Impact of inter-hospital transfers on the prevalence of resistant pathogens in a hospital-community system.

The spread of resistant bacteria in hospitals is an increasing problem worldwide. Transfers of patients, who may be colonized with resistant bacteria, are considered to be an important driver of promoting resistance. Even though transmission rates within a hospital are often low, readmissions of patients who were colonized during an earlier hospital stay lead to repeated introductions of resistant bacteria into hospitals. We developed a mathematical model that combines a deterministic model for within-hospital spread of pathogens, discharge to the community and readmission, with a hospital-community network simulation of patient transfers between hospitals. Model parameters used to create the hospital-community network are obtained from two health insurance datasets from Germany. For parameter values representing transmission of resistant Enterobacteriaceae, we compute estimates for the single admission reproduction numbers RA and the basic reproduction numbers R0 per hospital-community pair. We simulate the spread of colonization through the network of hospitals, and investigate how increasing connectedness of hospitals through the network influences the prevalence in the hospital-community pairs. We find that the prevalence in hospitals is determined by their RA and R0 values. Increasing transfer rates between network nodes tend to lower the overall prevalence in the network by diluting the high prevalence of hospitals with high R0 to hospitals where persistent spread is not possible. We conclude that hospitals with high reproduction numbers represent a continuous source of risk for importing resistant pathogens for hospitals with otherwise low levels of transmission. Moreover, high risk hospital-community nodes act as reservoirs of pathogens in a densely connected network.

Multielemental Analysis of Tobacco Plant and Tobacco Products by TXRF.

The aim of this research is to develop a fast analytical method for multielemental analysis of the tobacco plant Virginia tobacco (cultivated in Poland) and tobacco products (cigarettes, cigars, cigarillos, snuff and two kinds of properly crafted tobacco such as a shisha and cigarette tobacco) distributed in Polish markets by means of a low-power benchtop total reflection X-ray fluorescence (TXRF) system. For this purpose, a set of certified tobacco materials and real samples was employed. In leaves and stalks of V. tobacco and tobacco products, a concentration of 18 elements (P, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr and Pb) was determined. Analyzing elemental composition of tobacco plants, one can see that concentrations of S, Ca, Ti, Mn, Zn, Sr and Pb are higher in leaves, whereas the concentrations of P, Cl, K, Fe Cu and Br are higher in stalks; the levels of Cr, Ni, As and Rb are comparable in both these parts of the tobacco plant. All of the parameters affecting sample preparation and TXRF measurements conditions were carefully evaluated. The accuracy and precision of the TXRF measurements were verified using an internal standardization approach for quantification.

One session of exercise regulates cathepsin B activity in the livers of trained and untrained rats.

Physical exercise causes adaptive changes, mainly in muscles, but it also influences other organs, including liver. Most changes are beneficial; however, strenuous exercise is a strong stressor, and it can result in splanchnic hypoperfusion with subsequent disturbances in liver homeostasis and energy. Cathepsin B is a protease linked to protein turnover and extracellular matrix degradation. It is also involved in autophagy and the activation of proinflammatory and profibrotic pathways. This study investigated the influences of one session of exercise and endurance training on the mRNA, protein level, and activity of cathepsin B in rat liver. Healthy rats were randomly divided into two groups (n = 30, each); one group was untrained and the other received 6-weeks of endurance training with an increasing load. For each group, rats were sacrificed before (controls, n = 10), immediately after (n = 10), and 3 h after (n = 10) an acute bout of intense exercise. Liver gene expression was evaluated with quantitative real-time PCR. Liver protein content was measured with ELISA. Liver enzyme activity was measured fluorometrically. One session of exercise or training did not influence cathepsin B gene expression or protein concentration at any investigated time point. In untrained rats, cathepsin B activity decreased 3 hours after (P = 0.027) one session of exercise. In trained rats, cathepsin B activity increased immediately (P = 0.005) after one session of exercise. Training did not influence baseline cathepsin B activity. In conclusion, one session of exercise differentially influenced cathepsin B activity in the liver, depending on training status.

Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands.

Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.

The XRF mapping of archaeological artefacts as the key to understanding of the past.

The article describes the X-ray fluorescence (XRF) studies on the chemical composition of archaeological artefacts. The mapping of the concentration of selected elements has been used to recognise the way of object production and the use. The obtained data allowed to obtain the new information, which is impossible to gain by use of different methods. 'The data obtained from the chemical composition of the particular parts of the objects may be used for the interpretation of the manufacturing technology or the primal form of the objects. Additionally, the knowledge obtained from the chemical composition of the different parts of the artefacts may be essential for the selection of the protection and conservation methods. The present studies can be useful to improve knowledge about the level of former craftsmanship. These knowledge allow us to exam archaeological artefacts in a new light, and these findings can also broaden the archaeological knowledge horizons and provide good bases for further detailed studies.

Development and use of microsatellite markers to study diversity, reproduction and population genetic structure of the cereal pathogen Ramularia collo-cygni.

Ramularia collo-cygni (Rcc) is a major pathogen of barley that causes economically serious yield losses. Disease epidemics during the growing season are mainly propagated by asexual air-borne spores of Rcc, but it is thought that Rcc undergoes sexual reproduction during its life cycle and may also disperse by means of sexual ascospores. To obtain population genetic information from which to infer the extent of sexual reproduction and local genotype dispersal in Rcc, and by implication the pathogen's ability to adapt to fungicides and resistant cultivars, we developed ten polymorphic microsatellite markers, for which primers are presented. We used these markers to analyse the population genetic structure of this cereal pathogen in two geographically distant populations from the Czech Republic (n=30) and the United Kingdom (n=60) that had been sampled in a spatially explicit manner. Genetic diversity at the microsatellite loci was substantial, Ht=0.392 and Ht=0.411 in the Czech and UK populations respectively, and the populations were moderately differentiated at these loci (Θ=0.111, P<0.01). In both populations the multilocus genotypic diversity was very high (one clonal pair per population, resulting in >96% unique genotypes in each of the populations) and there was a lack of linkage disequilibrium among loci, strongly suggesting that sexual reproduction is an important component of the life cycle of Rcc. In an analysis of spatial genetic structure, kinship coefficients in all distance classes were very low (-0.0533 to 0.0142 in the Czech and -0.0268 to 0.0042 in the Scottish population) and non-significant (P>0.05) indicating lack of subpopulation structuring at the field scale and implying extensive dissemination of spores. These results suggest that Rcc possesses a high evolutionary potential for developing resistance to fungicides and overcoming host resistance genes, and argue for the development of an integrated disease management system that does not rely solely on fungicide applications.

Cecal enzyme activity in gilts following experimentally induced Fusarium mycotoxicosis.

The objective of the presented study was to examine the influence of Fusarium mycotoxins (zearalenone--ZEN and deoxynivalenol--DON), administered separately and in combination, on the activity of cecal enzymes (ß-glucosidase and ß-glucuronidase) in gilts which were fed fodder con- taminated with these mycotoxins. The activity of ß-glucosidase and ß-glucuronidase varied in the range of 0.170-1.236 µmol · h(-1) · mg(-1) and 8.701-96.704 µmol · h(-1) · mg(-1), respectively. In the first two weeks, the toxins had no significant effect on the activity of ß-glucosidase and ß-glucuronidase in the ascending and descending colon. After week 3 and later on, ZEN and DON administered as a mix- ture led to the highest increase in the activity of both enzymes. Administered separately, DON affected the activity of enzymes more than ZEN. From the third week of the experiment, an increase in the activity of CW ß-glucosidase and ß-glucuronidase was observed.

One session of exercise or endurance training does not influence serum levels of irisin in rats.

Irisin induces the browning of adipose tissue. The goal of this study was to investigate the influence of acute exercise in untrained and trained rats and endurance training on FNDC5 mRNA and irisin levels in white and red skeletal muscle and serum. Rats (n=60) were randomly divided into two groups: untrained and trained (subjected to 6-week endurance training with increasing load). Subgroups of rats from each group were sacrificed before (controls), immediately after, or 3 hours following acute exercise with the same work load. Muscle samples (red and white) and serum were collected. FNDC5 mRNA was evaluated using RT-PCR. Irisin levels were measured using an immunoenzymatic method. Muscle FNDC5 mRNA decreased immediately after acute exercise compared with baseline levels, but not in red muscle in trained rats. Atrend toward a return to baseline appeared 3 hours after the exercise, but only in white muscle in untrained group. Irisin protein levels increased after acute exercise in red muscle 3 hours post-exercise compared with samples taken immediately after exercise, and decreased 3 hours post-exercise compared to pre-exercise level in white muscles. FNDC5 mRNA did not change following training, whereas irisin protein levels increased in red muscle and decreased in white muscle. Serum irisin levels remained unchanged following acute exercise and training. We concluded that changes in irisin mRNA and protein levels in rat muscle after acute exercise are limited and depend on training status and the muscle type. Irisin serum levels remained stable after acute exercise or endurance training.

Antioxidant profile of salivary glands in high fat diet-induced insulin resistance rats.

OBJECTIVE: There is no study analyzing the salivary antioxidant profile in the course of the insulin resistance. MATERIALS AND METHODS: Rats were divided into two groups. One group was fed with a normal diet, another one with a high fat diet for 5 weeks. The analysis included: catalase (CAT), superoxide dismutase, peroxidase activities, uric acid, and total antioxidant status concentrations. RESULTS: The activity of peroxidase in both kind of glands of insulin resistance rats was significantly reduced than in the control rats. The protein concentration, total amount of total antioxidant status in the parotid glands of insulin resistance rats were significantly lower than in the control glands The total amount of superoxide dismutase, CAT, and uric acid in the parotid glands of insulin resistance rats were significantly elevated in comparison with the control rats. The median values of the total amount of superoxide dismutase, CAT, peroxidase, total antioxidant status were significantly higher in the parotid than in the submandibular glands of the insulin resistance and control rats. CONCLUSION: Parotid and submandibular glands of rats react differently when exposed to insulin resistance condition; however, the parotid glands seem to be more affected. The main source of antioxidants is parotid glands of rats.

Sphingolipid profiles are altered in prefrontal cortex of rats under acute hyperglycemia.

Diabetes type 1 is a common autoimmune disease manifesting by insulin deficiency and hyperglycemia, which can lead to dementia-like brain dysfunctions. The factors triggering the pathological processes in hyperglycemic brain remain unknown. We reported in this study that brain areas with different susceptibility to diabetes (prefrontal cortex (PFC), hippocampus, striatum and cerebellum) revealed differential alterations in ceramide (Cer) and sphingomyelin (SM) profiles in rats with streptozotocin-induced hyperglycemia. Employing gas-liquid chromatography, we found that level of total Cer increased significantly only in the PFC of diabetic animals, which also exhibited a broad spectrum of sphingolipid (SLs) changes, such as elevations of Cer-C16:0, -C18:0, -C20:0, -C22:0, -C18:1, -C24:1 and SM-C16:0 and -C18:1. In opposite, only minor changes were noted in other examined structures. In addition, de novo synthesis pathway could play a role in generation of Cer containing monounsaturated fatty acids in PFC during hyperglycemia. In turn, simultaneous accumulation of Cers and their SM counterparts may suggest that overproduced Cers are converted to SMs to avoid excessive Cer-mediated cytotoxicity. We conclude that broad changes in SLs compositions in PFC induced by hyperglycemia may provoke membrane rearrangements in some cell populations, which can disturb cellular signaling and cause tissue damage.

Fiber specific changes in sphingolipid metabolism in skeletal muscles of hyperthyroid rats.

Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, with diverse fiber compositions: soleus (slow-twitch oxidative), red (fast-twitch oxidative-glycolytic) and white (fast-twitch glycolytic) section of gastrocnemius. We demonstrated that T3 induced accumulation of sphinganine, ceramide, sphingosine, as well as sphingomyelin, mostly in soleus and in red, but not white section of gastrocnemius. Concomitantly, the activity of serine palmitoyltransferase and acid/neutral ceramidase was increased in more oxidative muscles. In conclusion, hyperthyroidism induced fiber specific changes in the content of sphingolipids that were relatively more related to de novo synthesis of ceramide rather than to its generation via hydrolysis of sphingomyelin.

Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes.

AIMS: To determine the presence and possible involvement of FAT/CD36, FABPpm and FATP-2, transporters in (i) fatty acids movement across plasma membrane and (ii) an induction of insulin resistance by palmitic (PA) and oleic (OA) fatty acids in primary hepatocytes. METHODS: Primary hepatocytes were treated with either PA and OA or combination of activators (AICAR, Insulin) or inhibitors (SSO, phloretin) of FA transport. Expression of FA and glucose transporters as well as insulin signalling proteins was determined using Western blot analyses. Palmitate and glucose transport was measured using radioactive isotopes. Intracellular lipid content [ceramide, diacylglycerols (DG) and triacylglycerols] and FA composition were estimated by GLC. RESULTS: In primary hepatocytes, adding phloretin diminished insulin, and AICAR stimulated palmitate transport. Both PA and OA fatty acids induced the protein expression of FAT/CD36 and FATP-2 with concomitant: (i) reduction in GLUT-2 protein content, (ii) inhibition of insulin-stimulated glucose uptake, (iii) reduction in insulin-stimulated activation of AKT and GSK, (iv) accumulation of either DG (PA and OA) or ceramide (only PA). CONCLUSIONS: FA transport into hepatocytes is, at least in part, protein-mediated process, and both PA and OA induce the protein expression of FAT/CD36 and FATP-2. Both saturated (PA) and unsaturated (OA) fatty acids induce insulin resistance in primary hepatocytes, associated with the accumulation of DG and/or ceramide.

Change in blood gelsolin concentration in response to physical exercise.

Plasma gelsolin (pGSN) produced by muscle is an abundant protein of extracellular fluids capable of severing actin filaments and eliminating actin from the circulation. Additionally, pGSN modulates the cellular effects of some bioactive lipids. In this study we test the hypothesis that hormonal and metabolic adaptations to exercise are associated with changes in gelsolin concentration in blood. Plasma samples were collected from twenty healthy males recruited from untrained (UT, n=10) and endurance trained (ET, n=10) groups that performed 30-60 minutes of exercise on a cycloergometer at a workload corresponding to 70% of VO2max. Gelsolin concentration was determined by quantitative Western blot analysis with an anti-human gelsolin antibody. The gelsolin concentration in UT and ET subjects before starting exercise ranged from 104 to 330 and 163 to 337 µg · ml(-1) respectively. After 30 minutes of exercise we observed a significant decrease of plasma gelsolin in the UT group (p<0.05) while the gelsolin concentration in the ET group rose on average from 244 to 271 µg · ml(-1). However, this increase did not reach statistical significance. Endurance training might increase the ability of muscle tissue to express plasma gelsolin as part of an adaptive mechanism.

Effects of hyperthyroidism on lipid content and composition in oxidative and glycolytic muscles in rats.

Triiodothyronine (T(3)) can influence lipid metabolism via multiple mechanisms, which generally result in an increase of fatty acids (FAs) oxidation. Consequently, we hypothesize that hyperthyroidism may influence intramuscular lipids accumulation. This increased intramuscular lipid turn-over is possibly accompanied by an increase in fatty acid transporters expression (FAT/CD36, FABPpm, FATP-1,4). In the present study we examined the lipid content and fatty acid saturation status of free fatty acids (FFA), triacylglycerols (TAG), diacylglycerols (DAG) and phospholipids (PL) in skeletal muscle of hyperthyroid rats (n=8). We measured also fatty acid transporters as well as AMP-activated protein kinase (pAMPK/AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), acetyl-CoA carboxylase (pACC/ACC), carnitine palmitoyltransferase I (CPT I) and citrate synthase (CS) protein expression in these muscles. In vivo T3 administration, decreased the content of FFA, particularly in the red gastrocnemius and the TAG fraction, in both the red and white portions of the gastrocnemius muscle. Concomitantly, saturated/unsaturated fatty acids (SFA/UFA) ratio was also decreased, but only in the FFA fraction, irrespectively of muscle's fiber composition. In contrast, T(3) treatment had no effect on the lipid content and saturation status in PL fraction. Triiodothyronine induced also modest activation of AMPK/ACC axis with subsequent increased expression of mitochondrial proteins: CPT I and CS. This was accompanied by increased content of FAT/CD36, but only in the red part of gastrocnemius muscle. These findings support the conclusion that hyperthyroidism increases lipid metabolism, especially in skeletal muscles with high capacity for fatty acid oxidation.

Not only accumulation, but also saturation status of intramuscular lipids is significantly affected by PPARγ activation.

AIM: Intramuscular lipid accumulation has been associated with insulin resistance, and after thiazolidinediones (TZD) treatment, it was shown to be reduced in some, but not all, studies. This work was undertaken to investigate the relationships between intramuscular lipids [free fatty acids (FFA), diacylglycerols (DAG), triacylglycerol (TAG) and phospholipids] and plasmalemmal expression of fatty acid (FA) transporter [FAT/CD36 and FABPpm] in the muscles of varying oxidative capacity, after peroxisome proliferator-activated receptors gamma (PPARγ) activation (rosiglitazone) in an animal model of high-fat-diet-induced insulin resistance. Endurance training was also included to further explore the differences in these relationships. METHODS: We have used gas liquid chromatography to estimate FA content and composition in each lipid fraction. For sarcolemmal expression of FA transporters, subfractionation of skeletal muscles with subsequent western blot technique was applied. RESULTS: High-fat diet induced intramuscular accumulation of FFA, DAG and TAG, irrespective of muscle's fibre composition. PPARγ activation (rosiglitazone) and, to a lesser extent, endurance training further increased TAG accumulation, while it reduced DAG in oxidative muscles (soleus and red gastrocnemius). Aforementioned interventions increased also sarcolemmal FAT/CD36 and FABPpm expressions in particular muscles. Irrespective of diet, rosiglitazone and exercise decreased significantly FA saturation status favouring proportionate enhancement in monounsaturated FA (rosiglitazone) or polyunsaturated FAs (endurance training). CONCLUSION: These findings support the conclusion that not only the change in total lipid content (DAG and TAG), but also FA composition is affected by rosiglitazone in an animal model of high-fat-diet-induced insulin resistance.

Eicosanoids in prevention and management of diseases.

Eicosanoids, which originate from polyunsaturated fatty acids (PUFAs), have a major impact on homeostasis maintenance as secondary signal transducers. Signal cascade, which includes reception, processing and signal transduction coming from the environment into the cell, determines the type of response evoked. Signal distortion may take place on every level of this cascade and this in consequence could lead to the development of many diseases. Any intervention into PUFAs metabolism leads to quantitative and qualitative changes of synthesized eicosanoids. Some of them promote, whereas others inhibit carcinogenesis, some are pro- or anti-inflammatory and the overall result depends on the outcome of these contradictory effects. The type and amount of produced eicosanoids depends on substrates' availability and activity of enzymes catalyzing different stages of their transformation. A particularly negative role was assigned to the over expression of phospholipase A2, cyclooxygenase-2, 5- and 12-lipoxygenases, while the contribution of other oxygenases and their metabolites is considerably less clear. The information about their interplay is extremely sparse and inadequate to understand intricacies of the mechanisms involved. There are indications that utilization of selected eicosanoids (their analogs, agonists or antagonists) could be a better way of disease prevention and treatment, more effective than excessive dietary supplementation of fatty acids. This review presents a more global picture of oxygenases and their PUFA metabolites giving a brief summary of our current understanding of perspectives and pitfalls of their regulation and mediatory action in human diseases.

The influence of the recipient's body weight on the probability to obtain a heart transplant-POLKARD HF registry.

INTRODUCTION: The aim of the study was to analyze the influence of body weight of the adult heart recipient on the chance to obtain a transplant. METHODS: We analyzed the data from all 658 patients listed for heart transplantation. RESULTS: During the follow-up period, 325 (49%) of listed patients underwent transplantation with 102 (15%) succumbing before heart transplantation. The mean weight of transplanted patients was 73.7 +/- 13.7 kg and 81.2 +/- 15.4 kg for those not transplanted (P < .00001). Patients were divided according to body weight in two groups: light = below 80 kg (n = 360) or heavy > or = 80 kg or above (n = 297). On the transplant list, 111 heavy patients (37%) versus 213 light patients (59%) underwent the procedure, a significant difference. The waiting time among light patients was 255 versus heavy patients of 395 days (P < .005). There was a similar number of deaths before transplantation among the light (n = 56 360 patients; 15.5%) versus the heavy group (49/297; 16%). Upon multivariate Cox mode analysis independent factors related to not receiving a heart transplant were greater weight, systolic blood pressure, pulmonary vascular resistance, Heart Failure Survival Score (HFSS) score and lower N-terminal pro-brain natriuretic peptide (NTproBNP) levels. CONCLUSIONS: Among adult heart transplant candidates, the chance to receive a heart transplant significantly decreased when the recipient's weight exceeded 80 kg. Patients with a body weight more than 110 kg had a poor chance to receive a heart transplantation.

Chronic, in vivo, PPARalpha activation prevents lipid overload in rat liver induced by high fat feeding.

PURPOSE: Peroxisome proliferator-activated receptors (PPAR's) are lipid sensors and when activated they modify gene expression of proteins regulating fatty acid (FA) metabolism in liver cells. The aim of the present study was to examine the in vivo effects of PPAR alpha and gamma activation combined with high fat diet (HFD) feeding on the lipid content and FA profile in the liver. MATERIAL/METHODS: We assessed whether in vivo activation of PPARs (alpha or gamma) affects lipid accumulation in the liver induced by HFD feeding. Furthermore, as PPAR activity may be a key factor regulating long chain fatty acids (LCFA) flux and subsequent LCFA utilization in the liver, we prompted to investigate also the FA profile in different lipid fractions in this tissue. RESULTS: PPARalpha agonist (WY 14,643) treatment reduced the accumulation of liver lipids free fatty acids (FFA:-30%, diacylglycerols DAG: -27% and triacylglycerols TAG: -60%, p<0.05) evoked by HFD feeding. Interestingly, with PPARgamma stimulation liver lipid content was further elevated comparing to the effects of HFD (phospholipids PL: +48%, DAG: +231%, TAG: +346%, p<0.05). CONCLUSIONS: These findings suggest that in vivo PPARalpha and PPARgamma activation combined with HFD feeding exert different effects on lipid content in rat's liver and in vivo PPARalpha activation may prevent lipid overload in the liver cells provoked by HFD feeding.

Differential effects of in vivo PPAR alpha and gamma activation on fatty acid transport proteins expression and lipid content in rat liver.

Peroxisome proliferator-activated receptors (PPAR;s) serve as lipid sensors and when activated modify gene expression of proteins highly involved in the regulation of fatty acid metabolism. Recently, the accumulation of lipids in liver was shown to be depended on the excessive protein-mediated transmembrane transport of long chain fatty acids (LCFAs). The aim of the present study was to determine the in vivo effects of PPARalpha and gamma activation at two levels: 1) on the expression of fatty acid transporters, 2) on the content and fatty acids saturation status of lipids in rats liver. PPARalpha agonist (WY 14,643) treatment upregulated the liver expression of FAT/CD36 (+20%, p<0.05) and did not significantly affect the content of FABPpm and FATP-1. Accordingly there was a significant increase in the content of phospholipid (+12%, p<0.05), diacylglycerol (+65%, p<0.05) and triacylglycerol (+46%, p<0.05) fractions followed PPARalpha activation. In contrast, pioglitazone (PPARgamma agonist) had no effect on the content of fatty acid transporters (FAT/CD36, FABPpm and FATP-1) as well as the content of liver lipid fractions with the exception for triacylglycerols, which have been reduced significantly (-89%, p<0.05). These findings suggest that in vivo PPARalpha and PPARgamma activation exert different effects on both the expression of fatty acid transporters and lipid content in rat's liver.

The effect of acute and prolonged endurance exercise on transforming growth factor-beta1 generation in rat skeletal and heart muscle.

The serum level of the transforming growth factor-beta1 (TGF-beta1) is elevated after acute bouts of exercise and prolonged training, as well as after myocardial infarction. However, the source of this increase remains unclear. Contracting skeletal muscles are known to be the source of many cytokines. To determine whether skeletal or heart muscles produce TGF-beta1 during exercise, we investigated the effect of a single bout of acute exercise on TGF-beta1 generation in skeletal and heart muscles in untrained rats (UT, n=30) and in rats subjected to prolonged (6-week) endurance training (T, n=29). The UT and T (a day after final training) groups were subjected to an acute bout of exercise with the same work load. Rats from both groups were sacrificed and skeletal and heart muscle samples were collected before (pre), immediately after (0 h), or 3 hours (3 h) after acute exercise. TGF-beta1 mRNA was quantified by RT-PCR in these samples, and basal TGF-beta1 protein levels were determined in skeletal muscle in the UTpre and Tpre subgroups by ELISA. Acute exercise caused a non-significant increase in TGF-beta1 mRNA in skeletal muscle in UT0h rats, in compare to UTpre rats. There was a significant decrease of TGF-beta1 mRNA in the T0h group (p=0.0013) in compare to Tpre rats. Prolonged training caused a significant increase in TGF-beta1 mRNA (p=0.02); however, the TGF-beta1 protein level decreased (p=0.02). In heart muscle, there was a significant decrease of TGF-beta1 mRNA in UT0h (p=0.01) and UT3h (p=0.04) compared to UTpre rats. TGF-beta1 mRNA levels were unchanged in T0h and T3h compared to Tpre; basal TGF-beta1 mRNA expression after training was also unchanged (UTpre vs. Tpre). We conclude that physical exercise is a potent stimulus for inducing TGF-beta1 gene expression in skeletal muscle, but does not increase the protein level. Thus, skeletal and heart muscle do not contribute to increased serum levels of TGF-beta1 after physical exercise.