Dequalinium Research Articles

Dequalinium chloride is an antagonists of α7 nicotinic acetylcholine receptors

Dequalinium chloride has been used primarily as antiseptic compounds, but recently has been investigated for its effects on specific targets, including muscarinic acetylcholine receptors. Here we investigated dequalinium chloride as an antagonist to α7 nicotinic acetylcholine receptors. The pharmacological properties of dequalinium were established using cell lines stably co-transfected with the calcium-permeable human α7 nicotinic acetylcholine receptors and its chaperone NACHO, calcium dye fluorescent measurements or a calcium-sensitive protein reporter, and patch clamp recording of ionic currents. Using calcium dye fluorescence plate reader measurements, we find dequalinium chloride is an antagonist of α7 nicotinic acetylcholine receptors with an IC50 of 672 nM in response to activation with 500 μM acetylcholine chloride and positive allosteric modulator PNU-120596. However, using a membrane-tethered GCAMP7s calcium reporter allowed detection of α7-mediated calcium flux in the absence of PNU-120596. Using this approach revealed an IC50 of 157 nM for dequalinium on 300 μM acetylcholine-evoked currents. Using patch clamp recordings with 300 μM acetylcholine chloride and 10 μM PNU-120596, we find lower concentrations are sufficient to block ionic currents, with IC50 of 120 nM for dequalinium chloride and 54 nM for the related UCL 1684 compound. In summary, we find that dequalinium chloride and UCL1684, which are generally used to block SK-type potassium channels, are also highly effective antagonists of α7 nicotinic acetylcholine receptors. This finding, in combination with previous studies of muscarinic acetylcholine receptors, clearly establishes dequalinium compounds within the class of general anti-cholinergic antagonists.

Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice

Organophosphates are used in agriculture as insecticides but are potentially toxic to humans when exposed at high concentrations. The mechanism of toxicity is through antagonism of acetylcholinesterase, which secondarily causes excess activation of cholinergic receptors leading to seizures, tremors, respiratory depression, and other physiological consequences. Here we investigated two of the major pathophysiological effects, seizures and respiratory depression, using subcutaneous injection into mice of the organophosphate diisopropylfluorophosphate (DFP) at sublethal concentrations (2.1 mg/Kg) alone and co-injected with current therapeutics atropine (50 mg/Kg) or acetylcholinesterase reactivator HI6 (3 mg/Kg). We also tested a non-specific cholinergic antagonist dequalinium chloride (2 mg/Kg) as a novel treatment for organophosphate toxicity. Electroencephalogram (EEG) recordings revealed that DFP causes focal delta frequency (average 1.4 Hz) tonic spikes in the parietal region that occur transiently (lasting an average of 171 ± 33 min) and a more sustained generalized theta frequency depression in both parietal and frontal electrode that did not recover the following 24 h. DFP also caused behavioral tremors that partially recovered the following 24 h. Using whole body plethysmography, DFP revealed acute respiratory depression, including reduced breathing rates and tidal volumes, that partially recover the following day. Among therapeutic treatments, dequalinium chloride had the most potent effect on all physiological parameters by reducing acute EEG abnormalities and promoting a full recovery after 24 h from tremors and respiratory depression. Atropine and HI6 had distinct effects on EEGs. Co-treatment with atropine converted the acute 1.4 Hz tonic spikes to 3 Hz tonic spikes in the parietal electrode and promoted a partial recovery after 24 h from theta frequency and respiratory depression. HI6 fully removed the parietal delta spike increase and promoted a full recovery in theta frequency and respiratory depression. In summary, while all anticholinergic treatments promoted survival and moderated symptoms of DFP toxicity, the non-selective anti-cholinergic dequalinium chloride had the most potent therapeutic effects in reducing EEG abnormalities, moderating tremors and reducing respiratory depression.

The antipsychotic aripiprazole induces peripheral antinociceptive effects through PI3Kγ/NO/cGMP/KATP pathway activation.

Aripiprazole is an antipsychotic drug used to treat schizophrenia and bipolar disorder. Recently, its peripheral analgesic component was evaluated, however, the mechanism involved in this effect is not fully established. Therefore, the aim of the study was to obtain pharmacological evidence for the involvement of the nitric oxide system in the peripheral antinociceptive effect induced by aripiprazole. The hyperalgesia was induced via intraplantar injection of prostaglandin E2 in mice and the nociceptive thresholds were evaluated using the paw pressure test. All drugs were injected locally into the right hind paw. The PI3K inhibitor (AS605240), but not rapamycin (mTOR kinase inhibitor), reversed the peripheral antinociceptive effect induced by Aripiprazole. Antinociception was antagonized by the non-selective inhibitor of the nitric oxide synthase (L-NOarg). The same response was observed using the selective iNOS, but not with the selective nNOS inhibitors. The selective guanylyl cyclase enzyme inhibitor (ODQ) and the non-selective potassium channel blocker tetraethylammonium were able to reverse the antinociceptive effect of aripiprazole. The same was seen using glibenclamide, an ATP-dependent K+ channel blocker. However, calcium-activated potassium channel blockers of small and high conductance, dequalinium chloride and paxilline, respectively, did not reverse this effect. The injection of cGMP-specific phosphodiesterase type 5 inhibitor zaprinast, potentiated the antinociceptive effect induced by a low dose of aripiprazole. The results provide evidence that aripiprazole induces peripheral antinociceptive effects via PI3K/NO/cGMP/KATP pathway activation.

Эмпирическая терапия – первая линия в лечении вульвовагинальных инфекций

Women with signs of urogenital system infections require diagnostic testing for timely and adequate verification of the pathogen and prescription of therapy considering pathogen eradication. However, the identification of specific pathogens in practice takes some time. Therefore, empirical therapy based on a subjective evaluation of the symptoms of vulvovaginal infections and assessment of drug susceptibility of pathogens is common in practical gynecology. At the same time, it is acceptable to use broad-spectrum agents that act on bacteria, fungi, and protozoa and do not contribute to the development of antibiotic resistance. These are topical antimicrobial agents – antiseptics. Objective. To study the efficacy of dequalinium chloride as first-line treatment of patients with signs of vulvovaginal noninflammatory and inflammatory diseases initiated by opportunistic pathogens and aerobic bacteria. Patients and methods. The study included 74 women aged 18 to 45 years (31.4 ± 0.5 years) who were diagnosed with other inflammation of vagina and vulva (N76) or other non-inflammatory disorders of vagina (N89) based on their complaints and examination during an initial visit to a gynecologist. Prior to treatment, laboratory testing of the vaginal microflora by real-time polymerase chain reaction using the test Femoflor was performed, and empirical therapy with dequalinium chloride was applied. Subsequently, the results of laboratory tests before and after treatment were analyzed, as well as the dynamics of clinical manifestations of vulvovaginal infections against the background of therapy with topical antiseptic. Results. The prescription of dequalinium chloride as empirical therapy is effective for both elimination of the clinical manifestations of vulvovaginal infections and for normalization of the qualitative and quantitative composition of the vaginal microbiota at the outpatient appointment. Conclusion. Dequalinium chloride (Fluomisin®) may be recommended to women for correcting disorders of the vaginal microbiocenosis at their initial visit before the results of laboratory tests are obtained. Key words: vulvovaginal infection, normal microbiota, empirical therapy, dequalinium chloride

Stemness Signature Predicts Outcomes and Identifies Candidates for Targeted Therapy in Diffuse Large B-Cell Lymphoma

Background: Mounting studies have shown that tumor cells have stem cell-like phenotypes called stemness. The stemness on prognosis and the immunological properties of diffuse large B-cell lymphoma (DLBCL) has not been systematically explored. This study aimed to explore the relationship between stemness, prognosis and immune microenvironment and further to identified potential therapeutic target related to stemness.Methods: The gene expression and clinical information of 1398 diffuse large B-cell lymphoma sample were obtained to calculated stemness based on the single-sample gene set enrichment analysis (ssGSEA). Survival analysis was performed for stemness phenotypes and the association of stemness with clinical features was assessed further. Weighted gene co-expression network analysis (WGCNA) to screen the relevant key genes systematically for stemness of DLBCL. Cell cycle assay and apoptosis assay were used to evaluate the role of cell division cycle 7 (CDC7) inhibitors in DLBCL cell lines.Results: Stemness was significantly associated with overall survival (OS) and progress free survival (PFS) of DLBCL patients. Notably, prolonged OS and PFS was observed in low stemness groups compared to high group, and the international prognostic index (IPI) with a high risk had higher stemness. Furthermore, DLBCL stemness were associated with tumor purity, immune score and stroma score. From stemness module, 16 genes in the co-expression were chosen as key genes and further identified CDC7 as candidate target gene for antitumor. CDC7 inhibitors involving in dequalinium chloride which was approved by Food and Drug Administration (FDA) for anti-microbial and simurosertib which in a phase I clinical trial for multiple solid tumors show antitumor in DLBCL cell line of SU-DHL-2 and SU-DHL-10.Conclusion: In a word, the study integrated DLBCL stemness, clinical characteristics and immunophenotyping, providing an idea of targeting for cold tumors of DLBCL, and also verified the efficacy of inhibitors of key gene of stemness CDC7 in DLBCL. It is significant to develop novel therapeutic targets for diffuse large B cell lymphoma.Figure Legends:Figure (A-B) An overview of the association between known clinical and molecular features (IPI, Hams, gender, and stage) and stemness index in DLBCL cohort. Columns represent samples sorted by stemness index from low to high (top row). Rows represent known clinical and molecular. (C-D) Overall survival and progression free survival of stemness index in DLBCL patients of GSE117556 by Kaplan-Meier analysis. (E-F) Overall survival and progression free survival of stemness index in DLBCL patients of GSE31312 by Kaplan-Meier analysis. (G-I) Boxplots of tumor purity, immune score, stromal score in individual samples stratified by stemness index. (J) WGCNA analysis of differentially expressed genes in DLBCL. Different colors correspond to related modules. (K) Correlation coefficient between the modules and clinical traits with stemness. P-values are listed in the modules. (L-N) Scatter plot analysis of different modules in the MEblue, MEbrown, and MEturquoise modules. (O) Signor analysis of 16 key genes in DisNor. (P) K-M curves of the expression of CDC7 for the DLBCL patients. (Q) Boxplots of the expression of CDC7 in individual samples stratified by Hams. (R) Apoptosis ratio of SU-DHL-10 cells were treated with dequalinium chloride and simurosertib for 48 h. Data are mean ± SD of triplicate experiments. For dequalinium chloride and simurosertib compared with control an unpairedt-test was used. (S) Cell cycle of SU-DHL-10 cells were treated with dequalinium chloride and simurosertib for 48 h. Data are mean ± SD of triplicate experiments. For dequalinium chloride and simurosertib compared with control an unpairedt-test was used. (T) Cell viability of SU-DHL-2 and SU-DHL-10 cells treated with dequalinium chloride and simurosertib at the IC50 concentrations. * p<0.05. ** p<0.01, *** p<0.001. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of the effectiveness of dequalinium chloride vaginal tablets in aerobic vaginitis: A placebo-controlled study

Background: Aerobic vaginitis is a disturbance of vaginal homeostasis caused by the colonization of enteric bacteria. They are not clinically well-defined and do not have standard treatment regimes. Hence, the present study was conducted to evaluate the effectiveness of dequalinium chloride topical vaginal administration in aerobic vaginitis in a placebo-controlled manner. Materials and Methods: This study was conducted in a placebo-controlled manner to demonstrate the effectiveness of vaginal 10 mg dequalinium chloride. A total of 30 patients with different vaginal infections were included in the study. The patients included in the study were divided between the drug group and the placebo group and were treated with one vaginal tablet daily for 6 days. The total symptom score, which consists of the assessment of discharge, itching, and burning sensation, and the lactobacillus grade evaluated microscopically, was determined. Results: It was found that the effectiveness of dequalinium chloride was very high compared to placebo (92% vs. 0%). The reproduction frequency in the first visit was statistically significantly lower in the drug group compared to the placebo group (P &lt; 0.001). Conclusion: It was found that dequalinium chloride is effective for the treatment of aerobic vaginitis. However, studies containing a larger sample group, including the long-term effects (efficacy and side effects) of the drug, should be conducted to prove our conclusion.

Comprehensive rehabilitation of patients of reproductive age with precancerous pathology of the cervix after organ saving surgeons

The frequency of cervical dysplasia (cervical neoplasia) in the population is up to 5%, and in the structure of cervical diseases – 17–20%. Malignant transformation of the multilayered squamous epithelium is observed in almost 30% of patients with cervical dysplasia. The main surgical method of treatment of these conditions is diathermoconization of the cervix. But quite often patients have complaints in the late postoperative period. Comprehensive rehabilitation of patients of reproductive age with precancerous pathology of the cervix should include early restoration of sexual, reproductive and social functions of women. Research objective: to study the clinical effectiveness of the drug Femiclean (dequalinium chloride) in the comprehensive rehabilitation of patients with precancerous pathology of the cervix after organ-sparing surgery. Materials and methods. The first (main) group included 25 patients who, on the background of traditional treatment (broad diathermoconization of the cervix) for 6 days before and 12 days after treatment were treated with vaginal suppositories once a day Femiclean. The second (control) group consisted of 25 patients who underwent traditional treatment (broad diathermoconization of the cervix) with iodine-containing vaginal suppositories. Results. In patients of reproductive age with precancerous pathology of the cervix, who applied the developed concept of management in the postoperative period, the recurrence rate was probably lower; the epithelialization time was significantly higher than in women of the control group. The epithelialization time of the cervix in patients who used Femiclean vaginally in the pre- and postoperative period was 7.8 days faster compared to women who used standard vaginal drugs. The drug of domestic production Femiclean, according to our data, is well tolerated by patients and does not cause side effects.Conclusions. The developed complex rehabilitation of reproductive aged patients with precancerous pathology of the cervix after organ-sparing surgery has shown high clinical efficiency in comparison with traditional treatment this pathology.

Application Enzymatic Method for Analysis Vaginal Tabletas “Fluomizin”

Introduction: Development of a new enzymatic kinetic-photometric method for analysis of Dequalinium chloride, based on the use of enzymatic hydrolysis of acetylcholine, for determine the amount of Dequalinium chloride in the vaginal tablets “Fluomizin” No 6.&#x0D; Method: The amount of Dequalinium chloride (DCh) was determined by the degree of inhibition of the enzymatic reaction, which was evaluated by the residual unreacted substrate - acetylcholine. Determination of the residual amount of acetylcholine in the reaction mixture was performed by a kinetic-photometric method using an indicator oxidation reaction of p-phenetidine with peracetic acid, which is formed during the auxiliary reaction of perhydrolysis with addition of excess hydrogen peroxide in the reaction mixture over a period of time.&#x0D; Results: Optimal conditions were determined: pH 8.35 was selected, influence of nature of buffer solution, concentration of acetylcholine (0.05 mg / ml), cholinesterase (0.4 mg / ml), hydrogen peroxide (10,0%) and p-phenethedine (1 %), the incubation time (10 min).&#x0D; Conclusions: The procedure for determination of Dequalinium chloride content in the vaginal tablets “Fluomizin” No 6 was developed. The kinetic parameters Km (Michaelis–Menten constant) and Vmax (maximal velocity) were determined.

Identification and validation of novel biomarkers and therapeutics for pulpitis using connectivity mapping.

To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis. The Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t-test or ANOVA with the level of significance set at p≤.05. Pulpitis gene signatures were created using differential gene expression analysis at cutoff points p=.0001 and .000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C-C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (p=.0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (p<.001) and MMP9 (p<.05) in the ex vivo pulpitis model, while dequalinium chloride reduced AQP9 (p<.001) but had no significant effect on the other biomarkers. AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licenced drugs is warranted.

Micellar Nanocarriers of Hydroxytyrosol Are Protective against Parkinson's Related Oxidative Stress in an In Vitro hCMEC/D3-SH-SY5Y Co-Culture System.

Hydroxytyrosol (HT) is a natural phenolic antioxidant which has neuroprotective effects in models of Parkinson’s disease (PD). Due to issues such as rapid metabolism, HT is unlikely to reach the brain at therapeutic concentrations required for a clinical effect. We have previously developed micellar nanocarriers from Pluronic F68® (P68) and dequalinium (DQA) which have suitable characteristics for brain delivery of antioxidants and iron chelators. The aim of this study was to utilise the P68 + DQA nanocarriers for HT alone, or in combination with the iron chelator deferoxamine (DFO), and assess their physical characteristics and ability to pass the blood–brain barrier and protect against rotenone in a cellular hCMEC/D3-SH-SY5Y co-culture system. Both HT and HT + DFO formulations were less than 170 nm in size and demonstrated high encapsulation efficiencies (up to 97%). P68 + DQA nanoformulation enhanced the mean blood–brain barrier (BBB) passage of HT by 50% (p < 0.0001, n = 6). This resulted in increased protection against rotenone induced cytotoxicity and oxidative stress by up to 12% and 9%, respectively, compared to the corresponding free drug treatments (p < 0.01, n = 6). This study demonstrates for the first time the incorporation of HT and HT + DFO into P68 + DQA nanocarriers and successful delivery of these nanocarriers across a BBB model to protect against PD-related oxidative stress. These nanocarriers warrant further investigation to evaluate whether this enhanced neuroprotection is exhibited in in vivo PD models.

Клинический случай: на приеме пациентка с вульвовагинальным кандидозом

Case study of acute vulvovaginal candidiasis treated with medication containing dequalinium chloride as an active ingredient has been reported. Patient A. aged 26 complaining of vaginal and perineal burning, itching, as well as of profuse white, whitish vaginal discharge, was under observation. Vulvovaginal candidiasis was diagnosed based on the laboratory tests. After verifying the diagnosis the patient was prescribed a medication containing dequalinium chloride, with beneficial effect. No vaginal dysbiosis was reported after exposure to medication.

Dequalinium chloride use in adult Spanish women with bacterial vaginosis: an observational study

Bacterial vaginosis (BV) represents the most frequent vaginal infection in women of childbearing age. The aim of this study was to characterise episodes of BV among adult Spanish women and their management with dequalinium chloride (DQC). Data from 573 DQC-treated BV adult women was obtained on medical records and questionnaires. The study shows that 20.6% had presented vaginal infections previously. Comorbid candidosis was significantly associated to other symptoms, such as pruritus or leucorrhoea. Most patients (64.3%) indicated a moderate-strong impact of the BV episode on their sexual life. After treatment, 84.8% of patients reported no BV symptoms. Patients were given instructions to prevent relapses. Most patients (83.1%) rated DQC as ‘satisfactory’ or ‘very/extremely satisfactory’ regarding symptom relief, prevention or treatment of the episode of BV. In conclusion, this study provides a better understanding of BV episodes and the impact of the treatment with DQC in real clinical practice in Spanish patients. IMPACT STATEMENT What is already known on this subject? Bacterial vaginosis (BV) is the most commonly reported vaginal infection among women of childbearing age. Despite the availability of antibiotic medications for the treatment of BV, management of this condition remains challenging. In fact, recurrence of BV has been reported for up to 50% of cases. However, antiseptic agents are considered an effective option for BV treatment. What the results of this study add? The study provides a better understanding of the prevalent symptomatology and the impact on quality of life of women with BV. Moreover, it has been observed that antiseptic dequalinium chloride (DQC) efficiently reduces symptoms and improves quality of life of the patients during episodes of BV. What the implications are of these findings for clinical practice and/or further research? In the context of the World Health Organisation recommendations on the rational use of antibiotics, we believe that the use of DQC may be a good alternative to antibiotics as a therapy for BV.

Dequalinium Chloride Effectively Disrupts Bacterial Vaginosis (BV) Gardnerella spp. Biofilms

Bacterial vaginosis (BV) is the most frequent vaginal infection worldwide. It is caused by the overgrowth of anaerobic vaginal pathogens such as Gardnerella spp. BV has been associated with the occurrence of dense multispecies biofilms on the vaginal mucosa. Treatment of biofilm-associated infections such as BV is challenging. In this study, we have tested the role of a quaternary ammonium compound, dequalinium chloride (DQC), in the eradication of Gardnerella spp. biofilms. The effects of the test substance on the biomass and the metabolic activity of the biofilm of Gardnerella spp. were assessed in vitro using a microtiter plate assay. In addition, the effect of DQC on the Gardnerella spp. biofilm was further assessed by using scanning electron microscopy and confocal laser scanning microscopy. The results showed that DQC was particularly effective in the destruction of BV-associated Gardnerella spp. biotypes, impacting both their biomass and metabolic activity. In addition, the disruption of biofilm architecture was evident and was probably caused by multiple mechanisms of action. We conclude that DQC is an antibiofilm agent and is able to efficiently destroy Gardnerella spp. BV-associated biofilms. Therefore, it is a valid option for BV therapy and has the potential to prevent BV recurrences.

The potential value of dequalinium chloride in the treatment of cancer: Focus on malignant glioma.

Dequalinium chloride has been known as one kind of antibiotic that displays a broad antimicrobial spectrum and has been clinically proven to be very safe. In recent years, studies have shown that dequalinium chloride can inhibit the growth of malignant tumours, and reports were mainly used for solid tumours. Glioblastoma is the most common malignant neuroepithelial tumour of the central nervous system in adults, and the prognosis of glioblastoma is poor as it has a high resistance to apoptosis. This review summarizes the current understanding of dequalinium chloride-induced cancer cell apoptosis and its potential role in glioblastoma resistance and progression. Particularly, we focus on dequalinium chloride as it exerts a wide range of anti-cancer activity through its ability to target and accumulate in the mitochondria, and it effectively inhibits the growth of glioblastoma cells in vitro and vivo. Dequalinium chloride is an inhibitor of XIAP and can also act as a mitochondrial targeting agent, which gives it an interesting perspective regarding recent advances in the treatment of malignant glioma.

Dequalinium-Derived Nanoconstructs: A Promising Vehicle for Mitochondrial Targeting.

The cell's power house, mitochondrion, is a vital organelle for drug targeting in the treatment of many diseases due to its fundamental duties and function related to cell proliferation and death. The mitochondrial membrane comprises bilayer artifact and poses extremely negative potential, creating hurdles for therapeutic molecules in reaching mitochondria. To accomplish mitochondrial targeting, the scientific community has explored diverse pharmaceutical formulations like liposomes, polymeric nanoparticles (NPs), and inorganic NPs. However, the game changing technology was a modification of these carriers by mitochondriotropic moiety, dequalinium chloride (DQA) or delivering the chemotherapeutics by DQAsomes. The DQA represents a distinctive mitochondriotropic delocalized cation that displays their selectivity towards accumulation in mitochondria of carcinoma cells. Attributed to this characteristics, DQAsomes have been formulated using DQA and explored for successful mitochondrial targeting of bioactives. In this review, it is discussed the effectiveness of DQA nanocarriers which efficiently and selectively transmit the cytotoxic drug to the tumor cell. The DQA based nanoformulations have evidently displayed augmented pharmacological and therapeutic outcomes than their counterparts both in vitro and in vivo. Thus, DQAsomes symbolizes an ideal carrier with excellent potential as mitochondrial targeting agent.

Оптимизация методов коррекции нарушений нормоценоза влагалища при первичном обращении пациенток

Objective. To study the efficacy and feasibility of using dequalinium chloride during the primary treatment of patients of reproductive age with the symptoms of disorders of vaginal normocenosis. Patients and methods. In 60 patients of reproductive age (31.43 ± 6.44 years), an observational study was conducted, in which the initial data characterizing the state of vaginal microbiota were evaluated, and also the dynamics of their change immediately after treatment and after one month were presented. The analysis of risk factors for vaginal normocenosis disorders and dynamics of changes in the clinical picture amid dequalinium chloride therapy (Fluomizin®) was performed. Results. Significant risk factors for disorders of vaginal normocenosis are: early sexual activity (28.3%), the number of sexual partners (4.32 ± 4.11), their frequent change (13.33%), which determine hormonal and immune changes in the mucosa against the background of endocrine pathology (hypothyroidism in 8.33%) and genital endometriosis (in 35.0%). The prescription of Fluomizin® led to the relief of symptoms (itching, burning, discomfort, discharge and hyperemia) after 6 days of its use, which is confirmed by the data of the study (vaginal swabs, Femoflor 16). Conclusion. Dequalinium chloride (Fluomizin®) can be used to correct the disorders of vaginal normocenosis in the initial treatment of patients before obtaining the results of laboratory studies. Key words: reproductive period, vaginal health, dequalinium chloride, treatment quality

Lactobacillus rhamnosus BMX 54 + Lactose, A Symbiotic Long-Lasting Vaginal Approach to Improve Women's Health.

The proposal to restore vaginal microbiota using biotherapeutic agents ended with controversial results. Vaginal microbiota modifications from eubiosis to dysbiosis (desquamative inflammatory vaginitis, “aerobic vaginitis”) and pathobiosis have recently been demonstrated to have a pivotal role in women’s clinical health. Bacterial vaginosis (BV) and its related women’s pathology seem to be “the most common vaginal infections” in women; the Center for Disease Control (CDC) recommended treatment for this pathology: metronidazole, clyndamicin or other well known treatment such as dequalinium chloride, unfortunately, has been demonstrated to fail in control of this infection and especially in its recurrence rates. A long-lasting vaginal approach with a symbiotic drug (Lactobacillus rhamnosus BMX 54 + lactose) (NORMOGIN™) has demonstrated on a large sample of women enrolled in clinical trials (more than 3000 patients) not only to be able to significantly reduce the BV recurrences, after the CDC standard of care administration, but also to control the vaginal pathobiosis pathway, restoring the physiological eubiosis from dysbiosis. These results are really very encouraging and clearly demonstrate that a symbiotic long-lasting vaginal application of a selected Lactobacillus population plus a prebiotic could be helpful if added to the recommended standard of care.

Inhibition of porcine reproductive and respiratory syndrome virus by PKC inhibitor dequalinium chloride in vitro

As a severe disease characterized by reproductive failure and respiratory distress, porcine reproductive and respiratory syndrome (PRRS) is one of the most leading threats to the swine industry worldwide. Highly evolving porcine reproductive and respiratory syndrome virus (PRRSV) strains with distinct genetic diversity make the current vaccination strategy much less cost-effective and thus urge alternative protective host directed therapeutic approaches. RACK1-PKC-NF-κB signalling axis was suggested as a potential therapeutic target for PRRS control, therefore we tested the inhibitory effect of PKC inhibitor dequalinium chloride (DECA) on the PRRSV infection in vitro. RT-qPCR, western blot, Co-IP and cytopathic effect (CPE) observations revealed that DECA suppressed PRRSV infection and protected Marc-145 cells and porcine alveolar macrophages (PAMs) from severe cytopathic effects, by repressing the PKCα expression, the interaction between RACK1 and PKCα, and subsequently the NF-κB activation. In conclusion, the data presented in this study shed more light on deeper understanding of the molecular pathogenesis upon PRRSV infection and more importantly suggested DECA as a potential promising drug candidate for PRRS control.

Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study

To compare the clinical response, microscopic examination and fungal culture between dequalinium chloride (DQC) and clotrimazole (CT) for treating vaginal candidiasis (VC). The double-blind, randomized study was conducted from September 2014 to September 2016 at Siriraj Hospital, Thailand. Eligible participants were Thai women diagnosed with VC by microscopic examination. The exclusion criteria included immunocompromised conditions, consumption of antifungal drugs, and having recurrent VC. Each participant was randomized with a 1:1 allocation to receive six vaginal tablets of 100mg CT or 10mg DQC. Two visits included 10 ± 2days (C1) and 38 ± 4days (C2). Outcome measures were improvement of VC symptoms, microscopic examination, culture, satisfaction and tolerability. Of 155 eligible participants, 150 were randomized and allocated into CT (N = 76) and DQC (N = 74). The average age was 31.1 ± 7.2years. Comparable improvement of clinical response was demonstrated (OR at C1 0.79, 95% CI 0.56-1.10, p = 0.197; and OR at C2 0.99, 95% CI 0.69-1.43, p = 0.985). Of CT and DQC groups, the microscopic examination was positive at 11/75 (14.9%) vs 18/72 (25.3%) at C1 and 18/74 (24.3%) vs 28/66 (42.4%) at C2. And the culture was positive at 25/75 (33.8%) vs 46/72 (65.7%) at C1 and at 26/74 (36.6%) vs 46/66 (69.7%) at C2. Most participants had high satisfaction and tolerability and none reported any side effects. DQC and CT show comparable clinical response but CT results in greater improvement of microscopic examination and fungal culture. The Clinical Trial Registry number was NCT02242695. (September 17, 2014).

Bis-Quinolinium Cyclophane Blockers of SK Potassium Channels Are Antagonists of M3 Muscarinic Acetylcholine Receptors.

Dequalinium is used as an antimicrobial compound for oral health and other microbial infections. Derivatives of dequalinium, the bis-quinolinium cyclophanes UCL 1684 and UCL 1848, are high affinity SK potassium channel antagonists. Here we investigated these compounds as M3 muscarinic receptor (mACHR) antagonists. We used the R-CEPIAer endoplasmic reticulum calcium reporter to functionally assay for Gq-coupled receptor signaling, and investigated the bis-quinolinium cyclophanes as antagonists of M3 mACHR activation in transfected CHO cells. Given mACHR roles in airway smooth muscle (ASM) contractility, we also tested the ability of UCL 1684 to relax ASM. We find that these compounds antagonized M3 mACHRs with an IC50 of 0.27 μM for dequalinium chloride, 1.5 μM for UCL 1684 and 1.0 μM for UCL 1848. UCL 1684 also antagonized M1 (IC50 0.12 μM) and M5 (IC50 0.52 μM) mACHR responses. UCL 1684 was determined to be a competitive antagonist at M3 receptors as it increased the EC50 for carbachol without a reduction in the maximum response. The Ki for UCL1684 determined from competition binding experiments was 909 nM. UCL 1684 reduced carbachol-evoked ASM contractions (>90%, IC50 0.43 μM), and calcium mobilization in rodent and human lung ASM cells. We conclude that dequalinium and bis-quinolinium cyclophanes antagonized M3 mACHR activation at sub- to low micromolar concentrations, with UCL 1684 acting as an ASM relaxant. Caution should be taken when using these compounds to block SK potassium channels, as inhibition of mACHRs may be a side-effect if excessive concentrations are used.