Miracle-dz/UniFAR-FTUs huggingface dataset:
Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine.

Biopharmacological evaluations of the protective effects of L-carnitine (a naturally occurring quaternary ammonium compound) against doxorubicin-induced metabolic damage were carried out in isolated cardiac myocytes and in isolated rat heart mitochondria. Perfusion of the heart with DOX (0.5 mM) caused a significant 70% inhibition of palmitate oxidation in cardiac myocytes, while L-carnitine (5 mM) perfusion caused stimulation which accounted for 37%. Perfusion of the heart with L-carnitine after 10-min perfusion with DOX (0.5 mM) caused 88% reversal of DOX-induced inhibition of palmitate oxidation in cardiac cells. In rat heart mitochondria, DOX has no effect on either palmitate oxidation or acyl-CoA synthetase activity, whereas Enoximone (c-AMP-dependent phosphodiesterase inhibitor), caused a significant inhibition of palmitate oxidation and acyl-CoA activity (40 and 27%, respectively). The oxidation of palmitoyl-CoA, an index of carnitine palmitoyltransferse reaction was significantly inhibited by DOX as a function of DOX concentration. Preincubation of mitochondria with L-carnitine caused reversal of DOX-induced inhibition of palmitoyl-CoA oxidation depending on the concentration of L-carnitine. Moreover, L-carnitine treatment did not interfere with the cytotoxic effect of doxorubicin against the growth of solid Ehrlich carcinoma. The findings of this study may suggest that inhibition of fatty acid oxidation in the heart is at least a part of doxorubicin cardiotoxicity and that L-carnitine can be used to prevent the doxorubcin-induced cardiac metabolic damage without interfering with its antitumour activities.
Acute restraint stress enhances hippocampal endocannabinoid function via glucocorticoid receptor activation

Exposure to behavioural stress normally triggers a complex, multilevel response of the hypothalamic–pituitary–adrenal (HPA) axis that helps maintain homeostatic balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic stress, few studies have directly addressed its response to acute stress. Here we show that acute restraint stress enhances eCB-dependent modulation of GABA release measured by whole-cell voltage clamp of inhibitory postsynaptic currents (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro. Both Ca2+-dependent, eCB-mediated depolarization-induced suppression of inhibition (DSI), and muscarinic cholinergic receptor (mAChR)-mediated eCB mobilization are enhanced following acute stress exposure. DSI enhancement is dependent on the activation of glucocorticoid receptors (GRs) and is mimicked by both in vivo and in vitro corticosterone treatment. This effect does not appear to involve cyclooxygenase-2 (COX-2), an enzyme that can degrade eCBs; however, treatment of hippocampal slices with the L-type calcium (Ca2+) channel inhibitor, nifedipine, reverses while an agonist of these channels mimics the effect of in vivo stress. Finally, we find that acute stress produces a delayed (by 30 min) increase in the hippocampal content of 2-arachidonoylglycerol, the eCB responsible for DSI. These results support the hypothesis that the ECS is a biochemical effector of glucocorticoids in the brain, linking stress with changes in synaptic strength.
Protective effect of HLA‐B57 on HCV genotype 2 infection in a West African population

Recovery from Hepatitis C virus (HCV) infection is considered infrequent (<20%) in western populations but reaches 50% in West Africa where genotype 2 infection is predominant. To investigate the role of cellular immune responses and host genetics in this phenomenon, samples from 104 Ghanaian blood donors reactive with anti‐HCV assays were collected between 2000 and 2005. HCV antibody was confirmed by Western blot using genotype 2 recombinant core, E2 and NS3 proteins. Viral load and genotype were determined. Samples were stratified into 37 chronic, 35 recovered infections and 32 false positive. Eighty‐one percentage of subjects with chronic infection (RNA positive) carried genotype 2 HCV. Cellular immune response was investigated in 35 frozen peripheral blood mononuclear cell (PBMC) samples suitable for interferon‐gamma ELISPOT assay. Twelve out of 24 confirmed recovered, 1 out of 5 chronically infected and none of the 6 false‐positive controls reacted to recombinant proteins. HLA‐A, ‐B and ‐DR types were determined by DNA methodology. HLA‐B*57 was significantly more frequent in the group which had recovered from HCV infection compared with chronically infected subjects (P = 0.0053, OR = 8.02). In conclusion, it is hypothesized that the dominance of genotype 2 HCV strains may be an important factor explaining the high rate of recovery from HCV infections in Ghana via an efficient contribution of HLA‐B*57 which is relatively frequent in the population. J. Med. Virol. 79: 724–733, 2007. © 2007 Wiley‐Liss, Inc.
Development of Cell Lines That Provide Tightly Controlled Temporal Translation of the Human Cytomegalovirus IE2 Proteins for Complementation and Functional Analyses of Growth-Impaired and Nonviable IE2 Mutant Viruses

ABSTRACT The human cytomegalovirus (HCMV) IE2 86 protein is essential for viral replication. Two other proteins, IE2 60 and IE2 40, which arise from the C-terminal half of IE2 86, are important for later stages of the infection. Functional analyses of IE2 86 in the context of the infection have utilized bacterial artificial chromosomes as vectors to generate mutant viruses. One limitation is that many mutations result in debilitated or nonviable viruses. Here, we describe a novel system that allows tightly controlled temporal expression of the IE2 proteins and provides complementation of both growth-impaired and nonviable IE2 mutant viruses. The strategy involves creation of cell lines with separate lentiviruses expressing a bicistronic RNA with a selectable marker as the first open reading frame (ORF) and IE2 86, IE2 60, or IE2 40 as the second ORF. Induction of expression of the IE2 proteins occurs only following DNA recombination events mediated by Cre and FLP recombinases that delete the first ORF. HCMV encodes Cre and FLP, which are expressed at immediate-early (for IE2 86) and early-late (for IE2 40 and IE2 60) times, respectively. We show that the presence of full-length IE2 86 alone provides some complementation for virus production, but the correct temporal expression of IE2 86 and IE2 40 together has the most beneficial effect for early-late gene expression and synthesis of infectious virus. This approach for inducible protein translation can be used for complementation of other mutations as well as controlled expression of toxic cellular and microbial proteins.
Conducting site‐specific assessments of selenium bioaccumulation in aquatic systems

Selenium (Se) is a chemical of concern at many locations across North America and elsewhere, and site‐specific conditions are important when evaluating its bioaccumulation and effects in aquatic ecosystems. Most regulatory criteria and guidelines are based on waterborne Se concentrations. In contrast, the draft water quality chronic criterion of the US Environmental Protection Agency (USEPA) is based on Se concentrations in whole‐body fish, and current information suggests the agency will issue a new draft criterion based in part on fish egg and/or ovary Se concentrations. However, implementation guidance is not available from the agency for either of these tissue‐based criteria. Therefore, we describe a phased approach for field and laboratory assessments of Se bioaccumulation in fish and aquatic‐dependent birds that can be applied in different environmental settings with the goal of developing and interpreting a tissue‐based Se value. We recommend here the use of decision trees, conceptual models, and data quality objectives toward defining what should be done during the assessment, plus sampling and monitoring procedures for the assessment. First, available tissue or waterborne Se concentrations should be compared to tissue residue guidelines or adopted water quality criteria and guidelines. When needed, reproductive toxicity testing and assessment of fish populations should also be conducted in the area of interest. In addition, extensive data on the effects of Se on fish and bird species have been developed, and describing the associations between fish or bird egg tissue, aqueous Se, and potential effects is important for sites where Se may be a concern. Selenium bioaccumulation and toxicity also are of concern for amphibians and oviparous reptiles, but interpretive information is very limited for those species. Recent science indicates that effects are more strongly related to tissue concentrations of Se (especially in the eggs or ovaries of oviparous vertebrates) than to waterborne concentrations. Overall, we conclude that the approach for site‐specific assessment must be flexible enough to allow what is appropriate for the situation. Furthermore, risk management and remediation decisions should be based on combined biology and chemistry data, using multiple lines of evidence in the assessment. Integr Environ Assess Manag 2011;7:314–324. © 2011 SETAC
TiQ: A Timeline Query Processing System over Road Traffic Data

Today many traffic information centers are collecting road traffic data from various sensors and require enhanced analytic processing to transform raw data into traffic information. One of the most effective ways is to visualize traffic information in a timeline view for better understanding the traffic behaviors. In this paper, we present TiQ, which is a timeline query processing system over road traffic data. The TiQ system is based on (1) a formal model that captures traffic congestion events from raw data, (2) a timeline query index (TQ-index) which exploits spatial and temporal features of traffic data, and (3) efficient query evaluating algorithms for a timeline query. We demonstrate the use of TiQ system and its effectiveness and efficiency by using real traffic datasets from a Busan Intelligent Transport System (ITS) center.
Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats.

We determined whether aquaporin of collecting duct (AQP-CD) is involved in pathogenesis of water retention in rats with experimental models of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and liver cirrhosis. SIADH rats were made by administering 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously and providing them with a liquid diet. Serum Na levels decreased to < 120 meq/l on day 2, and hyponatremia persisted throughout the rest of observation period. Six hours after the DDAVP infusion, the expression of AQP-CD mRNA significantly increased by 198%, followed by > 144% increases in its expression during the 14-day observation period. On day 7, the increased expression of AQP-CD mRNA was abolished after the administration of an antidiuretic, nonpeptide arginine vasopressin (AVP) antagonist, OPC-31260, which was closely related to a marked diuresis and a prompt normalization of serum Na levels in SIADH rats. Rats were made cirrhotic by injecting a mixture of carbon tetrachloride and olive oil subcutaneously for 3 mo. The expression of AQP-CD mRNA was increased by 164% in the decompensated cirrhotic rats. The blockade of AVP action by OPC-31260 significantly diminished its expression. These results indicate that water channel AQP-CD plays an important role in water retention in pathological states of SIADH and liver cirrhosis.
The impact of dementia on length of stay in acute hospitals in Ireland

The outcomes for those with dementia admitted to acute hospitals are often poor, with higher mortality, increased risk of institutionalisation and longer length of stay. The aim of this study was to examine the impact of dementia on length of stay and the associated cost of care in acute hospitals in Ireland. People with a recorded diagnosis of dementia were found to have a significantly longer length of stay than those with no recorded dementia. Multiplying the excess length of stay by the number of dementia-related admissions gave an estimate of 246,908 additional hospital days per annum due to dementia at an associated additional annual cost of over €199 million. Improving the experience of those with dementia in acute hospitals will likely lead to cost savings for the health service; however, it will require a number of measures including: earlier diagnosis, training for medical professionals and improvements in the built environment.
Safety of Ornithine Phenylacetate in Cirrhotic Decompensated Patients: An Open-label, Dose-escalating, Single-cohort Study

Aims: Confirm in patients with cirrhosis and gastrointestinal bleeding the safety of ornithine phenylacetate (OP) and assess the pharmacokinetic profile of OP and its effects on plasma ammonia. Background: OP is a drug that has shown experimentally to decrease hyperammonemia and improve hepatic encephalopathy. OP is safe in healthy subjects and in stable patients with cirrhosis, but there are no data in decompensated cirrhosis. Methods: We performed a study to assess safety and tolerance of OP in cirrhotic patients after an episode of upper gastrointestinal bleeding.Ten patients were included within 24 hours of an upper gastrointestinal bleeding. OP was administered as a continuous infusion up to a maximum of 10 g/24 h (0.42 g/h) for 5 days. The infusion was started at 33% of the target dose and increased at 12-hour intervals achieving target dose at 24 hours. Ammonia was also assessed in control group of 10 patients. Results: No severe adverse events were observed. Mild adverse events were reported in 4 patients. Plasma ammonia (baseline: 80±43 &mgr;mol/L) showed a progressive drop between baseline and 36 hours (42±15 &mgr;mol/L), 72 hours (44±15 &mgr;mol/L), 96 hours (40±24 &mgr;mol/L), and 120 hours (33±14 &mgr;mol/L). Plasma ammonia at 24 hours was significantly higher in the control group. Plasma glutamine showed a significant decrease (−37% at day 5) and its excretion in urine as phenylacetylglutamine, a progressive rise (52±35 mmol at day 5). Conclusions: OP is a safe and well-tolerated drug in decompensated cirrhotics that may decrease plasma ammonia by inducing its appearance as phenylacetylglutamine in urine.
Relation between Serum Calcium, Phosphate, Parathyroid Hormone and ‘Nondipper’ Circadian Blood Pressure Variability Profile in Patients with Normal Renal Function

Background and Aims: In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium×phosphate (Ca×P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. Methods: 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. Results: Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 ± 0.61 vs. 3.35 ± 0.44 mg/dl, p = 0.001), Ca×P product (35.4 ± 6.5 vs. 31.5 ± 5.0, p = 0.001) and PTH (75.7 ± 28.8 vs. 46.6 ± 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (β = 0.43, p = 0.001) and phosphate (β = 0.9, p = 0.03). Conclusion: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca×P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.
Effects of soft-drinks and remineralising treatment on teeth assessed by morphological and quantitative X-ray investigations.

AIM To morphologically and chemical-physically analyse both the surface and the subsurface of enamel undergoing soft- drink demineralisation and remineralisation treatment. MATERIALS AND METHODS Fifteen human premolars were split and immersed in saline or three popular soft drinks, as demineralising agent, 15 minutes per day, for seven days at room temperature. Half of drink-processed teeth was then treated with casein phosphopeptide-amorphous calcium phosphate, as remineralising agent, for an additional seven days. The surface morphology was evaluated by stereomicroscope and scanning electron microscope (SEM). Teeth were then re-embedded and sectioned, and analysed under SEM and X-ray microprobe. RESULTS Drink-processed teeth showed root pigmentation, opacification and deterioration of the superficial enamel. The enamel surface resulted greatly furrowed after drink processing, and apparently restored after remineralising treatment. However, in tooth sections, SEM showed always a subsurface demineralisation of dentine and enamel, in particular at the cementoenamel junction, also after reminalising treatment. The remineralising agent produced a partial remineralisation of the subsurface enamel, sometimes statistically significant, but not in hydroxyapatite stoichiometry. CONCLUSION Soft-drink erosion impaired not only the surface but also the subsurface enamel. The applied remineralising treatment, yielding some effects on surface and subsurface enamel reversing basically the decalcification process.
Even low physical activity levels improve vascular function in overweight and obese postmenopausal women

Objective Some individuals with cardiovascular risk are unable to achieve even the lower internationally recommended level of physical activity (PA). We aimed to study the impact of a lower-than-advised level of PA on small artery vascular function and oxidative stress in overweight and obese postmenopausal women. Methods Forty-seven overweight and obese postmenopausal women completed a 4-month program of 1-hour low-intensity PA for 2 days per week. Before and after the intervention, PA level (metabolic equivalent tasks/h/wk), endogenous antioxidant status (superoxide dismutase and erythrocyte lysate and glutathione peroxidase erythrocyte lysate concentrations, superoxide dismutase plasma and glutathione peroxidase plasma [GPXa] activities, and oxidized low-density lipoprotein), asymmetrical dimethylarginine concentrations, endothelial function by small artery reactive hyperemia index (saRHI), and resting heart rate (RHR) were assessed. Results After the intervention, a significant increase in GPXa and decreases in asymmetrical dimethylarginine concentrations and RHR (P < 0.001 for all) were observed. Increases in PA were positively associated with increases in saRHI (r = 0.330, P = 0.027) and GPXa (r = 0.299, P = 0.05) and a decrease in RHR (r = −0.297, P = 0.047). Multivariate analyses showed that the independent predictors of saRHI improvement were an increase in PA (&bgr; = 2.63; 95% CI, 1.24-4.19; P = 0.019), a decrease in RHR (&bgr; = 1.96; 95% CI, 1.01-5.03; P = 0.048), and an increase in GPXa (&bgr; = 2.64; 95% CI, 1.18-5.08; P = 0.021). Conclusions Even low-intensity PA improves antioxidant capacity, RHR, and saRHI in postmenopausal women. Advising postmenopausal women to increase their PA at any level seems warranted based on our preliminary and hypothesis-generating data.
Clinical value of ERG, TFF3, and SPINK1 for molecular subtyping of prostate cancer

In view of the marked molecular heterogeneity of prostate cancer (PCa), clinical and pathologic parameters alone may be unreliable for predicting disease outcomes after surgical intervention. The development of biomarkers may be helpful to estimate tumor heterogeneity and stratify patients in terms of their risk of progression. Levels of v‐ets avian erythroblastosis virus E26 oncogene homolog (ERG), trefoil factor 3 (TFF3), and serine peptidase inhibitor, Kazal type 1 (SPINK1) are commonly elevated in PCa, but it is unclear whether the evaluation of these 3 markers can help to discriminate patients who will have different clinical outcomes. The authors investigated whether assessment of ERG, TFF3, and SPINK1 expression could help to define clinically relevant, distinct subsets of patients with PCa.
Essential oils to control ichthyophthiriasis in pacu, Piaractus mesopotamicus (Holmberg): special emphasis on treatment with Melaleuca alternifolia.

In vitro effect of the Melaleuca alternifolia, Lavandula angustifolia and Mentha piperita essential oils (EOs) against Ichthyophthirius multifiliis and in vivo effect of M. alternifolia for treating ichthyophthiriasis in one of the most important South American fish, Piaractus mesopotamicus (Holmberg), were evaluated. The in vitro test consisted of three EOs, each at concentrations of 57 μL L(-1) , 114 μL L (-1) , 227 μL L(-1) and 455 μL L (-1) , which were assessed once an hour for 4 h in microtitre plates (96 wells). The in vitro results demonstrated that all tested EOs showed a cytotoxic effect against I. multifiliis compared to control groups (P < 0.05). The in vivo treatment for white spot disease was performed in a bath for 2 h day(-1) for 5 days using the M. alternifolia EO (50 μL L (-1) ). In this study, 53.33% of the fish severely infected by I. multifiliis survived after the treatment with M. alternifolia (50 μL L (-1) ) and the parasitological analysis has shown an efficacy of nearly 100% in the skin and gills, while all the fish in the control group died. Furthermore, the potential positive effect of M. alternifolia EO against two emergent opportunistic bacteria in South America Edwardsiella tarda and Citrobacter freundii was discussed.
Nematicidal Effects of 5-Aminolevulinic Acid on Plant-Parasitic Nematodes

Abstract Plant-parasitic nematodes are important agricultural pests and often cause serious crop losses. Novel, environmental friendly nematicides are urgently needed because of the harmful effects of some existing nematicides on human health. 5-Aminolevulinic acid (ALA) was reported as a potential biodegradable herbicide, insecticide, or plant-growth promoting agent. Lack of information on ALA against plant-parasitic nematodes prompted this investigation to determine the effects of ALA on Meloidogyne incognita, Heterodera glycines, Pratylenchus coffeae, and Bursaphelenchus xylophilus. A series of in vitro assays and one greenhouse trial were conducted to examine the nematicidal effects of ALA. The results demonstrated that ALA exhibited a strong effect of suppression against the four nematodes tested. ALA also inhibited hatching of M. incognita and H. glycines. Results from the greenhouse experiment indicated that treatment of soil with 6.0 mM ALA significantly reduced the root-gall index (RGI) and egg mass number per root system compared with the uninoculated control (P # 0.05). The metabolism assays indicated that ALA treatment significantly altered the nematode metabolism including the total protein production, malondialdehyde (MDA) content, and oxidase activities. This study suggested that ALA is a promising nematicide against plant-parasitic nematodes.