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Food & Function Jun 2024protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from...
protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from protein hydrolysates and validate the protective effects of YVYAETY on memory impairment in scopolamine-induced mice. The protein was hydrolyzed by simulated gastrointestinal digestion, followed by purification through ultrafiltration and gel chromatography. The fraction exhibiting the strongest neuroprotective activity was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main identified peptides (SDLKPADF, WNDHYY, YVYAETY, and WFHPLF) effectively mitigated excessive ROS production by increasing SOD and GSH-px activities while inhibiting cell apoptosis and mitochondrial membrane potential (MMP) collapse against oxidative stress in Aβ-induced HT22 cells. By molecular docking, the interaction between peptides and the active site of the Keap1-Kelch domain reveals their capacity to regulate the Keap1/Nrf2/HO-1 pathway. , the peptide YVYAETY had the best effect and can be further validated . The behavioral tests showed that YVYAETY improved scopolamine-induced cognitive impairment in mice. YVYAETY also alleviated neuron damage including neuron vacuolation and pyknotic nuclei in the hippocampus. Furthermore, it significantly inhibited oxidative stress and suppressed the activation of the Nrf2 pathway. Therefore, this study revealed that YVYAETY had the potential to serve as a novel neuroprotective agent.
Topics: Animals; Mice; Scopolamine; Neuroprotective Agents; Cognitive Dysfunction; Protein Hydrolysates; Flammulina; Male; Oxidative Stress; Peptides; Molecular Docking Simulation; Hippocampus; Apoptosis
PubMed: 38757389
DOI: 10.1039/d4fo00871e -
Critical Care Medicine Jun 2024
Topics: Epinephrine; Humans; Cardiopulmonary Resuscitation; Heart Arrest
PubMed: 38752814
DOI: 10.1097/CCM.0000000000006234 -
Arerugi = [Allergy] 2024We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered...
BACKGROUND AND AIM
We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered a questionnaire survey to pharmacists with experience handling EpiPen prescriptions. We investigated the relationship between the questionnaire results and the factors in the pharmacists' background regarding the explanation and guidance to patients.
RESULTS
The percentage of pharmacists working in pharmacies who provided guidance using visual information and demonstrations was insufficient. Moreover, this figure decreased after the second guidance session. Objective confirmation of patient understanding was also insufficient. The results indicated that self-examination and participation in drug information sessions were important background factors for pharmacists who provided detailed guidance to patients.
DISCUSSION
For appropriate long-term management of their condition, An patients must master the EpiPen technique. Pharmacists' guidance plays a critical role in this regard. A support system should be established for proper instruction of pharmacy patients by improving pharmacists' self-education and other educational opportunities.
Topics: Humans; Anaphylaxis; Patient Education as Topic; Pharmacists; Surveys and Questionnaires; Epinephrine; Female; Male; Adult; Middle Aged
PubMed: 38749712
DOI: 10.15036/arerugi.73.279 -
Journal of Bronchology & Interventional... Jul 2024Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent... (Observational Study)
Observational Study
BACKGROUND
Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure.
METHODS
In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups.
RESULTS
There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups.
CONCLUSIONS
We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.
Topics: Humans; Phenylephrine; Retrospective Studies; Bronchoscopy; Male; Female; Middle Aged; Aged; Vasoconstrictor Agents; Hypertension; Blood Pressure
PubMed: 38745445
DOI: 10.1097/LBR.0000000000000968 -
Neurosciences (Riyadh, Saudi Arabia) May 2024To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine.
OBJECTIVES
To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine.
METHODS
This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100 mg/kg AST, 2 mg/kg scopolamine (AD group), 100 mg/kg AST+2 mg/kg scopolamine, 3 mg/kg galantamine+2 mg/kg scopolamine, and 100 mg/kg AST+3 mg/kg galantamine+2 mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated.
RESULTS
The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress.
CONCLUSION
The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.
Topics: Animals; Xanthophylls; Alzheimer Disease; Scopolamine; Male; Mice; Neuroprotective Agents; Disease Models, Animal; Oxidative Stress; Hippocampus; Acetylcholinesterase; Galantamine; Memory, Short-Term
PubMed: 38740397
DOI: 10.17712/nsj.2024.2.20230060 -
Cureus Apr 2024This case report presents the clinical scenario of a 50-year-old man who developed swelling and itching around both eyes after applying tropicamide eye drops for an...
This case report presents the clinical scenario of a 50-year-old man who developed swelling and itching around both eyes after applying tropicamide eye drops for an ophthalmic examination. The swelling appeared suddenly, progressed over time, and was accompanied by redness, watery discharge, and conjunctival congestion. A dermoscopic examination revealed congestion and erythema in the affected area. Visual acuity was compromised in the left eye. Prompt identification of the eyedrops as plain tropicamide with chlorbutol as a preservative enabled timely treatment with intravenous hydrocortisone and topical steroids, resulting in symptom improvement within two days. Allergic reactions to mydriatic agents such as tropicamide are infrequent but should be considered in patients with acute ocular symptoms post-application. This case underscores the importance of recognising and managing allergic reactions to ophthalmic medications for optimal patient care.
PubMed: 38738153
DOI: 10.7759/cureus.57945 -
Harefuah May 2024The importance of myopia management lies in the desire to minimize the potential ocular risks that increase with high myopia.
INTRODUCTION
The importance of myopia management lies in the desire to minimize the potential ocular risks that increase with high myopia.
AIMS
To assess the decrease in myopia progression using topical low dose atropine combined with peripheral blur contact lenses (CL).
METHODS
This retrospective review study included 25 children between the ages of 8.5 years to 14 years. The children all had a minimal increase in myopia of 0.75D during the year prior to treatment. The children were divided into two groups. The control group included 14 children who wore single-vision spectacles )SV) averaging 3.20±0.9D ranging from 1.5-5.3D. The study group included 11 children who wore dual-focus CL, with an average prescription of 3.4±0.7D ranging from 2.5 to 4.3D, for one year. At that point, when an additional myopia increase was observed, the children were additionally treated with topical 0.01% atropine for two years (CL+A0.01).
RESULTS
There was an increase in myopia in the SV group of 1.12±0.52D, 1.08±0.56D and 0.96±0.53D in the first, second, and third years, respectively. The myopia increase in the CL+A0.01 group was 0.57±0.48D, 0.14±0.34D, and 0.17±0.29D in the first, second, and third years, respectively.
CONCLUSIONS
Low-dose atropine combined with peripheral blur contact lenses was effective in decreasing myopia progression in this study. Additional, larger-scale studies are required in the future.
DISCUSSION
This study found a significant decrease in myopia progression in the second and third years of treatment. The CL group showed less effectivity than the CL+A0.01 group.
Topics: Humans; Atropine; Child; Myopia; Retrospective Studies; Adolescent; Contact Lenses; Male; Disease Progression; Female; Treatment Outcome; Mydriatics; Ophthalmic Solutions; Eyeglasses
PubMed: 38734939
DOI: No ID Found -
European Journal of Pharmacology Jul 2024The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique...
The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 18:2) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 18:2 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1β, IL-6, and TNF-α in the hippocampus, serum, and colon were reduced by M 18:2. Furthermore, M 18:2 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified, as well as increased genera Muribaculaceae_unclassified, Muribaculum, Alistipes, and Bacteroides, which may be the possible biomarkers of cognitive aging. In summary, M 18:2 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota.
Topics: Animals; NF-E2-Related Factor 2; Alzheimer Disease; Gastrointestinal Microbiome; Signal Transduction; Neuroprotective Agents; Mice; Male; Disease Models, Animal; Acetylcholinesterase; Scopolamine; Neuronal Plasticity; Molecular Docking Simulation; CA1 Region, Hippocampal; Hippocampus
PubMed: 38734297
DOI: 10.1016/j.ejphar.2024.176638 -
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