The orienting response of Lake Michigan mottled sculpin is mediated by canal neuromasts

2001 ◽  
Vol 204 (2) ◽  
pp. 337-348 ◽  
Author(s):  
S. Coombs ◽  
C.B. Braun ◽  
B. Donovan
Keyword(s):  
Time Course ◽  
Lake Michigan ◽  
Cell Damage ◽  
Aminoglycoside Antibiotic ◽  
Response Rates ◽  
Orienting Response ◽  
Sensory Epithelium ◽  
Live Prey ◽  
Mottled Sculpin ◽  
Pre Treatment

Lake Michigan mottled sculpin, Cottus bairdi, exhibit a naturally occurring and unconditioned orienting response that can be triggered by both live prey and chemically inert vibrating spheres, even in blinded animals. CoCl(2)-induced reductions of the orienting response demonstrate that the lateral line is required for this behavior in the absence of non-mechanosensory cues (such as vision), but shed no light on the relative contributions of superficial and canal neuromasts to this behavior. To determine the relative roles of these two subsystems, we measured the frequency with which mottled sculpin oriented towards a small vibrating sphere before and after two treatments: (i) immersion of fish in a solution of gentamicin, an aminoglycoside antibiotic that damages hair cells in canal, but not superficial, neuromasts; and (ii) scraping the skin of the fish, which damages the superficial, but not the canal, neuromasts. To ensure that both superficial and canal neuromasts were adequately stimulated, we tested at different vibration frequencies (10 and 50 Hz) near or at the best frequency for each type of neuromast. At both test frequencies, response rates before treatment were greater than 70 % and were significantly greater than ‘spontaneous’ response frequencies measured in the absence of sphere vibration. Response rates fell to spontaneous levels after 1 day of gentamicin treatment and did not return to pre-treatment levels for 10–15 days. In contrast, response rates stayed approximately the same after superficial neuromasts had been damaged by skin abrasion. Scanning electron microscopy confirmed hair cell damage (loss of apical cilia) in canal, but not superficial, neuromasts of gentamicin-treated animals after as little as 24 h of treatment. The sensory epithelium of canal neuromasts gradually returned to normal, following a time course similar to behavioral loss and recovery of the orienting response, whereas that of superficial neuromasts appeared normal throughout the entire period. This study shows that the orienting response of the mottled sculpin is mediated by canal neuromasts.

scholarly journals Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 2798
Author(s):  
Zoran Todorović ◽  
Siniša Đurašević ◽  
Maja Stojković ◽  
Ilijana Grigorov ◽  
Slađan Pavlović ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Time Course ◽  
Membrane Lipids ◽  
Lipid Analysis ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Enzyme Inactivation ◽  
Critical Event ◽  
Tissue Ischemia ◽  
Insight Into

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.

19. Cold-induced endothelial cell damage is mediated by intracellular calcium: the role of catecholamine pre-treatment

Cryobiology ◽  
2006 ◽  
Vol 53 (3) ◽  
pp. 375
Author(s):  
Ulf Schnetzke ◽  
Paul Brinkkötter ◽  
Ralf Lösel ◽  
Fokko van der Woude ◽  
Benito Yard
Keyword(s):  
Endothelial Cell ◽  
Intracellular Calcium ◽  
Cell Damage ◽  
Endothelial Cell Damage ◽  
Pre Treatment

Activation of pp60(src) is critical for stretch-induced orienting response in fibroblasts

1999 ◽  
Vol 112 (9) ◽  
pp. 1365-1373 ◽  
Author(s):  
X. Sai ◽  
K. Naruse ◽  
M. Sokabe
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Orienting Response ◽  
Cyclic Stretch ◽  
Wild Type ◽  
Herbimycin A ◽  
Molecular Masses

When subjected to uni-axial cyclic stretch (120% in length, 1 Hz), fibroblasts (3Y1) aligned perpendicular to the stretch axis in a couple of hours. Concomitantly with this orienting response, protein tyrosine phosphorylation of cellular proteins (molecular masses of approximately 70 kDa and 120–130 kDa) increased and peaked at 30 minutes. Immuno-precipitation experiments revealed that paxillin, pp125(FAK), and pp130(CAS) were included in the 70 kDa, and 120–130 kDa bands, respectively. Treatment of the cells with herbimycin A, a tyrosine kinase inhibitor, suppressed the stretch induced tyrosine phosphorylation and the orienting response suggesting that certain tyrosine kinases are activated by stretch. We focused on pp60(src), the most abundant tyrosine kinase in fibroblasts. The kinase activity of pp60(src) increased and peaked at 20 minutes after the onset of cyclic stretch. Treatment of the cells with an anti-sense S-oligodeoxynucleotide (S-ODN) against pp60(src), but not the sense S-ODN, inhibited the stretch induced tyrosine phosphorylation and the orienting response. To further confirm the involvement of pp60(src), we performed the same sets of experiments using c-src-transformed 3Y1 (c-src-3Y1) fibroblasts. Cyclic stretch induced a similar orienting response in c-src-3Y1 to that in wild-type 3Y1, but with a significantly faster rate. The time course of the stretch-induced tyrosine phosphorylation was also much faster in c-src-3Y1 than in 3Y1 fibroblasts. These results strongly suggest that cyclic stretch induces the activation of pp60(src) and that pp60(src) is indispensable for the tyrosine phosphorylation of pp130(CAS), pp125(FAK) and paxillin followed by the orienting response in 3Y1 fibroblasts.

scholarly journals Comparison of Selenium Source in Preventing Oxidative Stress in Bovine Mammary Epithelial Cells

Animals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 842 ◽  
Author(s):  
Lingling Sun ◽  
Fang Wang ◽  
Zhaohai Wu ◽  
Lu Ma ◽  
Craig Baumrucker ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Cell Damage ◽  
Antioxidant Response ◽  
Mammary Epithelial ◽  
Mrna Abundance ◽  
Bovine Mammary Epithelial Cells ◽  
Pre Treatment ◽  
Species Production

Oxidative stress can cause cell damage. Hydroxy-selenomethionine (HMSeBA) is an organic Se source with emerging antioxidant advantages. The objective of this study was to compare the effects of HMSeBA, selenomethionine (SeMet) and sodium selenite (SS) on the antioxidant response and the ability to resist oxidative stress in bovine mammary epithelial cells (BMEC). The BMEC were treated with 0 (Control), 20, 50, 100 and 150 nM HMSeBA, 100 nM SeMet and100 nM SS for 48 h. The results showed that HMSeBA and SeMet treatments had higher glutathione peroxidase (p < 0.01) and catalase (p = 0.01) activities and mRNA abundance of GPX3 (p = 0.02), but lower superoxide dismutase activity compared with SS (p = 0.04). The catalase activity (p < 0.05) and mRNA abundance of GPX3 (p = 0.04) changed in a quadratic manner with the increase of HMSeBA levels. To assess the potential protection of different Se sources against oxidative stress on BMEC, 0 or 50 μM H2O2 was added to BMEC culture for 3 h after Se pre-treatment for 48 h. The results showed that HMSeBA and SeMet, which did not differ (p > 0.05), but further decreased malondialdehyde and reactive oxygen species production compared with SS (p < 0.05). In conclusion, HMSeBA showed an enhanced cellular antioxidant status to resist oxidative damage induced by H2O2 when compared with SS, whereas the effects were similar to SeMet.

scholarly journals Determination of Kanamycin by High Performance Liquid Chromatography

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1902 ◽  
Author(s):  
Xingping Zhang ◽  
Jiujun Wang ◽  
Qinghua Wu ◽  
Li Li ◽  
Yun Wang ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Solid Phase ◽  
Aminoglycoside Antibiotic ◽  
Therapeutic Index ◽  
Food Samples ◽  
Pulsed Electrochemical Detection ◽  
Practical Tool ◽  
Pre Treatment

Kanamycin is an aminoglycoside antibiotic widely used in treating animal diseases caused by Gram-negative and Gram-positive infections. Kanamycin has a relatively narrow therapeutic index, and can accumulate in the human body through the food chain. The abuse of kanamycin can have serious side-effects. Therefore, it was necessary to develop a sensitive and selective analysis method to detect kanamycin residue in food to ensure public health. There are many analytical methods to determine kanamycin concentration, among which high performance liquid chromatography (HPLC) is a common and practical tool. This paper presents a review of the application of HPLC analysis of kanamycin in different sample matrices. The different detectors coupled with HPLC, including Ultraviolet (UV)/Fluorescence, Evaporative Light Scattering Detector (ELSD)/Pulsed Electrochemical Detection (PED), and Mass Spectrometry, are discussed. Meanwhile, the strengths and weaknesses of each method are compared. The pre-treatment methods of food samples, including protein precipitation, liquid-liquid extraction (LLE), and solid-phase extraction (SPE) are also summarized in this paper.

Treatment of Myelodysplastic Syndromes with del 5q before the Lenalidomide Era: The GFM Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2678-2678 ◽  
Author(s):  
Charikleia Kelaidi ◽  
Sophie Park ◽  
Sabine Brechignac ◽  
Lionel Mannone ◽  
Norbert Vey ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Response Rate ◽  
Response Duration ◽  
Response Rates ◽  
Erythroid Response ◽  
Recent Introduction ◽  
Pre Treatment

Abstract Background: MDS with del 5q are characterized by profound anemia, which until the recent introduction of lenalidomide (N Engl J Med2005; 352: 549–57, J Clin Oncol2005;16S:5), was considered generally unresponsive to available treatments. In order to reevaluate the outcome of those patients in the pre-lenalidomide era, we analyzed response of anemia in MDS with del 5q treated with EPO ± G-CSF and thalidomide in previous GFM trials. Patients: MDS with del 5q included in 419 MDS treated with EPO or Darbepoetin (DAR) ± G-CSF by GFM centers (including 3 successive GFM trials: Blood2004; 104: 321–7; Blood2005;106 suppl 1: 712a; Br J Haematol2006;133: 513–9 and submitted to ASH 2006), and in 134 MDS treated with thalidomide in two successive GFM trials (Br J Haematol2005; 131: 609–18, and submitted to ASH 2006). Patients received at least 30,000 U/w of EPO or 300 mg/w of DAR and doses ranging from 50 to 800 mg/d of Thalidomide during at least 12 weeks. Results: 48 MDS with del 5q received EPO (or DAR) ± G-CSF, including 30 pts with del 5q alone, 9 with one and 9 with >1 additional cytogenetic abn; 21/48 had marrow blasts ≥5% (7 had >10%). 17 had the “5q- syndrome” according to WHO. Median pre-treatment EPO level was 287 UI/L (range 12–5,665), i.e. significantly more than in non del 5q cases (median 68, p<0.001). 22/48 pts (46%) had erythroid response, including 15 major and 7 minor (11 responses after EPO or DAR alone and 11 after EPO or DAR + G-CSF) vs. 64% in pts without del 5q (p=0.01) (p= 0.066 after adjustment for marrow blasts). The response rate was 52%, 55%, 22% and 33%, respectively in del 5q pts with the 5q- syndrome, one additional cytogenetic abn, >1 additional cytogenetic abn, and marrow blasts ≥5%. Response duration was significantly shorter in MDS with del 5q than in other MDS (mean 12 vs. 24 months, p=0.019) and in pts with 5q- syndrome vs. other MDS with marrow blasts <5% (mean 11vs. 24months, p=0.025). 20 pts with del 5q were treated with thalidomide. 6/20 had an erythroid response (30 %, including 3 major and 3 minor responses) vs. 29% of other MDS (p=NS) Conclusion: MDS with del 5q with ≤1 additional cytogenetic abn and no excess of marrow blasts may have erythroid response to EPO ± G-CSF but responses are generally very short, while response rates to thalidomide are low. Those results are clearly inferior to results obtained with lenalidomide in MDS with del 5q.

Mechanisms and Prevention of Fatal Cardiotoxicity Following High-Dose Cyclophosphamide Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5789-5789
Author(s):  
Takuro Nishikawa ◽  
Emiko Miyahara ◽  
Koichiro Kurauchi ◽  
Erika Watanabe ◽  
Yasuhiro Okamoto ◽  
...  
Keyword(s):  
Live Cell Imaging ◽  
Cell Imaging ◽  
Cell Damage ◽  
Live Cell ◽  
High Dose ◽  
Protective Effects ◽  
Ldh Release ◽  
Pre Treatment ◽  
High Doses ◽  
Control Samples

Abstract Background: High-dose Cyclophosphamide (CY) is a mainstay in most conditioning regimens for hematopoietic stem cell transplantation. Recently, high-dose, posttransplantation CY, a novel effective strategy for preventing graft-versus-host disease, has been attracting a lot of attention. CY is activated by the hepatic cytochrome P-450 (CYP) enzyme system to form 4-hydroxy-cyclophosphamide (HCY), which is in equilibrium with aldocyclophosphamide (AldoCY). Depending on the type of the cell, AldoCY decomposes to form cytotoxic phosphoramide mustard and the byproduct acrolein. Alternatively, aldoCY is oxidized to the inactive metabolite o-carboxyethylphosphoramide mustard (CEPM) by aldehyde dehydrogenase1 (ALDH1). The dose-limiting toxic effect of CY, observed only after administration of high-doses, is cardiotoxicity. Since the mechanism underlying this phenomenon has not yet been elucidated, we investigated the cardiotoxic mechanisms of high-dose CY. To determine preliminary mechanisms that may prevent the occurrence of CY-induced cytotoxicity in H9C2 cells, we also evaluated the protective effects of potential cardioprotectant agents (PCA). Methods: A rat cardiac myocardial cell line, H9C2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9). The concentration of CY in this experiment was determined based on values measured in blood samples from patients receiving CY in high doses. The degree of cytotoxicity was then evaluated by MTT assay, LDH release, production of reactive oxygen species (ROS), and incidence of apoptosis. We also investigated how the myocardial cellular effects of CYS9 were modified by acrolein scavenger N-acetylcysteine (NAC), antioxidant isorhamnetin (ISO), and ƒÀ-ionone (BIO) a CYP inhibitor. Quantifying CY and CY metabolites, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), we assayed culture supernatants of CYS9 with or without PCA and also tested with HCY, CEPM and acrolein. In addition, we observed the cytotoxicity of CYS9 and the protective effects of PCA using a live-cell imaging system. Finally, using leukemia cell lines, we confirmed whether each of the above PCAs inhibits the antileukemic effects of CYS9. Results: The peak average concentration of CY in three patients receiving high-dose CY therapy was 257 ± 46 ƒÊM. After 250 ƒÊM of CY was metabolized in S9 mix for 2 h, the concentration of HCY was 17.6 ± 4.3, CEPM 26.6 ± 5.3 ƒÊM, and acrolein 30.8 ± 1.3 ƒÊM. Assay results for MTT and LDH release showed that treatment with CY (500 ƒÊM) did not cause cytotoxicity. However, CYS9 (CY 250 ƒÊM) exhibited myocardial cytotoxicity. NAC, ISO, and BIO all inhibited CYS9-induced cytotoxicity (Fig.1). When treated with ISO or BIO, metabolism of CY was significantly inhibited. Pre-treatment with NAC, however, did not inhibit the metabolism of CY. Compared to control samples, we observed no difference in HCY, a significant increase of CEPM, and a significant decrease of acrolein (Fig.2). Furthermore, NAC pre-treatment did not affect intracellular ROS levels produced by CYS9. Live-cell imaging also confirmed that CYS9 induced acute cytotoxicity, which was inhibited by NAC. Finally, NAC did not inhibit the CYS9-induced antileukemic effect. Discussion: According to results from LC/MS/MS, we ascertained that, when metabolized in vitro by S9, CY would produce similar levels of metabolic substance concentrations as in vivo. When H9C2 was pre-treated with NAC, ISO, and BIO, each inhibited cell damage by CYS9. When treated with ISO and BIO, we observed that CY metabolism itself was inhibited. This result suggests that cardiac cell damage may depend on individual differences in CY metabolic capacity. As preventative drugs, however, both BIO and ISO seem likely to interfere with antitumor effects and are thought to be unsuitable.NAC pre-treatment did not inhibit CY metabolism: compared to control samples, there was no difference in HCY concentration, but there was a significant increase in CEPM concentration. Less acrolein, however, was present after exposure to NAC. The increase in CEPM suggests that scavenging of acrolein by NAC prevents inhibition of ALDH1; in the absence of acrolein, AldoCY is metabolized to CEPM. NAC attenuates high-dose CY induced cardiotoxicity through a mechanism related to its ability to decrease of acrolein. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Whole blood FOLH1 mRNA expression and treatment response in metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 188-188
Author(s):  
Edmond Michael Kwan ◽  
Sarah Q To ◽  
Heidi C Fettke ◽  
Maria M Docanto ◽  
Patricia Bukczynska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Blood ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Response Rates ◽  
Predictive Biomarker ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
Pre Treatment

188 Background: Identifying predictive biomarkers for mCRPC patients receiving androgen receptor signalling inhibitors (ARSI) or chemotherapy remains an unmet clinical need. FOLH1 encodes for Prostate-Specific Membrane Antigen (PSMA), a type II glycoprotein highly expressed on prostate cancer cells. We designed a whole blood assay to detect FOLH1 mRNA, and correlated expression with clinical outcomes in patients commencing ARSI (abiraterone or enzalutamide) or chemotherapy (docetaxel or cabazitaxel). Methods: mCRPC patients commencing ARSI or chemotherapy were prospectively recruited at three Australian centres from June 2016 to July 2018. A quantitative reverse transcription polymerase chain reaction assay was used to detect FOLH1 transcript from whole blood samples collected in PAXgene® RNA tubes. Pre-treatment FOLH1 expression was correlated with PSA response rate (Fisher’s exact test) and PSA progression-free survival (PSA-PFS) (log-rank test). Results: Median follow-up was 13.6 months (IQR 9.7–19.3). In total, 88 pre-treatment samples were analysed, of which 75 (85%) were FOLH1-positive. In patients receiving ARSI, outcomes favoured FOLH1-positive patients compared to FOLH1-negative patients, with higher PSA response rates (39/60, 65% vs. 2/7, 29%; p = 0.1) and longer PSA-PFS (median 9.0 months [95% CI, 7.2-10.8] vs. 2.8 months [95% CI, 2.3-3.3]; p = 0.03). Conversely, in chemotherapy-treated patients, inferior outcomes were observed in FOLH1-positive patients compared to FOLH1-negative patients, with lower PSA response rates (4/15, 27% vs. 5/6, 83%, p = 0.05) and shorter PSA-PFS (median 2.9 months [95% CI, 2.8-3.0] vs. 4.1 months [95% CI, 3.7-4.5]; p = 0.32). Conclusions: Pre-treatment FOLH1 expression may differentiate between outcomes on ARSI vs. chemotherapy in mCRPC patients. The utility of FOLH1 as a predictive biomarker in mCRPC warrants further evaluation in larger, independent cohorts. [Table: see text]

scholarly journals Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats

2021 ◽  
Author(s):  
Carlos Henrique Rocha Catalão ◽  
Anderson de Oliveira Souza ◽  
Nilton Nascimento Santos-Júnior ◽  
Luís Henrique Angenendt da Costa ◽  
Jonathas Rodrigo dos Santos ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Time Course ◽  
Bacterial Load ◽  
Treatment Strategies ◽  
Metabolic Parameters ◽  
Metabolic Disturbances ◽  
Continuous Administration ◽  
Plasma Cytokines ◽  
Experiment Control ◽  
Pre Treatment

Abstract Sepsis causes overproduction of inflammatory cytokines, organ dysfunction and cognitive impairment in survivors. In addition to inflammation, metabolic changes occur according to the stage and severity of the disease. Understanding the role and place of metabolic disturbances in the pathophysiology of sepsis is essential to evaluate the framework of septic patients, predict the syndrome progress and define treatment strategies. We investigated the effect of simvastatin on the disease time course and on metabolic alterations, especially with respect to their possible consequences in the CNS of surviving rats. The animals of this study were weighed daily and followed for 10 days to determine the survival rate. In the first experiment, control or CLP-animals were randomized in 24 h, 48 h and 10 days after septic induction, for bacterial load determination and, quantification of cytokines. In the second experiment, control or CLP-animals were treated or not with simvastatin and randomized in the same three time points for cytokines quantification and assessment of their body metabolism and locomotor activity (at 48 h and 10 days), as well as the evaluation of cytoarchitecture and astrogliosis (at 10 days). The CLP-rats treated with simvastatin showed a reduction in plasma cytokines and improvement in metabolic parameters and locomotor activity, followed by minor alterations compatible with apoptosis and astrogliosis in the hippocampus and prefrontal cortex. These results suggest that the anti-inflammatory effect of simvastatin plays a crucial role in restoring energy production, maintaining a hypermetabolic state necessary for the recovery and survival of these CLP-rats.

Sign in / Sign up

Export Citation Format

Share Document