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1.
Long Yu Yang Li Kang Zhao Yufei Tang Zhe Cheng Jun Chen Yuan Zang Jianwei Wu Liang Kong Shuai Liu Wei Lei Zixiang Wu 《PloS one》2013,8(4)
Background
Calcium phosphate cement (CPC) can be molded or injected to form a scaffold in situ, which intimately conforms to complex bone defects. Bioactive glass (BG) is known for its unique ability to bond to living bone and promote bone growth. However, it was not until recently that literature was available regarding CPC-BG applied as an injectable graft. In this paper, we reported a novel injectable CPC-BG composite with improved properties caused by the incorporation of BG into CPC.Materials and Methods
The novel injectable bioactive cement was evaluated to determine its composition, microstructure, setting time, injectability, compressive strength and behavior in a simulated body fluid (SBF). The in vitro cellular responses of osteoblasts and in vivo tissue responses after the implantation of CPC-BG in femoral condyle defects of rabbits were also investigated.Results
CPC-BG possessed a retarded setting time and markedly better injectability and mechanical properties than CPC. Moreover, a new Ca-deficient apatite layer was deposited on the composite surface after immersing immersion in SBF for 7 days. CPC-BG samples showed significantly improved degradability and bioactivity compared to CPC in simulated body fluid (SBF). In addition, the degrees of cell attachment, proliferation and differentiation on CPC-BG were higher than those on CPC. Macroscopic evaluation, histological evaluation, and micro-computed tomography (micro-CT) analysis showed that CPC-BG enhanced the efficiency of new bone formation in comparison with CPC.Conclusions
A novel CPC-BG composite has been synthesized with improved properties exhibiting promising prospects for bone regeneration. 相似文献2.
Background
Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth.Materials and Methods
The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant–bone interface was also investigated by push-out tests.Results
The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony defect.Conclusions
Our findings suggested a new bioactive bone cement for prosthetic fixation in total joint replacement. 相似文献3.
Background
Several randomized controlled trials (RCTs) have evaluated the effect of intra-aortic balloon counterpulsation pump(IABP) on the mortality of acute myocardial infarction (AMI).Objectives
To analyze the relevant RCT data on the effect of IABP on mortality and the occurrence of bleeding in AMI.Data Sources
Published RCTs on the treatment of AMI by IABP were retrieved in searches of Medline, EMBASE, Cochrane and other related databases. The last search was conducted on July 20, 2014.Study Eligibility Criteria
Randomized clinical trials comparing IABP to controls as treatment for AMI.Participants
Patients with AMI.Synthesis Methods
The primary endpoint was mortality, and the secondary endpoint was bleeding events. To account for to heterogeneity, a random-effects model was used to analyze the study data.Results
Ten trials with a total population of 973 patients that were included in the analysis showed no significant difference in 2-month mortality between the IABP and the control groups. The 6-month mortality in the IABP group was not significantly lower than in the control group in the four RCTs that enrolled 59 AMI patients with CS. But in the four that enrolled AMI 66 patients without CS, the data showed opposite conclusion.Conclusions
IABP cannot reduce within 2 months and 6–12 months mortality of AMI patients with CS as well as within 2 months mortality of AMI patients without CS, but can reduce 6–12 months mortality of AMI patients without CS. In addition, IABP can increase the risk of bleeding. 相似文献4.
Deok-Sang Yoo Jane Chang Joon-Tae Kim Min-Ji Choi Jina Choi Kang-Ho Choi Man-Seok Park Ki-Hyun Cho 《PloS one》2014,9(4)
Background
Hyperglycemia is common after stroke, and it is well known to worsen its outcome. However, it is important to consider that blood glucose (BG) levels can undergo dynamic changes during the acute stage of ischemic stroke. We sought to investigate the clinical significance of various glucose parameters within first 24 hours in acute ischemic stroke (AIS). The study focused on hyperacute stage patients who underwent IVT and investigated which parameters of glucose demonstrated to be helpful for predicting outcome.Methods
This was a retrospective study of consecutive patients with AIS at a single stroke center. Patients were consecutively enrolled if they were treated with IV-tPA within 3 hours of symptom onset. BG was measured immediately upon arrival in ER, after IVT and every 6–8 hours during the first 24 hours after IVT. The various parameters of BG were the following: BG before IVT, BG after IVT, mean BG (mBG), maximal BG (max BG), standard deviation of BG (sdBG), and standard deviation of mean BG (sdmBG).Results
207 patients (127 men and 80 women) were included in this study. Seventy seven of 207 patients had favorable outcomes at 3 months. High BG after IVT, mBG and max BG were independently associated with mRS>2 at 3 months (adjusted by age, NIHSS, and atrial fibrillation). Several parameters of BG were also independently associated with early mortality within 3 months (BG after IVT, mBG, and max BG). BG after IVT and mBG over 180 mg/dL were independently associated with early mortality within 3 months.Conclusion
Serial measurements of BG might be a better predictor of clinical outcome in patients with AIS treated with IVT than single BG measurements before IVT. Therefore, these results suggest that variable parameters of BG could be important for the prediction of clinical outcome in AIS treated with IVT. 相似文献5.
Anneleen S. E. Staelens Stefan Van Cauwelaert Kathleen Tomsin Tinne Mesens Manu L. N. Malbrain Wilfried Gyselaers 《PloS one》2014,9(8)
Objective
To determine intra-abdominal pressure (IAP) and to evaluate the reproducibility of IAP-measurements using the Foley Manometer Low Volume (FMLV) in term uncomplicated pregnancies before and after caesarean section (CS), relative to two different reference points and to non-pregnant values.Design
Observational cohort study.Setting
Secondary level referral center for feto-maternal medicine.Population
Term uncomplicated pregnant women as the case-group and non-pregnant patients undergoing a laparoscopic assisted vaginal hysterectomy (LAVH) as control group.Methods
IAP was measured in 23 term pregnant patients, before and after CS and in 27 women immediately after and 1 day after LAVH. The midaxillary line was used as zero-reference (IAPMAL) in all patients and in 13 CS and 13 LAVH patients, the symphysis pubis (IAPSP) was evaluated as additional zero-reference. Intraobserver correlation (ICC) was calculated for each zero-reference. Paired student''s t-tests were performed to compare IAP values and Pearson''s correlation was used to assess correlations between IAP and gestational variables.Main outcome measures
ICC before and after surgery, IAP before and after CS, IAP after CS and LAVH.Results
The ICC for IAPMAL before CS was lower than after (0.71 versus 0.87). Both mean IAPMAL and IAPSP were significantly higher before CS than after: 14.0±2.6 mmHg versus 9.8±3.0 mmHg (p<0.0001) and 8.2±2.5 mmHg versus 3.5±1.9 mmHg (p = 0.010), respectively. After CS, IAP was not different from values measured in the LAVH-group.Conclusion
IAP-measurements using FMLV is reproducible in pregnant women. Before CS, IAP is increased in the range of intra-abdominal hypertension for non-pregnant individuals. IAP significantly decreases to normal values after delivery. 相似文献6.
Valentina Calamia Lucía Lourido Patricia Fernández-Puente Jesús Mateos Beatriz Rocha Eulalia Montell Josep Vergés Cristina Ruiz-Romero Francisco J Blanco 《Arthritis research & therapy》2012,14(5):R202
Introduction
Chondroitin sulfate (CS) is a symptomatic slow-acting drug for osteoarthritis (OA) widely used in the clinic. The aim of this work is to find proteins whose secretion from cartilage cells under proinflammatory stimuli (IL-1β) is regulated by CS, employing a novel quantitative proteomic approach.Methods
Human articular chondrocytes released from three normal cartilages were grown in SILAC medium. When complete incorporation of the heavy isotope was achieved, chondrocytes were stimulated with IL-1β 5 ng/ml with or without CS pretreatment (200 µg/ml). Forty-eight hours later, chondrocyte secretomes were analyzed by nano-scale liquid chromatography-mass spectrometry. Real-time PCR, western blot and immunohistochemistry analyses were employed to confirm some of the results.Results
We could identify 75 different proteins in the secretome of human articular chondrocytes. Eighteen of these were modulated by CS with statistical significance (six increased and 12 decreased). In normal chondrocytes stimulated with IL-1β, CS reduces inflammation directly by decreasing the presence of several complement components (CFAB, C1S, CO3, and C1R) and also indirectly by increasing proteins such as TNFα-induced protein (TSG6). TSG6 overexpression correlates with a decrease in pro-matrix metalloproteinase activation (observed in MMP1 and MMP3 levels). Finally, we observed a strong CS-dependent increase of an angiogenesis inhibitor, thrombospondin-1.Conclusion
We have generated a quantitative profile of chondrocyte extracellular protein changes driven by CS in the presence of IL-1β. We have also provided novel evidences of its anti-angiogenic, anti-inflammatory, and anti-catabolic properties. Demonstration of the anti-angiogenic action of CS might provide a novel therapeutic approach for OA targeting. 相似文献7.
Background
In Sub-Saharan Africa, policy changes have begun to pave the way for community distribution of injectable contraceptives but sustaining such efforts remains challenging. Combining social marketing with community-based distribution provides an opportunity to recover some program costs and compensate workers with proceeds from contraceptive sales. This paper proposes a model for increasing access to injectable contraceptives in rural settings by using community-based distributers as social marketing agents and incorporating financing systems to improve sustainability.Methods
This intervention was implemented in three districts of the Central Zone of Tigray, Ethiopia and program data has been collected from November 2011 through October 2012. A total of 137 Community Based Reproductive Health Agents (CBRHAs) were trained to provide injectable contraceptives and were provided with a loan of 25 injectable contraceptives from a drug revolving fund, created with project funds. The price of a single dose credited to a CBRHA was 3 birr ($0.17) and they provide injections to women for 5 birr ($0.29), determined with willingness-to-pay data. Social marketing was used to create awareness and generate demand. Both quantitative and qualitative methods were used to examine important feasibility aspects of the intervention.Results
Forty-four percent of CBRHAs were providing family planning methods at the time of the training and 96% believed providing injectable contraceptives would improve their services. By October 2012, 137 CBRHAs had successfully completed training and provided 2541 injections. Of total injections, 47% were provided to new users of injectable contraceptives. Approximately 31% of injections were given for free to the poorest women, including adolescents.Conclusions
Insights gained from the first year of implementation of the model provide a framework for further expansion in Tigray, Ethiopia. Our experience highlights how program planners can tailor interventions to match family planning preferences and create more sustainable contraceptive service provision with greater impact. 相似文献8.
Priscila P. Santos Fernando Oliveira Vanessa C. M. P. Ferreira Bertha F. Polegato Meliza G. Roscani Ana Angelica Fernandes Pamela Modesto Bruna P. M. Rafacho Silmeia G. Zanati Annarita Di Lorenzo Luiz S. Matsubara Sergio A. R. Paiva Leonardo A. M. Zornoff Marcos F. Minicucci Paula S. Azevedo 《PloS one》2014,9(12)
Background/Aims
Experimental and clinical studies have shown the direct toxic effects of cigarette smoke (CS) on the myocardium, independent of vascular effects. However, the underlying mechanisms are not well known.Methods
Wistar rats were allocated to control (C) and cigarette smoke (CS) groups. CS rats were exposed to cigarette smoke for 2 months.Results
After that morphometric, functional and biochemical parameters were measured. The echocardiographic study showed enlargement of the left atria, increase in the left ventricular systolic volume and reduced systolic function. Within the cardiac metabolism, exposure to CS decreased beta hydroxy acyl coenzyme A dehydrogenases and citrate synthases and increased lactate dehydrogenases. Peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were expressed similarly in both groups. CS increased serum lipids and myocardial triacylglycerols (TGs). These data suggest that impairment in fatty acid oxidation and the accumulation of cardiac lipids characterize lipotoxicity. CS group exhibited increased oxidative stress and decreased antioxidant defense. Finally, the myocyte cross-sectional area and active Caspase 3 were increased in the CS group.Conclusion
The cardiac remodeling that was observed in the CS exposure model may be explained by abnormalities in energy metabolism, including lipotoxicity and oxidative stress. 相似文献9.
Baba P. D. Inusa Adeola Oyewo Felicity Brokke Gayathriy Santhikumaran K. Haran Jogeesvaran 《PloS one》2013,8(6)
Background
Distinguishing between acute presentations of osteomyelitis (OM) and vaso-occlusive crisis (VOC) bone infarction in children with sickle cell disease (SCD) remains challenging for clinicians, particularly in culture-negative cases. We examined the combined role of ultrasound scan (USS), C - reactive protein and White blood counts (WCC) in aiding early diagnosis in children with SCD presenting acutely with non-specific symptoms such as bone pain, fever or swelling which are common in acute osteomyelitis or VOC.Methods
We reviewed the records of all children with SCD who were discharged from our department from October 2003 to December 2010 with a diagnosis of osteomyelitis based on clinical features and the results of radiological and laboratory investigations. A case control group with VOC who were investigated for OM were identified over the same period.Results
In the osteomyelitis group, USS finding of periosteal elevation and/or fluid collection was reported in 76% cases with the first scan (day 0–6). Overall 84% were diagnosed with USS (initial +repeat). 16% had negative USS. With VOC group, USS showed no evidence of fluid collection in 53/58 admissions (91%), none of the repeated USS showed any fluid collection. Mean C-reactive protein (CRP), and white cell count (WCC) were significantly higher in the OM.Conclusion
The use of Ultrasound in combination with CRP and WCC is a reliable, cost-effective diagnostic tool for differentiating osteomyelitis from VOC bone infarction in SCD. A repeat ultrasound and/or magnetic resonance imaging (MRI) scan may be is necessary to confirm the diagnosis. 相似文献10.
Yang Peng Xiaohua Ye Ying Li Tao Bu Xiaofeng Chen Jiaqi Bi Junli Zhou Zhenjiang Yao 《PloS one》2013,8(11)
Objective
To evaluate whether teicoplanin could be an alternative to vancomycin for treatment of MRSA infection in Chinese population using a meta-analysis in randomized controlled trials.Methods
The following databases were searched: Chinese Biomedical Literature database (CBM), Chinese Journal Full-text database (CNKI), Wanfang database, Medline database, Ovid database and Cochrane Library. Articles published from 2002 to 2013 that studied teicoplanin in comparison to vancomycin in the treatment of MRSA infected patients were collected. Overall effects, publishing bias analysis and sensitivity analysis on clinical cure rate, microbiologic eradication rate and adverse events rate were performed by using Review Manager 5.2 and Stata 11.0 softwares.Results
Twelve articles met entry criteria. There was no statistically significant difference between the two groups regarding the clinical cure rate (risk ratio [RR], teicoplanin vs vancomycin, 0.94; 95% CI, 0.74∼1.19; P = 0.60), microbiological cure rate (risk ratio [RR], teicoplanin vs vancomycin, 0.99; 95% CI, 0.91∼1.07; P = 0.74) and adverse event rate (risk ratio [RR], teicoplanin vs vancomycin, 0.86; 95% CI, 0.40∼1.84; P = 0.70).Conclusions
The meta-analysis results indicate that the two therapies are similar in both efficacy and safety, thus teicoplanin can act as an effective alternative to vancomycin for treating patients infected by MRSA. 相似文献11.
Wouter Huvenne Ellen A Lanckacker Olga Krysko Ken R Bracke Tine Demoor Peter W Hellings Guy G Brusselle Guy F Joos Claus Bachert Tania Maes 《Respiratory research》2011,12(1):69
Background
Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation.Objective
To study the effect of Staphylococcus aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD.Methods
C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 μg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected.Results
Combined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8+ T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs.Conclusions
Combined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that Staphylococcus aureus could influence the pathogenesis of COPD. 相似文献12.
Background
It is incompletely understood how cigarette smoke (CS) exposure affects lung mucosal immune responses during viral respiratory infections. B cell activating factor belonging to the tumor necrosis factor family (BAFF) plays an important role in the induction of secretory immunoglobulin A (S-IgA) which is the main effector of the mucosal immune system. We therefore investigated the effects of CS exposure on BAFF expression and S-IgA responses in the lung during influenza virus infection.Methods
Mice were exposed to CS and/or infected with influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed for BAFF expression, influenza-specific S-IgA level and histological changes. Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda) expression was determined. BEAS-2B cells were treated with CS extract (CSE), influenza virus, interferon beta or N-acetylcysteine and BAFF expression was measured.Results
CS inhibited BAFF expression in the lung, particularly after long-term exposure. BAFF and S-IgA levels were increased during influenza virus infection. Three-month CS exposure prior to influenza virus infection resulted in reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary inflammation on day 7 after infection. Prior CS exposure also caused decreased Aicda expression in lung B cells during infection. Neutralization of BAFF in the lung resulted in reduced S-IgA levels during influenza virus infection. CSE inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B cells, while this inhibition of BAFF by CSE was prevented by pretreatment with the antioxidant N-acetylcysteine.Conclusions
Our findings indicate that CS may hinder early mucosal IgA responses in the lung during influenza virus infection through oxidative inhibition of BAFF, which might contribute to the increased incidence and severity of viral infections in smokers.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0201-y) contains supplementary material, which is available to authorized users. 相似文献13.
Background
Recommendations to prevent the spread of vancomycin resistance have been in place since 1995 and include guidelines for inpatient pediatric use of vancomycin. The emergence of large databases allows us to describe variation in pediatric vancomycin across hospitals. We analyzed a database with hospitalizations for children under 18 at 421 hospitals in 2008.Methodology/Principal Findings
The Premier hospital 2008 database, consisting of records for 877,201 pediatric hospitalizations in 421 hospitals, was analyzed. Stratified analyses and logistic mixed effects models were used to calculate the probability of vancomycin use while considering random effects of hospital variation, hospital fixed effects and patient effects, and the hierarchical structure of the data. Most hospitals (221) had fewer than 10 hospitalizations with vancomycin use in the study period, and 47 hospitals reported no vancomycin use in 17,271 pediatric hospitalizations. At the other end of the continuum, 21 hospitals (5.6% of hospitals) each had over 200 hospitalizations with vancomycin use, and together, accounted for more than 50% of the pediatric hospitalizations with vancomycin use. The mixed effects modeling showed hospital variation in the probability of vancomycin use that was statistically significant after controlling for teaching status, urban or rural location, size, region of the country, patient ethnic group, payor status, and APR-mortality and severity codes.Conclusions/Significance
The number and percentage of pediatric hospitalizations with vancomycin use varied greatly across hospitals and was not explained by hospital or patient characteristics in our logistic models. Public health efforts to reduce vancomycin use should be intensified at hospitals with highest use. 相似文献14.
Henar Ortega-Senovilla Ute Schaefer-Graf Katrin Meitzner Kristof Graf Michael Abou-Dakn Emilio Herrera 《PloS one》2013,8(12)
Background
Ligands of peroxisome-proliferator activated receptors (PPARs), such as non-esterified fatty acids (NEFAs), induce expression of angiopoietin-like protein 4 (ANGPTL4). Recently ANGPTL4 has been reported to be a mediator of intracellular adipose lipolysis induced by glucocorticoids.Objective
To determine the concentrations of ANGPTL4 in cord serum of neonates born by spontaneous vaginal delivery (SVD) and by pre-labor cesarean section (CS) from healthy women, and to relate them to parameters of neonatal lipolytic activity at birth.Measurements
In 54 neonates born by SVD and in 56 neonates born by CS, arterial cord blood was drawn to determine insulin, cortisol, triacylglycerols (TAGs), glycerol, non-esterified fatty acids (NEFAs), individual fatty acids, ANGPTL4, adiponectin, retinol binding protein 4 (RBP4) and leptin.Results
Birth weight and neonatal fat mass in SVD and CS showed no difference, but the concentrations of glycerol, adiponectin, RBP4, NEFAs and most individual fatty acids were higher in cord serum of neonates born by SVD compared to CS, indicating a higher adipose tissue breakdown in the SVD group. The concentrations of TAG and cortisol were also higher and that of insulin was lower in cord serum of SVD compared to the CS group. However, the concentration in cord serum of ANGPTL4 did not differ between the two groups and no positive correlation with either NEFA or glycerol concentrations were detected.Conclusion
ANGPTL4 is known to stimulate lipolysis in adults, but does not appear to mediate the increased activity in SVD, indicating the presence of different regulatory inputs. 相似文献15.
Segarra TJ Fakioglu E Cheshenko N Wilson SS Mesquita PM Doncel GF Herold BC 《PloS one》2011,6(11):e27675
Background
Despite significant protection in preclinical studies, cellulose sulfate (CS) failed to protect women against HIV-1/2 and was associated with a trend toward increased HIV-1 acquisition in one of the clinical trials. These results highlight the need for preclinical tests more predictive of clinical outcomes. The objective of this study was to test coded vaginal gels, including CS, in murine models of safety and efficacy to determine the models'' utility for evaluating future products.Methods
Four coded formulations, including 6% CS, 2% PRO 2000 and two placebo gels, were administered intravaginally to medroxyprogesterone-treated mice and their ability to prevent genital herpes (efficacy) or to alter the susceptibility to low dose HSV challenge (safety) was determined. Nonoyxnol-9 served as a positive toxicity control.Results
CS and PRO 2000 significantly protected mice from genital herpes following infection with a laboratory or clinical isolate of HSV-2 introduced in buffer (p<0.001). However, protection was reduced when virus was introduced in seminal plasma. Moreover, mice were significantly more susceptible to infection with low doses of HSV-2 when challenged 12 h after the 7th daily dose of CS or nonoxynol-9 (p<0.05). The increased susceptibility was associated with alterations in epithelial architecture.Conclusions
CS prevented genital herpes when present at the time of viral challenge, but increased the rate of infection when gel was applied daily for 7 days with a vaginal wash prior to viral inoculation. The findings presumably reflect altered epithelial architecture, which may have contributed to the trend towards increased HIV observed clinically. 相似文献16.
Liang Y Arakawa K Ueta K Matsushita Y Kuriyama C Martin T Du F Liu Y Xu J Conway B Conway J Polidori D Ways K Demarest K 《PloS one》2012,7(2):e30555
Background
Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM).Methods
14C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity.Results
Treatment with canagliflozin 1 mg/kg lowered RTG from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio.Conclusions
Canagliflozin lowered RTG and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity. 相似文献17.
Mark Rowland Pelagie Boko Abibatou Odjo Alex Asidi Martin Akogbeto Raphael N’Guessan 《PloS one》2013,8(7)
Background
Indoor residual spraying (IRS) is widely used for malaria transmission control in sub-Saharan Africa. Resistance to pyrethroids in the mosquito Anopheles gambiae is a growing problem. There is an urgent need to develop long-lasting alternative insecticides to reduce selection pressure for pyrethroid resistance and to provide control with a single IRS application in countries with long transmission seasons.Methods
Two capsule suspension formulations (CS) of the organophosphate pirimiphos methyl were evaluated as IRS treatments in experimental huts in an area of Benin where the mosquitoes Anopheles gambiae and Culex quinquefasciatus are resistant to pyrethroids but susceptible to organophosphates. The CS formulations were tested alongside an emulsifiable concentrate (EC) formulation of pirimiphos methyl and a CS formulation of the pyrethroid lambdacyhalothrin.Results
The two CS formulations of pirimiphos methyl gave prolonged control of An. gambiae and Cx. quinquefasciatus. In cement huts application rates of 0.5 g/m2 induced high mortality of An. gambiae for almost a year: overall mortality rates 87% (95% CI 82–91%) and 92% (95% CI 88–94%). In mud huts application rates of 1 g/m2 induced high mortality of An. gambiae for 10 months: overall mortality rates 75% (95% CI 69–81%) and 76% (95% CI 68–83%). The EC formulation of pirimiphos methyl failed to control An. gambiae two months after spraying. The pyrethroid lambdacyhalothrin demonstrated prolonged residual activity in bioassay tests but failed to control pyrethroid resistant An. gambiae that entered the huts. Pirimiphos methyl CS was highly active against Culex quinquefasciatus and gave control for 10 months in cement huts and 6 months in mud huts.Conclusion
Pirimiphos methyl CS (Actellic 300 CS) applied at 1 g/m2 shows great promise for providing prolonged control of pyrethroid-resistant An gambiae and for delaying pyrethroid resistance. An alternative to DDT, giving year-round transmission control in sub-Saharan Africa is now a realistic prospect. 相似文献18.
Objective
Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI). However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI) which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS) techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine.Methods
Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR), underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS.Results
HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract.Conclusions
Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery. 相似文献19.
L. X. van Nunen M. van ’t Veer S. Schampaert B. J. E. M. Steerneman M. C. M. Rutten F. N. van de Vosse N. H. J. Pijls 《Netherlands heart journal》2013,21(12):554-560
Background
Recent evidence questions the role of intra-aortic balloon counterpulsation (IABP) in the treatment of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). An area of increasing interest is the use of IABP for persistent ischaemia (PI). We analysed the use of IABP in patients with AMI complicated by CS or PI.Methods
From 2008 to 2010, a total of 4076 patients were admitted to our hospital for primary percutaneous coronary intervention (PCI) for AMI. Out of those, 239 patients received an IABP either because of CS or because of PI. Characteristics and outcome of those patients are investigated.Results
The mean age of the study population was 64 ± 11 years; 75 % were male patients. Of the patients, 63 % had CS and 37 % had PI. Patients with CS had a 30-day mortality rate of 36 %; 1-year mortality was 41 %. Patients with PI had a 30-day mortality rate of 7 %; 1-year mortality was 11 %.Conclusions
Mortality in patients admitted for primary PCI because of AMI complicated by CS is high despite IABP use. Outcome in patients treated with IABP for PI is favourable and mandates further prospective studies. 相似文献20.
Tonio Pera Reinoud Gosens Andries H Lesterhuis Riham Sami Marco van der Toorn Johan Zaagsma Herman Meurs 《Respiratory research》2010,11(1):48