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Environmental Science and Pollution... Oct 2023Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the...
Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the morphology, characterization, and effectiveness of TiO/graphene composite nanofiber photocatalysts in the treatment of pharmaceutical wastewater containing three different pharmaceutical groups, such as an antibiotic (rifampin), painkiller (phenazopyridine), and immunosuppressant (azathioprine). Various parameters such as pH, salt concentration, and initial pharmaceutical compound concentration were optimized to achieve maximum degradation kinetics and efficiency. The optimum conditions were determined to be 1.5% graphene content, 30 ppm initial concentration of pharmaceutical compound, pH=5, and a 0.5 g/L photocatalyst dose. The presence of salt slightly decreased the degradation kinetics, but it did not significantly affect the performance of the TiO/graphene composite nanofibers photocatalyst. At optimum condition, TiO/1.5% graphene composite nanofibers degraded 50% of phenazopyridine, 86.89% of rifampin, and completely azathioprine. Comparing with phenazopyridine, N heteroatom-rich molecule of azathioprine and hydroxyl-rich molecule of rifampin lead to being susceptible to photocatalytic degradation. The reuse of the photocatalyst in multiple cycles showed consistent performance, indicating its potential for practical and economic applications.
Topics: Phenazopyridine; Nanofibers; Azathioprine; Graphite; Rifampin; Titanium; Pharmaceutical Preparations; Catalysis
PubMed: 37747607
DOI: 10.1007/s11356-023-29869-9 -
Mini Reviews in Medicinal Chemistry 2021Azo molecules possess the characteristic azo bond (-N=N-) and are considered fascinating motifs in organic chemistry. Since the last century, these brightly colored... (Review)
Review
Azo molecules possess the characteristic azo bond (-N=N-) and are considered fascinating motifs in organic chemistry. Since the last century, these brightly colored compounds have been widely employed as dyes across several industries in applications for printing, food, paper, cosmetics, lasers, electronics, optics, material sciences, etc. The discovery of Prontosil, an antibacterial drug, propelled azo compounds into the limelight in the field of medicinal chemistry. Subsequent discoveries including Phenazopyridine, Basalazide, and Sulfasalazine enabled azo compounds to occupy a significant role in the drug market. Furthermore, azo compounds have been employed as antibacterial, antimalarial, antifungal, antioxidant, as well as antiviral agents. The metabolic degradation of many azo dyes can induce liver problems if ingested, posing a safety concern and limiting their application as azo dyes in medicinal chemistry. However, azo dyes remain particularly significant for applications in cancer chemotherapy. Recently, a paradigm shift has been observed in the use of azo dyes: from medicinal chemistry to biomedical sciences. The latter benefits from azo dye application are related to imaging, drug delivery, photo-pharmacology and photo switching. Herein, we have compiled and discussed recent works on azo dye compounds obtained so far, focusing on their medicinal importance and future prospects.
Topics: Azo Compounds; Biomedical Research; Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Molecular Structure
PubMed: 33231147
DOI: 10.2174/1389557520999201123210025 -
Female Pelvic Medicine & Reconstructive... Feb 2021The objective of our study was to determine if phenazopyridine reduces void trial (VT) failure rates after prolapse surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The objective of our study was to determine if phenazopyridine reduces void trial (VT) failure rates after prolapse surgery.
METHODS
A single-institution randomized controlled trial was conducted comparing a second dose of phenazopyridine 200 mg on postoperative day 1 versus no additional phenazopyridine in women undergoing prolapse surgery. All subjects (including controls) received 200 mg of phenazopyridine preoperatively for ureteral patency verification. The intervention group received a second dose of phenazopyridine 200 mg the morning of postoperative day 1. The primary outcome was assessed using a standardized VT. Secondary outcomes included pain, opioid usage, urinary tract infections, and prolonged or recurrent urinary retention. An intent-to-treat analysis was performed with a χ2 test to compare failure rates between the intervention and control groups.
RESULTS
We enrolled 152 women, and 76 were randomized to each group. There was no difference in VT failures between the 2 groups-34% failed without phenazopyridine on postoperative day 1, and 42% failed with phenazopyridine on postoperative day 1 (P = 0.326). Subject characteristics were similar across both groups. Pain scores immediately before the VT were 3 out of 10 in both groups (P = 0.206), with no difference in opioid consumption (P = 0.750). There were no differences in the rate of urinary tract infections or prolonged or recurrent urinary retention between the groups (P = 0.304 and P = 0.745).
CONCLUSIONS
While previous studies suggested an improvement in immediate postoperative voiding with phenazopyridine, our randomized controlled trial does not support this.
Topics: Anesthetics; Female; Humans; Middle Aged; Pelvic Organ Prolapse; Phenazopyridine; Postoperative Care; Postoperative Complications; Premedication; Urinary Retention
PubMed: 31033527
DOI: 10.1097/SPV.0000000000000737 -
European Journal of Pharmacology Mar 2023and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain...
BACKGROUND
and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain syndrome (BPS). Whereas the analgesic effect of PAP has been attributed to a local effect on the mucosa of the lower urinary tract (LUT), the molecular targets of PAP remain unknown. We investigated the effect of PAP on pain-related Transient Receptor Potential (TRP) channels expressed in sensory neurons that innervate the bladder wall.
EXPERIMENTAL APPROACH
The effects of PAP on the relevant TRP channels (TRPV1, TRPA1, TRPM8, TRPM3) expressed in HEK293 or CHO cells was investigated using Fura-2-based calcium measurements and whole-cell patch-clamp recordings. Activity of PAP on TRPM8 was further analysed using Fura-2-based calcium imaging on sensory neurons isolated from lumbosacral dorsal root ganglia (DRG) of mice.
KEY RESULTS
PAP rapidly and reversibly inhibits responses of TRPM8 expressed in HEK293 cells to cold and menthol, with IC values between 2 and 10 μM. It acts by shifting the voltage dependence of channel activation towards positive potentials, opposite to the effect of menthol. PAP also inhibits TRPM8-mediated, menthol-evoked calcium responses in lumbosacral DRG neurons. At a concentration of 10 μM, PAP did not significantly affect TRPA1, TRPV1, or TRPM3.
CONCLUSION AND IMPLICATIONS
PAP inhibits TRPM8 in a concentration range consistent with PAP levels in the urine of treated patients. Since TRPM8 is expressed in bladder afferent neurons and upregulated in patients with painful bladder disorders, TRPM8 inhibition may underlie the analgesic activity of PAP.
Topics: Animals; Cricetinae; Humans; Mice; Calcium; Cricetulus; Fura-2; Ganglia, Spinal; HEK293 Cells; Menthol; Pain; Phenazopyridine; Sensory Receptor Cells; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPM Cation Channels; Urinary Bladder
PubMed: 36657655
DOI: 10.1016/j.ejphar.2023.175512 -
Gene Jul 2023Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling...
BACKGROUND
Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling plays a crucial role in physiological bone mineralization and is associated with several cardiovascular diseases. However, the molecular changes underlying VC is ill defined and it remains unclear whether Hh signaling intervention affects VC.
METHODS
We constructed human primary vascular smooth muscle cell (VSMC) calcification model and performed RNA sequencing. Alizarin red staining and calcium content assay were conducted to identify the occurrence of VC. Three different R packages were applied to determine differentially expressed genes (DEGs). Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out to explore the biological roles of DEGs. qRT-PCR assay was then applied to validate the expression of key genes. By using Connectivity Map (CMAP) analysis, several small molecular drugs targeting these key genes were obtained, including SAG (Hedgehog signaling activator) and cyclopamine (CPN) (Hedgehog signaling inhibitor), which were subsequently used to treat VSMC.
RESULTS
Obvious Alizarin red staining and increased calcium content identified the occurrence of VC. By integrating results from three R packages, we totally obtained 166 DEGs (86 up-regulated and 80 down-regulated), which were significantly enriched in ossification, osteoblast differentiation, and Hh signaling. PPI network analysis identified 10 key genes and CMAP analysis predicted several small molecular drugs targeting these key genes including chlorphenamine, isoeugenol, CPN and phenazopyridine. Notably, our in vitro experiment showed that SAG markedly alleviated VSMC calcification, whereas CPN significantly exacerbated VC.
CONCLUSIONS
Our research provided deeper insight to the pathogenesis of VC and indicated that targeting Hh signaling pathway may represent a potential and effective therapy for VC.
Topics: Humans; Hedgehog Proteins; Calcium; Vascular Calcification; Signal Transduction; Myocytes, Smooth Muscle
PubMed: 37141952
DOI: 10.1016/j.gene.2023.147457 -
The Canadian Veterinary Journal = La... Jul 2021The objective of this study was to describe the clinical findings, medical management, and outcomes of horses with sabulous cystitis, and to describe a high flow bladder...
The objective of this study was to describe the clinical findings, medical management, and outcomes of horses with sabulous cystitis, and to describe a high flow bladder lavage procedure in horses that are standing or under general anesthesia. The medical records of 13 horses diagnosed with sabulous cystitis cystoscopy between 2013 and 2020 were reviewed. Geldings (92%) and Warmbloods (46%) were overrepresented. The most common presenting complaint was urinary incontinence (69%). Complete blood cell count, serum biochemistry profile and urine cytology results were non-specific. Six (46%) horses had various degrees of erosion, ulceration, and hemorrhage of the bladder mucosa. All horses were treated with bladder lavage either with standing sedation ( = 12) or general anesthesia ( = 2), as well as antimicrobials (54%), anti-inflammatory drugs (62%), bethanechol (15%), and phenazopyridine (15%). Most horses (85%) were discharged from the hospital, but only a small percentage (23%) was reported as having no urinary abnormalities on follow-up communication. Key clinical message: Copious bladder lavage with a high flow rate system could mitigate the acute clinical signs and improve the quality of life of horses with sabulous cystitis, but the prognosis for return to previous level of athletic performance and long-term survival is guarded.
Topics: Animals; Cystitis; Horse Diseases; Horses; Male; Quality of Life; Urinary Incontinence
PubMed: 34219784
DOI: No ID Found -
Journal of Infection and Chemotherapy :... Dec 2022Phenazopyridine is an azo dye, which exerts local anesthetic or analgesic action on urinary tract mucosa through an unknown mechanism. Besides its common complications...
INTRODUCTION
Phenazopyridine is an azo dye, which exerts local anesthetic or analgesic action on urinary tract mucosa through an unknown mechanism. Besides its common complications including orange discoloration of the urine and gastrointestinal problems, it may have rare side effects like hemolytic anaemia, methemoglobinemia, renal failure, and skin changes. We reported a paraplegic man with skin ulcers on scretom and right foot after about 3 days of phenazopyridine use CASE REPORT: A 62-year-old man presented with flesh shaped deep ulcers in lower parts of the body. He declared that at first a bluish discoloration was developed in the lower extremities and scrotum skin after use of eight phenazopyridine tablets (200 mg) and then these lesions turned to blisters and ulcers and they were prurient. The patient underwent sonography and CT-angiography; however, no pathologic findings were found. He just received losartan for many years as past drug history. According to the history, a delayed drug hypersensitivity reaction was suspected and the patient wounds healed after using special type of dressings and antibiotic therapy regarding positive wound cultures.
CONCLUSION
Phenazopyridine severe skin changes are hardly reported. We described a case who experienced severe skin reactions and ulcers following phenazopyridine use not related to other complications including renal dysfunction, methemoglobinemia, and hemolytic anemia.
Topics: Anemia, Hemolytic; Anesthetics, Local; Anti-Bacterial Agents; Azo Compounds; Humans; Losartan; Male; Methemoglobinemia; Middle Aged; Phenazopyridine; Skin Ulcer; Ulcer
PubMed: 35963601
DOI: 10.1016/j.jiac.2022.08.005 -
Cureus Jun 2023Sulfhemoglobin is formed by the irreversible bonding of sulfur atoms to the heme molecule. Oxygen is then unable to bind the heme molecule, rendering the hemoglobin...
Sulfhemoglobin is formed by the irreversible bonding of sulfur atoms to the heme molecule. Oxygen is then unable to bind the heme molecule, rendering the hemoglobin molecule unable to carry oxygen. The most common etiology of sulfhemoglobinemia is the use/misuse of sulfur-containing medications such as AZO. Unlike methemoglobin, sulfhemoglobin, due to its irreversible binding, has no antidote, and the treatment is ultimately supportive. We present a case of a 53-year-old female who presented to the emergency room endorsing dysuria and was noted to have abnormally low oxygen saturation (SpO2) despite having high arterial oxygen pressure (PaO2) on blood gas. History was significant for dysuria developed while traveling and the use of over-the-counter AZO four times daily for the past 10 days. She was diagnosed with a presumed dyshemoglobinemia and, upon return of send-out labs, was confirmed to have sulfhemoglobinemia attributed to phenazopyridine. This case highlights the importance of the recognition of potential dyshemoglobinemias and consideration of sulfhemoglobinemia as a potential causative etiology, especially in patients taking sulfur-containing medications.
PubMed: 37496545
DOI: 10.7759/cureus.40944 -
Clinical Pharmacology and Therapeutics Jun 2024Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or...
Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real-world study, we aimed to examine if the administration of presumably risky medications for G6PD-deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.7 million). Within the database, we identified all G6PD-deficient patients by G6PD <6 U/g Hb. Within the G6PD-deficient cohort, we identified all hospitalizations with a discharge diagnosis of hemolysis (January 1, 2010 to December 31, 2022), validated the cases, and identified the culprit event. For the rest of the G6PD-deficient patients with no-hemolysis, we recorded filled prescriptions of medications listed as presumably risky. We identified 31,962 G6PD-deficient patients. Within the cohort, there were 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), of whom 51 (71.8%) had been caused by ingestion of fava beans, six (8.5%) were associated with an infection, and three (4.2%) suggested to be associated with medications (nitrofurantoin, phenazopyridine, and a "pain killer"). Within the 31,875 patients with no major hemolysis, nitrofurantoin has been prescribed safely to 1,366 G6PD-deficient males and females; hundreds/thousands of G6PD-deficient patients had been prescribed safely ciprofloxacin, glibenclamide, ofloxacin, phenazopyridine, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, glimepiride, mesalazine, and sulfacetamide. In this real-world study, we are showing that a list of medications, suspected previously as carrying risks for hemolysis in G6PD-deficient patients, have been prescribed safely to G6PD-deficient patients, providing reassurance to patients, prescribers, and regulators.
PubMed: 38842030
DOI: 10.1002/cpt.3333 -
American Journal of Obstetrics and... Jan 2022Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with...
BACKGROUND
Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with its own associated cost, ease of use, and adverse reactions. Some agents, such as dextrose, are used as an instillation fluid to create a viscosity difference and aid the visualization of a ureteral jet. Others, such as oral phenazopyridine or the intravenous use of sodium fluorescein and indigo carmine, cause a color change of the urine to directly aid the visualization of ureteral jets. Recently, numerous studies have examined the efficacy and surgeon satisfaction of these agents. The studies have also emphasized certain options as associated with a lower cost. However, there have not been any cost studies comparing these agents.
OBJECTIVE
To compare the cost-effectiveness of the following 4 agents that are commonly used in assessing ureteral patency intraoperatively: oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine.
STUDY DESIGN
We constructed a decision-analytic model to compare cystoscopy using oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. Failure to see efflux resulted in work-ups for ureteral obstruction. The probabilities were obtained from published studies, and the probability of successfully seeing efflux ranged from 0.92 with oral phenazopyridine to 0.99 with intravenous indigo carmine. The costs of the agents, adverse effects, and ureteral obstruction work-ups were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, the Healthcare Cost and Utilization Project 2016 database and the FAIR Health Consumer database. The cost of a ureteral obstruction work-up used in our model ranged from $9755 for intraoperative evaluation with retrograde pyelograms and stents to $29,034 for hospitalization. Our primary outcome was the incremental cost-effectiveness ratio per unnecessary work-up for ureteral obstruction avoided. Sensitivity analyses were performed to identify the key uncertainties.
RESULTS
Oral phenazopyridine, followed by an intravenous agent if needed, had a mean cost of $110 per patient. Dextrose averaged $151 more per patient, with only a slight improvement in avoiding unnecessary ureteral obstruction work-ups and a higher cost associated with adverse reactions (incremental cost-effectiveness ratio, $62,000). Intravenous agents cost approximately $1000 more per patient and were less effective at preventing unnecessary work-ups. Sensitivity analyses did not identify any thresholds that would significantly change the outcomes.
CONCLUSION
Our model suggests that oral phenazopyridine and dextrose instillation are the least expensive and the most effective agents to aid in the visualization of ureteral patency during intraoperative cystoscopy, although dextrose is associated with higher costs owing to a higher rate of adverse reactions (primarily urinary tract infections). Intravenous sodium fluorescein and indigo carmine are historically popular first-choice agents. However, they were found to be more expensive and less effective as primary agents in our model and should likely be reserved for use as secondary agents in the event that the visualization of ureteral jets is unclear with the initial use of phenazopyridine or dextrose.
Topics: Coloring Agents; Cost-Benefit Analysis; Cystoscopy; Female; Fluorescein; Gynecologic Surgical Procedures; Humans; Indigo Carmine; Intraoperative Complications; North Carolina; Phenazopyridine; Ureteral Obstruction
PubMed: 34487702
DOI: 10.1016/j.ajog.2021.08.055