Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of dopaminergic inhibition on serum levels of thyrotrophin and prolactin in patients with hypothyroidism before and after prolonged oral administration of TRH.

Forty mg TRH/day given orally for 3 weeks to 8 patients with mild primary hypothyroidism decreased serum TSH from a mean of 4.0 ng/ml +/- 1.2 (SE) to 2.0 ng/ml +/- 0.4 (49%), and their mean incremental TSH response to iv TRH was equally reduced from 8.6 ng/ml +/- 2.5 to 4.0 ng/ml +/- 1.9 (46%). In the same patients serum Prl was 8.2 ng/ml +/- 2.2 before oral TRH treatment and 6.6 ng/ml +/- 1.5 (81%) after treatment, and the mean incremental Prl response to iv TRH was reduced from 43.5 ng/ml +/- 5.0 to 35.9 ng/ml +/- 7.5 (83%). The oral administration of 10 mg of the dopamine antagonist metoclopramide increased mean serum TSH from 0.6 ng/ml +/- 0.1 (SE) to 0.7 ng/ml +/- 0.1 (120%) in euthyroid subjects and from 4.0 ng/ml +/- 1.2 to 5.7 ng/ml +/- 1.6 (145%) in patients with primary hypothyroidism, and mean serum Prl from 8.6 ng/ml +/- 0.8 to 109.5 ng/ml +/- 24.3 (1251%) and from 8.2 ng/ml +/- 2.2 to 119.6 ng/ml +/- 45.5 (1460%), respectively. The incremental TSH responses to iv TRH increased 2.3-fold in euthyroid subjects pre-treated with metoclopramide, while no change was observed in the TSH responsiveness in patients with primary hypothyroidism following metoclopramide pre-treatment. In the euthyroid subjects metoclopramide treatment had no effect on the Prl response to iv TRH. (ABSTRACT TRUNCATED AT 250 WORDS)
Individualisation de l’entraînement physique chez la souris : influence du fonds génétique sur l’adaptation musculaire, applications aux maladies du motoneurone

La remarquable plasticite du muscle squelettique permet d’envisager de facon therapeutique l’exercice physique. Apres avoir valide un modele de mesure des capacites motrices (Vitesse Critique, VC) chez la souris saine, nous nous sommes bases sur cet index pour mettre en place un entrainement individualise de courte duree. Les resultats ont montre des ameliorations de la VC et de la capacite musculaire oxydative dependantes du fonds genetique des animaux. Ces donnees nous ont cependant conforte dans l’application de l’exercice chez des modeles murins de pathologies du motoneurone. Apres verification de l’adequation de la VC a l’evaluation des capacites motrices de modeles de paraplegie spastique hereditaire, d’amyotrophie spinale et de sclerose laterale amyotrophique, nous avons pu mettre respectivement en evidence chez ces modeles des declins moteurs tardif, precoce et modulable par l’entrainement physique. Cette derniere observation ouvre d’interessantes perspectives therapeutiques.
Extracorporeal Membrane Oxygenation Support in Trauma Versus Nontrauma Patients with Noninfectious Acute Respiratory Failure

The utility of extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS) of noninfectious origin remains unclear. Data on patients with ARDS of noninfectious origin who underwent ECMO were reviewed retrospectively. We compared the pre-ECMO characteristics and hospital outcomes of patients with traumatic and nontraumatic ARDS. In total, 23 patients (trauma, n = 9; nontrauma, n = 14) were included in the study. The mean patient age was 42 years, there were three females, and the mean pre-ECMO Simplified Acute Physiologic Score (SAPS) II was 60.0 (49.0-71.0). The hemoglobin level was lower and the prothrombin time (PT) more prolonged, prior to initiation of ECMO, in traumatic compared with nontraumatic ARDS patients. During the first 48 h of ECMO support, the coagulation parameters did not differ between the two groups, but the platelet counts, PT, and activated partial thromboplastin time indicated that coagulopathy was developing in all patients. The hospital and 28-day mortality rates were 21.7 and 13.0%, respectively, and serious neurological outcomes (cerebral performance category [CPC] of three points or more) developed in 26.1% of all patients; however, the extent of such outcomes did not differ between traumatic and nontraumatic ARDS patients. Upon multivariate analysis, the pre-ECMO SAPS II tended to be associated with composite events (i.e., hospital death and/or a CPC of three points or more) (P = 0.051). Additionally, a history of hypertension and an elevated pre-ECMO SAPS II were significant risk factors for serious neurological outcomes among hospital survivors (n = 18). In conclusion, ECMO support can be associated with favorable outcomes in patients with ARDS of noninfectious origin, irrespective of whether the ARDS is associated with trauma. The pre-ECMO SAPS II and a history of hypertension may be independent risk factors for poor outcomes.
Stepwise web-based questionnaires for diagnosing cluster headache: LUCA and QATCH

Background Cluster headache (CH) is a primary headache disorder that is diagnosed based on the patient's history. For large-scale epidemiologic and genetic studies, a web-based, preferably short, questionnaire can be a feasible alternative to replace time-consuming clinical interviews. Methods Self-reported CH patients were enrolled via our research website. Participants meeting screening criteria were directed to the Leiden University Cluster headache Analysis program (LUCA) questionnaire. Individual diagnoses were calculated using an algorithm based on International Headache Society criteria. Subsequently, semi-structured telephone interviews were carried out to validate the LUCA questionnaire. The shorter Quick Ascertainment of Cluster Headache (QATCH) questionnaire for diagnosing CH was constructed by using logistic regression to select the most predictive questions. Results Via our website 437 self-reported CH patients were recruited. Of these, 291 patients were included in this cross-sectional study. The LUCA questionnaire was valid and accurate. Using logistic regression, three questions (QATCH) provided similar sensitivity (53.8% vs. 57.2%), specificity (88.9% vs. 87.5%), positive predictive value (95.5% vs. 95.9%) and negative predictive value (30.8% vs. 28.8%) compared with the LUCA questionnaire. Conclusion The web-based LUCA questionnaire was accurate and reliable in diagnosing CH among self-reported patients. Males with headache attacks of short duration and long headache-free intervals (months to years) are very likely to have CH.
The ABCA1 cholesterol transporter associates with one of two distinct dystrophin‐based scaffolds in Schwann cells

Cytoskeletal scaffolding complexes help organize specialized membrane domains with unique functions on the surface of cells. In this study, we define the scaffolding potential of the Schwann cell dystrophin glycoprotein complex (DGC) by establishing the presence of four syntrophin isoforms, (α1, β1, β2, and γ2), and one dystrobrevin isoform, (α‐dystrobrevin‐1), in the abaxonal membrane. Furthermore, we demonstrate the existence of two separate DGCs in Schwann cells that divide the abaxonal membrane into spatially distinct domains, the DRP2/periaxin rich plaques and the Cajal bands that contain Dp116, utrophin, α‐dystrobrevin‐1 and four syntrophin isoforms. Finally, we show that the two different DGCs can scaffold unique accessory molecules in distinct areas of the Schwann cell membrane. Specifically, the cholesterol transporter ABCA1, associates with the Dp116/syntrophin complex in Cajal bands and is excluded from the DRP2/periaxin rich plaques. © 2008 Wiley‐Liss, Inc.
Associations between lipid measures and metabolic syndrome, insulin resistance and adiponectin. - Usefulness of lipid ratios in Korean men and women -.

BACKGROUND Several reports have raised the possibility that newly addressed lipid measures might be superior to the traditional ones for cardiovascular risk prediction. However, data on the associations between these lipid measures with metabolic syndrome (MetS) is limited. METHODS AND RESULTS A cross-sectional study of participants in routine health examinations was performed. The associations between lipid measure variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, LDL-C/HDL-C, TG/HDL-C ratio and non-HDL-C) and MetS, insulin resistance (IR) by homeostatic model assessment (HOMA) and adiponectin were analyzed in 6,546 participants (3,820 men; mean age 46.0+/-9.2 years in men, 44.6+/-9.5 years in women). In multivariable adjusted regression analysis, the 3 lipid ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C showed significant association with the number of MetS components, HOMA and log adiponectin level in both men and women without MetS (P<0.001, respectively), though these relations were weaker in participants with MetS. The mean levels of the lipid ratios also associated with increasing numbers of the MetS components, quartiles of HOMA and adiponectin. CONCLUSIONS Lipid ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C, as well as TG and HDL, were consistently associated with MetS and IR in participants without MetS. Lipid ratios might be used as integrated and simple lipid measures.
Development of Language and Speech Perception in Congenitally, Profoundly Deaf Children as a Function of Age at Cochlear Implantation

Like any other surgery requiring anesthesia, cochlear implantation in the first few years of life carries potential risks, which makes it important to assess the potential benefits. This study introduces a new method to assess the effect of age at implantation on cochlear implant outcomes: developmental trajectory analysis (DTA). DTA compares curves representing change in an outcome measure over time (i.e. developmental trajectories) for two groups of children that differ along a potentially important independent variable (e.g. age at intervention). This method was used to compare language development and speech perception outcomes in children who received cochlear implants in the second, third or fourth year of life. Within this range of age at implantation, it was found that implantation before the age of 2 resulted in speech perception and language advantages that were significant both from a statistical and a practical point of view. Additionally, the present results are consistent with the existence of a ‘sensitive period’ for language development, a gradual decline in language acquisition skills as a function of age.
A Fluorescence‐Activated Cell Sorter Analysis of the Relationship Between Protein Kinase G and Endothelial Nitric Oxide Synthase

The process of regulation of NOS after production of nitric oxide is not yet delineated. Protein kinase G may exert a feedback regulation of this enzyme. We used diaminofluorescein assays to detect changes in basal nitric oxide production caused by modulators of protein kinase G activity in freshly isolated ovine lung microvascular endothelial cells. We also used fluorescence activated cell sorter analysis (FACS) to determine molecular and phosphorylation changes caused by PKG activation with 8‐Br‐cGMP. The PKG activator, 8‐Br‐cGMP (100 μM) produced a shift in the basal NO production curve downward. The inhibition began within 5 min and was sustained over 4.5 hr. The two protein kinase G inhibitors 100 μM Rp‐8‐Br‐PET‐cGMPS and 50 nM guanosine 3′‐5′‐cyclic monophosphoro thionate‐8‐Br‐Rp isomer Na salt and the cGMP inhibitor 4 μM Rp‐8‐pCPT‐cGMPS all enhanced NO production as seen by the upward shift in the basal NO curve. Conversely, the PKG activator drug, 100 μM guanosine‐3′‐5′‐cyclic monophosphate‐β‐phenyl‐1NF‐ethano‐8‐bromo sodium salt decreased NO production causing a downward shift in the basal curve. FACS analysis revealed that 5 μM 8‐Br‐cGMP in <5 min caused an increase in N‐terminal labeling of NOS and a decrease in both C‐terminal and serine 1177 labeling of NOS. 8‐Br‐cGMP appeared to increase PKG 1α and to decrease PKG 1β labeling. Changes in other phosphorylation sites were less consistent but overall mean channel fluorescence increased from 19.92 to 217.36 for serine 116 and decreased from 329.27 to 254.03 for threonine 495 phosphorylation. Data indicated that PKG caused both molecular and phosphorylation changes in NOS. Anat Rec 293:1755–1765, 2010. © 2010 Wiley‐Liss, Inc.
Effects of Engineered Cerium Oxide Nanoparticles on Bacterial Growth and Viability

ABSTRACT Interest in engineered nanostructures has risen in recent years due to their use in energy conservation strategies and biomedicine. To ensure prudent development and use of nanomaterials, the fate and effects of such engineered structures on the environment should be understood. Interactions of nanomaterials with environmental microorganisms are inevitable, but the general consequences of such interactions remain unclear, due to a lack of standard methods for assessing such interactions. Therefore, we have initiated a multianalytical approach to understand the interactions of synthesized nanoparticles with bacterial systems. These efforts are focused initially on cerium oxide nanoparticles and model bacteria in order to evaluate characterization procedures and the possible fate of such materials in the environment. The growth and viability of the Gram-negative species Escherichia coli and Shewanella oneidensis, a metal-reducing bacterium, and the Gram-positive species Bacillus subtilis were examined relative to cerium oxide particle size, growth media, pH, and dosage. A hydrothermal synthesis approach was used to prepare cerium oxide nanoparticles of defined sizes in order to eliminate complications originating from the use of organic solvents and surfactants. Bactericidal effects were determined from MIC and CFU measurements, disk diffusion tests, and live/dead assays. For E. coli and B. subtilis, clear strain- and size-dependent inhibition was observed, whereas S. oneidensis appeared to be unaffected by the particles. Transmission electron microscopy along with microarray-based transcriptional profiling was used to understand the response mechanism of the bacteria. Use of multiple analytical approaches adds confidence to toxicity assessments, while the use of different bacterial systems highlights the potential wide-ranging effects of nanomaterial interactions in the environment.
Effects of AT1 receptor blockade on blood pressure and the renin-angiotensin system in spontaneously hypertensive rats of the stroke prone strain.

The aim of the study was to assess the effects of chronic angiotensin I receptor blockade on blood pressure, the renin-angiotensin system in plasma and kidney and the extent of renal damage in spontaneously hypertensive rats of the stroke prone strain (SHRsp). Four months old male SHRsp rats were orally treated with a high (10 mg/kg b.w. per day) or a low dose (1 mg/kg b.w. per day) of the AT1 receptor antagonist Telmisartan and compared to Losartan- (20 mg/kg b.w. per day), Captopril-treated (50 mg/kg b.w. per day) or untreated control groups for 38 days. Despite a similar extent of blood pressure reduction in all groups (except low dose Telmisartan), high dose Telmisartan but not Losartan or Captopril significantly reduced left ventricular weight by 24% compared to controls (p<0.05). Renal damage as assessed by urinary albumin or glomerulosclerosis index was significantly reduced in all treatment groups (p<0.02). Plasma renin concentration was significantly elevated (p<0.02) and plasma angiotensinogen significantly lowered (p<0.05) in all pharmacologically treated group compared to controls. In the kidney, renin-mRNA as well as AT1 receptor gene expression were elevated in all treatment groups, but no significant changes were found for renal angiotensinogen-mRNA. Chronic oral treatment of genetically hypertensive rats by the AT1 receptor antagonist Telmisartan reveals a blood pressure lowering and reno-protective effect of this drug comparable to other AT1 receptor antagonists or converting enzyme inhibitors, and demonstrates a marked reduction of cardiac hypertrophy by Telmisartan in this model.
Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone.

MoPn-specific T-cell clones were isolated from a T-cell line that was capable of curing chlamydial genital infection by the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) after adoptive transfer. Two clones (designated as 2.14-0 and 2.14-3) were characterized by flow cytometry techniques to be homogenous for L3T4, CD3, and alpha/beta T cell receptor (TcR) T-helper cell markers. The two clones were biovar specific, because they reacted to MoPn but not the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC) or C. trachomatis, serovar type E. Cytokine profile analysis, by a combination of bioassays, ELISA, and slot/Northern blotting for specific cytokine messenger RNAs, further revealed that cultures of antigen-stimulated clone 2.14-0 contained interleukin-2 (IL-2), tumor necrosis factor-alpha, and gamma interferon (a T helper 1 cell [Th1] profile). Clone 2.14-3 was also positive for gamma interferon, a level much lower than that of clone 2.14-0, and negative for IL-4 secretion, suggesting a Th1 profile as well. The ability of these clones to bring about the resolution of the chronic genital chlamydial infection of nude mice was tested by the adoptive transfer of 10(7) cells of each clone into the mice. By 4 weeks after cell transfer of clone 2.14-0, 81% of recipient nude mice (30 of 37) resolved the disease. In contrast, clone 2.14-3 or a control T-cell clone specific for a heterologous antigen were unable to resolve the infection in 20 recipients in each case, even after 100 days. (ABSTRACT TRUNCATED AT 250 WORDS)
Oxidative Stress and Neurodegenerative Disorders

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs.
Bovine oocyte cytoplasm supports nuclear remodeling but not reprogramming of murine fibroblast cells

Nuclear transfer (NT) is used to elucidate fundamental biological issues such as reversibility of cell differentiation and interactions between the cytoplasm and nucleus. To obtain an insight into interactions between the somatic cell nucleus and oocyte cytoplasm, nuclear remodeling and gene expression were compared in bovine oocytes that had received nuclei from bovine and mouse fibroblast cells. While the embryos that received nuclei from bovine fibroblast cells developed into blastocysts, those that received nuclei from mouse fibroblasts did not develop beyond the 8‐cell stage. Similar nuclear remodeling procedures were observed in oocytes reconstructed with mouse and bovine fibroblast cells. Foreign centrosomes during NT were introduced into embryos reconstructed with both fibroblast cell types. A number of housekeeping mouse genes (hsp70, bax, and glt‐1) were abnormally expressed in embryos that had received nuclei from mouse fibroblast cells. However, development‐related genes, such as Oct‐4 and E‐cad, were not expressed. The results collectively suggest that the bovine oocyte cytoplasm supports nuclear remodeling, but not reprogramming of mouse fibroblast cells. Mol. Reprod. Dev. 68: 25–34, 2004. © 2004 Wiley‐Liss, Inc.
Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression

Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug–drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs) in transporter regulations are summarized and discussed. Both solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner. PKCs are notably implicated in membrane insertion of bile acid transporters in liver and, in this way, are thought to contribute to cholestatic or choleretic effects of endogenous compounds or drugs. The exact clinical relevance of PKCs-related regulation of drug transporters in terms of drug resistance, pharmacokinetics, drug–drug interactions and drug toxicity remains however to be precisely determined. This issue is likely important to consider in the context of the development of new drugs targeting PKCs-mediated signaling pathways, for treating notably cancers, diabetes or psychiatric disorders.
Loss of Endothelial CXCR7 Impairs Vascular Homeostasis and Cardiac Remodeling After Myocardial Infarction: Implications for Cardiovascular Drug Discovery

Background: Genome-wide association studies identified the association of the CXCL12 genetic locus (which encodes the chemokine CXCL12, also known as stromal cell–derived factor 1) with coronary artery disease and myocardial infarction (MI). Unlike CXCR4, the classic receptor for CXCL12, the function of CXCR7 (the most recently identified receptor) in vascular responses to injury and in MI remains unclear. Methods: Tissue expression of CXCR7 was examined in arteries from mice and humans. Mice that harbored floxed CXCR7 and Cdh5-promoter driven CreERT2 were treated with tamoxifen to induce endothelium-restricted deletion of CXCR7. The resulting conditional knockout mice and littermate controls were studied for arterial response to angioplasty wire injury and cardiac response to coronary artery ligation. The role of CXCR7 in endothelial cell proliferation and angiogenesis was determined in vitro with cells from mice and humans. The effects of adenoviral delivery of CXCR7 gene and pharmacological activation of CXCR7 were evaluated in mice subjected to MI. Results: Injured arteries from both humans and mice exhibited endothelial CXCR7 expression. Conditional endothelial CXCR7 deletion promoted neointimal formation without altering plasma lipid levels after endothelial injury and exacerbated heart functional impairment after MI, with increased both mortality and infarct sizes. Mechanistically, the exacerbated responses in vascular and cardiac remodeling are attributable to the key role of CXCR7 in promoting endothelial proliferation and angiogenesis. Impressively, the impaired post-MI cardiac remodeling occurred with elevated levels of CXCL12, which was previously thought to mediate cardiac protection by exclusively engaging its cognate receptor, CXCR4. In addition, both CXCR7 gene delivery via left ventricular injection and treatment with a CXCR7 agonist offered cardiac protection after MI. Conclusions: CXCR7 represents a novel regulator of vascular homeostasis that functions in the endothelial compartment with sufficient capacity to affect cardiac function and remodeling after MI. Activation of CXCR7 may have therapeutic potential for clinical restenosis after percutaneous coronary intervention and for heart remodeling after MI.