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Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns.Frontiers in Endocrinology 2023Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally...
Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.
Topics: Rats; Animals; Histamine H1 Antagonists; Promethazine; Cetirizine; Midazolam; Pain; Histamine; Fentanyl
PubMed: 36843581
DOI: 10.3389/fendo.2023.1068925 -
Drug Safety Mar 2023Deliberate self-poisoning (DSP) using drugs is the preferred method of suicide at a global level. Its investigation is hampered by limited sample sizes and data...
INTRODUCTION
Deliberate self-poisoning (DSP) using drugs is the preferred method of suicide at a global level. Its investigation is hampered by limited sample sizes and data reliability. We investigate the role of the US FDA Adverse Event Reporting System (FAERS), a consolidated pharmacovigilance database, in outlining DSP habits and toxidromes.
METHODS
We retrieved cases of 'intentional overdose' and 'poisoning deliberate' from the FAERS (January 2004-December 2021). Using descriptive and disproportionality analyses, we estimated temporal trends, potential risk factors, toxidromes, case-fatality rates and lethal doses (LDs) for the most frequently reported drugs.
RESULTS
We retrieved 42,103 DSP cases (17% fatal). Most cases were submitted in winter. Reports of DSP involved younger people, psychiatric conditions, and alcohol use, compared with non-DSP, and fatality was higher in men and older patients. Suspected drugs were mainly antidepressants, analgesics, and antipsychotics. Multiple drug intake was recorded in more than 50% of the reports, especially analgesics, psychotropics, and cardiovascular agents. The most frequently reported drugs were paracetamol, promethazine, amlodipine, quetiapine, and metformin. We estimated LD25 for paracetamol (150 g).
CONCLUSION
Worldwide coverage of the FAERS complements existing knowledge about DSP and may drive tailored prevention measures to timely address the DSP phenomenon and prevent intentional suicides.
Topics: Male; United States; Humans; Suicide; Suicide, Attempted; Suicidal Ideation; Acetaminophen; United States Food and Drug Administration; Reproducibility of Results; Analgesics; Adverse Drug Reaction Reporting Systems
PubMed: 36689131
DOI: 10.1007/s40264-022-01269-x -
Molecules (Basel, Switzerland) Jan 2023Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the...
Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.
Topics: Mice; Animals; Promethazine; Nanocapsules; Nylons; Taste; Taste Perception; Histamine H1 Antagonists
PubMed: 36677806
DOI: 10.3390/molecules28020748 -
Clinical Surgery Journal 2022Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated...
BACKGROUND
Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated with prolonged and frequent use of high-dose cannabis. CHS in the pediatric population has been increasingly reported over the last decade and can lead to life-threatening complications such as pneumomediastinum, which warrant careful consideration for surgical intervention.
CASE PRESENTATION
A 17-year-old female with no significant past medical history presented to the emergency department with abdominal pain, nausea, and vomiting for 24 hours. She had four episodes of green-yellow emesis followed by dry heaves. She also complained of chest and back pain, worse with deep inspiration. Upon further history, the patient reported a similar episode of abdominal pain and repetitive vomiting six months prior to the current episode. She smoked cannabis at least once daily and has done so for the past two years. Chest X-ray revealed a subtle abnormal lucency along the anteroposterior window and anterior mediastinum, consistent with a small amount of pneumomediastinum without any other acute intrathoracic abnormalities. Follow-up chest computed tomography with contrast showed multiple foci of air within the anterior and posterior mediastinum tracking up to the thoracic inlet. There was no evidence of contrast extravasation; however, small esophageal perforation could not be excluded. Given uncomplicated pneumomediastinum without frank contrast extravasation, the patient was treated medically with piperacillin-tazobactam, metronidazole, and micafungin for microbial prophylaxis; hydromorphone for pain control; as well as with pantoprazole, ondansetron, and promethazine. Nutrition was provided via total parenteral nutrition. The patient was intensely monitored for signs of occult esophageal perforation, but none were detected. She was advanced to a soft diet on hospital day eight, solid food diet on day nine, at which point antibiotics were discontinued, and the patient was subsequently discharged.
CONCLUSION
CHS in an increasingly common disorder encountered in the pediatric setting due to rising prevalence of cannabis use. The management of CHS and potentially life-threatening complications such as pneumomediastinum should be given careful consideration. Pneumomediastinum can be a harbinger of more sinister pathology such as esophageal perforation, which may warrant urgent surgical intervention.
PubMed: 36438163
DOI: No ID Found -
ACS Omega Nov 2022Recently, there has been a worrying increase in the pollution of the aquatic ecosystem caused by emerging contaminants (ECs) detected in wastewater effluent discharges....
Recently, there has been a worrying increase in the pollution of the aquatic ecosystem caused by emerging contaminants (ECs) detected in wastewater effluent discharges. Although traces of ECs in waters have been found in low concentrations, it leads to negative effects for nontarget organisms. Antihistamines are a class of drugs largely used, whose metabolites are widespread in the aquatic ecosystem. The aim of the study was to evaluate the short-term effects of promethazine hydrochloride on nauplii of sp. A high percentage of mortality and morphological alterations were found. The results suggest a possible correlation between exposure to antihistamine and an acceleration of larval development.
PubMed: 36385863
DOI: 10.1021/acsomega.2c00856 -
Antibiotics (Basel, Switzerland) Nov 2022Persistent apical periodontitis occurs when the endodontic treatment fails to eradicate the intraradicular infection, and is mainly caused by Gram-positive bacteria and...
Persistent apical periodontitis occurs when the endodontic treatment fails to eradicate the intraradicular infection, and is mainly caused by Gram-positive bacteria and yeasts, such as and , respectively. Phenothiazines have been described as potential antimicrobials against bacteria and fungi. This study aimed to investigate the antimicrobial potential of promethazine (PMZ) and chlorpromazine (CPZ) against and dual-species biofilms. The susceptibility of planktonic cells to phenothiazines, chlorhexidine (CHX) and sodium hypochlorite (NaOCl) was initially analyzed by broth microdilution. Interaction between phenothiazines and CHX was examined by chequerboard assay. The effect of NaOCl, PMZ, CPZ, CHX, PMZ + CHX, and CPZ + CHX on biofilms was investigated by susceptibility assays, biochemical and morphological analyses. Results were evaluated through one-way ANOVA and Tukey's multiple comparison post-test. PMZ, alone or in combination with irrigants, was the most efficient phenothiazine, capable of reducing cell counts, biomass, biovolume, carbohydrate and protein contents of dual-species biofilms. Neither PMZ nor CPZ increased the antimicrobial activity of CHX. Further investigations of the properties of phenothiazines should be performed to encourage their use in endodontic clinical practice.
PubMed: 36358217
DOI: 10.3390/antibiotics11111562 -
Life Sciences Dec 2022This study sought to investigate the differentially expressed miRNAs in Aortic dissection (AD) and explore the downstream mechanisms in regulating AD.
OBJECTIVE
This study sought to investigate the differentially expressed miRNAs in Aortic dissection (AD) and explore the downstream mechanisms in regulating AD.
METHODS
Exosomes of AD patients and healthy people were isolated by differential centrifugation, and the differentially expressed miRNAs were evaluated by RNA sequencing. The downstream target of miR-222-3p was predicted by bioinformatics method and validated by dual-luciferase assay. Angiotensin II and Promethazine were used to establish AD mouse model and platelet-derived growth factor BB (PDGF-BB) was used to induce human vascular smooth muscle cells (HVSMCs) to elucidate the effect of miR-222-3p upregulation on AD in vivo and in vitro. The relative level of miR-222-3p was evaluated by RT-qPCR. The level of several proteins was investigated by Western blot. Immunofluorescence staining was used to detect the stress fiber formation. Cell migration was evaluated by wound healing and Transwell assay. The proliferation, cell cycle and apoptosis of HVSMCs were assessed by CCK-8 and flow cytometry, respectively.
RESULTS
MiR-222-3p was downregulated in AD and PDGF-BB induced HVSMCs. The upregulation of miR-222-3p alleviated the symptom of AD in vivo by targeting STAT3, and inhibited stress fiber formation, abnormal migration, proliferation and apoptosis of HVSMCs induced by PDGF-BB by regulating the expression of α-SMA, SM22α, MMP2, MMP9 and p-Smad2.
CONCLUSION
The upregulation of miR-222-3p attenuates the progression of AD. Our study provides a theoretical basis for exploring new strategies against AD.
Topics: Mice; Animals; Humans; Becaplermin; Cell Proliferation; Up-Regulation; MicroRNAs; Cell Movement; Aortic Dissection; STAT3 Transcription Factor
PubMed: 36216078
DOI: 10.1016/j.lfs.2022.121051 -
Chemphyschem : a European Journal of... Feb 2023Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an...
Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: specifically, dynamic disorder occurring in duloxetine hydrochloride (1), static disorder in promethazine hydrochloride (2), and trifluoperazine dihydrochloride (3). In all structures, the presence of crystallographic disorder was confirmed by C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3, H solid-state NMR provided additional confirmation. Applying Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3, while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from H, C, and Cl NMR, we show that 3 exhibits a unique case of disorder involving the N-H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy three distinct sites.
Topics: Humans; Chlorides; Magnetic Resonance Spectroscopy; Magnetic Resonance Imaging; Pharmaceutical Preparations
PubMed: 36195553
DOI: 10.1002/cphc.202200558 -
Biomedicine & Pharmacotherapy =... Sep 2022Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has...
Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1β, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.
Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclooxygenase 2; Edema; Granuloma; Histamine; Inflammation; Mice; Molecular Docking Simulation; Plant Extracts; Sesquiterpenes
PubMed: 36076580
DOI: 10.1016/j.biopha.2022.113478 -
European Journal of Translational... Sep 2022Examination and intervention are always the causes of agitation, anxiety, and fear in children's lives. This study aimed to investigate the effectiveness of promethazine...
Examination and intervention are always the causes of agitation, anxiety, and fear in children's lives. This study aimed to investigate the effectiveness of promethazine hydrochloride in reducing children's agitation during the ocular examination for trauma. In this interventional-clinical trial study, a total of 62 children referred to Al-Zahra Ophthalmology Hospital in Zahedan, Iran, were evaluated in two matched groups (case (n = 31) and control (n = 31)) for an initial examination of ocular trauma. Finally, the intervention was performed (giving placebo or promethazine hydrochloride cough syrup 20 minutes before the initial ocular examination at 0.5 mg/kg), and the demographic information form and researcher-made questionnaire modeled on the Cohen-Mansfield Agitation Inventory (CMAI) were completed. The obtained results revealed that the mean scores of physical/aggressive behaviors (p ˂ 0.001), physical/nonaggressive behaviors (p = 0.013), verbal/aggressive behaviors (p ˂ 0.001), and hiding behaviors (p ˂ 0.001) were significantly lower in the promethazine hydrochloride-receiving group than the placebo group. These findings demonstrated that promethazine hydrochloride cough syrup facilitated the examination among the pediatric patients who suffered from traumatic ocular injuries. However, further studies in this field need to be carried out through randomized controlled trials.
PubMed: 36073862
DOI: 10.4081/ejtm.2022.10808