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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 -
Multiple Sclerosis and Related Disorders May 2024Identification of therapies to promote repair in multiple sclerosis is challenged by the lack of an accepted trial model and associated outcome measures. The goal of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Identification of therapies to promote repair in multiple sclerosis is challenged by the lack of an accepted trial model and associated outcome measures. The goal of this study was to determine the feasibility of a new trial model that enrolls disease modifying therapy (DMT)-treated relapsing-remitting multiple sclerosis (RRMS) participants who have enhancing lesions on clinically indicated brain MRI, and to explore estimates of lesion repair using MRI.
METHODS
This was a single site randomized controlled clinical trial. Recruitment took place between November 2015 and January 2019, with final follow-up in February 2019. DMT-treated RRMS participants aged 18-60 years with at least one gadolinium-enhancing lesion on clinically indicated brain MRI were included. Participants were randomized 2:1 to oral domperidone add-on 10-mg three times daily for 16 weeks or no add-on treatment (control). The primary outcomes were feasibility of the model pre-defined as recruitment of 24 participants within 36 months with a 79 % completion rate, and MRI outcomes of lesion repair measured at 16 and 32 weeks using texture analysis, magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI). The impact of domperidone on serum prolactin at 6 and 16 weeks was also evaluated.
RESULTS
Of 237 RRMS participants screened, 17 (14 women) were randomized: 12 to domperidone add-on and 5 to control. All completed the study. Median (range) age was 38.9 (26.7-55.9) years; EDSS was 1.5 (1.0-3.5); and disease duration was 12.9 (2.9-23.3) years. Both groups showed improvement in MRI texture and diffusion fractional anisotropy (FA) at 32 weeks, and the domperidone group demonstrated additional recovery at 16 weeks in both texture and FA. There was no significant group difference in any MRI outcome. Of the 12 domperidone participants, 7 had ≥4x higher serum prolactin than normal. There were no serious adverse events.
CONCLUSION
The recruitment target was not met and therefore the trial model was not feasible despite a full completion rate. The imaging techniques performed well, especially MRI texture analysis, suggesting the sample size being sufficient for estimating lesion repair. The main challenge of this trial model may be recruiting gadolinium-enhancing lesions in DMT-treated RRMS participants. Prolactin is safe and may hold promise as a remyelination therapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02493049.
Topics: Humans; Adult; Multiple Sclerosis, Relapsing-Remitting; Female; Male; Feasibility Studies; Domperidone; Pilot Projects; Middle Aged; Magnetic Resonance Imaging; Young Adult; Brain; Immunologic Factors; Outcome Assessment, Health Care; Diffusion Tensor Imaging
PubMed: 38461731
DOI: 10.1016/j.msard.2024.105525 -
Saudi Pharmaceutical Journal : SPJ :... May 2024Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and...
BACKGROUND
Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc).
METHODS
A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25-80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks.
RESULTS
Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used.
CONCLUSIONS
Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.
PubMed: 38558884
DOI: 10.1016/j.jsps.2024.102039 -
Drug Delivery and Translational Research Apr 2024
Correction to: Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction.
PubMed: 38416387
DOI: 10.1007/s13346-024-01554-5 -
Reproductive Biology Sep 2023Hyperprolactinemia is a pathological condition resulting from increased prolactin that directly affects reproduction, as this condition inhibits the release of LH, FSH...
Hyperprolactinemia is a pathological condition resulting from increased prolactin that directly affects reproduction, as this condition inhibits the release of LH, FSH and gonadal steroidogenesis, bringing several negative clinical associations in reproduction. In contrast, melatonin (MEL) plays an important role in the regulation of steroidogenesis and modulates damages to the process of spermatogenesis. The objective was to analyze the protective effects of exogenous melatonin on the testis of hyperprolactinemic adult rats. Forty-eight male rats were used, divided into two treatment periods: 30 and 60 days, each treatment was subdivided into three groups: Control, Hyper (hyperprolactinemia), and Hyper+MEL (hyperprolactinemia and melatonin). Treatment with melatonin was 200 μg/100 g, subcutaneously. Induction of hyperprolactinemia was obtained with a dose of 4 mg/kg of domperidone, subcutaneously. The results of the histopathology demonstrated that the animals in the Hyper group presented degeneration of germ cells when compared to the control. In addition, the degenerations were presented in smaller quantities in the Hyper+MEL, in both treatment periods, evidencing the benefits of the melatonin in gonadal regeneration. The Hyper group of both treatment periods showed a decrease in tubular diameter, epithelium height, and tubular area, in addition to a decrease in Sertoli cells, when compared to the control and the Hyper+MEL group. In conclusion, the hyperprolactinemia can affect the germinal epithelium and testicular microstructure; the exogenous melatonin has a protective effect against hyperprolactinemia, reducing testicular damage.
Topics: Rats; Male; Animals; Testis; Melatonin; Hyperprolactinemia; Domperidone; Prolactin
PubMed: 37517145
DOI: 10.1016/j.repbio.2023.100791 -
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 -
Journal of Human Lactation : Official... Feb 2024Non-puerperal adoptive lactation sometimes requires long preparation and substantial expense for pharmacological intervention to be successful, which are not feasible in...
INTRODUCTION
Non-puerperal adoptive lactation sometimes requires long preparation and substantial expense for pharmacological intervention to be successful, which are not feasible in refugee camps. Here we report two case studies of non-puerperal adoptive breastfeeding of two infants in the Rohingya Refugee Camp of Cox's Bazar, Bangladesh.
MAIN ISSUE
Two non-pregnant, non-breastfeeding caregivers with previous experience of breastfeeding brought two adopted infants-one a 12-day-old female with severe acute malnutrition, and the other a 2-day-old male with normal anthropometric measurements-to a nutritional stabilization center for feeding. After counseling, both families opted for adoptive lactation.
MANAGEMENT
Both infants were treated with a modified Action Against Hunger protocol of in-patient management of severe acute malnutrition using the supplementary suckling technique, a procedure to feed the baby with supplementary feed. Diluted F100 was used as the supplementary feed; the energy and protein gained from it were just enough to maintain body physiology and were not responsible for any weight gain. When the infants gained weight, indicating that the caregivers were producing milk, we reduced the supplementary feed as per protocol guidelines. The caregivers were prescribed domperidone and counseled on their ability to breastfeed the infants. The cases required 35 days and 20 days, respectively, for the full establishment of breastfeeding.
CONCLUSION
This is the first report of successful adoptive breastfeeding in a refugee camp. With proper counseling and motivation of the caregiver, induced lactation can be started without a preparatory period and with very low-cost intervention.
Topics: Infant; Male; Female; Humans; Breast Feeding; Refugee Camps; Lactation; Weight Gain; Severe Acute Malnutrition
PubMed: 38078419
DOI: 10.1177/08903344231216091 -
International Journal of Pharmaceutics Sep 2023The present study aims to utilize green synthesis to fabricate stimuli-responsive, smart, quince/pectin cross-linked hydrogel sponges for the pH-regulated conveyance of...
The present study aims to utilize green synthesis to fabricate stimuli-responsive, smart, quince/pectin cross-linked hydrogel sponges for the pH-regulated conveyance of domperidone. The designed hydrogel sponges were evaluated for a sol-gel fraction (%), swelling studies and kinetics, drug loading (%), electrolyte-responsive character, scanning electron microscopy (SEM), thermal analysis, drug-excipient compatibility studies (FTIR), X-ray diffraction (XRD) analysis, mechanical testing, in-vitro drug release studies, and acute oral toxicity studies. The drug loading (%) ranged from 67 to 85%. Hydrogel sponges displayed pH-responsive swelling potential, with optimum swelling in a phosphate buffer (pH 7.4) and insignificant swelling in an acidic buffer of pH 1.2. The prepared hydrogel sponges displayed second-order swelling dynamics. The FTIR data revealed the successful fabrication of the hydrogel sponges with the primary drug peaks remaining unchanged, demonstrating excipients-drug compatibility. SEM confirmed the rough, porous surface of hydrogel sponges with numerous cracks. XRD measurements revealed the transformation of the crystalline nature of domperidone into an amorphous one within the developed hydrogel sponges. Dissolution studies revealed little domperidone release in an acidic environment. However, hydrogel sponges exhibited release up to 10 h in phosphate buffer.The sponge's non-toxic or biocompatible character was confirmed through toxicological studies. Thus, the finding indicates that quince/pectin cross-linked hydrogel sponges are durable enough to deliver the domperidone to the gut for a longer time.
Topics: Hydrogels; Domperidone; Pectins; Rosaceae; Excipients; Hydrogen-Ion Concentration; Phosphates
PubMed: 37572857
DOI: 10.1016/j.ijpharm.2023.123305 -
Heliyon Apr 2024Food accumulation fever (FAF), a common clinical disease in children, is generally induced by the excessive intake of high-calorie or high-fat foods. decoction (ZQCLD)...
OBJECTIVE
Food accumulation fever (FAF), a common clinical disease in children, is generally induced by the excessive intake of high-calorie or high-fat foods. decoction (ZQCLD) is a classical traditional Chinese medicine (TCM) that may have therapeutic effects on FAF.
METHODS
Network pharmacological analyses of ZQCLD and FAF were conducted. Animal experiments lasted for 14 days. Rats in the model, positive control, and low-, medium-, and high-dose groups were fed a high-calorie diet. On days 11-14, the positive group was given a domperidone solution. The low-, medium-, and high-dose groups were administered different concentrations of ZQCLD. The body temperature, gastric emptying rate, and intestinal propulsion rate were measured. Relevant indicators were determined by ELISA.
RESULTS
The main target proteins included IL-1β, C-C motif chemokine 2 (CCL2), prostaglandin G/H synthase 2 (PTGS2), transcription factor AP-1 (JUN), haem oxygenase 1 (HMOX1), interferon-gamma (IFN-γ), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and inducible nitric oxide synthase (NOS2/iNOS). Compared with those in the control group, body weight, gastric emptying rate, intestinal propulsion rate, and neuronal nitric oxide synthase (NOS1/nNOS) levels were significantly lower in the model group, whereas body temperature and endotoxin, interleukin-1β (IL-1β), PGE2, and iNOS levels were increased. In each treatment group, body temperature and PGE2 levels returned to normal levels. Compared with those in the model group, the gastric emptying rates in the positive group and the low- and medium-dose groups increased; the intestinal propulsion rates were higher in the medium- and high-dose groups, whereas the endotoxin and IL-1β levels were lower; and the nNOS level was higher in the high-dose group, whereas the iNOS level was lower.
CONCLUSIONS
ZQCLD may treat FAF by regulating jejunal IL-1β and nNOS, serum endotoxin, and hypothalamic PGE2 and iNOS levels.
PubMed: 38681542
DOI: 10.1016/j.heliyon.2024.e29813 -
Journal of Experimental Zoology. Part... May 2024Japanese eel (Anguilla japonica) is a commercially important fish species in Asia. Understanding factors like photoperiod, temperature, and lunar cycles is crucial for...
Japanese eel (Anguilla japonica) is a commercially important fish species in Asia. Understanding factors like photoperiod, temperature, and lunar cycles is crucial for successful aquaculture and managing its reproduction. Melatonin and dopamine (DA) are essential for regulating reproduction in vertebrates, including fish. This study investigated the effects of melatonin and DA on the reproductive system of mature male Japanese eels to better understand reproductive regulation in fish. To clarify the effects of these hormones on sexual maturation in eels, a critical stage in the reproductive process, sexual maturation was induced by injecting human chorionic gonadotropin, which stimulates the production of sex hormones. To check the effect of melatonin and DA on sexual maturation, DA, melatonin, and DA + domperidone were intraperitoneally injected into fish from each group (six per treatment) at a dose of 1 mg/kg body weight. The fish were then examined using quantitative RT-PCR by comparing the messenger RNA level of reproduction-related genes (gonadotropin releasing hormone 1; gnrh1, gonadotropin releasing hormone 2; gnrh2, follicle stimulating hormone; fshβ, luteinizing hormone; lhβ and DA receptor 2b; d2b), involved in the gonadotropic axis in eels, to those that received a control injection. The results indicate significant differences in the expression levels of gnrh1, gnrh2 and d2b in the brain and d2b, fshβ, lhβ in the pituitary at different stages of sexual maturation. Melatonin appears to enhance the production of sex gonadotropins, whereas DA inhibits them. These findings suggest an interaction between melatonin and DA in regulating reproduction in Japanese eels.
Topics: Humans; Male; Animals; Anguilla; Melatonin; Dopamine; Sexual Maturation; Gonadotropin-Releasing Hormone
PubMed: 38334250
DOI: 10.1002/jez.2788