William Weglicki

William Weglicki
  • George Washington University

About

294
Publications
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Introduction
Skills and Expertise
Current institution
George Washington University

Publications

Publications (294)
Article
Full-text available
Erlotinib, an EGFR-TKI, has been used as an effective anti-tumorigenesis agent against several cancers including lung, colon, head and neck. However, it has been reported to cause significant and severe cutaneous side effects. Our previous studies implicated substance P, a neuropeptide, as a significant mediator of skin toxicity. Our present study...
Article
Full-text available
The role of NADPH oxidase subunit, gp91 phox (NOX2) in development of oxidative stress and cardiac dysfunction due to iron (Fe)-overload was assessed. Control (C57BL/6J) and gp91 phox knockout (KO) mice were treated for up to 8 weeks with Fe (2.5 mg/g/wk, i.p.) or Na-dextran; echocardiography, plasma 8-isoprostane (lipid peroxidation marker), cardi...
Article
Full-text available
Hypomagnesemia occurs clinically as a result of restricted dietary intake, Mg-wasting drug therapies, chronic disease status and may be a risk factor in patients with cardiovascular disorders. Dietary restriction of magnesium (Mg deficiency) in animal models produced a proinflammatory / pro-oxidant condition, involving hematopoietic, neuronal, card...
Preprint
The role of NADPH oxidase subunit, gp91Phos (NOX2) in development of oxidative stress and cardiac dysfunction due to iron-overload was assessed. Control (C57BL/6J) and gp91Phox knockout (KO) mice were treated for up to 8 weeks with Fe (2.5 mg/g/wk, i.p.) or Na-dextran; echocardiography, plasma 8-isoprostane (lipid peroxidation marker), cardiac Fe a...
Article
Full-text available
Cutaneous changes like rash and hair loss, as well as other neurogenic inflammation side effects, occur frequently during anticancer treatment with the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), erlotinib. These adverse events may be so severe that they impair the patient’s compliance with the treatment or even cause its...
Article
Full-text available
We determined if HIV-1 expression in transgenic (HIV-1-Tg) rats enhanced hepatic genomic changes related to oxidative/nitrosative stress and lipogenesis during cART-treatment, and assessed effects of Mg-supplementation. A clinically used cART (atazanavir-ritonavir+Truvada) was given orally to control and HIV-1-Tg rats (18 weeks) with normal or 6-fo...
Data
Relevant PCR, Lipids data sets for Figs 1–4, and additional oxidative-nitrosative stress indices. (PDF)
Data
cART treatment for 18 weeks on plasma oxidative/nitrosative stress indices in control and HIV-Tg rats receiving normal Mg or high Mg diets. (DOCX)
Article
Full-text available
Chronic effects of a combination antiretroviral therapy (cART = tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation were assessed. cART (low doses) elicited no significant effects in normal rats, but induced time-dependent oxidative/nitros...
Article
Full-text available
Purpose In this clinical trial, we assessed the efficacy of magnesium (Mg) supplementation in hypomagnesemic type 2 diabetes patients in restoring serum and intracellular Mg levels. The study had two coprimary end points: the change in serum and intracellular Mg level between baseline and after 3 months of supplementation. We compared the efficacy...
Data
The study flow diagram, detailing the phases of the trial including enrollment, intervention allocation, follow-up, and data analysis.
Chapter
Full-text available
Highly active antiretroviral therapy (HAART) agents, azidothymidine (AZT), ritonavir (RTV), and efavirenz (EFV), were assessed in vivo for oxidative stress, cardiac injury, and dysfunction in rats, and dietary Mg-supplementation (Mg-Sup sixfold higher) was evaluated for antioxidant benefits. Three weeks AZT or up to 8. weeks of RTV- and EFV treatme...
Article
The risk relationship between hard water and reduced cardiovascular disease is well known, but it's the magnesium portion of the hardness that accounts for most of the beneficial effect. Magnesium is important in hundreds of biochemical processes, and adult daily requirements are approximately 300‐350 mg/day. Most Americans consume less than the op...
Conference Paper
We determined if clinically used cART promoted redox/nitrosative stress and cardiac toxicity in control and HIV-Tg rats and the effects of Mg. Treatment with cART (Truvada+atazanavir/ritonavir) up to 18 weeks, induced significant hypomagnesemia (-25%), elevated plasma 8-isoprostane, and RBC GSSG 2-3 folds (at 6 wks); plasma 3-nitrotyrosine (NT) inc...
Article
Full-text available
To determine whether the EGFR tyrosine kinase inhibitor, erlotinib may cause hypomagnesemia, inflammation and cardiac stress, erlotinib was administered to rats (10 mg/kg/day) for 9 weeks. Plasma magnesium decreased progressively between 3-9 weeks (-9 to -26%). Modest increases in plasma substance P (SP) occurred at 3 (+27%) and 9 (+25%) weeks. Neu...
Article
Full-text available
Use of protease inhibitors (PI) in HIV patients is associated with hyperlipidemia and increased risk of CHD. Chronic systemic and cardiac effects of ritonavir (RTV), a universal PI booster, and Mg-supplementation were examined. RTV was administered (75 mg/kg/day p.o.) to LewisXBrown-Norway hybrid (LBNF1) rats for up to 8 weeks; significant increase...
Article
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Background: Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients. Methods: To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA...
Data
Supplementary Table 1 lists all 260 transcripts differentially expressed between Group A and Group B, with a sub-listing of the 59 transcripts differentially expressed in both chemo-dependent (A vs. B) and chemo-independent low EF (C vs. D). Supplementary Table 2 lists all 1531 transcripts differentially expressed between Group C and Group D. All o...
Data
Full-text available
Supplementary Figure 1 presents an echocardiography from typical patients with, and without, chemo-induced cardiomyopathy.
Article
We assessed cardiac dysfunction using endocardiography in rats treated with the anticancer drug erlotinib (Tarceva) at a dose of 10 mg/kg/day over a 9 week period. We observed significant progressive hypomagnesemia (P<0.05) at 5 and 9 weeks, when a 3‐fold elevation (P<0.05) of neutrophil superoxide production was seen. Moderately decreased (P<0.05)...
Article
Full-text available
Angiotensin may promote endothelial dysfunction through iron accumulation. To research this, bovine endothelial cells (ECs) were incubated with iron (30 µmol·L–1) with or without angiotensin II (100 nmol·L–1). After incubation for 6 h, it was observed that the addition of angiotensin enhanced EC iron accumulation by 5.1-fold compared with a 1.8-fol...
Article
Full-text available
d-Propranolol (d-Pro: 2–8 mg·(kg body mass)–1·day–1) protected against cardiac dysfunction and oxidative stress during 3–5 weeks of iron overload (2 mg Fe–dextran·(g body mass)–1·week–1) in Sprague–Dawley rats. At 3 weeks, hearts were perfused in working mode to obtain baseline function; red blood cell glutathione, plasma 8-isoprostane, neutrophil...
Article
Full-text available
We determined whether the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) N- (3- chlorophenyl)- 6, 7- dimethoxy- 4- quinazolinamine (tyrphostin AG-1478) causes hypomagnesemia and cardiac dysfunction in rats. Tyrphostin was administered (3 times per week, intraperitoneal injection, to achieve 21.4 mg·(kg body mass)–1·day–1) t...
Article
In recent years, increasing awareness of hypomagnesemia has resulted in clinical trials that associate this mineral deficiency with diabetes, metabolic syndrome, and drug therapies for cancer and cardiovascular diseases. However, diagnostic testing for tissue deficiency of magnesium still presents a challenge. Investigations of animal and cellular...
Article
Full-text available
Background/objective: Hypomagnesemia (Hypo-Mg) in rodents leads to neurogenic inflammation associated with substance P (SP) elevations; neutral endopeptidase (NEP) is a principle cell surface proteolytic enzyme, which degrades SP. The effects of chronic Hypo-Mg on neutrophil NEP activity, cell activation and the associated cardiac dysfunction were...
Article
Full-text available
In rodents with dietary magnesium deficiency (Mg deficiency), hypomagnesemia, occurs leading to a rise in circulating substance P from neuronal tissues to trigger systemic inflammatory stress in cardiac and intestinal tissues. Sustained elevations of substance P may result from impaired neutral endopeptidase (NEP) activity due to reactive oxygen an...
Article
Full-text available
Hypomagnesemia continues to cause difficult clinical problems, such as significant cardiac arrhythmias where intravenous magnesium therapy can be lifesaving. Nutritional deficiency of magnesium may present with some subtle symptoms such as leg cramps and occasional palpitation. We have investigated dietary-induced magnesium deficiency in rodent mod...
Article
The role of NADPH oxidase in development of oxidative stress and cardiac dysfunction was assessed using Fe‐overloaded gp91phox (B6.129S6‐Cybbtm1Din/J) knockout (KO) and control (CL: C57BL/6J) mice. Mice were treated 6–8 wks with Fe (2.5 mg/g/wk i.p.)‐ or Na‐dextran; received echocardiography (echo) at 0, 3, & 6 or 8 wks; and plasma 8‐isoprostane le...
Article
Full-text available
During dietary deficiency of magnesium neurogenic inflammation is mediated, primarily, by elevated levels of substance P (SP). The enzyme most specific for degrading this neuropeptide is neutral endopeptidase (NEP). In recent studies we found that pharmacological inhibition of NEP by phosphoramidon resulted in elevated plasma levels of SP and great...
Article
Full-text available
Hypomagnesemia continues to be a significant clinical disorder that is present in patients with diabetes mellitus, alcoholism, and treatment with magnesuric drugs (diuretics, cancer chemotherapy agents, etc.). To determine the role of magnesium in cardiovascular pathophysiology, we have used dietary restriction of this cation in animal models. This...
Article
Full-text available
Cardiovascular effects of chronic AZT treatment on SD male rats (185 g) fed either a normal Mg diet (0.1% MgO) or a high Mg diet (0.6% MgO) were examined. AZT treatment (1 mg/ml drinking water) for 3 weeks led to a 5.5-fold (0.88 ± 0.11 nmol/min/106 cells, P < 0.05) elevation in neutrophil basal activity of O2 − production versus controls (0.16 ± 0...
Article
Full-text available
Hypertension and heart failure are worldwide health problems of ever-increasing proportions. A failure of the heart, during either systolic and/or diastolic phases of the cardiac cycle, has its origins rooted in an adverse structural, biochemical, and molecular remodelling of myocardium that involves its cellular constituents, extracellular matrix,...
Article
Full-text available
Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (approximately 50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days +/- NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s.c.). MgD alone induced a 9-fold (vs. MgS, p <...
Article
The aim of this study was to determine the effect of magnesium deficiency on small intestinal morphology and function. Rats were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 weeks. Infiltration of neutrophils and mucosal injury were assessed in stained sections of small intestine. Magnesium deficiency alone i...
Article
Severe Mg2+ deficiency provokes pro-oxidative and pro-inflammatory changes, and also has been shown to be pro-apoptotic in thymus and certain cell cultures. In this study we examined the extent that chronic severe dietary Mg2+ deficiency induces apoptosis in the heart. Sprague-Dawley rats were fed during three weeks with normal (25 mM, Mg-control)...
Article
In this study we have tested the effects of d-propranolol (D-Pro) on the iron uptake, iron release and oxidative response of iron-loaded cells in a cellular model of iron-overload using isolated rat peritoneal macrophages incubated with iron-dextran (Fe-D). Pretreatment of macrophages with D-Pro (5-200 microM) prior to Fe-D exposure decreased the c...
Article
Full-text available
The benefits of acute D-propranolol (D-Pro, non-beta-adrenergic receptor blocker) pretreatment against enhanced ischemia/reperfusion (I/R) injury of hearts from moderate iron-overloaded rats were examined. Perfused hearts from iron-dextran-treated rats (450 mg/kg/week for 3 weeks, intraperitoneal administration) exhibited normal control function, d...
Article
Full-text available
The influence of selected beta-receptor blockers on iron overload and oxidative stress in endothelial cells (ECs) was assessed. Confluent bovine ECs were loaded with iron dextran (15 muM) for 24 h and then exposed to dihydroxyfumarate (DHF), a source of reactive oxygen species, for up to 2 h. Intracellular oxidant formation, monitored by fluorescen...
Article
Full-text available
Magnesium is a micronutrient essential for the normal functioning of the cardiovascular system, and Mg deficiency (MgD) is frequently associated in the clinical setting with chronic pathologies such as CHF, diabetes, hypertension, and other pathologies. Animal models of MgD have demonstrated a systemic pro-inflammatory/pro-oxidant state, involving...
Article
Substance P is elevated in plasma and in other tissues during Mg-deficiency, and was found localised to neuronal C-fibres of cardiac and intestinal tissues, where it could promote neurogenic inflammation. Plasma prostaglandin E2 (PGE2), indicative of systemic inflammation, rose significantly (>or=4 fold, p<0.01) after 1 week and remained elevated t...
Article
Electrolyte balance is a critical issue in managing comorbid conditions in both diseased and elderly patients. Patients with hypertension and diabetes need careful regulation of their calcium and magnesium levels, whereas in patients with congestive heart failure, sodium and potassium levels also are critical. Herein we report the outcome of a roun...
Article
Full-text available
Elevated plasma levels of the neuropeptide substance P (SP) precede the perivascular inflammatory infiltrate seen in hearts of Mg(2+)-deficient (MgD) animals. The N-methyl-d-aspartate (NMDA) receptor is found in neurons, and activation of this receptor participates in SP release; under normal circumstances, this release can be blocked by Mg(2+). Th...
Article
The effects of zidovudine (AZT) and AZT-monophosphate (AZT-MP) on lipid peroxidation and oxidative cell injury were studied. When microsomal membranes from rat livers were peroxidized by a superoxide-driven, Fe-catalyzed oxy-radical system (ORS), both AZT-MP and, to a lesser extent AZT, but not thymidine, concentration dependently (2-100 microM) en...
Article
Azidothymidine (AZT) and AZT monophosphate (AZT-MP) in concentrations as low as 10 and 50 microM, respectively, promote oxidation of chemically deacetylated 2',7'-dichlorodihydrofluorescein (DCDHF) to 2',7'-dichlorofluorescein (DCF) by rat peritoneal macrophages activated with latex. Cells were incubated with AZT and AZT-MP for 18 h, washed out fro...
Article
Treatment of HIV with AZT (zidovudine) may have toxic side effects as a result of multiple mechanisms. It is known that patients with AIDS may suffer from magnesium deficiency (MgD). We studied selected biochemical and histopathologic consequences of AZT administration (0.7 mg/mL in drinking water) with concurrent Mg-deficient (20% of normal) diet...
Article
Full-text available
The antioxidant properties of 4-HO-propranolol (4HOP), a major metabolite of propranolol, were studied and compared with that of propranolol and vitamin E (Trolox). When isolated hepatic microsomal membranes were peroxidized by an iron-catalyzed .OH-generating system [dihydroxyfumarate + Fe (III)], 4HOP potently and concentration-dependently inhibi...
Article
Full-text available
The regulatory role of substance-P (SP) on neutrophil and endothelium activation as well as nitric oxide (NO) production induced by Mg-deficiency was examined. Male Sprague-Dawley rats (180 g) were fed either a Mg-deficient (MgD) or Mg-sufficient (MgS) diet for 3 weeks. Enriched neutrophil fractions (> 85%) isolated from whole blood of the Mg-defic...
Article
Full-text available
Severe dietary Mg restriction (Mg(9), 9% of recommended daily allowance [RDA], plasma Mg = 0.25 mM) induces a pro-inflammatory neurogenic response in rats (substance P [SP]), and the associated increases in oxidative stress in vivo and cardiac susceptibility to ischemia/reperfusion (I/R) injury were previously shown to be attenuated by SP receptor...
Article
Full-text available
Cardioprotection by Mg Sulfate (MgSO4) during ischemia/reperfusion (I/R) is attributed largely to the Mg2+ cation. However, Mg-gluconate (MgGl2) may provide added benefit, possibly through its anion's antioxidant properties. Protective effects of both Mg-salts and their anions during 30 min global I and 50 min R were assessed in Langendorff-perfuse...
Article
Background: Despite improvements in care, the prognosis for patients with congestive heart failure (CHF) remains poor. Fifty percent of patients with CHF suffer from arrhythmia and sudden cardiac death. This may be attributable in part to the use of medications that contribute to electrolyte imbalance.Objective: This article presents a case report...
Article
The antioxidant and lysosomotropic properties of a fluorescent analogue of propranolol, 9-amino-acridine-propranolol (9-AAP) were compared to those of propranolol. Using isolated microsomal membranes exposed to a superoxide and hydroxyl radical generating system, 9-AAP was found to be at least 10-fold more potent than propranolol (and about 50% as...
Article
Nitric oxide (NO) and superoxide anions (*O(2)(-) ), which are known to be generated by inflammatory cells under certain pathological conditions, may be cytotoxic to the endothelial cells (ECs) due to peroxynitrite formation. We reported previously that certain lipophilic dihydropyridine (DHP) Ca-blockers exhibit antioxidant activities. In the pres...
Article
Full-text available
We determined whether prior treatment of rats (study 1) with subthreshold doses of iron (no evidence of cardiac tissue overload), or in vitro ischemic pre-conditioning (IP: 5 min. Ischemia (I)/5 min. Reperfusion (R) x 2 cycles) of hearts from untreated rats (study 2), can modulate redox-active cardiac tissue iron levels or distribution, leading to...
Article
Full-text available
The potential anti-radical properties and cytoprotective effects of Mg-gluconate were studied. When microsomal membranes were peroxidized by a *O2- driven, Fe-catalyzed oxy-radical system (R* = dihydroxyfumarate + Fe2+), Mg-gluconate inhibited lipid peroxidation (TBARS formation) in a concentration-dependent manner with IC50 being 2.3 mM. For the e...
Chapter
Vitamin E deficiency was first described as a deficiency disease in 1922 by Evans and Bishop; it was found to prevent fetal resorption in the laboratory rat. Neurological disorders were first described in 1928, when researchers observed paralysis in suckling offspring of vitamin-E-deficient rats. In the following decade, nutritional encephalomalaci...
Article
To determine if an iron-chelating prodrug that must undergo intracellular hydrolysis to bind iron has antimalarial activity, we examined the action of dexrazoxane on Plasmodium falciparum cultured in human erythrocytes and P. yoelii cultured in mouse hepatocytes. Dexrazoxane was recently approved to protect humans from doxorubucin-induced cardiotox...
Article
The effects of selected aci-reductones, which are hydrophobic ascorbate-related analogs including 4-chlorophenyl-2-hydroxytetronic acid (Cpd A), 4-(1,1'-biphenyl)-2-hydroxytetronic acid (Cpd B), and 4-(4'-chloro-1,1'-biphenyl)-2-hydroxytetronic acid (Cpd C), on membrane and low density lipoprotein (LDL) oxidation were assessed. Hepatic microsomal l...
Article
The effect of exogenous Fe-citrate complex (Fe doses of 120 and 240 micromol/kg) on nitric oxide (NO) production in vivo has been studied in blood and liver tissue of endotoxin-treated mice. Fe-citrate complex was administered to mice subcutaneously at the same time with intravenous injection of Escherichia coli lipopolysaccharide (LPS). Iron-depen...
Article
Full-text available
Rodents fed on a Mg-deficient (Mg-D) diet develop cardiomyopathic lesions, as well as other types of cardiovascular dysfunction. In the rat, inflammatory cell infiltration of the myocardium begins to occur by week 1, and the lesions develop extensively in the third and fourth weeks on the Mg-D diet. Although the aetiologic mechanisms of Mg-D cardio...
Article
Sprague-Dawley rats (200 g) were fed either a Mg-deficient or Mg-sufficient diet for 3 weeks. An enriched neutrophil fraction (> 85%) was isolated from the blood by sodium metrizoate/dextran gradient centrifugation. Using the superoxide dismutase. (SOD)-inhibitable cytochrome c reduction assay, the basal activity of neutrophils isolated from the Mg...
Article
Vanin and co-workers (Kubrina et al., Biochim. Biophys. Acta 1176 (1993) 240-244; Mikoyan et al., Biochim. Biophys. Acta 1269 (1995) 19-24) reported that short term (30 min) iron (Fe) exposure potentiates nitric oxide (NO) production in tissues of septic shock mice, based on increased formation of NO complex by diethyldithiocarbamate (DETC). We hav...
Article
Full-text available
Spin-trapping techniques combined with electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (NO) production were compared in the ischemic-reperfused myocardium for the first time, using both aqueous-soluble and lipophilic complexes of reduced iron (Fe) with dithiocarbamate derivatives. The aqueous-soluble complex of Fe and N-m...

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