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1.
BMC Public Health ; 24(1): 1822, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38977988

ABSTRACT

BACKGROUND: There is limited information on the extent and patterns of disparities in COVID-19 mortality throughout the pandemic. We aimed to examine trends in disparities by demographics over variants in the pre- and post-vaccine availability period among Californian workers using a social determinants of health lens. METHODS: Using death certificates, we identified all COVID-19 deaths that occurred between January 2020 and May 2022 among workers aged 18-64 years in California (CA). We derived estimates for at-risk worker populations using the Current Population Survey. The waves of COVID-19 mortality in the pre-vaccine availability period were March 2020-June 2020 (wave 1), and July 2020-November 2020 (wave 2), and in the post-vaccine availability period: December 2020-May 2021 (wave 3), June 2021-January 2022 (wave 4), and February 2022-May 2022 (wave 5). Poisson regression models with robust standard errors were used to determine wave-specific mortality rate ratios (MRRs). We examined the change in MRR across waves by including an interaction term between each demographic characteristic and wave period in different models. The role of potential misclassification of Race/ethnicity on death certificates was examined using probabilistic quantitative bias analysis as sensitivity analysis. RESULTS: Among the 24.1 million working age CA population included in the study, there were 26,068 COVID-19 deaths in the period between January 2020 and May 2022. Compared with their respective reference groups, workers who were 50-64 years old, male, Native Hawaiian, Latino, or African American, foreign-born; individuals who had lower education; and unmarried were disproportionately affected by COVID-19 mortality. While disparities by sex, race/ethnicity and foreign-born status narrowed in later waves (post-vaccine availability), disparities by age, education level and marital status did not change substantially across waves. CONCLUSION: Demographic disparities in COVID-19 mortality narrowed in the post-vaccine availability waves. However, the existence of disparities across all waves of the pandemic, even in an era of widespread vaccine coverage, could indicate remaining gaps in prevention and differential vulnerability. Addressing the underlying social, structural, and occupational factors that contribute to these disparities is critical for achieving health equity.


Subject(s)
COVID-19 , Health Status Disparities , Humans , COVID-19/mortality , COVID-19/epidemiology , Adult , Middle Aged , California/epidemiology , Male , Female , Adolescent , Young Adult , Pandemics , SARS-CoV-2 , COVID-19 Vaccines/administration & dosage , Social Determinants of Health
2.
J Chromatogr A ; 1562: 128-133, 2018 Aug 10.
Article in English | MEDLINE | ID: mdl-29859686

ABSTRACT

The ability to tune chiral selectivity through mobile phase modifiers is a powerful tool in chiral separations. Beyond improving efficiency and/or resolution, some mobile phase systems can even invert elution order, a highly desirable result for trace analyses or preparative scale isolations. Previous work has demonstrated that acidic modifiers, such as ethanesulfonic acid (ESA), can greatly impact separations of enantiomers. However, prior studies were primarily performed on coated chiral stationary phases (CSPs), which limited the selection of the bulk mobile phase component. In this work, the effect of ESA modifier was studied for the enantioseparation of six pairs of amino acid esters on a CHIRALPAK® IA column, an immobilized amylose-based CSP, with different combinations of standard solvents (hexane and ethanol) as well as "non-standard" solvents, such as methyl t-butyl ether, ethyl acetate, tetrahydrofuran, acetone, or 1,4-dioxane. ESA generally improved selectivity, and multiple instances of elution order reversal were observed. A Van Deemter plot study reveals that ESA exerts its effect by pulling the enantiomer deeper into the chiral cavity of the chiral polymer to increase the interactions between the analytes and the stationary phase, which is the main reason for the increased enantioselectivity.


Subject(s)
Chemistry Techniques, Analytical/methods , Esters/chemistry , Amino Acids/chemistry , Amylose/chemistry , Chromatography, High Pressure Liquid , Ethanol/chemistry , Hexanes/chemistry , Solvents/chemistry , Stereoisomerism
3.
Disaster Med Public Health Prep ; 12(2): 211-221, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28760164

ABSTRACT

IntroductionFirst responders, including firefighters, police officers, emergency medical services, and company emergency response team members, have dangerous jobs that can bring them in contact with hazardous chemicals among other dangers. Limited information is available on responder injuries that occur during hazardous chemical incidents. METHODS: We analyzed 2002-2012 data on acute chemical incidents with injured responders from 2 Agency for Toxic Substances and Disease Registry chemical incident surveillance programs. To learn more about such injuries, we performed descriptive analysis and looked for trends. RESULTS: The percentage of responders among all injured people in chemical incidents has not changed over the years. Firefighters were the most frequently injured group of responders, followed by police officers. Respiratory system problems were the most often reported injury, and the respiratory irritants, ammonia, methamphetamine-related chemicals, and carbon monoxide were the chemicals more often associated with injuries. Most of the incidents with responder injuries were caused by human error or equipment failure. Firefighters wore personal protective equipment (PPE) most frequently and police officers did so rarely. Police officers' injuries were mostly associated with exposure to ammonia and methamphetamine-related chemicals. Most responders did not receive basic awareness-level hazardous material training. CONCLUSION: All responders should have at least basic awareness-level hazardous material training to recognize and avoid exposure. Research on improving firefighter PPE should continue. (Disaster Med Public Health Preparedness. 2018;12:211-221).


Subject(s)
Chemical Hazard Release/statistics & numerical data , Emergency Responders/statistics & numerical data , Occupational Injuries/epidemiology , Chemical Hazard Release/mortality , Humans , Population Surveillance/methods , Registries/statistics & numerical data , United States/epidemiology
4.
Invest Radiol ; 51(6): 349-64, 2016 06.
Article in English | MEDLINE | ID: mdl-27003227

ABSTRACT

The family of sparse reconstruction techniques, including the recently introduced compressed sensing framework, has been extensively explored to reduce scan times in magnetic resonance imaging (MRI). While there are many different methods that fall under the general umbrella of sparse reconstructions, they all rely on the idea that a priori information about the sparsity of MR images can be used to reconstruct full images from undersampled data. This review describes the basic ideas behind sparse reconstruction techniques, how they could be applied to improve MRI, and the open challenges to their general adoption in a clinical setting. The fundamental principles underlying different classes of sparse reconstructions techniques are examined, and the requirements that each make on the undersampled data outlined. Applications that could potentially benefit from the accelerations that sparse reconstructions could provide are described, and clinical studies using sparse reconstructions reviewed. Lastly, technical and clinical challenges to widespread implementation of sparse reconstruction techniques, including optimization, reconstruction times, artifact appearance, and comparison with current gold standards, are discussed.


Subject(s)
Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Algorithms , Humans , Reproducibility of Results
5.
J Mater Chem B ; 3(29): 6037-6045, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26509036

ABSTRACT

Arterial and venous thrombosis are among the most common causes of death and hospitalization worldwide. Nanotechnology approaches hold great promise for molecular imaging and diagnosis as well as tissue-targeted delivery of therapeutics. In this study, we developed and investigated bioengineered nanoprobes for identifying thrombus formation; the design parameters of nanoparticle shape and surface chemistry, i.e. incorporation of fibrin-binding peptides CREKA and GPRPP, were investigated. Two nanoparticle platforms based on plant viruses were studied - icosahedral cowpea mosaic virus (CPMV) and elongated rod-shaped tobacco mosaic virus (TMV). These particles were loaded to carry contrast agents for dual-modality magnetic resonance (MR) and optical imaging, and both modalities demonstrated specificity of fibrin binding in vitro with the presence of targeting peptides. Preclinical studies in a carotid artery photochemical injury model of thrombosis confirmed thrombus homing of the nanoprobes, with the elongated TMV rods exhibiting significantly greater attachment to thrombi than icosahedral (sphere-like) CPMV. While in vitro studies confirmed fibrin-specificity conferred by the peptide ligands, in vivo studies indicated the nanoparticle shape had the greatest contribution toward thrombus targeting, with no significant contribution from either targeting ligand. These results demonstrate that nanoparticle shape plays a critical role in particle deposition at the site of vascular injury. Shaping nanotechnologies opens the door for the development of novel targeted diagnostic and therapeutic strategies (i.e., theranostics) for arterial and venous thrombosis.

6.
Analyst ; 140(4): 1337-48, 2015 Feb 21.
Article in English | MEDLINE | ID: mdl-25574661

ABSTRACT

Toxicological assessments of human red blood cells (RBCs) are important in human health because RBCs are the most abundant cell type in our body. Erythrotoxicology testing guidelines using hemolysis have been established as a standard (e.g. by the ASTM International). However, many xenobiotics promote eryptosis (apoptosis in human RBCs) without causing hemolysis. Based on the major features of eryptosis, i.e. cell shrinkage and translocation of phosphatidylserine (PS) to the outer lipid bilayer of the plasma membrane, we report here a novel approach utilizing the quantitative tunable resistive pulse sensing (TRPS) technology, a widely adopted technique for characterizing nanoparticles in the field of nanotechnology, to measure the degree of eryptosis in a non-optical manner. With the TRPS system, we were able to determine PS externalization with microbeads functionalized with annexin-V for PS binding, cell swelling and shrinkage in physiological buffers (cell volume: 86 ± 12 fL) and solutions of different osmolarities with or without apoptotic trigger. After setting these standards, we then evaluated the toxicity of Polyphyllin D (PD), a potential anti-cancer drug that kills more liver cancer cells with multi-drug resistance, in erythrocytes to prove our concept. Data revealed that PD induced PS externalization and shrinkage in RBCs in a dose-dependent manner. Moreover, another feature of eryptosis, as small as 5 fL, was detected thus showing the PD-induced erythrotoxicity in human cells. Taken together, our results indicate that our approach using annexin-V-beads and TRPS is simple, safe and convenient, using only a small volume (35 µL) to evaluate the erythrotoxicity of xenobiotics.


Subject(s)
Annexin A5/analysis , Antineoplastic Agents/toxicity , Diosgenin/analogs & derivatives , Erythrocytes/cytology , Erythrocytes/drug effects , Phosphatidylserines/analysis , Apoptosis/drug effects , Cell Size/drug effects , Diosgenin/toxicity , Erythrocytes/chemistry , Erythrocytes/pathology , Hemolysis/drug effects , Humans , Saponins , Toxicity Tests/methods
7.
PLoS One ; 9(4): e94522, 2014.
Article in English | MEDLINE | ID: mdl-24732672

ABSTRACT

The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).


Subject(s)
Chlorocebus aethiops/genetics , Pan troglodytes/genetics , Papio/genetics , Prostate-Specific Antigen/genetics , Alternative Splicing/genetics , Amino Acid Sequence , Animals , Base Sequence , Bayes Theorem , Cloning, Molecular , Codon/genetics , Introns/genetics , Likelihood Functions , Macaca fascicularis , Male , Molecular Sequence Data , Phylogeny , Prostate-Specific Antigen/chemistry , RNA, Messenger/genetics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction
8.
Am J Trop Med Hyg ; 90(4): 627-33, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24567317

ABSTRACT

Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and cynomolgus monkeys (Macaca fascicularis) have been reported to be infected naturally with T. cruzi. In this study, we retrospectively reviewed cases of animals that were diagnosed with lymphocytic myocarditis and used a polymerase chain reaction (PCR)-based method (S36/S35 primer set) to amplify T. cruzi DNA from archived frozen and formalin-fixed paraffin-embedded (FFPE) cardiac tissues. We show that the PCR method is applicable in archived frozen and FFPE tissues and the sensitivity is in the femtogram range. A positive correlation between PCR positivity and lymphocytic myocarditis in both baboons and cynomolgus monkeys is shown. We also show epicarditis as a common finding in animals infected with T. cruzi.


Subject(s)
Chagas Cardiomyopathy/parasitology , DNA, Kinetoplast/analysis , Trypanosoma cruzi/genetics , Animals , Chagas Cardiomyopathy/pathology , Chagas Cardiomyopathy/veterinary , Female , Lymphocytes/pathology , Macaca fascicularis , Male , Monkey Diseases/parasitology , Myocarditis/parasitology , Myocarditis/pathology , Myocarditis/veterinary , Papio hamadryas , Polymerase Chain Reaction , Retrospective Studies , Texas , Trypanosoma cruzi/isolation & purification
9.
Article in English | MEDLINE | ID: mdl-23988480

ABSTRACT

Many animals undergo extended periods of fasting. During these fasts, animals oxidize a ratio of macronutrients dependent on the nutritional, energetic, and hydric requirements of the fasting period. In this study, we use Japanese quail (Coturnix coturnix japonica), a bird with natural intermediate fasting periods, to examine macronutrient use during a 6d fast. We raised groups of quail on isotopically labeled materials ((13)C-1-leucine, (13)C-U-glucose, or (13)C-1-palmitic acid) with the intent of labeling specific macronutrient/tissue pools in each treatment, and then traced their use as fuels by measuring the δ(13)C values of breath CO2. Based on changes in δ(13)C values during the fast, it appears that the carbohydrate label,(13)C-U-glucose, was largely incorporated into the lipid pool and thus breath samples ultimately reflected lipid use rather than carbohydrate use. In the lipid treatment, the (13)C-1-palmitic acid faithfully labeled the lipid pool and was reflected in the kinetics δ(13)C values in breath CO2 during the fast. Endogenous lipid oxidation peaked after 24h of fasting and remained constantly elevated thereafter. The protein label,(13)C-1-leucine, showed clear diurnal periods of protein sparing and degradation, with maximal rates of protein oxidation occurring at night and the lowest rates occurring during the day time. This stable isotope tracer method provides a noninvasive approach to study the nutrient dynamics of fasting animals and should provide new insights into how different types of animals use specific nutrient pools during fasting and possibly other non-steady physiological states.


Subject(s)
Coturnix/metabolism , Fasting/physiology , Lipid Metabolism , Animals , Body Temperature , Carbon Isotopes , Circadian Rhythm , Leucine/metabolism , Oxidation-Reduction , Palmitic Acid/metabolism
10.
Lab Chip ; 13(18): 3698-706, 2013 Sep 21.
Article in English | MEDLINE | ID: mdl-23881222

ABSTRACT

In this paper, we present a lab-in-a-droplet bioassay strategy for a centrifugal microfluidics or lab-on-a-disc (LOAD) platform with three important advancements including density difference pumping, power to disc and bidirectional flow control. First, with the water based bioassay droplets trapped in a micro-channel filled with mineral oil, centrifugal force due to the density difference between the water and oil phases actuates droplet movement while the oil based medium remains stationary. Second, electricity is coupled to the rotating disc through a split-core transformer, thus enabling on-chip real-time heating in selected areas as desired and wireless programmable functionality. Third, an inertial mechanical structure is proposed to achieve bidirectional flow control within the spinning disc. The droplets can move back and forth between two heaters upon changing the rotational speed. Our platform is an essential and versatile solution for bioassays such as those involving DNA amplification, where localized temperature cycling is required. Finally, without the loss of generality, we demonstrate the functionality of our platform by performing real-time polymerase chain reaction (RT-PCR) in a linear microchannel made with PTFE (Teflon) micro-tubing.


Subject(s)
Microfluidic Analytical Techniques/instrumentation , Mineral Oil/chemistry , Centrifugation , DNA/analysis , Electricity , Lab-On-A-Chip Devices , Real-Time Polymerase Chain Reaction/instrumentation , Real-Time Polymerase Chain Reaction/methods , Temperature , Water/chemistry , Wireless Technology
11.
Anal Chim Acta ; 782: 46-53, 2013 Jun 11.
Article in English | MEDLINE | ID: mdl-23708283

ABSTRACT

This report describes a novel diagnostic assay for rapid detection of the Panton-Valentine Leukocidin (PVL) toxin of methicillin-resistant Staphylococcus aureus (MRSA) utilizing resistive pulse sensing (RPS), loop-mediated isothermal DNA amplification (LAMP) in combination with gold nanoparticles (AuNPs). The PVL DNA from MRSA was specifically amplified by LAMP using four primers at one temperature (65 °C). The DNA products with biotin were then conjugated to a first AuNP1 (55±2 nm) through biotin-avidin binding. A second AuNP2 (30±1.5 nm) coated with a specific DNA probe hybridized with the LAMP DNA products at the loop region to enhance assay sensitivity and specificity, to generate supra-AuNP1-DNA-AuNP2 assemblies. Scanning electron microscopy confirmed the presence of these supra-assemblies. Using RPS, detection and quantitation of the agglomerated AuNPs were performed by a tunable fluidic nanopore sensor. The results demonstrate that the LAMP-based RPS sensor is sensitive and rapid for detecting the PVL DNA. This technique could achieve a limit of detection (LOD) up to about 500 copies of genomic DNA from the bacteria MRSA MW2 and the detection can be completed within two hours with a straightforward signal-to-readout setup. It is anticipated that this LAMP-based AuNP RPS may become an effective tool for MRSA detection and a potential platform in clinical laboratory to report the presence or absence of other types of infectious agents.


Subject(s)
Bacterial Toxins/analysis , Bacterial Toxins/genetics , DNA, Bacterial/analysis , Exotoxins/analysis , Exotoxins/genetics , Leukocidins/analysis , Leukocidins/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Nucleic Acid Amplification Techniques/methods , Base Sequence , DNA Probes , Gold , Limit of Detection , Molecular Sequence Data , Nanoparticles , Nucleic Acid Amplification Techniques/instrumentation , Polymerase Chain Reaction/methods , Sensitivity and Specificity
12.
Biomacromolecules ; 13(12): 3990-4001, 2012 Dec 10.
Article in English | MEDLINE | ID: mdl-23121655

ABSTRACT

The development of multifunctional nanoparticles for medical applications is of growing technological interest. A single formulation containing imaging and/or drug moieties that is also capable of preferential uptake in specific cells would greatly enhance diagnostics and treatments. There is growing interest in plant-derived viral nanoparticles (VNPs) and establishing new platform technologies based on these nanoparticles inspired by nature. Cowpea mosaic virus (CPMV) serves as the standard model for VNPs. Although exterior surface modification is well-known and has been comprehensively studied, little is known of interior modification. Additional functionality conferred by the capability for interior engineering would be of great benefit toward the ultimate goal of targeted drug delivery. Here, we examined the capacity of empty CPMV (eCPMV) particles devoid of RNA to encapsulate a wide variety of molecules. We systematically investigated the conjugation of fluorophores, biotin affinity tags, large molecular weight polymers such as poly(ethylene glycol) (PEG), and various peptides through targeting reactive cysteines displayed selectively on the interior surface. Several methods are described that mutually confirm specific functionalization of the interior. Finally, CPMV and eCPMV were labeled with near-infrared fluorophores and studied side-by-side in vitro and in vivo. Passive tumor targeting via the enhanced permeability and retention effect and optical imaging were confirmed using a preclinical mouse model of colon cancer. The results of our studies lay the foundation for the development of the eCPMV platform in a range of biomedical applications.


Subject(s)
Colonic Neoplasms/drug therapy , Comovirus/metabolism , Drug Delivery Systems/methods , Nanoparticles/chemistry , Animals , Biocompatible Materials , Blotting, Western , Chromatography, Gel , Disease Models, Animal , Electrophoresis, Agar Gel , HT29 Cells , HeLa Cells , Humans , Hydrophobic and Hydrophilic Interactions , Maleimides/metabolism , Mice , Microscopy, Confocal , Microscopy, Electron, Transmission , Particle Size
13.
Mol Cell Proteomics ; 11(12): 1690-708, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22956732

ABSTRACT

In Swiss 3T3 fibroblasts, long-term stimulation with PDGF, but not insulin-like growth factor 1 (IGF-1) or EGF, results in the establishment of an elongated migratory phenotype, characterized by the formation of retractile dendritic protrusions and absence of actin stress fibers and focal adhesion complexes. To identify receptor tyrosine kinase-specific reorganization of the Swiss 3T3 proteome during phenotypic differentiation, we compared changes in the pattern of protein synthesis and phosphorylation during long-term exposure to PDGF, IGF-1, EGF, and their combinations using 2DE-based proteomics after (35)S- and (33)P-metabolic labeling. One hundred and five differentially regulated proteins were identified by mass spectrometry and some of these extensively validated. PDGF stimulation produced the highest overall rate of protein synthesis at any given time and induced the most sustained phospho-signaling. Simultaneous activation with two or three of the growth factors revealed both synergistic and antagonistic effects on protein synthesis and expression levels with PDGF showing dominance over both IGF-1 and EGF in generating distinct proteome compositions. Using signaling pathway inhibitors, PI3K was identified as an early site for signal diversification, with sustained activity of the PI3K/AKT pathway critical for regulating late protein synthesis and phosphorylation of target proteins and required for maintaining the PDGF-dependent motile phenotype. Several proteins were identified with novel PI3K/Akt-dependent synthesis and phosphorylations including eEF2, PRS7, RACK-1, acidic calponin, NAP1L1, Hsp73, and fascin. The data also reveal induction/suppression of key F-actin and actomyosin regulators and chaperonins that enable PDGFR to direct the assembly of a motile cytoskeleton, despite simultaneous antagonistic signaling activities. Together, the study demonstrates that long-term exposure to different growth factors results in receptor tyrosine kinase-specific regulation of relatively small subproteomes, and implies that the strength and longevity of receptor tyrosine kinase-specific signals are critical in defining the composition and functional activity of the resulting proteome.


Subject(s)
Epidermal Growth Factor/pharmacology , Insulin-Like Growth Factor I/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Platelet-Derived Growth Factor/pharmacology , Proteome/analysis , 3T3 Cells , Animals , Benzamides/pharmacology , Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors , Cell Line , Chromones/pharmacology , Enzyme Inhibitors/pharmacology , Fibroblasts , Flavonoids/pharmacology , Isotope Labeling , Mice , Morpholines/pharmacology , Nucleosome Assembly Protein 1/metabolism , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Platelet-Derived Growth Factor/metabolism , Signal Transduction/drug effects
14.
Chem Commun (Camb) ; 48(72): 9044-6, 2012 Sep 18.
Article in English | MEDLINE | ID: mdl-22858632

ABSTRACT

The development of viral nanoparticles (VNP) displaying multiple copies of the buckyball (C(60)) and their photodynamic activity is described. VNP-C(60) conjugates were assembled using click chemistry. Cell uptake and cell killing using white light therapy and a prostate cancer cell line is demonstrated.


Subject(s)
Fullerenes/chemistry , Fullerenes/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Viruses/chemistry , Cell Line, Tumor , Click Chemistry , Humans
15.
J Diet Suppl ; 9(1): 45-56, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22432802

ABSTRACT

BACKGROUND: Cancer is one of the leading causes of deaths in the world. Current chemotherapeutic agents are associated with serious side effects in patients therefore researchers are trying to find an alternative agent that is effective against cancer as well as less toxic. Resveratrol (3,5,4'-trihydroxystilbene), commonly found in red wine and grape skins, is a phytoalexin agent that was originally extracted from the roots of Polygonum cuspidatum. Resveratrol is believed to work as a chemopreventive agent by producing its effect on cell apoptosis, antiproliferation, and anti-inflammation. PURPOSE: To determine whether resveratrol is effective as an anticancer agent. METHODS: A systematic review was performed by searching various databases for primary, secondary, and tertiary references. Databases included PubMed, EBSCO, Cochrane, AccessPharmacy, and StatRef by using key terms of "resveratrol," "cancer," and "anticancer." Review search looked at both animal and human studies limited within 10 years. FINDINGS: The major mechanisms of actions through which resveratrol works include proapoptotic, antiproliferation, and anti-inflammation. Numerous in vitro and in vivo studies have supported these mechanisms thus warranting further research in human studies for resveratrol's anticancer effects. Pharmacokinetic human studies suggest good tolerability in healthy subjects, although they have low absorptive characteristics. CONCLUSION: Resveratrol appears to have anticancer effects. Additionally, these studies indicate that resveratrol's chemoprevention effect is dose and duration dependent. It has synergistic effect with anticancer drugs in vitro. Further human studies need to be done.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Neoplasms/drug therapy , Outcome Assessment, Health Care , Phytotherapy , Plant Extracts/therapeutic use , Stilbenes/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Fallopia japonica/chemistry , Humans , Neoplasms/prevention & control , Plant Extracts/pharmacology , Resveratrol , Stilbenes/pharmacology , Vitis/chemistry , Wine
16.
Am J Physiol Gastrointest Liver Physiol ; 300(1): G12-20, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20966033

ABSTRACT

Heme oxygenase-1 (HO-1) induction by hemin or Panhematin protects against experimental pancreatitis. As a preclinical first step toward determining whether HO-1 upregulation is a viable target in acute pancreatitis (AP) patients, we tested the hypothesis that HO-1 expression in peripheral blood mononuclear cell (PBMC) subsets of hospitalized patients with mild AP is upregulated then normalizes upon recovery and that cells from AP patients have the potential to upregulate their HO-1 ex vivo if exposed to Panhematin. PBMCs were isolated on days 1 and 3 of hospitalization from the blood of 18 AP patients, and PMBC HO-1 levels were compared with PMBCs of 15 hospitalized controls (HC) and 7 volunteer healthy controls (VC). On day 1 of hospitalization, AP patients compared with VCs had higher HO-1 expression in monocytes and neutrophils. Notably, AP monocyte HO-1 levels decreased significantly upon recovery. Panhematin induced HO-1 in ex vivo cultured AP PBMCs more readily than in HC or VC PBMCs. Furthermore, PBMCs from acutely ill AP patients on day 1 were more responsive to HO-1 induction compared with day 3 upon recovery. Similarly, mouse splenocytes had enhanced HO-1 inducibility as their pancreatitis progressed from mild to severe. In conclusion, AP leads to reversible PBMC HO-1 upregulation that is associated with clinical improvement and involves primarily monocytes. Leukocytes from AP patients or mice with AP are primed for HO-1 induction by Panhematin, which suggests that Panhematin could offer a therapeutic benefit.


Subject(s)
Heme Oxygenase-1/biosynthesis , Leukocytes, Mononuclear/enzymology , Pancreatitis/enzymology , Adult , Animals , Blood Cells/enzymology , Enzyme Induction , Female , Hemin/pharmacology , Humans , Male , Mice , Middle Aged , Pancreatitis/genetics , Up-Regulation
17.
Glob Public Health ; 5(2): 129-35, 2010.
Article in English | MEDLINE | ID: mdl-20213563

ABSTRACT

'Sustainability' has become a central criterion used by funders - including foundations, governmental agencies and international agencies - in evaluating public health programmes. The criterion became important as a result of frustration with discontinuities in the provision of care. As a result of its application, projects that involve building infrastructure, training or relatively narrow objectives tend to receive support. In this article, we argue for a reconceptualisation of sustainability criteria in light of the idea that health is an investment that is itself sustaining and sustainable, and for the abandonment of conceptualisations of sustainability that focus on the consumable medical interventions required to achieve health. The implication is a tailoring of the time horizon for creating value that reflects the challenges of achieving health in a community. We also argue that funders and coordinating bodies, rather than the specialised health providers that they support, are best positioned to develop integrated programmes of medical interventions to achieve truly sustainable health outcomes.


Subject(s)
Global Health , Program Development , Program Evaluation , Africa/epidemiology , Dracunculiasis/epidemiology , Dracunculiasis/prevention & control , Financial Support , Poverty , Public Health Practice/economics
18.
J Biol Chem ; 283(26): 18177-86, 2008 Jun 27.
Article in English | MEDLINE | ID: mdl-18467332

ABSTRACT

The microtubule-associated protein tau can associate with various other proteins in addition to tubulin, including the SH3 domains of Src family tyrosine kinases. Tau is well known to aggregate to form hyperphosphorylated filamentous deposits in several neurodegenerative diseases (tauopathies) including Alzheimer disease. We now report that tau can bind to SH3 domains derived from the p85alpha subunit of phosphatidylinositol 3-kinase, phospholipase Cgamma1, and the N-terminal (but not the C-terminal) SH3 of Grb2 as well as to the kinases Fyn, cSrc, and Fgr. However, the short inserts found in neuron-specific isoforms of Src prevented the binding of tau. The experimentally determined binding of tau peptides is well accounted for when modeled into the peptide binding cleft in the SH3 domain of Fyn. After phosphorylation in vitro or in transfected cells, tau showed reduced binding to SH3 domains; no binding was detected with hyperphosphorylated tau isolated from Alzheimer brain, but SH3 binding was restored by phosphatase treatment. Tau mutants with serines and threonines replaced by glutamate, to mimic phosphorylation, showed reduced SH3 binding. These results strongly suggest that tau has a potential role in cell signaling in addition to its accepted role in cytoskeletal assembly, with regulation by phosphorylation that may be disrupted in the tauopathies including Alzheimer disease.


Subject(s)
GRB2 Adaptor Protein/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phospholipase C gamma/metabolism , src-Family Kinases/metabolism , tau Proteins/chemistry , Alzheimer Disease/metabolism , Amino Acid Sequence , Humans , Molecular Conformation , Molecular Sequence Data , Peptides/chemistry , Phosphorylation , Protein Binding , Protein Structure, Tertiary , src Homology Domains
19.
Arch Intern Med ; 168(6): 649-56, 2008 Mar 24.
Article in English | MEDLINE | ID: mdl-18362258

ABSTRACT

BACKGROUND: The epidemiology of acute alcoholic pancreatitis (AP), chronic alcoholic pancreatitis (CP), acute alcoholic hepatitis (AH), and chronic alcoholic hepatitis with cirrhosis (CH) alone or in combination is not well described. To better understand alcohol-related liver and pancreas effects on and associations with different ethnic groups and sexes, we analyzed the trends of AP, CP, AH, CH, AP plus AH, and CP plus CH in the United States. METHODS: We examined discharge records from the Nationwide Inpatient Sample, the largest representative sample of US hospitals. Hospital discharges, case-fatality, and sex and race contributions were calculated from patients with discharge diagnoses of AP, CP, AH, CH, AP plus AH, or CP plus CH between 1988 and 2004. RESULTS: The distribution of overall hospital discharges per 100 000 persons between 1988 and 2004 was as follows: AP, 49.2; CP, 8.1; AH, 4.5; and CH, 13.7. Overall hospital discharges per 100 000 persons for AP plus AH were 1.8; and for CP plus CH, 0.32. There were higher male to female ratios for AH and CH, and less so for AP and CP. A markedly higher frequency of AP (63.5) and CP (11.3) was seen among blacks than among whites (AP, 29.6 and CP, 5.1), Hispanics (AP, 27.1 and CP, 3.7), Asians (AP, 12.8 and CP, 1.4), and American Indians (AP, 15.5 and CP, 2.3). This higher frequency remained stable between 1994 and 2004. Overall case fatality steadily decreased in all categories, but remains highest in CH (13.6%) with similar racial distributions. CONCLUSIONS: In the United States, AP is the most common discharge diagnosis among alcohol-related liver or pancreas complications, while CH has the highest case fatality rate and male to female ratio. Blacks have the highest frequency of alcohol-related pancreatic disease.


Subject(s)
Liver Diseases, Alcoholic/epidemiology , Pancreatitis, Alcoholic/epidemiology , Adult , Age Factors , Chronic Disease , Female , Humans , Male , Middle Aged , Sex Factors , United States/epidemiology
20.
World J Surg ; 32(4): 537-42, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18320267

ABSTRACT

Although surgical care has not been seen as a priority in the international public health community, surgical disease constitutes a significant portion of the global burden of disease and must urgently be addressed. The experience of the nongovernmental organizations Partners In Health (PIH) and Zanmi Lasante (ZL) in Haiti demonstrates the potential for success of a surgical program in a rural, resource-poor area when services are provided through the public sector, integrated with primary health care services, and provided free of charge to patients who cannot pay. Providing surgical care in resource-constrained settings is an issue of global health equity and must be featured in national and international discussions on the improvement of global health. There are numerous training, funding, and programmatic considerations, several of which are raised by considering the data from Haiti presented here.


Subject(s)
Developing Countries , Emergency Medical Services/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Poverty Areas , Rural Health Services/statistics & numerical data , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Haiti , Humans , Infant , Infant, Newborn , Male , Middle Aged , Obstetric Surgical Procedures/statistics & numerical data , Retrospective Studies , World Health Organization
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