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Brazilian Journal of Microbiology :... Mar 2022Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for...
Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of S. aureus may generate weaker selection for resistant strains, anti-virulence agents disarm the pathogen instead of killing it. In this study, the ability of the FDA-approved drugs domperidone, candesartan, and miconazole as inhibitors of S. aureus virulence was investigated. The effect of tested drugs was evaluated against biofilm formation, lipase, protease, hemolysin, and staphyloxanthin production by using phenotypic and genotypic methods. At sub-inhibitory concentrations, candesartan, domperidone, and miconazole showed a significant inhibition of hemolysin (75.8-96%), staphyloxanthin (81.2-85%), lipase (50-65%), protease (40-64%), and biofilm formation (71.4-90%). Domperidone and candesartan have similar activity and were more powerful than miconazole against S. aureus virulence. The hemolysins and lipase inhibition were the greatest under the domperidone effect. Candesartan showed a remarkable reduction in staphyloxanthin production. The highest inhibitory effect of proteolytic activity was obtained with domperidone and candesartan. Biofilm was significantly reduced by miconazole. Expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes were significantly reduced under candesartan (68.98-82.7%), domperidone (62.6-77.2%), and miconazole (32.96-52.6%) at sub-MIC concentrations. Candesartan showed the highest inhibition activity against crtM, sigB, sarA, agrA, hla, and icaA expression followed by domperidone then miconazole. Domperidone showed the highest downregulation activity against fnbA gene. In conclusion, candesartan, domperidone, and miconazole could serve as anti-virulence agents for attenuation of S. aureus pathogenicity.
Topics: Anti-Bacterial Agents; Benzimidazoles; Biofilms; Biphenyl Compounds; Domperidone; Humans; Methicillin-Resistant Staphylococcus aureus; Miconazole; Staphylococcal Infections; Staphylococcus aureus; Tetrazoles; Virulence
PubMed: 34773629
DOI: 10.1007/s42770-021-00655-4 -
Indian Journal of Endocrinology and... 2018Recent increase in the non-specific use of prokinetics in clinical practice may alter the etiological profile of hyperprolactinemia and galactorrhea. Hence, we have...
BACKGROUND
Recent increase in the non-specific use of prokinetics in clinical practice may alter the etiological profile of hyperprolactinemia and galactorrhea. Hence, we have studied the etiological profile of patients presenting with galactorrhea and characteristics of drug-induced galactorrhea.
MATERIALS AND METHODS
This retrospective study was conducted at a tertiary health care center from South India. Patients who presented with or referred for galactorrhea and/or hyperprolactinemia to the Department of Endocrinology between January 2017 and December 2017 were included in the study.
RESULTS
Forty women presented with or referred for galactorrhea to the Department of Endocrinology during the study period. Thirty-two patients had received drugs that are associated with hyperprolactinemia (levosulpiride in 15, domperidone in 13, ranitidine in 2, oral contraceptive pill in 1, and amisulpiride in 1) of whom etiology was proved in 27 patients, whereas in four patients the cause was inconclusive due to lack of follow-up. The patient on amisulpiride was found to have concomitant pituitary microadenoma. Idiopathic galactorrhea ( = 2), idiopathic hyperprolactinemia ( = 2), and prolactinoma ( = 4) accounted for the remaining cases. Six patients with prokinetic-induced galactorrhea had received cabergoline inspite of which hyperprolactinemia and/or galactorrhea persisted and six patients had also undergone pituitary magnetic resonance imaging (MRI) for evaluation of galactorrhea.
CONCLUSIONS
Prokinetic use is the most common cause of galactorrhea in our study and often was investigated with costly tests and treated with D2 agonists unnecessarily. Hence, there is a need to ensure measures to reduce the non-specific use of prokinetics and increase awareness regarding the occurrence of galactorrhea with prokinetics use, to reduce unnecessary investigations and treatment.
PubMed: 30148095
DOI: 10.4103/ijem.IJEM_89_18 -
Clinical Case Reports Apr 2022Pityriasis rosea is a common, acute, self limiting inflammatory skin disease. Pityriasis rosea-like eruptions (PR-LE) have been reported after drugs. The clinical...
Pityriasis rosea is a common, acute, self limiting inflammatory skin disease. Pityriasis rosea-like eruptions (PR-LE) have been reported after drugs. The clinical presentation of PR-LE can be distinguished from pityriasis rosea. We reporte a 41-year-old woman who developed PR-LE 5 days after administration domperidone.
PubMed: 35414911
DOI: 10.1002/ccr3.5674 -
Journal of Dairy Science Jan 2016In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of... (Review)
Review
In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear, because inconsistent effects on milk yield have been observed with the short-term suppression of PRL by bromocriptine. Therefore, several experiments have been conducted to assess the galactopoietic role of PRL. In an initial experiment, cows in early lactation received daily injections of the dopamine agonist quinagolide for 9 wk. Quinagolide reduced milking-induced PRL release and caused a faster decline in milk production. Quinagolide also reduced mammary epithelial cell activity, survival, and proliferation. In goats, cabergoline, another dopamine agonist, caused a 28% decrease in milk yield the day after injection. In another experiment, cows were injected for 5d with quinagolide, with quinagolide plus bovine PRL injected at milking time, or with vehicles only. Again, quinagolide reduced milk, protein, and lactose yields. Although PRL injections were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of mammary epithelial cells purified from milk. Recently, our team stimulated PRL secretion with daily injections of the dopamine antagonist domperidone for 5 wk. Milk production increased gradually and was greater in domperidone-treated cows during the last 4 wk of the treatment period. In most experiments where PRL secretion was manipulated, feed intake paralleled the changes of PRL concentration, supporting the idea that PRL increases feed intake to provide the nutrients necessary to support lactation in dairy ruminants. In late-lactation cows, quinagolide and cabergoline decreased milk production within the first day of treatment and induced more rapid changes in several markers of mammary gland involution after drying-off. In addition, quinagolide improved the resistance to intramammary infection, suggesting that PRL inhibition could be an alternative strategy for facilitating drying-off. Prolactin appears to directly affect mammary gland functions, but mammary gland responsiveness to PRL appears to be modulated by local and systemic factors. Therefore, the modulation of the number and isoforms of the PRL receptors as well as the expression of intracellular modulators of cell signaling in the mammary gland require further investigation. In conclusion, these data, combined with those from other studies, provide a good body of evidence that PRL is galactopoietic in dairy ruminants.
Topics: Aminoquinolines; Animals; Cattle; Epithelial Cells; Female; Goats; Lactation; Lactose; Mammary Glands, Animal; Milk; Milk Proteins; Prolactin
PubMed: 26547648
DOI: 10.3168/jds.2015-10035 -
Annals of Palliative Medicine Jan 2019Cancer cachexia (CC) is one of the most distressing syndromes for both patients and their families. CC can have an impact on patient reported quality of life and overall... (Review)
Review
Cancer cachexia (CC) is one of the most distressing syndromes for both patients and their families. CC can have an impact on patient reported quality of life and overall survival. It is often associated with symptoms such as fatigue, depressed mood, early satiety, and anorexia. Prokinetic agents have been found to improve chronic nausea and early satiety associated with CC. Among the prokinetic agents, metoclopramide is one of the best studied medications. The role of the other prokinetic agents, such as domperidone, erythromycin, haloperidol, levosulpiride, tegaserod, cisapride, mosapride, renzapride, and prucalopride is unclear for use in cachectic cancer patients due to their side effect profile and limited efficacy studies in cancer patients. There has been an increased interest in the use of ghrelin-receptor agonists for the treatment of CC. Anamorelin HCl is a highly selective, novel ghrelin receptor agonist. A meta-analysis was conducted of the recent randomized trials using anamorelin (daily dose of 50 and 100 mg daily). Results show that both total body weight and lean body mass were significantly increased from baseline in the anamorelin group. Anamorelin did not improve overall survival or hand grip strength, and there were no significant differences between groups for frequency or severity of any adverse events. In this review, the authors discuss the available evidence for the use of prokinetics such as metoclopramide and ghrelin receptor agonists for the treatment of CC.
Topics: Cachexia; Forecasting; Gastrointestinal Agents; Ghrelin; Humans; Hydrazines; Metoclopramide; Neoplasms; Oligopeptides
PubMed: 30525771
DOI: 10.21037/apm.2018.11.01 -
Advances in Clinical and Experimental... Sep 2023Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover,...
BACKGROUND
Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate.
OBJECTIVES
The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment.
MATERIAL AND METHODS
We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3.
RESULTS
All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects.
CONCLUSION
Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure.
PubMed: 37665080
DOI: 10.17219/acem/171001 -
Toxins Jun 2023toxin (PT) and C2 toxin are ADP-ribosylating toxins causing severe diseases in humans and animals. They share a common translocation mechanism requiring the cellular...
toxin (PT) and C2 toxin are ADP-ribosylating toxins causing severe diseases in humans and animals. They share a common translocation mechanism requiring the cellular chaperones Hsp90 and Hsp70, cyclophilins, and FK506-binding proteins to transport the toxins' enzyme subunits into the cytosol. Inhibitors of chaperone activities have been shown to reduce the amount of transported enzyme subunits into the cytosol of cells, thus protecting cells from intoxication by these toxins. Recently, domperidone, an approved dopamine receptor antagonist drug, was found to inhibit Hsp70 activity. Since Hsp70 is required for cellular toxin uptake, we hypothesized that domperidone also protects cells from intoxication with PT and C2. The inhibition of intoxication by domperidone was demonstrated by analyzing the ADP-ribosylation status of the toxins' specific substrates. Domperidone had no inhibitory effect on the receptor-binding or enzyme activity of the toxins, but it inhibited the pH-driven membrane translocation of the enzyme subunit of the C2 toxin and reduced the amount of PTS1 in cells. Taken together, our results indicate that domperidone is a potent inhibitor of PT and C2 toxins in cells and therefore might have therapeutic potential by repurposing domperidone to treat diseases caused by bacterial toxins that require Hsp70 for their cellular uptake.
Topics: Animals; Humans; Bordetella pertussis; Domperidone; Botulinum Toxins; Bacterial Toxins; Pertussis Toxin; ADP Ribose Transferases
PubMed: 37505681
DOI: 10.3390/toxins15070412 -
Scientific Reports Jul 2020There has been controversy over the cardiovascular safety of domperidone, attributable to the lack of a well-designed study as well as inconsistent results. This study...
There has been controversy over the cardiovascular safety of domperidone, attributable to the lack of a well-designed study as well as inconsistent results. This study aimed to examine the risk of severe domperidone-induced ventricular arrhythmia (VA), compared to mosapride, itopride, or non-use of all three prokinetics, in the general population. We conducted a population-based, self-controlled case series analysis. Enrolled subjects were individuals who were diagnosed with severe VA and were prescribed domperidone, mosapride, or itopride from 2003 to 2013 in the National Health Insurance Service-National Sample Cohort. The incidence rate ratio for severe VA was measured during exposure to prokinetics and compared with unexposed periods and itopride (no-proarrhythmic effect)-exposure periods, as control. A total of 2,817 subjects were included. Domperidone, mosapride, or itopride use was associated with increased risk of severe VA, compared with non-use (adjusted incidence rate ratios (IRR) of 1.342 (95% CI 1.096-1.642), 1.350 (95% CI 1.105-1.650), and 1.486 (95% CI 1.196-1.845), respectively). The risk of severe domperidone-induced VA was lower, compared to that of itopride [adjusted IRR of 0.548 (95% CI 0.345-0.870)]. Of the subjects who had been prescribed all three prokinetics, domperidone-exposure was associated with a lower risk of severe VA, compared to itopride-exposure (crude IRR, 0.571; 0.358-0.912). Mosapride-exposure did not show IRR difference for severe VA, compared to itopride-exposure. Domperidone, mosapride, or itopride use is associated with an increased risk of severe VA. However, the magnitude of association was modest and domperidone use does not increase further the risk, compared with other prokinetics.
Topics: Adolescent; Adult; Aged; Antiemetics; Arrhythmias, Cardiac; Benzamides; Benzyl Compounds; Child; Child, Preschool; Databases, Factual; Domperidone; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Morpholines; Risk Factors; Severity of Illness Index; Young Adult
PubMed: 32699312
DOI: 10.1038/s41598-020-69053-4 -
Medicine Mar 2021Bowel preparation is essential to the success of colonoscopy. However, many patients cannot finish the preparation due to nausea and vomiting when taking polyethylene... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bowel preparation is essential to the success of colonoscopy. However, many patients cannot finish the preparation due to nausea and vomiting when taking polyethylene glycol (PEG). Dopamine-2 receptor antagonists, such as domperidone and sulpiride, are classical antiemetic drugs. This study aimed to explore the effect of domperidone and sulpiride on reducing the discomforts associated with PEG.
METHODS
Patients scheduled for colonoscopy were enrolled and randomly allocated into 3 groups. Patients in the domperidone group (Dom group) or sulpiride group (Sul group) took 2 doses of domperidone or sulpiride before PEG. Patients in the control group (Con group) followed the regular routine of PEG. Discomforts during bowel preparation and the quality of bowel preparation were assessed.
RESULTS
A total of 306 patients were enrolled. The participants in the Dom group and Sul group completed PEG better and had fewer abdominal discomforts than those in the Con group. The severity of nausea and abdominal fullness was lower in the Dom group and Sul group. The quality of bowel preparation was better in the Dom group and Sul group than Con group.
CONCLUSIONS
Domperidone and sulpiride could reduce the PEG-related discomfort and improve the quality of bowel preparation. This method may be a promising way to improve the satisfaction of bowel preparation for both patients and endoscopists.
Topics: Adult; Aged; Antiemetics; Cathartics; Colon; Colonoscopy; Domperidone; Female; Humans; Incidence; Intestinal Mucosa; Male; Middle Aged; Nausea; Patient Satisfaction; Polyethylene Glycols; Severity of Illness Index; Sulpiride; Treatment Outcome; Vomiting
PubMed: 33725858
DOI: 10.1097/MD.0000000000024947 -
Translational Pediatrics Feb 2021The complete examination rate of video capsule endoscopy can be increased by reduced gastric transit time (GTT) and or small bowel transit time (SBTT). This study aims...
BACKGROUND
The complete examination rate of video capsule endoscopy can be increased by reduced gastric transit time (GTT) and or small bowel transit time (SBTT). This study aims to examine whether the prokinetic domperidone reduces GTT and/or SBTT in pediatric patients undergoing video capsule endoscopy (VCE).
METHODS
We performed a single-center randomized controlled trial (n=200) to evaluate the effect of domperidone on GTT and SBTT among pediatric patients in a tertiary university-affiliated hospital for children. We explored whether patients randomized to domperidone had increased GTT, SBTT (primary outcomes) or higher complete examination rate (secondary outcome). The safety outcomes were the adverse effects in the domperidone group. This study was registered on ClinicalTrials.gov (NCT03662113).
RESULTS
Demographic features including gender and age were similar between the 100 patients of the domperidone group and the 100 patients of the control group. The median GTT was 67.5 minutes (44.8-117.5) in the domperidone group and 80.0 minutes (42.0-128.0) in the control group, while the median SBTT was 317 minutes (231-436) and 323 minutes (225-426), respectively. There were no significant differences in GTT (P=0.49) and SBTT (P=0.52) between the two groups. The complete examination rate was 97% and 98% in the domperidone and control groups, respectively (P=1.00).
CONCLUSIONS
Domperidone shows no effect on GTT, SBTT and complete examination rate in pediatric patients receiving VCE.
PubMed: 33708520
DOI: 10.21037/tp-20-273