Evaluation of the protective effect of isoprinosine against navelbine induced oxidative stress in mice

Many studies in vitro and in vivo have shown immunomodulating and antiviral activities of Isoprinosine [inosine pranobex]. Chemotherapy means the use of a drug which is most effective at, killing cells that are rapidly dividing. Vinorelbine [Navelbine, 5 oranhydrovinblastine] is a third-generation vinca alkaloid anti-tumor drug. It is widely used in the treatment of cancer such as advanced non-small-cell lung cancer [NSCLC] and advanced breast cancer. The aim of this study was to determine the possible protective effects of Isoprinosine in bacterially infected and non infected mice at a dose level of 8.75 mg/kg/day orally every second day for 15 days under the effect of anticancer Navelbine. Mitochondrial DNA fragmentation, Lipid pereoxidation [MDA], glutathione contents [GSH], phagocytosis test and serum level of immunoglobulin G and M antibodies were evaluated, a significant increase in liver homogenate and mitochondria protein carbonyl levels was observed in Navelbine alone treated mice when compared to control group. DNA fragmentation in homogenate and mitochondria was significantly increased in all test groups when compared to control group except Isoprinosine treated animal group which showed significant decrease in DNA fragmentation. The results of this study proved the immune protective and immunomodulatory effects of Isoprinosine against Navelbine induced toxicity in Pseudomonas aeruginosa infected and non infected mice

Use of a-interferon, amantadin and isoprinosine in subacute sclerosing panencephalitis [SSPE]: comparing the effectiveness

Sub acute Sclerosing Pan Encephalitis [SSPE], a progressive neurological disorder characterized by inflammation of the brain [encephalitis], is the result of an inappropriate immune response to the measles virus or measles vaccination. SSPE usually develops 2 to 10 years after the original viral attack. Some of the major signs and symptoms are mental deterioration, jerky movements, and seizures specially myoclonic type, involuntary movements, and/or behavioral changes, difficulty in walking, speech, and loss of cognition, respiratory distress and death. During the ten years, from July 1991 to July 2001, we admitted 45 cases of [SSPE], at different stages of the disorder. Regardless of their stage of disease, for intervention, randomly, we used one of three drugs; Amantadin, Interferon alfa and Isoprinosine, administered to the patients, for between one month to one year. Fourteen cases received Amantadin, 15 Alfa interferon, and 16 were given Isoprinosine. While the results show all three drugs to be relatively effective, Isoprinosine showed four times more effectiveness than Amantadin and twice as much as Interferon. The results showed Isoprinosine to be much more effective than Amantadin and Alfa interferon in treating the condition

Role of CSF serology in follow-up of subacute sclerosing panencephalitis patients on treatment.

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disease of the central nervous system with poor prognosis and high mortality. No effective treatment has a proven role; oral isoprinosine and intrathecal administration of alpha-interferon may prolong survival. We report an unusual case of adult onset SSPE patient on treatment with significant clinical improvement, even in the absence of conversion to seronegativity in either CSF or serum, on follow-up serological examination.

Panencefalitis esclerosante subaguda de inicio en edad adulta: presentación atípica en 2 pacientes / Adult onset subacute sclerosing panencephalitis: atypical presentation in 2 cases

Subacute sclerosing panencephalitis is an infrequent central nervous system viral disease and is a late manifestation of persistent infection by a mutant form of measles virus. Since it affects mainly children and teenagers, the diagnosis in older ages is difficult. Its main clinical symptoms are cognitive impairment, behavioral disturbances and myoclonia. We report two males, aged 21 and 22 years old, presenting with the disease with atypical manifestations. One had a catatonic syndrome and the other, amaurosis. The recognition of the different presentation forms of the disease, endemic in developing countries, allows an earlier diagnosis and a more efficient treatment, when available

Tratamiento de la alopecia areata / Treatment of the alopecia areata

En una patología como la alopecía areata, la que se presenta de distintas formas clínicas, con asociaciones variadas, donde las remiciones son posibles y los tratamientos disponibles no son 100 por ciento eficaces, es dificil evaluar la terapéutica más adecuada. lLos tratamientos disponibles pueden dividirse en tópicos y sistémicos. Los corticoides ocupan un lugar importante en el arsenal terapéutico, en especial los tópicos o en inyecciones intralesionales. Otrs productos se usan con resultados varioables como la inminoterapia tópica, en especial con el minoxidil, la difenciprona y la antralina. La medicación sistïrmica se reserva para casos severos (corticosteroides,ciclosporina A, etc). La mayoría actuarían alterando la respuesta inmune y en otros en controvertida. Consideramos a la afección dentro de su marco general, más que etético, pero sin descuidar la integridad del individuo y hacia esto debemos apuntar en nuestra estrategia de tratamiento. La relación paciente-médico es fundamental para manejar esta enfermedad en la que aún no tenemos una medicación curativa.

Logros de la inmunofarmacoterapia

Se trata sobre los procedimientos e inmunofarmacos (inmunoestimulantes e inmunosupresores) aplicados en un vasto campo clínico y experimental que abarca enfermedades infecciosas, inmunodeficiencias (primarias y secundarias), enfermedades autoinmunes, cáncer y enfermedades alérgicas. A lo largo del texto se habla sobre el transplante de médula ósea (TMO), timoestimulina (TP-1) y hormonas tímicas, interferones (IFNs), anticuerpos monoclonales e inmunoglobulinas (Igs), factor de transferencia (extracto leucocitario dializado), methisoprinol (Inosine pranobex), glicofos fopeptical (AM3) y levamisol. Se enumera a los antivirales inhibidores de la transcriptasa reversa. Asimismo, se hace referencia a los glucocorticosteroides (CSS), azatioprina (Aza) y ciclosporina A (C y A). Se menciona algunos tipos de ensayos inmunoterapéuticos antineoplasicos. Finalmente, se describe el tratamiento inmunitario de las enfermedades alérgicas en base a la desensibilización usando antígenos (alergenos) y al bloqueo terapéutico del enlace de IgE por medio de inmunoglobulinas (alergoglobulina).

Effect of isoprinosine on rotavirus replication in vitro

Isoprinosine (IPS) is a synthetic drug whose antiviral effect on rotavirus replication in vitro has been characterized in terms of the decrease in metachromasia after acridine orange staining. The present study describes the effect of IPS on the synthesis of viral RNA in vitro. MA-104 cell cultures infected with simian rotavirus strain SA-11 were incubated with zero, 250, 500 and 1,000 microg/ml IPS and 22, 24, 48, 52, 72 and 76 h after infection the cultures were submitted to a 1-h starvation period, followed by a 2-h pulse with 10 microCi/ml of [3H]-uridine. The homogenates of virus-infected cultures treated or not with IPS were submitted to phenol/chloroform extraction followed by polyacrylamide gel electrophoresis. The amount of radioactivity in viral RNA eluted from the gel strips was determined. Inhibition of viral RNA synthesis was highest at the IPS concentration of 1,000 microg/ml at 72 h after infection, corresponding to 78 percent inhibition. Although the results obtained in vitro suggest that IPS may be useful for the treatment of rotavirus infection, an in vivo demonstration of its efficacy is needed.

Clinical Experience of Subacute Sclerosing Panencephalitis treated with Alpha-interferon and Ionsiplex

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing, chronic persistent fatal central nervous system disease, involving gray and white matter, especially white matter caused by measles virus that affecting children and young adult. 45 to 68% of affected individuals had measles before the age of 2. Current knowledge of the pathogenesis of SSPE involves mutation of the measles virus, resulting in lack of production of the M(Matrix)-protein. No therapeutic maneuvour gas been proven conclusively to be of value. But recently intraventricular alpha-interferon (a-IFN) injection combined with oral inosiplex increase the length of survival and may bring remission or stabilization in SSPE. We report a case of SSPE which was diagnosed by history, clinical manifestation, typical EEG findings, high titer of measles antibodies in cerebrospinal fluid and serum by hemagglutinin inhibition method. We tried intraventricular a-IFN injection via Ommaya reservoir and oral inosiplex.

Alopecía areata: tratamiento / Alopecia areata: treatment

El tratamiento de la alopecía areata ha cambiado notablemente en la última década. Nuevas opciones terapéuticas están disponibles para los pacientes. Es deber del dermatólogo informar al paciente de todas las alternativas posibles para su caso, sus efectos colaterales y sus cifras de éxito. La decisión final es conjunta, entre el paciente, la familia del paciente (cuando corresponda) y el dermatólogo

Farmacología de las drogas empleadas en el tratamiento del SIDA / Pharmacology of the drugs employee in the treatment of AIDS

En esta revisión (transcripción de la presentación realizada en el Simposio SIDA, Avellaneda 1990) se enumeran las drogas empleadas para: 1)tratar las complicaciones del SIDA (solo algunos ejemplos, incluyendo foscarnet y glanciclovir); 2)realizar la inmunoterapia del SIDA; y 3)inhibir la replicación del HIV (quimioterápicos anti-HIV). En la segunda clase se enfatiza la necesidad de actuar precozmente (por ej., con valores no muy bajos de CD4), y se analizan evidencias preliminares sobre isoprinosina, timopentina y ditiocarb. En la tercera se analiza en detalle el mecanismo de acción de los dideoxinucleósidos, ejemplificando con la zidovudina, sus efectos adversos, sus limitaciones, en particular para tratamiento precoz, y el desarrrollo de resistencia en el HIV tanto in vitro como in vivo. Se analiza, también, el efecto del interferón * sobre la replicación viral y se esbozan los tratamientos más experimentales en farmacología clínica como el CD4 recombinante soluble) e in vitro (como los oligonucleótidos antisense). Pese a disponer de drogas efectivas en cada una de las tres categorías enunciadas, ninguna hace más que retrasar el curso de la infección hacia la destrucción del sistema inmune y muerte del paciente

Atualizaçäo terapêutica em herpes simplex vírus / Therapeutic actualization in herpes virus

É apresentada uma revisäo das publicaçöes mais recentes sobre o herpes simplex vírus, com ênfase às relaçöes com transmissäo, tratamento e controle

ACTH - inosine pranobex in the treatment of AIDS: encouraging results

Twenty patients with Acquired Immune Deficiency Syndrome (AIDS) received treatment with Inosine Pranobex and specific antibacterial and anti-parasitic therapy. Five died shortly after hospitalization, but a further fifteen who also received ACTH, survived, gained weight and improved and clinically, biochemically and haematologically

The in vitro antiviral activity of isoprinosine on simian rotavirus (SA-11)

The antiviral effect of isoprinosine on simian rotavirus (SA-11) replication was studied using MA-104 cell cultures from Rhesus monkey fetal kidney. Isoprinosine (N,N-dimethylamino-2-propanol-p-acetamidobenzoate in association with inosine) added after viral infection (therapeutic test) inhibited viral replication by more than 90%. In these experiments, the drug was added to the medium and replaced daily at concentrations varying from 62.5 microng/ml to l mg/ml. Viral inhibition activity was dependent on drug concentration. No antiviral effect was observed when isoprinosine was tested without replacement (200-500 microng/ml). When isoprinosine (l mg/ml) was added to cell cultures only before viral infection (prophylactic test), inhibition of viral replication occurred but was less than 90%. Inhibition by less than 90% is not considered to be significant in this type of test. Isoprinosine inhibited synthesis of both viral antigen (protein) and viral double-stranded nucleic acid, as monitored by immunofluorescence and acridine orange staining, respectively. Inhibiton of synthesis of viral macromolecules increased with drug concentration

Effect of inosiplex on the humoral and cell-mediated immune responses to intradermal human diploid cell rabies vaccine.

Antigen-stimulated lymphocyte transformation was studied in recipients of intradermal human diploid cell rabies vaccine (HDCV). HDCV was administered intradermally at 8 different anatomical sites, 0.1 ml each, on day 0; followed by another 4-site injection on day 7. Rabies antigen-stimulated in vitro proliferative response was evident as early as 7 days after starting immunization. It reached a peak on day 14 and had declined by day 28. The cellular proliferative response preceded and roughly correlated with the antirabies antibody response. Simultaneous administration of inosiplex, an antiviral and immunopotentiating drug, during the first 10 days of intradermal HDCV immunization did not result in heightened antibody titres or cell-mediated immune response to the vaccine. The number of T cells and the lymphocyte proliferative response to phytohaemagglutinin in inosiplex-treated vaccinees were similarly not significantly different from untreated controls. Our results confirm other previous findings that a specific cell-mediated immune response can be consistently and rapidly induced by an intradermal regimen of HDCV immunization. The addition of inosiplex to this regimen did not enhance the humoral or cell-mediated immune responses to the vaccine. The apparent lack of immunostimulating effect of inosiplex in this setting may be the result of several factors such as the immunization schedule and the immunologic parameters examined.

Herpes simples: tratamento imunológico de herpes simples com antígenos de virus dermotrópicos Alúmen precipitados em concentraçäo única associados a imuno-estimulantes e a um adjuvante / Herpes simplex: immunological treatment of herpes simplex with antigens of Alum Precipitate dermotropic virus in single concentration associated with an immuno-stimulant and an adjuvant

Os autores trataram 532 pacientes portadores de herpes simples em suas diversas localizaçöes, com suspensäo de vírus dermotrópico associado a polissacarídeos bacterianos e a lisado de germes do gênero Corynebacterium, por via intramuscular, em doses semanais e de 10 em 10 dias. Os resultados foram favoráveis em 82% dos casos tratados e as revisöes clínicas se estenderam a três anos após a alta médica. Quanto ao grupo controle, submetido somente ao tratamento clássico, os resultados favoráveis foram inferiores a 50% dos casos

Estudo da eficácia do inosiplex em comparaçäo com placebo em doentes portadores de herpes simples / Efficacy of inosiplex in comparison with placebs in patients with herpes simplex

Um estudo duplo-cego analisa os efeitos do inosiplex (Isoprinosine*) na infecçäo pelo herpes simples em 12 pacientes (5 placebo, 7 droga). Melhora completa das lesöes ocorreram ao redor de 5 dias em 6 dos 7 doentes que usaram a droga e 2 dos 5 doentes com placebo. Recidivas com 6 meses de acompanhamento ocorreram em 3 dos pacientes da droga e 4 dos 5 com placebo. O inosiplex parece ter algum efeito benéfico no curso clínico das infecçöes pelo herpes simples, sendo praticamente livre de efeitos colaterais