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International Journal of Molecular... Apr 2024In contrast to cats and dogs, here we report that the α-adrenergic receptor antagonist yohimbine is emetic and corresponding agonists clonidine and dexmedetomidine... (Comparative Study)
Comparative Study
A Comparative Study of the Antiemetic Effects of α-Adrenergic Receptor Agonists Clonidine and Dexmedetomidine against Diverse Emetogens in the Least Shrew () Model of Emesis.
In contrast to cats and dogs, here we report that the α-adrenergic receptor antagonist yohimbine is emetic and corresponding agonists clonidine and dexmedetomidine behave as antiemetics in the least shrew model of vomiting. Yohimbine (0, 0.5, 0.75, 1, 1.5, 2, and 3 mg/kg, i.p.) caused vomiting in shrews in a bell-shaped and dose-dependent manner, with a maximum frequency (0.85 ± 0.22) at 1 mg/kg, which was accompanied by a key central contribution as indicated by increased expression of c-, serotonin and substance P release in the shrew brainstem emetic nuclei. Our comparative study in shrews demonstrates that clonidine (0, 0.1, 1, 5, and 10 mg/kg, i.p.) and dexmedetomidine (0, 0.01, 0.05, and 0.1 mg/kg, i.p.) not only suppress yohimbine (1 mg/kg, i.p.)-evoked vomiting in a dose-dependent manner, but also display broad-spectrum antiemetic effects against diverse well-known emetogens, including 2-Methyl-5-HT, GR73632, McN-A-343, quinpirole, FPL64176, SR141716A, thapsigargin, rolipram, and ZD7288. The antiemetic inhibitory ID values of dexmedetomidine against the evoked emetogens are much lower than those of clonidine. At its antiemetic doses, clonidine decreased shrews' locomotor activity parameters (distance moved and rearing), whereas dexmedetomidine did not do so. The results suggest that dexmedetomidine represents a better candidate for antiemetic potential with advantages over clonidine.
Topics: Animals; Male; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Antiemetics; Clonidine; Dexmedetomidine; Disease Models, Animal; Emetics; Shrews; Vomiting; Yohimbine
PubMed: 38731821
DOI: 10.3390/ijms25094603 -
Molecules (Basel, Switzerland) May 2024The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has...
The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than . Thus, the bimolecular rate constant was found to be / = 7.7 × 10 M min. Rough estimates of catalytic parameters provided slow < 40 min and high = 0.3-3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug.
Topics: Butyrylcholinesterase; Atropine; Humans; Kinetics; Hydrolysis; Molecular Docking Simulation; Models, Molecular
PubMed: 38731631
DOI: 10.3390/molecules29092140 -
Molecular Biology Reports May 2024Alzheimer's disease is a leading neurological disorder that gradually impairs memory and cognitive abilities, ultimately leading to the inability to perform even basic...
BACKGROUND
Alzheimer's disease is a leading neurological disorder that gradually impairs memory and cognitive abilities, ultimately leading to the inability to perform even basic daily tasks. Teriflunomide is known to preserve neuronal activity and protect mitochondria in the brain slices exposed to oxidative stress. The current research was undertaken to investigate the teriflunomide's cognitive rescuing abilities against scopolamine-induced comorbid cognitive impairment and its influence on phosphatidylinositol-3-kinase (PI3K) inhibition-mediated behavior alteration in mice.
METHODS
Swiss albino mice were divided into 7 groups; vehicle control, scopolamine, donepezil + scopolamine, teriflunomide (10 mg/kg) + scopolamine; teriflunomide (20 mg/kg) + scopolamine, LY294002 and LY294002 + teriflunomide (20 mg/kg). Mice underwent a nine-day protocol, receiving scopolamine injections (2 mg/kg) for the final three days to induce cognitive impairment. Donepezil, teriflunomide, and LY294002 treatments were given continuously for 9 days. MWM, Y-maze, OFT and rota-rod tests were conducted on days 7 and 9. On the last day, blood samples were collected for serum TNF-α analysis, after which the mice were sacrificed, and brain samples were harvested for oxidative stress analysis.
RESULTS
Scopolamine administration for three consecutive days increased the time required to reach the platform in the MWM test, whereas, reduced the percentage of spontaneous alternations in the Y-maze, number of square crossing in OFT and retention time in the rota-rod test. In biochemical analysis, scopolamine downregulated the brain GSH level, whereas it upregulated the brain TBARS and serum TNF-α levels. Teriflunomide treatment effectively mitigated all the behavioral and biochemical alterations induced by scopolamine. Furthermore, LY294002 administration reduced the memory function and GSH level, whereas, uplifted the serum TNF-α levels. Teriflunomide abrogated the memory-impairing, GSH-lowering, and TNF-α-increasing effects of LY294002.
CONCLUSION
Our results delineate that the improvement in memory, locomotion, and motor coordination might be attributed to the oxidative and inflammatory stress inhibitory potential of teriflunomide. Moreover, PI3K inhibition-induced memory impairment might be attributed to reduced GSH levels and increased TNF-α levels.
Topics: Animals; Mice; Alzheimer Disease; Behavior, Animal; Brain; Chromones; Cognition; Cognitive Dysfunction; Crotonates; Disease Models, Animal; Donepezil; Hydroxybutyrates; Maze Learning; Memory; Morpholines; Nitriles; Oxidative Stress; Phosphatidylinositol 3-Kinases; Scopolamine; Toluidines
PubMed: 38722394
DOI: 10.1007/s11033-024-09502-9 -
Journal of Toxicology and Environmental... Aug 2024Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans...
Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans is rare and remains controversial. This study aimed to investigate the acute effects of exposure to noise and its different levels on stress hormone changes in task performance. Quasi-experimental noise exposure environment was established for 90 male university student volunteers in their twenties, and each was exposed to different noise levels during task performance. The stress hormones tested included cortisol, adrenocorticotropic hormone (ACTH), adrenaline, and noradrenaline. A one-way ANOVA was performed to investigate differences in hormone levels measured in the three groups according to the noise exposure levels (35, 45, or 75 dB). Analysis of covariance (ANCOVA) was used to adjust for confounding factors that might affect hormone levels. After adjusting for confounders, significant exposure-dependent differences were found in hormone levels in salivary cortisol, serum cortisol, serum ACTH, and serum adrenaline. The amount of hormonal increase in 75 dB exposure group compared to 35 or 45 dB groups was detected. Similar results were also seen in the rate of change analysis. Our findings indicate that short-term noise exposure during task performance elevates stress hormone levels. Further, the extent of stress hormone alterations varies with noise exposure levels. Changes in hormone levels are an objective measure that may be used to identify health effects and stress responses in various noise environments.
Topics: Humans; Male; Noise; Hydrocortisone; Young Adult; Epinephrine; Adrenocorticotropic Hormone; Republic of Korea; Norepinephrine; Saliva; Adult; Task Performance and Analysis
PubMed: 38721994
DOI: 10.1080/15287394.2024.2352122 -
Allergologia Et Immunopathologia 2024Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece.
BACKGROUND
Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece.
PURPOSE
The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments.
METHODS
We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention.
RESULTS
In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis.
CONCLUSIONS
This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.
Topics: Humans; Anaphylaxis; Greece; Child; Male; Female; Epinephrine; Child, Preschool; Adolescent; Infant; Surveys and Questionnaires; Histamine Antagonists; Adrenal Cortex Hormones; Injections, Intramuscular
PubMed: 38721950
DOI: 10.15586/aei.v52i3.1032 -
BMC Emergency Medicine May 2024This study compared out-of-hospital cardiac arrest (OHCA) patient outcomes based on intravenous (IV) access and prehospital epinephrine use.
BACKGROUND
This study compared out-of-hospital cardiac arrest (OHCA) patient outcomes based on intravenous (IV) access and prehospital epinephrine use.
METHODS
A retrospective study in Ulsan, South Korea, from January 2017 to December 2022, analyzed adult nontraumatic OHCA cases. Patients were grouped: Group 1 (no IV attempts), Group 2 (failed IV access), Group 3 (successful IV access without epinephrine), and Group 4 (successful IV access with epinephrine), with comparisons using logistic regression analysis.
RESULTS
Among 2,656 patients, Group 4 had significantly lower survival to hospital discharge (adjusted OR 0.520, 95% CI 0.346-0.782, p = 0.002) and favorable neurological outcomes (adjusted OR 0.292, 95% CI 0.140-0.611, p = 0.001) than Group 1. Groups 2 and 3 showed insignificant survival to hospital discharge (adjusted OR 0.814, 95% CI 0.566-1.171, p = 0.268) and (adjusted OR 1.069, 95% CI 0.810-1.412, p = 0.636) and favorable neurological outcomes (adjusted OR 0.585, 95% CI 0.299-1.144, p = 0.117) and (adjusted OR 1.075, 95% CI 0.689-1.677, p = 0.751). In the shockable rhythm group, Group 3 had better survival to hospital discharge (adjusted OR 1.700, 95% CI 1.044-2.770, p = 0.033).
CONCLUSIONS
Successful IV access with epinephrine showed worse outcomes in both rhythm groups than no IV attempts. Outcomes for failed IV and successful IV access without epinephrine were inconclusive. Importantly, successful IV access without epinephrine showed favorable survival to hospital discharge in the shockable rhythm group, warranting further research into IV access for fluid resuscitation in shockable rhythm OHCA patients.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Epinephrine; Male; Female; Retrospective Studies; Republic of Korea; Middle Aged; Aged; Emergency Medical Services; Cardiopulmonary Resuscitation; Adult; Administration, Intravenous
PubMed: 38710999
DOI: 10.1186/s12873-024-00998-9 -
Ophthalmic Epidemiology May 2024This study was aimed to evaluate the agreement between the swept-source optical coherence tomography (SS-OCT)-based biometry, fundus photographs, and their combination,...
PURPOSE
This study was aimed to evaluate the agreement between the swept-source optical coherence tomography (SS-OCT)-based biometry, fundus photographs, and their combination, in comparison to the gold standard spectral-domain optical coherence tomography (SD-OCT) for the detection of center-involving diabetic macular edema (CI-DME).
METHODS
We conducted a retrospective cross-sectional study involving 55 subjects (78 eyes) diagnosed with diabetic macular edema (DME) detected clinically and on SD-OCT (Carl Zeiss Meditec AG). Post-mydriatic 45-degree color fundus photograph (Crystal-Vue NFC-700), 1 mm macular scan obtained from SS-OCT-based biometry (IOL-Master 700), and macula cube scan obtained from SD-OCT was used to detect and grade DME into CI-DME and NCI-DME.
RESULTS
Our findings revealed that SS-OCT-based biometry was noted to have a high sensitivity of 1 (0.94-1.00) and a specificity of 0.63 (0.31-0.89) in detecting CI-DME compared to the gold standard (SD-OCT). When combined with data from fundus photographs, specificity decreased to 0.32 (0.15-0.53). Fundus photographs alone exhibited a low sensitivity of 0.52 (0.38-0.64) and a specificity of 0.45 (0.16-0.76) in CI-DME detection.
CONCLUSION
In conclusion, SS-OCT-based biometry can be used as an effective tool for the detection of CI-DME in diabetic patients undergoing cataract surgery and can serve as a screening tool in centers without SD-OCT facilities.
PubMed: 38709173
DOI: 10.1080/09286586.2024.2338824 -
Drug Design, Development and Therapy 2024Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the... (Randomized Controlled Trial)
Randomized Controlled Trial
Dose-Response Study of Phenylephrine for Preventing Spinal-Induced Hypotension During Cesarean Delivery with Combined Spinal-Epidural Anesthesia Under the Effect of Prophylactic Intravenous Ondansetron.
BACKGROUND
Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method.
METHODS
A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 μg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis.
RESULTS
The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) μg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups.
CONCLUSION
The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) μg/kg/min for phenylephrine to prevent SIH.
Topics: Adult; Female; Humans; Pregnancy; Anesthesia, Epidural; Anesthesia, Spinal; Cesarean Section; Dose-Response Relationship, Drug; Hypotension; Ondansetron; Phenylephrine
PubMed: 38707613
DOI: 10.2147/DDDT.S452983 -
Molecular Nutrition & Food Research May 2024Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes...
SCOPE
Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear.
METHODS AND RESULTS
Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS.
CONCLUSION
Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.
Topics: Animals; Pregnancy; Female; PPAR gamma; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Prenatal Exposure Delayed Effects; Vasoconstriction; Rats, Sprague-Dawley; Dietary Sucrose; Rats; Renal Artery; Male; Phenylephrine; Maternal Nutritional Physiological Phenomena
PubMed: 38704749
DOI: 10.1002/mnfr.202300871 -
Ugeskrift For Laeger Apr 2024Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose...
Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose anaphylaxis and treat promptly with adrenaline and fluids. Allergy investigation should be performed subsequently. This is a case report of perioperative anaphylaxis to propofol. Propofol contains refined soya oil and egg lecithin, but no connection between allergy to soy, egg or peanut and allergy to propofol has been proven, and international guidelines recommend that propofol can be used in patients with these food allergies.
Topics: Humans; Anaphylaxis; Anesthetics, Intravenous; Drug Hypersensitivity; Epinephrine; Propofol
PubMed: 38704709
DOI: 10.61409/V11230746