[The effect of viral infections on the cytokine profile in pregnant women with obstetric complications and immunotherapy with human alpha2b interferon].

The goal of this work was to examine the effects of infections caused by HSV1/2, CMV, and HPV on the cytokine profile in pregnant women with obstetric complications (OC) and to evaluate the efficacy of the therapy with recombinant human alpha2b interferon. Direct markers of the viruses were identified using PCR and rapid culture method in 85 pregnant women divided into 3 groups: group 1 (n = 21), women with visual HPV-related clinical manifestations; group 2 (n = 48), with detectable markers of viral infections and no clinical manifestations, and group 3 consisting of pregnant women with OC without markers and clinical manifestations of viral infections (n = 16). The rate of HPV DNA detection in pregnant women was higher than that of herpesviruses (HV) CMV and/ or HSV: 37.6% vs. 11.8%. The frequency of mixed HV/HPV infection in group 1 was 2.3-fold higher than in group 2. The cytokine levels of IFNalpha, IFNgamma, IL-4, IL-6, IL-8, and TNFalpha in blood plasma and vaginal washings were studied. Statistically significant differences in infected women (groups 1 and 2) in comparison with uninfected women (group 3) were detected: a) blood plasma concentration of IFNgamma increased in clinically manifested HPV infection; b) blood plasma IL-8 concentration increased in clinically manifested HPV and in mixed HV+HPV infections without clinical symptoms of HPV infection; c) blood plasma concentration of TNFalpha increased in women with asymptomatic HPV-infection; d) IL-6 concentration in vaginal washings increased in mixed infection in group 1. The effect of IFN-alpha2b was assessed by analyzing cytokine levels in women on basic therapy with and without Viferon. In infected women, Viferon caused a 2-3-fold decrease in the concentrations of IFNgamma and IL-8 in blood plasma, thus bringing them near those of uninfected women with OC. The analysis of the state of newborns health has shown that for women with OC the risk of giving birth to a child in critical condition is 4.3-fold higher when CMV is detected in the third trimester of pregnancy.

[Impact of herpesvirus infections on the level of proinflammatory cytokines in premature neonatal infants].

The aim of this study was to estimate the frequency of HSV and/or CMV among the pathogens causing intrauterine infections (IUI) and to investigate their impact on the level of proinflammatory cytokines in premature neonatal infants. Examinations were performed in 3 neonatal groups: 1) premature neonates with clinical manifestations of IUI; 2) those without IUI; 3) full-term newborns. In group 1, viral (HSV and/or CMV) and bacterial infections were detectable with the same frequency. Quantitative analysis of plasma IL-6 and IL-8 levels and the induced production of these cytokines by blood cells in vitro showed that in Group 1 neonates, IL-6 and IL-8 concentrations were substantially higher and the induced production of these cytokines was lowerthan those in Group 3. The detection of HSV and/or CMV markers in premature newborn infants was attended by a statistically significant rise in plasma IL-6 levels; the identification of the opportunistic bacterial microflora correlated with the higher concentration of IL-8. In Group 1, wiferon produced an immunomodulatory effect, by lowering IL-8 concentrations to the level observed in Group 3.

[Viferon efficacy in influenza in adult patients].

The therapeutic efficacy of Viferon (suppositories of human recombinant interferon alfa-2) was investigated in a double-blind controlled study with the use of Arbidol as a reference drug in the treatment of patients with influenza. Viferon and Arbidol lowered the signs of the fever, intoxication, catarrh and the disease as the whole.

[Perinatal transmission of hepatitis C virus].

The perinatal transmission of hepatitis C virus (HCV) is the major route of infection in infants. The understanding of the risk factors of perinatal infection and the continuation of studies in this area allow one to propose immunological algorithms of prediction and to work outa follow-up strategy of infected children. The authors have made virological and Immunological studies of infants born to mothers with HCV infection.

[Viferon suppositoria in therapy of relapsing herpesvirus infection in women].

The therapeutic efficacy of Viferon, a recombinant human interferon alpha-2b (rectal suppositoria) was studied in the therapy of relapsing herpesvirus infection in women. The clinical efficacy of the drug was recorded in 90% of the patients. The analysis of the remote results of the treatment made it possible to conclude that the Viferon suppositoria had an antirelapsing activity.

[Viferon suppositories in the treatment of influenza in adults].

One hundred and one patients at the age of 18 to 60 years suffering from influenza were observed during increased ratio of the sickness due to the influenza virus types A (H1N1 and H3N2) and B. The diagnosis of influenza was confirmed by the laboratory tests. Viferon was used in the treatment of 35 patients. The randomized double blind placebo-controlled study revealed high therapeutic efficacy ofviferon and its immunomodulating effect on the T-cells, the neutrophil phagocytic activity and the decrease of the levels of the circulating immune complexes. Viferon and arbidol decreased the fever periods and the toxicosis symptoms vs. the placebo. The therapeutic efficacies of viferon and arbidol were on the whole comparable, whereas the clinical findings and the results of the immunological tests were evident of the viferon higher therapeutic and immunomodulating efficacy. No side effects of the drugs were recorded. The tolerability was excellent. Viferon can be recommended for the treatment of influenza in adults.

[Viferon ointment for prophylaxis of acute viral respiratory tract infection in children].

Three hundred and fifty children at the age of 3 months to 6 years under diverse social conditions were observed in dynamics for the periods of 1 to 3 years. The main tasks of the study were development of schemes and methods for prophylactic use of the Viferon ointment and estimation of its efficacy in acute viral respiratory tract infection. Season changes in the interferon genesis were revealed and no such dynamics in the children with frequent infections was shown. The ointment was applied according to the developed procedure intranasally in a daily dose of 1 g every day for the first 2 weeks and 3 times a week for the following 2-4 weeks. Interferon correctable and immunomodulating effects of the ointment were detected, the same as its favourable impact on the number of the acute respiratory tract infection cases including those under the conditions of the infant school adaptation. Its favourable effect was also observed in children with frequent infections during their immunorehabilitation. The most pronounced clinical and immunomodulating effects were revealed in young children.

[Evaluation of the efficacy of wiferon and arbidol in adult influenza].

The therapeutic efficacy of wiferon (recombinant alpha2beta-interferon) versus arbidol was studied in a double-blind controlled study in patients with laboratorily verified influenza. Within the first 24-36 hours after the onset of the disease, wiferon and arbidol reduced the duration of fever, intoxication, and the catarrhal symptoms of the disease as a whole. The agents were shown to have an immunomodulating effect.

[Effect of tumor necrosis factor DNA on immune response to DNA immunization against herpes simplex virus]. / Vliianie DNK faktora nekroza opukholi na immunnyi otvet pri DNK-immunizatsii protiv virusa prostogo gerpesa.

A study was made of the adjuvant effect of the mouse tumor necrosis factor alpha (mTNF alpha) on DNA immunization against the herpes simplex virus type 1 (HSV1). The HSV1 gD gene (pDNAgD) served as an immunogen; mTNF alpha or its gene cloned in an eukaryotic expression vector (pDNAmTNF) were used to modulate the immune response. Double immunization with pDNAgD led to a sixfold increase in the in vitro T-cell response, a high (1:2000) titer of anti-HSV1 antibodies (including virus-neutralizing antibodies), an increase in IgG2a/IgG1 (suggesting a shift of the immune response to the Th1 type), and no change in CD4/CD8 T-cell ratio. A single injection of mTNF alpha along with inactivated HSV1 allowed a twice higher antibody titer and a fourfold higher T-cell response as compared with immunization with HSV1 alone. Double immunization with both pDNAgD and pDNAmTNF increased the titer of anti-HSV1 antibodies and the T-cell response by factors of 8 and 1.5, respectively, as compared with immunization with pDNAgD alone. However, the protective effect was significantly lower with the two plasmids than with pDNAgD (73 vs. 100%). Thus, DNA immunization with pDNAgD induced both B- and T-cell responses and completely protected mice from a lethal doze of HSV1. The adjuvant properties of mTNF alpha and pDNAmTNF need further investigation.

[The laboratory diagnosis of cytomegalovirus infection in infants in the first months of life]. / Laboratornaia diagnostika tsitomegalovirusnoi infektsii u detei pervykh mesiatsev zhizni.

The detection rate of IgM, specific to cytomegalovirus (CMV), in the umbilical blood was 2.0 +/- 1.8% in infants with antenatal complications in their medical history, 8.9 +/- 1.8% in hospitalized infants aged 7 days to 6 months; simultaneously, such IgM proved to be absent in healthy infants of the same age. The maximum primary detection rate of CMV-specific IgM in hospitalized infants was registered at the age of 1.5-4 months and the minimum detection rate, at the age of 6 months, as well as at the age of 1 month and younger. In sick infants aged 0-6 months CMV-specific IgM were detected, as a rule, for 2-4 weeks. 86% of infants with CMV-specific IgM detected in their blood were found to have cytomegaloviremia; in 80% of patients the virus was excreted with saliva and in 50% the virus was detected in blood plasma.

[Recombinant alpha2-interferon substances in treating patients with acute hepatitis B with a mild course]. / Preparaty rekombinantnogo alpha2-interferona v lechenii bol'nykh ostrym virusnym gepatitom v legkogo techeniia.

Interferon (viferon-500 and reaferon) is recommended for patients with light forms of acute virus hepatitis B to prevent chronic degeneration of the disease. The data of dynamic monitoring of the production of alpha-interferon helped develop a test for predicting threatened chronic degeneration of light forms of hepatitis B. Indications for antiviral therapy aimed at prevention of chronic disease have been defined.

[Assessment of the formation of antibodies to interferon in patients with juvenile respiratory papillomatosis on interferon therapy]. / Otsenka obrazovaniia antitel k interferonu u bol'nykh iuvenilnym respiratornym papillomatozom pri interferonoterapii.

Children with juvenile respiratory papillomatosis given alpha 2-INF had antibodies to alpha 2-INF in 67.7% of cases. In children treated with intramuscular recombinant alpha 2-INF (reaferon) alone antibodies to INF occurred in 92.3% of patients. The proportion of such patients fell to 28.5% if the children used recombinant alpha 2-INF as rectal suppositories viferon. The level of the antibodies in 4-48 hours decreased 2 times maximally and returned to the baseline on day 3 since intramuscular injection of alpha 2-INF. It is stated that interferon therapy had a positive effect on juvenile respiratory papillomatosis. Antibodies to INF had no negative effects on the treatment results.

[Experience in the use of viferon suppositories in young children with juvenile respiratory papillomatosis (preliminary report)]. / Opyt primeneniia viferona v svechakh u detei mladshego vozrasta s iuvenil'nym respiratornym papillomatozom (predvaritel'noe soobshchenie).

The authors tried a new medical form of interferon, rectal suppositories viferon, to treat severe juvenile respiratory papillomatosis in young children. Side effects were absent, antibodies to interferon in low titers were registered in 2 patients only. Further studies are needed to specify the promising effects of the above treatment.

[Antibodies to alpha-2A interferon in children with juvenile respiratory papillomatosis]. / Antitela k al'fa-2A interferonu u detei s iuvenil'nym respiratornym papillomatozom.

Follow-up of 36 JRP children and 12 controls (as shown by solid-phase enzyme immunoassay) has revealed that antibodies to IFN-alpha 2a with titers 1:20 to 1:1280 were present in 73.7% (14 of 19) of patients after interferon therapy and in 5.8% (1 of 17) of those who have not received interferon. None of the controls had the antibodies. Among the patients who have received only recombinant IFN-alpha 2a 88.8% carried the antibodies. In leukocytic interferon-treated group this number made up 20%. The primary results evidence that there is no negative effect of INF antibodies on the treatment results in the doses and schemes used. Positive results of INF in JRP were not reported either.

[The interferon system in acute tick-borne encephalitis and effect on the dynamics of clinical laboratory indicators using different methods of interferon therapy]. / Sistema interferona pri ostrom kleshchevom éntsefalite i vliianie na dinamiku kliniko-laboratornykh pokazatelei razlichnykh metodov interferonoterapii.

Study of the interferon system parameters, natural killer activity, and immunologic characteristics in patients with acute tick-borne encephalitis confirmed that addition of interferon preparations to combined therapy is pathogenetically justified. Reaferon was conducive to shortening of the manifest period of the disease and to alleviation of its symptoms, but it depressed its own interferonogenesis. Viferon had not only a positive impact on the time course of clinical parameters, but promoted a more active recovery of interferon production and immunologic parameters.

[Interferon status in predicting the outcome of acute viral hepatitis B]. / Interferonovyi status v prognozirovanii iskhodov ostrovo virusnogo gepatita B.

Analyzes the interferon status of patients with various outcomes of acute hepatitis B at different stages of the disease. Assesses the possibility of predicting cure and transformation of the acute disease into chronic hepatitis B. Enumerates factors influencing the efficacy of interferon therapy and the outcome of viral hepatitis B.