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Biomedical subjects

A Volk

Publications and source records attributed to A Volk.

At least 37 records · Page 2Linked to original sources
PubMed1999

Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

Adult↗
PubMed1997

Age dependence of the T2-weighted MRI signal in brain structures of a prosimian primate (Microcebus murinus).

Mouse lemurs (Microcebus murinus) are prosimian primates described to be convenient models of brain aging. We observed very high correlations between the T2-weighted magnetic resonance imaging (MRI) signal decrease and the natural logarithm of age in the basal ganglia. The correlation coefficient was higher for the pallidum (r = 0.95, P < 0.0001) than for other structures. We suggest that the ratio of the pallidum intensity divided by the amygdala and temporal lobe intensity should be a valuable non-invasive marker of age and of cerebral aging. It should be particularly useful for the non-invasive assessment of interventions and drugs that affect the aging process.

Aging↗
PubMed1997

The effects of a butanediol treatment on acute focal cerebral ischemia assessed by quantitative diffusion and T2 MR imaging.

Increased water T2 values indicates the presence of vasogenic edema. Decreased apparent diffusion coefficient (ADC) maps reveal ischemic areas displaying cytotoxic edema. ADC and T2 abnormalities spread through the middle cerebral artery (MCA) territory up to 24 h after middle cerebral artery occlusion (MCAO). Also, it was found that ADC and T2 contours closely match at 3.5 and 24 h. Since butanediol reduces vasogenic edema and improves energy status in various models of ischemia, we used these two techniques to investigate putative improvements in cytotoxic and vasogenic edema after permanent MCAO performed on rats. Rats were given no treatment (n = 8), or a treatment with 25 mmol/kg intraperitoneal (i.p.) butanediol (n = 5), 30 min before and 2.5 h after MCAO. Quantitative ADC and T2 maps of brain water were obtained, from which the volumes presenting abnormalities were calculated at various time points up to 24 h. Effects of butanediol on the ADC and T2 values in these areas were determined. Butanediol reduced neither the ADC volume nor the initial ADC decline. However, it reduced T2 volumes by 32% at 3.5 h and 15% at 24 h (p < 0.05), and reduced T2 increase in the striatum at 3.5 h post-MCAO. Therefore, our results show for the first time that a pharmacological agent such as butanediol can delay the development of vasogenic edema but does not limit the development of vasogenic edema but does not limit the development of cytotoxic edema. ADC imaging detects areas of severe metabolic disturbance but not moderately ischemic peripheral areas where butanediol is presumed to be more efficacious.

Animals↗
PubMed1997

Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC) of water should be sensitive to the cytotoxic edema triggered by energy failure during ischemia. Elevated values of T2. the nuclear MR transverse relaxation time of water, seen on T2 nuclear MR images detect vasogenic edema and infarcted areas. The temporal and spatial changes in ADC and T2 abnormalities after occlusion of the middle cerebral artery (MCAO) were therefore estimated by these two quantitative techniques. METHODS: Permanent MCAO was performed on rats. Quantitative ADC and T2 maps of brain water were obtained, from which the ischemic volumes were calculated at various times up to 48 hours after MCAO. RESULTS: The areas of decreased ADC represented 36 +/- 7% of the final infarct volume (24 hours) at 0.5 hours and 64 +/- 4% at 5 hours after MCAO, suggesting that there is recruitment of peripheral areas with disturbed energy metabolism and cytotoxic edema. The ADC and T2 contours closely matched at 3.5, 24, and 48 hours after MCAO. CONCLUSIONS: T2 imaging can assess ischemic insults as well as ADC imaging, but only 3.5 hours after the onset of ischemia. Assessment of edematous swelling (approximately 24.5% of total infarcted volume) demonstrates that ADC and therefore T2 imaging detect all the tissue that will become infarcted approximately 7 hours after occlusion. The spread of ADC and T2 abnormalities would therefore stop at approximately 7 hours, and any further increase in volume observed on the images would be mainly due to edematous swelling.

Animals↗
PubMed1996

A new model of experimental prosthetic joint infection due to methicillin-resistant Staphylococcus aureus: a microbiologic, histopathologic, and magnetic resonance imaging characterization.

Partial knee arthroplasty was done in rabbits with a silicone-elastomer implant. Immediately after closing the surgical wound, 5 x 10(6) cfu of methicillin-resistant Staphylococcus aureus was injected into the joint. Disease evolution was studied at different stages of infection up to 8 weeks. Prosthetic infection developed in all animals. Gross pathology and histopathologic changes were characteristic of joint and bone infection. Quantitative bacterial counts from infected bone confirmed disease chronicity. The mean number of colony-forming units per gram of bone +/- SD 1 week after infection was 4.84 +/- 0.24 log10 cfu/g and remained stable from week 1 to week 8. Magnetic resonance imaging showed evidence of prosthetic infection as of week 1, while only mild radiologic changes of bone were seen 2 weeks after infection. This model produces a prosthetic infection that is reproducible and close to that of human prosthetic infection.

Animals↗
PubMed1996

Displacement of valproic acid and carbamazepine from protein binding in normal and uremic sera by tolmetin, ibuprofen, and naproxen: presence of inhibitor in uremic serum that blocks valproic acid-naproxen interactions.

Displacement of valproic acid (90-95% bound to albumin) and carbamazepine (80% bound to albumin) by salicylate, leading to higher concentrations of pharmacologically active free drugs, has been reported. We studied the possibility of displacement of valproic acid and carbamazepine by other strongly albumin-bound nonsteroidal antiinflammatory drugs tolmetin, ibuprofen, and naproxen. We observed statistically significant displacement of carbamazepine from protein binding in uremic serum at higher therapeutic concentrations of all three antiinflammatory drugs we studied, whereas in normal serum, we observed statistically significant displacement only with 75 micrograms/ml of naproxen. For valproic acid, we observed significant displacement even at lower therapeutic concentrations with all three drugs when the study was conducted using a normal serum pool. In the uremic serum pool, we observed significant displacements only with tolmetin and ibuprofen, whereas we observed no significant displacement of valproic acid even with higher concentrations of naproxen. We conclude that tolmetin, naproxen, and ibuprofen can displace both carbamazepine and valproic acid from protein binding, but uremic serum contains an inhibitor that blocks valproic acid-naproxen interaction.

Binding, Competitive↗
PubMed1995

Different proliferative responses of periportal and pericentral rat hepatocytes to hepatocyte growth factor.

Stimulation of DNA-synthesis by HGF was compared in cultured periportal and pericentral hepatocyte populations. Periportal hepatocytes showed a higher maximal stimulation of the BrdU labeling index than pericentral hepatocytes (7-fold vs 4-fold), while the stimulation for total hepatocytes was in between (5-fold). The glutamine synthetase-positive hepatocytes adjacent to the central veins responded much less to HGF than did the pericentral cells in general. These inherent differences in the growth potential of hepatocytes from different lobular localizations may contribute to the enhanced growth of hepatocytes in the periportal zone in normal and regenerating liver.

Animals↗
PubMed1995

Magnetic resonance imaging for the visualization of cholesterol gallstones in hamster fed a new high sucrose lithogenic diet.

Cholesterol gallstone induction in hamster gallbladder is usually achieved by specific diets. An X-ray in vivo follow-up of cholelithiasis development in this species is impossible, since cholesterol gallstones are transparent as long as they are not calcified. Moreover, their size (0.2 to 1 mm) also prevents their detection by ultrasonography. The current study presents an in vivo cholesterol gallstone detection by magnetic resonance imaging in hamsters fed a new high sucrose diet containing a low proportion of cholesterol (0.015%) and a normal ratio of lipids (10%). The diet produced gallstones and an increase in the cholesterol saturation index in about 50% of animals after a 5-week feeding period. The visualization of gallstones by magnetic resonance imaging in anaesthetized animals required synchronization between breathing movements and image acquisition. A high magnetic field was also necessary to allow a fine image resolution, adapted to gallstone size. Two major advantages of this technique are a direct selection of lithiasic animals with a functional gallbladder (in spite of the presence of gallstones) and a possible adjustment of the treatment period of potential litholytic drugs.

Animals↗
PubMed1994

Comparative NMR study of a differentiated rat hepatoma and its dedifferentiated subclone cultured as spheroids and as implanted tumors.

H4IIEC3 (H4), a differentiated rat hepatoma line and H5, its dedifferentiated subclone, were investigated as proliferating spheroids and as implanted subcutaneous tumors in juvenile rats. H4 cells formed tight, round spheroids whereas H5 cells formed loose, grape-like structures. 31P MR spectra showed that phosphocreatine was present in H5 spheroids but not in H4 spheroids or tumors. [13C]Lactate production from [13C]glucose, with no detectable uptake of [13C]alanine, indicated that energy production in H5 spheroids was primarily via glycolysis. No [13C]glucose utilization was detected in H4 spheroids, but uptake of alanine and accumulation of labeled lactate, glutamate and glutamine indicated oxidation via the tricarboxylic acid (TCA) cycle. Tumors of H4 cells were well perfused, unlike tumors of H5 cells which were highly necrotic. Following i.v. infusion with [13C]alanine, [13C]lactate and glutamate, evidence of oxidation via the TCA cycle, were observed in H4 tumors. Thus the results obtained by 31P and 13C MRS correlated with the differentiation state of H4 and H5 spheroids and tumors.

Alanine↗
PubMed1994

An experimental approach for dynamic rat liver observation in vivo and ex vivo by 31P localized MR spectroscopy for follow-up of liver status at different steps of orthotopic transplantation--a feasibility study.

An experimental approach was evaluated to perform a follow-up of rat liver transplantation by 31P spectroscopy. The approach is based on the use of an implanted surface coil attached to the liver and inductively coupled to the receiver/transmitter line by an external coupling loop. Spatial localization to the liver was performed by selective excitation and dephasing of spins in a slice between the implanted and the coupling coil, the slice being positioned on a proton image acquired prior to spectroscopy. Characteristics of the protocol were established on a phantom and in vivo on non-transplanted rat livers indicating good localization and high signal-to-noise ratio. Preliminary results obtained on transplanted livers revealed a relation between evolution of the 31P spectrum and animal survival. As shown in separate experiments, the same technique also enabled easy acquisition of the 31P profile of livers stored at 4 degrees C in University of Wisconsin solution. Therefore, the experimental approach described here opens up the possibility of measuring changes of the 31P profile on the same liver during the whole transplantation procedure, i.e., in the donor, during preservation and after transplantation, and comparing evolution of spectra with transplantation outcome.

Animals↗
PubMed1994

Evaluation of a rabbit model for osteomyelitis by high field, high resolution imaging using the chemical-shift-specific-slice-selection technique.

The rabbit model of osteomyelitis introduced by C.W. Norden, based on injection of an infecting solution (Staphylococcus aureus, sodium morrhuate) into the tibia, was studied at 4.7 Tesla with a time-efficient chemical shift selective imaging technique, Chemical Shift Specific Slice Selection (C4S). The evolution of the disease over several weeks was followed on water-selective, fat-selective, and sum images obtained simultaneously with this imaging sequence. Experiments were performed either on different groups of rabbits at different times after infection with subsequent sacrifice of the animal and microbiological analysis of the infected tibia or on the same group of animals imaged several times after infection. Associated analysis of the water and fat selective images revealed marrow modifications very early (Day 5 after inoculation) demonstrating the high sensitivity of the employed imaging technique. Later on, bone modifications were best identified on the sum images. Additional experiments performed on animals injected with a noninfecting solution containing only sodium morrhuate showed however that the sclerosing agent alone can yield images similar to those produced by infection at early stages after inoculation. Therefore, the Norden model would not be suitable for monitoring quantitatively outcome of therapy by magnetic resonance imaging. It is however well adapted for the evaluation and optimization of MRI techniques or protocols intended to detect early changes of bone marrow produced by septic or aseptic infarct.

Adipose Tissue↗
PubMed1980

Studies on the disappearance of palmitate-1-14C from the plasma of pregnant rats.

Intravenously injected radioactive fatty acids disappear from the circulation at an ever-decreasing rate; about 1% of the injected label remains in plasma for hours. This slow elimination of label can be explained by an extensive recycling of label or by a slows turnover of a portion of the injected label. The results show that a recycling of label can not be responsible for the slow elimination of label, because 1. the specific activities of the tissue fatty acids were much lower than the specific activity of the plasma free fatty acids, and 2. reinjection of the remaining label of 1% into control animals showed the same slow elimination of label. An interpretation of the experiments could be that some fatty acids (about 1%) have a dissociation rate from albumin that is much lower than others, and thus they might be responsible for the late portion of the disappearance curve.

Adipose Tissue↗