RESUMO
α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone involved in cutaneous pigmentation in atopic dermatitis (AD) with severe itching. α-MSH elicits itch-related responses in mice. We, therefore, investigated whether α-MSH was involved in itching in AD. In the skin of AD patients and mice with atopy-like dermatitis, α-MSH and the prohormone convertase 2, which is the key processing enzyme for the production of α-MSH, were distributed mainly in keratinocytes. In the skin of mice with dermatitis, melanocortin receptors (MC1R and MC5R) were expressed at the mRNA level and were distributed in the dermis. In the dorsal root ganglion of mice with dermatitis, mRNAs encoding MC1R, MC3R, and MC5R were also expressed. MC1R antagonist agouti-signaling protein inhibited spontaneous scratching in mice with dermatitis. In healthy mice, intradermal α-MSH elicited itch-associated responses, which were inhibited by thromboxane (TX) A2 receptor antagonist ONO-3708. In mouse keratinocytes, α-MSH increased the production of TXA2, which was inhibited by adenylyl cyclase inhibitor SQ-22536 and Ca2+ chelator EGTA. In mouse keratinocytes treated with siRNA for MC1R and/or MC5R, α-MSH-induced TXA2 production was decreased. α-MSH increased intracellular Ca2+ ion concentration in dorsal root ganglion neurons and keratinocytes. These results suggest that α-MSH is involved in itching during AD and may elicit itching through the direct action of primary afferents and TXA2 production by keratinocytes.
Assuntos
Dermatite Atópica/complicações , Queratinócitos/patologia , Prurido/patologia , Pele/patologia , Tromboxano A2/metabolismo , alfa-MSH/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Células Cultivadas , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Feminino , Humanos , Queratinócitos/metabolismo , Masculino , Camundongos , Prurido/etiologia , Prurido/metabolismo , Receptores de Melanocortina/metabolismo , Pele/metabolismoRESUMO
Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer's patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer's patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections.
Assuntos
Antivirais/farmacologia , Clorófitas , Desoxiaçúcares/farmacologia , Terapia de Imunossupressão , Vírus da Influenza A/efeitos dos fármacos , Mananas/farmacologia , Administração Oral , Animais , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Desoxiaçúcares/administração & dosagem , Desoxiaçúcares/uso terapêutico , Modelos Animais de Doenças , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Japão , Mananas/administração & dosagem , Mananas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Oceanos e Mares , FitoterapiaRESUMO
The purpose of this study was to investigate the safety zone without any neurovascular injury to the medial compartment of hip joint through an anatomical method and describe the relationship of the extra-articular anatomic structures from the surface of the hip joint. Thirty-two fresh specimens from 17 adult Korean cadavers (8 males and 9 females, age range 54-79 years at death) were used for this study. For the measurements, the most superolateral point of the pubic symphysis (PS) and prominent point of the anterior superior iliac spine (ASIS) were identified before dissection. The line connecting the PS and ASIS was defined as a reference line and the PS was a starting point for measurements. All 19 variables measured in this study were related to the femoral head, neck, and surrounding neurovascular structures. The variables were measured according to the x- and y-coordinates in relation to the reference line. The femoral head was generally located 39.5-71.0 mm on the x-coordinate and located 33.5-34.6 mm on the y-coordinate. The junction of the femoral neck and body was located at 52.8 mm on the x-coordinate, and 65.3 mm on the y-coordinate. The junction of the femoral head and neck was located at 47.1 mm on the x-coordinate, and 51.4 mm on the y-coordinate. The location of the medial compartment of the hip joint was located from 38.0 to 43.0 % on the x-coordinate and located from 5.1 to 6.5 cm. These results of this study provide detailed anatomy for arthroscopic hip surgeons.
Assuntos
Artroscopia/normas , Articulação do Quadril/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause genital herpes, which can enhance the acquisition of human immunodeficiency virus. The development of anti-HSV agents with novel mechanisms of action is urgently required in the topical therapy of genital herpes. In this study, the in vitro and in vivo anti-HSV effects of Epomin SP-012(®), a highly cationic polyethylenimine, were evaluated. When the in vitro antiviral effects of SP-012 were assessed, this compound showed potent activity against HSV-1 and HSV-2. It inhibited the attachment of HSV-2 to host cells and cell-to-cell spread of infection in a concentration-dependent manner and exerted a virucidal effect. No SP-012-resistant HSV-2 was found when the virus was successively passaged in the presence of SP-012. In a mouse genital herpes model, topically administered SP-012 inhibited the progression of the disease caused by HSV infection. These data illustrate that SP-012 may be a novel class of HSV inhibitor that would be acceptable for long-term topical application.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Herpes Genital/prevenção & controle , Polietilenoimina/uso terapêutico , Administração Tópica , Animais , Anti-Infecciosos Locais/farmacologia , Modelos Animais de Doenças , Feminino , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Polietilenoimina/farmacologia , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacosRESUMO
The entry of herpes simplex virus into host cells involves a complex series of events that require concerted inputs from multiple HSV glycoproteins. Among these glycoproteins, the gD protein of HSV-1 and HSV-2 plays an important role for host receptor binding and membrane fusion. In the present study, we evaluated the ability of different sulfated saccharides to interfere with gD-host receptor (HVEM) interactions using our recently reported molecular assay (Gopinath, S. C. B.; Hayashi, K.; Kumar, P. K. R. J. Virol. 2012, 86, 6732-6744). Initially, we tested the ability of heparan sulfate to interfere with the HVEM-HSV-1 gD interaction and found that heparan sulfate is able to interfere efficiently, with an apparent EC50 of 2.1 µM. In addition, we tested different synthetic sulfated polysaccharides and natural sulfated polysaccharides from an edible alga, Sargassum horneri , after fractionation into different sizes and sulfate and uronic acid contents. Six polysaccharides isolated from S. horneri were found to efficiently interfere with the HVEM-gD interaction. Three others caused moderate interference, and five caused weak interference. These results were confirmed with plaque assays, and good agreement was found with the results of the SPR assay for the identification of compounds that interfere with HVEM-HSV-1 gD binding. These studies suggest that our molecular assay based on surface plasmon resonance is not only useful for the analysis of viral-host protein interactions but is also applicable for the routine screening of compounds to identify those that interfere with the first step of viral entry, thus facilitating the rapid development of novel antiviral compounds that target HSV.
Assuntos
Herpesvirus Humano 1/metabolismo , Receptores Virais/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Polissacarídeos/metabolismoRESUMO
Leaf tissues of Atropa belladonna were transformed by Sdrac2, a Rac GTPase gene, that is isolated from Scoparia dulcis, and the change in atropine concentration of the transformants was examined. Re-differentiated A. belladonna overexpressing Sdrac2 accumulated considerable concentration of atropine in the leaf tissues, whereas the leaves of plants transformed by an empty vector accumulated only a very low concentration of the compound. A. belladonna transformed by CASdrac2, a modified Sdrac2 of which translate was expected to bind guanosine triphosphate (GTP) permanently, accumulated very high concentrations of atropine (approximately 2.4-fold excess to those found in the wild-type plant in its natural habitat). In sharp contrast, the atropine concentration in transformed A. belladonna prepared with negatively modified Sdrac2, DNSdrac2, expected to bind guanosine diphosphate instead of GTP, was very low. These results suggested that Rac GTPases play an important role in the regulation of secondary metabolism in plant cells and that overexpression of the gene(s) may be capable of enhancing the production of natural products accumulated in higher plant cells.
Assuntos
Atropa belladonna/genética , Atropina/metabolismo , GTP Fosfo-Hidrolases/genética , Scoparia/genética , Atropa belladonna/crescimento & desenvolvimento , Atropina/genética , GTP Fosfo-Hidrolases/metabolismo , Regulação da Expressão Gênica de Plantas , Guanosina Difosfato/genética , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/genética , Guanosina Trifosfato/metabolismo , Folhas de Planta/genética , Plantas Geneticamente ModificadasRESUMO
We investigated the involvement of serine protease and proteinase-activated receptor 2 (PAR(2)) in dermatophyte-induced itch in mice. An intradermal injection of an extract of the dermatophyte Arthroderma vanbreuseghemii (ADV) induced hind-paw scratching, an itch-related behavior. ADV extract-induced scratching was inhibited by the opioid receptor antagonists naloxone and naltrexone, the serine protease inhibitor nafamostat mesylate, and the PAR(2) receptor antagonist FSLLRY-NH(2). ADV extract-induced scratching was not inhibited by the H(1) histamine receptor antagonist terfenadine or by mast cell deficiency. Heat pretreatment of the ADV extract markedly reduced the scratch-inducing and serine protease activities. Proteolytic cleavage within the extracellular N terminus of the PAR(2) receptor exposes a sequence that serves as a tethered ligand for the receptor. The ADV extract as well as tryptase and trypsin cleaved a synthetic N-terminal peptide of the PAR(2) receptor. The present results suggest that serine protease secreted by dermatophytes causes itching through activation of the PAR(2) receptors, which may be a causal mechanism of dernatophytosis itch.
Assuntos
Arthrodermataceae , Prurido/enzimologia , Receptor PAR-2/fisiologia , Serina Proteases/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Oligopeptídeos/farmacologia , Receptor PAR-2/antagonistas & inibidoresRESUMO
Scoparia dulcis produces unique biologically active diterpenoids such as scopadulcic acid B (SDB). They are biosynthesized from geranylgeranyl diphosphate (GGPP) via syn-copalyl diphosphate (syn-CPP) and scopadulanol as an important key intermediate. In this paper, we functionally characterized three diterpene synthases, SdCPS2, SdKSL1 and SdKSL2, from S. dulcis. The SdCPS2 catalyzed a cyclization reaction from GGPP to syn-CPP, and SdKSL1 did from syn-CPP to scopadulan-13α-ol. On the other hand, SdKSL2 was found to incorporate a non-sense mutation at 682. Therefore, we mutated the nucleotide residue from A to G in SdKSL2 to produce SdKSL2mut, and it was able to recover the catalytic function from syn-CPP to syn-aphidicol-16-ene, the precursor to scopadulin. From our results, SdCPS2 and SdKSL1 might be important key players for SDB biosynthesis in S. dulcis.
RESUMO
Three antiviral and immunostimulating substances (LC1, LC2 and LC3) were isolated from a hot water extract of seeds of Pimpinella anisum by combination of anion-exchange, gel filtration and hydrophobic interaction column chromatographies. Chemical and spectroscopic analyses revealed them to be lignin-carbohydrate-protein complexes. These lignin-carbohydrate complexes (LCs) showed antiviral activities against herpes simplex virus types 1 and 2 (HSV-1 and -2), human cytomegalovirus (HCMV) and measles virus. LCs were also found to interfere with virus adsorption to the host cell surface and directly inactivate viruses. Furthermore, they enhanced nitric oxide (NO) production by inducing iNOS mRNA and protein expression in RAW 264.7 murine macrophage cells. The induced mRNA expression of cytokines including IL-1ß and IL-10 was also apparent. These results suggest that the lignin-carbohydrate-protein complexes from P. anisum possessed potency as functional food ingredients against infectious diseases.
Assuntos
Antivirais/farmacologia , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Ligação Viral/efeitos dos fármacos , Animais , Antivirais/química , Carboidratos/química , Carboidratos/isolamento & purificação , Linhagem Celular , Chlorocebus aethiops , Cromatografia em Gel , Cromatografia por Troca Iônica , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/crescimento & desenvolvimento , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/crescimento & desenvolvimento , Humanos , Fatores Imunológicos/química , Interleucina-10/biossíntese , Interleucina-1beta/biossíntese , Lignina/química , Lignina/isolamento & purificação , Vírus do Sarampo/efeitos dos fármacos , Vírus do Sarampo/crescimento & desenvolvimento , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Pimpinella/química , Extratos Vegetais/química , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Sementes/química , Viroses/tratamento farmacológico , Viroses/virologiaRESUMO
In this study, the antipruritic effect of the methanol extract of Ganoderma lucidum (MEGL) was studied in mice. Oral administration of MEGL (10-1000 mg/kg) produced a dose-dependent inhibition of scratching, an itch-related response, induced by intradermal 5-hydroxytryptamine (5-HT) (100 nmol/site), alpha-methyl-5-HT (100 nmol/site), and proteinase-activated receptor-2 (PAR(2))-activating peptide SLIGRL-NH(2) (50 nmol/site). However, MEGL (100-1000 mg/kg) did not inhibit the scratching induced by histamine (100 nmol/site), substance P (100 nmol/site), and compound 48/80 (10 microg/site). These results raise the possibility that MEGL is effective against pruritus mediated by proteinases and 5-HT and that primary afferents expressing PAR(2) and 5-HT(2A) receptors are the sites of its action.
Assuntos
Comportamento Animal/efeitos dos fármacos , Produtos Biológicos/uso terapêutico , Fitoterapia , Prurido/tratamento farmacológico , Reishi , Pele/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Animais , Produtos Biológicos/farmacologia , Relação Dose-Resposta a Droga , Histamina , Masculino , Camundongos , Camundongos Endogâmicos ICR , Oligopeptídeos , Prurido/induzido quimicamente , Receptor PAR-2 , Receptores de Serotonina/metabolismo , Serotonina , Pele/inervação , Substância P , p-Metoxi-N-metilfenetilaminaRESUMO
A hot-water extract of Aphanothece sacrum, an edible aquacultured blue-green alga, was found to show a remarkable inhibitory effect on the replication of enveloped viruses including herpes simplex virus type 2 (HSV-2) and influenza virus type A (IFV-A, H1N1) in vitro. The main active components were suggested to be sulfated polysaccharides in non-dialyzable portion (ASWPH). ASWPH was found to inhibit the viral adsorption to the receptor of the host cells involved in the replication process of HSV-2 and IFV-A. In addition, while the penetration stage of HSV-2 was also significantly suppressed with ASWPH, no such effect was observed in the replication of IFV-A. These results suggest that ASWPH might be useful in the prevention of infectious diseases caused by HSV-2 as well as IFV-A.
Assuntos
Misturas Complexas/farmacologia , Cianobactérias/química , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/fisiologia , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/fisiologia , Replicação Viral/efeitos dos fármacos , Adsorção/efeitos dos fármacos , Animais , Fracionamento Químico , Chlorocebus aethiops , Misturas Complexas/química , Misturas Complexas/isolamento & purificação , Cianobactérias/fisiologia , Herpesvirus Humano 2/metabolismo , Temperatura Alta , Vírus da Influenza A/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/farmacologia , Ácidos Sulfúricos/química , Células Vero , Água/químicaRESUMO
Three polysaccharides including a neutral polysaccharide (RN), an acidic polysaccharide (RA) and a pectic polysaccharide (RP) were isolated from aerial part of Portulaca oleracea L. and evaluated for their anti-herpes simplex virus type 2 (HSV-2) and anti-influenza A virus (IFV-A). RN was found to consist of glucose (Glc), mannose (Man) and arabinose (Ara) with small amounts of galactose (Gal), and identified to be an arabinoglucomannan. RA was mainly composed of Gal and Ara with a small proportion of glucuronic acid (GlcA). It was characterized as a type II arabinogalactan (AGII), which consisted of a 1,3-, 1,6- and 1,3,6-linked galactopyranosyl (Galp) and non-reducing terminal and 1,5-linked arabinofuranosyl (Araf) residues. RP was deduced to be a pectin, which consisted of a predominant amount of galacturonic acid (GalA) with small amounts of Gal, rhamnose (Rha) and Ara. The GalA residues were found to be highly methyl-esterified and partially acetylated. Results of antiviral tests showed that only RP had anti-HSV-2 activity. Furthermore, its anti-HSV-2 target was elucidated to be the step of virus penetration into host cells. No marked virucidal activity of RP was observed.
Assuntos
Antivirais/química , Antivirais/farmacologia , Herpesvirus Humano 2/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Portulaca/química , Animais , Antivirais/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cães , Herpes Simples/tratamento farmacológico , Humanos , Estrutura Molecular , Infecções por Orthomyxoviridae/tratamento farmacológico , Polissacarídeos/isolamento & purificação , Células VeroRESUMO
This is a case report of an arthroscopic treatment performed on a patient with piriformis syndrome due to perineural cyst on piriformis muscle and sciatic nerve. Confirmation, incision, and drainage of benign cystic lesion on the sciatic nerve below the piriformis muscle were performed following the release of the piriformis tendon through the posterior and posteroinferior arthroscopic portal. Recurrence of the symptoms has not been observed since postoperative period of 20 months. Nor did the MRI taken after the procedure reveal any such recurrence.
Assuntos
Artroscopia/métodos , Síndrome do Músculo Piriforme/cirurgia , Nervo Isquiático/lesões , Cistos de Tarlov/cirurgia , Adulto , Feminino , Humanos , Síndrome do Músculo Piriforme/etiologia , Recuperação de Função Fisiológica , Cistos de Tarlov/complicaçõesRESUMO
The limited efficacy and significant clinical toxicity of combination interferone and ribavirin therapy have generated strong interest in developing novel inhibitors of hepatitis C virus (HCV) replication. Recently, a growing understanding of the structure and function of critical viral enzymes and the development of HCV replicons have accelerated the development of highly specific candidate antiviral agents. In the life cycle of HCV, enveloped virions bind and penetrate into host cell using viral envelope glycoproteins. In the cytoplasm, the viral RNA genome serves as mRNA, and produces viral protein as a long polyprotein that is cleaved by both host and viral proteases. Progeny virions assemble by budding into ER/Golgi apparatus, where the glycoproteins maturate, and are released at the cell surface. All stages of replication cycle from the attachment of virus to the release of progeny should be antiviral targets. We have searched for antiviral candidates from natural resources for about 20 years. So far, we have found several classes of compounds with unique antiviral action. Among them, anionic substances interfere with virus attachment and/or entry, several substances inhibit the maturation of virus-specific glycoproteins, low molecules can inhibit the virus release from infected cells, glycerol derivatives reduce the pathogenicity of virus, and some compounds exert virucidal action that impairs the ability of virus to infect host cells. These substances might be worthy to be evaluated as novel anti-HCV agents by using HCV replication systems in cultured cell lines.
Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Hepacivirus/fisiologia , Hepacivirus/patogenicidade , Hepatite C/terapia , Hepatite C/virologia , Replicação Viral/efeitos dos fármacos , Depressão Química , Glicoproteínas/metabolismo , Hepacivirus/genética , Humanos , Replicon/efeitos dos fármacos , Proteínas Virais/metabolismoRESUMO
Chikusetsusaponin IVa and calenduloside E were isolated from the whole plant of Alternanthera philoxeroides (Mart.) Griseb (Amaranthaceae) and evaluated for their antiviral activities. Chikusetsusaponin IVa showed antiviral activities against HSV-1, HSV-2, human cytomegalovirus, measles virus, and mumps virus with selectivity indices (CC (50)/IC (50)) of 29, 30, 73, 25, and 25, respectively. On the other hand, calenduloside E showed no antiviral effects against any of the viruses tested. The mode of HSV-2 action of chikusetsusaponin IVa was determined under different experimental conditions. The anti-HSV-2 target of the compound might be mainly related to direct inactivation of virus particles and to the inhibition of release of progeny viruses from infected cells, but it is not related to inhibition of viral attachment, cell penetration, and viral protein synthesis. This compound also provided in vivo efficacy in a mouse model of genital herpes caused by HSV-2. These results demonstrate that chikusetsusaponin IVa might be a candidate of antiherpetic agents.
Assuntos
Amaranthaceae/química , Antivirais/farmacologia , Ácido Oleanólico/análogos & derivados , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Viroses/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/isolamento & purificação , Linhagem Celular , Herpes Genital/tratamento farmacológico , Herpes Genital/virologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Fitoterapia , Extratos Vegetais/isolamento & purificação , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/uso terapêuticoRESUMO
A monogalactosyl diacylglyceride (MGDG) was isolated as an antiviral component from Coccomyxa sp. KJ (IPOD FERM BP-22254) via bioassay-guided fractionation. α-Linolenic acid (C18:3) and 7,10,13-hexadecatrienoic acid (C16:3) accounted for approximately 72% and 23%, respectively, of the MGDG total fatty acids of the MGDG. The MGDG showed virucidal activity against herpes simplex virus type 2 (HSV-2), a pathogen that causes genital herpes. Physical changes in HSV-2 shape were observed after treatment with MGDG, including a decrease in particle size, and possible damage to the viral envelope, as assessed using electron microscopy. In accordance with the morphological findings, virus particles lost their ability to bind to host cells. HSV-2 treated with high concentrations of MGDG resulted in no pathogenicity in an animal model, indicating that MGDG exhibits irreversible virucidal activity against HSV-2 particles. In the animal model of HSV-2-induced genital herpes, intravaginally administered MGDG exerted a prophylactic effect by suppressing viral yields in the genital cavity and formation of herpetic lesions, resulting in a higher survival rate in treated mice than control mice administered solvent. Thus, MGDG offers a novel prophylactic option against HSV infections.
Assuntos
Antivirais/farmacologia , Galactolipídeos/farmacologia , Herpes Genital/terapia , Herpesvirus Humano 2/efeitos dos fármacos , Microalgas/química , Administração Intravaginal , Animais , Antivirais/análise , Chlorocebus aethiops , Modelos Animais de Doenças , Ácidos Graxos Insaturados/análise , Feminino , Galactolipídeos/análise , Herpes Genital/virologia , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Células Vero , Ácido alfa-Linolênico/análiseRESUMO
We examined whether different itch signals converge on the same dorsal horn neurons in mice. Intradermal injections of histamine and SLIGRL-NH2 (protease-activated receptor-2 agonist) induced scratching in naive mice and so did mosquito allergen in sensitized mice. These stimuli induced Fos expression in cells in the superficial dorsal horn. Fos-positive cells were mainly distributed within the isolectin B4-labeled region (inner aspect of lamina II) after histamine injection. In contrast, they were in the region dorsal to the isolectin B4-labeled region after injections of SLIGRL-NH2 and mosquito allergen. These results suggest that allergic itch signal is mediated by primary afferents expressing protease-activated receptor-2 and the neurons receiving signals of protease-associated itch and allergy-associated itch are different from those of histamine-induced itch.
Assuntos
Histamina/farmacologia , Hipersensibilidade/metabolismo , Células do Corno Posterior/citologia , Prurido/etiologia , Vias Aferentes/citologia , Vias Aferentes/metabolismo , Animais , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos ICR , Células do Corno Posterior/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Prurido/metabolismo , Receptor PAR-2/metabolismo , Pele/inervaçãoRESUMO
Recently, the development of antiviral agents with novel mechanisms of action has been required since many types of infectious disease have become a serious problem in our society. In the present study, we isolated a novel acidic polysaccharide, nostoflan (NSF), from a terrestrial blue-green alga, Nostoc flagelliforme, and examined its structure and antiviral activity. The sugar composition and methylation analyses of NSF revealed that it is mainly composed of (-->4)- D-Glcp-(1-->, -->6,4)-D-Glcp-(1-->, -->4)-D-Galp-(1-->, -->4)-D-Xylp-(1-->, D-GlcAp-(1-->, D-Manp-(1-->) with a ratio of ca. 1:1:1:1:0.8:0.2. Oligosaccharide analysis after partial acid hydrolysis of NSF revealed that this polysaccharide might be mainly composed of the sugar sequences of (-->4)-beta-D-Glcp-(1-->4)-D-Xylp-(1 and-->4)-[beta-D-GlcAp-(1-->6)-]-beta-D-Glcp-(1-->4)-D-Galp-(1-->). NSF showed potent antiviral activities against several enveloped viruses including herpes simplex virus type 1, type 2 (HSV-1, HSV-2), human cytomegalovirus, and influenza A virus (IFV). NSF selectively inhibited the attachment of HSV-1 to host cells but not its penetration phase. In an experimental animal study where IFV-infected mice received NSF intranasally, the mortality of mice was significantly decreased. Neutralizing titers in sera of mice treated with NSF were higher than in those treated with oseltamivir. From these results, NSF was found to be a novel polysaccharide that shows antiviral activity in vitro and in vivo in spite of a nonsulfated polysaccharide.
Assuntos
Antivirais , Nostoc/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Configuração de Carboidratos , Modelos Animais de Doenças , Humanos , Influenza Humana/tratamento farmacológico , Camundongos , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêuticoRESUMO
Gibberellins (GAs) are ubiquitous diterpenoids in higher plants, whereas some higher plants produce unique species-specific diterpenoids. In GA biosynthesis, ent-kaurene synthase (KS) and ent-kaurene oxidase (KO) are key players which catalyze early step(s) of the cyclization and oxidation reactions. We have studied the functional characterization of gene products of a KS (SdKS) and two KOs (SdKO1 and SdKO2) involved in GA biosynthesis in Scoparia dulcis. Using an in vivo heterologous expression system of Escherichia coli, we found that SdKS catalyzed a cyclization reaction from ent-CPP to ent-kaurene and that the SdKOs oxidized ent-kaurene to ent-kaurenoic acid after modification of the N-terminal region for adaptation to the E. coli expression system. The real-time PCR results showed that the SdKS, SdKO1 and SdKO2 genes were mainly expressed in the root and lateral root systems, which are elongating tissues. Based on these results, we suggest that these three genes may be responsible for the metabolism of GAs in S. dulcis.