Therapeutic efficacy of various formulations of cycloferon in the treatment of infectious mononucleosis in children

One hundred twenty six children at the age of 4 to 7 years with infectious mononucleosis were observed. The subjects under the complex therapy were treated with cycloferon suppositoria (1st group), intramuscular cycloferon (2nd group) or placebo (3rd group). The results demonstrated similar therapeutic efficacy of the parenteral cycloferon and rectal suppositoria (a novel cycloferon formulation).     

Evaluation of safety and pharmacotherapeutic efficacy of cycloferon in treatment of Astrakhan rickettsial fever

Clinicopathogenetic impact of cycloferon, an endogenous interferon inductor, on the process of Astrakhan rikettsial fever, its complications and outcomes was analysed. The treatment scheme with addition of cycloferon to the complex therapy was optimized. The specificity of the disease clinical process and the level of the interferon status in the patients treated with cycloferon alone or with combination of the standard therapy and cycloferon was shown. It was observed that in the patients with moderate severity of the disease the combined use of the standard therapy and cycloferon was in favour of arresting the disease clinical signs (fever, headache, weakness, eruption, hepatomegaly, arthralgia and myalgia, lymphatic gland inflammation, primary affect) and lowered the hospitalization term vs. the standard therapy alone. In the patients with moderate severity of the disease the levels of the serous interferon-alpha before the treatment were found lower, while those of interferon-gamma were higher. The use of cycloferon in the treatment scheme resulted in increase of the interferon-alpha levels and decrease of the higher levels of interferon-gamma. The standard therapy in combination with cycloferon in the patients with moderate severity of the disease provided changes in the immune status: increase of the relative content of T- and B-lymphocytes and normalization of their absolute number. Normalization of the phagocytic activity and the coefficient of the active phagocytes, as well as increase of the phagocytic index, the levels of immunoglobulins G, A and M and the number of the circulating immune cells were stated. The standard therapy with addition of cycloferon resulted in normalization of the levels not only of succinic denydrogenase, lactate dehydrogenase and glucose-6-dehydrogenase but also of alpha-naphthylacetate esterase and alpha-naphthylbutirate esterase in the neutrophils, as well as of the whole spectrum of the monocyte enzymes, except NAD-diaphorase. The adverse reactions were observed in 2.5% of the cases (9 subjects). All of them were mild and did not require discontinuation of the drugs use.     

Cycloferon efficacy in viral and bacterial diseases of children (clinical review)

The authors' findings and literature data on the pharmacotherapeut efficacy of cycloferon, an interferon inductor (immunomodulators) are described. The drug effect in the treatment of various socially significant children' diseases, including acute respiratory tract viral infection, bronchial asthma, allergic conditions with infection protection disturbances, mycoplasmic infection, bronchopulmonary complications of acute respiratory tract viral infection with low intensity of free radical oxidation is indicated. The use of cycloferon at the background of vaccination was shown to provide inhibition of the autoimmune processes causing postvaccinal complications in frequently ill children. The results of the use of cycloferon in the treatment of gastrointestinal tract and intestinal infections of both the viral and bacterial genesis are discussed. Cycferon is recommended to be used for correction of the intestine dysbiosis (the microflora level came to normal in 95% of the children). The use of the drug in surgical pathology and in particular in appendicular peritonitis for decreasing the postoperative complications and correction of the immune disturbances due to chronic viral hepatitis C and B in children under the complex therapy is described. The cycloferon safety and efficacy were confirmed by the postmarketing randomized trials.     

Rational pharmacotherapy and correction of immunity disorders in children with chronic hepatitis (clinical review)

The data on the efficacy of antivirals and their impact on the virologic and immunologic indices in HCV- and HBV-infected children are presented. The best therapeutic effect in the management of children with chronic virus hepatitis was provided by combined antiviral therapy of different action. In the treatment of babies the drugs of choice could be viferon or cycloferon, for the 2-year older children with chronic hepatitis B the combination of viferon + cycloferon should be recommended and for those with chronic hepatitis C the combination of interal + cycloferon could be used. The cycloferon combination with interferons-a makes it possible to generate the Th1 cellular immune response, to minimize the side effects of interferons and chemotherapeutics and to improve their tolerability. The complex therapy of patients with chronic hepatitis B and lambliasis, using cycloferon and macmiror, provided stable effect, less frequent relapses oflambliasis and minimum side effects of the specific therapy. The repeated isolation of lamblia within a 1-year observation period was recorded only in 16.6% of the children treated with cycloferon vs. the control (40.0%).     

Cycloferon efficacy of therapy of chronic hepatitis B (results of randomized multicentre study)

The best therapeutic effect in the treatment of patients with chronic hepatitis B was observed with the use of cycloferon in the scheme of the antiviral therapy. The combination of cycloferon with lamivudine provided complete stable remission in 54.1% of the patients, whereas the use of a-interferon in combination with cycloferon provided remission in 44.1% of the lamivudine-resistant patients. The use of cycloferon in the therapy of chronic hepatitis B made it possible to lower the frequency and manifestation level of the side effects and prevented the lamivudine resistance development and generation of the virus mutants.     

Improvement of herpetic stomatitis therapy in patients with chronic tonsillitis

To determine the clinicopathogenetic efficacy of cycloferon liniment in combined therapy of herpetic stomatitis, 60 patients with herpetic stomatitis and chronic tonsillitis were examined and treated. It was shown that the use of cycloferon liniment in the combined therapy of herpetic stomatitis in the patients with chronic tonsillitis allowed to lower the infection load in the parodontal recesses and the local inflammation, to normalize the immunity indices and to reduce the level of the endogenous intoxication, that provided acceleration of the recuperation processes and decreased the frequency of stomatitis backsets.     

Rational approach to treatment of patients with polytrauma complicated by urinary tract infection

Development of secondary immune dysbalance in patients with polytrauma complicated by urinary tract infection (acute pyelonephritis) was observed. In such cases bacterial complications were highly possible, that required the use of immunotropic drugs (cycloferon) increasing the host nonspecific resistance, responsible for Th1 immune response. The cycloferon therapy of the patients with chronic pyelonephritis normalized the lymphocyte electrophoretic mobility promoting efficient recovery of the immune homeostasis. Cycloferon was shown to be effective in the prophylaxis and therapy of infective inflammation in the patients with polytrauma, that was evident of the antibacterial therapy efficacy increasing and more rapid healing of the infective inflammation.     

Interferon inductors in treatment of associative forms of tick-borne infection in children

Thirty three children with associative forms of thick-borne infection (thick-borne encephalitis with ixodic borreliosis) were clinically observed. The disease was characterized by subfebrile temperature, moderate intoxication, rare erythema (39.5%) and frequent cardiovascular disorders with development of Lyme carditis (32.6 +/- 7.2%) and further rise of hepatomegalia in the diseases dynamics and development of meningeal symptoms. There were observed changes in the cytokine spectrum, characterized by INF-gamma high levels, and hypersecretion of the whole spectrum cytokines in the dynamics, that provided the Th2 type immune response. High clinicoimmunological efficacy of the complex therapy with cycloferon as an immunomodulator providing more balanced production of pro- and anti-inflammatory cytokines (IL-1alpha, INF-gamma and IL-10) was shown.     

Clinicoimmunological monitoring of therapy in patients with associated forms of yersiniosis

Characteristics of the clinical process and immunological profile in children with yersiniosis as a monoinfection or in association with acute intenstinal infections and virus hepatitis A are presented. The efficacy of the immunotropic therapy with cycloferon, an interferon inductor, and recombinant interferon in the patients with the viral and bacterial association of the disease (yersiniosis + hepatitis A) and initial disbalance of the serum cytokines was estimated. Dependence of the interferon clinicolaboratory efficacy on the initial levels of serum y-interferon, IL2 and IIA, promoting shorter terms of hyperthermia, diarrhea syndrome and cytolysis syndrome was shown. It allowed to optimize the scheme of the pathogenetic therapy of Yersinia mixed infection.     

Cytokinin inducing and antiviral activity of cycloferon on experimental herpetic infection

Experimental data on the protective activity and the capacity for inducing the biosynthesis of some cytokins, the low molecular inductors of cycloferon, endogenic interferon of the acridanon group, in herpetic infection are presented. The herpes infection was modelled by intraperitoneal injection of herpes simplex virus, type 1 into BALB/c mice. In the animals with normal immune status cycloferon induced the formation of serum interferon (INF) in high titers (up to 1:20,000) with the peak achieved 4-8 hours after the injection of the preparation. In addition, cycloferon stimulated the synthesis of IL-2 and gamma INF, but decreased the concentration of IL-1b. Following immunosuppression caused by gamma-radiation or cyclophosphamide the titers of serum interferon decreased 4-8 times. In generalized herpes infection in non-inbred white mice with undamaged immune status cycloferon increased survival rate by 30-100% in comparison with the controls (untreated mice), while in case of immunosuppression the protective effect of this preparation was considerably lower. In infected mice the concentrations of gamma INF, IL-2, IL-1b were found to be elevated in comparison with their concentrations in healthy animals. In the course of the infectious process cycloferon suppressed the production of IL-2 and IL-1b, but did not influence the synthesis of gamma INF.     

Combined therapy of patients with recurring anogenital herpes infection

Up-to-date conceptions of etiology and epidemiology of anogenital herpetic infection are described. The main mechanisms of immunological shifts in subjects with anogenital Herpes infection are discussed. The efficacy and safety of cycloferon in the combined treatment of patients with recurring anogenital herptic infection were estimated. The clinical efficacy of the combined therapy (acyclovir in a dose of 200 mg 5 times a day for 5 days + cycloferon liniment applied topically on the eruptions twice a day for 5 days) was 85% or 25% higher vs. the control.     

Increase in NK-activity using superlow doses of the immunomodulator cycloferon

A possibility of rising the antitumor activity of natural killers using various doses of the immunomodulator cycloferon was evaluated. A direct correlation has been revealed between the killer activity and the cycloferon dose. However, on a decrease in cycloferon concentrations by several orders, as compared with commonly accepted doses, this correlation changed for inverse. A possible mechanism of this effect is discussed in addition to practical significance of the obtained results.     

Effects of a core stability exercise program on balance and coordination in children with cerebellar ataxic cerebral palsy

Objective:To evaluate the effects of a core stability exercise program on balance, coordination, and severity of ataxia in children with cerebellar ataxic cerebral palsy (CP).Methods:Forty children with cerebellar ataxic CP (mean age: 6.75±1.35 years) were randomly assigned to a control group and an intervention group for 2 months of follow-up. The control group received a standard physical therapy program three times weekly (1 h per session), while the intervention group received a core stability program for 30 min, in addition to the selected physical therapy program. Both groups were evaluated pre-treatment and post-treatment using the Scale for the Assessment and Rating of Ataxia, the Balance Error Scoring Systems scale, Bruininks-Oseretsky tests of motor proficiency, and HUMAC balance system scores.Results:We found statistically significant reductions in the severity of ataxia, as well as improved balance and coordination in both groups, with stronger effects observed in the intervention group (P<0.05).Conclusion:The core stability program can improve balance and coordination in children with cerebellar ataxic CP when incorporated with a standard physical therapy program.     

微生态制剂在儿童幽门螺杆菌根除治疗中应用效果的Meta分析

目的 系统评价微生态制剂联合标准三联疗法或贯序疗法在儿童幽门螺杆菌（H. pylori）治疗中应用的临床疗效及其对治疗中抗生素相关不良反应发生的改善情况。方法 计算机检索CNKI、VIP、Wan Fang Data、Pub Med、Web of science和The Cochrane Library数据库,搜集国内外公开发表的关于微生态制剂在治疗儿童H. pylori感染中应用的随机对照试验（RCT）,检索时限均为从建库至2017年10月,同时人工检索相关文献的参考文献,以补充获取研究文献。由2位研究员独立筛选文献、提取数据并对纳入研究进行质量评价,采用RevMan 5.3软件进行Meta分析。结果 共纳入17个RCT,共2 033例H. pylori 阳性的儿童患者。Meta分析结果显示,微生态制剂+标准三联或贯序疗法vs标准三联或贯序疗法：微生态制剂+标准三联或贯序疗法在儿童H. pylori根除率方面优于对照组[OR=2.66,95%CI（2.09,3.40）,P<0.00001];总不良反应发生率明显低于对照组[OR=0.28,95%CI（0.21,0.37）,P<0.00001],差异均有统计学意义。微生态制剂+标准三联或贯序疗法组的恶心呕吐（P<0.001）、腹痛（P=0.015）、腹泻（P<0.001）、便秘（P=0.023）、纳差（P<0.001）、味觉障碍或口腔炎（P<0.001）发生率明显低于对照组,差异有统计学意义。结论 与标准三联或贯序疗法相比,微生态制剂+标准三联或贯序疗法安全、有效,能提高儿童H. pylori的根除率,降低H. pylori治疗中抗生素相关不良反应的发生。受纳入研究质量的限制,上述结论尚需开展高质量的RCT 进一步验证。     

Investigation of luromarin efficacy on mice with experimental tick-borne encephalitis

Oral use of Luromarin, extracted from sea algae Zostera asiatica, was efficient in protection of mice from lethal infection induced by highly pathogenic strain of TBE virus, by extending their average lifespan. Luromarin demonstrated potentiating action in combination with ribavirin and cycloferon.     

布拉氏酵母菌散剂联合三联疗法对儿童幽门螺杆菌感染的治疗

目的 观察布拉氏酵母菌散剂联合以质子泵抑制剂（PPI）为基础的标准三联疗法对儿童幽门螺杆菌（H. pylori）感染的疗效,以探索根除率高且不良反应少的H. pylori根除方案。方法 采用前瞻性随机对照研究,从确诊为H. pylori感染的患儿中选取120例作为研究对象,再随机分为布拉氏组和标准三联疗法组,每组各60例。标准三联疗法组口服阿莫西林［50 mg/（kg·d）,饭后分两次服］、克拉霉素［20 mg/（kg·d）,饭后分两次服］和奥美拉唑［0.7~0.8 mg/（kg·d）,饭前半小时一次服完］治疗,布拉氏组在标准三联疗法的基础上加服布拉氏酵母菌散剂（250 mg/次,2次/d）。两组患者均治疗14 d,由患儿家属记录治疗过程中发生不良反应的情况。停药后4周内不再口服任何抗生素,后行14C呼气试验以评估H. pylori根除情况。比较两组患者根除率及不良反应发生率。 结果 治疗后三联疗法组H. pylori根除率为76.7%（46/60）,布拉氏组为90.0%（54/60）,二者差异有统计学意义（P＜0.05）。治疗过程中布拉氏组患者腹泻发生率低于三联疗法组,差异有统计学意义（P＜0.05）。结论 布拉酵母联合三联疗法能提高H. pylori的根除率,降低治疗过程中的不良反应。     

Lifestyle intervention in obese children with variations in the melanocortin 4 receptor gene

Because information on weight changes after lifestyle intervention in children with mutations in the melanocortin 4 receptor (MC4R) gene is scarce, we compared weight changes after lifestyle intervention between children with and without MC4R variations. A group of 514 overweight children (aged 5-16 years), who presented to participate in a 1-year lifestyle intervention based on exercise, behavior, and nutrition therapy were screened for MC4R mutations. For comparison, children with MC4R mutations leading to reduced receptor function (group A) were each of them randomly matched with five children of same age and gender without MC4R mutations (group B). Changes of weight status were analyzed as change of BMI standard deviation scores (BMI-SDSs). Furthermore, 16 children (3.1%) harbored MC4R mutations leading to reduced receptor function, and 17 (3.3%) children carried variations not leading to reduced receptor function. Children with and without MC4R mutations reduced their overweight at the end of intervention to a similar degree (P = 0.318 between groups based on an intention-to-treat analysis). The maintenance of weight loss after intervention among children with MC4R mutations leading to reduced receptor function failed in contrast to children without such mutations (P < 0.001 adjusted for BMI-SDS at baseline, age, and gender in an intention-to-treat analysis). In conclusion, children with MC4R mutations leading to reduced receptor function were able to lose weight in a lifestyle intervention but had much greater difficulties to maintain this weight loss supporting the impact of these mutations on weight status.     

Circadian characteristics of plasma cortisol in children with standard and short stature

Cortisol (CT) concentrations (in micrograms/dl) were determined by radioimmunoassay in plasma obtained at about 3-hr intervals during a 24-hr sampling span from 42 boys and 13 girls of short stature (2-4 standard deviations below their peer group mean), and from a reference group of 11 boys and 10 girls with standard stature, before any treatment were administered to the former. Subjects were 11.20 +/- 0.37 years of age at the time of study, and were living on a diurnal waking (approximately 07:30 to approximately 22:30), nocturnal resting routine during sampling, consuming the usual hospital diet. Circadian rhythm parameters were computed separately for each group by the single and population-mean cosinor fits of a 24-hr cosine curve. A comparison of circadian parameters indicates a statistically significant difference in acrophase (phi; P = 0.033) between short and standard children, as well as added differences in rhythm-adjusted mean (M; P = 0.011) and phi (P = 0.035) between boys and girls of short stature. These differences, as well as any other added information from relevant marker rhythms, should be taken into account for the time-specification of therapy before treatment starts in children of short stature.     

The effect of growth hormone therapy on craniofacial growth and dental maturity in children with Down syndrome.

Craniofacial growth was evaluated 3 years after termination of growth hormone (GH) therapy in ten Down syndrome (DS) children. The control group consisted of 16 age-matched children with DS. The treatment started at 6-9 months of age, and the duration was 36 months. There were no statistically significant differences in craniofacial development between DS children treated with GH or DS children not treated. In conclusion, the results of this study indicate that GH therapy for 36 months in children with DS did not change the craniofacial morphology compared to a group of DS children not given GH.     

Treatment of acute otitis media: a controlled study of 142 children

Results of the use of ampicillin, penicillin G and symptomatic therapy in the treatment of acute otitis media in 142 children were compared. Antibiotic therapy conveyed significant benefit. No major differences were observed between penicillin and ampicillin, except in the age group under 3 years where ampicillin was associated with the best results. Ampicillin appears to be the drug of choice. Its superiority over symptomatic therapy was statistically significant. Long-term sequelae were not observed in any of the three treatment groups. The relative merits of erythromycin and ampicillin require further study.