Specific Damaging Effect Research Articles

Toxic and hygienic evaluation of the pyridine derivative — 2-ethyl-4-nitropyridine N-oxide

Introduction. The toxic and hygienic assessment of both the final product and intermediate synthesis products remains the key preventive measure to avoid intoxication of workers’ body by industrial xenobiotics in the chemical and pharmaceutical industry and in the context of a constant increase in the range of used compounds. In recent years, nitrogen-containing heterocyclic compounds of the pyridine group have been widely used in various industries. One of these substances is the anti-tuberculosis drug ethionamide, the intermediate product in the synthesis of which is 2-ethyl-4-nitropyridine N-oxide. Materials and methods. In experiments, the toxic properties of 2-ethyl-4-nitropyridine N-oxide were studied. The investigations were carried out on outbred rats and mice, rabbits and guinea pigs. The effect of the substance on experimental animals was assessed using standard physiological, biochemical, hematological and morphological indices. Intermediate toxicity was studied with different methods of substance administration (oral, percutaneous and inhalation) both in single and repeated experiments. The obtained results were processed using the Statistic 10.0 software package. Results. Mean lethal doses of 2-ethyl-4-nitropyridine N-oxide for female rats and male mice were 1250 mg/kg (976.6÷1600.0 mg/kg) and 430 mg/kg (355.4÷520.3mg/kg), respectively; for female mice - 675 mg/kg. The ability of the substance to accumulate was average: the cumulation coefficient was 4.0. There were no significant differences in the effect of the substance on animals of different species and gender. The substance didn’t show a local irritating effect on the skin, skin-resorptive and allergic effects, but a pronounced irritating effect on the mucous membranes of the eyes was revealed. In the subacute experiment, 2-ethyl-4-nitropyridine N-oxide showed a toxic effect mainly on the blood system. A specific damaging effect was revealed, which was expressed in an imbalance of the content of oxyhemoglobin and methemoglobin with a significant increase in the latter. The threshold index of acute inhalation effect was 76.7 mg/m3. The tentative safe exposure level in the air of the working area for the substance was calculated at the level of 0.5 mg/m3. Limitations. The investigation is limited to the study of the toxicological characteristics of 2-ethyl-4-nitropyridine N-oxide. In accordance with the directive documents on the protection of experimental animals, the limited number of in vivo experiments is connected with the dangers for animals and with public ethical views on in vivo experiments. Conclusion. The proposed tentative safe level of exposure to 2-ethyl-4-nitropyridine N-oxide in the air of the working area at the level of 0.5 mg/m3 makes it possible to attribute the xenobiotic to hazard class II. Under the conditions of compliance with the specified standard, the dose absorbed by the worker under the production conditions will be no more than 5-10 mg per work shift, which guarantees safety for health and minimizes the risk to the health of workers. Information on the toxicity of 2-ethyl-4-nitropyridine N-oxide can be useful for solving a wide range of tasks fixed in the control and supervisory activities of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing, hygienic rationing and monitoring, and will contribute to the prevention and reduction of incidence rate associated with the exposure to harmful factors of the production environment.

RNA protects a nucleoprotein complex against radiation damage.

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. Here, a methodology has been developed whereby per-atom density changes could be quantified with increasing dose over a wide (1.3-25.0 MGy) range and at higher resolution (1.98 Å) than the previous systematic specific damage study on a protein-DNA complex. Specific damage manifestations were determined within the large trp RNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. Additionally, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.

The efficacy of post porosity plasma protection against vacuum-ultraviolet damage in porous low-k materials

As of today, plasma damage remains as one of the main challenges to the reliable integration of porous low-k materials into microelectronic devices at the most aggressive node. One promising strategy to limit damage of porous low-k materials during plasma processing is an approach we refer to as post porosity plasma protection (P4). In this approach, the pores of the low-k material are filled with a sacrificial agent prior to any plasma treatment, greatly minimizing the total damage by limiting the physical interactions between plasma species and the low-k material. Interestingly, the contribution of the individual plasma species to the total plasma damage is not fully understood. In this study, we investigated the specific damaging effect of vacuum-ultraviolet (v-UV) photons on a highly porous, k = 2.0 low-k material and we assessed the P4 protective effect against them. It was found that the impact of the v-UV radiation varied depending upon the v-UV emission lines of the plasma. More importantly, we successfully demonstrated that the P4 process provides excellent protection against v-UV damage.

Caring Teachers and Symbolic Violence: Engaging the Productive Struggle in Practice and Research

Symbolic violence may not be a desirable theory to apply to public schooling—its structuralist limitations render it deterministic, lacking in human agency, and unpalatable to researchers and educators who see schools as viable and productive sites of social transformation. Perhaps for these reasons, it seems little has been written about symbolic violence in schools, and what has been written tends to focus primarily on the symbolic, institutionalized violence imparted by schools and teachers upon students. In this article, I offer a shift in these perspectives. I present symbolic violence as a productive analytical tool in identifying modes of resistance to specific damaging effects of schooling institutions. I also illustrate how symbolic violence victimizes one particularly caring teacher, rendering her compliant in her own victimization, without voice to accurately name her struggles, and—because of her ethic of care—complicit in reproducing damaging institutionalizing practices. Using ethnographic data, I explore symbolic violence via one teacher's reflective, critical narratives. I draw upon the tenets of dialogicality in language to help make more visible the often intangible elements of symbolic violence. And at various points in the article, I discuss the implications of engaging an analytic that ultimately runs counter to my own epistemology, turning to Maxine Greene for insight in the struggle.

Why have you both come? Emotional, relationship, sexual and social issues raised by heterosexual couples seeking sexual therapy (in women referred to a sexual difficulties clinic with a history of vulval pain)

Women diagnosed by a dermatologist with vulvodynia, the majority with vulvovestibulitis, were interviewed prior to commencing couple sexual therapy by a research psychotherapist. The transcribed interviews were analysed for themes by the research psychotherapist, which identified five themes as experienced by most of the couples. These were: the concept of emotional distress; issues of failure and loss; a specific damaging effect on the couple relationship; emotional isolation; and feeling uncared for by the medical profession who had “sent them” (for therapy). All the couples described their medical problems in detail. The women were still on occasions able to accept penetration from their partner despite experiencing pain. The couples were seeking to find a “cure” for the problem and all expressed relief at being heard and of being taken seriously. These themes, the other shared issues and the relevance to therapy is discussed.

T08-O-09 Why have you both come for sex therapy?

What emotional, relationship, sexual and social issues did heterosexual couples raise when requesting sexual therapy (where a female partner was referred to a sexual difficulties clinic with a history of vulval pain) in a qualitative interview, prior to commencing couple psychotherapy? The purpose of this study was a project which attempts to gain more understanding and insight into the syndrome and its effects on the individual and the couple relationship. This study hopes to describe in more detail what vulval pain and concurrent vaginal dryness means to the couple, and the effects on a couple of this chronic problem, in an area of the body which is currently taboo to many health professionals. This further research analysis showed themes which had been experienced by most of the couples. These were the concept of emotional distress; failure and loss issues; specific damaging effect on the couple relationship; emotional isolation; and feeling uncared for by the medical profession who had ‘sent them’. These themes, the other raised issues, their relevance to sexual therapy and to using appropeiate physical treatments, including increased and appropriate vaginal lubrication, will be discussed. Psychotherapy was viewed as more likely to be helpful when the client views the professional as believing that the pain is real. The client may not initially consider therapy to be useful, particularly if the realistic goal of therapy may need to be to help the couple adjust to new sexual activities, where pain and dryness may be managed rather than cured.

Cadmium alters the localization of N-cadherin, E-cadherin, and β-catenin in the proximal tubule epithelium

Recent studies on proximal tubule-derived cells in culture have shown that Cd has relatively specific damaging effects on the cadherin-dependent junctions between the cells. The objective of the present study was to determine whether Cd can affect cadherin-dependent junctions in the proximal tubule epithelium in vivo. Male Sprague–Dawley rats received subcutaneous injections of Cd (0.6 mg/kg in isotonic saline, 5 days per week for up to 6 weeks). One day each week, 24-h urine samples were collected and analyzed for protein and creatinine. After 5–6 weeks, the Cd-treated animals developed significant proteinuria, with no change in creatinine excretion. Visualization of pan-cadherin immunoreactive materials by immunoperoxidase labeling showed that Cd caused a marked reduction in the intensity of cadherin labeling associated with the apical and the basolateral surfaces of the epithelial cells of the proximal tubule, but no change in the pattern of cadherin labeling in other segments of the nephron. Results of studies utilizing specific antibodies against N-cadherin, E-cadherin, and β-catenin showed changes in the localization of all three molecules in the proximal tubule. Assessment of cell membrane integrity with trypan blue and ethidium homodimer showed no overt evidence of death in the proximal tubule epithelial cells. Additional results showed that Cd caused only a slight increase in the total levels of glutathione and no significant peroxidation of membrane lipids, indicating only a modest level of oxidative stress. These results indicate that Cd can disrupt cadherin-dependent cell–cell junctions in the proximal tubule, and they raise the possibility that a loss of cadherin-mediated adhesion may contribute to the nephrotoxic effects of Cd.

Microdamage at the pin-bone interface of external skeletal fixation pins after short-term cyclical loading ex-vivo

SummaryThis study determined microdamage associated with external fixation pin insertion and short-term cyclical loading, using an ex vivo ovine tibial model. Orthofix tapered blunt-tipped 3.5/4.5 mm fixation pins and Apex® self-drilling self-tapping fixation pins, 4 mm in diameter, were used. After insertion, the constructs were either loaded in cantilever bending or not loaded. Constructs were then bulk-stained in basic fuchsin, and calcified sections were made. The sections were reviewed qualitatively and the microcrack surface density (Cr.S.Dn, μm/mm2) was quantified at the pin-bone interface. The pattern and quantity of microdamage induced was significantly influenced by fixation pin design and cortical region within the cisor transcortex, but not short-term cyclical loading. Overall, Cr.S.Dn was significantly increased with use of the Orthofix fixation pin (P < 0.01). Cr.S.Dn was also increased in the medial cis-cortex, compared with the lateral transcortex (P < 0.05). Diffuse damage within the medial cis-cortex was higher with the Orthofix pin. In contrast, the Howmedica Apex® fixation pin caused fracture of the periosteal region of the lateral transcortex, but relatively little microdamage within the medial cis-cortex. In this model as a consequence of pin insertion, fixation pin design had significant specific damage effects on both the medial cis-cortex and the lateral trans-cortex

Surface binding and uptake of cadmium (Cd2+) by LLC-PK1 cells on permeable membrane supports.

Recent studies have shown that Cd2+ has relatively specific damaging effects on cell-cell junctions in the renal epithelial cell line, LLC-PK1. The objective of the present studies was to examine the surface binding and uptake of Cd2+ by LLC-PK1 cells in relation to the disruption of cell-cell junctions. LLC-PK1 cells on Falcon Cell Culture Inserts were exposed to CdCl2 containing trace amounts of 109Cd2+ from either the apical or the basolateral compartments, and the accumulation of 109Cd2+ was monitored for up to 8 h. The integrity of cell-cell junctions was assessed by monitoring the transepithelial electrical resistance. The results showed that the cells accumulated 3-4 times more Cd2+ from the basolateral compartment than from the apical compartment. The accumulation of Cd2+ from the basolateral compartment occurred in two phases: a rapid, exponential phase that occurred in 1-2 h and coincided with a decrease in transepithelial resistance, and a slower, linear phase that continued for 6-8 h. The Cd2+ that accumulated during the rapid phase was easily removed by washing the cells in EGTA, indicating that most of it was bound to sites on the cell surface. By contrast, most of the Cd2+ that accumulated during the slower phase could not be removed by EGTA, indicating that it had been taken up by the cells. Additional studies showed that the rapid phase of Cd2+ accumulation was enhanced when Ca2+ was present at low concentrations (0.1 mM), and was greatly reduced when Ca2+ was present at high concentrations (10 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Cadmium (Cd 2+) disrupts Ca 2+-dependent cell-cell junctions and alters the pattern of E-cadherin immunofluorescence in LLC-PK 1 cells

Recent findings from our laboratories have shown that Cd 2+ has relatively specific damaging effects on the adhering and occluding junctions in the established porcine renal epithelial cell line, LLC-PK 1. Results of the present studies show that the junction-perturbing effects of Cd 2+ in LLC-PK 1 cells are more pronounced when Cd 2+ is applied to the basolateral cell surface than when it is applied to the apical surface, and that the severity of the effects is inversely related to the concentration of Ca 2+ in the medium. Additional results show that exposure to sublethal concentrations of Cd 2+ decreases the amount of E-cadherin that is associated with cell-cell contacts. These results suggest that Cd 2+ damages Ca 2+-dependent cell-cell junctions in LLC-PK 1 cells by interacting with E-cadherin or a similar Ca 2+-sensitive site that is oriented toward the basolateral cell surface.

Effects of Aphis fabae and Uromyces viciae‐favae on the growth of a susceptible and an aphid resistant cultivar of Vicia faba

SummaryDamaging effects of either black bean aphid (Aphis fabae), broad bean rust (Uromyces viciae‐fabae), or the combination of both were investigated on a susceptible (cv. Diana) and an aphid resistant (cv. Bolero) cultivar of Vicia faba. When compared with rust, aphids caused greater reductions of root dry weight, shoot dry weight, leaf area, and mean relative growth rate. The mean unit leaf rate was also reduced whereas the leaf area ratio was not affected. The damage caused per aphid was highest on the susceptible cultivar. Rust induced damage did not differ between the cultivars. Concomitant infestation with both pests only resulted in additive damage. The population development of aphids was delayed on partially resistant plants. High temperature and rust infection reduced the total number of aphids the plants were able to support but not the level of resistance. Thus the specific damaging effect per aphid was increased.

Cadmium (Cd 2+) disrupts intercellular junctions and actin filaments in LLC-PK 1 cells

Studies reported in the literature suggest that cadmium (Cd 2+) may disrupt the junctions between cells in some tissues and cell culture systems. In order to examine this possibility in more detail, we have studied the effects of Cd 2+ on the integrity of intercellular junctions in the established porcine renal epithelial cell line, LLC-PK 1. Junctional integrity was assessed by monitoring the collapse of domes and by measuring changes in the transepithelial electrical resistance in confluent cell monolayers. Exposure to Cd 2+ caused a rapid decrease in transepithelial resistance and the concomitant collapse of domes. These effects occurred at Cd 2+ concentrations (20–60 μ m) and durations of exposure (as little as 1 hr) that did not alter levels of ATP or kill the cells. Electron microscopic studies showed that Cd 2+ caused time-dependent changes in adhering and occluding junctional complexes, which eventually resulted in the complete separation of the cells. Additional studies, in which rhodamine-coupled phalloidin was used to visualize F-actin, showed that Cd 2+ altered the structure of actin filaments in the cells; there was a significant reduction in the amount of junction-associated F-actin and in the number of stress fibers. These results indicate that Cd 2+ has relatively specific damaging effects on the adhering and occluding junctions between LLC-PK 1 cells and that these effects may involve the disruption of cytoskeletal actin filaments.

Contribution of ethanol and cigarette smoking to pulmonary dysfunction in chronic alcoholics.

Ethanol is claimed to have a specific damaging effect on the lung and to be at least partially responsible for pulmonary dysfunction in alcoholics. Adequate allowance for the damaging effects of cigarette smoking has not, however, been made hitherto. Pulmonary function studies were undertaken in 27 alcoholic subjects. Although there was a high prevalence of symptoms and abnormalities of pulmonary function, these were largely confined to current smokers: most of those who had never smoked and the ex-smokers who were symptom free and had normal pulmonary function. A case controlled study of alcoholics and matched controls showed no significant difference in pulmonary function between the two groups. It is concluded that the high prevalence of respiratory disease in alcoholics is largely attributable to their smoking habits: no evidence of a specific pulmonary toxic effect of ethanol was identified in the study.

Chemical sympathectomy by 6-hydroxydopamine and arterial enzymes and lactate in the rabbit

The effect of 6-hydroxydopamine (6-OHDA) on the activity of arterial enzymes and lactate was investigated in rabbits. It is known that 6-OHDA exerts a specific damaging effect on the adrenergic nerve endings and produces gangliopetal degeneration, thus eliminating the adrenergic effect pathway. Eight weeks following chemical sympathectomy malate dehydrogenase, isocitrate dehydrogenase, lipoamide dehydrogenase, and creatine phosphokinase exhibited significantly lower activity in the iliofemoral arteries of the 6-OHDA-treated animals as compared to those of the control rabbits. A direct inhibition of the activity of the enzymes by 6-OHDA can be reasonably excluded on the basis of in vitro studies. The aortas of the 6-OHDA-treated animals revealed an increase of pyruvate kinase only, without any significant change in activity of the other enzymes studied. The results dealing with enzymes in the iliofemoral arteries resemble the findings obtained previously in injured or atherosclerotic or “preatherosclerotic” human and animal arteries. The lactate level in the abdominal aortas, which are structurally similar to the iliofemoral arteries, was significantly higher in the 6-OHDA-treated animals than in the control rabbits. It appears that alterations of arterial innervation produce a metabolic pattern which may contribute to increased susceptibility to atherosclerosis.

Toxic Effects of Local Anesthetics

To the Editor.— The recent review by de Jong on Toxic Effects of Local Anesthetics (239:1166,1978) contains a serious omission in that it does not mention the specific damaging effects of local anesthetics on the eye. The severe contact keratitis that can develop from prolonged use of topical anesthetics in the eye should be emphasized. Although the toxic reaction had been pointed out numerous times in the past, 1 failure to recognize the effect continues to occur, not only in this country but also in Europe. 2 It has long been known that local anesthetics inhibit the rate of movement of corneal epithelial cells migrating to cover wounds. The cellular basis of this toxicity may lie in disruption of cytoplasmic actin filaments, 3 which are believed to be responsible for the movement of cells across corneal wounds. 4 In a report of chronic toxicity of local anesthetics on the cornea,

Selective adrenal necrosis and apoplexy induced by 7, 12-dimethylbenz(a)anthracene.

Invariably in every normal rat a single dose of 7, 12-dimethylbenz(a)anthracene, by mouth or injected in a vein, was found to cause apoplexy and massive necrosis in the inner zones of the adrenal cortex; the zona glomerulosa, the adrenal medulla, and a small region of cortex adjacent to the great adrenal vessels were spared from damage. DMBA caused these selective lesions in females and in males of 2 strains of rats. Hemorrhage and necrosis were observed in no organ other than the adrenal gland. Whereas adrenal glands were heavily damaged by DMBA, pituitary and ovary escaped injury by the compound. A single huge but sublethal feeding of o, p'-DDD caused degenerative changes of minor magnitude in the adrenals and only in a small percentage of rats; the property of inducing adrenal damage was not shared by other polynuclear aromatic hydrocarbons which were investigated, including strong carcinogens. Presence of adrenal medulla is not a prerequisite to damage of the adrenal cortex by DMBA. The adrenal damage occurred in rats, given DMBA, from which the pituitary had been removed but the lesions were smaller in extent and less in incidence as post-hypophysectomy atrophy of the adrenal cortex progressed. The entire DMBA molecule was necessary to induce adrenal damage; fragments of this molecule did not induce adrenal lesions. Two components which are of cardinal importance in this specific damaging effect are: (a) electronic factor; (b) steric factor. The level of isocitric dehydrogenase in adrenal is modified considerably by presence or absence of estradiol-17beta.