Anti-influenza properties of herbal extract of Althaea rosea in mice / 대한수의학회지

Althaea rosea has been used in traditional Chinese medicine to treat numerous diseases, but no studies have investigated its anti-influenza properties to date. In this study, we investigated the anti-influenza effects of Althaea rosea. BALB/c mice orally pretreated with Althaea rosea (200 µL, 0.1 mg/mL concentration in phosphate-buffered saline) and followed by infection of influenza A virus nasally showed higher survivability and lower lung virus titer against divergent subtypes of influenza A virus infection. We also found that oral administration of Althaea rosea elicited antiviral innate immune responses in serum, bronchoalveolar lavage fluid, small intestinal fluid, and the lungs. Taken together, these findings suggest that aqueous extracts of Althaea rosea are a potential candidate for use as an anti-influenza drug.

Interferon-inducible systemic lupus associated gene, IFIT1 in systemic lupus erythematosus patients

Systemic lupus erythematosus [SLE] is a prototype of human systemic autoimmune diseases. Although the definite etiopathogenesis of SLE remains unclear, many different mechanisms may contribute to the pathogenesis of SLE. Interferons [IFNs] are important immune system mediators that could impact the initiation or amplification of autoimmunity and tissue damage through their diverse actions on dendritic cells. T, B lymphocytes, natural killer cells, and mononuclear phagocytes. Recent studies suggest an important role of interferon alpha in the immunopatahogenesis of SLE. Data demonstrating a correlation between IFN alpha and SLE range from elevated IFN alpha level in patients serum and induction of interferon regulated genes in peripheral blood mononuclear cells to drug induced lupus in hepatitis C or cancer patients treated with recombinant IFN alpha. In the present work we studied the mRNA expression level of the interferon-inducible with tetratricopeptide repeats 1 [IFIT1] gene using Real-time PCR to examine the hypothesis that increased disease severity and activity, as well as distinct autoantibody specificities, characterize SLE patients with activation of type 1 interferon pathway. Expression of IFIT1 gene was significantly higher in SLE when compared to the control group and the level of expression showed a positive correlation with disease activity index. Renal affection was more frequently encountered in SLE patients with IFIT1 overexpression. The gene expression profiles seems to be the molecular basis of the diverse immune phenotype of SLE. Defining the nature of the major IFNs or other factors, that drive the IFN-regulated gene expression noted in SLE is an important area of investigation that may lead to new approaches to targeted therapy of SLE

The efficacy of 5% imiquimod cream in the prevention of recurrence of excised keloids.

OBJECTIVE: To evaluate the efficacy of 5% imiquimod cream in the prevention of recurrence of excised keloids. MATERIAL AND METHOD: The patients with keloids that had occurred over 1 year and could be excised and primary sutured were enrolled in the study. Imiquimod 5% cream was applied to the scar 7 days after stitches removal. The patients were follow-up for recurrence and drug side effect at 4, 6, 8, 16, and 24 weeks. RESULTS: Forty-five patients enrolled to the study but only 35 patients finished the study. The keloids were at the pinnas in 22 patients, at the backs or shoulders in 7 patients, and at chest walls or necks in 6 patients. Imiquimod 5% cream was applied on the wound area 2 weeks after the operation, at alternate night for 8 weeks. The follow-up period ranged from 6 to 9 months. Ten of the treated keloids recurred (28.6% recurrent rate). The lesion at the pinna had the lowest recurrent rate (2.9% recurrent of the total patients). The highest recurrent rate occurred at the chest wall or neck (83.3% recurrent of the chest wall or neck or 14.3% of the total patients). Side effects were found in thirteen patients (37.1%). These were abrasions of the skin around the wound areas in ten patients and hyperpigmentation of the skin around the wounds in three patients. CONCLUSION: Imiquimod 5% cream could effectively prevent recurrence of the excised keloids, especially in the area that had less tension such as pinna.

Serum gamma INF inducing factor [IL18] levels in patients with chronic liver disease

Interleukin 18 [IL18] is likely to play a role in inflammatory liver disease, it is currently regarded as the primary inducer of INF gamma in inflammatory reaction, in chronic hepatitis C a significant up regulation of IL 18 in the inflammatory infiltrate has been demonstrated. The study aimed to evaluate the serum levels of IL18 in patients with chronic liver disease and to assess its role in the clinical outcome of patients with liver injury. The cohort consisted of 60 subjects age ranged from 32-65 ys, they were stratified into 4 groups; G1: 15 patients with chronic liver diseases. G2: 15 patients with liver cirrhosis G3: 15 patients with Hepatoma. G4: 15 healthy subjects serving as control Beside full routine laboratory tests. The patients were tested for autoantibodies [ANA,SMA, AMA] ,viral markers and determination of IL18 serum by ELISA. At presentation a significant increase of serum IL18 was found in all groups compared to control in addition IL18 was significantly higher in G3 than G2, furthermore it was significantly higher in G2 than G1. Moreover IL18 showed also a significant positive correlation with AST, ALT,TB,DB. in contrast a negative correlation was detected with albumin and PT It can be concluded that IL18 is likely to be involved in the pathogene-sisof human liver diseases

Efectos biológicos en células HEp-2, en la multiplicación del adenovirus tipo 6 y en la concentración de interferón en plasma humano en presencia de un RNA de transferencia fúngico / Biological effects in HEp-2 cells, adenovirus type 6 and interferon concentration in human plasma in the presence of a fungal transfer RNA

Introducción: Trabajos previos mostraron la capacidad antiviral in vitro, así como la utilidad como inductor de interferón natural (IFN-n) in vivo de un RNA de transferencia (tRNA) de origen fúngico, por este motivo se sigue estudiando esta molécula como una alternativa para el tratamiento antiviral. Objetivos: Estudiar el efecto del tRNA fúngico en la viabilidad, síntesis de DNA y en la multiplicación del adenovirus tipo 6 (AV-6) en células HEp-2, comparado su efecto con el producido por el polyl:polyC o por IFN-Ó. Valorar su capacidad como unductor a largo plazo de la síntesis de IFN-n in vivo. Material y métodos: Células HEp-2 se incubaron con diferentes concentraciones de las moléculas mencionadas durante 24 horas, y se determinó la viabilidad y la síntesis de DNA celular; adicionalmente cultivos tratados en las mismas condiciones se infectaron con 200 unidades formadoras de placas (ufp) del AV-6, se incubaron cinco días adicionales, y se valoró el grado de protección. In vivo a siete voluntarios clínicamente sanos se les administró intramuscularmente una dosis única de 100 mg del tRNA, y se determinó mediante la técnica de inhibición del efecto citopático (ECP) el nivel sérico de IFN-n, cinco días después de la inoculación. Resultados. El tRNA protegió a las células HEp-2 contra la infección por AV-6, mejor que el polyl:polyC y de forma similar al IFN-Ó. Ninguna de las tres sustancias afectó significativamente la viabilidad celular. En cambio, la síntesis de DNA sí disminuyó de manera directa en relación con la concentración de los inductores, no así con el IFN-Ó. En los plasmas de los sujetos tratados con el tRNA fúngico se encontró un aumento en la concentración de IFN-n (de 84.2 ñ 107.6 a 171.42 ñ 129.5 UI/mL) a los cinco días, aunque la diferencia no fue estadísticamente significativa. Conclusión. El tRNA fúngico mostró actividad antiviral contra el AV-6, no afectó la viabilidad pero sí la síntesis celular de DNA, y con una capacidad de mantener elevada hasta por cinco días la concentración plasmática de IFN-n en humanos

Los inductores de la síntesis de interferón endógeno ¿una posible opción terapéutica? / Endogenous interferon synthesis inducers. A possible therapeutic option?

La linfocina conocida como interferón (IFN) existe en tres tipos principales (-Ó, -ß y -ç), cada uno de ellos con diferente capacidad como agente antiviral, antitumoral o como inmunomodulador, esta características motivaron su aplicción exógena desde su descubrimiento como terapia para el tratamiento de diversos padecimientos, esto sin embargo, trajo consigo severos efectos colaterales del IFN exógeno, y de estimular la síntesis endógena en el organismo para aprovechar sus propiedades en la eliminación de alguna enfermedad (viral, tumoral, etc.), se han probado una enorme cantidad de compuestos, tanto de origen natural como sintético (inductores), lamentablemente hasta el momento no se ha encontrado al inductor idóneo, debido principalmente a factores, como: el tipo y grado de la infección o proceso tumoral, población estudiada, toxicidad de la molécula, etc., por estos motivos son necesarios la realización de un mayor número de trabajos para encontrar al mejor inductor, capaz de utilizarse con fines terapéuticos y que además muestre un mínimo de efectos secundarios al paciente al cual se aplique. En el presente trabajo se revisan algunos estudios que hablan de la utilidad, así como de los efectos secundarios de los inductores de la síntesis de IFN como el polyA:polyU, el PolyI:polyC, PolyI:polyC12U, Ridostine, Bropirimine y de un ARNt de orgien fúngico utilizados en el tratamiento de procesos infecciosos y tumorales

Hemangioendotelioma kaposiforme associado à síndrome de Kasabach-Merritt / Kaposiform hemangioendothelioma associated with Kasabach-Merritt

Objetivo: Descrever um caso de hemangioendotelioma kaposiforme, único tumor malígno de origem vascular específico da infância. Métodos: Relata-se o caso de lactente do sexo feminino com 40 dias de vida que apresentava um hemagioma gigante da face. O tumor evoluiu com crescimento rápido levando à compressäo da laringe com insuficiência grave. A criança tinha ainda uma coagulopatia trombocitopênica de consumo (síndrome de Kasabach-Merritt). Resultados: Ela foi admitica à UTI Pediátrica do Hospital das Clínicas da Universidade Estadual de Campinas e foi iniciada ventilaçäo mecânica. O tratamento durante dez dias com dexametasona levou à melhora por curto período. Foi inciado interferon alfa-2a na dose de 1,8 milhöes de unidades/m²/dia por via subcutânea, porém a paciente foi à óbito 4 dias após o início dessa terapia. A necrópcia revelou o diagnóstico de um hemangioendotelioma kapasiforme. Conclusäo: Discutem-se a evoluçäo fatal pouco freqüente de um hemangioma gigante e suas complicaçöes hematológicas.

Indución a la producción de interferón endógeno en humanos e inhibición de la replicación in vitro de adenovirus tipo 6, virus herpes simple tipo 1 y virus sincitial respiratorio utilizando un ARN de transferencia / Induction of endogenous interferon production in humans and inhibition of the in vitro replication of type 6 adenovirus, type I herpes simplex virus, and respiratory syncytial virus using a transfer RNA

El interferón (IFN) es una linfocina con actividad inmunomoduladora, antitumoral y antiviral; por esta razón en numerosos laboratorios se trabaja intensamente en la búsqueda de nuevas moléculas capaces de inducir su producción de manera natural en el organismo humano, y de este modo utilizarlas contra diferentes padecimientos (virales y tumorales). Con este fin, en el presente trabajo se evaluó la capacidad de un ARN de transferencia (ARNt) de origen fúngico, como agente inductor de la síntesis de interferón tanto in vivo como in vitro. Para ésto, se aplicaron por vía intramuscular 200 mg del inductor a siete sujetos clínicamente sanos; a cada uno de ellos se les tomó dos muestras de sangre para obtener el plasmo, una antes de la aplicación del ARNt y otra 2 horas después. A las muestras de plasma se les determinó el nivel de interferón mediante la técnica de inhibición del efecto citopático utilizando el virus de la estomatitis vesicular. Los niveles de interferón en los plasmas variaron de 10 a 320 unidades internacionales (UI) por mL, antes de la aplicación y de 80 a 1,280 UI/mL 2 horas después de la misma, al realizar el análisis estadístico las diferencias encontradas fueron significativas. Para valorar la capacidad del ARNt en la protección contra las infecciones virales in vitro, se incubaron células Vero con diferentes concentraciones del ARNt durante 24 h, posteriormente se infectaron con adenovirus tipo 6 (AV-6), virus de herpes simple tipo 1 (VHS-1) o virus sincitial respiratorio (VSR), los cultivos se incubaron cinco días adicionales y se cuantificó el efecto del inductor sobre la multiplicación viral. Los cultivos incubados previamente con el ARNt de origen fúngico, e infectados posteriormente con uno de los virus mencionados, presentaron menor daño citopático que los cultivos usados como controles virales; dicha reducción del efecto citopático fue dependiente de la dosis. Los resultados indican que el ARNt utilizado es capaz de estimular la síntesis de IFN in vivo e in vitro, lo cual abre la posibilidad de utilizarlo en el tratamiento de las infecciones virales, sólo en el tratamiento de las infecciones virales, sólo o en combinación con antivirales ya conocidos

Effect of 6-MFA, an interferon inducer obtained from fungus Aspergillus ochraceus on hepatic mixed function oxidase system in rats.

Effect of 6-MFA (sixth mycelial fraction of acetone), an interferon inducer obtained from fungus A. ochraceus on hepatic mixed function oxidase system (MFO) of rat has been investigated. Treatment with 6-MFA, 100 mg/kg/day, ip for 1-5 days to adult rats inhibited significantly the different indices of MFO system, viz. hepatic cytochrome P-450, cytochrome b5 content, cytochrome c reductase, aminopyrine-N-demethylase and acetanilide hydroxylase activities. Similar treatment for 3 days in young growing rats significantly inhibited MFO system's components except acetanilide hydroxylase activity which showed marked elevation. These effects seem to be specific as in vitro experiments suggested that 6-MFA does not compete with subsdtrates nor it acts as a sponge reacting with the end product to give false inhibitory effect. It is concluded from the present study that 6-MFA like other interferon inducers depresses MFO system in rats. Its possible clinical implications are discussed.

A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.

The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.

Induçäo de interferon humano de membrana aminiótica: papel de particulas defectivas interferentes / induction of human amniotic interferon by strains of paramyxovirus: Role of defective interfering particles

Resumo: A amostra Cantell de vírus parainfluenza 1 necessita de partículas defectivas interferentes (DI) para a produçäo de interferon (IFN) humano. A amostra Mill Hill do vírus da doença de Newcastle aparentemente näo as requer, embopra seja um indutor de IFN ainda mais potente. Para examinar este comportamento diverso, foram feitas passagens seriadas em ovos embrionados em baixa e alta multiciplidade de infecçäo com estes vírus, sendo que esta última propicia a formaçäo de particulas DI. Após cada passagem, o interferon humano de membrana aminiótica (IFN-MA) foi induzido e foram determinados os títulos hemaglutinante e infeccioso dos vírus e o do IFN-MA. A amostra Cantell mostrou uma reduçäo de 10.000 vezes em seu titulo infeccioso com as passagens em alta multiciplidade. Os títulos de IFN-MA produzidos foram cerca de 300 unidades por ml nas passagens em baixa multiciplidade. Contudo, a capacidade indutora desta amostra subiu de 1.200 para 4.200 unidades por ml nas passagens com alta multiplicidade. Coma amostra Mill Hill, as passagens seriadas em baixa ou alta multiplicidade de infecçäo näo modificaram os títulos infectantes ou as quantidades geradas de IFN-MA pela amostrra Cantell. Com a amostra Mill Hill, todavia, näo pode ser demonstrada a formaçäo de partículas DI, nem modificaçöes dos títulos de IFN-MA foram observados com a adiçäo de partículas DI da amostra Cantell (au)

Protective effect of 6-MFA, a fungal interferon inducer against Japanese encephalitis virus in bonnet macaques.

6-MFA, an extract from the fungus Aspergillus ochraceus was administered to 8 bonnet macaques. An equal number of monkeys matched for age, sex and weight received placebo and served as controls. Twenty hours after the administration of the 6-MFA/placebo the monkeys were challenged with an Indian strain of Japanese encephalitis virus by the intranasal route. Signs and symptoms of the disease such as fever, tremors, loss of appetite, dehydration, flaccid paraplegia or quadriplegia were pronounced in all the control monkeys, while in the 6-MFA treated group only two developed symptoms. Virus could be isolated from only one of the 6-MFA treated monkeys on day 6, and from four control monkeys; one each from CSF, spinal cord, blood and from both nasal swab and blood of the fourth monkey. The appearance of HI and N antibodies in 6-MFA treated group was either delayed or completely suppressed. The results indicate that 6-MFA is a potential antiviral agent which can be used to reduce the morbidity and mortality in bonnet macaques (Macaca radiata) experimentally infected with Japanese encephalitis virus.

Jacalin: an excellent lectin for obtaining T cell growth activity from rat spleen cells

The parameters involved in the choice of an optimal T cell growth activity (TCGAc) induction protocol using rat spleen cells simultated with jacalin were studied. In the absence of serum, 5 microng/ml jacalin was sufficient to obtain maximal TCGAc, Supernatants could be harvested at any time between 24 and 72 h since significant consumption of TCGAc was not observed during this interval. TCGAc recovery was increased in the presence of 5% fetal calf serum, with the optimal jacalin dose being about 25 microng/ml. The recommended harvesting time was 24 h to reduce TCGAc loss due to cellular proliferation. Human or rat sera were not suitable since they absorb significant amounts of jacalin, thus shifting the optimal lectin concentration to > 800 microng/ml. Indomethacin (1 microng/ml) had little enchancing effect on TCGAc production by rat cells but rendered conditioned media less inhibitory of cytotoxic T lymphocyte L (CTLL) proliferation. Addition of 50 ng/ml phorbol myristate acetate is not recommended if the supernatants are to be used for T cell line maintenance, since the agent interferes with CTL function, while only doubling TCGAc production. Jacalin-stimulated TCGAc recovery is comparable, in titer, to that obtained with concanavalin A under the best conditions, but the former is less expensive due to the large quantities of lectin recovered from a single jackfruit, besides being less toxic for rat spleen cells