Clinical characteristics and risk factors of gastroesophageal reflux disease in Vietnamese patients with upper gastrointestinal symptoms undergoing esophagogastroduodenoscopy.

BACKGROUND AND AIM: The risk factors associated with the increase in prevalence of gastroesophageal reflux disease (GERD) are not consistent across countries and there have been few studies in Asia in the past 10 years. This study was conducted to assess the features and risk factors of GERD in Vietnamese patients. METHODS: A cross-sectional study was conducted on 1947 out-patients ≥18 years of age who were presented with upper gastrointestinal symptoms and underwent esophagogastroduodenoscopy. Reflux esophagitis was graded according to the Los Angeles classification. Endoscopically suspected Barrett's esophagus (BE) was recorded according to the Prague C and M criteria and biopsy was taken for histologic examination. RESULTS: There were 511 (26.2%) patients with GERD, 242 (47.4%) with nonerosive reflux disease, and 269 (52.6%) with reflux esophagitis and/or BE. Epigastric pain, regurgitation, and heartburn were the chief complaints in 36.8%, 27.0%, and 9.2% of patients, respectively. Most of the patients with mucosal injury had reflux esophagitis in mild grade and BE in the form of C0M ≤2 (99.6%, 231/232 and 97.8%, 46/47, respectively). In multivariate analysis, hiatal hernia, male gender, waist-to-hip ratio (independent from general obesity), and smoking were risk factors for GERD while Helicobacter pylori infection was negatively associated with GERD. CONCLUSIONS: The majority of GERD patients had none or mild mucosal injury. Typical reflux symptoms, however, may not be the chief complaints. Central obesity would be more important than general obesity as a risk factor, while H. pylori infection was a "protective" factor for GERD in Vietnamese patients.

Prevalence, clinical characteristics, and risk factors of Barrett esophagus in Vietnamese patients with upper gastrointestinal symptoms.

The current barrier for investigation of Barrett esophagus (BE) in Asia is diagnostic standardization, which is a challenge to identify its true risk factors. This study aimed to investigate the prevalence, clinical characteristics and risk factors of BE in Vietnamese patients with upper gastrointestinal symptoms.A cross-sectional study was conducted on consecutive outpatients who underwent upper gastrointestinal endoscopy. Endoscopically suspected esophageal metaplasia (ESEM) which was clearly visible at least 1 cm above the gastroesophageal junction at endoscopy was taken biopsy. At least 1 biopsy per 2 cm in tongues of ESEM and 4 biopsies per 2 cm of circumferential ESEM were taken. The diagnostic criterion for BE was replacement of the normal squamous epithelial lining by columnar epithelium confirmed by histology.A total of 1947 patients were recruited. Forty-seven out of 58 patients with ESEM were histologically confirmed BE. The prevalences of BE and hiatal hernia (HH) were 2.4% (95% confidence interval [CI], 1.7-3.1%) and 2.3% (95% CI, 1.6-2.9%), respectively. Heartburn and/or regurgitation presented in only 61.7% (95% CI, 46.4-75.5%) of patients with BE. In multivariate analysis, the only 2 factors significantly associated with BE were HH (OR 7.53; 95% CI, 3.13-18.11; P < .001) and typical reflux symptom (OR 2.07; 95% CI, 1.12-3.83; P = .020).BE is not uncommon in Vietnamese patients with upper gastrointestinal symptoms. In addition, typical reflux symptoms and HH are the risk factors for BE in Vietnamese.

Psychotropic medication use in adults with intellectual disability in Queensland, Australia, from 1999 to 2015: a cohort study.

BACKGROUND: Longitudinal data on medication use in adults with intellectual disability (ID) are scarce. We describe the longitudinal use of and factors associated with psychotropic medication prescribing in adults with ID living in the Australian community. METHODS: Longitudinal data were obtained from adults with ID in the community in Queensland, Australia, between 1999 and 2015. Participant characteristics and medication use information were extracted from baseline questionnaires and health check booklets. Logistic regression was used to investigate the associations between participant characteristics and psychotropic medication use, commencement or cessation. RESULTS: Longitudinal data were available for 138 participants on 697 reviews. The proportion of participants prescribed psychotropic medications increased from 43% to 54% between 1999 and 2015. The rates of commencement and cessation of psychotropic medications between consecutive time periods ranged from 9% to 18% and 7% to 15%, respectively. Challenging behaviour was associated with psychotropic medication use (adjusted odds ratio = 4.1; 95% confidence interval: 2.1-7.9). Presence of challenging behaviour, either consistent or newly identified, was positively associated with ongoing use or commencement of psychotropic medications. CONCLUSIONS: Psychotropic medications are commonly prescribed to adults with ID. Challenging behaviour is positively associated with ongoing use and commencement.

Strategic investment in tuberculosis control in the Republic of Bulgaria.

As Bulgaria transitions away from Global Fund grant, robust estimates of the comparative impact of the various response strategies under consideration are needed to ensure sustained effectiveness of the tuberculosis (TB) programme. We tailored an established mathematical model for TB control to the epidemic in Bulgaria to project the likely outcomes of seven intervention scenarios. Under existing programmatic conditions projected forward, the country's targets for achieving TB elimination in the coming decades will not be achieved. No interventions under consideration were predicted to accelerate the baseline projected reduction in epidemiological indicators significantly. Discontinuation of the 'Open Doors' program and activities of non-governmental organisations would result in a marked exacerbation of the epidemic (increasing incidence in 2035 by 6-8% relative to baseline conditions projected forward). Changing to a short course regimen for multidrug-resistant TB (MDR-TB) would substantially decrease MDR-TB mortality (by 21.6% in 2035 relative to baseline conditions projected forward). Changing to ambulatory care for eligible patients would not affect TB burden but would be markedly cost-saving. In conclusion, Bulgaria faces important challenges in transitioning to a primarily domestically-financed TB programme. The country should consider maintaining currently effective programs and shifting towards ambulatory care to ensure program sustainability.

Therapeutic efficacy of intra-articular delivery of encapsulated human mesenchymal stem cells on early stage osteoarthritis.

Mesenchymal stem cells (MSCs) represent a great therapeutic promise in pre-clinical models of osteoarthritis (OA), but many questions remain as to their therapeutic mechanism of action: engraftment versus paracrine action. Encapsulation of human MSCs (hMSCs) in sodium alginate microspheres allowed for the paracrine signaling properties of these cells to be isolated and studied independently of direct cellular engraftment. The objective of the present study was to quantitatively assess the efficacy of encapsulated hMSCs as a disease-modifying therapeutic for OA, using a medial meniscal tear (MMT) rat model. It was hypothesized that encapsulated hMSCs would have a therapeutic effect, through paracrine-mediated action, on early OA development. Lewis rats underwent MMT surgery to induce OA. 1 d post-surgery, rats received intra-articular injections of encapsulated hMSCs or controls (i.e., saline, empty capsules, non-encapsulated hMSCs). Microstructural changes in the knee joint were quantified using equilibrium partitioning of a ionic contrast agent based micro-computed tomography (EPIC-µCT) at 3 weeks post-surgery, an established time point for early OA. Encapsulated hMSCs significantly attenuated MMT-induced increases in articular cartilage swelling and surface roughness and augmented cartilaginous and mineralized osteophyte volumes. Cellular encapsulation allowed to isolate the hMSC paracrine signaling effects and demonstrated that hMSCs could exert a chondroprotective therapeutic role on early stage OA through paracrine signaling alone. In addition to this chondroprotective role, encapsulated hMSCs augmented the compensatory increases in osteophyte formation. The latter should be taken into strong consideration as many clinical trials using MSCs for OA are currently ongoing.

Risk factors for infectiousness of patients with tuberculosis: a systematic review and meta-analysis.

We performed a systematic review and meta-analyses of studies assessing tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity, lung cavitation and HIV seropositivity of index patients with both crude and adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven studies were included in the review. We found that demographic characteristics such as age and sex were not significant risk factors, while behaviours such as smoking and alcohol intake were associated with infectiousness although inconsistently. Treatment delay of >28 days was a significant predictor of greater infectiousness. Contacts of sputum smear-positive index patients were found to be more likely to be infected than contacts of sputum smear-negative patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47-3.17, I 2 = 38%). Similarly, contacts of patients with the cavitary disease were around twice as likely to be infected as contacts of patients without cavitation (pooled AOR 1.9, 95% CI 1.26-2.84, I 2 = 63%). In contrast, HIV seropositive patients were associated with few contact infections than HIV seronegative patients (AOR 0.45, 95% CI 0.26-0.80, I 2 = 52%). In conclusion, behavioural and clinical characteristics of TB patients can be used to identify highly infectious patients for targeted interventions.

Novel Rechargeable M3V2(PO4)3//Zinc (M = Li, Na) Hybrid Aqueous Batteries with Excellent Cycling Performance.

A rechargeable hybrid aqueous battery (ReHAB) containing NASICON-type M3V2(PO4)3 (M = Li, Na) as the cathodes and Zinc metal as the anode, working in Li2SO4-ZnSO4 aqueous electrolyte, has been studied. Both of Li3V2(PO4)3 and Na3V2(PO4)3 cathodes can be reversibly charge/discharge with the initial discharge capacity of 128 mAh g(-1) and 96 mAh g(-1) at 0.2C, respectively, with high up to 84% of capacity retention ratio after 200 cycles. The electrochemical assisted ex-XRD confirm that Li3V2(PO4)3 and Na3V2(PO4)3 are relative stable in aqueous electrolyte, and Na3V2(PO4)3 showed more complicated electrochemical mechanism due to the co-insertion of Li(+) and Na(+). The effect of pH of aqueous electrolyte and the dendrite of Zn on the cycling performance of as designed MVP/Zn ReHABs were investigated, and weak acidic aqueous electrolyte with pH around 4.0-4.5 was optimized. The float current test confirmed that the designed batteries are stable in aqueous electrolytes. The MVP//Zn ReHABs could be a potential candidate for future rechargeable aqueous battery due to their high safety, fast dynamic speed and adaptable electrochemical window. Moreover, this hybrid battery broadens the scope of battery material research from single-ion-involving to double-ions -involving rechargeable batteries.

Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis.

INTRODUCTION: Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. METHODS: Electronic searches in PubMed, Scopus, the MEDION database and the Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. RESULTS: Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square P = 0.1009, I(2) = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. CONCLUSIONS: To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers.

Genetic manipulation of the renin-angiotensin system.

The renin-angiotensin system is widely known for its importance in control of blood pressure, electrolyte homeostasis and volume regulation. Recently, renin-angiotensin system function was studied using homologous recombination in embryonic stem cells to manipulate the mouse genome. Angiotensinogen, angiotensin-converting enzyme and angiotensin II receptors were each eliminated in separate lines of mice. These null animals share similar phenotypes, such as a lowering of blood pressure, abnormal renal development, malfunction of the kidney and, unexpectedly, a decrease in hematocrit. In addition, angiotensin-converting enzyme null male mice sire far smaller litters than male wild-type mice. This suggests an unexplored role for angiotensin-converting enzyme in conception. Future studies with these and other genetically engineered mice lines will reveal novel physiological effects of angiotensin II.

Tyrosine kinase activation by the angiotensin II receptor in the absence of calcium signaling.

The angiotensin II type 1 (AT(1)) receptor signals via heterotrimeric G-proteins and intracellular tyrosine kinases. Here, we investigate a modified AT(1) receptor, termed M5, where the last five tyrosines (residues 292, 302, 312, 319, and 339) within the intracellular carboxyl tail have been mutated to phenylalanine. This receptor did not elevate cytosolic free calcium or inositol phosphate production in response to angiotensin II, suggesting an uncoupling of the receptor from G-protein activation. Despite this, the M5 receptor still activated tyrosine kinases, induced STAT1 tyrosine phosphorylation, and stimulated cell proliferation. We also studied another AT(1) mutant receptor, D74E, stably expressed in Chinese hamster ovarian cells and a fibroblast cell line from mice with a genetic inactivation of Galpha(q/11). Both cell lines have a deficit in calcium signaling and in G-protein activation, and yet in both cell lines, angiotensin II induced the time-dependent tyrosine phosphorylation of STAT1. These studies are the first to show the ability of a seven-transmembrane receptor to activate intracellular tyrosine kinase pathways in the absence of a G-protein-coupled rise in intracellular calcium.

Contribution of the hyperpolarization-activated current to the resting membrane potential of rat nodose sensory neurons.

1. The voltage- and time-dependent characteristics of the hyperpolarization-activated current (IH) and its contribution to the resting membrane potential of neonatal rat nodose sensory neurons were investigated using the whole-cell tight seal method of voltage and current clamp recording. 2. IH was found in all neonatal nodose neurons in vitro, contrary to previous reports where its presence was particular for A-type neurons. We used the presence of both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents to distinguish C- from A-type neurons (TTX-S only). We obtained further support for the presence of IH in C-type neurons with experiments in which IH was demonstrated in a subset of neurons sensitive to capsaicin. 3. In both groups IH activated at potentials negative to -50 mV, developed slowly with time and was inhibited by 1-5 mM extracellular caesium. At -120 mV, IH activated with a fast time constant of 73 +/- 3 ms in A-type neurons and 163 +/- 37 ms in C-type neurons (P < 0.05). A second, slower time constant of 682 +/- 83 ms was observed in A-type neurons and 957 +/- 122 ms in C-type neurons. 4. A- and C-type neurons differed in the amplitude of IH. The mean magnitude of IH at -110 mV was -2338 +/- 258 pA in A-type neurons but only -241 +/- 40 pA (P < 0.001) in C-type neurons. This disparity persisted when currents were normalized for capacitance. The reversal potentials for IH were -39 +/- 4 mV for A-type neurons and -37 +/- 5 mV for C-type neurons (P > 0.05). 5. During current clamp recording IH caused time-dependent rectification in response to hyperpolarizing current injections from the resting membrane potential. CsCl abolished the rectification and hyperpolarized the resting potential of A-type neurons from -55 +/- 3 mV to -61 +/- 4 mV and C-type neurons from -62 +/- 2 mV to -71 +/- 3 mV. Taken together, the results in these studies indicate that IH contributes to the resting membrane potential in all nodose neurons.

Effect of feed intake on antimicrobially induced increases in porcine serum insulin-like growth factor I.

This study was conducted to determine whether an antimicrobially induced (ASP-250) increase in serum IGF-I was the result of differences in feed intake. Serum IGF-I concentrations were measured in crossbred pigs that were fed a control diet or a diet supplemented with ASP-250 either for ad libitum consumption or limited to 85% of the control pigs' consumption. The pigs that consumed either diet ad libitum, control or ASP-250, consumed similar quantities of feed. The ASP-250 ad libitum-intake pigs had serum IGF-I concentrations that were greater (P<.01) than those of their ad libitum-intake control littermates. Similarly, the ASP-250 limit-fed pigs had serum IGF-I concentrations that were greater (P<.01) than those of the controls. Although the serum IGF-I concentrations of pigs fed the ASP-250-supplemented diet for ad libitum intake were greater than the serum IGF-I concentrations of the pigs limit-fed the ASP-250-supplemented diet, the differences were not significant (P<.08). The ASP-250-fed pigs had higher serum IGF binding protein (BP)-3 concentrations than did their control littermates (P<.003). A time course of antimicrobially induced alterations in serum IGF-I concentrations revealed that the effect of increased serum IGF-I levels in ASP-250-supplemented pigs (P<.02) was observed within 4 d and was maintained throughout the 4-wk study. These findings show that feed intake is not responsible for the increase in serum IGF-I observed with ASP-250 supplementation. Additionally, the antimicrobially induced increase in serum IGF-I concentrations occurs within a few days after initiation of the treatment.

Angiotensin II signal transduction pathways.

It has been 100 years since the discovery of renin by Tigerstedt and Bergman. Since that time, numerous discoveries have advanced our understanding of the renin-angiotensin system, including the observation that angiotensin II is the effector molecule of this system. A remarkable aspect of angiotensin II is the many different physiological responses this simple peptide induces in different cell types. Here, we focus on the signal transduction pathways that are activated as a consequence of angiotensin II binding to the AT1 receptor. Classical signaling pathways such as the activation of heterotrimeric G proteins by the AT1 receptor are discussed. In addition, recent work examining the role of tyrosine phosphorylation in angiotensin II-mediated signal transduction is also examined. Understanding how these distinct signaling pathways transduce signals from the cell surface will advance our understanding of how such a simple molecule elicits such a wide variety of specific cellular responses.

Reductant substrate for glutathione peroxidase modulates oxidant inhibition of Ca2+ signaling in endothelial cells.

Oxidant stress mediated by tert-butyl hydroperoxide (t-BOOH) inhibits agonist-stimulated Ca2+ entry and internal store Ca2+ release in cultured endothelial cells. The role of intracellular glutathione in modulating the effects of oxidant stress on Ca2+ signaling was determined in cells preincubated with buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, or 1-chloro-2,4-dinitrobenzene (CDNB), a cosubstrate for glutathione-S-transferase. BSO and CDNB decreased endothelial cell glutathione content by 85 and 97%, respectively (control glutathione, 21.5 +/- 2.3 nmol/mg protein). Each agent accelerated the time-dependent effects of t-BOOH on Ca2+ signaling in fura 2-loaded cells and potentiated the inhibition of bradykinin-stimulated 45Ca2+ efflux induced by t-BOOH. These results indicate that decreased availability of reduced glutathione, the primary cosubstrate for glutathione peroxidase, potentiates the effect of hydroperoxide oxidant stress on receptor-operated Ca2+ entry across the plasmalemma and Ca2+ release from internal stores. The present findings suggest that intracellular glutathione availability and/or glutathione redox cycle activity are critically important modulators of oxidant inhibition of Ca(2+)-dependent signal transduction.

Hydrogen peroxide activates agonist-sensitive Ca(2+)-flux pathways in canine venous endothelial cells.

The effect of the biological oxidant H2O2 on purinergic-receptor-stimulated Ca2+ signalling was determined in canine venous endothelial cells. H2O2 increased cytosolic free [Ca2+] ([Ca2+]i), the rate of rise of which was dose-dependently related to H2O2 concentration. The response of [Ca2+]i to H2O2 resulted in part from release of Ca2+ from internal stores. The H2O2-sensitive intracellular Ca2+ pool was characterized in cells suspended in Ca(2+)-free/EGTA buffer and stimulated in sequence with H2O2 and ionomycin or ATP. Under this condition, the rank order of apparent compartment size sensitive to each compound was ionomycin > H2O2 > ATP. Stimulation of cells with H2O2 eliminated any response of [Ca2+]i to subsequent addition of ATP. To test more directly whether H2O2 accesses the inositol trisphosphate-sensitive Ca2+ store, cells were pretreated with thapsigargin, a selective inhibitor of that store's Ca2+ pump. Release of Ca2+ from internal Ca2+ stores by H2O2 declined as the interval after thapsigargin addition increased, a finding that supports the contention that H2O2 accesses the inositol trisphosphate-sensitive Ca2+ store. H2O2-stimulated Ca2+ influx across the cell membrane was sensitive to Ni2+, La3+, and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole HCl (SKF-96365), a selective inhibitor of the agonist-stimulated Ca(2+)-influx pathway. Ca2+ entry triggered by H2O2 appears to occur via the agonist-sensitive Ca2+ influx pathway. Together, these results suggest that H2O2, which is normally secreted by activated neutrophils and monocytes, may act as an intercellular messenger and stimulate Ca2+ signalling in target endothelial cells.

Oxidant stress inhibits the store-dependent Ca(2+)-influx pathway of vascular endothelial cells.

Oxidant stress induced by t-butyl hydroperoxide (t-BuOOH) inhibits bradykinin-stimulated Ca2+ signalling in vascular endothelial cells. The effect of t-BuOOH on intracellular Ca2+ pools was determined by addition of Ca(2+)-releasing agents to fura-2-loaded cells suspended in Ca(2+)-free/EGTA buffer. In control cells, sequential additions of bradykinin and ionomycin produced similar increases in cytosolic free [Ca2+] ([Ca2+]i). By contrast, incubation with t-BuOOH progressively decreased the response of [Ca2+]i to bradykinin and increased that to ionomycin, suggesting that the total (ionomycin-releasable) Ca2+ pool remains replete during oxidant stress. The effect of t-BuOOH on the InsP3-sensitive Ca2+ pool was measured by the increase in [Ca2+]i or efflux of 45Ca2+ stimulated by 2,5-di-t-butylhydroquinone (BHQ). Incubation with t-BuOOH did not inhibit BHQ-stimulated increases in [Ca2+]i or 45Ca2+ efflux, suggesting that the InsP3-sensitive Ca2+ pool remains replete and releasable. Activity of the Ca(2+)-influx pathway stimulated by release of internal Ca2+ stores was determined via re-addition of Ca2+ to BHQ-stimulated cells suspended in Ca(2+)-free/EGTA buffer and via BHQ-stimulated 45Ca2+ uptake. Incubation of cells with t-BuOOH for 1 h significantly inhibited the influx pathway. At later time points, t-BuOOH increased basal [Ca2+]i and potentiated the response of [Ca2+]i to BHQ. Similar results were demonstrated with thapsigargin. Together, these findings suggest that (1) the inhibitory effect of t-BuOOH on bradykinin-stimulated release of Ca2+ from internal stores is not related to depletion of these stores, and (2) inhibition of the store-dependent Ca(2+)-influx pathway occurs by a direct effect of the influx pathway or by inhibition of the mechanism which links the internal Ca2+ store to plasmalemmal Ca2+ influx.

Role of lipid peroxidation in tert-butylhydroperoxide-induced inhibition of endothelial cell calcium signaling.

The potential of lipid peroxidation in inhibition of Ca++ signaling by the membrane-permeant oxidant, tertiary butylhydroperoxide (tert-buOOH), was investigated in calf pulmonary vascular endothelial cells. The oxidant dose-dependently increased lipid peroxidation between concentrations of 10(-5) and 10(-3) M, with an ED50 of approximately 0.05 mM. In addition, the effect of tert-buOOH was time-dependent through the experimental period (3 h). Preincubation of cells with the 21-amino-steroid compound, 21-[4-(5,6-bis(diethylamino)-2-pyridinyl)-1-piperazinyl]-16 alpha-methyl-pregna-1,4,9(11)-triene-3,20-dione hydrochloride (U74500A), reduced tert-buOOH-induced lipid peroxidation to undetectable levels. The effect of U74500A was dose dependent with an IC50 of approximately 10(-6) M. Brief incubation of cells with the aminosteroid resulted in greater than 90% inhibition of lipid peroxidation during subsequent 2-h incubations with tert-buOOH and addition of U74500A during treatment of cells with tert-buOOH halted further lipid peroxidation. In contrast, the iron-containing moiety, hemin, potentiated the effect of tert-buOOH on lipid peroxidation. The ED50 of hemin was approximately 10(-6) M when cells were preincubated with this agent before treatment with tert-buOOH. The potentiating effect of hemin was time-dependent and reached a near maximum upon incubation of cells for 1 h before tert-buOOH. Preincubation of cells with U74500A before treatment with hemin and tert-buOOH decreased lipid peroxidation by 75%. Ca++ signaling was monitored in-cells loaded with the Ca(++)-sensitive fluorescent indicator, fura-2.(ABSTRACT TRUNCATED AT 250 WORDS)