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At least 505 records · Page 28Linked to original sources
PubMed1989

Effectiveness of atracurium in preventing succinylcholine myalgia.

A comparison was made of the incidence of postoperative myalgia (POM) and fasciculations when atracurium (ATR) or d-Tubocurarine (DTC) was given prior to succinylcholine (SDC) for facilitation of tracheal intubation. The subjects were 44 ASA physical status I or II outpatient females undergoing laparoscopy. They were assigned to one of three groups: Group 1 received 0.025 mg/kg ATR; Group 2 received 0.05 mg/kg DTC, and Group 3 received saline (NS). Thiopental was administered one minute and 45 seconds after pretreatment. Three minutes after pretreatment, SDC 1.5 mg/kg was given, and fasciculations were recorded on a scale of 0-3. The patients were questioned one and three days postoperatively about POM and their responses recorded using a scale of 0-3. Fasciculations occurred in 79% of patients given saline, in 46% of those receiving ATR and in 12% of those given DTC. Eighty-five percent of ATR patients were free of POM on postoperative day one. The corresponding figures for DTC and NS were 59% and 43%, respectively. The difference between ATR and NS achieved statistical significance, leading to the conclusion that DTC is a better defasciculant than ATR. DTC was, however, not significantly better than NS in the prevention of POM. Findings suggest that ATR may be the drug of choice for the prevention of POM.

Adolescent↗
PubMed1987

Comparison of atracurium and d-tubocurarine for prevention of succinylcholine myalgia.

We compared the incidence of postoperative myalgia (POM) and fasciculations when atracurium (ATR) or d-tubocurarine (DTC) was given prior to succinylcholine (SDC) for tracheal intubation in 44 ASA class I or II outpatient females undergoing laparoscopy. The subjects were assigned to one of three groups: group 1 received 0.025 mg/kg ATR; group 2 received 0.05 mg/kg DTC; and group 3 received saline (NS), all in a double-blind manner. Thiopental was administered 1 min and 45 sec after pretreatment in doses adequate to allow control of ventilation. Three minutes after pretreatment, SDC 1.5 mg/kg was given, and fasciculations were recorded on a scale of 0-3. All patients were questioned 1 and 3 days postoperatively about POM, using a scale of 0-3. Fasciculations occurred in 79% of patients given saline, in 46% of those receiving ATR, and in 12% of those given DTC. Eighty-five percent of ATR patients were free of POM on postoperative day 1. The corresponding figures for DTC and NS were 59% and 43%, respectively. Only the difference between ATR and NS achieved statistical significance. On the third postoperative day, POM was rare and there were no significant differences among the groups. We conclude that DTC is a better defasciculant than ATR. DTC was, however, not significantly better than NS in the prevention of POM. The findings suggest that ATR may be the drug choice for the prevention of POM.

Adolescent↗
PubMed1981

[Inhibitory action of urogastrone from pregnant horses urine on gastric acid secretion (author's transl)].

Inhibitory actions of urogastrone (UG) on gastric acid secretion induced by tetragastrin (TG), histamine (Hist) and carbachol (Cach) were compared with cimetidine (Cime), atropine (Atr), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) in acute conscious fistula rats. The inhibitory actions of UG were TG greater than Cach greater than or equal to Hist; those of Cime, Cach greater than TG greater than or equal to Hist; those of Atr or PGE2, Cach greater than TG greater than Hist; and those of EGF, TG greater than Hist greater than or equal to Cach. The times required for the maximal inhibition were faster in the order of EGF greater than Cime greater than Atr greater than UG on TG and Hist; Cime greater than EGF=Atr greater than UG on Cach. After vagotomy, the type of inhibition of UG changed to that of Atr and Cach was more evidently inhibited than methacholine by UG. The above data suggest that the inhibitory actions of UG or EGF on gastrin are more specific than Cime, Atr or PGE2 and inhibitory action of UG is slower and longer than Cime, Atr, PGE2 or EGF.

Animals↗
PubMed1985

Hemodynamic evaluation of stenotic cardiac valves: I. Effect of ventriculography and atropine on mitral stenosis.

Mitral area is the parameter used for quantitating mitral stenosis (MS) severity. When mitral gradient (MG) is low and reduction of mitral valve area (MVA) might be critical, interventions presumably increasing mitral valve flow (MVF), such as stress or atrial pacing, have been carried out. The purpose of this study was to analyze in 28 patients the combined effect of left ventriculography (LVG) and intravenous atropine (ATR) in the hemodynamic evaluation of MS. The rationale for combining these two interventions is to add up the ATR-positive chronotropic effect to the LVG potentiation of cardiac output. The LVG plus ATR markedly accelerated heart rate (from 80 +/- 14 to 104 +/- 18 bts/min, P less than 0.001), mildly increased cardiac index (from 2.6 +/- 0.6 to 2.9 +/- 0.6 1/min/m2, P less than 0.05), and importantly increased MVF (from 136 +/- 30 to 172 +/- 46 ml/bt, P less than 0.001). Pulmonary wedge pressure increased (from 14 +/- 5 to 21 +/- 5 mmHg, P less than 0.001) because of an important increment of MG (from 12 +/- 6 to 18 +/- 7 mmHg, P less than 0.001). None of six cases with mild MS (MVA greater than 1.5 cm2) and nine of ten cases with severe MS (MVA less than or equal to 1.0 cm2) had MG after LVG plus ATR greater than 12 mmHg. The remaining case with severe MS and the two cases (out of 12) with moderate MS having MG after LVG plus ATR less than or equal to 12 mmHg had, at surgical evaluation, noncritically reduced MVA. This study shows that LVG plus ATR is a valid and easy intervention for increasing MVF during cardiac catheterization. It also allows the reclassification of patients with low baseline MG and reduced MVA into two subgroups: Cases with critically reduced MVA at surgery achieve a postintervention MG greater than 12 mmHg and those cases with noncritically reduced MVA achieve a postintervention MG less than or equal to 12 mmHg.

Adult↗
PubMed2004

Adaptive acid tolerance response in Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Typhi.

The survival of bacteria in various environments depends on a number of protective responses including acid tolerance response (ATR). In this study, ATR phenomenon was compared in Salmonella enterica serovar Typhi 6 and Salmonella enterica serovar Typhimurium 98 under different culture conditions. Survival of the adapted culture (pre-acid shocked to pH 5.5) was significantly better (p < 0.05) as compared to control, unadapted culture after acid shock at pH 3.3. However, the ATR varied with the serovar, incubation temperature and the growth medium used (all p-values < 0.05). S. Typhi 6 failed to grow in pH 3.3 at 45 degrees C. The addition of tetracycline or chloramphenicol (1.0 microg ml(-1)) to adapted cultures during or after acid shock (pH 3.3) had no effect on ATR expression. In S. Typhimurium 98, growth was increased by 10% or greater in adapted culture (when grown at pH 3.3) as compared to growth observed with an unadapted culture (when grown at pH 7.3) on transfer to fresh growth medium at pH 7.3. A poor ATR observed in non-growing S. Typhimurium 98 suspensions clearly showed that ATR is an energy-consuming process. Storage of S. Typhimurium 98 cultures in pH 4.5 nutrient broth at 4 degrees C demonstrated that prolonged exposure to acidic conditions is more detrimental in comparison to the cultures stored at pH 7.3 at this temperature.

Acids↗
PubMed2000

[Inhibition of proliferation of retinal pigment epithelium in vitro: vitamin A pharmacodynamics I].

BACKGROUND: In proliferative vitreoretinopathy and choroidal neovascularization, retinal pigment epithelial (RPE) cells proliferate among other cell types. Cell proliferation is controlled by many factors. One such factor is the "superfamily" of nuclear receptors. Ligands of these receptors are vitamin A and D, triiodothyronine and dexamethasone. All-trans-retinal (atR) inhibits human RPE-cell proliferation. AtR binds to the nuclear ligand-dependent transcription factors RAR (retinoic acid receptor) and RXR (retinoid X receptor). Pharmacodynamics of atR were investigated with respect to inhibition of RPE cell proliferation. MATERIALS AND METHODS: Primary human RPE cell lines were used up to passage 5. RPE cells were incubated with atR ranging from 1 pM up to 1 microM. AtR was added every other day for 7 days. Cell proliferation was determined by cell counting. RESULTS: AtR inhibited RPE cell proliferation in a biphasic manner. Two IC50 values were calculated, one in the picomolar range, 10 pM (5-24, 95% confidence interval) and one in the nanomolar range, 17 nM (8-37). Furthermore, inhibition of cell proliferation was examined using specific RAR agonists. Agonists of the RAR-b subgroup inhibited cell proliferation at the lowest concentrations. CONCLUSIONS: RPE cell proliferation in vitro is inhibited by agonists of RAR. Agonists of the RAR-b subgroup inhibit RPE cell proliferation at the lowest concentrations.

Cell Count↗
PubMed2006

Phosphorylation of replication protein A by S-phase checkpoint kinases.

The major eukaryotic single-stranded DNA (ssDNA) binding protein, replication protein A (RPA), is a heterotrimer with subunits of 70, 32 and 14 kDa (RPA70, RPA32 and RPA14). RPA-coated ssDNA has been implicated as one of the triggers for intra-S-phase checkpoint activation. Phosphorylation of RPA occurs in cells with damaged DNA or stalled replication forks. Here we show that human RPA70 and RPA32 can be phosphorylated by purified S-phase checkpoint kinases, ATR and Chk1. While ATR phosphorylates the N-terminus of RPA70, Chk1 preferentially phosphorylates RPA's major ssDNA binding domain. Chk1 phosphorylated RPA70 shows reduced ssDNA binding activity, and binding of RPA to ssDNA blocks Chk1 phosphorylation, suggesting that Chk1 and ssDNA compete for RPA's major ssDNA binding domain. ssDNA stimulates RPA32 phosphorylation by ATR in a length dependent manner. Furthermore, 3'-, but not 5'-, recessed single strand/double strand DNA junctions produce an even stronger stimulatory effect on RPA32 phosphorylation by ATR. This stimulation occurs for both RNA and DNA recessed ends. RPA's DNA binding polarity and its interaction to 3'-primer-template junctions contribute to efficient RPA32 phosphorylation. Progression of DNA polymerase is able to block the accessibility of the 3'-recessed ends and prevent the stimulatory effects of primer-template junctions on RPA phosphorylation by ATR. We propose models for the role of RPA phosphorylation by Chk1 in S-phase checkpoint pathways, and the possible regulation of ATR activity by different nucleic acid structures.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2001

Ca2+ - and cross-bridge-dependent changes in N- and C-terminal structure of troponin C in rat cardiac muscle.

Linear dichroism of 5'-tetramethylrhodamine (5'ATR)-labeled cardiac troponin C (cTnC) was measured to monitor cTnC structure during Ca2+-activation of force in rat skinned myocardium. Mono-cysteine mutants allowed labeling at Cys-84 (cTnC(C84), near the D/E helix linker); Cys-35 (cTnC(C35), at nonfunctional site I); or near the C-terminus with a cysteine inserted at site 98 (cTnC-C35S,C84S,S98C, cTnC(C98)). With 5'ATR-labeled cTnC(C84) and cTnC(C98) dichroism increased with increasing [Ca2+], while rigor cross-bridges caused dichroism to increase more with 5'ATR-labeled cTnC(C84) than cTnC(C98). The pCa50 values and n(H) from Hill analysis of the Ca2+-dependence of force and dichroism were 6.4 (+/-0.02) and 1.08 (+/-0.04) for force and 6.3 (+/-0.04) and 1.02 (+/-0.09) (n = 5) for dichroism in cTnC(C84) reconstituted trabeculae. Corresponding data from cTnC(C98) reconstituted trabeculae were 5.53 (+/-0.03) and 3.1 (+/-0.17) for force, and 5.39 (+/-0.03) and 1.87 (+/-0.17) (n = 5) for dichroism. The contribution of active cycling cross-bridges to changes in cTnC structure was determined by inhibition of force to 6% of pCa 4.0 controls with 1.0 mM sodium vanadate (Vi). With 5'ATR-labeled cTnC(C84) Vi caused both the pCa50)of dichroism and the maximum value at pCa 4.0 to decrease, while with 5'ATR-labeled cTnC(C98) the pCa50 of dichroism decreased with no change of dichroism at pCa 4.0. The dichroism of 5'ATR-labeled cTnC(C35) was insensitive to either Ca2+ or strong cross-bridges. These data suggest that both Ca2+ and cycling cross-bridges perturb the N-terminal structure of cTnC at Cys-84, while C-terminal structure is altered by site II Ca2+-binding, but not cross-bridges.

Animals↗
PubMed1998

Steady-state fluorescence polarization studies of the orientation of myosin regulatory light chains in single skeletal muscle fibers using pure isomers of iodoacetamidotetramethylrhodamine.

The regulatory light chain (RLC) from chicken gizzard myosin was covalently modified on cysteine 108 with either the 5- or 6-isomer of iodoacetamidotetramethylrhodamine (IATR). Labeled RLCs were purified by fast protein liquid chromatography and characterized by reverse-phase high-performance liquid chromatography (HPLC), tryptic digestion, and electrospray mass spectrometry. Labeled RLCs were exchanged into the native myosin heads of single skinned fibers from rabbit psoas muscle, and the ATR dipole orientations were determined by fluorescence polarization. The 5- and 6-ATR dipoles had distinct orientations, and model orientational distributions suggest that they are more than 20 degrees apart in rigor. In the rigor-to-relaxed transition (sarcomere length 2.4 microm, 10 degrees C), the 5-ATR dipole became more perpendicular to the fiber axis, but the 6-ATR dipole became more parallel. This orientation change was absent at sarcomere length 4.0 microm, where overlap between myosin and actin filaments is abolished. When the temperature of relaxed fibers was raised to 30 degrees C, the 6-ATR dipoles became more parallel to the fiber axis and less ordered; when ionic strength was lowered from 160 mM to 20 mM (5 degrees C), the 6-ATR dipoles became more perpendicular to the fiber axis and more ordered. In active contraction (10 degrees C), the orientational distribution of the probe dipoles was similar but not identical to that in relaxation, and was not a linear combination of the orientational distributions in relaxation and rigor.

Animals↗
PubMed2001

Synergism between cocaine and atropine at the caudal ventrolateral medulla of cats.

We have previously reported that the anticholinergic properties of cocaine may be important in cocaine induced apneusis. We have studied the effects of the cholinergic muscarinic antagonist atropine (ATR) on cocaine induced apneusis at the caudal chemosensitive areas of the ventrolateral medulla oblongata (CVLM). Experiments were performed in urethane anesthetized and tracheotomized cats with the CVLM surgically exposed. Topical application of ATR (44 mM ) to the CVLM produced significant decrements in minute ventilation (V(E)) and mean arterial blood pressure (MABP) (P<0.05) but the effects on tidal volume (V(T)), respiratory frequency (f) and heart rate (HR) were not significant. Administration of cocaine (37 mM) to ATR pretreated animals increased the incidence of cocaine induced respiratory arrest to more than twofold greater than when cocaine was administered in the absence of pretreatment. The ATR pretreated animals that did not experience inspiratory arrest after cocaine were shown to exhibit significant decrements in f and V(E) as a consequence of prolonged inspiratory pauses. The reduction in MABP after cocaine in ATR pretreated animals was also significant. These results suggest that ATR enhances the central respiratory toxicity of cocaine by acting synergistically at CVLM chemosensitive sites.

Animals↗
PubMed2003

Gas chromatography/mass spectrometry applied for the analysis of triazine herbicides in environmental waters.

The excess use of triazine herbicides in agriculture causes severe contamination to the environment especially for ground water. Gas chromatography coupled with mass spectrometry (GC/MS) was used to analyze simazine, atrazine (ATR), cyanazine, as well as the degradation products of ATR such as deethylatrazine and deisopropylatrazine in environmental water samples. These compounds were baseline separated by the established GC method. The water samples were pre-concentrated by solid-phase-extraction (SPE) and analyzed by ion trap MS at sub- to low-ppt levels. Recovery of ATR by the SPE pre-concentration using a C18 cartridge was determined as 90.5 +/- 3.5%. Detection limit of the method using selected ion monitoring technique for ATR was 1.7 ppt when one liter water was analyzed. The relative analytical error for ATR fortified water samples at 200 ppt was -12.5% (n=12) with triple analysis and the relative standard deviation was 3.2%. Trace levels of ATR at 3.9 and 9.7 ppt were determined in water samples collected from a reservoir and a river in Hong Kong.

Atrazine↗
PubMed2003

Effect of acid shock on protein expression by biofilm cells of Streptococcus mutans.

Streptococcus mutans is a component of the dental plaque biofilm and a major causal agent of dental caries. Log-phase cells of the organism are known to induce an acid tolerance response (ATR) at sub-lethal pH values ( approximately 5.5) that enhances survival at lower pH values such as those encountered in caries lesions. In this study, we have employed a rod biofilm chemostat system to demonstrate that, while planktonic cells induced a strong ATR at pH 5.5, biofilm cells were inherently more acid resistant than such cells in spite of a negligible induction of an ATR. Since these results suggested that surface growth itself triggered an ATR in biofilm cells, we were interested in comparing the effects of a pH change from 7.5 to 5.5 on protein synthesis by the two cell types. For this, cells were pulse labeled with [(14)C]-amino acids following the pH change to pH 5.5, the proteins extracted and separated by two-dimensional (2D) electrophoresis followed by autoradiography and computer-assisted image analysis. A comparison between the cells incubated at pH 5.5 and the control biofilm cells revealed 23 novel proteins that were absent in the control cells, and 126 proteins with an altered relative rate of synthesis. While the number of changes in protein expression in the biofilm cells was within the same range as for planktonic cells, the magnitude of their change was significantly less in biofilm cells, supporting the observation that acidification of biofilm cells induced a negligible ATR. Mass spectrometry and computer-assisted protein sequence analysis revealed that ATR induction of the planktonic cells resulted in the downregulation of glycolytic enzymes presumably to limit cellular damage by the acidification of the external environment. On the other hand, the glycolytic enzymes in control biofilm cells were significantly less downregulated and key enzymes, such as lactate dehydrogenase were upregulated during pH 5.5 incubation, suggesting that the enhanced acid resistance of biofilm cells is associated with the maintenance of pH homeostasis by H+ extrusion via membrane ATPase and increased lactate efflux.

Acids↗
PubMed2002

Attenuated total reflection Fourier transform infrared spectroscopy of redox transitions in photosynthetic reaction centers: comparison of perfusion- and light-induced difference spectra.

Chemically induced Fourier transform infrared difference spectra associated with redox transitions of several primary electron donors and acceptors in photosynthetic reaction centers (RCs) have been compared with the light-induced FTIR difference spectra involving the same cofactors. The RCs are deposited on an attenuated total reflection (ATR) prism and form a film that is enclosed in a flow cell. Redox transitions in the film of RCs can be repetitively induced either by perfusion of buffers poised at different redox potentials or by illumination. The perfusion-induced ATR-FTIR difference spectra for the oxidation of the primary electron donor P in the RCs of the purple bacteria Rb. sphaeroides and Rp. viridis and P700 in the photosystem 1 of Synechocystis 6803, as well as the Q(A)/Q(A) transition of the quinone acceptor (Q(A)) in Rb. sphaeroides RCs are reported for the first time. They are compared with the light-induced ATR-FTIR difference spectra P+Q(A)/PQ(A) for the RCs of Rb. sphaeroides and P700+/P700 for photosystem 1. It is shown that the perfusion-induced and light-induced ATR-FTIR difference spectra recorded on the same RC film display identical signal to noise ratios when they are measured under comparable conditions. The ATR-FTIR difference spectra are very similar to the equivalent FTIR difference spectra previously recorded upon photochemical or electrochemical excitation of these RCs in the more conventional transmission mode. The ATR-FTIR technique requires a smaller amount of sample compared with transmission FTIR and allows precise control of the aqueous environment of the RC films.

Light↗
PubMed2002

Single-pass attenuated total reflection Fourier transform infrared spectroscopy for the analysis of proteins in H2O solution.

The application of single-pass attenuated total reflection Fourier transform infrared (ATR-FT-IR) microscopy was investigated for secondary structure analysis of 15 representative proteins in H2O solution. This is the first reported application of single-pass ATR-FT-IR for protein analysis; thus, the method was validated using transmission FT-IR and multipass ATR-FT-IR as referee methods. The single-pass ATR-FT-IR technique was advantageous since the single-pass geometry permits rapid secondary structure analysis on small volumes of protein in H2O solution without the use of demountable thin path length sample cells. Moreover, the fact that H2O backgrounds were small allowed the simultaneous observation of the amide I-III, A, and B regions without having to perform H2O subtraction. A comparison of replicate protein spectra indicated that the single-pass ATR-FT-IR method yields more reproducible data than those acquired by transmission FT-IR. The observed trends for the amide I-III and A bands obtained by single-pass ATR-FT-IR agreed with those in the literature for conventional transmission FT-IR.

Animals↗
PubMed1985

P NMR and mass spectrometry of atropinesterase and some serine proteases phosphorylated with a transition-state analogue.

The serine residue in the active center of atropinesterase (AtrE), alpha-chymotrypsin (Chymo), and subtilisin A (Sub) and in alpha-chymotrypsinogen (Chymogen) was labeled with a diisopropylphosphoryl (DP) group. The labeled proteins were studied in buffered aqueous solution under various native and denaturing conditions with 31P NMR before and after being subjected to "ageing", a process leading to conversion of the DP group into a monoisopropylphosphoryl (MP) group. Besides, the model compounds Gly-Ser(DP), Gly-Glu-Ser(DP)-Gly-OEt, and diisopropyl hydrogen phosphate were investigated under similar conditions and in other solvents with different hydrogen-bonding capacity. Mass spectrometry was used to analyze products resulting from ageing in the presence of H2(18)O. The 31P chemical shift of the DP proteins increases according to a simple titration curve upon lowering the pH from 9.0 to 5.0. This is ascribed to protonation of a particular histidine residue in the active center that interacts with a nearby isopropoxy group by hydrogen bonding with the ester oxygen. In DP-AtrE, hydrogen bonding at the phosphoryl oxygen dominates the interaction between substituent and protein; in the other DP proteins, nonbonding interactions become more dominant in the order Chymogen less than Chymo less than Sub. DP-AtrE, DP-Chymo, and DP-Sub age according to first-order kinetics. The pH dependence of the reaction rate constant ka indicates that ageing is catalyzed by the protonated histidine, which is responsible for the increase in chemical shift. The direct interaction between the phosphoryl group and the histidine is lost upon ageing whereas there is an increase in the nonbonding interaction of the remaining isopropyl group with the protein in the order Chymo less than Sub less than AtrE. The maximum value of ka when the histidine is fully protonated (kam) increases in the same order. Ageing of the DP enzymes occurs exclusively by C-O fission, yielding 2-propanol and propene. Since the amount of 2-propanol decreased and that of propene increased in the order Chymo to Sub to AtrE, the increase in kam has been interpreted as a shift in character of ageing from mainly SN2 for Chymo to considerably SN1 for AtrE and Sub. This has been attributed to preferential stabilization of the SN1 transition state by an interplay of hydrogen-bonding and nonbonding interactions between the phosphoryl group and the protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Uptake of atrazine and cadmium from soil by maize (Zea mays L.) in association with the arbuscular mycorrhizal fungus Glomus etunicatum.

A greenhouse pot experiment was carried out to investigate the effect of the arbuscular mycorrhizal fungus Glomus etunicatum on the uptake of atrazine (ATR) and cadmium (Cd) from soil by maize (Zea mays L.). Mycorrhizal colonization led to an increase in the accumulation of Cd and ATR in maize roots but a decrease in the shoots. Atrazine alleviated the adverse effects of Cd on maize growth, and this was more pronounced in the inoculated plants. An increase in Cd accumulation by maize roots was observed when ATR was also present. After harvest, the residual ATR concentration in the soil decreased markedly. With mycorrhizal inoculation the amount of residual ATR decreased more in the bulk soil but less in the rhizosphere soil compared to the noninoculated controls. Cadmium application significantly decreased the ATR residual concentrations in both the rhizosphere and bulk soils irrespective of inoculation treatment.

Atrazine↗
PubMed2002

Mitochondrial permeability transition as a novel principle of hepatorenal toxicity in vivo.

Atractyloside (Atr) binds to the adenine nucleotide translocator (ANT) and inhibits ANT-mediated ATP/ADP exchange on the inner mitochondrial membrane. In addition, Atr can trigger opening of a non-specific ion channel, within the ANT-containing permeability transition pore complex (PTPC), which is subject to redox regulation and inhibited by cyclosporin A (CsA). Here we show that the cytotoxic effects of Atr, both in vivo and in vitro, are determined by its capacity to induce PTPC opening and consequent mitochondrial membrane permeabilization (MMP). Thus, the Atr-induced MMP and death of cultured liver cells are both inhibited by CsA as well as by glutathione (GSH) and enhanced by GSH depletion. Similarly, the hepatorenal toxicity of Atr, assessed in vivo, was reduced by treating mice with CsA or a diet rich in sulfur amino acids, a regime which enhances mitochondrial GSH levels. Atr injection induced MMP in hepatocytes and proximal renal tubular cells, and MMP was reduced by either CsA or GSH. Acetaminophen (paracetamol)-induced acute poisoning was also attenuated by CsA and GSH, both in vitro and in vivo. Altogether these data indicate that PTPC-mediated MMP may determine the hepatorenal toxicity of xenobiotics in vivo.

Animals↗
PubMed2003

Evaluation of the pH-dependent, stationary-phase acid tolerance in Listeria monocytogenes and Salmonella Typhimurium DT104 induced by culturing in media with 1% glucose: a comparative study with Escherichia coli O157:H7.

AIMS: To comparatively evaluate the adaptive stationary-phase acid tolerance response (ATR) in food-borne pathogens induced by culturing in glucose-containing media, as affected by strain variability and antibiotic resistance, growth temperature, challenge pH and type of acidulant. METHODS AND RESULTS: Antibiotic resistant or sensitive strains of Listeria monocytogenes, Salmonella including S. Typhimurium DT104, and Escherichia coli O157:H7 were cultured (30 degrees C for 24 h; 10 degrees C for up to 14 days) in trypticase soya broth with yeast extract (TSBYE) with 1% or without glucose to induce or prevent acid adaptation, respectively. Cultures were subsequently exposed to pH 3.5 or 3.7 with lactic or acetic acid at 25 degrees C for 120 min. Acid-adapted cultures were more acid tolerant than nonadapted cultures, particularly those of L. monocytogenes and Salmonella. No consistent, positive or negative, influence of antibiotic resistance on the pH-inducible ATR or acid resistance (AR) was observed. Compared with 30 degrees C cultures, growth and acid adaptation of L. monocytogenes and S. Typhimurium DT104 at 10 degrees C markedly reduced their ATR and AR in stationary phase. E. coli O157:H7 had the greatest AR, relying less on acid adaptation. A 0.2 unit difference in challenge pH (3.5-3.7) caused great variations in survival of acid-adapted and nonadapted cells. CONCLUSIONS: Culturing L. monocytogenes and Salmonella to stationary phase in media with 1% glucose induces a pH-dependent ATR and enhances their survival to organic acids; thus, this method is suitable for producing acid-adapted cultures for use in food challenge studies. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial pathogens may become acid-adapted in foods containing glucose or other fermentable carbohydrates. Low storage temperatures may substantially decrease the stationary-phase ATR of L. monocytogenes and S. Typhimurium DT104, but their effect on ATR of E. coli O157:H7 appears to be far less dramatic.

Acetic Acid↗