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Biomedical subjects

E G Janzen

Publications and source records attributed to E G Janzen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Comparison of magnetic resonance images and the histopathological findings of lesions induced by interstitial laser photocoagulation in the brain.

Interest has developed in using magnetic resonance (MR) imaging to monitor the volume of tissue destroyed by interstitial laser photocoagulation (ILP). In these experiments, ILP was induced in the normal brains of 9 anesthetized cats by delivering 1.5 W of continuous-wave Nd:YAG laser energy (1,064 nm) from a single 400-microns core optical fiber for 1,000 s. The irradiations were monitored using proton spin-echo MR imaging during and immediately after ILP and at postirradiation survival times of 2, 5, and 14 days. At 2 days postirradiation, the necrotic thermal lesion consisted of a central cavity surrounded by 2 concentric zones of coagulative necrosis, one dense and the other dispersed. The lesion shrank and the zonal appearance became less obvious over the 14 day survival period. An enhancing halo on contrast-enhanced T1-weighted images acquired immediately postirradiation best approximated the total lesion diameter at 2 days. These images also indicated that the volume of tissue destroyed during ILP corresponded better to the necrotic volume determined at 2 days than at 5 days and 14 days postirradiation. T2-weighted images acquired during and immediately after ILP consistently underestimated the total lesion diameter at 2 days.

Animals↗
PubMed1993

Free radicals and septic shock in primates: the role of tumor necrosis factor.

The role of free radicals in septic-shock-associated tissue injury and the mechanisms underlying the generation of free radicals in sepsis was investigated in a primate model using electron spin resonance (ESR) spectroscopy and spin-trapping techniques paired with physiological measurements. Baboons were administered the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) during infusions of live Escherichia coli (E. coli) with or without challenge with tumor necrosis factor (TNF). ESR spectra suggesting the trapping of carbon-centered and oxygen-centered radicals were detected in liver lipid extracts of E. coli infused animals which exhibited pathophysiological changes indicative of sepsis. In animals demonstrating a toxic response to E. coli. TNF challenge appeared to intensify the ESR signal observed. These data provide evidence of free radical production during sepsis and suggest a role for TNF in the production of these radicals.

Animals↗
PubMed1993

MRI study of the inhibitory effect of new spin traps on in vivo CCl4-induced hepatotoxicity in rats.

Acute CCl4 hepatotoxicity is thought to occur as a result of free radicals generated from the metabolism of CCl4 in the liver. With the use of MRI it is possible to detect in vivo a CCl4-induced localized edematous region surrounding the major branch of the hepatic portal vein in the right lobe. Inhibition of the CCl4-induced response has been obtained by pretreatment with the spin trap, PBN, 30 min prior to CCl4 exposure. The inhibitory effect of two new spin traps, M3PO or methyl-DMPO, and PhM2PO or phenyl-DMPO, on in vivo CCl4-induced acute hepatotoxicity was investigated. Both PhM2PO and M3PO were found to inhibit the CCl4-induced response at lower concentrations (0.35 M/kg body weight) than PBN (0.70 M/kg body weight). However, both M3PO and PhM2PO were also found to induce an edematous response at the same concentrations used for the PBN studies (0.70 M/kg body weight). PhM2PO, at a concentration of 0.35 M/kg body weight, was 93% as efficient as PBN, at a concentration of 0.70 M/kg body weight; whereas M3PO, at a concentration of 0.35 M/kg, was 89% as efficient as PBN at 0.70 M/kg body weight. Electron micrographs were obtained from small liver sections taken in proximity to the major branch of the hepatic portal veins of all treatment groups. The electron microscopy investigations support the MRI findings.

Animals↗
PubMed1993

In vivo 31P NMR spectroscopy studies of halothane induced porcine stress syndrome. No effect of C-phenyl N-tert-butyl nitrone (PBN).

Porcine stress syndrome (PSS) which is an example of malignant hyperthermia (MH) in swine has previously been attributed to oxidative stress primarily due to an inherited antioxidant abnormality in MH susceptible (MHS) animals. C-phenyl-N-tert-butyl nitrone (PBN), a free radical spin trap, was selected to investigate whether free radicals are involved in MH. If free radicals cause the MH stress attack, then PBN should alter the time required for the onset of the stress attack, or perhaps protect the animal from experiencing the stress attack. In vivo phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) was used to monitor metabolism in three to four week old normal and MHS piglets administered halothane as the stress challenge. Malignant hyperthermia was not reproducibly induced by halothane anesthesia. For those animals which did develop MH a dramatic fall in the level of PCr and a rise in the level of Pi was detected by 31P MRS. Intravenous administration of PBN prior to halothane exposure had no effect on the number of animals experiencing the stress attack. PBN does not appear to prevent, delay or reverse the onset of halothane-induced MH in three to four week old MHS piglets. The primary events leading to the MH syndrome do not appear to be influenced by the intervention of the type of free radicals normally trapped by PBN.

Animals↗
PubMed1993

Use of nitroxides as MRI contrast agents to study in vivo carbon tetrachloride induced hepatotoxicity in rats.

CCl4 and related compounds, such as halothane, are metabolized by the liver to form free radical intermediates, which are thought to be implicated in the hepatotoxic response. Two to three hours following CCl4 exposure (i.p.) there is a localized edematous region surrounding the portal vein which is observable by proton MRI in vivo. Enhancement of the CCl4-induced edematous region was possible using Gd-DTPA, a paramagnetic contrast agent. However, with the use of a nitroxide contrast agent (3-PCA) there was no enhancement, but rather a significant diminution of the CCl4-induced edematous response. These results suggest that the nitroxide contrast agents, which are themselves free radicals, act as free radical scavengers and therefore reduce the formation of the CCl4-induced hepatic 'damage' observed in proton MR images.

Animals↗
PubMed1993

In vivo nuclear magnetic resonance spectroscopy of chicken embryos from two broiler strains of varying fat content.

In vivo nuclear magnetic resonance (NMR) imaging and spectroscopy techniques were used to monitor changes in P- and H-containing molecules in embryos of two broiler strains (30 and 31) differing genetically in fat content and ranging in age from 0 to 20 days of incubation. Chemical analysis showed that Strain 30 has more carcass fat than Strain 31 at market age (7 wk). Proton (1H) and 31P spectra were obtained on four eggs per strain at Days 0, 2, 4, 6, 8, 11, 12, 14, 16, 17, 19, and 20 of incubation. Fat:water, phosphomonoester (PME):phosphodiester (PDE), and adenosine triphosphate (ATP):PDE ratios were calculated. Chicks were hatched, grown to market weight (2,000 g for females and 2,300 g for males at 7 wk), and the whole intact carcasses were analyzed for crude fat. Hydrogen-1 NMR spectroscopy studies of incubated eggs indicated no significant difference (P > .05) in the fat:water ratio between the two strains. The difference in the PME:PDE ratios between the two strains as obtained by 31P-NMR spectroscopy over all days of incubation analyzed was not significant (P > .05); however, there was a significant difference in this ratio between the two strains at Days 4, 6, and 11. Up to Day 16, Strain 30 had a slightly, but not significantly (P > .05), higher ATP:PDE ratio as shown on 31P-NMR spectra, whereas after Day 17 the ATP:PDE ratio was significantly higher (P < .01) for Strain 31. Strain 31 birds had a significantly lower (P < .05) crude fat content. There was a significant difference (P < .05) in 7-wk carcass fat content between sexes, males having significantly (P < .01) less fat than females, which was correlated with a significantly higher (P < .01) ATP:PDE ratio in male embryos. It might be possible to use ATP:PDE ratios obtained during embryonic development by 31P-NMR to select strains of birds for low fat content at market weight and to distinguish between sexes during late embryonic development.

Adipose Tissue↗
PubMed1992

Spin trapping of free radical metabolites of carbon tetrachloride in vitro and in vivo: effect of acute ethanol administration.

A single dose of ethanol, when administered 18 hr prior to CCl4, potentiates the hepatotoxicity of the halocarbon. In these studies, spin trapping and electron spin resonance (ESR) spectroscopy methods were utilized to determine whether a single ethanol dose increased the metabolism of CCl4 to free radical intermediates. When hepatic microsomes from ethanol-treated or control rats were incubated with CCl4 and the spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN), the ESR signal of the trichloromethyl radical adduct of PBN was of similar intensity in both groups. The ethanol dose also failed to induce p-nitrophenol hydroxylase activity. When PBN and CCl4 were administered to rats, liver extracts contained ESR signals resulting primarily from the trichloromethyl radical adduct of PBN, and the signals were of similar intensity in both experimental groups. Higher concentrations of the carbon dioxide anion radical adduct of PBN were detected in plasma samples from ethanol-treated rats. However, when hepatocytes from ethanol-treated and control rats were incubated with PBN and CCl4, ESR signals of the carbon dioxide adduct were of similar intensity. These data suggest that the higher concentrations of the carbon dioxide adduct in the blood of ethanol-treated rats may be explained by early CCl4-induced damage to liver cell membranes, rather than increased rates of formation. The data in this report fail to support the hypothesis that a single dose of ethanol stimulates the hepatic metabolism of CCl4 to the trichloromethyl radical. Alternatively, ethanol may potentiate CCl4 toxicity by affecting some critical metabolic step subsequent to trichloromethyl radical formation.

Animals↗
PubMed1992

Use of 1H/23Na and 1H/31P double frequency tuned birdcage coils to study in vivo carbon tetrachloride-induced hepatotoxicity in rats.

In vivo 1H and 23Na magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) techniques were used to study CCl4-induced acute hepatotoxicity in rats in situ. One or two hours following exposure to CCl4, a localized edematous region was detected in the liver by 1H MRI. The CCl4-induced edema was localized in a region surrounding the hepatic portal vein. With the use of a 23Na/1H double frequency tuned bird-cage imaging coil an increase in Na+ ion flux was also observed in the same region as the edematous region detected by 1H-MRI. Pretreatment with alpha-phenyl-tert-butyl nitrone (PBN), a free radical spin trap, 30 min prior to CCl4 exposure, was found to reduce the CCl4-induced edematous response in the liver observed in either 1H or 23Na-NMR images. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the key causal agents in the initiation of the edematous response. In addition, with the use of a 31P/1H double frequency tuned bird-cage imaging/spectroscopy coil, localized 31P spectra (ISIS) were obtained from the regions of CCl4-induced "tissue damage" observed in the 1H-MRI images. The most notable changes observed from the 31P spectra were an increase in inorganic phosphate (Pi) and a decrease in hepatocytosolic pH in the CCl4-treated rat livers in comparison to saline-treated control livers.

Animals↗
PubMed1992

Stabilities of hydroxyl radical spin adducts of PBN-type spin traps.

The stability of the hydroxyl spin adduct of nine different PBN-type spin traps has been examined in phosphate buffer solutions of various pH. The hydroxyl adduct is produced by short illumination of hydrogen peroxide with UV light in the presence of spin trap and the decay of its EPR signal followed. The stability measured by the half life of the first-order decay is strongly dependent on the pH of the solution and the structure of the aromatic ring used in the trap. All hydroxyl adducts are more stable in acidic media. tert-Butyl hydroaminoxyl is detected as a degradation product of the hydroxyl adduct from all spin traps.

Cyclic N-Oxides↗
PubMed1992

Research note: an assessment of egg yolk structure using magnetic resonance imaging.

The purpose of the present experiment was to examine the inner structure of the egg using magnetic resonance imaging (MRI). Proton images of fertile and infertile eggs and eggs from hens fed a corn-based or a flax-based diet were generated using a Spectroscopy Imaging Systems unit. Phantom eggs, made from homogenized albumen and homogenized yolk in a plastic shell, were imaged as controls. Eggs were imaged individually on their side, in the sagittal plane. A single image was generated through the center of the yolk. Images clearly distinguished the eggshell, air space, albumen, and yolk. Within the yolk of both fertile and infertile eggs, the latebra, the neck of the latebra, and four to six pairs of concentric yolk rings were visible, although the rings were less clearly defined in eggs from hens fed the flax-based diet. The embryo was not visible after 24 h of incubation but yolk stratification could still be resolved. Rings were not evident in the phantom eggs. It was concluded that MRI can be used successfully in assessing the microanatomy of eggs.

Animal Feed↗
PubMed1991

Enhancement of carbon tetrachloride-induced liver injury by a single dose of ethanol: proton magnetic resonance imaging (MRI) studies in vivo.

Magnetic resonance imaging (MRI) and localized magnetic resonance spectroscopy (MRS) were used to study the effects of a single dose of ethanol, given 18 h prior to experiments, on CC14-induced acute hepatotoxicity in rats in situ. Localized edema in the centrilobular region of the liver, following exposure to ethanol and CCl4, was detected by 1H-MRI techniques. The edema was characterized by a volume selective spectroscopy (VOSY) method, which measured an increase in water concentration from ethanol and CCl4-treated rat livers, in comparison to control livers. Electron microscopy (EM) of the high intensity regions of the ethanol/CCl4 treated liver sections revealed dramatic subcellular changes such as fragmentation of the granular endoplasmic reticulum (ER), formation of large vacuoles and lipid droplets in the cytoplasmic matrix and extensive swelling of the mitochondria as well as disruption of the cristae. Pretreatment with alpha-phenyl tert-butyl nitrone (PBN), a free radical spin trap, prior to halocarbon exposure, was found to reduce the CC14-mediated high intensity region in the liver images. Electron microscopy of the PBN pretreated CCl4 exposed rat liver sections revealed only minor observable differences in subcellular organization, such as some swelling of the mitochondria, when compared to controls. In addition, these data suggest that ethanol may potentiate CCl4 hepatotoxicity by increased formation of free radical intermediates. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the causal factor in the initiation of the edema.

Animals↗
PubMed1991

Detection of spin adducts in blood after administration of carbon tetrachloride to rats.

Rats were treated with CCl4 and the spin trapping agent alpha-phenyl-N-t-butyl nitrone (PBN), followed by ESR investigations on samples of heparinized blood. The major signal detected was the ascorbate semidione radical, but smaller concentrations of the carbon dioxide radical anion spin adduct of PBN could also be detected. The ESR signals were more intense when experiments were conducted with plasma, rather than blood. The spin adducts detected were not associated with the red blood cells, and their apparent concentrations increased when the cells were removed by centrifugation. The addition of ascorbate oxidase to the samples markedly diminished the intensity of the ascorbate semidione radical. When plasma samples from CCl4-treated rats were extracted into toluene, the ESR spectrum of the trichloromethyl adduct of PBN was observed in the extract. Because the spectrum of this adduct was not observed in direct ESR studies of plasma, it is possible that immobilization occurred in the presence of plasma proteins. Evidence to support this hypothesis was developed by adding bovine serum albumin (BSA) to an aqueous solution of the trichloromethyl radical adduct of PBN. As the BSA concentration was increased, the intensity of the ESR spectrum was markedly diminished, and displayed features of an immobilized adduct.

Animals↗
PubMed1991

In vivo proton magnetic resonance imaging and localized spectroscopic analysis of polycystic kidney disease in DBA/2FG-pyc mice.

Proton magnetic resonance imaging (MRI) and localized spectroscopy techniques were used to study polycystic kidney disease (PKD) in DBA/2FG-pcy (pcy) mice, which are an animal model for the adult form of human PKD. A volume selective spectroscopy (VOSY) method was used to obtain localized proton spectra as well as apparent T1 and T2 relaxation times of the kidneys of either pcy or DBA/2FG normal (DBA) mice. Localization of the proton spectra was based on spatial coordinates determined from the proton images. Increases in apparent kidney T1 and T2 relaxation times were observed for pcy mice in comparison to those measured in DBA mice. Localized kidney T1 values from pcy mice were found to range from 799 to 1395 msec whereas DBA mice kidney T1 values were 617 to 774 msec. Localized T2 values measured from pcy mice kidneys ranged from 90 to 172 msec in comparison to kidney T2 values of 50 to 72 msec for DBA mice. The onset of cyst formation in the kidneys of pcy mice as a function of age was also studied. As early as 4 to 5 weeks of age it was possible to detect in vivo changes in pcy mice kidney T1 and T2 values.

Age Factors↗
PubMed1991

Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: in vivo detection of 1-hydroxyethyl radicals with PBN.

The generation of free radicals in rat liver following the acute oral administration of ethanol was studied with the spin-trapping method, using a deuterated derivative of phenyl-N-tert-butylnitrone (PBN-d14) as the spin-trapping agent. After administration of ethanol and PBN-d14 to rats, organic extracts of the liver were prepared and subjected to ESR spectroscopy. In the case of ethanol-treated rats, the ESR spectra indicated that mixtures of radicals had been trapped, while spectra from control rats were essentially negative. The predominant spin adduct detected after ethanol treatment is proposed to be from a carbon-centered, primary alkyl radical, based on gamma-hydrogen hyperfine splitting patterns observed with PBN-d14. Oxygen-centered radicals also contributed to the ESR spectra. Liver extracts also contained low concentrations of the 1-hydroxyethyl radical spin adduct, which was indicated by weak spectral lines corresponding to those of the 1-13C-ethanol adduct. These data confirm previous suggestions that ethanol is metabolized to a free radical metabolite in rat liver. In addition, some information on types of lipid radicals generated during alcohol intoxication has been obtained.

Alcoholic Intoxication↗
PubMed1991

The role of mixed function oxidase (MFO) in the metabolism of the spin trapping agent alpha-phenyl-N-tert-butyl-nitrone (PBN) in rats.

It has been previously demonstrated that alpha-phenyl-N-tert-butyl-nitrone (PBN), one of the most widely used free radical trapping agents, is rapidly absorbed, evenly distributed among a wide range of tissues, and metabolized to form one metabolite. The objective of this study was to determine if the distribution and metabolism of PBN can be affected by inducers or inhibitors of the microsomal mixed function oxidase (MFO) system. Rats were pretreated with MFO inducers (phenobarbital and 3-methylcholanthrene) or MFO inhibitors (metyrapone and piperonyl butoxide) before 14C-PBN was injected (i.p.) The concentrations of 14C-PBN and its metabolite were measured in plasma, urine, liver, lung and kidney 2 hours after injection. The results indicated that when MFO was induced, the concentration of 14C-PBN metabolite was significantly reduced in all tissues measured. The maximum concentration of PBN parent compound in the tissues where MFO was induced was 50% of that found in saline controls. Manipulation of tissue MFO levels with inducers and inhibitors altered the ratio of 14C-PBN parent compound to the PBN-metabolite. When 14C-PBN was incubated with rat liver microsomes at 37 degrees C in the presence of NADPH, the rate of metabolism was 1,752 dpm of 14C-PBN-metabolite formed/nmole P-450/min. Inactivation of MFO by heat (80 degrees C for 1 min) or deletion of NADPH diminished the formation of PBN metabolite in vitro. It is concluded that the MFO system may be responsible for the metabolism of PBN. Tissue concentrations of PBN can be affected by drugs or toxins which are inducers or inhibitors of MFO.

Animals↗
PubMed1991

Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study.

In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2-hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.

3,3'-Diaminobenzidine↗