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61.
Mammalian cell cytotoxicity and genotoxicity analysis of drinking water disinfection by-products 总被引:19,自引:0,他引:19
Plewa MJ Kargalioglu Y Vankerk D Minear RA Wagner ED 《Environmental and molecular mutagenesis》2002,40(2):134-142
Cytotoxicity and genotoxicity assays were used to analyze drinking water disinfection by-products (DBPs) in Chinese hamster ovary (CHO) AS52 cells. The DBPs were chosen because they are common in drinking water, resulting from conventional disinfection using chlorination and chloramination. Data were also available to compare these results with cytotoxicity and mutagenicity studies in Salmonella typhimurium. The rank order in decreasing chronic cytotoxicity measured in a microplate-based assay was bromoacetic acid (BA) > 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) > dibromoacetic acid (DBA) > chloroacetic acid (CA) > KBrO(3) > tribromoacetic acid (TBA) > EMS (ethylmethanesulfonate, positive control) > dichloroacetic acid (DCA) > trichloroacetic acid (TCA). The induction of DNA strand breaks by these agents was measured by alkaline single-cell gel electrophoresis (SCGE, comet assay) and the rank order in decreasing genotoxicity was BA > MX > CA > DBA > TBA > EMS > KBrO(3), while DCA and TCA were refractory. BA was more cytotoxic (31x) and genotoxic (14x) than MX in CHO cells. BA was over 400x more genotoxic than potassium bromate. The brominated haloacetic acids (HAAs) were more cytotoxic and genotoxic than their chlorinated analogs. The HAAs expressed a statistically significant inverse relationship in CHO cell cytotoxicity and genotoxicity as a function of increased numbers of halogen atoms per molecule. A quantitative comparison was conducted with results from a previous study with cytotoxicity and mutagenicity in S. typhimurium. There was no correlation between chronic CHO cell and bacterial cell cytotoxicity. DBP-induced CHO cell cytotoxicity was not related to mutagenic potency in S. typhimurium. Cytotoxicity in CHO cells was statistically significant and highly correlated to CHO cell genotoxicity. Finally, we determined that the DBP genotoxic potency in CHO cells and the mutagenic potency in S. typhimurium were not related. This suggests that toxicity data in S. typhimurium did not quantitatively predict the toxic effects of DBPs in mammalian cell systems. The microplate CHO cell cytotoxicity and genotoxicity assays were well suited for the analysis of DBPs, especially when the quantity of test material is limited. 相似文献
62.
Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice 总被引:2,自引:0,他引:2
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Negrão-Corrêa D Souza DG Pinho V Barsante MM Souza AL Teixeira MM 《Infection and immunity》2004,72(2):1135-1142
We describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR(-/-)) and wild-type mice after a single Strongyloides venezuelensis infection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR(-/-) and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR(-/-) mice. Although PAFR(-/-) infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR(-/-) mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR(-/-) mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR(-/-) mice than in the corresponding preparations from wild-type mice. Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity. 相似文献
63.
The patterns of exochorion ornaments on eggs of seven South American Lutzomyia sand fly species were analyzed by scanning electron microscopy (SEM): Lutzomyia (Lutzomyia) cruzi (Mangabeira 1938), Lutzomyia (Micropygomyia) evandroi (Costa Lima and Antunes 1936), L. (Nyssomyia) intermedia (Lutz and Neiva 1912), L. longipalpis (Lutz and Neiva 1912), L. migonei (Franca 1920), L. (Nyssomyia) neivai (Pinto 1926), and L. renei (Martins, Falcao, and Silva 1957). Different patterns were observed, which showed the distinction between some species. Egg ornaments in L. cruzi and L. longipalpis appear as single, parallel, unconnected ridges, whereas eggs of L. migonei appear as single, parallel, connected ridges. Eggs of L. (Nyssomyia) intermedia and L. (N.) neivai present a new variation of the single, unconnected, parallel ridges pattern: small tubercles are present, distributed between the ridges. Eggs of L. renei present an elliptical pattern, with most structures connected by straight ridges. Eggs of L. (M.) evandroi present a polygonal pattern, with alternate rows of small and large hexagons. Our data emphasize the advantages of the SEM approach in the study of the exochorion patterns of Lutzomyia eggs and in the distinction of the sand fly species. 相似文献
64.
Dick DM Foroud T Edenberg HJ Miller M Bowman E Rau NL DePaulo JR McInnis M Gershon E McMahon F Rice JP Bierut LJ Reich T Nurnberger J 《American journal of medical genetics》2002,114(4):407-412
Analyses of a replication sample of families collected as part of the National Institute of Mental Health (NIMH) Genetics Initiative for bipolar disorder provide further evidence for linkage to a region of chromosome 16. Families who had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SABP) first-degree relative were ascertained for the purpose of identifying genes involved in bipolar affective disorder. A series of hierarchical models of affected status was used in linkage analyses. Initial genetic analyses of chromosomes 3, 5, 15, 16, 17, and 22, completed at Indiana University in 540 subjects from 97 families, suggested evidence of linkage to chromosomes 5, 16, and 22 [Edenberg et al., 1997: Am J Med Genet 74:238-246]. Genotyping was subsequently performed on these chromosomes in a replication sample of 353 individuals from 56 families. Nonparametric linkage analyses were performed using both affected relative and sibling pair methods. Analyses in the new sample on chromosome 16, using the broadest model of affected status, corroborate previously reported suggestive linkage to the marker D16S2619. Combining the initial and replication samples further increased the evidence of linkage to this region, with a peak lod score of 2.8. 相似文献
65.
Lotfi Aarab Sylvie Siaume-Perez Danielle Chabardès 《Pflügers Archiv : European journal of physiology》1993,425(5-6):417-425
Previous studies have demonstrated that prostaglandin E2 (PGE2) inhibits arginine vasopressin-(AVP)dependent adenosine 3,5-cyclic monophosphate (cAMP) accumulation in microdissected rat outer medullary collecting tubules (OMCD), by a mechanism unrelated to the inhibition of cAMP synthesis. The potential role of the activation of protein kinase C (PKC) to explain the negative regulation elicited by PGE2 was investigated in this study. Single OMCD samples were pre-incubated (10 min, 30°C) in the presence or absence of either activators of PKC, phorbol 12-myristate 13-acetate (PMA), 1-oleoyl-2-acetyl-glycerol (OAG), dioctanoylglycerol (DOG) or an inhibitor of PKC, staurosporine (SSP). These compounds were present also with the agonists tested during the incubation period (4 min, 35°C). In contrast to PGE2, activators of PKC did not decrease AVP-dependent cAMP accumulation (mean ±SEM): 1nM AVP=47.1±6.8 fmol · mm–1· 4 min–1; AVP + 0.3 M PGE2=20.1±2.7, P<0.01 versus AVP; AVP + 10 nM PMA=42.0±4.7, NS versus AVP; AVP + 50 g/ml OAG=44.1±4.8. NS versus AVP, N= 5 experiments. However, 10 nM PMA prevented PGE2-induced inhibition: AVP + PGE2= 44.2±3.5% of the response to AVP and 90.3±3.2% without and with PMA respectively, N= 16. Similar results were obtained with either 50 g/ml OAG or 25 g/ ml DOG (AVP + PGE2 + OAG=92.9±6.6% of the response to AVP, N= 8; AVP + PGE2 + DOG=94.1 ±5.3%, N= 7). OAG, DOG, PMA or PMA + PGE2 had no intrinsic agonist activity in the rat OMCD and the addition of an inactive phorbol ester did not prevent PGE2-induced inhibition. SSP, 50 nM or 0.1 M, did not affect the inhibition due to PGE2 but abolished the reversion by PMA of PGE2-induced inhibition. A similar regulation was observed on forskolin-(FK)dependent cAMP accumulation: 5 M FK + 0.3 M PGE2= 37.7±6.2% of the response to FK; FK + PGE2 + 10 nM PMA=89.5±6.7%; FK + PGE2 + PMA + 0.1 M SSP=43.1±7.9%, N= 4. The inhibition induced by an
2-adrenergic agonist, clonidine 1 M, was not blocked by the activation of PKC. In fura-2-loaded OMCD samples, 10nM PMA decreased by 63.3±5.0% and by 57.2±7.1% the peak and plateau phases, respectively, of the increase in intracellular calcium concentration ([Ca2+]i) obtained with PGE2 when compared to control responses in the same tubules (n=12) and did not affect the increase in [Ca2+]i induced by 0.1 mM carbachol. It is concluded that: (1) in the rat OMCD the activation of PKC by PMA or analogues of diacylglycerol did not reproduce PGE2-induced inhibition of AVP- or FK-dependent cAMP accumulation, but prevented specifically this inhibitory action; and (2) this reversion might be the consequence of the effect of PKC activation which impaired the rises in [Ca2+]i induced by PGE2. 相似文献
66.
67.
Danielle Scerri Christian Borg Xuereb Josianne Scerri 《Health & social care in the community》2022,30(1):e195-e203
Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease that is on the rise globally. The disease is associated with significant morbidity and hence poses significant challenges for their informal carers, particularly daughters in mid-adulthood, who struggle with their own personal demands and that of their ill parents. Yet there is a dearth of literature on the experiences of these specific carers. Hence, the purpose of this study is to explore the lived experiences of daughters caring for a parent with pulmonary fibrosis within a community setting. This was explored using a phenomenological qualitative framework that was conducted between January and April 2017. Semi-structured audio-recorded interviews were conducted with six adult daughters who provided care to a parent having pulmonary fibrosis. Purposive sampling was used to recruit study participants. Transcribed data were analysed using Interpretative Phenomenological Analysis. Three main themes were extracted which communicate the essence of the daughters’ lived experiences: “Walking on tiptoes”, “Flooded by emotions” and “Shifts in family dynamics.” Participants described experiencing the toll of being constantly vigilant for symptoms. They also expressed a range of emotions that included guilt, helplessness and worry related to their care experience. However, these emotional struggles were suppressed in order to present an external facade of strength and control. A shift in roles was also described where the daughters became the informal carers/support for both their ill and well parent, albeit in different ways. Caring for a person with pulmonary fibrosis is an emotional and life changing experience and hence, there is the need for individualised interventions that target the unique perceptions of these informal carers. 相似文献
68.
Danielle M. Logue Laura Mahony Clare A. Corish David Tobin Ronan Doherty Grainne OHiggins Sharon M. Madigan 《Nutrients》2021,13(6)
Background: Low energy availability results in physiological adaptations which contribute to unfavourable health outcomes. Little information exists on perceptions of nutritional advice to eat more food to maintain health and enhance performance. The aim of this study was to explore athletes’ and coaches’ perceptions towards advice to athletes to eat larger than their current quantities of food and to explore how nutritionists could deliver this advice. Methods: Semi-structured interviews (~20 min in length) were conducted using online communication technology, audio-recorded, and transcribed verbatim. The interview explored perceptions of the nutritional advice provided, its role in health and performance, and the challenges to eating larger amounts of food. Data were analysed using NVIVO 1.2 using an inductive thematic approach. Results: Nine elite athletes (female = 6; males = 3) and nine high-performance coaches (female = 3; male = 6) completed the semi-structured interviews. Athletes reported improved training consistency, fewer injuries and illnesses, and improved resilience when consuming adequate energy and nutrients to meet their needs. Lack of time and meal preparation difficulties were the main challenges faced to fuelling. Conclusions: Although education about under-fuelling is important, motivating, enabling, and supporting athletes to change behaviour is pivotal to increasing athlete self-awareness and to make long-term nutritional changes. 相似文献
69.
Ren Verreault Danielle Laurin Joan Lindsay Gaston De Serres 《Canadian Medical Association journal》2001,165(11):1495-1498
70.
Molly E. Baumann Danielle M. DeBruler Britani N. Blackstone Rebecca A. Coffey Steven T. Boyce Dorothy M. Supp J. Kevin Bailey Heather M. Powell 《Burns : journal of the International Society for Burn Injuries》2021,47(2):466-478
IntroductionDetermining the efficacy of anti-scar technologies can be difficult as qualitative, subjective assessments are often utilized instead of systematic, objective measures. Perceptions regarding the reliability of instruments for quantitative measurements along with their high cost and increased data collection time may discourage their use, leading to use of scar scales which are relatively quick and low-cost. To directly evaluate the reliability of instruments for quantitative measurements of scar properties, instruments and two qualitative scales were compared by assessing a variety of cutaneous scars.MethodsScar height and surface texture were evaluated using a 3D scanner and a mold/cast technique. Scar color was evaluated by using a spectroscopy-based tool, the Mexameter®, and digital photography with image analysis. Scar biomechanics were evaluated using the BTC-2000?, Dermal Torque Meter (DTM®), and ballistometer®. The Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to qualitatively evaluate the same scar properties. Intraclass correlation coefficients (ICC) were used to determine inter- and intra-user reliability (poor, moderate, good, excellent) with all instruments and the kappa reliability statistic was used to asses inter-user reliability (poor, fair, moderate, good, very good) for VSS and POSAS. Time for measurement collection and after collection analysis was also recorded.ResultsThe Mexameter® was the most reliable method for evaluating erythema and pigmentation compared to digital photography and image processing, POSAS and VSS. Digital photography and analysis was more reliable than POSAS and VSS. Assessment of scar height was significantly more reliable when using a 3D scanner versus VSS and POSAS. The 3D scanner and mold-cast techniques also offered an additional benefit of providing an absolute value of scar height relative to the surrounding tissue. Intra-user reliability for all mechanical tests was moderate to good. Inter-user reliability was greater when using the BTC-2000? and ballistometer® versus the DTM®. All quantitative measurements took less than 90 s for collection, with the exception of the mold/cast technique.ConclusionNon-invasive instruments allow scar properties to be quantitatively assessed with high sensitivity and as a function of time and/or treatment without the need for biopsy collection. Overall, the reliability of scar assessments was significantly improved when quantitative instruments were utilized versus scar scales. Quantitative assessment of color and biomechanics were swift, requiring less than 90 s per measurement while assessments of texture and height required additional analysis time after collection. With proper training of clinical staff and well-defined protocols for measurement collection, reliable, quantitative assessments of scar properties can be collected with little disruption to the clinical workflow. 相似文献