Isoprinosine Research Articles

Issues of treatment and prevention of recurrent inflammatory diseases of the upper respiratory tract: An immunologist's view. A review

Often ill people are, first of all, patients with recurrent infectious and inflammatory diseases of the upper respiratory tract (URT). They put a significant financial burden on the healthcare system. The leading etiological factors of recurrent inflammatory diseases of URT, in addition to pathogenic bacterial microflora, are viral agents (viruses of the viral respiratory infections group, herpes viruses). The chronic infection and recurrence of local inflammation is due to the persistence of resident bacterial and viral flora (including herpes viruses), and as a result, the insufficiency of the mucosal immune response. In order to optimize therapeutic and preventive measures for frequently ill adults and children, the most promising is the use of immunotherapy and immunoprophylaxis. The immunomodulator inosine pranobex, due to its unique combined (immunotropic and antiviral) properties, demonstrates effectiveness in the complex treatment of viral respiratory infections, including in combination with herpes viruses, and is successfully used to prevent frequent relapses of infectious and inflammatory diseases of the URT. The domestic analogue of inosine pranobex Normomed® [JSC "Valenta Pharm"», ЛП-№(002470)-(РГ-RU), ЛП-№(005542)-(РГ-RU)], has a good safety and bioequivalence profile, and occupies a worthy field in the Russian pharmaceutical market among drugs recommended for the treatment of viral infections in adults and children.

Contemporary Treatment Practices for Subacute Sclerosing Panencephalitis: A Nationwide Survey Among Adult and Pediatric Neurologists in India.

Subacute sclerosing panencephalitis (SSPE) is a progressive disorder caused due to the persistence of mutant measles virus in the brain. Treatment strategies for SSPE remain largely undefined, and there exists no information on how neurologists are currently managing SSPE. A survey-based study was conducted among Indian neurologists managing pediatric and adult patients with SSPE. A questionnaire-based survey was circulated by email regarding respondent demographics, preference for disease-modifying strategies, and symptomatic therapy. Survey response was obtained from 298 neurologists (responder rate 9.5%) and eventually analyzed from 266 respondents who managed SSPE in routine practice. This included 222 (83.5%) adult and 44 (16.5%) pediatric neurologists from 21 states of India. Ninety-five respondents (35.7%) indicated that they always advised Isoprinosine (inosine pranobex) to their patients. Regarding interferon therapy, 121 (45.5%) reported never advising it, whereas 56 (21.1%) always advised it. For myoclonus, the most frequently used first-line drug was valproate (181, 68%), followed by levetiracetam (58, 21.8%). Most (150, 56.4%) of the respondents favored personalized therapy for the individual patient in terms of the duration of disease-modifying treatment. The patient follow-up was reported to be poor, with most (171, 64.3%) of the patients following up only occasionally and 24 (9%) respondents indicating that patients are lost to follow-up promptly after the initial visit. While SSPE remains a vaccine-preventable illness and the focus should be on prevention through vaccination, there is an unmet urgent need among Indian neurologists for better-defined treatment strategies for patients with SSPE.

THE EFFECTIVENESS OF THE IMMUNE-BOOSTING PREPARATIONS IN PREVENTION AND TREATMENT OF RESPIRATORY INFECTIONS

Respiratory infections are undoubtedly one of the most common diseases that both primary care physicians and specialists working in hospitals have to deal with. The percentage of these diseases is particularly high in children and, depending on the child's age, may range from 6% to even 25%. A major clinical problem is the recurrent nature of these infections and their complications. This results in receiving an increased number of medications that can cause numerous side effects. Overprescription of antibiotics and consequently, increase of antibiotic resistance are also observed. Looking forward, the prevention of the recurrent infections is the key problem. The aim of our work was to evaluate the efficacy of the most popular preparations available on the pharmaceutical market that can improve immunity and complement conventional methods of treating infections or completely replace them. These include: elderberry, β-Glucans, lactoferrin, colostrum, black cumin preparations, echinacea, propolis, Streptococcus salivarius K12, inosine pranobex, ginseng, OM-85 bacterial lysate. We reviewed the literature from 2012 to 2024 using Pubmed and Google Scholar. The assesment of the effectiveness of preparations for immunity was based primarily on the systematic reviews, meta-analyses and randomised controlled trials. The above-mentioned preparations are largely characterized by a positive impact on improving the immunity of people supplementing them by activating non-specific immunity mechanisms. Thanks to this, some of the respondents can observe the regulation of the body's inflammatory response and, consequently, a decrease in the number of infections and their course. Due to the still insufficient number of studies on these preparations and the discrepancies in the results obtained among authors, further researches are needed to take a clear stance on their effectiveness.

Changes in serum levels of pro- and anti-inflammatory cytokines in women with papillomavirus infection before and after therapy”

Papillomavirus infections (PVI) are among the most common sexually transmitted diseases in the young population. A long, sluggish inflammatory process sufficiently worsens adequate preparation for normal pregnancy. Herpesvirus and Chlamydia infections are the most frequent associations with papillomavirus infection. Many authors believe that PVI may cause dysregulation of pro- and anti-inflammatory cytokines revealed in blood serum. Currently, there are no uniform standards for management and treatment of women with papillomavirus infection without pronounced clinical manifestations, in order to prevent morphofunctional disorders of genitourinary system leading to reproductive disorders. However, most authors believe that antiviral and immunomodulatory drugs are the main tool of therapy against expansion of pathogens in the body. The aim of our study was to compare changes in the levels of IL-17, IL-12 p70, IL-12 p40, IL-13 and TGF-p1 in blood serum of women with papillomavirus infection before and after therapy with Inosine pranobex (IP) and Solanum tuberosum (ST). We conducted a survey of 137 patients with papillomavirus infection treated with drugs containing Inosine pranobex and Solanum tuberosum as active substances. The levels of IL-17, IL-12 p70, IL-12 p40, IL-13, and TGF-p1 in blood serum were determined using specific reagents from RD Diagnostics Inc. (USA). Changes in pro- and anti-inflammatory cytokines before therapy were as follows: decreased levels were found for IL-12 p70, p40; increased values were revealed for IL-13, IL-17, and TGF-p1. After the courses of therapy, we have registered the following changes in PVI-infected patients treated with synthetic drug Inosine pranobex (IP): the levels of IL-12 p70, IL-12 p40 were increased, along with decrease in IL-13 and TGF-p1. Meanwhile, ST therapy was associated with increase in IL-12 p70, IL-12 p40, and a decrease in IL-13 and TGF-p 1. With IP therapy, patients with combined HPV + HV infection showed an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13, while TGF-p1 did not change. Following ST therapy, these patients exhibited higher IL-12 p70, IL-12 p40, decreased IL-13, whereas TGF-p 1 remained unchanged. In the group of women with HPV + Chlamydia infection, an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TGF-p1 was associated with IP therapy. An increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TGF-p 1 were shown after ST therapy. In all groups of patients, IL-17 remained at high levels after therapy without significant differences between the mentioned subgroups. In the groups of patients treated with IP. we have recorded a general normalization of immune disorders.

Inosine pranobex-derived coordination complexes for self-adjuvant, self-carrier, and self-assembled vaccines in cancer immunotherapy

Inosine pranobex (InP), an immunomodulatory drug approved for clinical use worldwide, is a potential adjuvant for cancer vaccines with a low clinical translation barrier. However, the administration of soluble InP agents in free format is associated with drawbacks of a short half-life period and limited efficacy. In this study, a rapid self-assembly approach was proposed for the synthesis of cancer vaccines due to the coordination interaction of ferric ion and acedoben (Ace) in InP. The self-assembled cancer vaccines can be readily adjusted from the microscale to the nanoscale, with shapes including rods, fibers, and spheres. Herein, Fe-Ace coordination complexes not only serve as carriers for tumor antigens, but also enhance antigen-specific antitumor immunity due to their intrinsic adjuvant properties. Nanofibrous self-assembled cancer vaccines based on Fe-Ace coordination complexes more effectively induced an antitumor immune response, exerted a remarkable therapeutic effect, and inhibited the tumor growth at distant site in vivo, compared to free InP and other self-assembled cancer vaccines. The presented work provides a promising strategy for the rapid manufacture of InP-derived self-adjuvant, self-carrier, and self-assembled vaccines for cancer immunotherapy.

The study of anti‐rabies virus effect of Shougong powder

AbstractRabies is a lethal infectious disease caused by rabies virus (RABV). The mortality rate is very high after the appearance of clinical symptoms, with a survival rate of almost 0%. There is presently no cure for rabies. In the present study, we investigated whether the extract of Shougong powder—a calcium powder prepared from gecko that has demonstrated immunomodulatory properties in mice—is an effective treatment for rabies. The antiviral effects of the extract were evaluated both in vitro and in vivo with the cytotoxicity and antiviral assays and by immunofluorescence analysis, quantitative real‐time (qRT)‐PCR, and western blotting. The results showed that Shougong powder and its extract increased survival rate in RABV‐infected mice is up to 60% and 50%, respectively, even in 20 times of LD50, whereas the control groups treated with isoprinosine (IPS) or saline are only 20% and 0% survival (p = .011). qRT‐PCR and western blotting analyses showed that the extract strongly inhibited viral mRNA expression and protein synthesis in vitro: expression of the N, P, M, G, and L genes of RABV was decreased by 28.8%–45.0% in the IPS group (p < .05) and by 50.1%–59.0% in the extract group (p < .05) relative to the control group. These results demonstrate that Shougong powder has certain antiviral effects against RABV and can potentially be used for the treatment for rabies.

Rational approaches to therapy for combined urogenital infections in married couples

The purpose of the study. The aim of the study was to evaluate the effectiveness of antiviral therapy in urogenital infection caused by the herpes simplex virus in combination with human papillomavirus (HSV‑1, -2 and HPV) in couples with impaired reproductive function.Materials and methods. The study included 149 married couples with complaints about the absence or pathological course of pregnancy with termination in the first trimester. Urogenital infection caused by the herpes simplex virus was detected in 80 couples. A combination with human papillomavirus was detected in 36 cases. The effectiveness of antiviral therapy was evaluated.Results. After the first course of treatment with the use of an antiherpetic drug in 80 couples who had manifestations of active herpes infection, pregnancy and the birth of a healthy child were registered in 44 cases (55%). Combination therapy with acyclovir or valacyclovir and inosine pranobex was required, which led to a positive dynamic of indicators in case of a combined infection. The onset and normal course of pregnancy were registered after treatment in 33% of couples in this group.Conclusions. A possible cause of reproductive dysfunction with the absence or termination of pregnancy in the early stages may be a urogenital infection caused by HSV types 1, 2. In most cases, antiviral therapy promotes the birth of a healthy child. The ineffectiveness of therapy may be associated with the simultaneous presence of two or more infectious significant agents. For the treatment of couples who have an active persistence of HSV‑1, -2 in combination with HPV, the appointment of inosine pranobex in combination with acyclovir or valacyclovir is recommended.

Effectiveness of inosine pranobex in the treatment and prevention of infectious diseases (system review)

The purpose of the article is a systematic review of studies conducted in recent decades in children and adults, with an emphasis on domestic works, on the use of inosine pranobex preparations, in the treatment of infectious diseases. The clinical and immunological effectiveness of inosine pranobex in the treatment and prevention of relapses in patients with recurrent respiratory viral infections against the background of persistent herpesviruses types 4-6 has been demonstrated. Using the example of multicenter comparative as well as placebo-controlled studies, not only the effectiveness, but also the safety of long-term courses of therapy is shown. A promising direction is the use of inosine pranobex in the treatment of COVID-19 and post-Covid conditions, taking into account its immunomodulatory effect without the risk of increasing the “cytokine storm”, as well as studies of the direct antiviral effect on the SARS-CoV-2 virus in vitro.

Влияние противовирусной терапии на течение острых респи- раторных вирусных инфекций у детей в современных условиях

Aim: to assess the efficacy of antiviral therapy in the treatment of acute respiratory viral infections in children in the context of contemporary clinical practice Patients and Methods: the study employed a pharmacoepidemiologic approach, utilizing a questionnaire survey of physicians to collect data on 6,116 children aged 3 to 7 years with mild to moderate acute respiratory infections. The study group included 5,144 (84%) children who received inosine pranobex. Comparison group 1 included 654 (11%) children who received other antivirals or immunomodulators. Comparison group 2 included 318 (5%) children who did not receive any etiological therapy. The clinical manifestations of acute respiratory viral infections, their duration, disease duration, complications, therapy, and the rationale for the choice of medications by the physician were analyzed. Results: disease duration in the study group (5.97±1.57 days) was significantly lower than in comparison group 1 (6.82±1.84 days, p<0.001) and comparison group 2 (6.79±1.88 days, p<0.001). Persistent complaints during convalescence were observed in 288 (5.6%) children in the study group, 154 (23.5%) children in comparison group 1, and 61 (19.2%) children in comparison group 2. Complications were reported in 164 (3.2%) children of the study group (n=169), 104 children (n=107, 15.9%; p<0.0001) in the comparison group 1, and 34 (n=34, 10.7%; p<0.0001) children of the comparison group 2. Conclusion: inosine pranobex has been demonstrated to reduce the rate of complications, prolonged cough, runny nose, and sore throat during convalescence, as well as overall disease duration, duration of the febrile period, and catarrhal phenomena in acute respiratory viral infections in children KEYWORDS: acute respiratory viral infections, COVID-19, herpesvirus infections, inosine pranobex, nasopharyngitis, acute tonsillitis, tonsillopharyngitis, real clinical practice, children. FOR CITATION: Ruzhentsova T.A., Garbuzov A.A., Meshkova N.A., Popova R.V., Slyusar O.I. Effect of antiviral therapy on the course of acute respiratory viral infections in children in contemporary conditions. Russian Journal of Woman and Child Health. 2024;7(2):163–170 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-12.

Эффективность применения Гроприносина в комплексной терапии гипертрофии глоточной миндалины и хронических аденоидитов у детей

Objective. Evaluation of the effectiveness of including the drug with immunostimulating and antiviral effects Groprinosin® in the combined treatment of children with hypertrophy of the pharyngeal tonsil (PHT) / chronic adenoiditis (DCA). Patients and methods. A comparative prospective study was conducted involving 355 children with PHT and DCA. 253 children received surgical treatment with the recommended basic therapy, 102 – the same, but with the addition of 2 courses of Groprinosin®. The children were observed for a year after surgery, and the frequency of episodes of acute respiratory infections (ARI) and relapses of HGM was assessed. Statistical analysis of the results was carried out using the Statistica 8 (USA) program. Results. In 81.4% of children with GGT/CA, DNA of lymphotropic herpes viruses with a significant predominance of the Epstein–Barr virus was found in the nasopharyngeal wash. In all groups after treatment, there was a statistically significant decrease in the frequency of ARI episodes: up to 2 (IQR 2–3) times a year with Groprinosin® treatment and up to 5 (IQR 2–4) without it, p = 0.023. In 29 children (8.2%) a relapse of HGM was observed: in one of the group treated with Groprinosin®, in 28 – without it. Conclusion. The high efficacy and safety of the drug Groprinosin® allows us to recommend its inclusion in the treatment protocol for children with clinically significant hypertrophy of the pharyngeal tonsil in combination with active Epstein–Barr viral infection after adenoidectomy. Key words: hypertrophy of the pharyngeal tonsil, chronic adenoiditis, treatment, relapses, inosine pranobex, children

Study of the role of various diagnostic methods in patients with benign and neoplastic cervical diseases

Introduction. Cervical intraepithelial neoplasias that have been recognized as a precursor of squamous cell carcinoma are subject to active detection for the purpose of eradication. Human papillomavirus (HPV) exposure of women is the major risk factor for carcinogenesis, which is a necessary part for the formation of a pre-tumour and malignant phenotype. Cervical intraepithelial neoplasias that precede the development of squamous cell carcinoma should be actively detected and treated early. The identification of patients with HPV is an important part of subsequent therapies. Inosine pranobex is used as one of the components of the treatment of HPV-associated diseases.Aim. To study the role of various diagnostic methods in patients with benign and neoplastic cervical processes.Materials and methods. The study included 311 women who were 21–64 years old. Colposcopy, cytological examination, HPV testing, preliminary biopsy, cervical excise with histological evaluation of tissue sampling were carried out.Results. HPV 16 was more often detected in a malignant tumour and CIN 3; HPV type 31 and 33 were more often detected in CIN 2 and CIN 3; HPV type 18 was detected in almost all patient with CIN, and malignant and benign neoplastic disorders in preliminary biopsy, that was not typical of results of the excision. In excision CIN 1 were confirmed in 17.07%, CIN 2 in 31.88%, CIN 3 in 66.67%. Preliminary results of benign process in 6.67% turned out to be CIN 1, and in 6.67% – CIN 2, that confirms the need for a comprehensive evaluation. Studies of prevalence of various types of HPV showed that the established sequence of recommended tests, which consists of extended colposcopy, cytology and identification of HPV types, if necessary, does not always correspond to the biopsy results and histological findings on cervical excision specimens. According to our sources, the final result can be determined after excision procedure of cervical tissue and histological examination of the tissue obtained.Conclusion. No strong correlations between examination methods and cervical pathology have been revealed. The final diagnosis is made after cervical biopsy. High prevalence of different types of HPV raises the question of need for complex therapy with inclusion the inosine pranobex.

Physicochemical properties of acedoben and its trifluoroacetamido derivative

Acedoben (4-acetamidobenzoic acid, AcPABA) is a component of the antiviral drug inosine pranobex. The introduction of fluorine has been proven to change the physicochemical properties of molecules. For example, the trifluoromethyl group generally improves the lipophilicity of molecules, which is an important physical property for the bioavailability of drugs. A trifluoroacetamido derivative of acedoben (3F-AcPABA) was synthesized and its physicochemical properties were compared to AcPABA. The acidity of AcPABA and 3F-AcPABA is equivalent as demonstrated by the observed pKa values of their carboxylic acid functional groups. However, octanol–water partition coefficients determined at pH 2.0 (Kow) show that 3F-AcPABA is over seven times more lipophilic than AcPABA. In addition, distribution coefficients (logD) measured using an octanol–water partition experiment at pH 7.4 demonstrate that AcPABA has a greater than four-fold increased distribution in the aqueous phase relative to 3F-AcPABA. These results suggest that 3F-AcPABA would have an improved ability to passively cross cellular membranes at physiologically relevant pH environments in comparison to AcPABA based on the increased lipophilicity of 3F-AcPABA relative to AcPABA. These results indicate that 3F-AcPABA would likely have improved bioavailability relative to AcPABA.

Histomorphometric evaluation of melanomacrophage centers (MMCs) and CD3+ T cells of two morphs of brown trout (Salmo trutta) fed diets with immunostimulants

The brown trout (Salmo trutta) is a salmonid residing in riverine and coastal waters throughout the Northern Hemisphere, whose various populations evolved into distinct ecological morphs, differing in their migratory tendencies and preferred habitats. Unfortunately, due to progressing degradation of natural environment, the conservation of these populations is of growing importance and is undoubtedly a challenging task. Therefore, various means to refine the preparatory protocols for restocking using hatchery-reared fish are being pursued, some of which involve the administration of immunity-boosting substances. The current study assessed the effects of two dietary immunostimulants: Bioimmuno (4% inosine pranobex and 96% β-glucan) and Focus Plus (commercial preparation by Biomar, Denmark) on two morphs of the brown trout – the river trout (S. trutta morpha fario) and the sea trout (S. trutta morpha trutta). Tissue samples were obtained from ∼75 to 100g fish after 0, 2 and 4 weeks of experimental feeding. Multi-factorial analysis of conducted histological measurements of melanomacrophage centers (MMCs) revealed no changes of their parameters within spleens, but showed a decrease of the occupied tissue area and MMC counts in the livers, progressing with time regardless of the applied diet. Immunohistochemical analysis of CD3+ T cells showed their increased recruitment into mucosal folds of pyloric caeca in the 2-week sampling of trouts fed with the diet with 2% Bioimmuno addition, but this effect was not present in the 4-week sampling. When studying all groups jointly within each morph, there was a significant difference in terms of maintained CD3+ T cells levels, as sea trouts showed significantly higher tissue areas occupied by these cells than river trouts, both in the pyloric caeca and hepatic parenchyma. The study revealed that feeding with a diet enriched with Bioimmuno for 2 weeks may be a favorable enhancement of rearing protocols of brown trout stocks prior to their release, but more studies need to be conducted to test the possibility of an even shorter feeding period.

Dynamics of matrix metalloproteinases and their tissue inhibitors in patients with herpesvirus and papillomavirus infection

Sexually transmitted infections are of great importance for the proper reproductive function in women. Chronic inflammatory process leads to reproductive disorders. A special role in the chronic inflammatory process is attributed to papillomavirus (PVI) and herpetic infection. MMP-2 and MMP-9 enzymes cleave type 4 collagen which makes the scaffold of basement membranes and contributes to the separation of endothelial cells from the membranes, followed by their further migration and direct participation in angiogenesis thus affecting the growth of tumors, in particular cervical cancer. Tissue inhibitors of matrix metalloproteinases are known to limit the collagen breakdown. However, the imbalance of MMP and TIMP is accompanied by accumulation of extracellular matrix and increased risk for reproductive disorders. The aim of our study was to evaluate the dynamics of acute-phase proteins affecting the state of intercellular matrix (MMP-2, MMP-9 and MMP tissue inhibitors (type 1, 2) in blood serum of patients with PVI or coinfection of PVI and HSV before and after therapy with drugs exhibiting antiviral and immunomodulatory effects, i.e., a synthetic compound (Inosine pranobex) and vegetable substance (Solanum tuberosum). We have examined 141 patients with papillomavirus and herpetic infections treated with Inosine pranobex and Solanum tuderosum. Determination of MMP-2, MMP-9 and TIMP-1, TIMP-2 levels of in blood serum was carried out using specific reagents from RD Diagnostics Inc. (USA). The drug therapy with active substances of Inosine pranobex and Solanum tuberosum was associated with positive dynamics of the level of MMP-2, MMP-9 and tissue inhibitors of types 1 and 2 in all groups under studies. However, Inosine Pranobex exerts more pronounced changes, especially in subgroups with viral coinfections.

Ways to promote the efficiency of herpetic stomatitis treatment

The treatment of herpetic stomatitis should be etiotropic, pathogenetic, symptomatic, and local. The research determined the effectiveness of inosine pranobex (1000 mg 4 times a day) in herpetic stomatitis treatment. Addition of inosine pranobex to the pharmacotherapy of herpetic stomatitis reduced hospital stay and duration of treatment. The drug suppresses the synthesis of the virus due to the structure of inosinic acid in the polyribosomes of the cell affected by the virus, and also helps to eliminate the deficiency or dysfunction of immunity that occurred in the case of herpetic stomatitis, it affects the activity of T-cytotoxic lymphocytes and natural killers, enhances the action of neutrophil granulocytes, chemotaxis and phagocytosis of monocytes and macrophages, increases the synthesis of interleukins IL-1 and IL-2, affects the number of Ig G immunoglobulins. Applying inosine pranobex also significantly decreased pain syndrome manifestations from the start of the treatment. It contributed to body temperature normalization 2 days earlier which shortened the treatment period at the in-patient department. Applying inosine pranobex in the combination therapy of herpetic stomatitis has shown a potent clinical efficacy and can be an alternatіve to acyclic nucleosides in patients with herpetic stomatitis of the oral mucosa.

Evaluation of the influence of Inosine pranobex on the matrix protein system in patients with chronic viral cervicitis

The reproductive potential of both women and men is declining every year. Many factors contribute to the violation of the reproductive function – chemical, physical, mechanical, psychogenic, however, biological factors have the most pronounced effect on reproduction. Chronic viral cervicitis can be not only the cause of infertility and reproductive losses, but also the development of intraepithelial dysplasia, as well as cervical cancer. PVI, as a monoinfection, is quite rare along with HPV. Other UGIs (urogenital infections) act as common routes of transmission and entry gates. The most common association with PVI is herpesvirus infection. An increase in MMP, both systemically and at the local level, may indicate a violation of cell modeling processes, which contributes to the development of autoimmune inflammation with further destruction of the tissues of the reproductive tract. Activation of MMP promotes the release of HSV from the nerve ganglia and reactivation of the infection. Therapy for HPV and HVI (herpes virus infections) are debatable. There is no single standard of treatment, but there are a number of drugs that have antiviral and immunomodulatory effects. Currently, there are no studies on the dynamics of the effect of HPV and HSV infection on the state of MMPs and TIMPs during Inosine pranobex therapy. Objective: to evaluate changes in matrix metalloproteinases 2 and 9 and their tissue inhibitors types 1 and 2 in patients with human papillomavirus and herpes infections after Inosine pranobex therapy. 6 patients with papillomavirus and herpetic infections were examined and treated with drugs containing the active ingredient Inosine pranobex. The levels of MMP-2, MMP-9 and TIMP-1, TIMP-2 in blood serum were determined using specific reagents from R&D Diagnostics Inc. (USA). The dynamics of indicators in the blood serum of patients with PVI showed a decrease in the level of MMP-2, MMP-9, TIMP-1 with a simultaneous increase in TIMP-2 relative to the values before therapy. In patients with PVI and HVI, Inosine pranobex therapy showed a decrease in MMP-2 and MMP-9 levels, no changes in the content of TIMP-1, but an increase in the serum content of TIMP-2. Prior to the use of therapy, an increase in the ratio in the main groups in comparison with the control group was found, however, the largest increase was found in the group with the association of infections. After therapy, positive dynamics was established in the main groups. Thus, the ratio in group I decreased and became equal to the control values. In the II group of patients, the ratio, despite the decrease, remained higher than the control values and higher in comparison with the I group of women.

Герпесвирусные инфекции в формировании эпизодов ОРВИ у детей

Aim: to evaluate the detection rate of the herpesvirus activity in children with acute respiratory viral infection (ARVI) signs for determination of the optimal treatment tactics. Patients and Methods: the study included 1120 children aged 3 to 18 years (mean age 7.48±3.91 years) who were observed on an outpatient basis (n=650) or hospitalized (n=379) due to the lack of improvement on the 3rd day after the first ARVI symptoms onset (n=1029) or due to the detected complication (n=91). The herpesvirus DNA was detected in throat swabs by PCR. Enzyme immunoassay was used to evaluate the levels of IgG, IgM, and IgA antibodies. Results: the presence of IgG antibodies to at least one of the herpes viruses was detected in 1097 (97.9%) of patients: in the children group over 6 years old in 723 (100%) patients. The presence of herpesvirus DNA in smears from the posterior pharyngeal wall and tonsils was detected in 234 (20.9%) children: 178 (15.9%) — isolated, 56 (5.0%) — in various combinations. IgM antibodies to Epstein-Barr virus and cytomegalovirus were detected in all cases in the herpesvirus DNA presence in the blood. The herpes simplex virus DNA has not been detected in any case. However, antibodies were detected in 63 (5.6%) children: IgA in 57 (5.1%) and IgM in 6 (0.5%) children. Conclusions: in children with ARVI symptoms, signs of an active infection caused by one or another type of herpes were detected in 26.5% of cases, and in 5% — their combination. The high prevalence of the herpesvirus activity comparable with the detection rate of seasonal respiratory viral infections, along with the adverse effect of herpesvirus infection on the immune system with the severe somatic pathology probability, necessitates the use of a drug with a wide spectrum of antiviral action for the ARVI signs in children — inosine pranobex. In the presence of complications caused by herpesvirus, inosine pranobex does not cause negative trend of antibody activity indicators, inosine pranobex, Groprinosin® KEYWORDS: HHV-6, human herpesvirus type 6, herpes simplex virus, Epstein-Barr virus, herpes, herpesvirus infection, herpes infection, ARVI, cytomegalovirus, inosine pranobex, Groprinosin. FOR CITATION: Ruzhentsova T.A., Popova R.V., Garbuzov A.A., Shushakova E.K., Khalyastov I.N., Meshkova N.A. Herpesvirus infections in ARVI episodes in children. Russian Journal of Woman and Child Health. 2023;6(4):399–404 (in Russ.). DOI: 10.32364/2618-8430- 2023-6-4-12.

Рецидивирующие респираторные заболевания и активные герпесвирусные инфекции у детей: проблемы и варианты их решения

Background: recurrent respiratory infections (RRI) in children are a relevant medical and social issue. Reactivation of latent herpes simplex virus (HSV) infections is recognized as one of the leading causes of recurrent respiratory infections. Its rate in children is up to 40%. Therapeutic options for recurrent respiratory infections in children are discussed given the activity of HSV infections and immune disorder treatment. Aim: to assess the efficacy of inosine pranobex (Normomed®) for recurrent respiratory infections and active HSV infection in children. Patients and Methods: we examined 96 children aged 1–17 years who requested medical care in an outpatient department with complaints typical of recurrent respiratory infections and laboratory-confirmed active HSV infection. Children received inosine pranobex (50–75 mg/kg/day) in three 10-day courses (10-day breaks). 5±1 weeks after finishing therapy, control clinical and laboratory tests and virology were performed. The nature of ARI episodes during the follow-up period and HSV infection activity over time were evaluated. Results: during treatment, a reduction in the rate and severity of respiratory diseases was reported in 94% of children. Fever severity decreased twice (p=0.035), oropharynx condition improved in 66.7% (p<0.01), and the severity of lymphoproliferative syndrome reduced in 62.5% (tonsil hypertrophy in 52.1%, lymphadenopathy in 50.6%, hepatomegaly in 55.3%, splenomegaly in 66.7%). During treatment with inosine pranobex, a decrease in HSV infection activity was reported in 88.6% of children. The active HSV count also decreased. A significant (p<0.01) reduction in the percentage of patients with active HHV 6A/B (from 78.1% to 12.5%), Epstein– Barr virus (from 45.8% to 7.3%), and HSV type 1 (from 14.6% to 1.0%) was reported. Conclusion: significant improvement in the somatic and virological status of children with recurrent respiratory infections and HSV infection after a course of inosine pranobex, which is characterized by antiviral and immunomodulatory effects, was established. KEYWORDS: monthly respiratory infections, recurrent respiratory infections, Epstein–Barr virus, human herpes virus 6A/B, children, inosine pranobex, Normomed. FOR CITATION: Melekhina E.V., Preobrazhenskaia D.V., Muzyka A.D., Soldatova E.Yu., Gorelov A.V. Recurrent respiratory infections and active herpesvirus infections in children: problems and solutions. Russian Medical Inquiry. 2023;7(11):704–712 (in Russ.). DOI: 10.32364/2587- 6821-2023-7-11-2.

Герпесвирусные инфекции в формировании острой и хронической патологии: обоснование необходимости своевременной терапии

Objective. To determine the frequency and possible clinical significance of herpesvirus DNA detection in various organs. Materials and methods. The study included 168 samples of the cerebral cortex, myocardium, vascular walls, liver, kidneys, and lungs from 28 deceased people. The causes of death were cardiopulmonary insufficiency due to decompensation of atherosclerosis (15 (54%) patients, study group) or intoxication due to septic conditions (13 (46%) patients, comparison group). DNA viruses were detected using the polymerase chain reaction. Results. The most frequently detected virus was human herpes virus type 6 (HHV-6) (82%), less frequently – Epstein-Barr virus (58%), cytomegalovirus and herpes simplex virus type 1 (17% each). In the study group, HHV-6 DNA was more often found in the myocardium (87%), cerebral cortex (47%) and liver (40%). Conclusion. In 87% of cases of death from decompensation of atherosclerotic changes, HHV-6 DNA was found in altered areas of the myocardium. In the brain, liver, kidneys and lungs, HHV-6 was detected less frequently. The association of the presence of HHV-6 DNA with the severity of changes in the heart, brain, liver and kidneys and the presence of other herpesviruses with symptoms of acute respiratory viral infection require the prescription of an antiviral agent with a broad spectrum of action. Inosine pranobex is indicated to prevent the progression of somatic pathology by stopping the activity of herpesvirus infection, which often accompanies or is the main factor in the symptoms of acute respiratory viral infection. Key words: HHV-6, atherosclerosis, human herpes virus type 6, herpes, herpesvirus infection, ARVI, PCR, inosine pranobex

Психологический стресс и папилломавирусная инфекция. Взаимосвязь и пути решения

Stress is a non-specific response of the body to stimuli that disrupt homeostasis. Stress can suppress the immune function and therefore increase the risk of immunodeficiency disorders, including human papillomavirus (HPV) infection. Stress-induced immunosuppression is especially important for infection-related cancer since damage to cellular immunity can stimulate the development of oncogenic viral infection. A connection was established between psychosocial stress and the development of SILs (squamous intraepithelial lesions) in women (formerly known as ‘cervical intraepithelial neoplasia (CIN)’ in the International Classification of Diseases (ICD-10)). This connection ends with immune response, which, in turn, depends on the duration of exposure to stressors: a shorter duration of stress shifts specific immunity to innate immunity, and chronic stress shifts it from a Th1-type response to a Th2-type response. Against the background of cognitive behavioral therapy, the incidence of severe SILs/CIN is significantly lower than in the absence of psychological treatment. However, the use of adaptive ways of coping with stress does not exclude the need for pathogenetic (antiviral) therapy for HPV infection. One of the most demanded medications in the pharmaceutical market of Russia is inosine pranobex. It is included in the register of antiviral medications used for HPV treatment. It enhances antiviral protection against HPV, slows or stops oncogenesis in the cervix, which together contribute to a rapid virus elimination. Key words: stress, immunosuppression, human papillomavirus infection, SILs/CIN, inosine pranobex