RESUMEN
We estimated the efficacy of combined treatment and metaphylaxis of urate and mixed urolithiasis in 87 patients aged 18-87 years. The patients were divided into two groups: 68 patients of group 1 (the size of the concrements between 5-25 mm) have undergone parenteral litholysis of the drug trometamol N and metaphylaxis with biologically active additives prolit and urisan; 19 patients of group 2 have undergone extracorporeal shock-wave lithotripsy with parenteral litholysis and metaphylaxis by using biologically active additives prolit septo and urisan. Positive results were achieved in all the patients. In group 1 the concrements dissolved completely. In group 2 small fragments up to 4 mm eliminated after partial solution.
Asunto(s)
Antiinfecciosos Urinarios/administración & dosificación , Excipientes/administración & dosificación , Litotricia , Ácido Pipemídico/administración & dosificación , Trometamina/administración & dosificación , Ácido Úrico/metabolismo , Urolitiasis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urolitiasis/metabolismo , Urolitiasis/patología , Urolitiasis/terapiaRESUMEN
The evaluation of clinical efficacy of combined treatment and metaphylaxis in 58 patients with gout complicated by nephropathy and urolithiasis was performed. The study included 41 (71%) men and 27 (29%) women aged 44 to 88 years (mean age - 58 +/- 7 years). All patients received parenteral therapy with trometamol H, 5 -10 infusion for the course, an average of 7 infusions. For the metaphylaxis, all patients received biologically active supplement urisan 2 tablets 2 times a day during next three months against the background of drug therapy. Findings indicate a high clinical efficacy of the trometamol H in the combined treatment of patients with gout, complicated by nephropathy and urolithiasis, considering that improvement of renal function, microcirculation in the renal parenchyma, increased glomerular filtration rate, normalization of nitrogenous wastes levels, partial or complete dissolution of concretions of the kidneys, a significant decrease in the tophs size, an increase in motor activity were observed, which ultimately improves the quality of life for these patients. Metaphylaxis using urisan for 3 months on a background of traditional therapy contributed to a stable normalization of blood uric acid levels, which prevented the exacerbation of underlying disease and recurrent stone formation. These data allow to recommend reducing the dose of traditional anti-gout drugs and conducting repeated course of metaphylaxis with the urisan after 5-6 months during 3 months.
Asunto(s)
Antiinfecciosos Urinarios/administración & dosificación , Excipientes/administración & dosificación , Gota , Enfermedades Renales , Ácido Pipemídico/administración & dosificación , Trometamina/administración & dosificación , Urolitiasis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Gota/sangre , Gota/complicaciones , Gota/fisiopatología , Gota/prevención & control , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Enfermedades Renales/prevención & control , Masculino , Persona de Mediana Edad , Factores de Tiempo , Ácido Úrico/sangre , Urolitiasis/sangre , Urolitiasis/etiología , Urolitiasis/fisiopatología , Urolitiasis/prevención & controlRESUMEN
Human papilloma viruses (HPV) of high carcinogenesis risk play important role in development of cancer of oropharyngeal and anogenital areas. Possible malignant transformation of cells, infected by HPV, is due to the expression of three proteins, E6, E7 and E5. These proteins mostly influence on mechanisms that regulate cellular cycle, proliferation and apoptosis inducing and maintaining oncogenesis. This review briefly presents data on malignant tumors induced by HPV as well as biology of these viruses and their vital cycle. Special accent is made on description of current trends in molecular basis of oncogenesis, induced by HPV, which understanding is necessary for elaboration of new methods of treatment for HPV-infection such as therapeutic vaccines.
Asunto(s)
Alphapapillomavirus/patogenicidad , Transformación Celular Neoplásica , Neoplasias/metabolismo , Neoplasias/virología , Proteínas Oncogénicas Virales/metabolismo , Infecciones por Papillomavirus/complicaciones , Neoplasias del Ano/metabolismo , Neoplasias del Ano/virología , Apoptosis/genética , Ciclo Celular/genética , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Neoplasias de los Genitales Femeninos/metabolismo , Neoplasias de los Genitales Femeninos/virología , Neoplasias de los Genitales Masculinos/metabolismo , Neoplasias de los Genitales Masculinos/virología , Genoma Viral , Inestabilidad Genómica , Humanos , Masculino , Ciclo Menstrual , Mutación , Neoplasias/genética , Proteínas Oncogénicas Virales/genética , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virología , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/metabolismo , Proteínas Represoras/metabolismoRESUMEN
A role for TNF-alpha in the pathogenesis of chronic inflammatory disease is now firmly established. Paradoxically, TNF also has potent immunomodulatory effects on CD4(+) T lymphocytes, because Ag-specific proliferative and cytokine responses are suppressed following prolonged exposure to TNF. We explored whether TNF attenuated T cell activation by uncoupling proximal TCR signal transduction pathways using a mouse T cell hybridoma model. Chronic TNF exposure induced profound, but reversible, T cell hyporesponsiveness, with TNF-treated T cells requiring TCR engagement with higher peptide concentrations for longer periods of time for commitment to IL-2 production. Subsequent experiments revealed that chronic TNF exposure led to a reversible loss of TCRzeta chain expression, in part through a reduction in gene transcription. Down-regulation of TCRzeta expression impaired TCR/CD3 assembly and expression at the cell surface and uncoupled membrane-proximal tyrosine phosphorylation events, including phosphorylation of the TCRzeta chain itself, CD3epsilon, ZAP-70 protein tyrosine kinase, and linker for activation of T cells (LAT). Intracellular Ca(2+) mobilization was also suppressed in TNF-treated T cells. We propose that TNF may contribute to T cell hyporesponsiveness in chronic inflammatory and infectious diseases by mechanisms that include down-regulation of TCRzeta expression. We speculate that by uncoupling proximal TCR signals TNF could also interrupt mechanisms of peripheral tolerance that are dependent upon intact TCR signal transduction pathways.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Regulación hacia Abajo/inmunología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/biosíntesis , Complejo Receptor-CD3 del Antígeno de Linfocito T/antagonistas & inhibidores , Complejo Receptor-CD3 del Antígeno de Linfocito T/biosíntesis , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T/biosíntesis , Factor de Necrosis Tumoral alfa/farmacología , Acetilcisteína/farmacología , Animales , Señalización del Calcio/inmunología , Proteínas Portadoras/metabolismo , Línea Celular Transformada , Membrana Celular/genética , Membrana Celular/inmunología , Membrana Celular/metabolismo , Supresión Clonal , Relación Dosis-Respuesta Inmunológica , Regulación hacia Abajo/efectos de los fármacos , Humanos , Hibridomas , Tolerancia Inmunológica/efectos de los fármacos , Interleucina-2/antagonistas & inhibidores , Interleucina-2/biosíntesis , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Transgénicos , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Tirosina Quinasas/metabolismo , Complejo Receptor-CD3 del Antígeno de Linfocito T/genética , Complejo Receptor-CD3 del Antígeno de Linfocito T/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Proteínas Recombinantes de Fusión/fisiología , Transducción de Señal/genética , Transducción de Señal/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Proteína Tirosina Quinasa ZAP-70RESUMEN
OBJECTIVE: The complement system is important in the development of autoimmune inflammation, including rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Complement receptor 1 (CR1) is involved in regulation of complement activity. Studies on models of autoimmunity have demonstrated that soluble CR1 (sCR1) is a potent therapeutic agent. The present study was thus undertaken to investigate the feasibility of antiinflammatory gene therapy to prevent CIA by delivery of genes encoding truncated sCR1 (tsCR1) and dimeric tsCR1-Ig. METHODS: Syngeneic fibroblasts or arthritogenic splenocytes, engineered to express tsCR1 using retrovirus-mediated gene transfer, were injected into DBA/1 recipients that had been immunized with bovine type II collagen (CII). In separate experiments, naked DNA containing tsCR1 and tsCR1-Ig genes was injected intramuscularly into the immunized animals. The clinical development of arthritis was monitored, anti-CII levels measured, and antigenic T cell response studied. Affinity-purified tsCR1-Ig was assayed for its inhibitory effect on the alternative complement pathway in mouse serum. RESULTS: Treatment of CII-immunized mice with the tsCR1-expressing cells inhibited development of CIA, reduced anti-CII antibody levels, and inhibited T cell response to CII in vitro. Intramuscular injections of DNA encoding the CR1 genes prevented the progression of disease. Furthermore, compared with full-length sCR1, purified tsCR1-Ig was more active in inhibiting the murine alternative complement pathway. CONCLUSION: Our findings demonstrated that tsCR1 and tsCR1-Ig, when delivered via gene therapy, had a beneficial effect on autoimmune inflammation. These results indicate that targeting the complement system in RA patients may be of clinical importance.
Asunto(s)
Artritis Reumatoide/terapia , Fibroblastos/virología , Terapia Genética/métodos , Receptores de Complemento/uso terapéutico , Infecciones por Retroviridae/fisiopatología , Animales , Artritis/tratamiento farmacológico , Artritis/inmunología , Artritis Reumatoide/inducido químicamente , Enfermedades Autoinmunes/tratamiento farmacológico , Colágeno , Vía Alternativa del Complemento/efectos de los fármacos , ADN/administración & dosificación , Progresión de la Enfermedad , Inyecciones , Inyecciones Intramusculares , Masculino , Ratones , Receptores de Complemento/genéticaRESUMEN
The chimeric cell surface receptor scC2Fv/CD8/zeta was constructed to engineer primary mouse T lymphocytes with antibody-type specificity to type II collagen (CII). Such cells could be used as gene carriers in the anti-inflammatory gene therapy of an autoimmune arthritis. This receptor includes the single chain Fv domain (scFv) of the anti-CII monoclonal antibody (mAb) C2, hinge region of CD8alpha and the transmembrane and cytoplasmic domains of TCRzeta. The scC2Fv/CD8/zeta gene was transduced into T cell hybridomas and primary mouse lymphocytes using retrovirus-mediated gene transfer. The chimeric receptor scC2Fv/CD8/zeta forms covalently bound homodimers, as demonstrated in T cell hybridomas and packaging fibroblasts. It does not associate with endogenous signalling subunits of the TCR complex. When scC2Fv/CD8/zeta-expressing clones of T cell hybridomas MD.45 and HCQ6 were stimulated with CII they produced IL-2. The level of their IL-2 response correlated with the expression level of the chimeric receptor on the cell surface. Splenocytes isolated from DBA/1 mice were stimulated with Con A in vitro to facilitate retrovirus-mediated transfer of the scC2Fv/CD8/zeta gene. As a result of transduction, approximately 4% of the Con A-activated splenocytes expressed the chimeric receptor scC2Fv/CD8/zeta on the cell surface. These cells proliferated in response to stimulation with CII.
Asunto(s)
Artritis/terapia , Enfermedades Autoinmunes/terapia , Colágeno/inmunología , Terapia Genética/métodos , Linfocitos T/inmunología , Transfección/métodos , Animales , Concanavalina A/farmacología , Hibridomas/inmunología , Fragmentos de Inmunoglobulinas/genética , Interleucina-2/inmunología , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos DBA , Receptores de Antígenos de Linfocitos T/genética , Estimulación QuímicaRESUMEN
Animal models of autoimmune disease have been developed that mimic some aspects of the pathophysiology of human disease. These models have increased our understanding of possible mechanisms of pathogenesis at the molecular and cellular level and have been important in the testing, development and validation of new immunotherapies. The susceptibility to develop disease in the majority of these models is polygenic as is the case in humans. The exceptions to this rule are gene knock outs and transgenic models of particular genes which, in particular genetic backgrounds, have also contributed to the understanding of single gene function and their possible contribution to pathogenesis. Gene therapy approaches that target immune functions are being developed with encouraging results, despite the polygenic nature of these diseases. Basically this novel immuno-genetic therapy harnesses the knowledge of immunology with the myriad of biotechnological breakthroughs in vector design and delivery. Autoimmune disease is the result of genetic dysregulation which could be controlled by gene therapy. Here we summarize the genetic basis of these human diseases as well as some of the best characterized murine models. We discuss the strategies for their treatment using immuno- and gene therapy.
Asunto(s)
Enfermedades Autoinmunes/terapia , Terapia Genética , Inmunoterapia , Animales , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Artritis Reumatoide/terapia , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/terapia , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Ratones , Ratones Noqueados , Ratones Transgénicos , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapiaAsunto(s)
Enfermedades Autoinmunes/terapia , Técnicas de Transferencia de Gen , Inmunoterapia/métodos , Adyuvantes Inmunológicos/genética , Animales , Artritis/etiología , Artritis/inmunología , Artritis/terapia , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Terapia Genética/métodos , Humanos , Ratones , Ratones Endogámicos DBA , Linfocitos T/inmunología , Linfocitos T/trasplante , Trasplante IsogénicoRESUMEN
T cell hybridomas HCQ6 and MD.45 acquired Ab-type specificity to collagen type II, when engrafted with a chimeric cell surface receptor, scC2Fv/gamma, which includes the single-chain Fv domain (scFv) of the anti-collagen type II mAb C2 and the signaling gamma subunit of the Fc epsilonRI. When transduced into MD.45 cells, scC2Fv/gamma or its mutated form lacking immunoreceptor tyrosine-based activation motif (ITAM), scC2Fv/gammaIC-, formed mainly homodimers. A small proportion of these molecules formed heterodimers with endogenous CD3zeta in these hybridoma cells. By contrast, in HCQ6 cells, the majority of scC2Fv/gamma and scC2Fv/gammaIC- molecules formed heterodimers with CD3zeta, and only a small proportion of them was expressed as homodimers. Stimulation with plastic-immobilized collagen induced IL-2 production in scC2Fv/gamma-transduced MD.45 cells, but not in MD.45 cells transduced with the ITAM-less chimera scC2Fv/gammaIC-. HCQ6 cells transduced with scC2Fv/gamma responded to plastic-bound collagen. Due to the high content of CD3zeta-associated chimeras, HCQ6 cells transduced with the ITAM-less scC2Fv/gammaIC- chimera were also responsive to plastic-bound collagen. When cells were stimulated with collagen in solution, MD.45 cells transduced with scC2Fv/gamma produced IL-2, whereas transduced HCQ6 cells were unresponsive, hence suggesting that the ability of cells transduced with scC2Fv chimeras to respond to soluble collagen correlated with predominant expression of divalent scC2Fv/gamma homodimers, but not monovalent scC2Fv/gamma-CD3zeta or scC2Fv/gammaIC(-)-CD3zeta heterodimers. Of interest, expression of CD3 subunits in hybridomas transduced with scC2Fv chimeras was reduced, resulting in decreased response to cognate Ags.
Asunto(s)
Complejo CD3/inmunología , Colágeno/inmunología , Hibridomas/inmunología , Fragmentos de Inmunoglobulinas/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de IgE/inmunología , Linfocitos T/inmunología , Animales , Complejo CD3/biosíntesis , Complejo CD3/genética , Cartílago Articular/inmunología , Regulación de la Expresión Génica , Hibridomas/metabolismo , Fragmentos de Inmunoglobulinas/genética , Interleucina-2/metabolismo , Ratones , Plásticos , Complejo Receptor-CD3 del Antígeno de Linfocito T/inmunología , Receptores de IgE/genética , Proteínas Recombinantes de Fusión/inmunología , Solubilidad , TransfecciónRESUMEN
Current understanding of the pathogenesis of rheumatoid arthritis has provided evidence that therapeutic benefit can be achieved by using antagonists targeted to the inflammatory cytokines involved, mainly tumour necrosis factor-alpha and interleukin-1. Gene delivery of antagonists, which can inhibit the production or action of these cytokines and other mediators, has been achieved in experimental animal models. This new method of delivery can produce therapeutic effects at lower concentrations and in a local environment, overcoming the adverse effects that often accompany protein therapy. However, several technological and biological restraints preclude the immediate adaptation of this method to human treatment. Based on the experimental evidence, possible target therapeutic genes, cell types and vector systems that could be used are discussed in this article.
Asunto(s)
Artritis Reumatoide/terapia , Terapia Genética , Artritis Reumatoide/inmunología , Vectores Genéticos , HumanosRESUMEN
In this study we have compared the ligand binding activity of the two closely related beta 2 integrins, Mac-1 and p150,95, which are expressed separately as receptors permanently transfected into K562 cells. Mac-1 has previously been shown to associate with Fc gamma R, particularly Fc gamma RIII, but K562 cells express only endogenous Fc gamma RIIA. We have, therefore, taken advantage of this situation to examine a possible relationship between Fc gamma RIIA with Mac-1 and p150,95 in the absence of other Fc gamma R. The main finding is that anti-Fc gamma RII mAb have a profound inhibitory effect on cell adhesion mediated by Mac-1, but not on the adhesion mediated by p150,95. Thus, in spite of the fact that Mac-1 and p150,95 bind to the same or at least a very similar selection of ligands, their association with other receptors on the cellular membrane, and therefore their mode of regulation may be different.
Asunto(s)
Integrina alfaXbeta2/metabolismo , Integrinas/metabolismo , Antígeno de Macrófago-1/metabolismo , Receptores de IgG/metabolismo , Anticuerpos Monoclonales/farmacología , Especificidad de Anticuerpos , Adhesión Celular/inmunología , Epítopos/efectos de los fármacos , Epítopos/inmunología , Humanos , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/inmunología , Leucemia Eritroblástica Aguda/metabolismo , Unión Proteica , Receptores de IgG/inmunología , Células Tumorales CultivadasRESUMEN
Biocompatibility assessed by values of dialysis leukopenia, complement system activation, that of blood elements was compared in the first and second use of capillary dialyzers equipped with various membranes. In the dialyzers re-use biocompatibility improved. Electron microscopy of hollow fiber sections suggested the role of protein layer safety on the membrane surface in biocompatibility under successive employment of the dialyzers. Treatment of the latter with acetic and peracetic acids mixture proved advantageous against other methods. Clinical effect due to dialyzer re-use changed positively.
Asunto(s)
Diálisis Renal/instrumentación , Análisis de Varianza , Proteínas del Sistema Complemento/análisis , Equipo Reutilizado/estadística & datos numéricos , Seguridad de Equipos , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Recuento de Leucocitos , Leucotrieno B4/sangre , Masculino , Membranas Artificiales , Diálisis Renal/estadística & datos numéricos , Esterilización/métodos , Factor de Necrosis Tumoral alfa/análisis , beta-Tromboglobulina/análisisRESUMEN
We have investigated TNF-alpha secretory response of peripheral blood mononuclear cells (PBMC) from 13 uraemic patients undergoing regular haemodialysis with cuprophane membrane (CM). Sixteen healthy subjects and five uraemic patients under conservative therapy were also studied as controls. Cells of haemodialysis patients exhibited increased TNF-alpha release in vitro in the absence of activating stimuli other than culture conditions, as compared with normal and uraemic controls. In contrast to normal cells, this spontaneous secretion of TNF-alpha from dialysis PBMC could not be significantly reduced by addition of polymyxin B to culture medium, thus indicating its independence of trace amount of lipopolysaccharide (LPS) present in the medium as contaminant. Furthermore, predialysis PBMC were considerably more sensitive to stimulation with 10(7) pg/ml of LPS under in vitro culture conditions than normal and uraemic controls. To elucidate a role of direct contact with CM in stimulation of TNF-alpha release from monocytes, PBMC were cultured on CM in vitro. Contact with CM stimulated TNF-alpha secretion from PBMC above the level of cells cultured on tissue culture plastic. This response persisted with time in culture in contrast to a transient LPS-induced TNF-alpha release. Furthermore, PBMC stimulated by contact with CM for 2 days did not lose the capacity to secrete TNF-alpha in response to a subsequent LPS stimulation, while a 2-day treatment of cells with LPS was followed by LPS refractory state. Therefore, direct contact with CM induces in PBMC a long-lasting TNF-alpha response which is not down-regulated by the acquisition of refractoriness in a manner similar to that which occurs in the case of LPS stimulation. These in vitro findings provide a possible explanation of the observation that predialysis PBMC exhibit elevated TNF-alpha secretory capacity.
Asunto(s)
Celulosa/análogos & derivados , Fallo Renal Crónico/terapia , Leucocitos Mononucleares/metabolismo , Diálisis Renal/métodos , Factor de Necrosis Tumoral alfa/metabolismo , Celulosa/inmunología , Relación Dosis-Respuesta Inmunológica , Humanos , Técnicas In Vitro , Fallo Renal Crónico/sangre , Lipopolisacáridos/administración & dosificación , Membranas Artificiales , Monocitos/inmunología , Factores de TiempoRESUMEN
The present study demonstrates that with time in culture blood monocytes (MO) lose their ability to express procoagulant activity (PCA) and secrete tumor necrosis factor-alpha (TNF alpha) in culture medium in response to lipopolysaccharide (LPS) stimulation. Thus, upon 10 micrograms/ml LPS stimulation for 4 hours 2-day-old MO produced lower levels of PCA and TNF alpha than fresh MO. The decrease in responsiveness was not caused by cell death, since in the case of TNF alpha it was fully reversible by interferon-gamma (IFN-gamma). Compared with cells pre-incubated in medium alone, the responsiveness of MO pre-incubated in LPS was further decreased. Thus, in MO LPS pre-incubation was followed by an LPS refractory state. It was expected that the decrease in responsiveness induced by cultivation in medium alone was mediated by LPS contamination of culture medium. However, as we were unable to prevent this decrease by neutralizing LPS contamination of the culture medium with polymyxin B, the loss in LPS-induced activities of cultured MO is likely to be mediated by culture conditions other than LPS contamination. Taken together the present data demonstrate that LPS-dependent as well as LPS-independent pathways of MO desensitization to LPS exist.
Asunto(s)
Lipopolisacáridos/fisiología , Monocitos/efectos de los fármacos , Células Cultivadas , Medios de Cultivo , Contaminación de Medicamentos , Humanos , Lipopolisacáridos/sangre , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Direct and immune electron microscopy was used to determine the frequency of finding of hepatitis A virus (HAV) and other viral agents in feces of patients in relation to the diagnosis and epidemiological situation. HAV-containing excretions from patients were analysed ultrastructurally. The highest frequency of HAV detection was established in patients in a water-borne and food-borne outbreak of hepatitis A (HA) and was 40.9% and 36.9%, respectively. In patients with HA diagnosis in the period of a seasonal rise of HA incidence HAV particles were found in 11.8%, and in the interseasonal period in 5%. Apart from HAV particles, in a small per cent of patients with HA diagnosis adenovirus and enterovirus particles were found. In patients with the disease diagnosed as hepatitis B (HB) only adenovirus and enterovirus particles were found. In contrast to the patients with HAV and HB diagnosis, the patients who were combined into a conditional "non-hepatitis" group were found to have, in addition to HAV (in the period of seasonal rise of HA incidence), adenovirus and enterovirus particles, also particles of astrovirus, coronavirus, and rotavirus. In fecal specimens of patients containing typical HAV particles structures were found resembling individual fragments of empty HAV particles, antibody-covered 17-22 nm and 27 nm spherical structures poorly reacting with antibody.