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Food and Chemical Toxicology : An... Nov 2023Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and...
BACKGROUND
Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and movement. Nevertheless, preventing emesis during chemotherapy or other situations is a significant issue for researchers. Hence, the majority view contends that successfully combining therapy is the best course of action. In-vivo analysis offers a more comprehensive grasp of how compounds behave within a complex biological environment, whereas in-silico evaluation refers to the use of computational models to forecast biological interactions.
OBJECTIVES
The objectives of the present study were to evaluate the effects of Sclareol (SCL) on copper sulphate-induced emetic chicks and to investigate the combined effects of these compounds using a conventional co-treatment approach and in-silico study.
METHODS
SCL (5, 10, and 15 mg/kg) administered orally with or without pre-treatment with anti-emetic drugs (Ondansetron (ODN): 24 mg/kg, Domperidone (DOM): 80 mg/kg, Hyoscine butylbromide (HYS): 100 mg/kg, and Promethazine hydrochloride (PRO): 100 mg/kg) to illustrate the effects and the potential involvement with 5HT, D, M/ACh, H, or NK receptors by SCL. Furthermore, an in-silico analysis was conducted to forecast the role of these receptors in the emetic process.
RESULTS
The results suggest that SCL exerted a dose-dependent anti-emetic effect on the chicks. Pretreatment with SCL-10 significantly minimized the number of retches and lengthened the emesis tendency of the experimental animals. SCL-10 significantly increased the anti-emetic effects of ODN and DOM. However, compared to the ODN-treated group, (SCL-10 + ODN) group considerably (p < 0.0001) extended the latency duration (109.40 ± 1.03 s) and significantly (p < 0.01) decreased the number of retches (20.00 ± 0.70), indicating an anti-emetic effect on the test animals. In in-silico analysis, SCL exhibited promising binding affinities with suggesting receptors.
CONCLUSION
SCL-10 exerted an inhibitory-like effect on emetic chicks, probably through the interaction of the 5HT and D receptors. Further studies are highly appreciated to validate this study and determine the precise mechanism(s) behind the anti-emetic effects of SCL. We expect that SCL-10 may be utilized as an antiemetic treatment in a single dosage form or that it may function as a synergist with other traditional medicines.
Topics: Animals; Antiemetics; Serotonin; Emetics; Vomiting
PubMed: 37863383
DOI: 10.1016/j.fct.2023.114068 -
Annals of Medicine 2023The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care.
INTRODUCTION
The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion.
PATIENTS AND METHODS
The efficacy of oral domperidone plus standard of care (SOC; = 87) versus placebo plus SOC ( = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes.
RESULTS
A significant reduction in the viral load was observed ( < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized.
CONCLUSION
Results do not prove the use of domperidone as antiviral in patients with COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Domperidone; Double-Blind Method; Viral Load; Treatment Outcome; Antiviral Agents; Primary Health Care
PubMed: 37847999
DOI: 10.1080/07853890.2023.2268535 -
The Journal of Comparative Neurology Feb 2024Dopamine is a neurotransmitter involved in oxygen sensing and control of reflex hyperventilation. In aquatic vertebrates, oxygen sensing occurs in the gills via...
Dopamine is a neurotransmitter involved in oxygen sensing and control of reflex hyperventilation. In aquatic vertebrates, oxygen sensing occurs in the gills via chemoreceptive neuroepithelial cells (NECs), but a mechanism for dopamine in autonomic control of ventilation has not been defined. We used immunohistochemistry and confocal microscopy to map the distribution of tyrosine hydroxylase (TH), an enzyme necessary for dopamine synthesis, in the gills of zebrafish. TH was found in nerve fibers of the gill filaments and respiratory lamellae. We further identified dopamine active transporter (dat) and vesicular monoamine transporter (vmat2) expression in neurons of the gill filaments using transgenic lines. Moreover, TH- and dat-positive nerve fibers innervated NECs. In chemical screening assays, domperidone, a D receptor antagonist, increased ventilation frequency in zebrafish larvae in a dose-dependent manner. When larvae were confronted with acute hypoxia, the D agonist, quinpirole, abolished the hyperventilatory response. Quantitative polymerase chain reaction confirmed expression of drd2a and drd2b (genes encoding D receptors) in the gills, and their relative abundance decreased following acclimation to hypoxia for 48 h. We localized D receptor immunoreactivity to NECs in the efferent gill filament epithelium, and a novel cell type in the afferent filament epithelium. We provide evidence for the synthesis and storage of dopamine by sensory nerve terminals that innervate NECs. We further suggest that D receptors on presynaptic NECs provide a feedback mechanism that attenuates the chemoreceptor response to hypoxia. Our studies suggest that a fundamental, modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution.
Topics: Animals; Zebrafish; Gills; Dopamine; Hypoxia; Oxygen; Larva
PubMed: 37837632
DOI: 10.1002/cne.25548 -
Heliyon Sep 2023Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which...
Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.
PubMed: 37809676
DOI: 10.1016/j.heliyon.2023.e19904 -
BMJ Open Oct 2023Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.
METHODS AND ANALYSIS
We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.
ETHICS AND DISSEMINATION
This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.
TRIAL REGISTRATION NUMBER
International Clinical Trial Registry Platform: NL9438.
Topics: Humans; Feasibility Studies; Fecal Microbiota Transplantation; Feces; Levodopa; Parkinson Disease; Pilot Projects; Prospective Studies; Treatment Outcome
PubMed: 37798034
DOI: 10.1136/bmjopen-2023-071766 -
Parasites & Vectors Oct 2023Domperidone (Leisguard) is an immunomodulatory drug used as a preventive measure in healthy dogs. However, no studies have been published in healthy Leishmania...
A blinded, randomized and controlled multicenter clinical trial to assess the efficacy and safety of Leisguard as an immunotherapeutic treatment for healthy Leishmania infantum-seropositive dogs.
BACKGROUND
Domperidone (Leisguard) is an immunomodulatory drug used as a preventive measure in healthy dogs. However, no studies have been published in healthy Leishmania infantum-seropositive dogs. The aim of this study was to evaluate the clinical efficacy and safety of domperidone as immunotherapy in Leishmania-seropositive healthy dogs.
METHODS
Sixty-seven dogs were treated with domperidone at 0.5 mg/kg and 44 dogs received placebo, once daily for 4 consecutive weeks. Monthly treatments were repeated every 4 months until the end of the 1-year follow-up period. Veterinary examinations were performed on days 0, 30, 120, 150, 240, 270 and 360. Samples of blood and urine were collected on days 0, 120, 240 and 360 for routine laboratory tests and quantitative in-house ELISA for the detection of L. infantum-specific antibodies. Furthermore, Leishmania real-time PCR and IFN-γ ELISA were performed at day 0 and the end of the study. Dogs that developed disease were withdrawn from the study and classified as sick dogs. Adverse drug reactions were reported.
RESULTS
Thirty dogs developed disease during the follow-up period: 13/67 (19.4%) in the group treated with domperidone and 17/44 (38.6%) in the placebo-treated group (P = 0.03). Low-seropositive dogs treated with domperidone (4/40, 9.1%) were significantly less likely to develop disease compared to low-seropositive dogs treated with placebo (7/24, 29.2%; P = 0.04), while no differences were found between domperidone (9/23, 39.1%) and placebo (10/20, 50%) in medium- to high-seropositive dogs. At the end of the study, a higher proportion of Leishmania PCR-positive dogs was observed in the placebo-treated group (16/33, 48.5%) compared to the domperidone group (13/51, 25.5%; P = 0.04). Furthermore, low-seropositive dogs treated with domperidone with an increase of IFN-γ concentration presented a higher increase than those treated with placebo at the end of the study. Four dogs treated with domperidone presented self-limiting diarrhea.
CONCLUSIONS
Healthy dogs with low L. infantum antibody levels treated with domperidone were less likely to develop disease compared to placebo-treated dogs. Furthermore, domperidone presented a good safety profile.
Topics: Animals; Dogs; Leishmania infantum; Leishmaniasis, Visceral; Domperidone; Antibodies, Protozoan; Real-Time Polymerase Chain Reaction; Dog Diseases; Immunotherapy
PubMed: 37794502
DOI: 10.1186/s13071-023-05903-0 -
African Journal of Reproductive Health Jul 2023Plook-Fire-Thatu is a traditional Thai medication designed to assist breastfeeding moms. However, no documented clinical research on its efficacy exists. Therefore, the...
Plook-Fire-Thatu is a traditional Thai medication designed to assist breastfeeding moms. However, no documented clinical research on its efficacy exists. Therefore, the authors recruited women who had a singleton baby vaginally between June 2019 and July 2020 and randomly allocated them to one of three groups: Plook-Fire-Thatu, Domperidone, or Placebo. The test-weight method was used to compare breastmilk amounts. During the hospital stay, all volunteers and newborns were followed for adverse effects. There were three groups of participants: Plook-Fire-Thatu 78, Domperidone 74, and Placebo 76. On the third postpartum day, the Plook-Fire-Thatu group exhibited a statistically significant increase in breastmilk quantity (F=15.11, p≤0.01). The mean body temperature of postpartum women in the Plook-Fire-Thatu group on the third day was significantly higher than in the placebo group. (F=4.22, p=0.016). Participants and infants in the intervention groups experienced a few adverse effects. In comparison to domperidone, Plook-Fire-Thatu has been discovered to be a natural way to increase postpartum breastmilk supply.
PubMed: 37742337
DOI: 10.29063/ajrh2023/v27i7.9 -
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 -
International Journal of Rheumatic... Oct 2023Systemic sclerosis (SSc) patients often become refractory to proton pump inhibitors (PPI)-a standard treatment for gastroesophageal reflux disease (GERD)-and intolerant...
BACKGROUND
Systemic sclerosis (SSc) patients often become refractory to proton pump inhibitors (PPI)-a standard treatment for gastroesophageal reflux disease (GERD)-and intolerant to PPI in combination with domperidone. PPI with alginic acid is an alternative treatment option, but alginic acid is costly.
OBJECTIVES
We compared the costs and effectiveness of alginic acid plus PPI versus standard treatments (PPI with/without antacids as needed and lifestyle modifications) for GERD in SSc patients unsuitable for, or intolerant to, domperidone.
METHODS
An economic evaluation using the Markov model was conducted among SSc patients aged between 40 and 65 years with GERD, having a partial or non-response to 4 weeks of standard-dose omeprazole (40 mg/day) and being unsuitable for or intolerant to domperidone. Using a societal perspective, we computed the incremental cost-effectiveness ratios (ICERs) in terms of Thai baht (THB) per quality-adjusted life-year (QALY) between a combination of alginic acid plus PPI and standard treatment for GERD. The lifetime time horizon was used.
RESULTS
The ICER for alginic acid plus PPI versus standard treatments was 377 101 THB/QALY. According to the one-way sensitivity analysis, the cost of alginic acid was the most impactful parameter. If the market prices of alginic acid plus PPI were reduced by 61%, this treatment option would become cost-effective at the willingness-to-pay threshold of 160 000 THB/QALY (34.68 THB/USD data on 25 May 2023). Furthermore, if alginic acid were included in the public health insurance program, the national budget would be increased by 66 313 THB per patient, resulting in an overall budget increase of 5 106 101 to 8 885 942 THB compared with the standard treatment.
CONCLUSIONS
Alginic acid plus PPI does not represent good value for money compared with the standard treatment among such SSc patients in Thailand unless its price is reduced significantly.
Topics: Humans; Infant, Newborn; Proton Pump Inhibitors; Alginic Acid; Cost-Benefit Analysis; Domperidone; Gastroesophageal Reflux; Scleroderma, Systemic
PubMed: 37665078
DOI: 10.1111/1756-185X.14868 -
International Journal of Medical... 2023Herbal galactagogues have been widely used as a treatment for postpartum hypogalactia due to the potential side effects associated with pharmacological therapy....
Herbal galactagogues have been widely used as a treatment for postpartum hypogalactia due to the potential side effects associated with pharmacological therapy. Tri-Than-Thip (Tri-TT) is a Thai herbal medicine remedy that contains three main components: . These components are believed to have properties that contribute to milk production. However, despite the traditional use of Tri-TT, there is a lack of academic evidence supporting its efficacy in enhancing milk production. Therefore, the purpose of this study was to investigate the effect of Tri-TT on milk production and determine if it has a galactagogue effect. The weight suckle weight model was used to determine total milk production in lactating rats, while histological analysis was performed to assess the alveolar diameter of the mammary gland. The findings of this study revealed a significant increase in total milk production among lactating rats treated with 500 mg/kg of Tri-TT, compared to the control group. Furthermore, both the Tri-TT and Domperidone-treated groups exhibited a larger alveolar diameter of the mammary gland in comparison to the control group. In summary, these findings provide supportive evidence for the galactagogue activity of Tri-TT. The observed enhancement in milk production may be associated with Tri-TT could potentially be attributed to its ability to widen the alveolar diameter of the mammary gland, thereby facilitating increased milk volume.
Topics: Female; Rats; Animals; Milk; Lactation; Galactogogues
PubMed: 37575273
DOI: 10.7150/ijms.83869