Drug repositioning of anti-microbial agent nifuratel to treat mast cell-mediated allergic responses.

Objectives: Our objective was to assess the effects and mechanisms of nifuratel on IgE-mediated mast cell (MC) degranulation and anaphylaxis in both in vitro and in vivo settings.Methods: The anti-allergic activity of nifuratel was evaluated in mast cell cultures and the passive cutaneous anaphylaxis (PCA) model. The effects of nifuratel on signaling pathways stimulated by antigen in mast cells were measured by immunoblotting, immunoprecipitation, in vitro protein tyrosine kinase assay, and other molecular biological methods.Results: Nifuratel reversibly inhibited antigen-induced degranulation of MCs (IC50, approximately 0.34 µM for RBL-2H3 cells; approximately 0.94 µM for BMMCs) and suppressed the secretion of inflammatory cytokines IL-4 (IC50, approximately 0.74 µM) and TNF-α (IC50, approximately 0.48 µM). Mechanism studies showed that nifuratel inhibited the phosphorylation of Syk by antigen via the inhibition of recruitment of cytosolic Syk to the É£ subunit of FcεRI, and decreased the activation of Syk downstream signaling proteins LAT, Akt, and MAPKs. Finally, nifuratel dose-dependently suppressed the IgE-mediated passive cutaneous anaphylaxis in mice (ED50, approximately 22 mg/kg).Conclusion: Our findings suggest that nifuratel inhibits pathways essential for the activation of mast cells to suppress anaphylaxis, thereby indicating that the anti-microbial drug, nifuratel, could be a potential drug candidate for IgE-mediated allergic disorders.

Chemotherapeutic options for the treatment of human trichomoniasis.

Trichomonas vaginalis is the causative agent of the most common non-viral sexually transmitted disease worldwide. The infection may be associated with severe complications, including infertility, preterm labour, cancer and an increased risk of human immunodeficiency virus (HIV) transmission. Treatment remains almost exclusively based on 5-nitroimidazoles, but resistance is on the rise. This article provides an overview of clinically evaluated systemic and topical treatment options for human trichomoniasis and summarises the current state of knowledge on various herbal, semisynthetic and synthetic compounds evaluated for their anti-Trichomonas efficacy in vitro.

[THE EFFECTIVENESS OF A 10-DAY DRUG THERAPY IN CHILDREN WITH CHRONIC GASTRODUODENAL PATHOLOGY ASSOCIATED WITH CAGA-POSITIVE STRAINS OF HELICOBACTER PYLORI].

The results of triple Helicobacter-therapy (omeprazole, amoxicillin, nifuratel) in the treatment of chronic gastroduodenal pathology in children depending on the duration of it's use. The effectiveness of drug therapy was evaluated in terms of eradication of Helicobacter pylori and dynamics of pain, dyspeptic syndrome and astenovegetative syndrome.

[Multipurpose treatment of vaginal infections].

Untreated bacterial vaginosis is related with many complications for non-pregnant women in reproductive age, most common from them are vaginal discharge and postoperative infections. The aim of our investigation was to compare the effectiveness of two therapeutic regimes which consist in Macmiror/Macmiror Complex alone and in combination with Feminella Vagi C for treatment of bacterial vaginosis (BV) and/or mycotic infection. 117 non-pregnant women with symptoms of vaginal infection were prospectively enrolled into two groups according their treatment. First group consist 66 women treated with Macmiror tablets and vaginal capsules followed with local application of Feminella Vagi C, the second group consist 54 women treated with Macmiror tablets and vaginal capsules only. The impact of treatment on clinical symptoms was observed at the end of medication and 20 days after it. Microbiological testing was repeated 20 days after treatment. Over than 80% (78.6 divided by 86.7%) of the cases with vaginal infection (BV and mycotic one) were successfully treated with Macmiror/Macmiror Complex. Supplement treatment with Feminella Vagi C lead to higher percentage of clinically recovery (86.7% vs 84.6%), better microbiological cleaning (86.7% vs 82.1%) and longer effect of treatment. Used medication showed higher efficacy against BV than to fungal infection. According obtained results we may conclude that bacterial vaginosis was better treated with multipurpose treatment (Nifuratel, Nistatin and vit. C) than with Macmiror alone.

Bacterial vaginosis, Atopobium vaginae and nifuratel.

As bacterial vaginosis (BV) is a potential cause of obstetric complications and gynecological disorders, there is substantial interest in establishing the most effective treatment. Standard treatment - metronidazole or clindamycin, by either vaginal or oral route � is followed by relapses in about 30% of cases, within a month from treatment completion. This inability to prevent recurrences reflects our lack of knowledge on the origins of BV. Atopobium vaginae has been recently reported to be associated with BV in around 80% of the cases and might be involved in the therapeutic failures. This review looks at the potential benefits of nifuratel against A. vaginae compared to the standard treatments with metronidazole and clindamycin. In vitro, nifuratel is able to inhibit the growth of A. vaginae, with a MIC range of 0.125-1 µg/mL; it is active against G. vaginalis and does not affect lactobacilli. Metronidazole is active against A. vaginae only at very high concentrations (8-256 µg/mL); it is partially active against G. vaginalis and also has no effect on lactobacilli. Clindamycin acts against A. vaginae with an MIC lower than 0.125 µg/mL and is active on G. vaginalis but it also affects lactobacilli, altering the vaginal environment. These observations suggest that nifuratel is probably the most valid therapeutic agent for BV treatment.

[Statement of the Polish Gynecological Society Expert Group on the use of Macmiror Complex 500]. / Stanowisko Zespolu Ekspertów Polskiego Towarzystwa Ginekologicznego dotyczace preparatu Macmiror Complex 500.

The group of experts representing the Polish Gynecologic Society has issued this statement based on the review of available literature on the potential benefits of the use of Macmiror Complex 500 in obstetrical and gynecologic practice. Mixed Vaginitis (MV) eg. the vaginal infection caused by at least two out of the triad of pathogens (fungi, bacteria and Trichomonas Vaginalis [TV]), constitutes the type of vaginitis which is underestimated as for its prevalence. Mixed pathogens are responsible for as much as one third of all vaginal infections. Macmiror Complex 500 contains two active ingredients: nifuratel and nystatin. Macmiror Complex 500 affects all common causes of vulvovaginitis, i.e. bacteria, yeasts and TV. At the same time, it is not effective against Lactobacillus spp., which is a clear advantage in the treatment of vaginal infections. The antibacterial spectrum of nifuratel includes aerobic and anaerobic bacteria. Moreover nifuratel is effective against Chlamydia trachomatis and Mycoplasma spp., it has an anti-trichomonal effect comparable to metranidazole and shows certain activity against Candida spp. Nystatin is effective against Candida albicans and is even very effective against Candida glabrata which is usually more resistant to imidazole antifungal agents. Nystatin's importance is rising due to the current increase of candidoses caused by non-albicans types. This increase is especially perceptible in recurring candidoses. The review of the available literature on the effectiveness of Macmiror Complex 500 in the OB/GYN practice leads to the following conclusions: the exeptionally broad antibacterial and antifungal and trichomonicidal activity of this formulation makes it a drug of choice in cases where MV is suspected. The possibility to treat both partners, favorable safety profile in pregnant patients and the availability of both vaginal ovules and the cream with applicator makes this drug an effective and suitable treatment option in obstetrical and gynecologic practice.

In vitro activity of nifuratel on vaginal bacteria: could it be a good candidate for the treatment of bacterial vaginosis?

Bacterial vaginosis is characterized by a shift of the physiological flora to a diverse spectrum of bacteria, where Gardnerella vaginalis and Atopobium vaginae are the most important markers. In this study, the antimicrobial activity of nifuratel against G. vaginalis, A. vaginae, and lactobacilli was compared with that of the two currently used antibiotics metronidazole and clindamycin. Results suggest that nifuratel has a better spectrum of activity, being highly active against G. vaginalis and A. vaginae without affecting lactobacilli.

[Rifaksimin in complex treatment of Helicobacter pylori infection in children (a pilot study)].

AIM: To provide a pilot study of empiric rifaximin, bismuth subcitrate, furazolidone/nifuratel triple therapy for H. pylori gastritis in childhood. MATERIALS AND METHODS: Forty one pediatric outpatients (27 females, mean age 14.5+/-1.4 ys) with H. pylori-associated chronic gastritis who underwent endoscopy for dyspeptic symptoms received the combination of bismuth subcitrate (8 mg/kg/day, q. d. s.) for 14 days, rifaximin (800 mg/day) for 10 days and furazolidone (10 mg/kg/day, q. d. s.) or nifuratel (15 mg/kg/two times daily) for 10 days. H. pylori status was determined before the treatment by modified Giemsa staining/urease test and after the treatment (in 4-6 weeks) by ammonia breath test. RESULTS: H. pylori was eradicated in 35 children (85.4%; 95%CI: 75.4-96.4 ITT and PP tests). There were no serious adverse reactions and were no withdrawals due to any side effects. CONCLUSION: The combination of rifaximin, bismuth subcitrate and furazolidone/nifuratel was an effective and tolerable regimen for initial H. pylori eradication.

Nifuratel-containing initial anti-Helicobacter pylori triple therapy in children.

BACKGROUND: Proton pump inhibitor-containing triple therapy with amoxicillin and metronidazole is recommended as initial treatment of Helicobacter pylori in childhood. However, eradication rate with this "classic" regimen is relatively low in Russia. AIM: To evaluate empiric nifuratel, amoxicillin, and bismuth triple therapy for H. pylori gastritis in childhood. MATERIALS AND METHODS: Pediatric outpatients with H. pylori-associated chronic gastritis who underwent endoscopy for dyspeptic symptoms received the combination of bismuth subcitrate (8 mg/kg/day, q.d.s.), nifuratel (30 mg/kg/day, q.d.s.), and amoxicillin (50 mg/kg/day, q.d.s.) for 10 days. H. pylori status was determined before and after the treatment (in 4-6 weeks) by modified Giemsa staining. RESULTS: Seventy-three children (48 boys, 25 girls, age range 9-14) were entered. H. pylori was eradicated in 63 patients (86%; 95% confidence interval: 76.6-93.2; intention-to-treat and per protocol). There were no serious adverse reactions and were no withdrawals due to any side-effects. All of side-effects were self-limiting (dark stools, urine discoloration, blackening of the tongue, and others). CONCLUSIONS: The combination of nifuratel, bismuth subcitrate, and amoxicillin was an effective and tolerable regimen for H. pylori eradication.

Helicobacter pylori eradication in childhood after failure of initial treatment: advantage of quadruple therapy with nifuratel to furazolidone.

BACKGROUND: Failures of Helicobacter pylori eradication in children are common. AIM: To evaluate the efficacy of amoxicillin, bismuth subcitrate and omeprazole and nifuratel or furazolidone for H. pylori eradication in children who failed initial treatment with a standard triple therapy. METHODS: Seventy-six consecutive H. pylori-positive paediatric out-patients (aged 12-16 years; mean age 13.7 +/- 1.4) with chronic abdominal complaints who had failed one attempt of eradication of H. pylori using metronidazole-containing triple therapy were enrolled. It was an open prospective study. Patients were randomized to receive a 2-week course of bismuth subcitrate (8 mg/kg/day, q.d.s.), amoxicillin (50 mg/kg/day, q.d.s.), with either nifuratel (15 mg/kg/day, q.d.s.) or furazolidone (10 mg/kg/day, q.d.s.), plus omeprazole (0.5 mg/kg, once daily). RESULTS: There were 37 patients in the nifuratel group and 39 in the furazolidone group. Helicobacter pylori was eradicated in 33 of 37 (89%; 95% CI: 74.5-96.9; intention-to-treat) in nifuratel group and in 34 of 39 (87%; 95% CI: 72.5-95.7) in furazolidone group, respectively. Frequency of severe side-effects was greater with furazolidone (21%) than with nifuratel (3%; P = 0.0289). CONCLUSIONS: Nitrofuran-containing therapies consisting of a proton-pump inhibitor, amoxicillin and bismuth citrate plus either nifuratel or furazolidone produced good cure rates even among those who had failed prior therapy. Nifuratel is preferred because of the lower frequency of side-effects.

[The Melkersson-Rosenthal syndrome as a problem of complex treatment]. / Zespól Melkerssona-Rosenthala jako problem interdyscyplinarny.

The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema of lips, recurrent facial nerve paralysis and lingua plicata. Treatment is usually symptomatic and required cooperation of different specialists as: dermatologists, neurologists, dentists, laryngologists, surgeons. A rare case of Melkersson-Rosenthal syndrome in 49-year-old man was observed in the Clinic of Dermatology Silesian Medical Academy in Katowice.

Clinical study on the dose-effect relationship of a nifuratel-nystatin combination in the treatment of vulvo-vaginal infections.

OBJECTIVE: The dose-effect relationship of nifuratel (CAS 4936-47-4) + nystatin (CAS 1400-61-9, CAS 34786-70-4) (Macmiror Complex) in topical treatment of vulvo-vaginitis was studied. METHOD: Sixty patients with Trichomoniasis and/or Candidiasis were randomized to: 1) nifuratel 125 mg/nystatin 50000 IU, 2) nifuratel 250 mg/nystatin 100000 IU, 3) nifuratel 500 mg/nystatin 200000 IU. Undistinguishable ovules were intravaginally applied qd for 10 days. The dose-effect relationship was assessed by ANCOVA. RESULT: After 5 days the microbiological cure rate occurred in 10% of patients in the least dose, in 40% in the middle dose and in 85% in the highest dose group (P = 0.000). After 10 days of treatment, the microbiological cure rate increased to 45%, 84%, and 95%, respectively (P = 0.007). Clinical signs and symptoms gradually disappeared in a dose- and time-dependent manner. No relapse has been observed after 10 day-follow up on 46 patients. CONCLUSION: The results confirmed a linear relationship between nifuratel + nystatin dose and effect. The least effective dose was nifuratel 250 mg + nystatin 100,000 IU once daily for 5 days and the best dose in terms of risk/benefit ratio was nifuratel 500 mg + nystatin 200,000 IU once daily for 5 days.

Clinical effects of nifuratel in vulvovaginal infections. A meta-analysis of metronidazole-controlled trials.

Nifuratel (CAS 4936-47-4) displays a strong antiprotozoarian and antibacterial activity and is provided with certain fungicidal effect, but it is not active against the physiologic flora. Its therapeutic effectiveness has been evaluated in more than 12,000 patients. The wide clinical experience with nifuratel confirms that the drug is safe and effective for the treatment of trichomoniasis, bacterial vaginosis, candidosis, and, particularly, in patients suffering from mixed vaginal infection. A meta-analysis of clinical trials comparing nifuratel and metronidazole (CAS 443-48-1) in vulvovaginal infections was performed. All parallel-group metronidazole-controlled trials carried out in patients with vulvovaginal infections have been included, complying with the following criteria: 1) cure assessed both as disappearance of symptoms and signs, and negative microbiological findings; 2) microbiological tests performed with valid methods still used in current practice. Seven clinical trials have been selected, including overall 1767 patients, 832 out of whom were treated with nifuratel and 935 with metronidazole. The results of the meta-analysis confirmed the equivalence between nifuratel and metronidazole: overall proportion of cured patients in the two groups were 88.5% and 90.0%, respectively, in the presence of homogeneity among studies (p = 0.342). In the fixed and random effect analyses, the confidence interval of Odds ratio included 1 and the p values for testing the hypothesis of no difference between treatments were 0.656-1.266, p = 0.582 (fixed effects) and 0.643-1.290, p = 0.599 (random effects), respectively, indicating equivalence. Furthermore, some controlled studies and the wide clinical experience showed that the cure rate of nifuratel in patients with mixed infections due to Trichomonas vaginalis + Candida or Trichomonas vaginalis + bacteria or with bacterial vaginosis and mixed bacterial flora is higher than that of metronidazole, due to the wide spectrum of action of nifuratel.

Microbiological and pharmaco-toxicological profile of nifuratel and its favourable risk/benefit ratio for the treatment of vulvo-vaginal infections. A review.

Nifuratel (CAS 4936-47-4) is a furane-derivative provided with a strong trichomonicidal activity equivalent to that of metronidazole (CAS 443-48-1); it has a broad antibacterial spectrum of action, including both Gram-negative and Gram-positive organisms. It is active against Chlamydia trachomatis and Mycoplasma spp. and has also some degree of activity against Candida spp. and mycetes. Its broad spectrum of action, confirmed by in vitro and in vivo studies, covers virtually all the micro-organisms responsible for the infections of the genito-urinary tract. Nifuratel has a very safe toxicological profile. It is practically non-toxic in acute tests in mice and rats and is also well tolerated after repeated oral and intravaginal administrations. Nifuratel is devoid of teratogenic effects. The comparison among past and recent clinical studies confirms that, in contrast to metronidazole, no resistance phenomena to the treatment with nifuratel are reported. The drug can be used during pregnancy due to the absence of teratogenic effects. In conclusion, nifuratel shows a very favourable risk/benefit ratio for the treatment of patients with vulvo-vaginal infections.

[A multicenter study of the antimicrobial effect of Macmiror and Macmiror Complex in the treatment of vaginal infections]. / Multitsentrichno prouchvane antimikrobniia efekt na Macmiror & Macmiror Complex v lechenieto na vaginalnite infektsii.

UNLABELLED: The aim of the present multicentre study was to examine the therapeutic possibilities of the wide-spectrum medicament MACMIROR & MACMIROR COMPLEX for the treatment of the vaginal infections. MATERIALS AND METHODS: The study included 159 nonpregnant women among 15 and 54 years (middle age 35.6) with different by kind and intensity colpitis complaints. The following microbiological characteristic was established: in 26 cases Gardnerella vaginalis, in 46 Candida spp., and in the rest 87-mixed aerobic bacterial flora, with a combination of Gardnerella, yeast and Trichomonas. The treatment of the patients was done in combined scheme: peroral and vaginal administration, simultaneously with local treatment of the partner. The control examination was performed bistagely: on 7-10 day and on 30-40 day. RESULTS: The good clinical and microbiological influence of the treated patients was established, for the first control examination the effect was found in 88.1% and 86.8% and for the second--respectively in 81.1% and 82.4%. CONCLUSIONS: The received results give us a cause to approve, that the combination "Nifuratel and Nystatin" (Macmiror & Macmimor complex) has the good possibilities to influence the mixed forms of vaginal infection.

[The treatment of vaginal infections with Macmiror and Macmiror Complex]. / Lechenie na vaginalni infektsii c Macmiror & Macmiror Complex.

UNLABELLED: The aim of the present study was to examine the therapeutic possibilities of the wide-spectrum medicament Macmiror & Macmiror Complex for the treatment of the vaginal infections. MATERIALS AND METHODS: The study included 52 nonpregnant women among 20 u 54 years (middle age 30.5) with different by kind and intensity colpitis complains. The following microbiological characteristic was established: in 26 cases Candida spp., in 19 Gardnerella vaginalis, in 1 Trichomonas vaginalis and in the rest 6 mixed infection. The treatment of the patients was done in combined scheme: peroral and vaginal administration simultaneously with local treatment of the partner. The control examination was performed bistagely: on 7-10 day and on 30-40 day. RESULTS: The good clinical and microbiological influence of the treated patients was established for the first control examination the effect was found in 89.5% u 84.2% go of the cases with bacterial vaginosis and in 84.6% u 69.2% in those with mycotic colpitis. Relatively high values were found also at the second control, respectively 83.3% and 72.2% for the amine colpitis and 69.5% and 52.2% for vaginal candidosis. The similar favorable influence received also in the rest of the patients. CONCLUSIONS: Our results do show good possibilities of the nifuratel and nystatin combination (Macmiror & Macmiror complex) to influence vaginitis with different etiology, which give us founding to consider, that the drug is suitable for the mixed forms of vaginal infection.