bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNAs in platelet production and activation
Authors: Edelstein Leonard C. , Bray Paul F.
Published: March 2011

MicroRNAs are small RNA molecules that modulate protein expression by degrading mRNA or repressing translation. They have been shown to play important roles in hematopoiesis, including embryonic stem cell differentiation, erythropoiesis, granulocytopoiesis/monocytopoiesis, lymphopoiesis, and megakaryocytopoiesis. miR-150 and miR-155 play divergent roles in megakaryocytopoiesis, with the former promoting development of megakaryocytes at the expense of erythrocytes and the latter causing a reduction in megakaryocyte colony formation. Platelets also contain fully functional miRNA machinery, and certain miRNA levels in platelets have been found to coordinate with reactivity to specific agonists and to pathologic states. This review will cover the current state of knowledge of miRNAs in megakaryocytes and platelets and the exciting possibilities for future research.
Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review
Authors: De Luca D. , Cogo P. , Zecca E. , Piastra M. , Pietrini D. , Tridente A. , Conti G. , Carnielli V.P.
Published: March 2011

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants.

This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs.

We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.
Pulmonary arterial hypertension: a comparison between children and adults
Authors: Barst R.J. , Ertel S.I. , Beghetti M. , Ivy D.D.
Published: March 2011

The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults.

The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension.

Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children.

Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines.

In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).
Autoimmunity-related demyelination in infection by Japanese encephalitis virus
Authors: Tseng Yu-Fen , Wang Chien-Chih , Liao Shuen-Kuei , Chuang Ching-Kai , Chen Wei-June
Published: March 2011

Japanese encephalitis (JE) virus is the most common cause of epidemic viral encephalitis in the world. The virus mainly infects neuronal cells and causes an inflammatory response after invasion of the parenchyma of the brain. The death of neurons is frequently observed, in which demyelinated axons are commonly seen. The mechanism that accounts for the occurrence of demyelination is ambiguous thus far. With a mouse model, the present study showed that myelin-specific antibodies appeared in sera, particularly in those mice with evident symptoms. Meanwhile, specific T cells proliferating in response to stimulation by myelin basic protein (MBP) was also shown in these mice. Taken together, our results suggest that autoimmunity may play an important role in the destruction of components, e.g., MBP, of axon-surrounding myelin, resulting in demyelination in the mouse brain after infection with the JE virus.
Inhibition of granulocyte migration by tiotropium bromide
Authors: Vacca Gabriela , Randerath Winfried J , Gillissen Adrian
Published: March 2011

Study objectives

Neutrophil influx into the airways is an important mechanism in the pathophysiology of the inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD). Previously it was shown that anticholinergic drugs reduce the release of non-neuronal paracrine mediators, which modulate inflammation in the airways. On this basis, we investigated the ability of the long-acting anticholinergic tiotropium bromide to inhibit a) alveolar macrophage (AM)-mediated chemotaxis of neutrophils, and b) cellular release of reactive oxygen species (ROS).

Method

AM and neutrophils were collected from 71 COPD patients. Nanomolar concentrations of tiotropium bromide were tested in AM cultured up to 20 h with LPS (1 μg/ml). AM supernatant was tested for TNFα, IL8, IL6, LTB4, GM-CSF, MIPα/β and ROS. It was further used in a 96-well chemotaxis chamber to stimulate the migration of fluorescence labelled neutrophils. Control stimulants consisted of acetylcholine (ACh), carbachol, muscarine or oxotremorine and in part PMA (phorbol myristate acetate, 0.1 μg/ml). Potential contribution of M1-3-receptors was ascertained by a) analysis of mRNA transcription by RT-PCR, and b) co-incubation with selective M-receptor inhibitors.

Results

Supernatant from AM stimulated with LPS induced neutrophilic migration which could be reduced by tiotropium in a dose dependent manner: 22.1 ± 10.2 (3 nM), 26.5 ± 18,4 (30 nM), and 37.8 ± 24.0 (300 nM, p < 0.001 compared to non-LPS activated AM). Concomitantly TNFα release of stimulated AM dropped by 19.2 ± 7.2% of control (p = 0.001). Tiotropium bromide did not affect cellular IL8, IL6, LTB4, GM-CSF and MIPα/β release in this setting. Tiotropium (30 nM) reduced ROS release of LPS stimulated AM by 36.1 ± 15.2% (p = 0.002) and in carbachol stimulated AM by 46.2 ± 30.2 (p < 0.001). M3R gene expression dominated over M2R and M1R. Chemotaxis inhibitory effect of tiotropium bromide was mainly driven by M3R inhibition.

Conclusion

Our data confirm that inhibiting muscarinic cholinergic receptors with tiotropium bromide reduces TNFα mediated chemotactic properties and ROS release of human AM, and thus may contribute to lessen cellular inflammation.
An expression profile analysis of ES cell-derived definitive endodermal cells and Pdx1-expressing cells
Authors: Ogaki Soichiro , Harada Seiko , Shiraki Nobuaki , Kume Kazuhiko , Kume Shoen
Published: March 2011

Background

We developed an efficient in vitro method to differentiate mouse ES cells into the definitive endoderm (DE) and then Pdx1-expressing pancreatic lineages using mesodermal-derived supporting cells, M15. Using this method, resulting ES cell-derived DE and Pdx1-expressing cells were isolated by cell sorting, and their gene expression profiles were investigated with DNA microarray. Genes that were specifically expressed in DE and/or in Pdx1-expressing cells were extracted and their expression patterns in normal embryonic development were studied.

Results

Genes whose expression increased in DE and Pdx1 positive cells compared to the undifferentiated ES cells were chosen and in situ hybridizations were performed. Out of 54 genes examined, 27 were expressed in the DE of E8.5 mouse embryos and 15 genes were expressed in distinct domains in the pancreatic buds of E14.5 embryos. Among those genes expressed were Foxq1, CpM, Foxp4, Pcdh1, and Zmiz1, which were previously reported in other endodermal tissues. Genes, such as Parm1, Tmem184a, Hipk2 and Sox4 were reported to be expressed during early pancreatic development. Nptx2, C2cd4b, Tcf7l2 and Kiss1r were reported to be associated with beta cell or pancreatic functions in the adult. Akr1c19, Aebp2, Pbxip1 and Creb3l1, were novel and have not been described as being expressed either in DE or the pancreas.

Conclusions

We identified 27 genes, including 4 novel genes expressed in DE and pancreatic progenitor cells during normal development using an ES cell in vitro differentiation system. These results showed that DE cells and Pdx1/GFP-expressing cells obtained from our M15 based differentiation method mimic cells during the normal developmental processes. Additionally, ES cells are an excellent model for studies of early developmental processes.
Coordinated gene expression during gilthead sea bream skeletogenesis and its disruption by nutritional hypervitaminosis A
Authors: Fernández Ignacio , Darias Maria , Andree Karl B , Mazurais David , Zambonino-Infante Jose Luís , Gisbert Enric
Published: March 2011

Background

Vitamin A (VA) has a key role in vertebrate morphogenesis, determining body patterning and growth through the control of cell proliferation and differentiation processes. VA regulates primary molecular pathways of those processes by the binding of its active metabolite (retinoic acid) to two types of specific nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which promote transcription of downstream target genes. This process is well known in most of higher vertebrates; however, scarce information is available regarding fishes. Therefore, in order to gain further knowledge of fish larval development and its disruption by nutritional VA imbalance, the relative expression of some RARs and RXRs, as well as several genes involved in morpho- and skeletogenesis such as peroxisome proliferator-activated receptors (PPARA, PPARB and PPARG); retinol-binding protein (RBP); insulin-like growth factors I and II (IGF1 and IGF2, respectively); bone morphogenetic protein 2 (Bmp2); transforming growth factor β-1 (TGFB1); and genes encoding different extracellular matrix (ECM) proteins such as matrix Gla protein (mgp), osteocalcin (bglap), osteopontin (SPP1), secreted protein acidic and rich in cysteine (SPARC) and type I collagen α1 chain (COL1A1) have been studied in gilthead sea bream.

Results

During gilthead sea bream larval development, specific expression profiles for each gene were tightly regulated during fish morphogenesis and correlated with specific morphogenetic events and tissue development. Dietary hypervitaminosis A during early larval development disrupted the normal gene expression profile for genes involved in RA signalling (RARA), VA homeostasis (RBP) and several genes encoding ECM proteins that are linked to skeletogenesis, such as bglap and mgp.

Conclusions

Present data reflects the specific gene expression patterns of several genes involved in larval fish RA signalling and skeletogenesis; and how specific gene disruption induced by a nutritional VA imbalance underlie the skeletal deformities. Our results are of basic interest for fish VA signalling and point out some of the potential molecular players involved in fish skeletogenesis. Increased incidences of skeletal deformities in gilthead sea bream fed with hypervitaminosis A were the likely ultimate consequence of specific gene expression disruption at critical development stages.
Recent evolution of the NF-κB and inflammasome regulating protein POP2 in primates
Authors: Atianand Maninjay K , Fuchs Travis , Harton Jonathan A
Published: March 2011

Background

Pyrin-only protein 2 (POP2) is a small human protein comprised solely of a pyrin domain that inhibits NF-κB p65/RelA and blocks the formation of functional IL-1β processing inflammasomes. Pyrin proteins are abundant in mammals and several, like POP2, have been linked to activation or regulation of inflammatory processes. Because POP2 knockout mice would help probe the biological role of inflammatory regulation, we thus considered whether POP2 is common in the mammalian lineage.

Results

BLAST searches revealed that POP2 is absent from the available genomes of not only mice and rats, but those of other domestic mammals and New World monkeys as well. POP2 is however present in the genome of the primate species most closely related to humans including Pan troglodytes (chimpanzees), Macaca mulatta (rhesus macaques) and others. Interestingly, chimpanzee POP2 is identical to human POP2 (huPOP2) at both the DNA and protein level. Macaque POP2 (mqPOP2), although highly conserved is not identical to the human sequence; however, both functions of the human protein are retained. Further, POP2 appears to have arisen in the mammalian genome relatively recently (~25 mya) and likely derived from retrogene insertion of NLRP2.

Conclusion

Our findings support the hypothesis that the NLR loci of mammals, encoding proteins involved in innate and adaptive immunity as well as mammalian development, have been subject to recent and strong selective pressures. Since POP2 is capable of regulating signaling events and processes linked to innate immunity and inflammation, its presence in the genomes of hominids and Old World primates further suggests that additional regulation of these signals is important in these species.
Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds
Authors: Shi Cheng-Ying , Yang Hua , Wei Chao-Ling , Yu Oliver , Zhang Zheng-Zhu , Jiang Chang-Jun , Sun Jun , Li Ye-Yun , Chen Qi , Xia Tao , Wan Xiao-Chun
Published: March 2011

Background

Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes.

Results

Using high-throughput Illumina RNA-seq, the transcriptome from poly (A)+ RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs). Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010). Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG) found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were analyzed by RT-PCR and quantitative real time PCR (qRT-PCR).

Conclusions

An extensive transcriptome dataset has been obtained from the deep sequencing of tea plant. The coverage of the transcriptome is comprehensive enough to discover all known genes of several major metabolic pathways. This transcriptome dataset can serve as an important public information platform for gene expression, genomics, and functional genomic studies in C. sinensis.
Improving Salmonella vector with recmutation to stabilize the DNA cargoes
Authors: Zhang Xiangmin , Wanda Soo-Young , Brenneman Karen , Kong Wei , Zhang Xin , Roland Kenneth , Curtiss Roy
Published: March 2011

Background

Salmonella has been employed to deliver therapeutic molecules against cancer and infectious diseases. As the carrier for target gene(s), the cargo plasmid should be stable in the bacterial vector. Plasmid recombination has been reduced in E. coli by mutating several genes including the recA, recE, recF and recJ. However, to our knowledge, there have been no published studies of the effect of these or any other genes that play a role in plasmid recombination in Salmonella enterica.

Results

The effect of recA, recF and recJ deletions on DNA recombination was examined in three serotypes of Salmonella enterica. We found that (1) intraplasmid recombination between direct duplications was RecF-independent in Typhimurium and Paratyphi A, but could be significantly reduced in Typhi by a ΔrecA or ΔrecF mutation; (2) in all three Salmonella serotypes, both ΔrecA and ΔrecF mutations reduced intraplasmid recombination when a 1041 bp intervening sequence was present between the duplications; (3) ΔrecA and ΔrecF mutations resulted in lower frequencies of interplasmid recombination in Typhimurium and Paratyphi A, but not in Typhi; (4) in some cases, a ΔrecJ mutation could reduce plasmid recombination but was less effective than ΔrecA and ΔrecF mutations. We also examined chromosome-related recombination. The frequencies of intrachromosomal recombination and plasmid integration into the chromosome were 2 and 3 logs lower than plasmid recombination frequencies in Rec+ strains. A ΔrecA mutation reduced both intrachromosomal recombination and plasmid integration frequencies.

Conclusions

The ΔrecA and ΔrecF mutations can reduce plasmid recombination frequencies in Salmonella enterica, but the effect can vary between serovars. This information will be useful for developing Salmonella delivery vectors able to stably maintain plasmid cargoes for vaccine development and gene therapy.
Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2 -hydroxylase
Authors: Meixner Marion , Jungnickel Julia , Grothe Claudia , Gieselmann Volkmar , Eckhardt Matthias
Published: March 2011

Background

The sphingolipids galactosylceramide (GalCer) and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt
-/-) mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA)-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated Cgt
-/- mice with an additional deletion of the fatty acid 2-hydroxylase (Fa2h) gene.

Results

Fa2h
-/-/Cgt-/- double-deficient mice lack sulfatide, GalCer, and in addition HFA-GlcCer and sphingomyelin. Interestingly, compared to Cgt
-/- mice the amount of GlcCer in CNS myelin was strongly reduced in Fa2h
-/-/Cgt
-/- mice by more than 80%. This was accompanied by a significant increase in sphingomyelin, which was the predominant sphingolipid in Fa2h
-/-/Cgt
-/- mice. Despite these significant changes in myelin sphingolipids, compact myelin was formed in Fa2h
-/-/Cgt
-/- mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old Fa2h
-/-/Cgt
-/- mice did not differ significantly from that of Cgt
-/- mice, and there was no obvious phenotypic difference between Fa2h
-/-/Cgt
-/- and Cgt
-/- mice

Conclusions

These data show that compact myelin can be formed with non-hydroxylated sphingomyelin as the predominant sphingolipid and suggest that the presence of HFA-GlcCer and HFA-sphingomyelin in Cgt
-/- mice does not functionally compensate the loss of HFA-GalCer.
Validation of a case definition to define chronic dialysis using outpatient administrative data
Authors: Clement Fiona M , James Matthew T , Chin Rick , Klarenbach Scott W , Manns Braden J , Quinn Robert R , Ravani Pietro , Tonelli Marcello , Hemmelgarn Brenda R ,   the Alberta Kidney Disease Network
Published: March 2011

Background

Administrative health care databases offer an efficient and accessible, though as-yet unvalidated, approach to studying outcomes of patients with chronic kidney disease and end-stage renal disease (ESRD). The objective of this study is to determine the validity of outpatient physician billing derived algorithms for defining chronic dialysis compared to a reference standard ESRD registry.

Methods

A cohort of incident dialysis patients (Jan. 1 - Dec. 31, 2008) and prevalent chronic dialysis patients (Jan 1, 2008) was selected from a geographically inclusive ESRD registry and administrative database. Four administrative data definitions were considered: at least 1 outpatient claim, at least 2 outpatient claims, at least 2 outpatient claims at least 90 days apart, and continuous outpatient claims at least 90 days apart with no gap in claims greater than 21 days. Measures of agreement of the four administrative data definitions were compared to a reference standard (ESRD registry). Basic patient characteristics are compared between all 5 patient groups.

Results

1,118,097 individuals formed the overall population and 2,227 chronic dialysis patients were included in the ESRD registry. The three definitions requiring at least 2 outpatient claims resulted in kappa statistics between 0.60-0.80 indicating "substantial" agreement. "At least 1 outpatient claim" resulted in "excellent" agreement with a kappa statistic of 0.81.

Conclusions

Of the four definitions, the simplest (at least 1 outpatient claim) performed comparatively to other definitions. The limitations of this work are the billing codes used are developed in Canada, however, other countries use similar billing practices and thus the codes could easily be mapped to other systems. Our reference standard ESRD registry may not capture all dialysis patients resulting in some misclassification. The registry is linked to on-going care so this is likely to be minimal. The definition utilized will vary with the research objective.
Maternal and perinatal factors associated with hospitalised infectious mononucleosis in children, adolescents and young adults: record linkage study
Authors: Mahmud Imran , Abdel-Mannan Omar A , Wotton Clare J , Goldacre Michael J
Published: March 2011

Background

There is current interest in the role of perinatal factors in the aetiology of diseases that occur later in life. Infectious mononucleosis (IM) can follow late primary infection with Epstein-Barr virus (EBV), and has been shown to increase the risk of multiple sclerosis and Hodgkin's disease. Little is known about maternal or perinatal factors associated with IM or its sequelae.

Methods

We investigated perinatal risk factors for hospitalised IM using a prospective record-linkage study in a population in the south of England. The dataset used, the Oxford record linkage study (ORLS), includes abstracts of birth registrations, maternities and in-patient hospital records, including day case care, for all subjects in a defined geographical area. From these sources, we identified cases of hospitalised IM up to the age of 30 years in people for whom the ORLS had a maternity record; and we compared perinatal factors in their pregnancy with those in the pregnancy of children who had no hospital record of IM.

Results

Our data showed a significant association between hospitalised IM and lower social class (p = 0.02), a higher risk of hospitalised IM in children of married rather than single mothers (p < 0.001), and, of marginal statistical significance, an association with singleton birth (p = 0.06). The ratio of observed to expected cases of hospitalised IM in each season was 0.95 in winter, 1.02 in spring, 1.02 in summer and 1.00 in autumn. The chi-square test for seasonality, with a value of 0.8, was not significant.

Other factors studied, including low birth weight, short gestational age, maternal smoking, late age at motherhood, did not increase the risk of subsequent hospitalised IM.

Conclusions

Because of the increasing tendency of women to postpone childbearing, it is useful to know that older age at motherhood is not associated with an increased risk of hospitalised IM in their children. We have no explanation for the finding that children of married women had a higher risk of IM than those of single mothers. Though highly significant, it may nonetheless be a chance finding. We found no evidence that such perinatal factors as birth weight and gestational age, or season of birth, were associated with the risk of hospitalised IM.
Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study
Authors: Zhang Jie , She Danyang , Feng Dan , Jia Yanhong , Xie Lixin
Published: March 2011

Background

We examined the utility of serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for the diagnoses, severity assessments, and predicting the prognoses of patients with sepsis and compared sTREM-1 values with those of C-reactive protein (CRP) and procalcitonin (PCT).

Methods

Fifty-two patients with sepsis were included: 15 sepsis cases and 37 severe sepsis cases (severe sepsis + septic shock). Serum levels of sTREM-1, CRP, and PCT were determined on days 1, 3, 5, 7, 10, and 14 after admission to an ICU.

Results

Serum sTREM-1 levels of patients with severe sepsis were significantly higher than for those with sepsis on day 1 (240.6 pg/ml vs. 118.3 pg/ml; P < 0.01), but CRP and PCT levels were not significantly different between the two groups. The area under an ROC curve for sTREM-1 for severe sepsis patients was 0.823 (95% confidence interval: 0.690-0.957). Using 222.5 pg/ml of sTREM-1 as the cut-off value, the sensitivity was 59.5%, the specificity was 93.3%, the positive predictive value was 95.6%, the negative predictive value was 48.3%, the positive likelihood ratio was 8.92, and the negative likelihood ratio was 0.434. Based on 28-day survivals, sTREM-1 levels in the surviving group showed a tendency to decrease over time, while they tended to gradually increase in the non-surviving group. sTREM-1 levels in the non-surviving group were higher than those in the surviving group at all time points, whereas CRP and PCT levels showed a tendency to decrease over time in both groups. sTREM-1 levels and Sequential Organ Failure Assessment (SOFA) scores were positively correlated (r = 0.443; P < 0.001), and this correlation coefficient was greater than the correlation coefficients for both CRP and PCT.

Conclusions

Serum sTREM-1 levels reflected the severity of sepsis more accurately than those of CRP and PCT and were more sensitive for dynamic evaluations of sepsis prognosis.

Trial Registration

Current controlled trials ChiCTR-OCH-09000745
Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts
Authors: Meng Wenxia , Xia Qingjie , Wu Lanyan , Chen Sixiu , He Xin , Zhang Lin , Gao Qinghong , Zhou Hongmei
Published: March 2011

Background

The purpose of this study was to assess the expression levels for TβRI, TβRII, and TβRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TβRs in carcinogenesis of oral mucosa.

Methods

Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches.

Results

IHC signals for TβRII and TβRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TβRI, in OLK and OSCC (P > 0.05); and TβRII and TβRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-β1 led to a remarkable decrease in the expression of TβRII and TβRIII in CAFs (P < 0.05).

Conclusion

This study provides the first evidence that the loss of TβRII and TβRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TβRII and TβRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.
Evaluating the impact of decentralising tuberculosis microscopy services to rural township hospitals in gansu province, china
Authors: Wei Xiaolin , Zou Guanyang , Zhang Hui , Li Renzhong , Walley John D , Jiang Shiwen , Yin Jia , Jin Shuigao , Li You , Sun Qiang , Newell James N , Griffiths Sian , Wang Lixia
Published: March 2011

Background

In 2004, the Ministry of Health issued the policy of decentralising microscopy services (MCs) to one third of all township hospitals in China. The study was conducted in Gansu Province, a poor western one in China. Ganzhou was one county in Gansu Province. Ganzhou County was identified as a unique case of further decentralisation of tuberculosis (TB) treatment services in township hospitals. The study evaluated the impact of the MC policy on providers and patients in Gansu Province. The second objective was to assess the unique case of Ganzhou County compared with other counties in the province.

Methods

Both quantitative and qualitative methods were used. All 523 MCs in the province completed an institutional survey regarding their performance. Four counties were selected for in-depth investigation, where 169 TB suspects were randomly selected from the MC and county TB dispensary registers for questionnaire surveys. Informant interviews were conducted with 38 health staff at the township and county levels in the four counties.

Results

Gansu established MCs in 39% of its township hospitals. From January 2006 to June 2007, 8% of MCs identified more than 10 TB sputum smear positive patients while 54% did not find any. MCs identified 1546 TB sputum smear positive patients, accounting for 9% of the total in the province. The throughputs of MCs in Ganzhou County were eight times of those in other counties. Interviews identified several barriers to implement the MC policy, such as inadequate health financing, low laboratory capacity, lack of human resources, poor treatment and management capacities, and lack of supervisions from county TB dispensaries.

Conclusion

Microscopy centre throughputs were generally low in Gansu Province, and the contribution of MCs to TB case detection was insignificant taking account the number of MCs established. As a unique case of full decentralisation of TB service, Ganzhou County presented better results. However, standards and quality of TB care needed to be improved. The MC policy needs to be reviewed in light of evidence from this study.
Simultaneous multiple-excitation multiphoton microscopy yields increased imaging sensitivity and specificity
Authors: Butko Margaret T , Drobizhev Mikhail , Makarov Nikolay S , Rebane Aleksander , Brinkman Brendan C , Gleeson Joseph G
Published: March 2011

Background

Multiphoton microscopy (MPM) offers many advantages over conventional wide-field and confocal laser scanning microscopy (CLSM) for imaging biological samples such as 3D resolution of excitation, reduced phototoxicity, and deeper tissue imaging. However, adapting MPM for critical multi-color measurements presents a challenge because of the largely overlapping two-photon absorption (TPA) peaks of common biological fluorophores. Currently, most multi-color MPM relies on the absorbance at one intermediate wavelength of multiple dyes, which introduces problems such as decreased and unequal excitation efficiency across the set of dyes.

Results

Here we describe an MPM system incorporating two, independently controlled sources of two-photon excitation whose wavelengths are adjusted to maximally excite one dye while minimally exciting the other. We report increased signal-to-noise ratios and decreased false positive emission bleed-through using this novel multiple-excitation MPM (ME-MPM) compared to conventional single-excitation MPM (SE-MPM) in a variety of multi-color imaging applications.

Conclusions

Similar to the tremendous gain in popularity of CLSM after the introduction of multi-color imaging, we anticipate that the ME-MPM system will further increase the popularity of MPM. In addition, ME-MPM provides an excellent tool to more rapidly design and optimize pairs of fluorescence probes for multi-color two-photon imaging, such as CFP/YFP or GFP/DsRed for CLSM.
Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum
Authors: Ganie Showkat Ahmad , Haq Ehtishamul , Hamid Abid , Qurishi Yasrib , Mahmood Zahid , Zargar Bilal Ahmad , Masood Akbar , Zargar Mohmmad Afzal
Published: March 2011

Background

The present study was conducted to evaluate the in vitro and in vivo antioxidant properties of aqueous extract of Podophyllum hexandrum. The antioxidant potential of the plant extract under in vitro situations was evaluated by using two separate methods, inhibition of superoxide radical and hydrogen peroxide radical. Carbon tetrachloride (CCl4) is a well known toxicant and exposure to this chemical is known to induce oxidative stress and causes tissue damage by the formation of free radicals.

Methods

36 albino rats were divided into six groups of 6 animals each, all animals were allowed food and water ad libitum. Group I (control) was given olive oil, while the rest groups were injected intraperitoneally with a single dose of CCl4 (1 ml/kg) as a 50% (v/v) solution in olive oil. Group II received CCl4 only. Group III animals received vitamin E at a concentration of 50 mg/kg body weight and animals of groups IV, V and VI were given extract of Podophyllum hexandrum at concentration dose of 20, 30 and 50 mg/kg body weight. Antioxidant status in both kidney and lung tissues were estimated by determining the activities of antioxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and superoxide dismutase (SOD); as well as by determining the levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). In addition, superoxide and hydrogen peroxide radical scavenging activity of the extract was also determined.

Results

Results showed that the extract possessed strong superoxide and hydrogen peroxide radical scavenging activity comparable to that of known antioxidant butylated hydroxy toluene (BHT). Our results also showed that CCl4 caused a marked increase in TBARS levels whereas GSH, SOD, GR, GPX and GST levels were decreased in kidney and lung tissue homogenates of CCl4 treated rats. Aqueous extract of Podophyllum hexandrum successfully prevented the alterations of these effects in the experimental animals.

Conclusion

Our study demonstrated that the aqueous extract of Podophyllum hexandrum could protect the kidney and lung tissue against CCl4 induced oxidative stress probably by increasing antioxidant defense activities.
Beneficial effect of Mentha suaveolens essential oil in the treatment of vaginal candidiasis assessed by real-time monitoring of infection
Authors: Pietrella Donatella , Angiolella Letizia , Vavala Elisabetta , Rachini Anna , Mondello Francesca , Ragno Rino , Bistoni Francesco , Vecchiarelli Anna
Published: March 2011

Background

Vaginal candidiasis is a frequent and common distressing disease affecting up to 75% of the women of fertile age; most of these women have recurrent episodes. Essential oils from aromatic plants have been shown to have antimicrobial and antifungal activities. This study was aimed at assessing the anti-fungal activity of essential oil from Mentha suaveolens (EOMS) in an experimental infection of vaginal candidiasis.

Methods

The in vitro and in vivo activity of EOMS was assessed. The in vitro activity was evaluated under standard CLSI methods, and the in vivo analysis was carried out by exploiting a novel, non-invasive model of vaginal candidiasis in mice based on an in vivo imaging technique.

Differences between essential oil treated and saline treated mice were evaluated by the non-parametric Mann-Whitney U-test. Viable count data from a time kill assay and yeast and hyphae survival test were compared using the Student's t-test (two-tailed).

Results

Our main findings were: i) EOMS shows potent candidastatic and candidacidal activity in an in vitro experimental system; ii) EOMS gives a degree of protection against vaginal candidiasis in an in vivo experimental system.

Conclusions

This study shows for the first time that the essential oil of a Moroccan plant Mentha suaveolens is candidastatic and candidacidal in vitro, and has a degree of anticandidal activity in a model of vaginal infection, as demonstrated in an in vivo monitoring imaging system. We conclude that our findings lay the ground for further, more extensive investigations to identify the active EOMS component(s), promising in the therapeutically problematic setting of chronic vaginal candidiasis in humans.
Increased number of Judo therapy facilities in Japan and changes in their geographical distribution
Authors: Inoue Satoshi , Nakao Mutsuhiro , Nomura Kyoko , Yano Eiji
Published: March 2011

Background

Judo therapy is a well established Japanese co-medical profession specializing in outpatient manual treatment of fractures and sprains. Recently, the number of judo therapists has been rapidly increasing as a result of proliferation judo therapy academies. This study examines whether such rapid increases have improved geographical distribution of judo therapy facilities in Japan.

Methods

The number of judo therapy facilities and the population in each municipality were obtained from the Web yellow pages and from Japanese census data for 2004, 2006, and 2008, respectively. Lorenz curves and Gini indices were calculated to demonstrate distributions of judo therapy facilities per 100,000 people. A bootstrapped method was used to identify statistical significances of differences in Gini indices.

Results

In all municipalities, the mean numbers of judo therapy facilities per 100,000 people were 15.3 in 2004, 15.8 in 2006, and 17.6 in 2008. The Gini indices for judo therapy facilities nationally were 0.273 in 2004, 0.264 in 2006, and 0.264 in 2008. The numbers of judo therapy facilities increased significantly between 2006 and 2008 (p < 0.05) but the indices did not change significantly in the same period. The Gini indices for local towns and villages remained unchanged and were consistently higher (p < 0.05) than those in urban areas throughout the study periods.

Conclusion

Our results suggest that recent increases in the number of judo therapy facilities have not necessarily led to greater equality in their geographic distribution in terms of Gini indices.
Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRC
Authors: Onyamboko Marie A , Meshnick Steven R , Fleckenstein Lawrence , Koch Matthew A , Atibu Joseph , Lokomba Victor , Douoguih Macaya , Hemingway-Foday Jennifer , Wesche David , Ryder Robert W , Bose Carl , Wright Linda L , Tshefu Antoinette K , Capparelli Edmund V
Published: March 2011

Background

In many malaria-endemic countries, increasing resistance may soon compromise the efficacy of sulphadoxine-pyrimethamine (SP) for intermittent preventative treatment (IPT) of malaria in pregnancy. Artemisinin-based IPT regimens represent a promising potential alternative to SP. Pharmacokinetic and safety data supporting the use of artemisinin derivatives in pregnancy are urgently needed.

Methods

Subjects included pregnant women with asymptomatic falciparum parasitaemia between 22-26 weeks (n = 13) or 32-36 weeks gestation (n = 13), the same women at three months postpartum, and 25 non-pregnant parasitaemic controls. All subjects received 200 mg orally administered AS. Plasma total and free levels of AS and its active metabolite DHA were determined using a validated LC-MS method. Non-compartmental pharmacokinetic analysis was performed using standard methods.

Results

All pregnant women delivered live babies. The median birth weight was 3025 grams [range 2130, 3620]; 2 of 26 babies had birth weights less than 2500 grams. Rates of parasite clearance by 12 hours post-dose were high and comparable among the groups. Rapid elimination of AS was observed in all three groups. The 90% CI for the pregnancy:postpartum ratio of geometric means for total and free AUC fell within the pre-specified 0.66 - 1.50 therapeutic equivalence interval. However, more pronounced pharmacokinetic differences were observed between the pregnancy and control subjects, with the 90% CI for the pregnancy:control ratio of geometric means for both total 0.68 (90% CI 0.57-0.81) and free AUC 0.78 (90% CI 0.63-0.95) not fully contained within the 0.66 - 1.50 interval. All subjects cleared parasites rapidly, and there was no difference in the percentage of women who were parasitaemic 12 hours after dosing.

Conclusions

A single dose of orally administered AS was found to be both effective and without adverse effects in this study of second and third trimester pregnant women in the DRC. Although DHA AUC during pregnancy and postpartum were similar, the AUC for the pregnant group was less than the non-pregnant controls. The findings of this study suggest that additional studies on the pharmacokinetics of AS in pregnant women are needed.

Trial Registration

ClinicalTrials.gov: NCT00538382
Diabetes and the socioeconomic and built environment: geovisualization of disease prevalence and potential contextual associations using ring maps
Authors: Stewart John E , Battersby Sarah E , Lopez-De Fede Ana , Remington Kevin C , Hardin James W , Mayfield-Smith Kathy
Published: March 2011

Background

Efforts to stem the diabetes epidemic in the United States and other countries must take into account a complex array of individual, social, economic, and built environmental factors. Increasingly, scientists use information visualization tools to "make sense" of large multivariate data sets. Recently, ring map visualization has been explored as a means of depicting spatially referenced, multivariate data in a single information graphic. A ring map shows multiple attribute data sets as separate rings of information surrounding a base map of a particular geographic region of interest. In this study, ring maps were used to evaluate diabetes prevalence among adult South Carolina Medicaid recipients. In particular, county-level ring maps were used to evaluate disparities in diabetes prevalence among adult African Americans and Whites and to explore potential county-level associations between diabetes prevalence among adult African Americans and five measures of the socioeconomic and built environment—persistent poverty, unemployment, rurality, number of fast food restaurants per capita, and number of convenience stores per capita. Although Medicaid pays for the health care of approximately 15 percent of all diabetics, few studies have examined diabetes in adult Medicaid recipients at the county level. The present study thus addresses a critical information gap, while illustrating the utility of ring maps in multivariate investigations of population health and environmental context.

Results

Ring maps showed substantial racial disparity in diabetes prevalence among adult Medicaid recipients and suggested an association between adult African American diabetes prevalence and rurality. Rurality was significantly positively associated with diabetes prevalence among adult African American Medicaid recipients in a multivariate statistical model.

Conclusions

Efforts to reduce diabetes among adult African American Medicaid recipients must extend to rural African Americans. Ring maps can be used to integrate diverse data sets, explore attribute associations, and achieve insights critical to the promotion of population health.
Novel anti-inflammatory role of SLPI in adipose tissue and its regulation by high fat diet
Authors: Adapala Venkata J , Buhman Kimberly K , Ajuwon Kolapo M
Published: March 2011

Background

Secretory leucocyte protease inhibitor (SLPI) is an anti-inflammatory protein that is constitutively expressed in multiple cell types where it functions to counteract localized tissue inflammation by its anti-inflammatory, antimicrobial and anti-protease properties. Little is known about the expression and implication of SLPI in the regulation of adipose tissue inflammation. Therefore, we tested the hypothesis that obesity induces expression of SLPI in adipose tissue where it functions to counteract adipocyte inflammation.

Methods

Male C57BL6 mice were fed a high fat (60% fat calories) or a control diet (10% fat calories) diet for 12 weeks. Adipose tissue expression of SLPI was determined by western blotting and PCR. Fully differentiated adipocytes (3T3-L1) were treated with lipopolysaccharide (LPS, 100 ng/ml) or peptidoglycan (10 μg/ml) for 24 hours in the presence or absence of SLPI. Media was collected for interleukin 6 (IL-6) analysis by enzyme-linked immune absorbent assay (ELISA). RNA was isolated for gene expression analysis by real-time polymerase chain reaction (RT-PCR).

Results

Visceral fat (mesenteric and epididymal) express a higher level of SLPI than subcutaneous fat. The expression of SLPI is mostly in the stromal vascular fraction compared to adipocytes. We also confirmed in vitro that activation of TLR2 and 4 with peptidoglycan and LPS respectively leads to induction of SLPI. Finally, we confirmed that SLPI exerted an anti-inflammatory effect in adipocytes treated with LPS by causing a reduction in expression of IL-6 via a mechanism that included stabilization of cellular IKBα expression.

Conclusion

Our results show that SLPI is also expressed in adipocytes and adipose tissue where it could play an important feedback role in the resolution of inflammation.