bluuebunny/crossref_metadata_2025 huggingface dataset:
Polysaccharide of Cordyceps sinensis Enhances Cisplatin Cytotoxicity in Non–Small Cell Lung Cancer H157 Cell Line
Authors: Ji Ning-Fei , Yao Le-Sheng , Li Yan , He Wei , Yi Kai-Sheng , Huang Mao
Published: March 2011

Background and objective: The extracts of Cordyceps sinensis (Berk) Sacc (CS) have been used as a traditional medicine for centuries. However, few studies have examined the adjuvant action of CS in the treatment of non–small cell lung cancer (NSCLC). So the aim of this study is to investigate the adjuvant role of CS in the treatment of NSCLC. Methodology: The effects of the combination treatment of the polysaccharide-rich fraction of CS and cisplatin on H157 NSCLC cells were investigated through MTT assay for cell viability, lactate dehydrogenase and fluorescein diacetate and propidium iodide assay for cytotoxicity, and with flow cytometric analysis for apoptosis. The expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in H157 cells were detected by immunohistochemistry. Results: Compared with the cells treated with cisplatin alone, cell viability was significantly decreased and the expression levels of VEGF and bFGF protein were significantly reduced in the cells treated with a combination of CS and cisplatin. Conclusion: The current study indicates that the polysaccharide of CS inhibits tumor growth in NSCLC and that CS may be a potential adjuvant chemotherapeutic agent in NSCLC therapy.
Exercise Preconditioning Provides Long-Term Protection Against Early Chronic Doxorubicin Cardiotoxicity
Authors: Hydock David S. , Lien Chia-Ying , Jensen Brock T. , Schneider Carole M. , Hayward Reid
Published: March 2011

Acute doxorubicin (DOX) cardiotoxicity can be attenuated by exercise preconditioning, but little is known of whether this cardioprotection continues beyond 10 days post-DOX administration. The purpose of this study was to determine the effects of exercise preconditioning on early chronic DOX-induced cardiotoxicity. Male rats were randomly assigned to sedentary, treadmill, or wheel running groups. Treadmill and wheel running animals participated in a progressive treadmill training protocol or voluntary wheel running, respectively, for 10 weeks. Following the intervention, animals were further randomized to receive either DOX (sedentary + DOX, treadmill + DOX, wheel running + DOX) or saline (sedentary + saline, treadmill + saline, wheel running + saline). All animals then remained sedentary for 4 weeks. A 22% reduction in fractional shortening was observed in left ventricles from previously sedentary animals receiving DOX when compared with sedentary + saline. This degree of decline was not observed in treadmill + DOX and wheel running + DOX. Sedentary + DOX possessed significantly depressed mitral and aortic valve blood flow velocities when compared with sedentary + saline, but these decrements were not observed in treadmill + DOX and wheel running + DOX. Ex vivo analysis revealed that left ventricular developed pressure and maximal rate of pressure development were significantly lower in sedentary + DOX when compared to sedentary + saline. Treadmill and wheel running prior to DOX treatment protected against these decrements. Exercise cardioprotection was associated with preserved myosin heavy chain but not sarcoendoplasmic reticulum Ca2+ ATPase 2a expression. In conclusion, 10 weeks of prior exercise protected against early chronic DOX cardiotoxicity suggesting that training status may be a determining factor in the degree of late-onset cardiotoxicity experienced by cancer patients undergoing treatment with DOX.
Concurrent Sulforaphane and Eugenol Induces Differential Effects on Human Cervical Cancer Cells
Authors: Hussain Arif , Priyani Anita , Sadrieh Lida , Brahmbhatt Kruti , Ahmed Musthaq , Sharma Chhavi
Published: March 2011

Background. The concept of combination of chemoprevention holds great potential for cancer management as lower, clinically tolerable doses of individual agents could be achieved through therapeutic synergy. However, elucidation of their possible interactions—additive, synergistic, or antagonistic—must be thoroughly studied before considering for clinical use. Methods. To evaluate the effect of combination treatment of sulforaphane (SFN) and eugenol on HeLa cells, the authors performed cell viability assay, apoptosis assay, and reverse transcription polymerase chain reaction for gene expression analysis. Calculations of combination effects were expressed as a combination index (CI) with CI < 1, CI = 1, or CI > 1 representing synergism, additivity, or antagonism, respectively. Results. Simultaneous treatment with variable dose combinations of SFN and eugenol resulted in differential effects with an antagonistic effect at lower and synergistic at higher sub-lethal doses as reflected in cell cytotoxicity and apoptosis induction. Importantly, gemcitabine used in conjunction with the low- and high-dose combinations showed no significant cell death at lower doses suggesting that cell cytotoxicity is proportional to gemcitabine alone, whereas at higher sublethal doses of SFN and eugenol, it was found to act in a synergistic manner with gemcitabine. Furthermore, SFN and eugenol combinations at synergistic dose significantly downregulated the expression of Bcl-2, COX-2 and IL-β but not the antagonistic combinations. Conclusion. This study clearly indicates that 2 (or more) chemopreventive agents can act antagonistically or synergistically necessitating elucidation of possible mechanistic interactions for favorable and reliable outcomes of dietary components in the field of cancer prevention.
The efficacy and safety of fasciectomy and fasciotomy for Dupuytren’s contracture in European patients: a structured review of published studies
Authors: Crean S. M. , Gerber R. A. , Le Graverand M. P.Hellio , Boyd D. M. , Cappelleri J. C.
Published: March 2011

A structured review of published papers was done to assess the efficacy and safety of fasciectomy and fasciotomy in European patients with Dupuytren’s contracture. The outcomes varied across 48 studies. For fasciectomy, outcomes and results were as follows: the proportions of patients with a 100% correction in contracture angle ranged from 61 to 97%, the mean improvement in contracture angle ranged from 58 to 79%, and cases judged excellent/good ranged from 63 to 90%. Fasciotomy had similar outcomes, with a mean improvement in contracture angle ranging from 46 to 88%. Immediate failures upon recovery were reported for both procedures. The average recurrence rates were 39% after a fasciectomy and 62% after a fasciotomy at a median time of about 4 years. Overall, about 20% of fasciectomy and fasciotomy patients experienced an adverse event. In summary, postoperative outcomes were successful, but surgical complications were common and recurrence of a contracture was likely within a few years.
Deactivation of the lipopolysaccharide antagonist eritoran (E5564) by high-density lipoprotein-associated apolipoproteins
Authors: Fleischer Jacklyn G , Rossignol Dan , Francis Gordon A , Chan Teddy , Lynn Melvyn , Wasan Kishor M
Published: March 2011

Lipid A, the active moiety of LPS, exerts its effects through interaction with TLR4, triggering a signalling cascade that results in the release of pro-inflammatory cytokines. Eritoran is a lipid A analogue that competes with LPS for binding to TLR4; however, after intravenous administration, it undergoes a time-dependent deactivation as a consequence of binding to high-density lipoproteins (HDLs). The site of eritoran association with HDL remains unknown. Therefore the aim of this study was to determine if HDL-associated apolipoproteins A1, A2, serum amyloid A (SAA) and C1, inhibit the ability of eritoran to block LPS-induced TNF-α release from whole blood. Eritoran activity after LPS stimulation in human whole blood was assessed in the presence of reconstituted HDL (rHDL) containing different apos. In rHDL, the major apolipoproteins in both the healthy and septic state, A1 and SAA, caused a significant reduction in eritoran antagonistic activity and had a greater effect than minor apolipoproteins A2 and C1. Apolipoproteins associated with HDL are likely to facilitate eritoran deactivation. Apolipoproteins A1 and SAA should be of particular focus as they are the major apos found on HDL in both the healthy and septic state. Further evaluation of the physical association between apolipoproteins and eritoran should be explored.
Role of inflammation in bladder function and interstitial cystitis
Authors: Grover Sonal , Srivastava Abhishek , Lee Richard , Tewari Ashutosh K. , Te Alexis E.
Published: March 2011

Cystitis, or inflammation of the bladder, has a direct effect on bladder function. Interstitial cystitis is a syndrome characterized by urinary bladder pain and irritative symptoms of more than 6 months duration. It commonly occurs in young to middle-aged women with no known cause and in fact represents a diagnosis of exclusion. Many factors have been suggested, including chronic or subclinical infection, autoimmunity and genetic susceptibility, which could be responsible for initiating the inflammatory response. However, a central role of inflammation has been confirmed in the pathogenesis of interstitial cystitis. Patients with interstitial cystitis are usually managed with multimodal therapy to break the vicious cycle of chronic inflammation at every step. Patients who develop irreversible pathologies such as fibrosis are managed surgically, which is usually reserved for refractory cases.
Erectile preservation following radical prostatectomy
Authors: Segal Robert , Burnett Arthur L.
Published: March 2011

Prostate cancer is the most common cancer among men, representing approximately 25% of all new cancer diagnoses in the USA. For clinically localized prostate cancer, the gold standard for therapy remains radical prostatectomy. One of the main adverse effects of this procedure is erectile dysfunction, which can have a significant impact on the patient’s quality of life. There are several mechanisms of erectile dysfunction postprostatectomy, including arteriogenic, venogenic and neurogenic types, as well as the potentially heightened risk of postprostatectomy patients to develop Peyronie’s disease. The purpose of this review is to explain the various treatment options available, including phosphodiesterase type 5 inhibitors, intracavernosal injections, intraurethral alprostadil suppositories, vacuum erection devices, and penile prostheses. The role of these therapies in an erectile-dysfunction-treatment function, as well as in penile rehabilitation, will be discussed. Finally, a review of research on novel therapies will also be presented. A comprehensive literature review was performed using the PubMed database. Articles were chosen based on topical relevance and assessed for methodology and major findings. There are data to support the use of each of the therapeutic options in both treatment and rehabilitative roles. More study is needed, however, specifically in regard to penile rehabilitation, to confirm its benefits, as well as to determine optimal rehabilitation protocols.
Evidence of Sustained Vertebral and Nonvertebral Antifracture Efficacy with Ibandronate Therapy: A Systematic Review
Authors: Adami Silvano , Idolazzi Luca , Rossini Maurizio
Published: March 2011

Background:

The antifracture efficacy of ibandronate at vertebral and nonvertebral sites was assessed.

Methods:

A literature review of randomized phase III clinical trials, meta-analyses or observational studies that reported fracture endpoints or surrogate markers, and compared ibandronate with placebo or an active comparator.

Results:

In a phase III study, 2.5 mg daily oral ibandronate reduced the incidence of new vertebral fractures versus placebo and the relative risk reduction (RRR) was sustained over 3 years (62%; p = 0.0001). In two bridging studies, oral ibandronate 150 mg once monthly and 3 mg quarterly intravenous (i.v.) were superior to oral 2.5 mg daily in producing bone mineral density (BMD) increases at all sites over 2 years ( p < 0.05). These improvements were sustained over 5 years. In meta-analyses of pivotal ibandronate studies, doses equivalent to annual cumulative exposure (ACE) ≥ 10.8 mg (including 150 mg once monthly and 3 mg quarterly i.v.) significantly reduced the incidence of nonvertebral fractures versus placebo or ACE 5.5 mg (2.5 mg daily) (RRR 29.9% and 38%, respectively; p < 0.05). Therefore, prevention of nonvertebral fractures was found in all patients with the commercially available highest doses, and not only in high-risk patients as observed in randomized clinical trials with lower doses. Finally, a 12-month, observational study of claims databases reported comparable rates of nonvertebral fractures and a statistically significantly lower rate of vertebral fractures ( p < 0.01) with ibandronate versus weekly bisphosphonates.

Conclusion:

A large body of evidence suggests that ibandronate has sustained vertebral and nonvertebral antifracture efficacy in women with postmenopausal osteoporosis.
Latest advances on interventions that may prevent, delay or ameliorate dementia
Authors: Wilson Danielle , Peters Ruth , Ritchie Karen , Ritchie Craig W.
Published: March 2011

Objectives: In this paper we aim to: (1) identify and review midlife risk factors that may contribute to the development of dementia and that may be amenable to intervention; (2) review advances made in our understanding of the most common cause of dementia, Alzheimer’s disease (AD), where current pharmacological studies have aimed to modify the disease course; and (3) explore other interventions that may slow cognitive decline in those with AD.

Methods: A review of the literature was conducted to look for interventions that may modify the risk of incident dementia or that may modify symptom progression in those with diagnosed dementia.

Results: (1) Midlife risks identified as amenable to intervention include blood pressure, diabetes, elevated cholesterol, poor psychosocial and lifestyle factors. (2) The leading drugs in development can be grouped by their principal target: anti-amyloid, anti-tau and mitochondrial stability. However to date, there have been no successes in late stage Phase III trials of putative disease-modifying drugs for AD. (3) Once the diagnosis of dementia has been made there is little that can slow the rate of decline. Possible exceptions include the use of exercise and antihypertensive medication with some nootropic medication showing promise in small trials.

Conclusion: (1) It is clear that there are several risk factors in midlife that may lead to a greater likelihood of developing dementia. However, there is no simple intervention to modify these risks. It seems sensible to conclude from the data that avoiding high blood pressure, controlling cholesterol and diabetes as well as maintaining a healthy diet and lifestyle may lower the risk of developing dementia. (2) The need for better outcome measures in clinical trials is evident and may, in part, explain the numerous failures in late-stage clinical trials of disease-modifying drugs. Improved diagnostic test batteries to reduce population heterogeneity in early intervention studies will be required for robust clinical trials in the future. (3) Current research indicates that there is little that can delay decline; however, future trials may wish to focus on nootropics.
AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance
Authors: Avvisati Giuseppe , Lo-Coco Francesco , Paoloni Francesca Paola , Petti Maria Concetta , Diverio Daniela , Vignetti Marco , Latagliata Roberto , Specchia Giorgina , Baccarani Michele , Di Bona Eros , Fioritoni Giuseppe , Marmont Filippo , Rambaldi Alessandro , Di Raimondo Francesco , Kropp Maria Grazia , Pizzolo Giovanni , Pogliani Enrico M. , Rossi Giuseppe , Cantore Nicola , Nobile Francesco , Gabbas Attilio , Ferrara Felicetto , Fazi Paola , Amadori Sergio , Mandelli Franco ,   for the GIMEMA, AIEOP, and EORTC Cooperative Groups
Published: March 2011

All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed acute promyelocytic leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction–negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction–negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.
Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile
Authors: Hoorens Prisca R , Rinaldi Manuela , Li Robert W , Goddeeris Bruno , Claerebout Edwin , Vercruysse Jozef , Geldhof Peter
Published: March 2011

Background

Mucins are large glycoproteins implicated in protection of all mucosal surfaces. In humans and rodents, the mucin gene family has been well described and previous studies have investigated the distribution and function of mucins in the gastrointestinal (GI) tract. In contrast, little data is available on the mucin gene family in polygastric species, such as cattle. The aim of the current study was to identify all members of the bovine mucin family by genome mining and subsequently investigate the transcription pattern of these mucins in the GI tract.

Results

Nine bovine membrane-associated mucins (MUC1, MUC3A, MUC4, MUC12, MUC13, MUC15, MUC16, MUC20 and MUC21) and six secreted mucins (MUC2, MUC5AC, MUC5B, MUC6, MUC7 and MUC19) were identified in the bovine genome. No homologues could be identified for MUC3B, MUC8 and MUC17. In general, domain architecture of the membrane-associated mucins was found to be similar between humans and cattle, while the protein architecture of the gel-forming mucins appeared to be less conserved. Further analysis of the genomic organization indicated that the previously reported bovine submaxillary mucin (BSM) may be part of a larger gene encoding for MUC19. Analysis of the transcription profile showed that the secreted mucins were transcribed from the abomasum onwards, whereas the membrane associated mucins MUC1 and MUC20 were transcribed throughout the whole GI tract. In contrast to humans, MUC5B transcript was found in both the small and large intestine, but was absent in oesophageal tissue.

Conclusions

This study provides the first characterization of the mucin gene family in cattle and their transcriptional regulation in the GI tract. The data presented in this paper will allow further studies of these proteins in the physiology of the GI tract in ruminants and their interactions with pathogens.
Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Piceaspp.)
Authors: Keeling Christopher I , Weisshaar Sabrina , Ralph Steven G , Jancsik Sharon , Hamberger Britta , Dullat Harpreet K , Bohlmann Jörg
Published: March 2011

Background

In conifers, terpene synthases (TPSs) of the gymnosperm-specific TPS-d subfamily form a diverse array of mono-, sesqui-, and diterpenoid compounds, which are components of the oleoresin secretions and volatile emissions. These compounds contribute to defence against herbivores and pathogens and perhaps also protect against abiotic stress.

Results

The availability of extensive transcriptome resources in the form of expressed sequence tags (ESTs) and full-length cDNAs in several spruce (Picea) species allowed us to estimate that a conifer genome contains at least 69 unique and transcriptionally active TPS genes. This number is comparable to the number of TPSs found in any of the sequenced and well-annotated angiosperm genomes. We functionally characterized a total of 21 spruce TPSs: 12 from Sitka spruce (P. sitchensis), 5 from white spruce (P. glauca), and 4 from hybrid white spruce (P. glauca × P. engelmannii), which included 15 monoterpene synthases, 4 sesquiterpene synthases, and 2 diterpene synthases.

Conclusions

The functional diversity of these characterized TPSs parallels the diversity of terpenoids found in the oleoresin and volatile emissions of Sitka spruce and provides a context for understanding this chemical diversity at the molecular and mechanistic levels. The comparative characterization of Sitka spruce and Norway spruce diterpene synthases revealed the natural occurrence of TPS sequence variants between closely related spruce species, confirming a previous prediction from site-directed mutagenesis and modelling.
Proteomic analysis of chicken embryonic trachea and kidney tissues after infection in ovo by avian infectious bronchitis coronavirus
Authors: Cao Zhongzan , Han Zongxi , Shao Yuhao , Geng Heyuan , Kong Xiangang , Liu Shengwang
Published: March 2011

Background

Avian infectious bronchitis (IB) is one of the most serious diseases of economic importance in chickens; it is caused by the avian infectious coronavirus (IBV). Information remains limited about the comparative protein expression profiles of chicken embryonic tissues in response to IBV infection in ovo. In this study, we analyzed the changes of protein expression in trachea and kidney tissues from chicken embryos, following IBV infection in ovo, using two-dimensional gel electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS).

Results

17 differentially expressed proteins from tracheal tissues and 19 differentially expressed proteins from kidney tissues were identified. These proteins mostly related to the cytoskeleton, binding of calcium ions, the stress response, anti-oxidative, and macromolecular metabolism. Some of these altered proteins were confirmed further at the mRNA level using real-time RT-PCR. Moreover, western blotting analysis further confirmed the changes of annexin A5 and HSPB1 during IBV infection.

Conclusions

To the best of our knowledge, we have performed the first analysis of the proteomic changes in chicken embryonic trachea and kidney tissues during IBV infection in ovo. The data obtained should facilitate a better understanding of the pathogenesis of IBV infection.
Hepatitis B virus in Pakistan: A systematic review of prevalence, risk factors, awareness status and genotypes
Authors: Ali Muhammad , Idrees Muhammad , Ali Liaqat , Hussain Abrar , Ur Rehman Irshad , Saleem Sana , Afzal Samia , Butt Sadia
Published: March 2011

In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%), military recruits (4.276% ± 1.646%), healthcare persons (3.25% ± 1.202%), pregnant women (5.872% ± 4.984), prisoners (5.75% ± 0.212%), surgical patients (7.397% ± 2.012%), patients with cirrhosis (28.87% ± 11.90%), patients with HCC (22% ± 2.645%), patients with hepatitis (15.896% ± 14.824%), patients with liver diseases (27.54% ± 6.385%), multiple transfused patients (6.223% ± 2.121%), opthalmic patients (3.89% ± 1.004%) and users of injectable drugs (14.95% ± 10.536%). Genotype D (63.71%) is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%.
Single-dose liposomal amphotericin B (AmBisome®) for the treatment of Visceral Leishmaniasis in East Africa: study protocol for a randomized controlled trial
Authors: Edwards Tansy , Omollo Raymond , Khalil Eltahir AG , Yifru Sisay , Musa Brima , Musa Ahmed , Wasunna Monique , Smith Peter G , Royce Catherine , Ellis Sally , Balasegaram Manica , Hailu Asrat
Published: March 2011

Background

AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified.

Methods/Design

An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®.

Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose.

Discussion

An effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies.

Trial Registration

ClinicalTrials.gov NCT00832208
Recruitment of high risk women for HIV prevention trials: baseline HIV prevalence and sexual behavior in the CAPRISA 004 tenofovir gel trial
Authors: Karim Quarraisha Abdool , Kharsany Ayesha BM , Frohlich Janet A , Baxter Cheryl , Yende Nonhlanhla , Mansoor Leila E , Mlisana Koleka P , Maarschalk Silvia , Arulappan Natasha , Grobler Anneke , Sibeko Sengeziwe , Omar Zaheen , Gengiah Tanuja N , Mlotshwa Mukelisiwe , Samsunder Natasha , Abdool Karim Salim S
Published: March 2011

Background

Young women in sub-Saharan Africa bear a disproportionate burden of HIV infection compared to men but have limited options to reduce their HIV risk. Microbicides could fill an important HIV prevention gap for sexually active women who are unable to successfully negotiate mutual monogamy or condom use.

Purpose

This paper describes the baseline sample characteristics in the CAPRISA 004 trial which assessed the safety and effectiveness of the vaginal microbicide, 1% tenofovir gel for HIV prevention in South Africa.

Methods

This analysis assessed the baseline demographic, clinical and sexual behavior data of women screened and enrolled into the trial. The characteristics were summarized using descriptive summary measures; expressed as means and percent for categorical variables.

Results

HIV prevalence at screening was 25.8% [95% Confidence Interval (CI):23.9-27.7). Of the 889 eligibly enrolled women who contributed follow-up data, rural participants recruited from a family planning (FP) clinic were younger, more likely to be living apart from their regular partner, reported lower coital frequency, had lower condom use (p < 0.001). In contrast, urban participants recruited from a sexually transmitted disease (STD) clinic reported higher numbers of lifetime sexual partners, new partners in the last 30 days and receiving money in exchange for sex (p < 0.001).

Conclusion

The populations selected provide suitable diverse target groups for HIV prevention intervention studies.

Trial registration

ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT00441298
The faunal drugstore: Animal-based remedies used in traditional medicines in Latin America
Authors: Alves Rômulo RN , Alves Humberto N
Published: March 2011

Zootherapy is the treatment of human ailments with remedies made from animals and their products. Despite its prevalence in traditional medical practices worldwide, research on this phenomenon has often been neglected in comparison to medicinal plant research. This review discusses some related aspects of the use of animal-based remedies in Latin America, identifies those species used as folk remedies, and discusses the implications of zootherapy for public health and biological conservation. The review of literature revealed that at least 584 animal species, distributed in 13 taxonomic categories, have been used in traditional medicine in region. The number of medicinal species catalogued was quite expansive and demonstrates the importance of zootherapy as an alternative mode of therapy in Latin America. Nevertheless, this number is certainly underestimated since the number of studies on the theme are very limited. Animals provide the raw materials for remedies prescribed clinically and are also used in the form of amulets and charms in magic-religious rituals and ceremonies. Zootherapeutic resources were used to treat different diseases. The medicinal fauna is largely based on wild animals, including some endangered species. Besides being influenced by cultural aspects, the relations between humans and biodiversity in the form of zootherapeutic practices are conditioned by the social and economic relations between humans themselves. Further ethnopharmacological studies are necessary to increase our understanding of the links between traditional uses of faunistic resources and conservation biology, public health policies, sustainable management of natural resources and bio-prospecting.
Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse
Authors: Takamura Ayumi , Okamoto Yasuhide , Kawarabayashi Takeshi , Yokoseki Tatsuki , Shibata Masao , Mouri Akihiro , Nabeshima Toshitaka , Sun Hui , Abe Koji , Urisu Tsuneo , Yamamoto Naoki , Shoji Mikio , Yanagisawa Katsuhiko , Michikawa Makoto , Matsubara Etsuro
Published: March 2011

Background

Several lines of evidence indicate that memory loss represents a synaptic failure caused by soluble amyloid β (Aβ) oligomers. However, the pathological relevance of Aβ oligomers (AβOs) as the trigger of synaptic or neuronal degeneration, and the possible mechanism underlying the neurotoxic action of endogenous AβOs remain to be determined.

Results

To specifically target toxic AβOs in vivo, monoclonal antibodies (1A9 and 2C3) specific to them were generated using a novel design method. 1A9 and 2C3 specifically recognize soluble AβOs larger than 35-mers and pentamers on Blue native polyacrylamide gel electrophoresis, respectively. Biophysical and structural analysis by atomic force microscopy (AFM) revealed that neurotoxic 1A9 and 2C3 oligomeric conformers displayed non-fibrilar, relatively spherical structure. Of note, such AβOs were taken up by neuroblastoma (SH-SY5Y) cell, resulted in neuronal death. In humans, immunohistochemical analysis employing 1A9 or 2C3 revealed that 1A9 and 2C3 stain intraneuronal granules accumulated in the perikaryon of pyramidal neurons and some diffuse plaques. Fluoro Jade-B binding assay also revealed 1A9- or 2C3-stained neurons, indicating their impending degeneration. In a long-term low-dose prophylactic trial using active 1A9 or 2C3 antibody, we found that passive immunization protected a mouse model of Alzheimer's disease (AD) from memory deficits, synaptic degeneration, promotion of intraneuronal AβOs, and neuronal degeneration. Because the primary antitoxic action of 1A9 and 2C3 occurs outside neurons, our results suggest that extracellular AβOs initiate the AD toxic process and intraneuronal AβOs may worsen neuronal degeneration and memory loss.

Conclusion

Now, we have evidence that HMW-AβOs are among the earliest manifestation of the AD toxic process in mice and humans. We are certain that our studies move us closer to our goal of finding a therapeutic target and/or confirming the relevance of our therapeutic strategy.
Genotype networks, innovation, and robustness in sulfur metabolism
Authors: Matias Rodrigues João F , Wagner Andreas
Published: March 2011

Background

A metabolism is a complex network of chemical reactions. This network synthesizes multiple small precursor molecules of biomass from chemicals that occur in the environment. The metabolic network of any one organism is encoded by a metabolic genotype, defined as the set of enzyme-coding genes whose products catalyze the network's reactions. Each metabolic genotype has a metabolic phenotype. We define this metabolic phenotype as the spectrum of different sources of a chemical element that a metabolism can use to synthesize biomass. We here focus on the element sulfur. We study properties of the space of all possible metabolic genotypes in sulfur metabolism by analyzing random metabolic genotypes that are viable on different numbers of sulfur sources.

Results

We show that metabolic genotypes with the same phenotype form large connected genotype networks - networks of metabolic networks - that extend far through metabolic genotype space. How far they reach through this space depends linearly on the number of super-essential reactions. A super-essential reaction is an essential reaction that occurs in all networks viable in a given environment. Metabolic networks can differ in how robust their phenotype is to the removal of individual reactions. We find that this robustness depends on metabolic network size, and on other variables, such as the size of minimal metabolic networks whose reactions are all essential in a specific environment. We show that different neighborhoods of any genotype network harbor very different novel phenotypes, metabolic innovations that can sustain life on novel sulfur sources. We also analyze the ability of evolving populations of metabolic networks to explore novel metabolic phenotypes. This ability is facilitated by the existence of genotype networks, because different neighborhoods of these networks contain very different novel phenotypes.

Conclusions

We show that the space of metabolic genotypes involved in sulfur metabolism is organized similarly to that of carbon metabolism. We demonstrate that the maximum genotype distance and robustness of metabolic networks can be explained by the number of superessential reactions and by the sizes of minimal metabolic networks viable in an environment. In contrast to the genotype space of macromolecules, where phenotypic robustness may facilitate phenotypic innovation, we show that here the ability to access novel phenotypes does not monotonically increase with robustness.
Six rapid assessments of alcohol and other substance use in populations displaced by conflict
Authors: Ezard Nadine , Oppenheimer Edna , Burton Ann , Schilperoord Marian , Macdonald David , Adelekan Moruf , Sakarati Abandokoth , van Ommeren Mark
Published: March 2011

Background

Substance use among populations displaced by conflict is a neglected area of public health. Alcohol, khat, benzodiazepine, opiate, and other substance use have been documented among a range of displaced populations, with wide-reaching health and social impacts. Changing agendas in humanitarian response-including increased prominence of mental health and chronic illness-have so far failed to be translated into meaningful interventions for substance use.

Methods

Studies were conducted from 2006 to 2008 in six different settings of protracted displacement, three in Africa (Kenya, Liberia, northern Uganda) and three in Asia (Iran, Pakistan, and Thailand). We used intervention-oriented qualitative Rapid Assessment and Response methods, adapted from two decades of experience among non-displaced populations. The main sources of data were individual and group interviews conducted with a culturally representative (non-probabilistic) sample of community members and service providers.

Results

Widespread use of alcohol, particularly artisanally-produced alcohol, in Kenya, Liberia, Uganda, and Thailand, and opiates in Iran and Pakistan was believed by participants to be linked to a range of health, social and protection problems, including illness, injury (intentional and unintentional), gender-based violence, risky behaviour for HIV and other sexually transmitted infection and blood-borne virus transmission, as well as detrimental effects to household economy. Displacement experiences, including dispossession, livelihood restriction, hopelessness and uncertain future may make communities particularly vulnerable to substance use and its impact, and changing social norms and networks (including the surrounding population) may result in changed - and potentially more harmful-patterns of use. Limited access to services, including health services, and exclusion from relevant host population programmes, may exacerbate the harmful consequences.

Conclusions

The six studies show the feasibility and value of conducting rapid assessments in displaced populations. One outcome of these studies is the development of a UNHCR/WHO field guide on rapid assessment of alcohol and other substance use among conflict-affected populations. More work is required on gathering population-based epidemiological data, and much more experience is required on delivering effective interventions. Presentation of these findings should contribute to increased awareness, improved response, and more vigorous debate around this important but neglected area.
Time for gender mainstreaming in editorial policies
Authors: Heidari Shirin , Eckert Mirjam J , Kippax Susan , Karim Quarraisha Abdool , Sow Papa Salif , Wainberg Mark A
Published: March 2011

The HIV epidemic has been continuously growing among women, and in some parts of the world, HIV‐infected women outnumber men. Women's greater vulnerability to HIV, both biologically and socially, influences their health risk and health outcome. This disparity between sexes has been established for other diseases, for example, autoimmune diseases, malignancies and cardiovascular diseases. Differences in drug effects and treatment outcomes have also been demonstrated.

Despite proven sex and gender differences, women continue to be underrepresented in clinical trials, and the absence of gender analyses in published literature is striking. There is a growing advocacy for consideration of women in research, in particular in the HIV field, and gender mainstreaming of policies is increasingly called for. However, these efforts have not translated into improved reporting of sex‐disaggregated data and provision of gender analysis in published literature; science editors, as well as publishers, lag behind in this effort.

Instructions for authors issued by journals contain many guidelines for good standards of reporting, and a policy on sex‐disaggregated data and gender analysis should not be amiss here. It is time for editors and publishers to demonstrate leadership in changing the paradigm in the world of scientific publication. We encourage authors, peer reviewers and fellow editors to lend their support by taking necessary measures to substantially improve reporting of gender analysis. Editors' associations could play an essential role in facilitating a transition to improved standard editorial policies.
Establishment of clonal myogenic cell lines from severely affected dystrophic muscles - CDK4 maintains the myogenic population
Authors: Stadler Guido , Chen Jennifer CJ , Wagner Kathryn , Robin Jerome D , Shay Jerry W , Emerson Charles P , Wright Woodring E
Published: March 2011

Background

A hallmark of muscular dystrophies is the replacement of muscle by connective tissue. Muscle biopsies from patients severely affected with facioscapulohumeral muscular dystrophy (FSHD) may contain few myogenic cells. Because the chromosomal contraction at 4q35 linked to FSHD is thought to cause a defect within myogenic cells, it is important to study this particular cell type, rather than the fibroblasts and adipocytes of the endomysial fibrosis, to understand the mechanism leading to myopathy.

Results

We present a protocol to establish clonal myogenic cell lines from even severely dystrophic muscle that has been replaced mostly by fat, using overexpression of CDK4 and the catalytic component of telomerase (human telomerase reverse transcriptase; hTERT), and a subsequent cloning step. hTERT is necessary to compensate for telomere loss during in vitro cultivation, while CDK4 prevents a telomere-independent growth arrest affecting CD56+ myogenic cells, but not their CD56- counterpart, in vitro.

Conclusions

These immortal cell lines are valuable tools to reproducibly study the effect of the FSHD mutation within myoblasts isolated from muscles that have been severely affected by the disease, without the confounding influence of variable amounts of contaminating connective-tissue cells.
Vascular pedicle width in acute lung injury: correlation with intravascular pressures and ability to discriminate fluid status
Authors: Rice Todd W , Ware Lorraine B , Haponik Edward F , Chiles Caroline , Wheeler Arthur P , Bernard Gordon R , Steingrub Jay S , Hite Duncan R , Matthay Michael A , Wright Patrick , Ely Wesley E ,   the NIH NHLBI ARDS Network
Published: March 2011

Introduction

Conservative fluid management in patients with acute lung injury (ALI) increases time alive and free from mechanical ventilation. Vascular pedicle width (VPW) is a non-invasive measurement of intravascular volume status. The VPW was studied in ALI patients to determine the correlation between VPW and intravascular pressure measurements and whether VPW could predict fluid status.

Methods

This retrospective cohort study involved 152 patients with ALI enrolled in the Fluid and Catheter Treatment Trial (FACTT) from five NHLBI ARDS (Acute Respiratory Distress Syndrome) Network sites. VPW and central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) from the first four study days were correlated. The relationships between VPW, positive end-expiratory pressure (PEEP), cumulative fluid balance, and PAOP were also evaluated. Receiver operator characteristic (ROC) curves were used to determine the ability of VPW to detect PAOP <8 mmHg and PAOP ≥18 mm Hg.

Results

A total of 71 and 152 patients provided 118 and 276 paired VPW/PAOP and VPW/CVP measurements, respectively. VPW correlated with PAOP (r = 0.41; P < 0.001) and less well with CVP (r = 0.21; P = 0.001). In linear regression, VPW correlated with PAOP 1.5-fold better than cumulative fluid balance and 2.5-fold better than PEEP. VPW discriminated achievement of PAOP <8 mm Hg (AUC = 0.73; P = 0.04) with VPW ≤67 mm demonstrating 71% sensitivity (95% CI 30 to 95%) and 68% specificity (95% CI 59 to 75%). For discriminating a hydrostatic component of the edema (that is, PAOP ≥18 mm Hg), VPW ≥72 mm demonstrated 61.4% sensitivity (95% CI 47 to 74%) and 61% specificity (49 to 71%) (area under the curve (AUC) 0.69; P = 0.001).

Conclusions

VPW correlates with PAOP better than CVP in patients with ALI. Due to its only moderate sensitivity and specificity, the ability of VPW to discriminate fluid status in patients with acute lung injury is limited and should only be considered when intravascular pressures are unavailable.
Lentiviral vector mediated modification of mesenchymal stem cells & enhanced survival in an in vitro model of ischaemia
Authors: McGinley Lisa , McMahon Jill , Strappe Padraig , Barry Frank , Murphy Mary , O'Toole Daniel , O'Brien Timothy
Published: March 2011

Introduction

A combination of gene and cell therapies has the potential to significantly enhance the therapeutic value of mesenchymal stem cells (MSCs). The development of efficient gene delivery methods is essential if MSCs are to be of benefit using such an approach. Achieving high levels of transgene expression for the required period of time, without adversely affecting cell viability and differentiation capacity, is crucial. In the present study, we investigate lentiviral vector-mediated genetic modification of rat bone-marrow derived MSCs and examine any functional effect of such genetic modification in an in vitro model of ischaemia.

Methods

Transduction efficiency and transgene persistence of second and third generation rHIV-1 based lentiviral vectors were tested using reporter gene constructs. Use of the rHIV-pWPT-EF1-α-GFP-W vector was optimised in terms of dose, toxicity, cell species, and storage. The in vivo condition of ischaemia was modelled in vitro by separation into its associated constituent parts i.e. hypoxia, serum and glucose deprivation, in which the effect of therapeutic gene over-expression on MSC survival was investigated.

Results

The second generation lentiviral vector rHIV-pWPT-EF1-α-GFP-W, was the most efficient and provided the most durable transgene expression of the vectors tested. Transduction with this vector did not adversely affect MSC morphology, viability or differentiation potential, and transgene expression levels were unaffected by cryopreservation of transduced cells. Over-expression of HSP70 resulted in enhanced MSC survival and increased resistance to apoptosis in conditions of hypoxia and ischaemia. MSC differentiation capacity was significantly reduced after oxygen deprivation, but was preserved with HSP70 over-expression.

Conclusions

Collectively, these data validate the use of lentiviral vectors for efficient in vitro gene delivery to MSCs and suggest that lentiviral vector transduction can facilitate sustained therapeutic gene expression, providing an efficient tool for ex vivo MSC modification. Furthermore, lentiviral mediated over-expression of therapeutic genes in MSCs may provide protection in an ischaemic environment and enable MSCs to function in a regenerative manner, in part through maintaining the ability to differentiate. This finding may have considerable significance in improving the efficacy of MSC-based therapies.