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Identification of Myeloid Derived Suppressor Cells in Dogs with Naturally Occurring Cancer  [PDF]
Michelle R. Goulart, G. Elizabeth Pluhar, John R. Ohlfest
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033274
Abstract: Dogs with naturally occurring cancer represent an important large animal model for drug development and testing novel immunotherapies. However, poorly defined immunophenotypes of canine leukocytes have limited the study of tumor immunology in dogs. The accumulation of myeloid derived suppressor cells (MDSCs) is known to be a key mechanism of immune suppression in tumor-bearing mice and in human patients. We sought to identify MDSCs in the blood of dogs with cancer. Peripheral blood mononuclear cells (PBMCs) from dogs with advanced or early stage cancer and from age-matched healthy controls were analyzed by flow cytometry and microscopy. Suppressive function was tested in T cell proliferation and cytokine elaboration assays. Semi-quantitative RT-PCR was used to identify potential mechanisms responsible for immunosuppression. PBMCs from dogs with advanced or metastatic cancer exhibited a significantly higher percentage of CD11b+CD14?MHCII? cells compared to dogs diagnosed with early stage non-metastatic tumors and healthy dogs. These CD11b+ CD14?MHCII? cells constitute a subpopulation of activated granulocytes that co-purify with PBMCs, display polymorphonuclear granulocyte morphology, and demonstrate a potent ability to suppress proliferation and IFN-γ production in T cells from normal and tumor-bearing donors. Furthermore, these cells expressed hallmark suppressive factors of human MDSC including ARG1, iNOS2, TGF-β and IL-10. In summary our data demonstrate that MDSCs accumulate in the blood of dogs with advanced cancer and can be measured using this three-marker immunophenotype, thereby enabling prospective studies that can monitor MDSC burden.
Preparation and In Vitro Evaluation of Sustained-Release Matrix Tablets of Flutamide Using Synthetic and Naturally Occurring Polymers
Jaber Emami,Mona Tajeddin,Fatemeh Ahmadi
Iranian Journal of Pharmaceutical Research , 2008,
Abstract: Frequent dosing of the potent anti-androgen, flutamide, is necessary to reach a therapeutic level for the treatment of prostatic carcinoma. Sustained delivery of the drug could reduce the adverse effects such as gastrointestinal disorders and improve patient compliance. In the present study sustained-release matrix tablets of flutamide were prepared by direct compression method using different polymers. Cellulose ethers (HPMC and NaCMC), natural gums (guar and xanthan gums) and compressible Eudragits (RSPO and RLPO) and their combinations were used in different ratios to examine their influence on tablet properties and drug release profile. Tablets were evaluated by measurement of hardness, friability, content uniformity, weight variation and drug release pattern. All the tablets met the pharmacopoeial requirements for physical tests, based on USP 29. Almost in all formulations, with increasing the percentage of polymer, release rate decreased, though drug release pattern was mainly dependent on the type of polymer. Formulations H2F4 (contained 25% HPMC) and S3F4 (contained around 40% RSPO) met the desired requirements for a sustained-release dosage form. These two formulations released their drug content with a first order kinetic.
Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy  [PDF]
Roger Kenneth Whealands Smith, Natalie Jayne Werling, Stephanie Georgina Dakin, Rafiqul Alam, Allen E. Goodship, Jayesh Dudhia
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075697
Abstract: Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X107 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in enhancing normalisation of biomechanical, morphological, and compositional parameters. These data in natural disease, with no adverse findings, support the use of this treatment for human tendon injuries.
A Naturally-Occurring Histone Acetyltransferase Inhibitor Derived from Garcinia indica Impairs Newly Acquired and Reactivated Fear Memories  [PDF]
Stephanie A. Maddox, Casey S. Watts, Valérie Doyère, Glenn E. Schafe
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054463
Abstract: The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA) impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.
Naturally Occurring Food Toxins  [PDF]
Laurie C. Dolan,Ray A. Matulka,George A. Burdock
Toxins , 2010, DOI: 10.3390/toxins2092289
Abstract: Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States.
Naturally occurring radionuclides and Earth sciences  [cached]
G. Ferrara
Annals of Geophysics , 1997, DOI: 10.4401/ag-3860
Abstract: Naturally occurring radionuclides are used in Earth sciences for two fundamental purposes: age determination of rocks and minerals and studies of variation of the isotopic composition of radiogenic nuclides. The methodologies that are in use today allow us to determine ages spanning from the Earth's age to the late Quaternary. The variations of isotopic composition of radiogenic nuclides can be applied to problems of mantle evolution, magma genesis and characterization with respect to different geodynamic situations and can provide valuable information not obtainable by elemental geochemistry.
Naturally Occurring Xanthones: Chemistry and Biology  [PDF]
J. S. Negi,V. K. Bisht,P. Singh,M. S. M. Rawat,G. P. Joshi
Journal of Applied Chemistry , 2013, DOI: 10.1155/2013/621459
Abstract: Xanthones are one of the biggest classes of compounds in natural product chemistry. A number of xanthones have been isolated from natural sources of higher plants, fungi, ferns, and lichens. They have gradually risen to great importance because of their medicinal properties. This review focuses on the types, isolation, characterization, biological applications, and biosynthesis of naturally occurring xanthones isolated so far. Different physicochemical and instrumental methods such as liquid-solid and liquid-liquid extraction, TLC, flash chromatography, column chromatography, IR, 1H NMR and 13C NMR spectroscopy, GLC, HPLC, GC, and LCMS have been widely used for isolation and structural elucidation of xanthones. Hepatoprotective, anticarcinogenic, antileprosy, antimalarial, antioxidant, anticholinergic, mutagenicity, radioprotective, immunomodulatory, antibone resorption, antiparasitic, neuraminidase inhibitory, anticomplement, antibacterial, antifungal, algicidal, anti-HIV, cardioprotective, antitumoral, antidiabetes, antihyperlipidemic, antiatherogenic, anti-inflammatory, antiulcer, antidiabetic, hypolipidemic, analgesic, antiasthmatic, antihistaminic, antiamoebic, diuretic, antidiarrheal, larvicidal, and ovicidal activities have been reported for natural occurring xanthones. To a certain extent, this review provides necessary foundation for further research and development of new medicines. 1. Introduction Xanthones are secondary metabolites commonly occurring in higher plant families, fungi, and lichen [1]. Their pharmacological properties have raised great interest. Structures of xanthones are related to that of flavonoids and their chromatographic behaviours are also similar. Flavonoids are frequently encountered in nature, whereas xanthones are found in limited number of families. Xanthones always occur in the families Gentianaceae, Guttiferae, Moraceae, Clusiaceae, and Polygalaceae. Xanthones are sometimes found as the parent polyhydroxylated compounds but most are mono- or polymethyl ethers or are found as glycosides [2]. Unlike iridoids, xanthones are apparently not present in all plant species investigated in the family Gentianaceae. This is documented by the systematic work of Hostettmann et al. [3]. Natural occurrence of 12 xanthones in higher plants and 4 in fungi has been reviewed by Roberts in 1961 and by Dean in 1963 [4, 5]. Gottlieb [6] mentioned the isolation of 60 xanthones from higher plants and 7 from fungi, whereas Carpenter et al. [7] listed 82 xanthones from higher plants. Gunasekera [8] recorded 183 xanthones from 5 families of
Naturally occurring anti M complicating ABO grouping  [cached]
Khalid Safoorah,Dantes Roelyn,Varghese Sunu,Al Hakawati Imadeddin
Indian Journal of Pathology and Microbiology , 2011,
Abstract: Anti M is considered a naturally occurring antibody that is usually active at temperatures below 37°C and is thus of no clinical significance. This antibody, if present in an individual, can lead to a discrepancy between forward and reverse ABO grouping and thus creates diagnostic difficulties for blood bank staff. We report a case of a 58-year-old lady who had an unexpected reaction in reverse grouping due to anti M that posed a problem for us in the interpretation of results of her blood group. We also reviewed the literature to find out the significance of such discrepancy in blood grouping.
Altered Dopamine Signaling in Naturally Occurring Maternal Neglect  [PDF]
Stephen C. Gammie, Michelle N. Edelmann, Caleigh Mandel-Brehm, Kimberly L. D'Anna, Anthony P. Auger, Sharon A. Stevenson
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001974
Abstract: Background Child neglect is the most common form of child maltreatment, yet the biological basis of maternal neglect is poorly understood and a rodent model is lacking. Methodology/Principal Findings The current study characterizes a population of mice (MaD1) which naturally exhibit maternal neglect (little or no care of offspring) at an average rate of 17% per generation. We identified a set of risk factors that can predict future neglect of offspring, including decreased self-grooming and elevated activity. At the time of neglect, neglectful mothers swam significantly more in a forced swim test relative to nurturing mothers. Cross-fostered offspring raised by neglectful mothers in turn exhibit increased expression of risk factors for maternal neglect and decreased maternal care as adults, suggestive of possible epigenetic contributions to neglect. Unexpectedly, offspring from neglectful mothers elicited maternal neglect from cross-fostered nurturing mothers, suggesting that factors regulating neglect are not solely within the mother. To identify a neurological pathway underlying maternal neglect, we examined brain activity in neglectful and nurturing mice. c-Fos expression was significantly elevated in neglectful relative to nurturing mothers in the CNS, particularly within dopamine associated areas, such as the zona incerta (ZI), ventral tegmental area (VTA), and nucleus accumbens. Phosphorylated tyrosine hydroxylase (a marker for dopamine production) was significantly elevated in ZI and higher in VTA (although not significantly) in neglectful mice. Tyrosine hydroxylase levels were unaltered, suggesting a dysregulation of dopamine activity rather than cell number. Phosphorylation of DARPP-32, a marker for dopamine D1-like receptor activation, was elevated within nucleus accumbens and caudate-putamen in neglectful versus nurturing dams. Conclusions/Significance These findings suggest that atypical dopamine activity within the maternal brain, especially within regions involved in reward, is involved in naturally occurring neglect and that MaD1 mice are a useful model for understanding the basis of naturally occurring neglect.
Adsorption of fluoride ions onto naturally occurring earth materials
M Karthikeyan, V Gopal, KP Elango
Journal of Applied Sciences and Environmental Management , 2010,
Abstract: Batch sorption system using two naturally occurring earth materials (EM) as adsorbents was investigated to remove fluoride ions from aqueous solution. The system variables studied include initial concentration of the sorbate, agitation time, adsorbent dose, pH, co-ions and temperature. The experimental data fitted well to the Freundlich isotherm. The amount of fluoride ions adsorbed per unit mass of the adsorbent was found to be 0.011 and 0.007 mg/g, at 30 °C from 4 mg/L fluoride solution, for EM1 and EM2 respectively. Thermodynamic parameters such as ΔH°, ΔS° and ΔG° were calculated which indicates that the removal of fluoride ions is an endothermic process. Kinetic studies reveal that the adsorption follows reversible first order kinetics. X-ray diffraction patterns of the adsorbents before and after adsorption and Dubinin-Radushkevick (D-R) isotherm indicate that the adsorption of fluoride ions onto these materials is a physisorption process. @ JASEM J. Appl. Sci. Environ. Manage. December, 2010, Vol. 14 (4) 90 - 95
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