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1.
J Vis Exp ; (141)2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30474644

RESUMO

Inflammatory bowel disease (IBD) is one of the immune-related gastrointestinal disorders, including ulcerative colitis and Crohn's disease, that affects the life quality of millions of people worldwide. IBD symptoms include abdominal pain, diarrhea, and rectal bleeding, which may result from the interactions among gut microbiota, food components, intestinal epithelial cells, and immune cells. It is of particular importance to assess how each key gene expressed in intestinal epithelial and immune cells affects inflammation in the colon. G protein-coupled taste receptors, including G protein subunit α-gustducin and other signaling proteins, have been found in the intestines. Here, we use α-gustducin as a representative and describe a dextran sulfate sodium (DSS)-induced IBD model to evaluate the effect of gustatory gene mutations on gut mucosal immunity and inflammation. This method combines gene knockout technology with the chemically induced IBD model, and thus can be applied to assess the outcome of gustatory gene nullification as well as other genes that may exuberate or dampen the DSS-induced immune response in the colon. Mutant mice are administered with DSS for a certain period during which their body weight, stool, and rectal bleeding are monitored and recorded. At different timepoints during administration, some mice are euthanized, then the sizes and weights of their spleens and colons are measured and gut tissues are collected and processed for histological and gene expression analyses. The data show that the α-gustducin knockout results in excessive weight loss, diarrhea, intestinal bleeding, tissue damage, and inflammation vs. wild-type mice. Since the severity of induced inflammation is affected by mouse strains, housing environment, and diet, optimization of DSS concentration and administration duration in a pilot experiment is particularly important. By adjusting these factors, this method can be applied to assess both anti- and pro-inflammatory effects.

2.
Brain Behav Immun ; 71: 23-27, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29678794

RESUMO

Inflammatory bowel disease (IBD) is a debilitating immune-related condition that affects over 1.4 million Americans. Recent studies indicate that taste receptor signaling is involved in much more than sensing food flavor, and taste receptors have been localized in a variety of extra-oral tissues. One of the newly revealed functions of taste receptors and downstream signaling proteins is modulation of immune responses to microbes and parasites. We previously found that components of the taste receptor signaling pathway are expressed in subsets of the intestinal epithelial cells. α-Gustducin, a key G-protein α subunit involved in sweet, umami, and bitter taste receptor signaling, is expressed in the intestinal mucosa. In this study, we investigated the role of α-gustducin in regulation of gut mucosal immunity and inflammation using α-gustducin knockout mice in the dextran sulfate sodium (DSS)-induced IBD model. DSS is a chemical colitogen that can cause intestinal epithelial damage and inflammation. We analyzed DSS-induced colitis in α-gustducin knockout versus wild-type control mice after administration of DSS in drinking water. Our results show that the knockout mice had aggravated weight loss, diarrhea, intestinal bleeding, and inflammation over the experimental period compared to wild-type mice, concurrent with augmented immune cell infiltration and increased expression of TNF and IFN-γ but decreased expression of IL-13 and IL-5 in the colon. These results suggest that the taste receptor signaling pathway may play critical roles in regulating gut immune balance and inflammation.

3.
Huan Jing Ke Xue ; 37(8): 3160-3168, 2016 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964746

RESUMO

The environmental behavior and bioavailability of selenium (Se) in soils are greatly affected by its adsorption on soil components, which are largely discrepant with the different physicochemical properties of soils. 18 kinds of farmland soils with various physicochemical properties in China were used in batch adsorption experiments in this study to explore the influencs of soil pH, amorphous iron, aluminum oxides, organic matter and mechanical composition on the adsorption of SeO42-. The results showed that the adsorption of SeO42- on 18 soils was an initially fast phase followed by a slow process, during which the adsorption equilibrium was reached at 24 h. Second-order kinetic model(R2>0.976)and Freundlich isothermal model(R2>0.842)were the fittest for most of the adsorption process. SeO42- adsorption capacity of soil was negatively correlated with soil pH value (P<0.01) and the content of carbonate (P<0.05), while positively correlated with the content of amorphous iron, aluminum oxides (P<0.01) and organic matter content (P<0.05). The partition coefficient of solid to liquid (Kd values) of SeO42- in adsorption process for all the 18 soil types were very low and without big differences(0.99 L·kg-1-18.18 L·kg-1). The desorption rates for all tested soils were above 80%, which indicated the reversibility of SeO42- adsorption in soil. It was inferred from the above that the low Kd and high desorption rate reflected that selenate was featured by easy migration and leaching in soil, which should be emphasized in the regional evaluation and regulation of Se level.

4.
Acta Crystallogr C Struct Chem ; 71(Pt 8): 679-82, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26243414

RESUMO

A new linear bismuth(III) coordination polymer, catena-poly[[chloridobismuth(III)]-µ3-1,10-phenanthroline-2,9-dicarboxylato-κ(6)O(2):O(2),N(1),N(10),O(9):O(9)], [Bi(C14H6N2O4)Cl]n, has been obtained by an ionothermal method and characterized by elemental analysis, energy-dispersive X-ray spectroscopy, IR spectroscopy, thermal stability studies and single-crystal X-ray diffraction. The structure is constructed by Bi(C14H6N2O4)Cl fragments in which each Bi(III) centre is seven-coordinated by one Cl atom, four O atoms and two N atoms. The coordination geometry of the Bi(III) cation is distorted pentagonal-bipyramidal (BiO4N2Cl), with one bridging carboxylate O atom and one Cl atom located in the axial positions. The Bi(C14H6N2O4)Cl fragments are further extended into a one-dimensional linear polymeric structure via subsequent but different centres of symmetry (bridging carboxylate O atoms). Neighbouring linear chains are assembled via weak C-H···O and C-H···Cl hydrogen bonds, forming a three-dimensional supramolecular architecture. Intermolecular π-π stacking interactions are observed, with centroid-to-centroid distances of 3.678 (4) Å, which further stabilize the structure. In addition, the solid-state fluorescence properties of the title coordination polymer were investigated.


Assuntos
Bismuto/química , Complexos de Coordenação/síntese química , Fenantrolinas/síntese química , Polímeros/química , Complexos de Coordenação/química , Cristalografia por Raios X , Fluorescência , Ligações de Hidrogênio , Estrutura Molecular
5.
Brain Behav Immun ; 49: 32-42, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25911043

RESUMO

Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases.


Assuntos
Quinina , Percepção Gustatória/fisiologia , Paladar/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Comportamento Animal/fisiologia , Nervo da Corda do Tímpano/fisiologia , Ácido Cítrico , Feminino , Inosina Monofosfato , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sacarina , Cloreto de Sódio , Glutamato de Sódio , Papilas Gustativas/citologia , Papilas Gustativas/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Int J Nanomedicine ; 10: 633-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25609965

RESUMO

BACKGROUND: Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). PURPOSE: The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. METHODS: Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. RESULTS: The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil(®), 13.44% Cremophor(®) RH40, 6.72% Labrasol(®), and 5.04% Transcutol(®) HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro(®)). The microemulsion gel irritated the skin less than Neupro. CONCLUSION: A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.


Assuntos
Portadores de Fármacos , Emulsões , Hidrogel de Polietilenoglicol-Dimetacrilato , Pele/efeitos dos fármacos , Tetra-Hidronaftalenos , Tiofenos , Administração Tópica , Animais , Disponibilidade Biológica , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Emulsões/administração & dosagem , Emulsões/efeitos adversos , Emulsões/química , Emulsões/farmacocinética , Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Hidrogel de Polietilenoglicol-Dimetacrilato/efeitos adversos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacocinética , Ratos , Testes de Irritação da Pele , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Tetra-Hidronaftalenos/química , Tetra-Hidronaftalenos/farmacocinética , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Tiofenos/química , Tiofenos/farmacocinética
7.
RNA ; 20(4): 568-79, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24563514

RESUMO

RNase E, a central component involved in bacterial RNA metabolism, usually has a highly conserved N-terminal catalytic domain but an extremely divergent C-terminal domain. While the C-terminal domain of RNase E in Escherichia coli recruits other components to form an RNA degradation complex, it is unknown if a similar function can be found for RNase E in other organisms due to the divergent feature of this domain. Here, we provide evidence showing that RNase E forms a complex with another essential ribonuclease-the polynucleotide phosphorylase (PNPase)-in cyanobacteria, a group of ecologically important and phylogenetically ancient organisms. Sequence alignment for all cyanobacterial RNase E proteins revealed several conserved and variable subregions in their noncatalytic domains. One such subregion, an extremely conserved nonapeptide (RRRRRRSSA) located near the very end of RNase E, serves as the PNPase recognition site in both the filamentous cyanobacterium Anabaena PCC7120 and the unicellular cyanobacterium Synechocystis PCC6803. These results indicate that RNase E and PNPase form a ribonuclease complex via a common mechanism in cyanobacteria. The PNPase-recognition motif in cyanobacterial RNase E is distinct from those previously identified in Proteobacteria, implying a mechanism of coevolution for PNPase and RNase E in different organisms.


Assuntos
Cianobactérias/metabolismo , Endorribonucleases/metabolismo , Oligopeptídeos/metabolismo , Polirribonucleotídeo Nucleotidiltransferase/metabolismo , RNA Bacteriano/genética , Sequência de Aminoácidos , Domínio Catalítico , Biologia Computacional , Cianobactérias/genética , Cianobactérias/crescimento & desenvolvimento , Endorribonucleases/genética , Immunoblotting , Dados de Sequência Molecular , Polirribonucleotídeo Nucleotidiltransferase/genética , RNA Bacteriano/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Técnicas do Sistema de Duplo-Híbrido
8.
J Neurosci ; 34(7): 2689-701, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24523558

RESUMO

Although inflammatory responses are a critical component in defense against pathogens, too much inflammation is harmful. Mechanisms have evolved to regulate inflammation, including modulation by the anti-inflammatory cytokine interleukin-10 (IL-10). Previously we have shown that taste buds express various molecules involved in innate immune responses, including the proinflammatory cytokine tumor necrosis factor (TNF). Here, using a reporter mouse strain, we show that taste cells also express the anti-inflammatory cytokine IL-10. Remarkably, IL-10 is produced by only a specific subset of taste cells, which are different from the TNF-producing cells in mouse circumvallate and foliate taste buds: IL-10 expression was found exclusively in the G-protein gustducin-expressing bitter receptor cells, while TNF was found in sweet and umami receptor cells as reported previously. In contrast, IL-10R1, the ligand-binding subunit of the IL-10 receptor, is predominantly expressed by TNF-producing cells, suggesting a novel cellular hierarchy for regulating TNF production and effects in taste buds. In response to inflammatory challenges, taste cells can increase IL-10 expression both in vivo and in vitro. These findings suggest that taste buds use separate populations of taste receptor cells that coincide with sweet/umami and bitter taste reception to modulate local inflammatory responses, a phenomenon that has not been previously reported. Furthermore, IL-10 deficiency in mice leads to significant reductions in the number and size of taste buds, as well as in the number of taste receptor cells per taste bud, suggesting that IL-10 plays critical roles in maintaining structural integrity of the peripheral gustatory system.


Assuntos
Interleucina-10/biossíntese , Papilas Gustativas/citologia , Papilas Gustativas/metabolismo , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Hibridização In Situ , Interleucina-10/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Interleucina-10/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Papilas Gustativas/imunologia , Fator de Necrose Tumoral alfa/biossíntese
9.
Chem Senses ; 39(1): 3-16, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24287552

RESUMO

The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.


Assuntos
Envelhecimento , Homeostase , Papilas Gustativas/citologia , Distúrbios do Paladar/etiologia , Animais , Morte Celular , Diferenciação Celular , Humanos , Papilas Gustativas/metabolismo , Papilas Gustativas/patologia , Distúrbios do Paladar/metabolismo , Distúrbios do Paladar/patologia
10.
Zhong Yao Cai ; 36(2): 188-90, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23901639

RESUMO

OBJECTIVE: To optimize the extracting condition of fatty constituents from Tabanus bivittatus and analyse by GC-MS. METHODS: Taking fatty yield as index, the extraction technology parameters of fatty constituents of Tabanus bivittatus ere optimized by single factor test and orthogonal test. RESULTS: The optimum extraction parameters were as follows: the ratio of acetone to petroleum ether 1: 2, extraction time 2 h, solid-liquid ratio 1: 50. Twenty-one fatty acids were identified by GC-MS. CONCLUSION: The process is reasonable and with good reproducibility. The main components of fatty acids in Tabanus bivittatus are palmitoleic acid, palmitic acid, linoleic acid, oleic acid and stearic acid.


Assuntos
Dípteros/química , Ácidos Graxos/análise , Materia Medica/análise , Acetona/química , Animais , Ácidos Graxos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Ácido Linoleico/análise , Materia Medica/isolamento & purificação , Ácido Oleico/análise , Ácido Palmítico/análise , Reprodutibilidade dos Testes , Solventes/química , Fatores de Tempo
11.
PLoS One ; 7(8): e43140, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22905218

RESUMO

Taste buds are chemosensory structures widely distributed on the surface of the oral cavity and larynx. Taste cells, exposed to the oral environment, face great challenges in defense against potential pathogens. While immune cells, such as T-cells and macrophages, are rarely found in taste buds, high levels of expression of some immune-response-associated molecules are observed in taste buds. Yet, the cellular origins of these immune molecules such as cytokines in taste buds remain to be determined. Here, we show that a specific subset of taste cells selectively expresses high levels of the inflammatory cytokine tumor necrosis factor-α (TNF-α). Based on immuno-colocalization experiments using taste-cell-type markers, the TNF-α-producing cells are predominantly type II taste cells expressing the taste receptor T1R3. These cells can rapidly increase TNF-α production and secretion upon inflammatory challenges, both in vivo and in vitro. The lipopolysaccharide (LPS)-induced TNF-α expression in taste cells was completely eliminated in TLR2(-/-)/TLR4(-/-) double-gene-knockout mice, which confirms that the induction of TNF-α in taste buds by LPS is mediated through TLR signaling pathways. The taste-cell-produced TNF-α may contribute to local immune surveillance, as well as regulate taste sensation under normal and pathological conditions.


Assuntos
Regulação da Expressão Gênica , Papilas Gustativas/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Sistema Imunitário , Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Paladar , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
12.
PLoS One ; 7(4): e35588, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22536412

RESUMO

While our understanding of the molecular and cellular aspects of taste reception and signaling continues to improve, the aberrations in these processes that lead to taste dysfunction remain largely unexplored. Abnormalities in taste can develop in a variety of diseases, including infections and autoimmune disorders. In this study, we used a mouse model of autoimmune disease to investigate the underlying mechanisms of taste disorders. MRL/MpJ-Fas(lpr)/J (MRL/lpr) mice develop a systemic autoimmunity with phenotypic similarities to human systemic lupus erythematosus and Sjögren's syndrome. Our results show that the taste tissues of MRL/lpr mice exhibit characteristics of inflammation, including infiltration of T lymphocytes and elevated levels of some inflammatory cytokines. Histological studies reveal that the taste buds of MRL/lpr mice are smaller than those of wild-type congenic control (MRL/+/+) mice. 5-Bromo-2'-deoxyuridine (BrdU) pulse-chase experiments show that fewer BrdU-labeled cells enter the taste buds of MRL/lpr mice, suggesting an inhibition of taste cell renewal. Real-time RT-PCR analyses show that mRNA levels of several type II taste cell markers are lower in MRL/lpr mice. Immunohistochemical analyses confirm a significant reduction in the number of gustducin-positive taste receptor cells in the taste buds of MRL/lpr mice. Furthermore, MRL/lpr mice exhibit reduced gustatory nerve responses to the bitter compound quinine and the sweet compound saccharin and reduced behavioral responses to bitter, sweet, and umami taste substances compared with controls. In contrast, their responses to salty and sour compounds are comparable to those of control mice in both nerve recording and behavioral experiments. Together, our results suggest that type II taste receptor cells, which are essential for bitter, sweet, and umami taste reception and signaling, are selectively affected in MRL/lpr mice, a model for autoimmune disease with chronic inflammation.


Assuntos
Doenças Autoimunes/patologia , Distúrbios do Paladar/patologia , Potenciais de Ação/efeitos dos fármacos , Animais , Doenças Autoimunes/metabolismo , Doenças Autoimunes/fisiopatologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células , Nervo da Corda do Tímpano/fisiologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Epitélio/patologia , Feminino , Nervo Glossofaríngeo/fisiologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Quinina/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/metabolismo , Sacarina/farmacologia , Linfócitos T/patologia , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Papilas Gustativas/metabolismo , Papilas Gustativas/patologia , Distúrbios do Paladar/metabolismo , Distúrbios do Paladar/fisiopatologia , Língua/patologia , Transcrição Genética , Transducina/genética , Transducina/metabolismo
13.
Indian J Exp Biol ; 48(6): 554-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20882756

RESUMO

Anti-bone resorption activity of pilose antler blood (Cervus nippon Temminck) were evaluated in ovariectomized Wistar rats. The rats were randomly divided into sham operated group (SHAM), ovariectomized group (OVX) and pilose antler blood treated group. The ovariectomized rats were treated with pilose antler blood orally in 4000 microl/kg daily doses for 10 weeks. Compared with SHAM group, serum 17 beta-estradiol level decreased significantly and osteocalcin level increased significantly in OVX group, indicating successful model of osteoporosis. The experiments showed that the bone mineral density of the lumbar spine and left femur in OVX group decreased remarkably compared to SHAM group but normalized by treatment with pilose antler blood. Additionally, serum levels of insulin-like growth factor-land testosterone were lower obviously in OVX group than those in SHAM group but preserved by pilose antler blood treatment. However, no obvious changes in serum levels of calcium, phosphorus, total alkaline phosphatase and osteoprotegerin were observed among three groups. These results suggested that administration of pilose antler blood was effective in alleviating osteoporosis in ovariectomized rats.


Assuntos
Chifres de Veado/química , Reabsorção Óssea/tratamento farmacológico , Materia Medica/farmacologia , Osteoporose/tratamento farmacológico , Ovariectomia , Fosfatase Alcalina/sangue , Animais , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Estradiol/sangue , Feminino , Masculino , Materia Medica/isolamento & purificação , Osteocalcina/sangue , Fósforo/sangue , Ratos , Ratos Wistar
14.
Microb Pathog ; 49(6): 330-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20688146

RESUMO

Previous studies from our laboratory demonstrated that mice treated with morphine pellets are sensitized to Salmonella enterica, serovar Typhimurium infection. However, the opioid receptor antagonist, naltrexone, only partially blocked the effect of morphine, raising the possibility that the opioid might have some of its effects through a nonopioid receptor. To further clarify whether sensitization to infection is an opioid receptor-dependent phenomenon, µ-opioid receptor knockout (MORKO) mice were used in the present study. Wild-type (WT) and MORKO mice were treated with morphine and their sensitivity to oral Salmonella infection was assessed by mortality, bacterial burdens in gut associated lymphoid tissue and in blood and peritoneal fluid, and by levels of pro-inflammatory cytokines in plasma. MORKO animals treated with morphine were refractory to a sublethal dose of Salmonella, while similar treatment of WT animals resulted in 100% mortality. WT animals treated with morphine had high bacterial loads in all organs tested, while morphine-treated MORKO animals had no culturable Salmonella in any organs. Pro-inflammatory cytokine levels were elevated in morphine-treated WT but not MORKO mice infected with Salmonella. These results provide definitive evidence that the morphine-mediated enhancement of oral Salmonella infection is dependent on the µ-opioid receptor.


Assuntos
Suscetibilidade a Doenças/induzido quimicamente , Morfina/toxicidade , Receptores Opioides mu/efeitos dos fármacos , Salmonelose Animal/microbiologia , Salmonella typhimurium/patogenicidade , Animais , Líquido Ascítico/microbiologia , Carga Bacteriana , Sangue/microbiologia , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Tecido Linfoide/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Opioides mu/deficiência , Análise de Sobrevida
15.
Chem Senses ; 35(6): 501-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20457570

RESUMO

A healthy taste system is important to the maintenance of nutrition and overall quality of life, and taste disorders are associated with many inflammatory states. We previously determined the immune cells in normal human gustatory tissue; they are predominantly dendritic cells and CD4 T cells with a few macrophages and B lymphocytes present. There are, however, few reports of the subtypes of resident lymphocytes in or near taste tissues. The present study further characterized the distribution and population of the major subtypes of T cells in situ within biopsies of healthy human fungiform papillae (FP). Immunohistochemical analyses indicated that T-helper (Th)1 cells (CCR5+) were more predominant in FP than Th2 T cells (CCR4+). CD45RO+ memory T cells were the principal T cells in gustatory tissue, whereas CD45RA+ naive T cells were uncommon. Regarding subcompartments of the tissue, most intraepithelial lymphocytes of FPs were gamma/delta T cells, whereas the major subtype of lymphocytes in the lamina propria were alpha/beta T cells. Regulatory T cells that express CTLA-4 (CD152) and interleukin-2 receptors (IL-2R, CD25) were found at low levels in FP. The T cells stand ready to respond to inflammatory and infectious insults and may play a role in the taste alterations observed during acute and chronic inflammatory states.


Assuntos
Memória Imunológica , Subpopulações de Linfócitos T/imunologia , Papilas Gustativas/imunologia , Células Th1/imunologia , Adulto , Antígenos CD/metabolismo , Antígeno CTLA-4 , Feminino , Humanos , Imuno-Histoquímica , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Receptores CCR4/metabolismo , Receptores CCR5/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Língua/citologia
16.
Am J Rhinol Allergy ; 24(2): 110-20, 2010 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20021743

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a complex heterogeneous inflammatory disease that affects the nasal cavity, but the pathological examination of the olfactory mucosa (OM) in this disease has been limited. METHODS: Nasal biopsy specimens were obtained from 20 control subjects and 50 CRS patients in conjunction with clinical assessments. Histopathology of these nasal biopsy specimens was performed and immunohistochemistry was used to characterize nonneuronal, neuronal, and inflammatory cells in the OM. These OM characteristics were then evaluated to determine the degree to which pathological features may be related to smell loss in CRS. RESULTS: Histopathological examination of control and CRS OM revealed changes in the normal pseudostratified olfactory epithelium (OE): intermixing of goblet cells, metaplasia to squamous-like cells, and erosion of the OE. Lower percentages of normal epithelium and olfactory sensory neurons were found in CRS OE compared with controls. Relative to other CRS patients, those with anosmia had the greatest amount of OE erosion, the highest density of eosinophils infiltrating the OE, and exhibited the most extensive abnormalities on CT and endoscopic examination, including being significantly more likely to exhibit nasal polyposis. CONCLUSION: Our results suggest that OM pathology observed in nasal biopsy specimens can assist in understanding the degree of epithelial change and sensorineural damage in CRS and the potential for olfactory loss.


Assuntos
Mucosa Olfatória/patologia , Neurônios Receptores Olfatórios/patologia , Rinite/patologia , Sinusite/patologia , Adolescente , Adulto , Biópsia , Doença Crônica , Feminino , Humanos , Imuno-Histoquímica , Masculino , Metaplasia , Pessoa de Meia-Idade , Pólipos Nasais , Transtornos do Olfato , Neurônios Receptores Olfatórios/metabolismo , Prognóstico , Rinite/diagnóstico , Rinite/fisiopatologia , Sinusite/diagnóstico
17.
Ann N Y Acad Sci ; 1170: 590-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19686198

RESUMO

The impact of chronic rhinosinusitis (CRS) on the olfactory mucosa (OM) is dramatic. Cellular profiles and epithelial integrity in OM biopsies were evaluated using histological and immunohistochemical methods to define a strategy for future histological studies of CRS. We have examined nasal biopsies of 54 CRS patients (18-63 years old) and have defined specific histopathological patterns of the OM: normal pseudostratified, goblet cell hyperplasia, squamous metaplasia, and erosion. Goblet cell hyperplasia was most similar to a normal pseudostratified OM pattern but with goblet cells intermixed in the apical layers. Squamous metaplasia exhibited an absence of olfactory supporting cells and had olfactory sensory neurons that were morphologically abnormal. It is unknown if these neurons would be functional in this type of tissue transformation. The pattern of erosion exhibited a severe loss of epithelial layers and a higher prevalence of infiltrating inflammatory cells within the olfactory epithelium when compared to the other OM patterns. Although it is not known if the OM patterns we have noted correspond to specific stages or distinct pathways of the disease, the template proposed here can be used in further studies to understand how the histopathological progression of CRS relates to olfactory loss and the response to treatment.


Assuntos
Mucosa Olfatória/patologia , Rinite/patologia , Sinusite/patologia , Doença Crônica , Humanos
18.
Brain Behav Immun ; 23(6): 760-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19268521

RESUMO

Taste loss or alterations can seriously impact health and quality of life due to the resulting negative influence on eating habits and nutrition. Infection and inflammation are thought to be some of the most common causes of taste perception disorders. Supporting this view, neuro-immune interactions in the peripheral gustatory system have been identified, underlying the importance of this tissue in mucosal immunity, but we have little understanding of how these interactions influence taste perception directly or indirectly. This limited understanding is evident by the lack of even a basic knowledge of the resident immune cell populations in or near taste tissues. The present study characterized the distribution and population of the major immune cells and their subsets in healthy human anterior, lingual, fungiform papillae (FP) using immunohistochemistry. Dendritic cells (DCs) were the predominant innate immune cells in this tissue, including four subtypes: CD11c(+) DCs, DC-SIGN+ immature DCs, CD83(+) mature DCs, and CD1a(+) DCs (Langerhans cells). While most DCs were localized beneath the lamina propria and only moderately in the epithelium, CD1a(+) Langerhans cells were exclusively present within the epithelium and not in sub-strata. A small number of macrophages were observed. T lymphocytes were present throughout the FP with CD4(+) T cells more prevalent than CD8(+) T cells. Very few CD19(+) B lymphocytes were detected. The results show that DCs, macrophages, and T lymphocytes are the constitutive guardians of human FP taste tissue, with DCs and CD4 T cells being dominant, while B lymphocytes are rare under normal, healthy conditions. These observations provide a basic anatomical foundation for the immune response in the healthy human tongue as a basis for subsequent disease-related studies, but none of the present data indicate that the immune cell populations identified are, in fact, altered in individuals with abnormal taste perception.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Imunidade Celular/imunologia , Papilas Gustativas/imunologia , Paladar/imunologia , Adulto , Antígenos CD/imunologia , Antígeno CD11c/imunologia , Contagem de Células , Feminino , Genes MHC da Classe II/genética , Humanos , Processamento de Imagem Assistida por Computador , Imunoglobulinas/imunologia , Imuno-Histoquímica , Células de Langerhans/imunologia , Macrófagos/imunologia , Masculino , Glicoproteínas de Membrana/imunologia , Papilas Gustativas/fisiologia , Língua/citologia
19.
Infect Immun ; 74(9): 5221-6, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16926415

RESUMO

Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine withdrawal on spontaneous sepsis and on oral infection with Salmonella enterica serovar Typhimurium was examined. Mice were chronically exposed to morphine for 96 h by implantation of a slow-release morphine pellet. Abrupt withdrawal was induced by removal of the pellet. In the sepsis model, bacterial colonization was examined and bacterial species were identified by necropsy of various tissues. It was found that at 48 h postwithdrawal, morphine-treated mice had enteric bacteria that were detected in the Peyer's patches (4/5), mesenteric lymph nodes (4/5), spleens (4/10), livers (6/10), and peritoneal cavities (8/10). In placebo pellet-withdrawn mice, only 2/40 cultures were positive. The most frequently detected organisms in tissues of morphine-withdrawn mice were Enterococcus faecium followed by Klebsiella pneumoniae. Both organisms are part of the normal gastrointestinal flora. In the infection model, mice were orally inoculated with S. enterica 24 h post-initiation of abrupt withdrawal from morphine. Withdrawal significantly decreased the mean survival time and significantly increased the Salmonella burden in various tissues of infected mice compared to placebo-withdrawn animals. Elevated levels of the proinflammatory cytokines were observed in spleens of morphine-withdrawn mice, compared to placebo-withdrawn mice. These findings demonstrate that morphine withdrawal sensitizes to oral infection with a bacterial pathogen and predisposes mice to bacterial sepsis.


Assuntos
Dependência de Morfina/imunologia , Salmonelose Animal/imunologia , Salmonella typhimurium , Sepse/imunologia , Síndrome de Abstinência a Substâncias/complicações , Animais , Citocinas/metabolismo , Suscetibilidade a Doenças , Enterococcus faecium/isolamento & purificação , Tolerância Imunológica , Klebsiella pneumoniae/isolamento & purificação , Fígado/microbiologia , Linfonodos/microbiologia , Camundongos , Dependência de Morfina/microbiologia , Boca/microbiologia , Cavidade Peritoneal/microbiologia , Nódulos Linfáticos Agregados/microbiologia , Baço/microbiologia , Síndrome de Abstinência a Substâncias/imunologia , Síndrome de Abstinência a Substâncias/microbiologia
20.
Eur J Pharmacol ; 534(1-3): 250-7, 2006 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-16513108

RESUMO

Our laboratory has shown previously that subcutaneously implanted, slow-release morphine pellets markedly enhanced susceptibility to oral infection with Salmonella typhimurium. Further, morphine, kappa and delta opioid receptor agonists infused via osmotic minipumps were immunosuppressive. The present study compared morphine pellets to morphine pumps and also examined the differential effects of morphine versus U50,488H (kappa agonist), deltorphin II (delta2 agonist), and (D-Pen2, D-Pen5)-enkephalin (DPDPE, delta1 agonist), administered via Alzet minipumps, on oral Salmonella infection and on gastrointestinal transit. The results show that all morphine-pelleted mice (26/26) had a marked increase in Salmonella burden in the Peyer's Patches, mesenteric lymph nodes and spleen. In comparison, only 8/20 mice receiving morphine by minipump at doses ranging from 1 to 25 mg/kg/day had any culturable Salmonella in their organs and the number of bacteria was very low. The level of Salmonella colonization correlated with blood morphine levels and gut transit measured using an intragastric charcoal meal. Morphine pellets inhibited gut transit by 38%, while mice receiving morphine by minipump at doses of 1 to 25 mg/kg/day showed only a dose-dependent 7% to 17% inhibition. Mice receiving various doses of U50,488H or DPDPE had no culturable Salmonella in the three sites. Deltorphin II given by minipump resulted in a moderate level of Salmonella in the spleen. Deltorphin II and U50,488H (0.1 to 10 mg/kg/day) did not suppress gut transit. The present studies indicate that a predominantly mu opioid receptor agonist, morphine, given by slow-release pellet, potentiated Salmonella infection and inhibited gastrointestinal transit. In contrast, morphine in pumps slightly inhibited intestinal transit, but did not sensitize to Salmonella infection. A delta1 opioid receptor agonist did not sensitize to infection, and a delta2 and a kappa opioid receptor agonist had minimal effects on either parameter.


Assuntos
Analgésicos Opioides/farmacologia , Trânsito Gastrointestinal/efeitos dos fármacos , Morfina/farmacologia , Salmonelose Animal/prevenção & controle , Salmonella typhimurium/efeitos dos fármacos , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Suscetibilidade a Doenças , Relação Dose-Resposta a Droga , Implantes de Medicamento , D-Penicilina (2,5)-Encefalina/farmacologia , Feminino , Bombas de Infusão Implantáveis , Linfonodos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Morfina/administração & dosagem , Oligopeptídeos/farmacologia , Nódulos Linfáticos Agregados/microbiologia , Receptores Opioides delta/efeitos dos fármacos , Receptores Opioides kappa/efeitos dos fármacos , Receptores Opioides mu/efeitos dos fármacos , Salmonelose Animal/microbiologia , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/isolamento & purificação , Baço/microbiologia
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