout the central 30 degrees visual field. After more than 8 years of cross-sectional and longitudinal studies of patients with early glaucoma, ocular hypertensive patients, and age-matched control subjects, SWAP has been shown to be a sensitive indicator of early damage and progression of loss in glaucoma. It is now available as an optional visual test procedure for routine clinical use on the most widely distributed automated perimeter. Recent investigations have been directed toward refinement and standardization of the technique, as well as toward the influence of other clinical factors (ocular media opacities, macular pigment, statistical interpretation, and related issues) on SWAP. This paper provides a brief overview of current research on SWAP as a clinical diagnostic test procedure.

1/f noise as an early indicator of electromigration damage in thin metal films

Electromigration in thin films of aluminium and aluminium alloys is shown to lead to stepwise increases of the electrical 1/f noise. These are attributed to the generation of highly mobile defect configurations by a nucleation-and-growth process. It is conjectured that among them may be the defects that are responsible for the eventual failure of VLSI electronic devices by electromigration damage. 1/f noise promises to be an early indicator of this damage.

Early damage indicators in the lung: V. Biochemical and cytological response to NO 2 inhalation

In an extension of earlier work on the usefulness of analysis of pulmonary lavage fluid as a probe to detect lung injury, we have examined lavage fluid from animals with a multifocal, terminal bronchiolitis induced by exposure to an oxidant gas. Syrian hamsters were exposed to concentrations of 0, 12, 17, and 22 ppm NO 2 gas for 48 hr. Bronchopulmonary lavage fluids were profiled biochemically and cytologically to determine (1) the indicators of a multifocal, deep lung injury that could be detected in the lung washings and (2) the lowest level of this type of injury that could be detected by the lavage fluid screen. Lung homogenates were assayed for the enzymatic activities measured in lavage fluid and the lungs were evaluated histologically. Highest response for all parameters measured was at 2 days (end of the exposure) when the lavage fluid showed dose-dependent elevations in lactate dehydrogenase, alkaline phosphatase, acid phosphatase, glutathione reductase, and glutathione peroxidase activities, sialic acid, and total protein content, as well as increases in macrophage and neutrophil cell counts. By far the most sensitive indicator of this type of injury, as measured by the lavage fluid screen, was the neutrophil cell count, which showed a 10-fold increase even at the lowest level of exposure. The greatest change seen in the biochemical parameters measured in lavage fluid was the increase in sialic acid and protein content. There was good correlation between the degree of alteration of biochemical and cytologic indicators of injury seen in the lavage fluid and the morphological alterations seen in tissue.

Early damage indicators in the lungs. IV. Biochemical and cytologic response of the lung to lavage with metal salts

A rapid screening test for estimating the acute toxicity level of substances in the lung has been developed and evaluated using metal salts as the toxic agents. In the test, animals were exposed in vivo to the metal salts by bronchopulmonary lavage, and toxicity was determined by the enzymatic and cytologic response observed in the airways 1 day after exposure. The airway response was determined by analysis of bronchopulmonary lavage fluid for lactate dehydrogenase, acid and alkaline phosphatase, and β-glucuronidase activity as well as for total sialic acid and protein content and total and differential cell counts. These values showed a dose-dependent response in the lavage fluid. The enzymatic response of the lung tissue itself was not as marked as that seen in the lavage fluid. Histopathological evaluations of lung tissue were made in order to correlate morphological change with the airway response. The test allowed a rapid determination of the lung dose of metal salt which caused acute toxicity. Based on the biochemical response in the airway, the relative toxicity of the heavy-metal-containing compounds tested was: CdCl 2>SeO 2, NH 4VO 3, NiCl 2>CrCl 3.

Early damage indicators in the lung. III. Biochemical and cytological response of the lung to inhaled metal salts

The validity of using the enzymatic and cytologic profile of airway fluids to indicate lung damage was tested in animals exposed by inhalation to either a known toxic metallic salt (CdCl 2) or a relatively innocuous salt (CrCl 3). The enzymatic and cytologic response of the airways was compared to histopathological evaluation of lung damage. Syrian hamsters were exposed to an aerosol of CdCl 2 (aerodynamic diameter = 1.7 μm, σ g ⋍ 1.7 ) to achieve an initial lung burden (ILB) of 0.6 ± 0.3 and 4.4 ± 1.2 μg of CdCl 2 or to an aerosol of CrCl 3 (count median diameter = 1.2 μm, σ g ⋍ 1.5 ) to achieve an ILB of 0.7 ± 0.2 or 20 ± 10 μg of CrCl 3. Animals were sacrificed at 2 hr, 1, 7, and 21 days after exposure. A sample of airay fluid was obtained by bronchopulmonary lavage and examined for the enzymatic profile of the cell-free fraction and the cytological profile of the cell fraction. Lung tissue enzyme activities were also measured and histopathologic evaluations were made on lung tissue from exposed, but nonlavaged, animals. In the lavage fluid from animals exposed to CdCl 2, the enzymatic and cytologic data demonstrated a dose-response pattern and the airway response preceded enzymatic changes in the lung tissue. Tissue morphological changes correlated well with the biochemical changes. The response of the lung to CrCl 3 was minimal by both morphological and biochemical evaluations. Airway enzymatic and cytologic responses were shown to be potentially useful as indicators of lung damage in toxicological screening programs.

Early Damage Indicators in the Lung: II. Time Sequence of Protein Accumulation and Lipid Loss in the Airways of Beagle Dogs with Beta Irradiation of the Lung

HENDERSON, R. F., MUGGENBURG, B. A., MAUDERLY, J. L., AND TUTTLE, W. A. Early Damage Indicators in the Lung. II. Time Sequence of Protein Accumulation and Lipid Loss in the Airways of Beagle Dogs with Beta Irradiation of the Lung. Radiat. Res. 76, 145-158 (1978). The protein and lipid content of the airways, as measured in the fluid from bronchopulmonary lavage, were evaluated as indicators of damage to the lung in Beagle dogs exposed to , irradiation from inhaled, relatively insoluble forms of g0Y or 4Ce. The increase in total protein level in the lavage fluid from the airways proved to be a more sensitive indicator of lung damage than was the decrease in total lipid content. Other parameters which changed rapidly and early in the injury model were the sterol ester content of the neutral lipids (increased) and the dipalmitoyl lecithin content of the total lecithins (decreased) in the airways. Airway contents can be sampled by bronchopulmonary lavage in nonsacrifice studies and should prove useful in evaluating lung damage in toxicological screening programs.

Early damage indicators in the lung I. Lactate dehydrogenase activity in the airways

The rapid determination of damage in the lung is important in developing screening methods for ranking the toxicity of inhalable pollutants. The presence of lactate dehydrogenase (LDH) activity in the airways was found to be a sensitive indicator of acute toxicity to lung cells. The airway content of LDH increased after bronchopulmonary lavage of Syrian hamsters with increasing amounts of Triton X-100, with a correlation coefficient of 0.98. No increase in iron content of the lavage fluid occurred, indicating that lysed erythrocytes were not the source of the LDH. The isoenzyme pattern of the LDH activity in the lavage fluid suggested the LDH was released from lung cells. The method of detecting early lung injury by the presence of LDH in the airways can be used in one of two ways: The toxic material to be tested may be introduced into the lung by pulmonary lavage and the released LDH may be measured in the same lavage fluid; or in animals exposed to toxicants in aersol form, a lavage can be performed after exposure to obtain a sample of the LDH in the airways.