RESUMEN
The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Edema Corneal/terapia , Facoemulsificación/efectos adversos , Anciano , Anciano de 80 o más Años , Segmento Anterior del Ojo , Edema Corneal/etiología , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/terapia , Estudios RetrospectivosRESUMEN
Theoretical validation for local express autocytokine therapy (LEACKT), used in recent years with good results for the treatment of viral and nonviral diseases of the eyes, is provided. In vitro experiments showed that autologous cytokine complex appearing after stimulation of patient's peripheral whole blood with poludan (polyA:polyY complex, 200 micrograms) includes all three interferon types (alpha, beta, and gamma) and interleukin-8 (IL-8) and tumor necrosis factor (TNF). It was shown for the first time that poludan stimulated the production of IL-8, the main chemotactic cytokine inducing chemotaxis, neutrophil activation, angiogenesis stimulation, and regeneration. This was not paralleled by an increase in the production of TNF, the key mediator of inflammation, whose level in whole blood did not increase. Addition of poludan to cell culture led to a 2-fold decrease of lymphocyte apoptosis in comparison with that after treatment with dexamethasone alone. The results of experiments indicate that LEACKT with poludan is characterized by pronounced antiinflammatory, interferonogenic, regeneratory, and antiapoptosis effects in various diseases of the anterior segment of the eye and is a simple and safe method.
Asunto(s)
Citocinas/uso terapéutico , Oftalmopatías/tratamiento farmacológico , Polirribonucleótidos/farmacología , Adolescente , Adulto , Antiinflamatorios/farmacología , Apoptosis , Células Cultivadas , Quimiotaxis , Medios de Cultivo , Dexametasona/farmacología , Infecciones del Ojo/tratamiento farmacológico , Fibroblastos/efectos de los fármacos , Humanos , Interferones , Interleucinas , Leucocitos/efectos de los fármacos , Regeneración , Factores de Tiempo , Factor de Necrosis Tumoral alfaRESUMEN
A promising dosage form of interferon inductor poludan has been developed for the treatment of patients with genital herpes and ophthalmic herpes: suppositoria. High interferon-producing and antiviral activity of poludan in suppositoria is potentiated by hyaluronic acid and antioxidants.
Asunto(s)
Antivirales/administración & dosificación , Herpes Genital/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Inductores de Interferón/administración & dosificación , Queratitis Herpética/tratamiento farmacológico , Polirribonucleótidos/administración & dosificación , Supositorios , Antivirales/uso terapéutico , Sinergismo Farmacológico , Humanos , Inductores de Interferón/uso terapéutico , Polirribonucleótidos/uso terapéuticoAsunto(s)
Antivirales/uso terapéutico , Infecciones Virales del Ojo/tratamiento farmacológico , Inductores de Interferón/uso terapéutico , Polirribonucleótidos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Vías de Administración de Medicamentos , Evaluación de Medicamentos , Humanos , Inductores de Interferón/administración & dosificación , Inductores de Interferón/efectos adversos , Seguridad , Resultado del TratamientoRESUMEN
Titres of antibodies to various viral antigens, levels of immunoglobulins, and the rate of detection of specific IgM to measles virus were studied in the blood sera of 50 patients with multiple sclerosis and 50 normal subjects. High antibody titres to measles, mumps, rubella and parainfluenza type 3 virus antigens were revealed. Specific IgM to measles virus were detected in 50% of multiple sclerosis patients and in none of the normal subjects. The patients with multiple sclerosis showed no significant differences in the levels of immunoglobulins of the three main classes (G, A, M).
Asunto(s)
Anticuerpos Antivirales/análisis , Virus ADN/inmunología , Esclerosis Múltiple/inmunología , Virus ARN/inmunología , Adolescente , Adulto , Especificidad de Anticuerpos , Femenino , Humanos , Inmunidad , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Masculino , Persona de Mediana EdadRESUMEN
The antiviral action of herpes vaccine and poludan, an interferon-inducing agent, has been studied in experimental herpes infection, and the synergic effect of these preparations has been obtained. The best result (survival rate equal to 100% after the intraperitoneal inoculation of herpes simplex virus and 85.7% after its intracerebral inoculation) has been registered after the multiple vaccination of experimental animals and the injection of poludan 1 day before the challenge of the animals with the virus. The protective effect of the synergic action of the preparations under study coincides with the period of the maximum content of antibodies in the blood sera of the animals.
Asunto(s)
Herpes Simple/prevención & control , Inductores de Interferón/uso terapéutico , Polirribonucleótidos , Simplexvirus/inmunología , Vacunas Virales/uso terapéutico , Animales , Anticuerpos Antivirales/análisis , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Herpes Simple/inmunología , Herpes Simple/mortalidad , Interferones/sangre , Ratones , Factores de TiempoAsunto(s)
Inmunoterapia/métodos , Queratitis Dendrítica/terapia , Polirribonucleótidos , Adyuvantes Inmunológicos/uso terapéutico , Adolescente , Adulto , Anciano , Femenino , Humanos , Inductores de Interferón/uso terapéutico , Interferones/análisis , Queratitis Dendrítica/inmunología , Masculino , Persona de Mediana Edad , Recurrencia , Lágrimas/inmunología , Hormonas del Timo/uso terapéutico , Factores de TiempoRESUMEN
Fractions of immunoglobulins G isolated from highly active hyperimmune rabbit sera and inhibitor-free antisera for influenza A viruses of the "Spanish" era different periods (1930-1978) were tested with a wide spectrum of human and animal viruses by the HI and CF tests. In hemagglutinins of Hswl, H0, and H1 viruses common antigens were found dissimilarly expressed in different variants as indicated by both various degrees of serological activity of the viruses and by great differences in the availability of cross-reactive antibody in various sera.
Asunto(s)
Epítopos/análisis , Hemaglutininas Virales/análisis , Virus de la Influenza A/inmunología , Animales , Reacciones Cruzadas , Epítopos/inmunología , Variación Genética , Hemaglutininas Virales/inmunología , Humanos , Sueros Inmunes/aislamiento & purificación , Inmunización , Inmunoglobulina G/inmunología , Conejos , RatasRESUMEN
Antiviral activity was evaluated in sera from 65 patients with chronic glomerulonephritis (GN), 58 patients with SLE and 59 healthy controls. Antibodies to influenza A2 and B, and parainfluenza I-II-III viruses occurred much more frequently in GN than in healthy controls. Geometric mean antibody titers to measles, influenza A2 and B, and parainfluenza I-II-III were found to be elevated. The frequency of antiviral antibodies and their level in GN patients were similar to those in SLE patients. Detection of increased antiviral activity in sera of patients with chronic GN extends the range of diseases where persistent latent viral infection may be relevant.
Asunto(s)
Anticuerpos Antivirales/análisis , Glomerulonefritis/inmunología , Adolescente , Adulto , Enfermedad Crónica , Femenino , Glomerulonefritis/microbiología , Humanos , Inmunidad , Lupus Eritematoso Sistémico/inmunología , Masculino , Sarampión/inmunología , Persona de Mediana Edad , Orthomyxoviridae/inmunología , Respirovirus/inmunologíaRESUMEN
The interferon-synthesizing activity of the peripheral blood leukocytes and serum interferon in the blood of patients with multiple sclerosis were studied. A reverse relationship was found between antibody production (high titers of measles antibody) and the interferon-synthesizing activity of peripheral blood leukocytes in these patients. A 3-fold decline in serum interferon titers was observed in patients with multiple sclerosis as compared with the control group.
Asunto(s)
Interferones/sangre , Leucocitos/análisis , Esclerosis Múltiple/sangre , Formación de Anticuerpos , Humanos , Interferones/biosíntesis , Leucocitos/metabolismo , Virus del Sarampión , Esclerosis Múltiple/inmunologíaRESUMEN
Lyophilized arboviruses of the following taxonomic groups: alfaviruses, flaviviruses, Bunyamwera supergroup viruses, as well as arenaviruses were used in the study. These viruses had been stored for a long time at --20 degree C. Determinations of the infectious titers in suckling mice showed that in a period of over 10 years (up to 21 years) no complete loss of infectivity occurred in any virus groups.
Asunto(s)
Arbovirus/patogenicidad , Preservación Biológica/métodos , Animales , Animales Lactantes , Liofilización , Ratones , Factores de TiempoRESUMEN
Sodium nucleinate increased essentially the insusceptibility of mice to pathogenic escherichia, strain O26, Pr. vulgaris, Ps. aeruginosa, Ser. marcescens, and produced a total stimulating effect on the nonspecific bacterial resistance; analogous stimulating activity was found in the homologous low polymeric RNA from the liver. Sodium nucleinate intensified the insusceptibility of the animals to the tick-born encephalitis and encephalomyelitis viruses, and increased the antibody-forming cells count. The side-effect of heat-inactivated vaccine from pathogenic escherichia was reduced in animals inoculated with sodium nucleinate preliminarily.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antivirales/biosíntesis , Inmunidad Innata/efectos de los fármacos , ARN/inmunología , Animales , Células Productoras de Anticuerpos/inmunología , Relación Dosis-Respuesta Inmunológica , Virus de la Encefalitis Equina del Oeste/patogenicidad , Virus de la Encefalitis Transmitidos por Garrapatas/patogenicidad , Escherichia coli/patogenicidad , Inmunización , Ratones , Ratones Endogámicos CBA , Ácidos Nucleicos/inmunología , Proteus vulgaris/patogenicidad , Pseudomonas aeruginosa/patogenicidad , Serratia marcescens/patogenicidad , Factores de TiempoRESUMEN
The investigation of antiviral antibody titers to 8 different antigens: measles, influenza A2 and B, parainfluenza types 1, 2, 3, adenovirus and smallpox, of interferon in the blood serum, the interferon-synthesizing activity of the peripheral blood leukocytes in patients with autoimmune diseases in the period of the disease exacerbation revealed a number of immunological features. Thus, in all groups of patients antibody titers were high to measles, influenza, parainfluenza type 3 viruses, and titers of leukocyte interferon and interferon in the blood serum were 3-4-fold lower than in the control group.