bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of serotonin transporter polymorphisms on cortical activity: A resting EEG study
Authors: Lee Tien-Wen , Yu Younger WY , Hong Chen-Jee , Tsai Shih-Jen , Wu Hung-Chi , Chen Tai-Jui
Published: April 2011

Background

The serotonin transporter gene (5-HTT) is a key regulator of serotonergic neurotransmission and has been linked to various psychiatric disorders. Among the genetic variants, polymorphisms in the5-HTTgene-linked polymorphic region (5-HTTLPR) and variable-number-of-tandem-repeat in the second intron (5-HTTVNTR) have functional consequences. However, their genetic impact on cortical oscillation remains unclear. This study examined the modulatory effects of5-HTTLPR(L-allele carriers vs. non-carriers) and5-HTTVNTR(10-repeat allele carriers vs. non-carriers) polymorphism on regional neural activity in a young female population.

Methods

Blood samples and resting state eyes-closed electroencephalography (EEG) signals were collected from 195 healthy women and stratified into 2 sets of comparisons of 2 groups each: L-allele carriers (N= 91) vs. non-carriers for5-HTTLPRand 10-repeat allele carriers (N= 25) vs. non-carriers for5-HTTVNTR. The mean power of 18 electrodes across theta, alpha, beta, gamma, gamma1, and gamma2 frequencies was analyzed. Between-group statistics were performed by an independent t-test, and global trends of regional power were quantified by non-parametric analyses.

Results

Among5-HTTVNTRgenotypes, 10-repeat allele carriers showed significantly low regional power at gamma frequencies across the brain. We noticed a consistent global trend that carriers with low transcription efficiency of 5-HTT possessed low regional powers, regardless of frequency bands. The non-parametric analyses confirmed this observation, withPvalues of 3.071 × 10-8and 1.459 × 10-12for5-HTTLPRand5-HTTVNTR, respectively.

Conclusions and Limitations

Our analyses showed that genotypes with low 5-HTT activity are associated with less local neural synchronization during relaxation. The implication with respect to genetic vulnerability of 5-HTT across a broad range of psychiatric disorders is discussed. Given the low frequency of 10-repeat allele of5-HTTVNTRin our research sample, the possibility of false positive findings should also be considered.
The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in pre-operative patients with brain tumor in China
Authors: Cheng Jin-xiang , Liu Bo-lin , Zhang Xiang , Zhang Yong-qiang , Lin Wei , Wang Rui , Zhang Yong-qin , Zhang Hong-ying , Xie Li , Huo Jun-li
Published: April 2011

Background

Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery.

Methods

The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status.

Results

Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms.

Conclusions

The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.
A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)
Authors: Ahmad Waqar , Ijaz Bushra , Javed Fouzia T , Gull Sana , Kausar Humera , Sarwar Muhammad T , Asad Sultan , Shahid Imran , Sumrin Aleena , Khaliq Saba , Jahan Shah , Pervaiz Asim , Hassan Sajida
Published: April 2011

Background

Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.

Methods

We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].

Results

Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.

Conclusions

The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.
Pathological femoral neck fracture caused by an echinococcus cyst of the vastus lateralis - case report
Authors: Csotye János , Sisák Krisztián , Bardócz Loránt , Tóth Kálmán
Published: April 2011

Background

Musculoskeletal hydatid cysts are rare, but being locally invasive, can potentially cause significant deformity or pathological fracture.

Case presentation

A 39 y.o. male presented to our orthopaedic outpatient clinic complaining of severe right hip pain, and inability to ambulate. Symptoms were not preceded by trauma. Subsequent imaging confirmed a large, 17 × 3 × 5 cm echinococcus cyst in the vastus lateralis, causing erosion of the proximal metaphysis of the femur. As a consequence the patient suffered a non-traumatic pathological intertrochanteric femur fracture. The patient was treated with an en-bloc excision of the lesion - the affected soft tissue envelope containing the large cyst - and as a second surgical step a cemented total hip replacement (THR) was implanted under the same anaesthetic.

The manuscript reviews the literature regarding musculoskeletal hydatid disease.
A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability
Authors: Khan Muzammil Ahmad , Rafiq Muhammad Arshad , Noor Abdul , Ali Nadir , Ali Ghazanfar , Vincent John B , Ansar Muhammad
Published: April 2011

Background

Intellectual disability (ID) is a serious disorder of the central nervous system with a prevalence of 1-3% in a general population. In the past decades, the research focus has been predominantly on X-linked ID (68 loci and 19 genes for non syndromic X linked ID) while for autosomal recessive nonsyndromic ID (NSID) only 30 loci and 6 genes have been reported to date.

Methods

Genome-wide homozygosity mapping with 500 K Nsp1 array (Affymetrix), CNV analysis, PCR based breakpoint mapping and DNA sequencing was performed to explore the genetic basis of autosomal recessive nonsyndromic ID in a large Pakistani family.

Results

Data analysis showed linkage at 8p23 locus with common homozygous region between SNPs rs6989820 and rs2237834, spanning a region of 12.494 Mb. The subsequent CNV analysis of the data revealed a homozygous deletion of 170.673 Kb which encompassed the TUSC3 gene.

Conclusion

We report a novel deletion mutation in TUSC3 gene which is the second gene after TRAPPC9 in which mutation has been identified in more than one family with autosomal recessive NSID. The study will aid in exploring the molecular pathway of cognition.
A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone
Authors: Altenburg Jeffrey D , Bieberich Andrew A , Terry Colin , Harvey Kevin A , VanHorn Justin F , Xu Zhidong , Jo Davisson V , Siddiqui Rafat A
Published: April 2011

Background

Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone.

Methods

Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED50. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC.

Results

CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER- PR- Her2+) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes involved in cancer development and progression, metastasis, and cell cycle progression were downregulated. Cellular pools of PPARγ and phospho-p53 were increased by CCM+DHA relative to either compound alone. DHA enhanced cellular uptake of CCM in SK-BR-3 cells without significantly enhancing CCM uptake in other cell lines.

Conclusions

The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon molecular phenotype. DHA enhancement of cellular curcumin uptake is one potential mechanism for observed synergy in SK-BR-3 cells; however, transcriptomic data show that the antiproliferation synergy accompanies many signaling events unique to the combined presence of the two compounds.
Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice
Authors: Xiao Chun-Li , Tao Zhong-Hua , Guo Lin , Li Wei-Wei , Wan Jin-Liang , Sun Hui-Chuan , Wang Lu , Tang Zhao-You , Fan Jia , Wu Wei-Zhong
Published: April 2011

Background

Hepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model.

Methods

The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells.

Results

IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS.

Conclusions

IMOS is a potential anti-HCC candidate through inhibition of ERK and JNK signaling independent of p53 and worth studying further in patients with HCC, especially at advanced stages.
Factors affecting staff morale on inpatient mental health wards in England: a qualitative investigation
Authors: Totman Jonathan , Hundt Gillian Lewando , Wearn Elizabeth , Paul Moli , Johnson Sonia
Published: April 2011

Background

Good morale among staff on inpatient psychiatric wards is an important requirement for the maintenance of strong therapeutic alliances and positive patient experiences, and for the successful implementation of initiatives to improve care. More understanding is needed of mechanisms underlying good and poor morale.

Method

We conducted individual and group interviews with staff of a full range of disciplines and levels of seniority on seven NHS in-patient wards of varying types in England.

Results

Inpatient staff feel sustained in their potentially stressful roles by mutual loyalty and trust within cohesive ward teams. Clear roles, supportive ward managers and well designed organisational procedures and structures maintain good morale. Perceived threats to good morale include staffing levels that are insufficient for staff to feel safe and able to spend time with patients, the high risk of violence, and lack of voice in the wider organisation.

Conclusions

Increasing employee voice, designing jobs so as to maximise autonomy within clear and well-structured operational protocols, promoting greater staff-patient contact and improving responses to violence may contribute more to inpatient staff morale than formal support mechanisms.
Establishment of a murine epidermal cell line suitable for in vitro and in vivo skin modelling
Authors: Segrelles Carmen , Holguín Almudena , Hernández Pilar , Ariza José M , Paramio Jesús M , Lorz Corina
Published: April 2011

Background

Skin diseases are a major health problem. Some of the most severe conditions involve genetic disorders, including cancer. Several of these human diseases have been modelled in genetically modified mice, thus becoming a highly valuable preclinical tool for the treatment of these pathologies. However, development of three-dimensional models of skin using keratinocytes from normal and/or genetically modified mice has been hindered by the difficulty to subculture murine epidermal keratinocytes.

Methods

We have generated a murine epidermal cell line by serially passaging keratinocytes isolated from the back skin of adult mice. We have termed this cell line COCA. Cell culture is done in fully defined media and does not require feeder cells or any other coating methods.

Results

COCA retained its capacity to differentiate and stratify in response to increased calcium concentration in the cell culture medium for more than 75 passages. These cells, including late passage, can form epidermis-like structures in three-dimensional in vitro models with a well-preserved pattern of proliferation and differentiation. Furthermore, these cells form epidermis in grafting assays in vivo, and do not develop tumorigenic ability.

Conclusions

We propose that COCA constitutes a good experimental system for in vitro and in vivo skin modelling. Also, cell lines from genetically modified mice of interest in skin biology could be established using the method we have developed. COCA keratinocytes would be a suitable control, within a similar background, when studying the biological implications of these alterations.
Exploiting the high-resolution crystal structure of Staphylococcus aureus MenH to gain insight into enzyme activity
Authors: Dawson Alice , Fyfe Paul K , Gillet Florian , Hunter William N
Published: April 2011

Background

MenH (2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase) is a key enzyme in the biosynthesis of menaquinone, catalyzing an unusual 2,5-elimination of pyruvate from 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate.

Results

The crystal structure of Staphylococcus aureus MenH has been determined at 2 Å resolution. In the absence of a complex to inform on aspects of specificity a model of the enzyme-substrate complex has been used in conjunction with previously published kinetic analyses, site-directed mutagenesis studies and comparisons with orthologues to investigate the structure and reactivity of MenH.

Conclusions

The overall basic active site displays pronounced hydrophobic character on one side and these properties complement those of the substrate. A complex network of hydrogen bonds involving well-ordered water molecules serves to position key residues participating in the recognition of substrate and subsequent catalysis. We propose a proton shuttle mechanism, reliant on a catalytic triad consisting of Ser89, Asp216 and His243. The reaction is initiated by proton abstraction from the substrate by an activated Ser89. The propensity to form a conjugated system provides the driving force for pyruvate elimination. During the elimination, a methylene group is converted to a methyl and we judge it likely that His243 provides a proton, previously acquired from Ser89 for that reduction. A conformational change of the protonated His243 may be encouraged by the presence of an anionic intermediate in the active site.
Suppression of low-density lipoprotein oxidation, vascular smooth muscle cell proliferation and migration by a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii
Authors: Chan Judy Y , Koon Johnny C , Leung Ping-Chung , Che Chun-Tao , Fung Kwok-Pui
Published: April 2011

Background

Atherosclerosis is a major cause of death in developed world. Atherosclerosis is characterized by low-density lipoprotein deposition in the arterial wall which ultimately begets the formation of lesions. Rupture of lesions finally leads to clinical events such as heart attack and stroke. Atherosclerosis is a complication associated with diabetes. In patients with diabetes, the risk of atherosclerosis is three to five folds greater than in non-diabetics. Our previous study showed that a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii, namely SR10, could improve glucose homeostasis both in vitro and in vivo. In this study, we want to further investigate the efficacy of SR10 in treating atherosclerosis.

Method

The inhibitory effect of SR10 on low-density lipoprotein oxidation was investigated using free radical-induced erythrocyte hemolysis model and copper ion-induced low-density lipoprotein oxidation model. Since vascular smooth muscle cell proliferation and migration are important processes in atherogenesis, we also examined the effect of SR10 in inhibiting these events.

Results

Our results showed that SR10 inhibited erythrocyte hemolysis with IC50 value at 0.25 mg/ml and significantly prolonged low-density lipoprotein oxidation in vitro. SR10 attenuated platelet derived growth factor-BB-induced vascular smooth muscle cell proliferation by promoting cell cycle arrest at G0/G1 phase as well as inhibiting vascular smooth muscle cell migration.

Conclusion

The potential application of SR10 in treating atherosclerosis has been implied in this study. Animal model will be needed to further verify the efficacy of SR10 in future.
Evaluation of the Pichia pastoris expression system for the production of GPCRs for structural analysis
Authors: Asada Hidetsugu , Uemura Tomoko , Yurugi-Kobayashi Takami , Shiroishi Mitsunori , Shimamura Tatsuro , Tsujimoto Hirokazu , Ito Keisuke , Sugawara Taishi , Nakane Takanori , Nomura Norimichi , Murata Takeshi , Haga Tatsuya , Iwata So , Kobayashi Takuya
Published: April 2011

Background

Various protein expression systems, such as Escherichia coli (E. coli), Saccharomyces cerevisiae (S. cerevisiae), Pichia pastoris (P. pastoris), insect cells and mammalian cell lines, have been developed for the synthesis of G protein-coupled receptors (GPCRs) for structural studies. Recently, the crystal structures of four recombinant human GPCRs, namely β2 adrenergic receptor, adenosine A2a receptor, CXCR4 and dopamine D3 receptor, were successfully determined using an insect cell expression system. GPCRs expressed in insect cells are believed to undergo mammalian-like posttranscriptional modifications and have similar functional properties than in mammals. Crystal structures of GPCRs have not yet been solved using yeast expression systems. In the present study, P. pastoris and insect cell expression systems for the human muscarinic acetylcholine receptor M2 subtype (CHRM2) were developed and the quantity and quality of CHRM2 synthesized by both expression systems were compared for the application in structural studies.

Results

The ideal conditions for the expression of CHRM2 in P. pastoris were 60 hr at 20°C in a buffer of pH 7.0. The specific activity of the expressed CHRM2 was 28.9 pmol/mg of membrane protein as determined by binding assays using [3H]-quinuclidinyl benzilate (QNB). Although the specific activity of the protein produced by P. pastoris was lower than that of Sf9 insect cells, CHRM2 yield in P. pastoris was 2-fold higher than in Sf9 insect cells because P. pastoris was cultured at high cell density. The dissociation constant (Kd) for QNB in P. pastoris was 101.14 ± 15.07 pM, which was similar to that in Sf9 insect cells (86.23 ± 8.57 pM). There were no differences in the binding affinity of CHRM2 for QNB between P. pastoris and Sf9 insect cells.

Conclusion

Compared to insect cells, P. pastoris is easier to handle, can be grown at lower cost, and can be expressed quicker at a large scale. Yeast, P. pastoris, and insect cells are all effective expression systems for GPCRs. The results of the present study strongly suggested that protein expression in P. pastoris can be applied to the structural and biochemical studies of GPCRs.
Revealing the beneficial effect of protease supplementation to high gravity beer fermentations using "-omics" techniques
Authors: Piddocke Maya P , Fazio Alessandro , Vongsangnak Wanwipa , Wong Man L , Heldt-Hansen Hans P , Workman Chris , Nielsen Jens , Olsson Lisbeth
Published: April 2011

Background

Addition of sugar syrups to the basic wort is a popular technique to achieve higher gravity in beer fermentations, but it results in dilution of the free amino nitrogen (FAN) content in the medium. The multicomponent protease enzyme Flavourzyme has beneficial effect on the brewer's yeast fermentation performance during high gravity fermentations as it increases the initial FAN value and results in higher FAN uptake, higher specific growth rate, higher ethanol yield and improved flavour profile.

Results

In the present study, transcriptome and metabolome analysis were used to elucidate the effect on the addition of the multicomponent protease enzyme Flavourzyme and its influence on the metabolism of the brewer's yeast strain Weihenstephan 34/70. The study underlines the importance of sufficient nitrogen availability during the course of beer fermentation. The applied metabolome and transcriptome analysis allowed mapping the effect of the wort sugar composition on the nitrogen uptake.

Conclusion

Both the transcriptome and the metabolome analysis revealed that there is a significantly higher impact of protease addition for maltose syrup supplemented fermentations, while addition of glucose syrup to increase the gravity in the wort resulted in increased glucose repression that lead to inhibition of amino acid uptake and hereby inhibited the effect of the protease addition.
ABO blood group and the risk of placental malaria in sub-Saharan Africa
Authors: Adegnika Ayola A , Luty Adrian JF , Grobusch Martin P , Ramharter Michael , Yazdanbakhsh Maria , Kremsner Peter G , Schwarz Norbert G
Published: April 2011

Background

In malarious areas of the world, a higher proportion of the population has blood group O than in non-malarious areas. This is probably due to a survival advantage conferred either by an attenuating effect on the course of or reduction in the risk of infection by plasmodial parasites. Here, the association between ABO blood group and incidence of placental malaria was assessed in order to determine the possible influence of the former on the latter.

Methods

Data from a study in Lambaréné, Gabon, and data from three previously published reports of studies in The Gambia, Malawi and Sudan, were compiled and compared. ABO blood groups were cross-tabulated with placental malaria stratified by parity. Odds ratios (OR), stratified by parity, were calculated for the outcome, placental parasitaemia, and compared between blood group O vs. non-O mothers in all four studies. Random effects meta-analysis of data from individual studies from areas with perennial hyper/holoendemic transmission was performed.

Results

In Gabon, the odds ratio (OR) for active placental parasitaemia in mothers with group O was 0.3 (95% CI 0.05-1.8) for primiparae and 0.7 (95% CI 0.3-1.8) for multiparae. The OR for primiparae in the published study from The Gambia was 3.0 (95% CI 1.2-7.3) and, in Malawi, 2.2 (95% CI 1.1-4.3). In the Sudanese study, no OR for primiparae could be calculated. The OR for placental parasitaemia in group O multiparae was 0.8 (95% CI 0.3-1.7) in the Gambia, 0.6 (95% CI 0.4-1.0) in Malawi and 0.4 (95% CI 0.1-1.8) in Sudan. Combining data from the three studies conducted in hyper-/holo-endemic settings (Gambia, Malawi, Gabon) the OR for placental malaria in blood group O multiparae was 0.65 (95% CI 0.44-0.96) and for primiparae 1.70 (95% CI 0.67-4.33).

Conclusion

Studies conducted in The Gambia and Malawi suggest that blood group O confers a higher risk of active placental infection in primiparae, but a significantly lower risk in multiparae. These findings were not confirmed by the study from Gabon, in which statistically non-significant trends for reduced risk of placental parasitaemia in those with blood group O, regardless of parity, were observed.
Molecular epidemiology of Plasmodium vivax anti-folate resistance in India
Authors: Prajapati Surendra K , Joshi Hema , Dev Vas , Dua Virendra K
Published: April 2011

Background

Sulphadoxine and pyrimethamine are anti-folate drugs that show synergistic anti-malarial effect. Point mutations in dihydrofolate reductase (dhfr) and dihydropteorate synthatase (dhps) cause anti-folate drug resistance phenotype in human malaria parasites. This study presents pattern of point mutations in dhfr/dhps genes among Indian sub-continent.

Methods

Microscopically diagnosed one hundred Plasmodium vivax field isolates were collected from five widely separated geographical regions of India. Dhfr and dhps genes were PCR amplified and sequenced. Previously published mutations data were collected and analyzed using Chi square test to identify geographical cluster of mutant/wild type genotypes.

Results

Sequence analysis revealed single (S58R), double (S58R/S117N) and quadruple (F57L/S58R/T61M/S117T/) point mutations at dhfr and single (A383G) to double (A383G/A553G) mutations at dhps in P. vivax field isolates. In addition, three new mutations were also observed at dhfr. Both, dhfr and dhps genes revealed tandem repeat variations in field isolates. Dhps revealed very low mutation frequency (14.0%) compared to dhfr (50.70%). Comparative analysis revealed a progressive increase in frequency of quadruple mutant dhfr genotype (p < 0.001) within five years in north-eastern state (Kamrup, Assam). Frequency of dhfr genotypes revealed three distinct geographical clusters of wild (northern India), double mutant (southern India), and quadruple mutant (north-eastern and island regions of India) on the Indian sub-continent.

Conclusion

Study suggests that SP may be susceptible to P. vivax in India, except Andaman and north-eastern state. The distinction of geographical regions with sensitive and resistant parasite phenotypes would be highly useful for designing and administering national anti-malarial drug policy.
A practical guide to bioelectrical impedance analysis using the example of chronic obstructive pulmonary disease
Authors: Walter-Kroker Anja , Kroker Axel , Mattiucci-Guehlke Muriel , Glaab Thomas
Published: April 2011

Bioelectrical impedance analysis (BIA) is a simple, inexpensive, quick and non-invasive technique for measuring body composition. The clinical benefit of BIA can be further enhanced by combining it with bioelectrical impedance vector analysis (BIVA). However, there is a substantial lack of information on the practical aspects of BIA/BIVA for those primarily interested in learning how to use and interpret this method in practice. The purpose of this article is to provide some guidance on the use of BIA/BIVA with special attention to practical considerations.

This report reflects the authors' practical experience with the use of single-frequency BIA in combination with BIVA, particularly in COPD patients. First, the method and principles of BIA/BIVA are briefly described. Then, a practice-oriented approach to the interpretation and analysis of characteristic examples of altered nutritional and fluid status as seen with BIA/BIVA in COPD patients (e.g. malnutrition in obese and underweight patients with COPD, water retention) is presented.

As our examples show BIA/BIVA is an attractive and easy-to-learn tool for quick nutritional assessment and is therefore of great clinical benefit in daily practice.
Asthma exacerbation and proximity of residence to major roads: a population-based matched case-control study among the pediatric Medicaid population in Detroit, Michigan
Authors: Li Shi , Batterman Stuart , Wasilevich Elizabeth , Elasaad Huda , Wahl Robert , Mukherjee Bhramar
Published: April 2011

Background

The relationship between asthma and traffic-related pollutants has received considerable attention. The use of individual-level exposure measures, such as residence location or proximity to emission sources, may avoid ecological biases.

Method

This study focused on the pediatric Medicaid population in Detroit, MI, a high-risk population for asthma-related events. A population-based matched case-control analysis was used to investigate associations between acute asthma outcomes and proximity of residence to major roads, including freeways. Asthma cases were identified as all children who made at least one asthma claim, including inpatient and emergency department visits, during the three-year study period, 2004-06. Individually matched controls were randomly selected from the rest of the Medicaid population on the basis of non-respiratory related illness. We used conditional logistic regression with distance as both categorical and continuous variables, and examined non-linear relationships with distance using polynomial splines. The conditional logistic regression models were then extended by considering multiple asthma states (based on the frequency of acute asthma outcomes) using polychotomous conditional logistic regression.

Results

Asthma events were associated with proximity to primary roads with an odds ratio of 0.97 (95% CI: 0.94, 0.99) for a 1 km increase in distance using conditional logistic regression, implying that asthma events are less likely as the distance between the residence and a primary road increases. Similar relationships and effect sizes were found using polychotomous conditional logistic regression. Another plausible exposure metric, a reduced form response surface model that represents atmospheric dispersion of pollutants from roads, was not associated under that exposure model.

Conclusions

There is moderately strong evidence of elevated risk of asthma close to major roads based on the results obtained in this population-based matched case-control study.
Role of bile salt in regulating Mcl-1 phosphorylation and chemoresistance in hepatocellular carcinoma cells
Authors: Liao Mingmei , Zhao Jinfeng , Wang Ton , Duan Jinghua , Zhang Yangde , Deng Xingming
Published: April 2011

Background

Glycochenodeoxycholate (GCDA) is one of the major human bile salts. Bile salts stimulate cell survival and proliferation through the mitogen-activated protein kinase, but the downstream signaling mechanism(s) remains enigmatic. Mcl-1 is an antiapoptotic molecule of the Bcl2 family that is extensively overexpressed in tumor tissues of patients with hepatocellular carcinoma (HCC).

Results

Here we found that exposure of HepG2 cells to GCDA results in activation of ERK1 and ERK2 and phosphorylation of Mcl-1 in a PD98059 (MEK inhibitor)-sensitive manner. GCDA stimulates Mcl-1 phosphorylation in cells expressing WT but not T163A Mcl-1 mutant, indicating that GCDA-induced Mcl-1 phosphorylation occurs exclusively at the T163 site in its PEST region. GCDA-induced Mcl-1 phosphorylation at T163 enhances the half-life of Mcl-1. Treatment of HepG2 cells with GCDA facilitates Mcl-1 dissociation from Mule (a physiological Mcl-1 ubiquitin E3 ligase). Specific depletion of Mcl-1 from HepG2 cells by RNA interference increases sensitivity of HepG2 cells to chemotherapeutic drugs (i.e. cisplatin and irinotecan). In addition to activation of the ERK/Mcl-1 survival pathway, GCDA can also induce dose-dependent apurinic/apyrimidinic (AP) sites of DNA lesions, which may partially neutralize its survival activity.

Conclusion

Our findings suggest that bile salt may function as a survival agonist and/or potential carcinogen in the development of HCC. Molecular approaches that inactivate Mcl-1 by blocking its T163 phosphorylation may represent new strategies for treatment of HCC.
Characteristics of High-density Lipoprotein Subclasses Distribution for Subjects with Desirable Total Cholesterol Levels
Authors: Tian Li , Long Shiyin , Fu Mingde , Liu Yinghui , Xu Yanhua , Jia Lianqun
Published: April 2011

Background

To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels, mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms.

Methods

ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection. 486 Chinese Adults subjects were assigned to different TC groups according to the third Report of NCEP (ATP- III) guidelines.

Results

The increase in contents of small preβ1-HDL, HDL3c, HDL3b, and HDL3a particles clustered and reduce in HDL2b with increased of TC. The distribution of HDL subclasses have shown abnormality characterized by the lower HDL2b (324.2 mg/L) contents and the higher preβ1-HDL (90.4 mg/L) contents for desirable TC Chinese subjects. Among 176 desirable TC subjects, 58.6% subjects with triglyceride (TG) < 2.26 mmol/L, 61.2% subjects with HDL-C ≥1.03 mmol/L and 88.6% subjects with low density lipoprotein cholesterol(LDL-C) < 3.34 mmol/L, and the profile of HDL subclasses distribution for above these subjects was reasonable.

Conclusions

The particles size of HDL subclasses shifted towards smaller with increased TC levels. The TC was liner with HDL2b contents and those can be reduced 17 mg/L for 0.5 mmol/L increment in TC levels. The HDL subclasses distribution phenotype was not expectation for Chinese Population with desirable TC levels. Thus, from the HDL subclasses distribution point, when assessing the coronary heart disease(CHD) risk not only rely on the TC levels, but also the concentrations of TG, HDL-C and LDL-C must considered in case the potential risk for desirable TC subjects with other plasma lipids metabolism disorders.
The protective effect of Malva sylvestris on rat kidney damaged by vanadium
Authors: Marouane Wafa , Soussi Ahlem , Murat Jean-Claude , Bezzine Sofiane , El Feki Abdelfattah
Published: April 2011

Background

The protective effect of the common mallow (Malva sylvestris) decoction on renal damages in rats induced by ammonium metavanadate poisoning was evaluated. On the one hand, vanadium toxicity is associated to the production of reactive oxygen species, causing a lipid peroxidation and an alteration in the enzymatic antioxidant defence. On the other hand, many medicinal plants are known to possess antioxidant and radical scavenging properties, thanks to the presence of flavonoids. These properties were confirmed in Malva sylvestris by two separate methods; namely, the Diphenyl-2-picrylhydrazyl assay and the Nitroblue Tetrazolium reduction assay.

Results

In 80 rats exposed to ammonium metavanadate (0.24 mmol/kg body weight in drinking water) for 90 days, lipid peroxidation levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in kidney. A significant increase in the formation of free radicals and antioxidant enzyme activities was noticed. In addition, a histological examination of kidney revealed a structural deterioration of the renal cortical capsules and a shrinking of the Bowman space. In animals intoxicated by metavanadate but also given a Malva sylvestris decoction (0.2 g dry mallow/kg body weight), no such pathologic features were observed: lipid peroxidation levels, antioxidant enzyme activities and histological features appeared normal as compared to control rats.

Conclusion

Malva sylvestris is proved to have a high antioxidative potential thanks to its richness in phenolic compounds.
Differentiation associated regulation of microRNA expression in vivo in human CD8+ T cell subsets
Authors: Salaun Bruno , Yamamoto Takuya , Badran Bassam , Tsunetsugu-Yokota Yasuko , Roux Antoine , Baitsch Lukas , Rouas Redouane , Fayyad-Kazan Hussein , Baumgaertner Petra , Devevre Estelle , Ramesh Anirudh , Braun Marion , Speiser Daniel , Autran Brigitte , Martiat Philippe , Appay Victor , Romero Pedro
Published: April 2011

Background

The differentiation of CD8+T lymphocytes following priming of naïve cells is central in the establishment of the adaptive immune response. Yet, the molecular events underlying this process are not fully understood. MicroRNAs have been recently shown to play a key role in the regulation of haematopoiesis in mouse, but their implication in peripheral lymphocyte differentiation in humans remains largely unknown.

Methods

In order to explore the potential implication of microRNAs in CD8+T cell differentiation in humans, microRNA expression profiles were analysed using microarrays and quantitative PCR in several human CD8+T cell subsets defining the major steps of the T cell differentiation pathway.

Results

We found expression of a limited set of microRNAs, including the miR-17~92 cluster. Moreover, we reveal the existence of differentiation-associated regulation of specific microRNAs. When compared to naive cells, miR-21 and miR-155 were indeed found upregulated upon differentiation to effector cells, while expression of the miR-17~92 cluster tended to concomitantly decrease.

Conclusions

This study establishes for the first time in a large panel of individuals the existence of differentiation associated regulation of microRNA expression in human CD8+T lymphocytesin vivo, which is likely to impact on specific cellular functions.
Pro-apoptotic activity of α-bisabolol in preclinical models of primary human acute leukemia cells
Authors: Cavalieri Elisabetta , Rigo Antonella , Bonifacio Massimiliano , de Prati Alessandra Carcereri , Guardalben Emanuele , Bergamini Christian , Fato Romana , Pizzolo Giovanni , Suzuki Hisanori , Vinante Fabrizio
Published: April 2011

Background

We previously demonstrated that the plant-derived agent α-bisabolol enters cells via lipid rafts, binds to the pro-apoptotic Bcl-2 family protein BID, and may induce apoptosis. Here we studied the activity of α-bisabolol in acute leukemia cells.

Methods

We tested ex vivo blasts from 42 acute leukemias (14 Philadelphia-negative and 14 Philadelphia-positive B acute lymphoid leukemias, Ph-/Ph+B-ALL; 14 acute myeloid leukemias, AML) for their sensitivity to α-bisabolol in 24-hour dose-response assays. Concentrations and time were chosen based on CD34+, CD33+my and normal peripheral blood cell sensitivity to increasing α-bisabolol concentrations for up to 120 hours.

Results

A clustering analysis of the sensitivity over 24 hours identified three clusters. Cluster 1 (14 ± 5 μM α-bisabolol IC50) included mainly Ph-B-ALL cells. AML cells were split into cluster 2 and 3 (45 ± 7 and 65 ± 5 μM IC50). Ph+B-ALL cells were scattered, but mainly grouped into cluster 2. All leukemias, including 3 imatinib-resistant cases, were eventually responsive, but a subset of B-ALL cells was fairly sensitive to low α-bisabolol concentrations. α-bisabolol acted as a pro-apoptotic agent via a direct damage to mitochondrial integrity, which was responsible for the decrease in NADH-supported state 3 respiration and the disruption of the mitochondrial membrane potential.

Conclusion

Our study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.
Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models
Authors: Song Hua , Geng Hongquan , Ruan Jing , Wang Kan , Bao Chenchen , Wang Juan , Peng Xia , Zhang Xueqing , Cui Daxiang
Published: April 2011

Docetaxel (DTX) is a very important member of taxoid family. Despite several alternative delivery systems reported recently, DTX formulated by Polysorbate 80 and alcohol (Taxotere®) is still the most frequent administration in clinical practice. In this study, we incorporated DTX into Polysorbate 80/Phospholipid mixed micelles and compared its structural characteristics, pharmacokinetics, biodistribution, and blood compatibility with its conventional counterparts. Results showed that the mixed micelles loaded DTX possessed a mean size of approximately 13 nm with narrow size distribution and a rod-like micelle shape. In the pharmacokinetics assessment, there was no significant difference between the two preparations (P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process. However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver. The blood compatibility assessment study revealed that the mixed micelles were safe for intravenous injection. In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.
Study on the visible-light-induced photokilling effect of nitrogen-doped TiO2 nanoparticles on cancer cells
Authors: Li Zheng , Mi Lan , Wang Pei-Nan , Chen Ji-Yao
Published: April 2011

Nitrogen-doped TiO2 (N-TiO2) nanoparticles were prepared by calcining the anatase TiO2 nanoparticles under ammonia atmosphere. The N-TiO2 showed higher absorbance in the visible region than the pure TiO2. The cytotoxicity and visible-light-induced phototoxicity of the pure- and N-TiO2 were examined for three types of cancer cell lines. No significant cytotoxicity was detected. However, the visible-light-induced photokilling effects on cells were observed. The survival fraction of the cells decreased with the increased incubation concentration of the nanoparticles. The cancer cells incubated with N-TiO2 were killed more effectively than that with the pure TiO2. The reactive oxygen species was found to play an important role on the photokilling effect for cells. Furthermore, the intracellular distributions of N-TiO2 nanoparticles were examined by laser scanning confocal microscopy. The co-localization of N-TiO2 nanoparticles with nuclei or Golgi complexes was observed. The aberrant nuclear morphologies such as micronuclei were detected after the N-TiO2-treated cells were irradiated by the visible light.
Structural and electronic properties of Eu- and Pd-doped ZnO
Authors: Assadi Mohammad Hussein Naseef , Zhang Yuebin , Zheng Rong-Kun , Ringer Simon Peter , Li Sean
Published: April 2011

Doping ZnO with rare earth and 4d transition elements is a popular technique to manipulate the optical properties of ZnO systems. These systems may also possess intrinsic ferromagnetism due to their magnetic moment borne on 4f and 4d electrons. In this work, the structural, electronic, and magnetic properties of Eu- and Pd-doped ZnO were investigated by the ab initio density functional theory methods based on generalized gradient approximation. The relative stability of incorporation sites of the doped elements in the ZnO host lattice was studied. The ground state properties, equilibrium bond lengths, and band structures of both the ZnO:Eu and ZnO:Pd systems were also investigated. The total and partial densities of electron states were also determined for both systems. It was found that in the ZnO:Eu system, ambient ferromagnetism can be induced by introducing Zn interstitial which leads to a carrier-mediated ferromagnetism while the ZnO:Pd system possesses no ferromagnetism.

PACS 31.15.E-, 75.50.Pp, 75.30Hx