RESUMEN
AIM: Determination of values of coefficients of thermal stability of TEOVac for prognosis of conservation of the vaccine (specific biological activity) during the process of warranty period storage. MATERIALS AND METHOD: TEOVac (masticatory tablets) in primary packaging was kept at increased temperature (accelerated and stress-tests) and at the conditions established by PAP for the preparation (long-term tests). Biological activity of the vaccine was determined by titration on 12-day chicken embryos. RESULTS: A correlation between the value of coefficients of thermal stability and conservation of the prepared series of the condition preparation at the final date of storage was experimentally established. CONCLUSION: Coefficients of thermal stability could be used as a prognostic indicator of quality of the produced pelleted formulation of the preparation for evaluation of conservation of the vaccine during warranty period storage.
Asunto(s)
Vacuna contra Viruela/metabolismo , Viruela/prevención & control , Vacunas Atenuadas/metabolismo , Animales , Química Farmacéutica , Embrión de Pollo , Pollos , Humanos , Viruela/virología , Vacuna contra Viruela/uso terapéutico , Temperatura , Vacunas Atenuadas/uso terapéuticoRESUMEN
KNOX transcription factors (TFs) regulate different aspects of plant development essentially through their effects on phytohormone metabolism. In particular, KNOX TF SHOOTMERISTEMLESS activates the cytokinin biosynthesis ISOPENTENYL TRANSFERASE (IPT) genes in the shoot apical meristem. However, the role of KNOX TFs in symbiotic nodule development and their possible effects on phytohormone metabolism during nodulation have not been studied to date. Cytokinin is a well-known regulator of nodule development, playing the key role in the regulation of cell division during nodule primordium formation. Recently, the activation of IPT genes was shown to take place during nodulation. Therefore, it was hypothesized that KNOX TFs may regulate nodule development and activate cytokinin biosynthesis upon nodulation. This study analysed the expression of different KNOX genes in Medicago truncatula Gaertn. and Pisum sativum L. Among them, the KNOX3 gene was upregulated in response to rhizobial inoculation in both species. pKNOX3::GUS activity was observed in developing nodule primordium. KNOX3 ectopic expression caused the formation of nodule-like structures on transgenic root without bacterial inoculation, a phenotype similar to one described previously for legumes with constitutive activation of the cytokinin receptor. Furthermore, in transgenic roots with MtKNOX3 knockdown, downregulation of A-type cytokinin response genes was found, as well as the MtIPT3 and LONELYGUY2 (MtLOG2) gene being involved in cytokinin activation. Taken together, these findings suggest that KNOX3 gene is involved in symbiotic nodule development and may regulate cytokinin biosynthesis/activation upon nodule development in legume plants.
Asunto(s)
Genes Homeobox , Genes de Plantas , Genes Reguladores , Medicago truncatula/genética , Pisum sativum/genética , Nódulos de las Raíces de las Plantas/genética , Factores de Transcripción/genética , Citocininas/biosíntesis , Citocininas/genética , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Glucuronidasa/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rhizobium leguminosarum/fisiología , Simbiosis , Regulación hacia ArribaRESUMEN
In the present work, the potential for the enhancement of the adaptive capacity of microbe-plant systems (MPSs) through the integration of the symbiosis partners' genomes is considered on the example of different types of symbiotic relationships. The accumulated data on the genetic control of interactions for both the plant and microbe, which are discussed in the paper with respect to signaling genes, suggest that it is the complementarity of genetic determinants that underlies the successful formation of MPSs. A eukaryotic genome with limited information content, which is stable throughout a generation, is complemented by a virtually unlimited prokaryotic metagenome. The microsymbiont's ability to adapt to different living conditions is based on the restructuring of the accessory genome by different mechanisms, which are likely to be activated under the influence of plants, although the details of such a regulation remain unknown. Features of the genetic control of the interaction, particularly its universal character for different symbionts, allow us to formulate a principle of genome-complementarity with respect to interacting organisms and consider it an important factor, an adaptation that enhances the abilities of M PSs for their sustainable development in natural ecosystems and for high plant productivity in agrocenoses.
Asunto(s)
Adaptación Fisiológica/genética , Genes de Plantas/fisiología , Metagenoma/fisiología , Plantas/genética , Simbiosis/genéticaRESUMEN
The review summarizes the results of studies on the comigration of tubercular bacteria and bean plants to new habitats, which is often accompanied by a decrease in the symbiosis efficiency due to a loss of the diversity of genes responsible for the interaction. This migration may lead to a rise in new symbionts as a result of gene transfers from initial symbionts to local bacteria. It was demonstrated that typically new symbionts lack an ability for N2 fixation but are highly competitive, blocking the inoculation of bean cultures by industrial strains. The design of coadapted systems of recognition and signal interaction of partners is a perspective approach to ensure competitive advantages of efficient rhizobia strains introduced into agrocenoses, together with host plants, over inactive local strains.
Asunto(s)
Fabaceae/genética , Rhizobium/genética , Nódulos de las Raíces de las Plantas/genética , Simbiosis/genética , Ecosistema , Fijación del Nitrógeno/genética , Fenómenos Fisiológicos de las Plantas , Raíces de Plantas , Nódulos de las Raíces de las Plantas/microbiología , Nódulos de las Raíces de las Plantas/fisiología , Especificidad de la EspecieRESUMEN
The paper presents results of testing a modified algorithm for predicting virus ID50 values in a host of interest by extrapolation from a model host taking into account immune neutralizing factors and thermal inactivation of the virus. The method was tested for A/Aichi/2/68 influenza virus in SPF Wistar rats, SPF CD-1 mice and conventional ICR mice. Each species was used as a host of interest while the other two served as model hosts. Primary lung and trachea cells and secretory factors of the rats' airway epithelium were used to measure parameters needed for the purpose of prediction. Predicted ID50 values were not significantly different (p = 0.05) from those experimentally measured in vivo. The study was supported by ISTC/DARPA Agreement 450p.
Asunto(s)
Algoritmos , Interacciones Huésped-Patógeno , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/inmunología , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/virología , Animales , Células Cultivadas , Susceptibilidad a Enfermedades , Femenino , Inmunidad Innata , Subtipo H3N2 del Virus de la Influenza A/fisiología , Pulmón/inmunología , Pulmón/virología , Ratones , Ratones Endogámicos ICR , Ratas , Ratas Wistar , Especificidad de la Especie , Tráquea/inmunología , Tráquea/virologíaRESUMEN
Arbuscular mycorrhiza (AM) is an ancient mutualistic symbiosis formed by 80-90 % of land plant species with the obligatorily biotrophic fungi that belong to the phylum Glomeromycota. This symbiosis is mutually beneficial, as AM fungi feed on plant photosynthesis products, in turn improving the efficiency of nutrient uptake from the environment. The garden pea (Pisum sativum L.), a widely cultivated crop and an important model for genetics, is capable of forming triple symbiotic systems consisting of the plant, AM fungi and nodule bacteria. As transcriptomic and proteomic approaches are being implemented for studying the mutualistic symbioses of pea, a need for a reference transcriptome of genes expressed under these specific conditions for increasing the resolution and the accuracy of other methods arose. Numerous transcriptome assemblies constructed for pea did not include mycorrhizal roots, hence the aim of the study to construct a reference transcriptome assembly of pea mycorrhizal roots. The combined transcriptome of mycorrhizal roots of Pisum sativum cv. Frisson inoculated with Rhizophagus irregularis BEG144 was investigated, and for both the organisms independent transcriptomes were assembled (coverage 177x for pea and 45x for fungus). Genes specific to mycorrhizal roots were found in the assembly, their expression patterns were examined with qPCR on two pea cultivars, Frisson and Finale. The gene expression depended on the inoculation stage and on the pea cultivar. The investigated genes may serve as markers for early stages of inoculation in genetically diverse pea cultivars.
RESUMEN
Recent data on the plant control of early stages of mutually beneficial (mutualistic) symbioses of legumes, the mechanisms of perception and transmission of the microsymbiont's molecular signals in the macrosymbiont's cells, and induction of the genetic programs of the development of symbiotic compartments and organs of the plant are summarized. It is demonstrated that the genetic system of the plant controlling the development of nitrogen-fixing symbiosis of legumes (symbiotic root nodules), which emerged 70-80 Ma ago, has undoubtedly evolved on the basis of the genetic system controlling the development of the symbiosis with arbuscular mycorrhizal fungi (which emerged 40-500 Ma ago. Interactions between genes and between gene products, as well as exchange of molecular signals, form the basis of mutually beneficial (mutualistic) plant-bacterium interactions. Even in the case of a highly specific nitrogen-fixing symbiosis of legumes (symbiotic nodules), the receptors perceiving the signal from root-nodule bacteria may function in different ways. The development of arbuscular mycorrhiza and nitrogen-fixing symbiosis in legumes is a multistep process involving hundreds of genes of both the macro- and microsymbionts. For the symbioses to develop successfully, these genes should act in a coordinated way in the newly formed superorganismal system. Further studies are necessary to shed light onto the complexity of the plant genetic control of the development of mutualistic symbioses in legumes and provide information required for improving their functions in adaptive plant-breeding systems.
Asunto(s)
Fabaceae/fisiología , Genoma Fúngico/fisiología , Genoma de Planta/fisiología , Micorrizas/fisiología , Simbiosis/fisiología , Fabaceae/microbiologíaRESUMEN
Secretory factors were isolated by lung wash followed by centrifugation to remove cells, dialysis of supernatant to remove NaCl salt, lyophilization of the lavage fluid and resuspention of the lyophilization product in an isotonic NaCl solution. It was shown that biological activity of influenza virus /Aichi/2/68 (3N2) significantly decreased (p = 0,01) from 8,17 +/- 0,10 to 7,14 +/- 0,20 IgEID50/ml during its incubation with secretory factors at 37 degrees C for 1 hr and to 7,92 +/- 0,17 IgEID50/ml in isotonic NaCl solution in the absence of these factors. Their concentration in the incubation medium was estimated to be 9.1 +/- 0.7% of their level in the lungs.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Pulmón/metabolismo , Infecciones por Orthomyxoviridae/metabolismo , Alveolos Pulmonares/metabolismo , Surfactantes Pulmonares/metabolismo , Mucosa Respiratoria/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/citología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Pulmón/patología , Pulmón/virología , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , Alveolos Pulmonares/virología , Ratas , Ratas Wistar , Mucosa Respiratoria/virologíaRESUMEN
The levels of susceptibility to influenza virus A/Aichi/2/68 H3N2 and the virus yield were determined using primary cells of the trachea and lungs of CD-1 mice and Wistar rats, and for 3 sets of cells obtained from primary lung cells of the both species by centrifugation in the gradient of density and by sedimentation on a surface. The values of ID50 virus dose for 10(6) cells and virus yield per 1 infected cell determined for primary mice cells were 4.0+/-0.47 and 3.2+/-0.27 IgEID50 (lung cells), 3.8+/-0.17 and 3.3+/-0.20 IgEID50 (tracheal cells), and those determined for primary rat cells were 4.0+/-0.35 and 2.1+/-0.24 IgEID50 (lung cells), 3.7+/-0.27 and 2.2+/-0.46 IgEID50 (tracheal cells). The values of ID50 and yield measured for mixtures of cells obtained from primary lung cells by centrifugation in gradient of density and by sedimentation on a surface differed insignificantly (p = 0.05) from the values of the corresponding parameters measured for lung and tracheal cells for both rats and mice. The analysis of data on the variation of the concentrations of different cell types in the experimental cell mixtures shows that type 1 and 2 alveolocytes possess significantly lower (p = 0.05) susceptibility and productivity vs. ciliated cells of the both species. The investigation was conducted within the frame of the ISTC/DARPA#450p project.
Asunto(s)
Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/patología , Alveolos Pulmonares/patología , Infecciones del Sistema Respiratorio/patología , Animales , Recuento de Células , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Ratones , Infecciones por Orthomyxoviridae/virología , Alveolos Pulmonares/virología , Ratas , Ratas Wistar , Infecciones del Sistema Respiratorio/virologíaRESUMEN
Experimental hyperthyreosis was stimulated by intraventricular injections of sodium solithyroxin (T4) suspension on 1% starch gel during 10 days at a dose of 10 microg/100 g of body mass (n = 15) or 20 microg/100 g of body mass (n = 15). Renal function was tested by 5 % water loading after 24 hrs. since the last T4 injection. Urine and blood plasma samples were analyzed for creatinine; in addition, urine was analyzed for sodium and potassium ions of titrated acids, ammonium cations, and pH. Thyroxin was found to decrease creatinine clearance and expedite renal excretion of sodium and potassium ions irrespective of the amount of exogenous T4; at the same time, exaggerated excretion of titrated acids and ammonium cations correlated with T4 dose.
Asunto(s)
Equilibrio Ácido-Base/efectos de los fármacos , Transporte Iónico/efectos de los fármacos , Riñón/efectos de los fármacos , Tiroxina/farmacología , Animales , Creatinina/metabolismo , Masculino , Ratas , Tiroxina/administración & dosificaciónRESUMEN
The results of the study showed that subcutaneous kenalog (Kn) lowered the resistance of mice to influenza virus (InV), as was seen by a decrease in 50% lethal dose and an increase in the degree of pulmonary tissue lesion, and the susceptibility of the lungs to InV, seen by the fact that 50% aerogenic infective dose (AID50) was significantly higher in the main group (Kn+InV) than in controls, which received Hanks solution subcutaneously (HS+InV). In vitro, 50% infective doses of InV for suspension of pulmonary and tracheal cells, characterizing their susceptibility to InV, were similar in Kn mice and controls. At the same time, lower resistance and higher degree of pulmonary inflammation noted in Kn mice after receiving a dose of InV that was much higher than an infecting one, was accompanied by the prevalence in the number as well as phagocyte and superoxide-producing activity of neutrophiles (Nph) over the same parameters for alveolar macrophages (AMph) as early as two days after receiving InV dose, vs. InV-infected controls. Evidently, one of the reasons for lower resistance to InV after Kn administration is significant disbalance between the functional activity of AMph and Nph populations. Ineffective AMph clearance of the lungs from InV and excessive number of recruited Nph and products of tissue disintegration may favor the development of respiratory failure and infectious-toxic shock, which leads to lower resistance in animals which receive Kn before InV infection.
Asunto(s)
Glucocorticoides/farmacología , Inmunidad Celular/efectos de los fármacos , Terapia de Inmunosupresión , Macrófagos Alveolares/inmunología , Infecciones por Orthomyxoviridae/inmunología , Orthomyxoviridae , Animales , Modelos Animales de Enfermedad , Femenino , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/virología , Masculino , Ratones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/virologíaRESUMEN
To predict a potential value of a viral ID50 for a macro-organism of interest (e.g. humans), it is necessary to determine in vitro two parameters of the interaction of the virus with susceptible cells of the host, i.e. the probability of the virus' productive absorption on a susceptible cell and the average virus yield per cell. A different macroorganism (a model animal) and primary cells obtained from it can be used to determine the value of a scale factor, which accounts for the difference between the values of the probability of the virus' absorption measured in vivo and in vitro. An original mathematical model is used to convert the above-mentioned data to ID50 for the macroorganism of interest. It was shown that the method of cultivating influenza virus (A/ Aichi/2/68) in primary suspension culture of respiratory tract cells of rats and two breeds of mice may be used to estimate potential human susceptibility to novel influenza viruses. This work was sponsored by DAPRA, USA, and performed under the contract 450p to the International Science and Technology Center, Moscow.
Asunto(s)
Subtipo H3N2 del Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/virología , Enfermedades Respiratorias/virología , Replicación Viral/fisiología , Animales , Embrión de Pollo , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Infecciones por Orthomyxoviridae/patología , Pronóstico , Ratas , Ratas Wistar , Enfermedades Respiratorias/patología , Inactivación de VirusRESUMEN
The review sums up the long experience of the authors and other researchers in studying the genetic system of garden pea (Pisum sativum L.), which controls sthe development of nitrogen-fixing symbiosis and arbuscular mycorrhiza. A justified phenotypic classification of pea mutants is presented. Progress in identifying and cloning symbiotic genes is adequately reflected. The feasibility of using double inoculation as a means of increasing the plant productivity is demonstrated, in which the potential of a tripartite symbiotic system (pea plants-root nodule bacteria-arbuscular mycorrhiza) is mobilized.
Asunto(s)
Bacterias/genética , Micorrizas/genética , Fijación del Nitrógeno/genética , Pisum sativum/genética , Nódulos de las Raíces de las Plantas/genética , Simbiosis/genética , Mutación , Nódulos de las Raíces de las Plantas/microbiologíaRESUMEN
During their first participation in the external quality assessment program (EQAP), 78-81% of the laboratories detect positive samples of control panels containing 0.125 IU/ml of HBsAg; 95-97% of them identify negative samples of the control panels. The high efficiency of EQAP was established when the results of the same laboratories that had participated in two cycles were compared. For correct detection of positive samples of the control panel, it is necessary to use disposable containers and tips for example for solutions of conjugate concentrate, tetramethylbenzidine, buffer for conjugate dilution, and citrate-phosphate solution. The ranges of 95% confidence interval were established for the individual values of CV values of the commercial preparation ILC-HBsAg in the laboratories: from 0 to 11.3% with estimated convergence and from 0 to 14.2% with estimated reproducibility. In making an intralaboratory control of the quality of HBsAg test using ILC-HBsAg, one should be guided by the test accuracy indices given in the application sheet.
Asunto(s)
Técnicas de Laboratorio Clínico , Antígenos de la Hepatitis/sangre , Hepatitis/sangre , Técnicas de Laboratorio Clínico/normas , Hepatitis/diagnóstico , Humanos , Programas Nacionales de Salud , Garantía de la Calidad de Atención de Salud , Reproducibilidad de los ResultadosRESUMEN
The significant antigenic crossovers between West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) make the immunological diagnosis of these diseases difficult. The avidicity index of virus-specific class G immunoglobulins (IgG) was used as a criterion for the differentiation of an immune response to WNV or TBEV in patients and convalescents. The panels of the sera sampled from patients with tick-borne encephalitis and convalescents in the Novosibirsk and Tomsk Regions and in the Primorye Territory and from those with West Nile fever and convalescents in the Volgograd Region. The determination of the avidicity index could establish that in the convalescents' sera, the avidicity index of virus-specific IgG was much higher than that in the patients' sera in the acute phase of infection. In relation to heteroantigen, the avidicity index and the positivity coefficient were substantially less than those in the reaction with homoantigen. The findings have indicated that the determination of the value of the avidicity index of virus-specific IgG and the positivity coefficient makes it possible to differentiate West Nile fever and tick-borne encephalitis with confidence on the basis of solid-phase enzyme immunoassay in determining virus-specific IgG in the sera of patients and convalescents in different regions of Russia.
Asunto(s)
Anticuerpos Antivirales/sangre , Afinidad de Anticuerpos , Encefalitis Transmitida por Garrapatas/sangre , Encefalitis Transmitida por Garrapatas/diagnóstico , Inmunoglobulina G/sangre , Fiebre del Nilo Occidental/sangre , Fiebre del Nilo Occidental/diagnóstico , Anticuerpos Antivirales/inmunología , Afinidad de Anticuerpos/inmunología , Reacciones Cruzadas , Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas/inmunología , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Estudios Retrospectivos , Fiebre del Nilo Occidental/inmunología , Virus del Nilo OccidentalRESUMEN
The study demonstrates the effects of kenalog (Kn), a synthetic glucocorticoid hormone, on the course of virus A/Aichi/2/68 influenza in white mice. In doses of 5 and 10 mg/kg, Kn reduced the weight of the adrenal glands, thymus and spleen, which was accompanied by decrease of the resistance to the mentioned virus, judging by LD50 decrease vs. this index in the control infected group. Besides, four days after infecting with 5 LD50 of influenza virus (IV), lung virus and interferon titers were significantly lower in mice pretreated with Kn vs. mice treated with placebo. Lung cell susceptibility to IV in vitro was identical in mice treated with Kn or placebo. In ultrathin lung sections of IV-infected mice, both experimental and control ones, there was virus budding in bronchial epithelium cells and type I and II alveolocytes. Analysis of inflammatory effusion compound in semithin lung sections 6 days after IV infection, found a substantially smaller number of mature alveolar macrophages (AM) and a bigger number of neutrophiles vs. infected controls. The authors reckon that higher mortality of mice pretreated with Kn before infecting, is caused not by enhancement of IV reproduction in target lung cells during influenza development, but by the contribution of other pathogenic factors. One of those may be increase of neutrophilic migration into the lungs; neutrophiles are more able to realize their significant destructive potential under the condition of reduction in the clearing function of AM and IV infection.
Asunto(s)
Glucocorticoides/uso terapéutico , Terapia de Inmunosupresión/métodos , Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Infecciones por Orthomyxoviridae/inmunología , Neumonía Viral/inmunología , Resultado del TratamientoRESUMEN
This research investigates a promising antiviral compound based on polyprenols from Siberian silver fir (Abies sibirica). The physico-chemical characteristics of a preparation developed in aerosol form and an estimation of its protective efficacy against aerosol challenge of laboratory animals are presented. It is shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of three formulations studied with about 70% of its mass accumulated in the size range below 1.8 microm; (2) 40-100% of aerosol particles contain preparation for different formulations; (3) after delivering under specified schedules, the preparations as developed can protect up to 100% of mice against 5 LD(50) of influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the preparation doses (which were 100 times lower than injection ones of the same efficacy) and did not exceed 10 microg/mouse. It was shown that the mode of action of this immunomodulating preparation was nonspecific stimulation of immune cells' various activities.
Asunto(s)
Abies , Antivirales/uso terapéutico , Infecciones por Orthomyxoviridae/prevención & control , Fitoterapia , Preparaciones de Plantas , Aerosoles , Animales , Femenino , Virus de la Influenza A , Masculino , Ratones , Nebulizadores y VaporizadoresRESUMEN
A 50 mcg/100 g b.w. single dose of thyroxine was injected to non-inbred white rat males with body mass 140-180 g in conditions of 5% water and osmotic (3% solution of sodium chloride) load, then renal function was studied. This injection reduced creatinine clearance and phosphate excretion, raised nitrate and protein excretion. The kidney of the hyperthyroid animals retains ability to increase creatinine clearance in response to osmotic load. Thus, the above model demonstrates that in the absence of thyroxine renal toxicity it changes homeostatic renal functions both at the vascular-glomerular and tubular levels.
Asunto(s)
Hipertiroidismo/fisiopatología , Riñón/fisiopatología , Tiroxina/toxicidad , Animales , Modelos Animales de Enfermedad , Diuresis/efectos de los fármacos , Diuresis/fisiología , Hipertiroidismo/inducido químicamente , Riñón/efectos de los fármacos , Pruebas de Función Renal , Masculino , Concentración Osmolar , Ratas , Cloruro de Sodio/farmacología , Tiroxina/sangre , UrinálisisRESUMEN
This study demonstrates the possibility of achieving a prophylactic effect by intramuscular injection of Abies sibirica polyprenols for the control of influenza virus infection in mice. One of the five polyprenol preparations tested, preparation N1, which had the lowest hydrophilic-lipophilic balance (8.6), produced a significant protective effect when injected in a dose of 2000 microg/mouse 2 days before aerosol infection of mice with influenza virus. A moderate protective effect was also observed using a second preparation, designated N2. One day after aerosol infection, animals pre-treated with 2000 microg doses of the polyprenol preparations or Hanks' solution showed no difference in the level of interferon accumulation in the lungs. Three days after injection of preparation N2 and N1, a significant decrease in spleen and thymus weights was, observed in the mice. One day after injection of these preparations, the number of lymphocytes in the bronchoalveolar tract of the mice exceeded almost twice that seen in mice treated with placebo. After 3 days, relative and absolute numbers of macrophages decreased, whereas those of lymphocytes increased significantly. Three days after the administration of preparations N1 and N2, macrophages became approximately twice as active in absorbing zymozan granules. Preparation N1 affected the system of superoxide radical anion production to a greater extent than preparation N2. The production of radical anions by the macrophages of the bronchoalveolar tract in the mice, 1 day after intramuscular injection of preparation N1, was significantly higher than that seen on day 3 and that induced by preparation N2 1 and 3 days after injection. These data indicate that emulsions of polyprenols that have relatively low hydrophilic-lipophilic balance, inhibit influenza virus infection in mice through a modulation of the host immune response.
Asunto(s)
Antivirales/farmacología , Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/prevención & control , Terpenos/farmacología , Animales , Antivirales/aislamiento & purificación , Emulsiones , Femenino , Virus de la Influenza A/patogenicidad , Inyecciones Intramusculares , Interferones/metabolismo , Masculino , Ratones , Infecciones por Orthomyxoviridae/metabolismo , Fagocitos/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Bazo/efectos de los fármacos , Terpenos/aislamiento & purificación , Timo/efectos de los fármacosRESUMEN
It is suggested that (a) LD50 is the measure of the efficacy of antiviral drugs: (b) a disease is characterized by the "barrier" type of a pathological process when in pathogenesis there exists an event whose manifestation largely determines the outcome of a disease (recovery/severe form with a fatal outcome). If the event consists in the penetration of a pathogen into a susceptible cell and the consequent reproduction of an antigen, the value LD50 for man is expressed as the same parameter for a model animal and as the parameters determined by in vitro human and animal cell experiments. The parameters include the degree of viral production adsorption on the cell and the levels of its reproduction. The algorithms for evaluating the efficacy of viral drugs are based on the relationship. The adequacy of the relationship is illustrated by experimental findings.