-
Cureus Jan 2023Methemoglobinemia is a condition caused by increased methemoglobin, a reduced form of hemoglobin, in the blood. This causes the molecules to bind oxygen more tightly and...
Methemoglobinemia is a condition caused by increased methemoglobin, a reduced form of hemoglobin, in the blood. This causes the molecules to bind oxygen more tightly and decreases their ability to release that oxygen to tissue. Most cases of methemoglobinemia are acquired and occur either in pediatric populations or in individuals with predisposing conditions. This report illustrates a case of an otherwise healthy 31-year-old patient presenting to the emergency department with cyanosis of the hands and mouth and an O2 saturation of 78% after taking increased doses of the over-the-counter medication phenazopyridine. A "chocolate-brown" color of her arterial blood, and increased methemoglobin levels of 20.2%, confirmed the diagnosis of methemoglobinemia. She was treated with both methylene blue and ascorbic acid, and her oxygen saturation and serum chemistry returned to normal levels within a few hours. The case highlights the importance of discussing the dosage of all over-the-counter medications with patients and recognizing the signs and symptoms of methemoglobinemia.
PubMed: 36788851
DOI: 10.7759/cureus.33715 -
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 -
European Urology Focus Jul 2023The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required.
OBJECTIVE
To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs.
DESIGN, SETTING, AND PARTICIPANTS
This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml).
INTERVENTION
The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ and Fisher's exact tests; a p value <0.05 was considered significant.
RESULTS AND LIMITATIONS
Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated.
CONCLUSIONS
The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs.
PATIENT SUMMARY
Our results show that for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo.
Topics: Female; Humans; Mannose; Bacteriuria; Escherichia coli; Treatment Outcome; India; Urinary Tract Infections; Escherichia coli Infections; Dietary Supplements; Prebiotics
PubMed: 36621376
DOI: 10.1016/j.euf.2022.12.013 -
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 -
Clinics and Practice Oct 2022Methemoglobinemia is a rare blood disorder characterized by the oxidation of heme iron from ferrous (Fe) to ferric (Fe) state, which increases oxygen affinity and...
Methemoglobinemia is a rare blood disorder characterized by the oxidation of heme iron from ferrous (Fe) to ferric (Fe) state, which increases oxygen affinity and impairs oxygen release to the tissue causing hypoxia. It can be congenital or acquired; however, most cases are acquired and caused by exogenous substances such as medications, chemicals, and environmental substances. Phenazopyridine is an over-the-counter urinary analgesic medication commonly used for symptomatic relief of dysuria and has been reported to cause methemoglobinemia. However, only a handful of cases of phenazopyridine-induced methemoglobinemia have been reported. We present a case of an 89-year-old female who presented with severe hypoxia, shortness of breath, headache, nausea, and dizziness caused by phenazopyridine-induced methemoglobinemia. She was found to have a methemoglobin level of 21.5% and was treated with methylene blue, leading to a rapid improvement of her symptoms. She was taking one over-the-counter phenazopyridine 200 mg tablet three times daily for two weeks for her chronic dysuria. This case highlights the need to have a high index of suspicion of phenazopyridine-induced methemoglobinemia in a patient presenting with unexplained shortness of breath with a history of phenazopyridine use as it could lead to severe methemoglobinemia with hypoxia that could potentially be fatal if not promptly diagnosed.
PubMed: 36412668
DOI: 10.3390/clinpract12060089 -
Journal of Thermal Biology Oct 2022Injury to the intestinal epithelial cells and loss of the intestinal barrier are critical to heatstroke. To reveal the mechanism through which heatstroke leads to...
Injury to the intestinal epithelial cells and loss of the intestinal barrier are critical to heatstroke. To reveal the mechanism through which heatstroke leads to intestinal epithelial injury, the relationship between reactive oxygen species (ROS), c-Jun NH2-terminal kinase (JNK), and lysosomes were studied in intestinal epithelial cells subjected to heat stress. Cells of heat stress groups were incubated at 43 °C for 1 h, then incubated at 37 °C as indicated. Control group cells were incubated at 37 °C. Cell-counting kit-8 assay was used to assess cell viability. Cells were labeled with 2'-7'dichlorofluorescin diacetate and acridine orange (AO) staining, respectively, the total ROS and AO were detected by confocal laser scanning microscopy and flow cytometry. Apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate/prodium iodide staining, the expressions of mitogen-activated protein kinases were detected by western blotting. Heat stress induced apoptosis and inhibited cell viability, the production of ROS, and lysosomal injury in IEC-6 cells. After pretreatment with the lysosomal cathepsin inhibitor E64, the JNK inhibitor SP600125, or the ROS scavenger NAC, the effect of heat stress on apoptosis or lysosomal injury was significantly attenuated. In conclusion, heat stress induced apoptosis, lysosomal injury, and the accumulation of ROS in IEC-6 cells; mechanistically, this occurred through the ROS-induced activation of JNK signaling, which mediated the lysosomal injury and ultimately apoptosis.
Topics: Acridine Orange; Animals; Annexin A5; Apoptosis; Cathepsins; Epithelial Cells; Fluoresceins; Heat Stress Disorders; Heat Stroke; Heat-Shock Response; Intestinal Diseases; Iodides; Isothiocyanates; Lysosomes; Mitogen-Activated Protein Kinases; Phenazopyridine; Rats; Reactive Oxygen Species
PubMed: 36195392
DOI: 10.1016/j.jtherbio.2022.103326 -
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 -
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 -
Clinical Practice and Cases in... May 2022As ketamine gains traction as an alternative to opiates in the treatment of chronic pain, ketamine-induced ulcerative cystitis is now being recognized as a complication...
INTRODUCTION
As ketamine gains traction as an alternative to opiates in the treatment of chronic pain, ketamine-induced ulcerative cystitis is now being recognized as a complication of its use. The first-line treatment is phenazopyridine, an over-the-counter medication for dysuria that historically has been known to cause methemoglobinemia. This report details the case of a patient presenting to the emergency department (ED) with methemoglobinemia.
CASE REPORT
A 66-year-old woman with a complicated medical history presented to the ED with anemia and hypoxia after extended use of phenazopyridine for treatment of ketamine-induced ulcerative cystitis. She was found to have methemoglobinemia secondary to phenazopyridine used to treat her ketamine-induced ulcerative cystitis, a previously undocumented sequelae of chronic ketamine use. She was admitted to the hospital for three days and made a full recovery.
CONCLUSION
This case highlights the need to suspect ketamine-induced ulcerative cystitis in patients who use ketamine chronically and be judicious in the use of phenazopyridine for symptom management to prevent life-threatening complications.
PubMed: 35701344
DOI: 10.5811/cpcem.2022.1.55277