Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

Background

Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles.

Methods

This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC) database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses.

Results

Multivariate regression analysis indicated that income was negatively associated with BMI (p < 0.0005) and age (p = 0.023) at time of referral. The highest income quintiles were found to have lower serum triglycerides (p = 0.011) and higher HDL-c (p = 0.008) at time of referral. No significant differences were found in HBA1C, LDL-c or duration of diabetes. The Chi square analysis of medication use revealed that despite no significant differences in HBA1C, the lowest income quintiles used more metformin (p = 0.001) and sulfonylureas (p < 0.0005) than the wealthy. Use of other therapies were similar across income groups, including lipid lowering medications. High income patients were more likely to be treated with diet alone (p < 0.0005).

Conclusion

Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.     

Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced liver injury in mice

Oxidative stress has been recognized as a critical pathogenetic mechanism for the initiation and the progression of hepatic injury in a variety of liver disorders. Antioxidants, including many natural compounds or extracts, have been used to cope with liver disorders. The present study was designed to investigate the hepatoprotective effects of cassia seed ethanol extract (CSE) in carbon tetrachloride (CCl(4))-induced liver injury in mice. The animals were pre-treated with different doses of CSE (0.5, 1.0, 2.0 g/kg body weight) or distilled water for 5 days, then were injected intraperitoneally with CCl(4) (0.1% in corn oil, v/v, 20 ml/kg body weight), and sacrificed at 16 hours after CCl(4) exposure. The serum aminotransferase activities, histopathological changes, hepatic and mitochondrial antioxidant indexes, and cytochrome P450 2E1 (CYP2E1) activities were examined. Consistent with previous studies, acute CCl(4) administration caused great lesion to the liver, shown by the elevation of the serum aminotransferase activities, mitochondria membrane permeability transition (MPT), and the ballooning degeneration of hepatocytes. However, these adverse effects were all significantly inhibited by CSE pretreatment. CCl(4)-induced decrease of the CYP2E1 activity was dose-dependently inhibited by CSE pretreatment. Furthermore, CSE dramatically decreased the hepatic and mitochondrial malondialdehyde (MDA) levels, increased the hepatic and mitochondrial glutathione (GSH) levels, and restored the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione S-transferase (GST). These results suggested that CSE could protect mice against CCl(4)-induced liver injury via enhancement of the antioxidant capacity.     

In-vivo studies of mammary development in the goat using magnetic resonance imaging (MRI)

Mammary development and regression were measured in goats in vivo using magnetic resonance imaging (MRI). Measurements were made during the first and second cycles of pregnancy, lactation and involution. In primiparous goats, and exponential pattern of growth was evident during gestation and for the first 2 weeks of lactation. Parenchyma volume correlated significantly with milk yield across goats during early lactation, and across stage of lactation within goats. Milking was discontinued in Week 26 of the first lactation. Involution was characterized by an initial accumulation of fluid (over 2 days) followed by reabsorption; parenchyma volume did not decrease significantly until the 3rd week of involution, which was also the time at which these goats were mated to start their second gestation. Their udders still contained significant quantities of fluid (40-60% of the gross volume), but parenchyma volume was also greater (by 4.7-fold) than in goats beginning their first gestation. By Week 15 of gestation there was no longer a parity difference in parenchyma; the udders of first-gestation goats had grown significantly, but those of second-gestation goats had not. Conversely, between gestation Week 15 and lactation Week 2 mammary growth was significantly more rapid in the second cycle, such that the udder was larger at the start of the second lactation.     

In vivo moment arm calculations at the ankle using magnetic resonance imaging (MRI)

In vivo moment arm lengths for the Achilles tendon and tibialis anterior (TA) were determined in 10 adult male subjects. Moment arms were measured as the perpendicular distance between the joint center of rotation (CR) and the center of the muscle's tendon on a series of sagittal plane magnetic resonance images. The first set of calculations used a fixed CR and the second a moving CR. The position of the CR was determined using a modification of the graphical method of Reuleaux. For both moving and fixed CR conditions, moment arms increased by approximately 20% for the Achilles tendon and decreased by approximately 30% for the TA when the ankle moved from maximum dorsiflexion to maximum plantarflexion. Moment arms averaged 3.1% greater for the Achilles tendon and 2.5% greater for the TA when calculated using a fixed CR. These data suggest that the averaged moment arm lengths for the Achilles tendon and the TA were relatively unaffected by the use of a fixed vs moving CR.     

Effect of PGI2 in carbon tetrachloride-induced liver injury

The hepatoprotective effect of prostacycline was studied after in vitro and in vivo CCl4 liver injury. It was found that PGI2 could partly restore the amino acid incorporation after in vitro CCl4 poisoning. In the in vivo system PGI2 was capable of decreasing the elevated SGOT levels and the accumulated triglyceride in the liver, and to increase hepatic glycogen content 24 hours after CCl4 injury.     

Visualisation of metal deposition in biofilm reactors by three-dimensional magnetic resonance imaging (MRI)

Three-dimensional magnetic resonance imaging (MRI) was used to visualise polyurethane foam-immobilised Citrobacter after challenging with La³⁺ and/or Cu²⁺ in citrate buffer supplemented with glycerol 2-phosphate. Extensive phosphatase-mediated bioaccumulation of LaPO₄ was observed but no evidence for deposition of Cu₃(PO₄)₂ was obtained by X-ray diffraction and proton-induced X-ray emission analyses. Image analysis showed that La³⁺/Cu²⁺ is a good model system to study the function of this biofilm reactor non-invasively by MRI.     

In vivo assessment of microcystin-LR-induced hepatotoxicity in the rat using proton nuclear magnetic resonance (1H-NMR) imaging.

Microcystin-LR (MCLR)-induced hepatotoxicity was assessed in vivo in male Sprague-Dawley rats (150-350 g) using magnetic resonance imaging (MRI). Following the intraperitoneal administration of MCLR (LD(50)), a region of damage, characterised by increased signal intensity on T(2)-weighted images, was seen proximal to the hepatic portal vein in the liver. Similarly, increased signal intensity was seen in the chemical-shift selective images (CSSI) of water frequency, proximal to the hepatic portal vein in the liver. This indicates that the increased signal intensity observed in the T(2)-weighted images was due to an increased amount of magnetic resonance (MR) visible protons in the tissue which represents an oedematous response. Image analysis of regions of apparent damage around the hepatic portal vein indicated a statistically significant increase in signal intensity in this region. Mitochondrial swelling and lipid inclusions were observed by transmission electron microscopy (TEM) in samples obtained from the oedematous regions of the liver using spatial coordinates from the magnetic resonance (MR) images. Massive haemorrhagic necrosis and nuclear swelling were observed by light microscopy in the centrilobular regions of the lobules.     

Muscle geometry affects accuracy of forearm volume determination by magnetic resonance imaging (MRI)

Upper extremity musculoskeletal modeling is becoming increasingly sophisticated, creating a growing need for subject-specific muscle size parameters. One method for determining subject-specific muscle volume is magnetic resonance imaging (MRI). The purpose of this study was to determine the validity of MRI-derived muscle volumes in the human forearm across a variety of muscle sizes and shapes. Seventeen cadaveric forearms were scanned using a fast-spoiled gradient echo pulse sequence with high isotropic spatial resolution (1mm(3) voxels) on a 3T MR system. Pronator teres (PT), extensor carpi radialis brevis (ECRB), extensor pollicis longus (EPL), flexor carpi ulnaris (FCU), and brachioradialis (BR) muscles were manually segmented allowing volume to be calculated. Forearms were then dissected, muscles isolated, and muscle masses obtained, which allowed computation of muscle volume. Intraclass correlation coefficients (ICC(2,1)) and absolute volume differences were used to compare measurement methods. There was excellent agreement between the anatomical and MRI-derived muscle volumes (ICC = 0.97, relative error = 12.8%) when all 43 muscles were considered together. When individual muscles were considered, there was excellent agreement between measurement methods for PT (ICC = 0.97, relative error = 8.4%), ECRB (ICC = 0.93, relative error = 7.7%), and FCU (ICC = 0.91, relative error = 9.8%), and fair agreement for EPL (ICC = 0.68, relative error = 21.6%) and BR (ICC = 0.93, relative error = 17.2%). Thus, while MRI-based measurements of muscle volume produce relatively small errors in some muscles, muscles with high surface area-to-volume ratios may predispose them to segmentation error, and, therefore, the accuracy of these measurements may be unacceptable.     

Brain-stem auditory evoked potentials (BAEPs) and magnetic resonance imaging (MRI) in a case of facial myokymia

The case of a 37-year-old woman with facial myokymia is reported. Magnetic resonance imaging (MRI), electromyography (EMG) and brain-stem auditory evoked potentials (BAEPs) supported the clinical diagnosis of suspected multiple sclerosis (MS). MRI showed a single area of abnormal signal in the pontine region. The authors discuss the possible relationship between the brain-stem lesion and the electrophysiological abnormalities demonstrated by BAEPs and the EMG of facial muscles.     

Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats

Central neuropeptides play important roles in many physiological and pathophysiological regulation mediated through the autonomic nervous system. In regard to the hepatobiliary system, several neuropeptides act in the brain to regulate bile secretion, hepatic blood flow, and hepatic proliferation. Central injection of corticotropin-releasing factor (CRF) aggravates carbon tetrachloride (CCl4)-induced acute liver injury through the sympathetic nervous pathway in rats. However, still nothing is known about a role of endogenous neuropeptides in the brain in hepatic pathophysiological regulations. Involvement of endogenous CRF in the brain in CCl4-induced acute liver injury was investigated by centrally injecting a CRF receptor antagonist in rats. Male fasted Wistar rats were injected with CRF receptor antagonist alpha-helical CRF-(9-41) (0.125-5 microg) intracisternally just before and 6 h after CCl4 (2 ml/kg) administration, and blood samples were obtained before and 24 h after CCl4 injection for measurement of hepatic enzymes. The liver sample was removed 24 h after CCl4 injection, and histological changes were examined. Intracisternal alpha-helical CRF-(9-41) dose dependently (0.25-2 microg) reduced the elevation of alanine aminotransferase and aspartate aminotransferase levels induced by CCl4. Intracisternal alpha-helical CRF-(9-41) reduced CCl4-induced liver histological changes, such as centrilobular necrosis. The effect of central CRF receptor antagonist on CCl4-induced liver injury was abolished by sympathectomy and 6-hydroxydopamine pretreatment but not by hepatic branch vagotomy or atropine pretreatment. These findings suggest the regulatory role of endogenous CRF in the brain in experimental liver injury in rats.     

Magnetic resonance imaging (MRI) as a method for determination of freezing injury in strawberry crowns

In an experiment with controlled freezing, strawberry plants were exposed to 0, ?8, ?12, ?16 and ?20°C at a freeze and thaw rate of 2 °C/hour in March/April 1996. Crowns from the cultivar ‘Korona’ were examined using magnetic resonance imaging (MRI), showing a gradual increase of signal intensity from the centre of the crowns, as a result of the temperature drop, which might be caused by lipids. The increase in signal intensity was in accordance with the tissue browning of crowns, which increased substantially when the temperature dropped below ?12 °C. A similar reaction was shown in a field experiment comparing wintercovered and not wintercovered strawberry plants. The plants which had been exposed to temperatures between ?10 and ?16 °C were severely injured. This demonstrates that MRI has a potential as an objective method to determine freeze injury in the field, by «calibrating» the MRI instrument to freezing profiles in controlled experiments.     

Nuclear magnetic resonance imaging (MRI) of diesel oil migration in estuarine sediment samples

Magnetic resonance imaging (MRI) provides a means of monitoring the change in position and the eventual breakdown of oil within sediments. The multidimensional technique allows the position of nuclei (most commonly protons) to be located within a known volume of substrate, e.g. sediment, hence offering a method of assessing the harming potential of oils in near-shore environments. Two-dimensional (2D) and three-dimensional (3D) MRI analyses of the measurement and movement of oil in estuarine sediments show that, using appropriate parameters, movement of the oil can be both observed and quantified. To aid the quantification a sample holder fabricated from polyvinylsiloxane, an inert material visible in magnetic resonance images has been used as an internal intensity standard. The results show the great potential of MRI in studying protonated contaminants in these materials, notwithstanding the presence of paramagnetic species in estuarine sediments which might distort the image. Sediments studied thus far have been collected from the Tay Estuary, Northeast Scotland. Journal of Industrial Microbiology & Biotechnology (2001) 26, 77–82. Received 26 January 2000/ Accepted in revised form 07 June 2000     

Focused hyperthermia with a magnetic resonance imaging (MRI) unit and an interstitial grounded probe

The feasibility of using a commercial magnetic resonance imaging (MRI) scanner to do either imaging or hyperthermic treatment was demonstrated. Radiofrequency (RF) induced focal heating of phantoms and animal tissues was performed using a MRI scanner as the RF power source and a grounded interstitial probe as a device to produce hyperthermia via eddy current convergence. In the therapeutic mode, a pulse width of 900 microseconds and interval of 50 ms were used to give 2% duty cycle (closest simulation to continuous wave (CW) mode without bypassing imaging filters). Temperature in the vicinity of the grounded probe was measured with a field nonperturbing fluoroptic probe. Temperatures increased 4.5 degrees C in 5 minutes in a dielectrically uniform phantom, 3.1 degrees C in 6.7 minutes in rats' leg muscles, and 5.0 degrees C in 6.0 minutes in rats' peritoneum. The MRI of the phantom with the grounded probe and the fluoroptic probe was obtained using spin echo sequences. The potential advantage of this approach is visualization of deep-seated tumors and hyperthermic treatment with minimal modification of the MRI scanner.     

Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice

We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1β in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis.     

The proton magnetic resonance spectra of a cobalt(II) azurin

The proton magnetic resonance spectrum of a cobalt(II) derivative of $\text{Pseudomonas}\text{aeruginosa}$ azurin is reported. The temperature dependence of 26 resonances is described together with a study of the pH¹ titration behaviour over a range 4.7 to 9.3. A few resonances are observed shifted by more than 30 ppm from their diamagnetic positions. Of the remainder most extrapolate to the aliphatic region at T = ∞. Two lines are assigned to the C2 and C4 protons of a freely titrating histidine residue far from, and only slightly affected by, the Co(II) centre. A further two lines are assigned to the C2 hydrogen of protonated and deprotonated forms of a histidine residue in slow exchange with bulk aquaeous protons and closer to, but not bound to, the cobalt. The structure of the protein in the vicinity of the paramagnetic centre is found to be essentially insensitive to pH¹ over the range 4.7 to 9.3.     

Mechanism of in vivo carbon tetrachloride-induced liver microsomal cytochrome P-450 destruction.

Prior administration of aminotriazole (3-amino-1,2,4-triazole) or pyrazole to rats resulted in a significant prevention of the CCl₄-induced decrease in the liver microsomal P-450 content. In A/J mice the CCl₄ activation and P-450 destruction occurred in absolute absence of lipid peroxidation as determined by uv absorption. The data suggest that P-450 destruction is mainly mediated by direct attack of CCl₄ metabolites rather than by CCl₄-induced lipid peroxidation.