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1.
Respir Res ; 25(1): 120, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468259

ABSTRACT

BACKGROUND: Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. METHODS: COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. RESULTS: Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-ß (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. CONCLUSIONS: These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Quercetin , Humans , Quercetin/pharmacology , Quercetin/therapeutic use , Quercetin/metabolism , Interleukin-8/metabolism , Dimethyl Sulfoxide/metabolism , Dimethyl Sulfoxide/pharmacology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/genetics , Bronchi/metabolism , Epithelial Cells/metabolism , Cells, Cultured , Transcription Factors/metabolism , Homeodomain Proteins/metabolism , Homeodomain Proteins/pharmacology
2.
Res Sq ; 2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37546740

ABSTRACT

Background: Airway basal cells from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces goblet cell metaplasia and the expression of pro-inflammatory cytokines in COPD models. This study assessed whether quercetin improves epithelial regeneration from COPD airway basal cells. Methods: COPD airway basal cells were treated with DMSO or 1 µM quercetin for three days. The cells were then cultured at air/liquid interface (ALI) for up to 4 weeks. Basal cells from healthy donors cultured at air/liquid interface were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA. Microarray analysis was conducted on DMSO or quercetin-treated COPD basal cells to identify differentially regulated genes (DEG) and the enriched biological pathways. Bronchial brushings from COPD patients treated with either placebo or quercetin for 6 months were used to confirm the effects of quercetin on gene expression. Results: Compared to DMSO, quercetin-treated COPD basal cells showed an increase in TER and regenerated the airway epithelium with more ciliated cells, and less goblet cells and IL-8. Comparison of DMSO- and quercetin-treated COPD basal cell transcriptomic profiles indicated that quercetin upregulated genes associated with tissue and epithelial development and differentiation. COPD patients treated with quercetin, but not placebo showed significantly increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD basal cells. Bronchial brushings from active smokers showed significantly increased mRNA expression of TGF-ß and IL-8, and it was reduced after quercetin treatment. Conclusions: These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. Trial registration: This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.

3.
Biotechniques ; 75(2): 65-70, 2023 08.
Article in English | MEDLINE | ID: mdl-37498058

ABSTRACT

Transfection, a nonviral method of nucleic acid delivery, often exhibits poor efficiency in vivo. The needle-based in vivo delivery of transfection reagents can be invasive. Here, we report a noninvasive protocol for in vivo gene delivery via the needle-free MED-JET H4 MULTIJET (MJH4M) device using both "home-made" glucose-based and commercial transfection reagents. The objective of this study was to compare the relative transfection efficiencies of the needle-free system to that of the needle-based delivery method. We observed a 15-fold increase in transfection efficiency using the needle-free MJH4M device when compared to the needle-based delivery method. The highest transfection efficiency was achieved using a 5% glucose solution as the delivery vehicle.


Subject(s)
Nucleic Acids , Nucleic Acids/genetics , Transfection , Drug Delivery Systems , Genetic Therapy
4.
Artif Intell Med ; 119: 102130, 2021 09.
Article in English | MEDLINE | ID: mdl-34531004

ABSTRACT

As a widely used vital sign within cardiology, Electrocardiography (ECG) provides the basis for assessing heart function and diagnosing cardiovascular diseases. Automated anomaly detection for ECG plays an important role in improving patient diagnosis efficiency and reducing healthcare costs. Practically, due to the limits of electronics support or the medical system setting, image is a more common format for large-scale ECG storage in most clinical institutions. To guarantee an automated ECG detection model's scalability and practicality in clinical applications, taking good advantage of ECG images is crucial. However, existing time digital-based discriminative models fail to learn from images effectively for two reasons. First of all, the signals recorded on images have much lower resolution and higher noise, which makes it impractical to extract precise ECG signals following existing techniques. Meanwhile, the differences between abnormal signals are usually subtle, and they may be overwhelmed by the noises in the images as well. Towards this end, we design a novel neural framework that can be directly applied to massive ECG images determining various types of cardiology abnormalities. It classifies fine-grained ECG images based on weakly supervised strategy, in which case only image-level labeling is required. By eliminating the need for part annotations, the proposed method can result in significant savings in annotation time and cost. The effectiveness of the method is demonstrated by experimental results on two real ECG datasets.


Subject(s)
Electrocardiography , Neural Networks, Computer , Humans
6.
J Matern Fetal Neonatal Med ; 34(17): 2783-2792, 2021 Sep.
Article in English | MEDLINE | ID: mdl-31588827

ABSTRACT

OBJECTIVE: We compared post-partum outcomes between sickle cell disease (SCD) and non-sickle cell populations. METHODS: We conducted a retrospective analysis of discharge data for 6,911,916 inpatient deliveries in the states of California, Florida, New York, Maryland, and Kentucky from 2007 to 2014 using data from the State Inpatient Databases, Healthcare Cost and Utilization Project. We compared unadjusted rates and adjusted odds of 30- and 90-d readmission rates, in-hospital mortality, length of stay (LOS), and total hospital charges in SCD, sickle cell trait, and non-sickle cell patients. RESULTS: Compared to non-sickle cell patients, SCD patients were more than two times as likely to die in-hospital (aOR: 2.16, 95% CI: 1.15-4.04, p < .05), 27% as likely to be readmitted up to 30 d postdelivery (aOR: 1.27, 95% CI: 1.13-1.43, p < .001), and 92% as likely to be readmitted up to 90 d postdelivery (aOR 1.92, 95% CI: 1.75-2.11, p < .001). The SCD group also had a longer median LOS, greater total hospital charges, were more likely to experience a postpartum complication, and receive a blood transfusion than the non-SCD group. CONCLUSIONS: SCD in pregnancy is associated with increased inpatient mortality, readmissions, postpartum complications, LOS, and hospital charges.


Subject(s)
Anemia, Sickle Cell , Patient Readmission , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/therapy , Female , Humans , Inpatients , New York , Postpartum Period , Pregnancy , Retrospective Studies
7.
PLoS One ; 12(9): e0184025, 2017.
Article in English | MEDLINE | ID: mdl-28934243

ABSTRACT

BACKGROUND: Very little is known about the proportion of oncology trials that get published, the time it takes to publish them, or the reasons why oncology trials do not get published. METHODS: We analyzed all clinical trials that closed to accrual at our cancer center between 2009-2013. Trials were categorized by study purpose (therapeutic vs. diagnostic), phase (pilot, phase I, II, or III), and sponsor (industrial, cooperative group, institutional, or peer-reviewed). Final publications were identified in MEDLINE and EMBASE by NCT numbers, or by querying the principal investigator. For trials not published, we surveyed the principal investigators to identify the reason for non-publication. FINDINGS: 469 of 809 protocols (58%) had been published by November 2016. The calculated probability of publication 7 years after completing accrual was 70.4%; the calculated median time to publication was 47 months. Only 18.8% of protocols overall were estimated to be published within 2 years from completing accrual. The calculated probability of publication was higher for therapeutic trials than non-therapeutic trials, but there was no difference based on phase or sponsor. Among protocols not published, 45.3% had completed accrual, and among these, a majority had a manuscript in preparation or review, or the trial was still collecting data. Failure to publish due to a pharmaceutical sponsor was rare. 30.6% of unpublished trials had closed for various reasons before completing accrual, usually due to poor accrual or pharmaceutical sponsor issues. INTERPRETATION: Almost 30% of trials were calculated to be unpublished by 7 years after closing to accrual at our institution. Failure to reach accrual goals was an important factor in non-publication. We have devised new institutional policies that identify trials likely not to meet accrual goals and require early closure. We should be able to shorten the time from accrual completion to publication, especially for pilot and phase I trials for which long follow up is not needed.


Subject(s)
Clinical Trials as Topic , Medical Oncology , Publishing/statistics & numerical data , Humans , Probability , Time Factors
8.
Methods Mol Biol ; 1570: 301-313, 2017.
Article in English | MEDLINE | ID: mdl-28238146

ABSTRACT

The field of nanomedicine is steadily growing and several nanomedicines are currently approved for clinical use with even more in the pipeline. Yet, while the use of nanotechnology to improve targeted drug delivery to the lungs has received some attention, the use of nanoparticles for inhalation drug delivery has not yet resulted in successful translation to market as compared to intravenous drug delivery. The reasons behind the lack of inhaled nanomedicines approved for clinical use or under preclinical development are unclear, but challenges related to safety are likely to contribute. Although inhalation toxicology studies often begin using animal models, there has been an increase in the development and use of in vitro air-liquid interface (ALI) exposure systems for toxicity testing of engineered nanoparticle aerosols, which will be useful for rapid testing of candidate substances and formulations. This chapter describes an ALI cell exposure assay for measuring toxicological effects, specifically cell viability and oxidative stress, resulting from exposure to aerosols containing nanoparticles.


Subject(s)
Aerosols , Drug Delivery Systems , Nanomedicine , Nanoparticles , Cell Culture Techniques , Cell Line, Tumor , Cell Survival , Cells, Cultured , Drug Compounding , Ferric Compounds/chemistry , Humans , L-Lactate Dehydrogenase/metabolism , Oxidative Stress , Reactive Oxygen Species
9.
Crit Rev Toxicol ; 47(3): 225-262, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27648750

ABSTRACT

Little consistency exists in the methodology for toxicological testing of aerosolized nanoparticles used in in vitro, air-interfaced culture (AIC) exposure systems for engineered nanoparticles (ENPs) risk-assessment, preventing inter-laboratory comparisons to identify dose thresholds for adverse effects. These inconsistencies result from heterogeneity in particle types, exposure durations, exposure systems, and dose metrics reported. We screened 10,241 studies in the literature for toxicological assessment of ENPs, resulting in 110 publications included after meeting eligibility criteria. In this review, we critically analyzed methodology within these studies to answer whether: (1) the administered dose or the deposited dose correlated better with biological response, (2) a difference existed between various AIC exposure systems when depositing the same dose, (3) consistent results were generated for nanomaterials with similar physico-chemical properties, (4) the deposited dose in vitro correlated to the deposited dose in vivo, and (5) AIC studies reliably modeled acute toxicity in vivo. Methods used in delivering, measuring, and reporting ENP aerosol doses in vitro are summarized. Dosimetry and biological response comparisons of AIC, conventional suspensions, and in vivo exposures are discussed through case studies on silver, zinc oxide, titanium dioxide, and multi-walled carbon nanotube exposures. Finally, based on these findings, recommendations are offered for design of future AIC experiments to aid standardization and comparisons of results.


Subject(s)
Aerosols/toxicity , Air Pollutants/toxicity , Inhalation Exposure/analysis , Nanoparticles/toxicity , Toxicity Tests/methods , Humans , Models, Biological , Titanium , Zinc Oxide
10.
Nanoscale ; 8(23): 11834-9, 2016 Jun 09.
Article in English | MEDLINE | ID: mdl-27228183

ABSTRACT

Acute pancreatitis is a relatively common and potentially fatal condition, but the presenting symptoms are non-specific and diagnosis relies largely on the measurement of amylase activity by the hospital clinical laboratory. In this work we develop a point of care test for pancreatitis measuring concentration of secretory phospholipase A2 group IB (sPLA2-IB). Novel antibodies for sPLA2-IB were raised and used to design an ELISA and a lateral flow device (LFD) for the point of care measurement of sPLA2-IB concentration, which was compared to pancreatic amylase activity, lipase activity, and sPLA2-IB activity in 153 serum samples. 98 of these samples were obtained from the pathology unit of a major hospital and classified retrospectively according to presence or absence of pancreatitis, and the remaining 55 were obtained from commercial sources to serve as high lipase (n = 20), CA19-9 positive (n = 15), and healthy (n = 20) controls. sPLA2-IB concentration correlated well with the serum activity of both amylase and lipase, and performed at least as well as either markers in the differentiation of pancreatitis from controls.


Subject(s)
Amylases/blood , Lipase/blood , Pancreatitis/diagnosis , Phospholipases A2/blood , Point-of-Care Systems , Acute Disease , Humans
11.
Nanoscale ; 8(8): 4482-5, 2016 Feb 28.
Article in English | MEDLINE | ID: mdl-26854217

ABSTRACT

Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Group II Phospholipases A2/blood , Adult , Aged , Arthritis, Psoriatic/diagnosis , Biomarkers/blood , C-Reactive Protein , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Point-of-Care Testing
12.
Nutrients ; 7(6): 5051-64, 2015 Jun 23.
Article in English | MEDLINE | ID: mdl-26110253

ABSTRACT

Continuous infusion systems used for enteral nutrition support in the neonatal intensive care unit deliver as little as 60% of the fat in human milk to the neonate. This study determined the effect of mixing common feedings for preterm infants in the feeding bag and tubing on fat losses during enteral feeding. Laboratory models were developed to assess the contribution of various mixing techniques to delivered fat content. Fat content was measured periodically during feeding and compared to baseline measurements. A multistage approach incorporating a feeding bag inverter and a tubing circulation loop delivered >90% of milk fat when used in conjunction with a commercial continuous infusion system. With unfortified human milk, this approach delivered 91.9% ± 1.5% of fat content over a one hour feed, significantly greater (p < 0.01) than 77.5% ± 2.2% delivered by continuous infusion controls (Mean ± SEM). With fortified human milk, this approach delivered 92.1% ± 2.4% of fat content, significantly greater (p < 0.01) than 79.4% ± 1.0% delivered by a non-adapted infusion system (Mean ± SEM). Mixing human milk during continuous infusion improves fat delivery, which may improve nutrition and growth outcomes in low birth weight neonates.


Subject(s)
Dietary Fats/administration & dosage , Enteral Nutrition/methods , Equipment Design , Food, Fortified , Humans , Infant , Infant Nutritional Physiological Phenomena , Infant, Premature/growth & development , Infant, Very Low Birth Weight/growth & development , Intensive Care Units, Neonatal , Milk, Human
13.
Curr Med Res Opin ; 30(4): 537-45, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24329572

ABSTRACT

OBJECTIVE: To compare outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus, temsirolimus, and sorafenib following initial treatment with a tyrosine kinase inhibitor (TKI) in community and academic practices throughout the US. RESEARCH DESIGN AND METHODS: Medical records of mRCC patients who received everolimus, temsirolimus or sorafenib as their second therapy following a TKI were retrospectively reviewed from a nationally representative panel of oncologists. Overall survival (OS) and progression-free survival (PFS) of second targeted therapies were compared using multivariable Cox proportional hazard models, with adjustment for demographics, disease severity and prior treatments. RESULTS: A total of 233, 178, and 123 mRCC patients receiving everolimus, temsirolimus, and sorafenib, respectively, as second targeted therapies were included. Eighty-six percent used sunitinib and the remainder used sorafenib or pazopanib as their initial TKI. After adjusting for baseline characteristics, everolimus was associated with significantly prolonged OS (hazard ratio [HR] 0.60; CI 0.42-0.85; p = 0.004) and PFS (HR 0.73; CI 0.54-0.97; p = 0.032) compared to temsirolimus. Everolimus was associated with significantly longer OS (HR 0.66; CI 0.44-0.99; p = 0.045) and numerically longer PFS compared to sorafenib. No significant differences were observed between temsirolimus and sorafenib. LIMITATIONS: Despite adjustment for multiple patient characteristics, comparisons between treatment groups may be confounded by unobserved factors in this retrospective observational study. Tolerability outcomes were not collected. CONCLUSIONS: In this retrospective, non-randomized study of mRCC patients with prior TKI treatment, everolimus was associated with significantly prolonged OS and PFS compared to temsirolimus and significantly prolonged OS compared to sorafenib.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Sirolimus/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/mortality , Disease-Free Survival , Everolimus , Female , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Niacinamide/therapeutic use , Proportional Hazards Models , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Sirolimus/therapeutic use , Sorafenib , Treatment Outcome
14.
J Am Med Inform Assoc ; 21(2): 299-307, 2014.
Article in English | MEDLINE | ID: mdl-23813539

ABSTRACT

OBJECTIVE: To create a sense inventory of abbreviations and acronyms from clinical texts. METHODS: The most frequently occurring abbreviations and acronyms from 352,267 dictated clinical notes were used to create a clinical sense inventory. Senses of each abbreviation and acronym were manually annotated from 500 random instances and lexically matched with long forms within the Unified Medical Language System (UMLS V.2011AB), Another Database of Abbreviations in Medline (ADAM), and Stedman's Dictionary, Medical Abbreviations, Acronyms & Symbols, 4th edition (Stedman's). Redundant long forms were merged after they were lexically normalized using Lexical Variant Generation (LVG). RESULTS: The clinical sense inventory was found to have skewed sense distributions, practice-specific senses, and incorrect uses. Of 440 abbreviations and acronyms analyzed in this study, 949 long forms were identified in clinical notes. This set was mapped to 17,359, 5233, and 4879 long forms in UMLS, ADAM, and Stedman's, respectively. After merging long forms, only 2.3% matched across all medical resources. The UMLS, ADAM, and Stedman's covered 5.7%, 8.4%, and 11% of the merged clinical long forms, respectively. The sense inventory of clinical abbreviations and acronyms and anonymized datasets generated from this study are available for public use at http://www.bmhi.umn.edu/ihi/research/nlpie/resources/index.htm ('Sense Inventories', website). CONCLUSIONS: Clinical sense inventories of abbreviations and acronyms created using clinical notes and medical dictionary resources demonstrate challenges with term coverage and resource integration. Further work is needed to help with standardizing abbreviations and acronyms in clinical care and biomedicine to facilitate automated processes such as text-mining and information extraction.


Subject(s)
Abbreviations as Topic , Dictionaries, Medical as Topic , Unified Medical Language System , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , MEDLINE , Male , Medical Records , Middle Aged , Natural Language Processing , Young Adult
15.
Curr Med Res Opin ; 29(9): 1075-82, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23738923

ABSTRACT

OBJECTIVE: Molecular monitoring using quantitative polymerase chain reaction (qPCR) of BCR-ABL mRNA transcripts using the international scale (IS) is recommended by the National Comprehensive Cancer Network and the European LeukemiaNet for patients with chronic myelogenous leukemia in chronic phase (CML-CP). This study assessed the impact of the frequency of qPCR testing on progression-free survival (PFS). RESEARCH DESIGN AND METHODS: This retrospective chart review of 402 CML-CP patients on first line imatinib therapy, performed by 38 community-based US physicians, analyzed the impact of the frequency of molecular monitoring on the risk of progression and PFS. MAIN OUTCOME MEASURES: Time to progression and progression-free survival. RESULTS: Over the 3 year study, 13.2% of patients did not have any qPCR monitoring and 46.3% had 3-4 qPCR tests per year; 5.7% of CML-CP patients progressed to accelerated/blast phase or died. Compared to patients with no qPCR monitoring, those with 3-4 qPCR tests per year had a lower risk of progression (HR = 0.085; p = 0.001) and longer PFS (HR = 0.088; p = 0.001) after adjusting for potential confounders, as did those patients with 1-2 qPCR tests per year (both p < 0.02). Results were consistent after adjusting for Sokal score when available. CONCLUSION: This is the first study to document the clinical impact of frequent molecular monitoring, and the findings underscore the importance of regular molecular monitoring in delivering quality care for CML. These findings could be subject to unobserved confounders.


Subject(s)
Antineoplastic Agents/administration & dosage , Benzamides/administration & dosage , Blast Crisis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Piperazines/administration & dosage , Polymerase Chain Reaction , Pyrimidines/administration & dosage , Adult , Aged , Blast Crisis/blood , Blast Crisis/drug therapy , Blast Crisis/mortality , Disease-Free Survival , Female , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Male , Middle Aged , Monitoring, Physiologic , Retrospective Studies , Survival Rate
16.
PLoS One ; 8(5): e63550, 2013.
Article in English | MEDLINE | ID: mdl-23691064

ABSTRACT

Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable self-assembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpG-AuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG.


Subject(s)
Cell Division/drug effects , CpG Islands , Gold/chemistry , Immunotherapy , Macrophage Activation/drug effects , Macrophages/drug effects , Metal Nanoparticles/administration & dosage , Neoplasms/therapy , Animals , Base Sequence , Cell Line , DNA Primers , Mice , Mice, Inbred C57BL , Neoplasms/pathology
17.
Int J Polym Sci ; 20102010.
Article in English | MEDLINE | ID: mdl-22034584

ABSTRACT

The objective of our study was to determine the effects of composite formulation on the compressive modulus and ultimate strength of a biodegradable, in situ polymerizable poly(propylene fumarate) (PPF) and bone fiber scaffold. The following parameters were investigated: the incorporation of bone fibers (either mineralized or demineralized), PPF molecular weight, N-vinyl pyrrolidinone (NVP) crosslinker amount, benzoyl peroxide (BP) initiator amount, and sodium chloride porogen amount. Eight formulations were chosen based on a resolution III two level fractional factorial design. The compressive modulus and ultimate strength of these formulations were measured on a materials testing machine. Absolute values for compressive modulus varied from 21.3 to 271 MPa and 2.8 to 358 MPa for dry and wet samples, respectively. The ultimate strength of the crosslinked composites varied from 2.1 to 20.3 MPa for dry samples and from 0.4 to 16.6 MPa for wet samples. Main effects of each parameter on the measured property were calculated. The incorporation of mineralized bone fibers and an increase in PPF molecular weight resulted in higher compressive modulus and ultimate strength. Both mechanical properties also increased as the amount of benzoyl peroxide increased or the NVP amount decreased in the formulation. Sodium chloride had a dominating effect on the increase of mechanical properties in dry samples but showed little effects in wet samples. Demineralization of bone fibers led to a decrease in the compressive modulus and ultimate strength. Our results suggest that bone fibers are appropriate as structural enforcement components in PPF scaffolds. The desired orthopaedic PPF scaffold might be obtained by changing a variety of composite formulation parameters.

18.
Proc Natl Acad Sci U S A ; 106(29): 12115-20, 2009 Jul 21.
Article in English | MEDLINE | ID: mdl-19581582

ABSTRACT

Metastatic tumors can prepare a distant site for colonization via the secretion of factors that act in a systemic manner. We hypothesized that non- or weakly metastatic human tumor cells may act in an opposite fashion by creating a microenvironment in distant tissues that is refractory to colonization. By comparing cell lines with different metastatic potential, we have identified a tumor-secreted inhibitor of metastasis, prosaposin (Psap), which functions in a paracrine and endocrine fashion by stimulating the expression of thrombospondin-1 (Tsp-1) in fibroblasts present in both primary tumors and distant organs, doing so in a p53-dependent manner. Introduction of Psap in highly metastatic cells significantly reduced the occurrence of metastases, whereas inhibition of Psap production by tumor cells was associated with increased metastatic frequency. In human prostate cancer, decreased Psap expression was significantly associated with metastatic tumors. Our findings suggest that prosaposin, or other agents that stimulate p53 activity in the tumor stroma, may be an effective therapy by inhibition of the metastatic process.


Subject(s)
Endocrine Cells/metabolism , Neoplasm Metastasis/pathology , Paracrine Communication , Saposins/metabolism , Stromal Cells/metabolism , Thrombospondin 1/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Cell Line, Tumor , Fibroblasts/metabolism , Humans , Mice , Mice, Inbred C57BL , Organ Specificity , Proto-Oncogene Proteins c-myc/metabolism , Stromal Cells/pathology
19.
Urology ; 73(1): 109-14, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18950839

ABSTRACT

OBJECTIVES: To determine whether subjects engaged in horseback riding are more likely to be affected by sexual dysfunction and lower urinary tract symptoms than those engaged in sports with less perineal impact. MATERIAL AND METHODS: Surveys evaluating the presence of and the risk factors for sexual dysfunction and urinary symptoms were distributed among members of equestrian clubs, swimming clubs, and individual horseback riders and swimmers. About 327 surveys were distributed by hand at horse shows and swimming pools. A total of 2000 surveys were sent by direct mail to random members of 1 national equestrian organization and 1 national swimming organization. We also evaluated bicycle habits as a possible confounding factor. RESULTS: There was no significant association between horseback riding and lower urinary tract symptoms (P = .1759) and sexual dysfunction (P = .1793) in males. The same applies to the association of horseback riding and lower urinary tract symptoms (P = .5036) and sexual dysfunction (P > .05) in females, although there was a trend toward a protective association between horseback riding and stress incontinence (P = .0567). Years of bicycling (P = .04) and hardness of the bicycle seat (P = .02) were associated with an increased prevalence for lower urinary tract symptoms in women. CONCLUSIONS: Regular participation in horseback riding is not significantly associated with increased prevalence of lower urinary tract symptoms or sexual dysfunction, although it may be associated with decreased prevalence of stress urinary incontinence. Bicycle riding may be associated with higher prevalence of lower urinary tract symptoms in women.


Subject(s)
Athletic Injuries/complications , Perineum/injuries , Sexual Dysfunction, Physiological/etiology , Urination Disorders/etiology , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Swimming , Young Adult
20.
Int Braz J Urol ; 34(4): 451-4; discussion 455-6, 2008.
Article in English | MEDLINE | ID: mdl-18778496

ABSTRACT

PURPOSE: Catheter-based medical devices are an important component of the urologic armamentarium. To our knowledge, there is no population-based data regarding normal male urethral length. We evaluated the length of the urethra in men with normal genitourinary anatomy undergoing either Foley catheter removal or standard cystoscopy. MATERIALS AND METHODS: Male urethral length was obtained in 109 men. After study permission was obtained, the subject's penis was placed on a gentle stretch and the catheter was marked at the tip of the penis. The catheter was then removed and the distance from the mark to the beginning of the re-inflated balloon was measured. Alternatively, urethral length was measured at the time of cystoscopy, on removal of the cystoscope. Data on age, weight, and height was obtained in patients when possible. RESULTS: The mean urethral length was 22.3 cm with a standard deviation of 2.4 cm. Urethral length varied between 15 cm and 29 cm. No statistically significant correlation was found between urethral length and height, weight, body mass index (BMI), or age. CONCLUSIONS: Literature documenting the length of the normal male adult urethra is scarce. Our data adds to basic anatomic information of the male urethra and may be used to optimize genitourinary device design.


Subject(s)
Urethra/anatomy & histology , Adult , Aged , Aged, 80 and over , Body Height , Body Mass Index , Body Weight , Humans , Male , Middle Aged , Reference Values
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