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Food and Chemical Toxicology : An... Aug 2023Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are... (Review)
Review
Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are used as pharmaceuticals. Ingested azo compounds can be reduced by the action of bacteria in the gut, where the oxygen tension is low, and the development of microbiome science has allowed more precise delineation of the roles of specific bacteria in these processes. Reduction of the azo bond of an azo compound generates two distinct classes of aromatic amine metabolites: the starting material that was used in the synthesis of the azo compound and a product which is formed de novo by metabolism. Reductive metabolism of azo compounds can have toxic consequences, because many aromatic amines are toxic/genotoxic. In this review, we discuss aspects of the development and application of azo compounds in industry and medicine. Current understanding of the toxicology of azo compounds and their metabolites is illustrated with four specific examples - Disperse Dyes used for dyeing textiles; the drugs phenazopyridine and eltrombopag; and the ubiquitous food dye, tartrazine - and knowledge gaps are identified. SUBMISSION TO: FCT VSI: Toxicology of Dyes.
Topics: Azo Compounds; Coloring Agents; Tartrazine; Bacteria; Amines
PubMed: 37451600
DOI: 10.1016/j.fct.2023.113932 -
Obstetrics and Gynecology Feb 2024To assess and compile the current level of evidence regarding successful surgical treatment of vesicovaginal fistulae and how these perioperative interventions affect...
OBJECTIVE
To assess and compile the current level of evidence regarding successful surgical treatment of vesicovaginal fistulae and how these perioperative interventions affect anatomic, patient-centered, and adverse outcomes.
DATA SOURCES
PubMed and EMBASE were searched from inception through September 9, 2022.
METHODS OF STUDY SELECTION
This review included comparative studies (of any sample size) and single-group studies (1,000 or more participants) of primary or recurrent vesicovaginal fistula (ie, vesicovaginal fistula, urethrovaginal fistula, and bladder neck-vaginal fistula). We evaluated preintervention assessment or management, various techniques for intraoperative management, and postoperative management. Outcomes of interest included anatomic and objective outcomes (such as successful repair, fistula closure, urinary incontinence, recurrent fistula, perioperative complications) and subjective outcomes (such as voiding symptoms and quality of life). Abstracts and full-text articles were screened in duplicate, and study descriptions and findings were extracted into standardized extraction forms. Risk of bias was assessed independently by two investigators and adjudicated by a third. Study quality was summarized with standardized tools. We conducted random-effects model and restricted maximum-likelihood meta-analyses of relative risks when at least three studies compared similar interventions and reported similar outcome measures.
TABULATION, INTEGRATION, AND RESULTS
Forty-six studies met the inclusion criteria. Studies were categorized into 11 domains: 1) preoperative assessment, 2) preoperative and postoperative physical therapy, 3) route of surgery, 4) incorporation of a flap, 5) trimming, 6) layered closure, 7) intraoperative antibiotics, 8) fibrin glue, 9) fascial sling, 10) postoperative Foley catheter duration, and 11) quality of life. Although the strength of the data is insufficient, preoperative phenazopyridine, physical therapy, layered closure, and intraoperative antibiotics seemed to improve the rate of successful fistula repair. Route of surgery (vaginal vs abdominal laparotomy) was determined primarily by surgeon preference and showed no difference in successful fistula repair. In addition, use of interpositional flaps, trimming fistula edges, fibrin glue, and fascial sling did not show significant improvement in rates of fistula cure. Overall, quality-of-life scores improved postoperatively regardless of route of repair and use of interpositional flaps.
CONCLUSION
Our findings highlight the limited information available to guide evidence-based treatment of vesicovaginal fistula repair. Overall, high-quality evidence is lacking to provide guidelines; therefore, expert opinion remains the primary influence for fistula repair recommendations.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42021214948.
Topics: Female; Humans; Anti-Bacterial Agents; Fibrin Tissue Adhesive; Quality of Life; Urinary Bladder; Vesicovaginal Fistula
PubMed: 38033311
DOI: 10.1097/AOG.0000000000005468 -
Urologiia (Moscow, Russia : 1999) Sep 2020Cystoscopy is one of the most common procedures in urology. There is no single approach to pain relief. In the literature, there are conflicting data on the efficiency... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Cystoscopy is one of the most common procedures in urology. There is no single approach to pain relief. In the literature, there are conflicting data on the efficiency of intra-urethral gels. The use of non-steroidal anti-inflammatory drugs, intravenous sedation, and nitric oxide analgesia has been described. Phenazopyridine has been known for a long time. Acting on the bladder mucosa, it has a local analgesic effect. AN evaluation of phenazopyridine intake prior to cystoscopy in order to decrease pain during procedure and facilitate subsequent urination was performed.
MATERIALS AND METHODS
A total of 97 patients were included in the study. Indications for cystoscopy were as following: hematuria, lower urinary tract symptoms/pain, a need to remove ureteral stent. The patients were randomized into two groups. In the main group (n=50), phenazopyridine 200 mg was administered 20 minutes before cystoscopy and then at a dose of 200 mg every 8 hours (in total three doses) in combination with lidocaine gel. In the control group (n=47), only lidocaine gel was used. Heart rate was measured before and after the procedure. All patients were asked to complete a visual analogue scale (VAS) 3, 8 and 24 hours after cystoscopy with the assessment of the first urination.
RESULTS
After cystoscopy, the difference between groups in VAS score was 27.7% in favor of the main group (p<0.001). After 3 hours, the average score in the main group was two times less than in the Control (p=0.012), while 3 and 8 hours after cystoscopy, the proportion of "zero" results was 10% and 0%, 28% and 4%, respectively, p<0.005. The heart rate after the procedure in the main group was 75.1 beats/min, compared to 77.9 beats/min in the control group (p=0.016).
CONCLUSION
The intake of phenazopyridine allows to reduce pain intensity during and after cystoscopy and alleviate pain during first urination.
Topics: Cystoscopy; Humans; Pain; Phenazopyridine; Ureter
PubMed: 32897014
DOI: No ID Found -
Neuropsychopharmacology : Official... Nov 2022Alzheimer's disease (AD) is the most common form of dementia with no effective treatment options. A complete elucidation of its underlying molecular mechanisms,...
Alzheimer's disease (AD) is the most common form of dementia with no effective treatment options. A complete elucidation of its underlying molecular mechanisms, including the transcription regulation of genes critically involved in AD, may shed light on new therapeutic development. RPS23RG1 is a newly identified AD-associated gene, whose expression is decreased in AD and restoration can attenuate AD-like phenotypes in animal models. However, the transcription regulation of RPS23RG1 remains unknown. In this study, we explored the promoter of RPS23RG1 and identified its transcription initiation site (TSS) at 1525 bp upstream of the ATG translation start codon. Progressive deletion analysis determined the presence of a negative regulatory region and a positive regulatory region within nucleotide positions +1127 to +1187 and +732 to +1127 relative to the TSS (+1), respectively. We conducted a reporter system to screen for compounds that increase RPS23RG1 expression through antagonizing its negative regulatory elements and identified phenazopyridine. Importantly, we demonstrated that phenazopyridine not only promoted RPS23RG1/Rps23rg1 expression, but also reduced AD-like pathologies and cognitive impairments in the APP/PS1 AD model mice. We also determined a critical negative regulatory domain of RPS23RG1 within nucleotide positions +1177 to +1187 and found that the transcription factor SMAD3 bound to this domain. Inhibition of SMAD3 promoted RPS23RG1 expression. Moreover, phenazopyridine reduced SMAD3 binding to the RPS23RG1 promoter without affecting SMAD3 phosphorylation and nuclear localization. Taken together, our results determine the transcription regulation mechanism of RPS23RG1 and show that phenazopyridine has potential for AD treatment through regulating RPS23RG1 transcription.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Codon, Initiator; Disease Models, Animal; Mice; Mice, Transgenic; Nucleotides; Phenazopyridine; Phenotype; Transcription Factors
PubMed: 35821069
DOI: 10.1038/s41386-022-01373-7 -
BMJ Supportive & Palliative Care Jan 2024Methemoglobinemia, due to the oxidation of iron from ferrous to ferric form in the haemoglobin molecule, results in decreased oxygen delivery to the tissues....
Methemoglobinemia, due to the oxidation of iron from ferrous to ferric form in the haemoglobin molecule, results in decreased oxygen delivery to the tissues. Phenazopyridine, a commonly used medication for urinary symptoms, is a rare cause of methemoglobinemia. We report an elderly woman with advanced vaginal cancer, who developed methemoglobinemia following the use of phenazopyridine at a dose of 200 mg three times a day for 14 days. She presented with dyspnoea without cyanosis, oxygen saturation of 70%, methemoglobin concentration of 32.2% in arterial blood gas analysis and haemoglobin of 5 g/dL. This condition was identified and treated with methylene blue and oxygen support, which resulted in complete recovery in two days. Though rare, this highlights the importance of ascertaining reversible causes of symptoms, even in palliative care settings. Medications as an aetiology of symptoms should be considered even if they were used on a long-term basis.
PubMed: 38167589
DOI: 10.1136/spcare-2023-004692 -
Frontiers in Pharmacology 2021Phenazopyridine is a widely used drug against urinary tract pain. The compound has also been shown to enhance neural differentiation of pluripotent stem cells. However,...
Phenazopyridine is a widely used drug against urinary tract pain. The compound has also been shown to enhance neural differentiation of pluripotent stem cells. However, its mechanism of action is not understood. Based on its chemical structure, we hypothesized that phenazopyridine could be a kinase inhibitor. Phenazopyridine was investigated in the following experimental systems: 1) activity of kinases in pluripotent stem cells; 2) binding to recombinant kinases, and 3) functional impact on pluripotent stem cells. Upon addition to pluripotent stem cells, phenazopyridine induced changes in kinase activities, particularly involving Mitogen-Activated Protein Kinases, Cyclin-Dependent Kinases, and AKT pathway kinases. To identify the primary targets of phenazopyridine, we screened its interactions with 401 human kinases. Dose-inhibition curves showed that three of these kinases interacted with phenazopyridine with sub-micromolar binding affinities: cyclin-G-associated kinase, and the two phosphatidylinositol kinases PI4KB and PIP4K2C, the latter being known for participating in pain induction. Docking revealed that phenazopyridine forms strong H-bonds with the hinge region of the ATP-binding pocket of these kinases. As previous studies suggested increased autophagy upon inhibition of the phosphatidyl-inositol/AKT pathway, we also investigated the impact of phenazopyridine on this pathway and found an upregulation. In conclusion, our study demonstrates for the first time that phenazopyridine is a kinase inhibitor, impacting notably phosphatidylinositol kinases involved in nociception.
PubMed: 34421588
DOI: 10.3389/fphar.2021.664608 -
Spectrochimica Acta. Part A, Molecular... Oct 2020Three univariate and two multivariate spectrophotometric methods were developed and subsequently validated to determine phenazopyridine HCl (PHZ) and trimethoprim (TMP)...
Simultaneous determination of phenazopyridine HCl and trimethoprim in presence of phenazopyridine HCl impurity by univariate and multivariate spectrophotometric methods - Quantification of phenazopyridine HCl impurity by univariate methods.
Three univariate and two multivariate spectrophotometric methods were developed and subsequently validated to determine phenazopyridine HCl (PHZ) and trimethoprim (TMP) in the presence of 2,6-Diaminopyridine (2,6-DAP). The first univariate method depends on direct determination of phenazopyridine by measuring its absorbance at 412 nm and performed in concentration range of 1.00-10.00 μg/mL. Then the contribution of phenazopyridine is removed by dividing the mixture spectrum with PHZ divisor (5 μg/mL) after that the constant is mathematically subtracted and finally the generated spectrum is multiplied with the PHZ divisor. These steps eliminate PHZ contribution and the recovered spectrum is that of TMP and 2,6-DAP only where different methods can be applied to determine TMP and 2,6-DAP through this binary mixture spectrum. The first method to determine both components depends on measuring both TMP and 2,6-DAP through their first derivative (DD) spectra at 244.70 and 259.60 nm for TMP and 2,6-DAP, respectively with concentration ranges of 4.00-24.00 μg/mL TMP and 4.00-26.00 μg/mL 2,6-DAP. The second method depends on application of the isoabsorptive method which was used for TMP determination at its isoabsorptive point with 2,6-DAP at 242.64 nm with concentration range 1.00-20.00 μg/mL for TMP. The developed univariate methods were successfully applied to determine PHZ, TMP and PHZ impurity (2,6-DAP). Two multivariate methods were applied for determination of PHZ and TMP in presence of 2,6-DAP namely, Principle Component Regression (PCR) and Partial Least Squares (PLS). The results of the two models show that simultaneous determination of PHZ and TMP in presence of PHZ impurity can be performed in the concentration ranges of 6.00-14.00 μg/mL PHZ and 24.00-56.00 μg/mL TMP. All the proposed methods were successfully applied to analyze PHZ and TMP in pharmaceutical formulations without interference from the dosage form additives and the results were statistically compared with the reported method.
Topics: Least-Squares Analysis; Phenazopyridine; Spectrophotometry; Trimethoprim
PubMed: 32492634
DOI: 10.1016/j.saa.2020.118516 -
Urologiia (Moscow, Russia : 1999) Jun 2021To evaluate the analgesic effect, efficacy and tolerability of phenazopyridine in combination with fosfomycin for the treatment of acute uncomplicated cystitis in... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To evaluate the analgesic effect, efficacy and tolerability of phenazopyridine in combination with fosfomycin for the treatment of acute uncomplicated cystitis in working-age female.
MATERIAL AND METHODS
A total of 152 women with acute uncomplicated cystitis were included in multicenter, randomized, open-label study which were carried out in 5 polyclinics of the Perm Territory. All the patients were divided into 2 groups of 76 people each, depending on the treatment. In the main group, women received oral phenazopyridine 200 mg 3 times a day for 2 days (a total dose 1200 mg) and fosfomycin trometamol in a dose of 3 g once. In the control group, patients received a single dose of fosfomycin trometamol (3 g) and drotaverin 80 mg 3 times a day for 2 days. A visual analogue scale (VAS) was used for evaluation of pain intensity. The symptoms of cystitis were assessed using the ACSS scale. In addition, urinalysis, urine culture and other methods were done. The results were evaluated after 6, 12, 24, 48 hours, 3 and 6 days.
RESULTS
In the main group, the severity of pain according to the VAS decreased from the initial 7.2+/-0.5 points to 1.6+/-0.2 points after 12 hours, to 0.4 +/- 0.05 points after 24 hours. Pain syndrome completely disappeared in all patients after 48 hours. In the control group, at all time points, a significant less pronounced analgesic effect was seen (p<0.001). The overall ACSS score in the main group decreased from the 12.0+/-0.5 points to 2.1+/-0.3 after 3 days and to 0.28+/-0.04 points after 6 days (p<0.001), which indicated a more rapid resolution of symptoms compared to the control group. The symptomatic effect of phenazopyridine (relief of pain, dysuria and discomfort) provided a more pronounced improvement in the well-being in the main group in comparison to the control group, which was confirmed by Dynamics domain of the ACSS scale (p<0.001). The combination of fosfomycin and phenazopyridine was more effective than the combination of fosfomycin and drotaverine. The clinical and microbiological cure rate in the main group was 97.4% and 96.9%, respectively. Leukocyturia was resolved earlier, and the duration of treatment decreased by 30.1%. An undesirable effect of phenazopyridine (nausea) was detected only in 1 (1.3%) patient.
CONCLUSION
Phenazopyridine has a pronounced analgesic effect and is proved to be an effective and safe drug in patients with acute uncomplicated cystitis.
Topics: Anti-Bacterial Agents; Cystitis; Female; Fosfomycin; Humans; Phenazopyridine; Urinary Tract Infections
PubMed: 34251097
DOI: No ID Found -
International Urogynecology Journal Sep 2022To determine if administration of a standard 400 mg oral dose of riboflavin (vitamin B2) was comparable to phenazopyridine (pyridium) for evaluating ease of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION AND HYPOTHESIS
To determine if administration of a standard 400 mg oral dose of riboflavin (vitamin B2) was comparable to phenazopyridine (pyridium) for evaluating ease of visualization of ureteral jets at the time of cystoscopy.
METHODS
A three-arm double-blinded, randomized controlled study was performed consisting of thiamine as placebo, phenazopyridine, and riboflavin. Agents were administered the morning of surgery prior to surgical procedure. The primary outcome was the ease of visualization of the ureteral jets based on a grading of urine stain intensity on a 7-point color scale, where 1-2 were minimal yellow staining, 3-4 were moderate yellow staining, and 5-7 defined as intense yellow staining. Analysis of covariance (ANCOVA) was used with pairwise comparison to characterize urine stain intensity as a continuous variable among the three groups controlling for age, BMI, creatinine, and time from ingestion of medication to first cystoscopy.
RESULTS
Eighty-four subjects were randomized with a mean ± SD age of 46.25 + 11.36 and BMI of 32.46 + 6.59. Riboflavin did have moderate or intense staining in 57% of cases; however, there was no significant difference between urine staining intensity compared to placebo (p = 0.21). There was a statistically significant increased urine staining intensity for phenazopyridine compared to placebo (p = 0.001) and for phenazopyridine compared to riboflavin (p = 0.001).
CONCLUSIONS
Phenazopyridine provided statistically significantly greater urine staining compared to both riboflavin and placebo and should be considered primarily for ease of ureteral jet visualization.
Topics: Administration, Oral; Coloring Agents; Humans; Phenazopyridine; Riboflavin; Staining and Labeling; Ureter
PubMed: 34057543
DOI: 10.1007/s00192-021-04867-y -
Environmental Science and Pollution... Mar 2023Water pollution by antibiotics is a global crisis, and its risk is critically more severe due to the explosive use of these drug compounds. A critical effective removal...
Water pollution by antibiotics is a global crisis, and its risk is critically more severe due to the explosive use of these drug compounds. A critical effective removal method to diminish this risk is heterogeneous photocatalysis and optimizing the conditions to reach higher mineralization efficiency. CeO anoparticles (NPs) were synthesized and characterized by X-ray diffraction (XRD), UV-Vis diffuse reflection spectroscopy (DRS), and Fourier transform infrared spectroscopy (FTIR) techniques. A cubic structural crystallite phase was detected that had crystallite sizes of 17.9 and 16.7 nm estimated by the Scherrer and Williamson-Hall models. A typical FTIR absorption band for the Ce-O stretching absorption has appeared at 554 cm. Based on DRS data and the Kubelka-Munk and Tauc models, Eg values of 2.80, 3.06, 3.12, and 3.13 eV were obtained for n-values of 1/2, 2, 3/2, and 3, respectively. pHpzc of CeO NPs was about 5.7. The direct photolysis and surface adsorption processes have no critical role in phenazopyridine (PP) removal by appearing with 2.7 and 6.7% removal efficiencies, respectively. Due to the highest photocatalytic activity of CeO NPs toward PP, the effects of the critical operating variable on the activity were evaluated, and the optimal conditions were as catalyst dose, 0.7 g/L; pH, 6; irradiation time, 90 min; and C, 20 ppm. The Hinshelwood kinetics equation plot was y = - 6.6442 - 0.4677x (r = 0.9296), in which its slope as the rate constant of the photodegradation process was 0.4677 min (corresponding to a t value of 1.48 min).
Topics: Phenazopyridine; Anti-Bacterial Agents; Cerium
PubMed: 36434455
DOI: 10.1007/s11356-022-24260-6