bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term exposure of CdTe quantum dots on PC12 cellular activity and the determination of optimum non-toxic concentrations for biological use
Authors: Prasad Babu R , Nikolskaya Natalia , Connolly David , Smith Terry J , Byrne Stephen J , Gérard Valérie A , Gun'ko Yurii K , Rochev Yury 
Published: March 2010

Abstract

Background
The unique and tuneable photonic properties of Quantum Dots (QDs) have made them potentially useful tools for imaging biological entities. However, QDs though attractive diagnostic and therapeutic tools, have a major disadvantage due to their inherent cytotoxic nature. The cellular interaction, uptake and resultant toxic influence of CdTe QDs (gelatinised and non-gelatinised Thioglycolic acid (TGA) capped) have been investigated with pheochromocytoma 12 (PC12) cells. In conjunction to their analysis by confocal microscopy, the QD - cell interplay was explored as the QD concentrations were varied over extended (up to 72 hours) co-incubation times. Coupled to this investigation, cell viability, DNA quantification and cell proliferation assays were also performed to compare and contrast the various factors leading to cell stress and ultimately death.

Results
Thioglycolic acid (TGA) stabilised CdTe QDs (gel and non - gel) were co-incubated with PC12 cells and investigated as to how their presence influenced cell behaviour and function. Cell morphology was analysed as the QD concentrations were varied over co-incubations up to 72 hours. The QDs were found to be excellent fluorophores, illuminating the cytoplasm of the cells and no deleterious effects were witnessed at concentrations of ~10-9 M. Three assays were utilised to probe how individual cell functions (viability, DNA quantification and proliferation) were affected by the presence of the QDs at various concentrations and incubation times. Cell response was found to not only be concentration dependant but also influenced by the surface environment of the QDs. Gelatine capping on the surface acts as a barrier towards the leaking of toxic atoms, thus reducing the negative impact of the QDs.

Conclusion
This study has shown that under the correct conditions, QDs can be routinely used for the imaging of PC12 cells with minimal adverse effects. We have found that PC12 cells are highly susceptible to an increased concentration range of the QDs, while the gelatine coating acts as a barrier towards enhanced toxicity at higher QD concentrations.
Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells
Authors: Lee Davy CW , Mok Chris KP , Law Anna HY , Peiris Malik , Lau Allan SY 
Published: March 2010

Abstract
Avian influenza virus H9N2 isolates cause a mild influenza-like illness in humans. However, the pathogenesis of the H9N2 subtypes in human remains to be investigated. Using a human alveolar epithelial cell line A549 as host, we found that A/Quail/Hong Kong/G1/97 (H9N2/G1), which shares 6 viral "internal genes" with the lethal A/Hong Kong/156/97 (H5N1/97) virus, replicates efficiently whereas other H9N2 viruses, A/Duck/Hong Kong/Y280/97 (H9N2/Y280) and A/Chicken/Hong Kong/G9/97 (H9N2/G9), replicate poorly. Interestingly, we found that there is a difference in the translation of viral protein but not in the infectivity or transcription of viral genes of these H9N2 viruses in the infected cells. This difference may possibly be explained by H9N2/G1 being more efficient on viral protein production in specific cell types. These findings suggest that the H9N2/G1 virus like its counterpart H5N1/97 may be better adapted to the human host and replicates efficiently in human alveolar epithelial cells.
Complications in colorectal surgery: risk factors and preventive strategies
Authors: Kirchhoff Philipp , Clavien Pierre-Alain , Hahnloser Dieter 
Published: March 2010

Abstract

Backround
Open or laparoscopic colorectal surgery comprises of many different types of procedures for various diseases. Depending upon the operation and modifiable and non-modifiable risk factors the intra- and postoperative morbidity and mortality rate vary. In general, surgical complications can be divided into intraoperative and postoperative complications and usually occur while the patient is still in the hospital.

Methods
A literature search (1980-2009) was carried out, using MEDLINE, PubMed and the Cochrane library.

Results
This review provides an overview how to identify and minimize intra- and postoperative complications. The improvement of different treatment strategies and technical inventions in the recent decade has been enormous. This is mainly attributable to the increase in the laparoscopic approach, which is now well accepted for many procedures. Training of the surgeon, hospital volume and learning curves are becoming increasingly more important to maximize patient safety, surgeon expertise and cost effectiveness. In addition, standardization of perioperative care is essential to minimize postoperative complications.

Conclusion
This review summarizes the main perioperative complications of colorectal surgery and influencable and non-influencable risk factors which are important to the general surgeon and the relevant specialist as well. In order to minimize or even avoid complications it is crucial to know these risk factors and strategies to prevent, treat or reduce intra- and postoperative complications.
mspecLINE: bridging knowledge of human disease with the proteome
Authors: Handcock Jeremy , Deutsch Eric W , Boyle John 
Published: March 2010

AbstractBackgroundPublic proteomics databases such as PeptideAtlas contain peptides and proteins identified in mass spectrometry experiments. However, these databases lack information about human disease for researchers studying disease-related proteins. We have developed mspecLINE, a tool that combines knowledge about human disease in MEDLINE with empirical data about the detectable human proteome in PeptideAtlas. mspecLINE associates diseases with proteins by calculating the semantic distance between annotated terms from a controlled biomedical vocabulary. We used an established semantic distance measure that is based on the co-occurrence of disease and protein terms in the MEDLINE bibliographic database.ResultsThe mspecLINE web application allows researchers to explore relationships between human diseases and parts of the proteome that are detectable using a mass spectrometer. Given a disease, the tool will display proteins and peptides from PeptideAtlas that may be associated with the disease. It will also display relevant literature from MEDLINE. Furthermore, mspecLINE allows researchers to select proteotypic peptides for specific protein targets in a mass spectrometry assay.ConclusionsAlthough mspecLINE applies an information retrieval technique to the MEDLINE database, it is distinct from previous MEDLINE query tools in that it combines the knowledge expressed in scientific literature with empirical proteomics data. The tool provides valuable information about candidate protein targets to researchers studying human disease and is freely available on a public web server.
Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients
Authors: Singwe-Ngandeu Madeleine , Finckh Axel , Bas Sylvette , Tiercy Jean-Marie , Gabay Cem 
Published: March 2010

Abstract
Introduction
The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA).

Methods
Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of the School of Medicine, University of Yaoundé, Yaoundé, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays. Fifty-one patients with other inflammatory rheumatic diseases and 50 healthy individuals were included as controls.

Results
An anti-CCP2 assay showed the best diagnosis sensitivity (82%) and specificity (98%) with high positive predictive (PPV) (96%) and negative predictive values (NPV) (91%). Thirty percent of RA patients were carrying at least one copy of the HLA-DRB1 shared epitope (SE) compared to 10% and 14% of patients with other inflammatory rheumatic diseases and healthy individuals, respectively. The presence of the SE was associated with the production of ACPA.

Conclusions
Anti-CCP2 antibodies are useful markers of RA in African patients. In this cohort, the prevalence of the SE is higher in RA patients than in controls but lower than that reported in patient cohorts of European ancestry. The discrepancy between the high prevalence of ACPA-positive patients and the relatively low number of SE-positive cases suggest that, in addition to SE, other genetic factors control the development of ACPA in African RA patients.
Crucial involvement of the CX3CR1-CX3CL1 axis in dextran sulfate sodium-mediated acute colitis in mice
Authors: Kostadinova Feodora I , Baba Tomohisa , Ishida Yuko , Kondo Toshikazu , Popivanova Boryana K , Mukaida Naofumi 
Published: March 2010

AbstractDextran sulfate sodium ingestion causes CX3CR1-expressing macrophages to accumulate in intestinal submucosal areas and to express inducible NO synthetase, thereby causing acute colitis.Ingestion of DSS solution can induce in rodents acute colitis with a massive infiltration of neutrophils and macropahges, mimicking pathological changes observed in the acute phase of UC patients. Concomitantly, DSS ingestion enhanced the expression of a potent macrophage-tropic chemokine, CX3CL1/fractalkine, and its receptor, CX3CR1, in the colon. WT but not CX3CR1-deficient mice exhibited marked body weight loss and shortening of the colon after DSS ingestion. Moreover, inflammatory cell infiltration was attenuated in CX3CR1-deficient mice together with reduced destruction of glandular architecture compared with WT mice. DSS ingestion enhanced intracolonic iNOS expression by macrophages and nitrotyrosine generation in WT mice, but iNOS expression and nitrotyrosine generation were attenuated in CX3CR1-deficient mice. The analysis on bone marrow chimeric mice revealed that bone marrow-derived but not non-bone marrow-derived CX3CR1-expressing cells were a major source of iNOS. These observations would indicate that the CX3CL1-CX3CR1 axis can regulate the expression of iNOS, a crucial mediator of DSS-induced colitis. Thus, targeting the CX3CL1-CX3CR1 axis may be effective for the treatment of IBDs such as UC.
Discontinuation of Growth Hormone (GH) Treatment during the Transition Phase Is an Important Factor Determining the Phenotype of Young Adults with Nonidiopathic Childhood-Onset GH Deficiency
Authors: Kołtowska-Häggström Maria , Geffner Mitchell E. , Jönsson Peter , Monson John P. , Abs Roger , Hána Václav , Höybye Charlotte , Wollmann Hartmut A. 
Published: March 2010

Abstract
Context: Little is known about the impact of childhood-onset GH deficiency (GHD), in particular the duration of GH cessation during the transition phase, on adult phenotype.
Objective: We investigated the association between the manifestations and management of GHD during childhood/adolescence and the clinical features of GHD in adulthood.
Design/Setting/Patients/Intervention: Patients with reconfirmed childhood-onset GHD who resumed GH treatment as adults were identified from two sequential databases (n = 313). The cohort was followed up longitudinally from GH start in childhood to reinitiation of treatment in adulthood and 1 yr beyond. Analyses were performed in the total cohort and in subgroups of patients with idiopathic GHD (IGHD) and non-IGHD. The cohorts were stratified based on duration of GH cessation (short, ≤2 yr; long, &gt;2 yr).
Main Outcome Measures: Regimen of pediatric GH administration, duration of GH interruption, IGF-I sd score, lipid concentrations, and quality of life were measured.
Results: Mean duration of GH interruption was 4.4 yr. IGF-I sd score in adulthood was related to severity of childhood GHD. In non-IGHD patients, a longer duration of GH interruption was associated with a worse lipid profile (P &lt; 0.0001). Non-IGHD patients who gained more height during childhood GH treatment reported better quality of life than those who gained less height (P &lt; 0.05).
Conclusions: Pediatricians should tailor GH treatment, not only for its beneficial effect on growth but also for future health in adulthood. In adults with reconfirmed GHD, particularly those with non-IGHD, early recommencement of GH should be considered.
Effects of isoquinolonesulfonamides on action potential secretion coupling in pituitary cells
Authors: Popovic Marko A. , Stojilkovic Stanko S. , Gonzalez-Iglesias Arturo E. 
Published: March 2010

Abstract

Background: Pituitary lactotrophs fire action potentials spontaneously and the associated voltage-gated calcium influx is sufficient to maintain high and steady prolactin release. Several intracellular proteins can mediate the action of calcium influx on prolactin secretion, including calmodulin-dependent protein kinases. Here, we studied effects of isoquinolonesulfonamides KN-62 and KN-93, calmodulin-dependent protein kinase inhibitors, and KN-92, an inactive analog, on spontaneous electrical activity, voltage-gated calcium influx, cyclic nucleotide production, and basal prolactin release.

Methods: The effects of these compounds on electrical activity and calcium signaling was measured in single lactotrophs and cyclic nucleotide production and prolactin release were determined in static culture and perifusion experiments of anterior pituitary cells from postpubertal female rats.

Results: KN-62 and KN-93 blocked basal prolactin release in a dose- and time-dependent manner, suggesting that calmodulin-dependent protein kinase could mediate the coupling of electrical activity and secretion. However, a similar effect on basal prolactin release was observed on application of KN-92, which does not inhibit this kinase. KN-93 also inhibited cAMP and cGMP production, but inhibition of prolactin release was independent of the status of cyclic nucleotide production. Single cell measurements revealed abolition of spontaneous and depolarization-induced electrical activity and calcium transients in KN-92/93-treated cells, with a time course comparable to that observed in secretory studies.

Conclusions: The results suggest that caution should be used when interpreting data from studies using isoquinolonesulfonamides to evaluate the role of calmodulin-dependent protein kinases in excitable endocrine cells, because inactive compounds exhibit comparable effects on action potential secretion coupling to those of active compounds.
Monitoring gene expression in muscle tissue of macaca
fascicularis under the influence of testosterone and SARM
Authors: Reiter Martina , Tichopad Ales , Riedmaier Irmgard , Pfaffl Michael W. , Meyer Heinrich H.D. 
Published: March 2010

Abstract
The focus of this study was to evaluate data on the gene expression profiles induced by testosterone and a selective androgen receptor modulator (SARM, TAP Pharmaceutical Products Inc., Lake Forest, IL, USA) in androgen sensitive muscle tissue to obtain a better understanding on the molecular mechanisms of action and to identify biomarkers for SARM function in primate organs. A total of 24 male cyomolgus monkeys were divided into four groups: testosterone group, SARM1 group, SARM10 group, and control group, each consisting of six animals. The testosterone group was treated i.m. with 3.0 mg/kg Testostoviron®-depot-250 (Schering, Berlin, Germany) every 2 weeks, the SARM1 and SARM10 groups with 1 mg/kg or 10 mg/kg SARM LGD2941 daily, and the control group was not treated. Muscle biopsies from musculus
quadriceps and musculus
triceps were collected at three time points: baseline time point before SARM application (control), on day 16, and on day 90 of treatment. A total of 30 candidate genes were selected according to their functionality by screening the actual literature and were composed to the following functional groups: cell cycle, endocrine factors, energy metabolism, muscle fiber proteins, muscle specific transcription factors, protein metabolism, and satellite cell biology. Biomarkers were identified as genes regulated from baseline in any of the three treatment groups at day 16 or day 90 using analysis of variance with baseline defined as the contrast group. Out of 23 tested candidate genes, 3 were significantly regulated in m. quadriceps after 90 days treatment; in m. triceps no significant differences were identified. Cathepsin L, calpain 3, and insulin like growth factor binding protein 3 could be identified as first biomarkers, and first physiological differences between control and treatment samples were determined. Both testosterone and SARM LGD2941 appear to have similar effects after 90 days treatment, and thus a longer-term therapy with these substances can be recommended.
Sex hormone-binding globulin in congenital adrenal hyperplasia
Authors: Zamrazilová Ludmila , Dvořáková Marcela , Lisá Lidka , Stárka Luboslav , Hampl Richard 
Published: March 2010

Abstract

Background: Sex hormone-binding globulin biosynthesis is influenced by three hormonal systems: gonadal, insular and thyroid. Congenital adrenal hyperplasia is characterized by overproduction of adrenal androgens associated with impaired insulin sensitivity, hyperinsulinemia and often also with hypothyroidism. Only scarce data are available concerning congenital adrenal hyperplasia. The objective of this study was to determine the distribution of sex hormone-binding globulin and free testosterone levels in these patients and to what extent these values correlate with actual 17-hydroxyprogesterone and androstenedione levels, which are commonly used for monitoring of treatment effectiveness.

Materials and methods: A total of 300 retrospective laboratory records of 78 males and boys and 456 records of 162 girls and premenopausal women with diagnosis of congenital adrenal hyperplasia under common substitution treatment were evaluated statistically. The data were divided artificially into groups of low, normal and high levels, with respect to physiological concentrations for each sex and age. The percentages of the total in each group were calculated.

Results: Whereas an almost Gaussian distribution occurred for males, the data for females displayed a considerable shift to low sex hormone-binding globulin and accordingly high free testosterone levels. Sex hormone-binding globulin levels did not correlate with 17-hydroxyprogesterone.

Conclusion: Low sex hormone-binding globulin levels in congenital adrenal hyperplasia, at least in females, reflect their involvement in insular and eventually thyroid axes, rather than the effectiveness of substitution.
Sequential transformation of 4-androstenedione into dihydrotestosterone in prostate carcinoma (DU-145) cells indicates that 4-androstenedione and not testosterone is the substrate of 5α-reductase
Authors: Samson Melanie , Labrie Fernand , Luu-The Van 
Published: March 2010

AbstractBackground: Although it is well recognized that 5α-reductases possess higher affinity for 4-androstenedione than testosterone, and the affinity of 4-androstenedione is higher for 5α-reductases than 17β-hydroxysteroid dehydrogenases, it is generally believed that dihydrotestosterone is necessarily produced by the transformation of testosterone into dihydrotestosterone, suggesting that the step catalyzed by 17β-hydroxysteroid dehydrogenase precedes the step catalyzed by 5α-reductase. This interpretation is in contradiction with the enzymatic kinetic law that suggests that the 5α-reduction step that catalyzes the transformation of 4-dione into 5α-androstane-3,17-dione precedes the 17keto-reduction step.Materials and methods: To verify which of these two pathways is operative, we quantified mRNA expression levels of steroidogenic enzymes in prostate carcinoma DU-145 cells by real-time PCR and determined the metabolites produced after incubation with [14C]4-dione in the presence and absence of a 5α-reductase inhibitor and analyzed the metabolites produced by thin layer chromatography and HPLC.Results: Real-time PCR analysis strongly suggests that the new type 3 5α-reductase is responsible for 5α-reductase activity in DU-145 cells. Steroid profile analysis shows that in the absence of inhibitor 5α-androstanedione is first produced, followed by the production of androsterone and dihydrotestosterone. The concentration of testosterone was not detectable. In the presence of Finasteride, an inhibitor of 5α-reductase, there was no transformation of 4-androstenedione and also there was no production of testosterone. The present data clearly indicate that the biosynthesis of dihydrotestosterone in DU-145 cells does not require testosterone as intermediate, and the step catalyzed by 5α-reductase precedes the step catalyzed by 17β-hydroxysteroid dehydrogenase.
Inhibition of aromatase activity in MCF-7aro human breast cancer cells by the natural androgens testosterone and androstenedione
Authors: Chetrite Gérard S. , Pasqualini Jorge R. 
Published: March 2010

Abstract

Background: The human breast contains all the enzymes responsible for local bioformation of estradiol (E2). Two principal pathways are implicated in the last steps of E2 formation: the ‘aromatase’ which transforms androgens into estrogens, and the ‘sulfatase’ which converts estrogen sulfates into active unconjugated estrogens; activities found in both normal and cancerous breast. Aromatase inhibition by anti-aromatase agents is largely used with very positive results in the treatment of breast cancer patients. In this study, the effects of the natural androgens androstenedione and testosterone were explored on aromatase activity in a stable aromatase-expressing estrogen receptor-positive human breast cancer cell line MCF-7aro.

Materials and methods: The cells were incubated with physiological concentrations of [3H]-testosterone (5 nmol/L) alone or in the presence of either testosterone or androstenedione (0.5 and 50 μmol/L) 24 h at 37°C. Cellular radioactivity uptake was determined. [3H]-E2 was characterized by thin-layer chromatography.

Results: The MCF-7aro cells have a very high aromatase activity because conversion of [3H]-testosterone to [3H]-E2 was 3.02±0.17 pmol/mg DNA in non-treated cells. Testosterone, at concentrations of 0.5 and 50 μmol/L, provoked inhibition of E2 formation of 36% and 79%, respectively. The effect of androstenedione at 0.5 and 50 μmol/L was 56% and 76%, respectively.

Conclusion: In breast cancer cells, the natural androgens testosterone and androstenedione, have the capacity to control bioformation of estradiol by blocking aromatase activity. The data can provide important information on the control mechanism of estrogen intratumoral levels and open new possibilities in breast cancer treatment.