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International Journal of Molecular... May 2024Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research...
Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals' resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood-brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.
Topics: Animals; Organophosphate Poisoning; Mice; Disease Models, Animal; Humans; Acetylcholinesterase; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Atropine; Brain; Mice, Knockout; Cholinesterase Inhibitors; Acetylcholine
PubMed: 38891812
DOI: 10.3390/ijms25115624 -
Arerugi = [Allergy] 2024Although paramedics can use adrenaline autoinjectors (AAIs) during their duties, the actual conditions of their use and the challenges faced remain unclear. We...
BACKGROUND
Although paramedics can use adrenaline autoinjectors (AAIs) during their duties, the actual conditions of their use and the challenges faced remain unclear. We investigated the actual situation and issues pertaining to creating an environment in which paramedics can operate AAIs more effectively.
METHODS
A web-based survey was conducted among paramedics who participated in a web-based training session related to their latest knowledge on food allergies and emergency responses in 2022. The survey items included practice and training environments, practices of AAI administration, and regarding AAI administration.
RESULTS
Seventy paramedics responded to the survey. Twenty-eight respondents (40%) had experienced cases in which they wished they had an AAI in their work to date, but only one had actually administered one. Thirty-four (49%) indicated that it would be good to have an AAI in the ambulance at all times; 48 (69%) were not concerned about the use of AAI, and the level of concern about its use was significantly related to length of service. The study also revealed that paramedics do not have an adequate training environment regarding AAI.
CONCLUSION
Few paramedics have experience in administering AAI, although they are aware of the need for it. For more effective use of AAI, it is necessary to establish a training environment to familiarize paramedics with anaphylaxis and an environment that enables them to use AAI promptly in the field.
Topics: Epinephrine; Humans; Allied Health Personnel; Anaphylaxis; Surveys and Questionnaires; Adult; Female; Male; Middle Aged; Paramedics
PubMed: 38880633
DOI: 10.15036/arerugi.73.340 -
BMC Ophthalmology Jun 2024To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges.
OBJECTIVE
To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges.
METHODS
This was a retrospective study on people with type 2 diabetes mellitus (T2DM) who were screened for DR using the single-field non-mydriatic fundus photography at the point of care during routine follow-up visits at endocrinology clinic. Retinal images were uploaded and sent to a retina specialist for review. Reports indicating retinopathy status and the need for direct retinal examination were transmitted back to the endocrinology clinic. All patients were informed about DR status and, if needed, referred to the retina specialist for direct retinal examination.
RESULTS
Of the 1159 individuals screened for DR, 417 persons (35.98%) were screen-positive and referred to the retina specialist for direct retinal examination. A total of 121 individuals (29.01%) underwent direct retinal examination by the specialist. Diabetes macular edema (DME) was detected in 12.1%. In addition, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were detected in 53.4% and 2.6% of the patients, respectively.
CONCLUSION
Integrating DR screening program at the point of care at the secondary care services improves the rate of DR screening as well as detection of sight threatening retinopathy and provides the opportunity for timely intervention in order to prevent advanced retinopathy in people with T2DM.
Topics: Humans; Diabetic Retinopathy; Retrospective Studies; Telemedicine; Female; Male; Middle Aged; Diabetes Mellitus, Type 2; Aged; Mass Screening; Point-of-Care Systems; Adult
PubMed: 38877501
DOI: 10.1186/s12886-024-03508-4 -
International Journal of Circumpolar... Dec 2024It has previously been shown that EpiPen® autoinjectors are likely to activate normally following up to five excursions to -25°C but data about the post-freezing...
It has previously been shown that EpiPen® autoinjectors are likely to activate normally following up to five excursions to -25°C but data about the post-freezing performance of other brands of adrenaline autoinjectors has not previously been published. Additionally, conditions experienced by polar medics may be substantially colder than this and the performance of adrenaline autoinjectors following more extreme freeze-thaw cycles remains uncharacterised. Investigators in Antarctica and the United Kingdom performed laboratory testing on two brands of adrenaline autoinjector, EpiPen® and Jext® (12 devices of each type). A single freeze-thaw cycle involved freezing the device to -80°C then allowing it to come to room temperature. Devices were exposed to 0, 1, 5 or 15 freeze-thaw cycles. The mass of liquid ejected from each device, when activated, was then measured. No significant differences in the mass of the liquid ejected was found between the test groups. Multiple freeze-thaw cycles to -80°C are unlikely to significantly impact the amount of adrenaline solution expelled from EpiPen® and EpiPen® autoinjectors. This preliminary finding encourages further work investigating the safety and effectiveness of adrenaline autoinjectors after exposure to very low temperatures. This information would be valuable for future polar medics planning and delivering medical provision in extreme environments.
Topics: Epinephrine; Freezing; Humans; Cold Temperature; Injections, Intramuscular
PubMed: 38875453
DOI: 10.1080/22423982.2024.2367273 -
Medicine Jun 2024It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study,... (Observational Study)
Observational Study Randomized Controlled Trial
It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study, 172 adolescents aged 8 to 12 years who were admitted to the diopter department of Hengshui People Hospital from April 2021 to May 2022 were selected. According to the equivalent spherical diopter measured at the time of initial diagnosis, myopic patients were randomly divided into low myopia group (group A) and moderate myopia group (group B). At the same time, according to the different treatment methods, the patients were divided into the group wearing frame glasses alone (group c), the group wearing frame glasses with low-concentration Atropine (group d), the group wearing corneal shaping glasses alone at night (group e), and the group wearing corneal shaping glasses at night with low-concentration Atropine (group f). The control effect of myopia development and axial elongation in group f was better than that in groups d and e (P < .05). The effect of controlling myopia development and axial elongation in group f is with P > .05. The probability of postoperative adverse reactions in group f was lower and lower than that in the other groups. Low-concentration atropine combined with OK lens could effectively delay the development of juvenile myopia, and had a high safety. Low-concentration of Atropine would not have a significant impact on the basic tear secretion and tear film stability. Nightwear of OK lens also had no significant impact, but it would significantly reduce the tear film rupture time in the first 3 months, and at the same time, the tear film rupture time would be the same after 6 months as before treatment.
Topics: Humans; Atropine; Child; Myopia; Male; Female; Orthokeratologic Procedures; Prospective Studies; Mydriatics; Treatment Outcome; Ophthalmic Solutions; Contact Lenses
PubMed: 38875374
DOI: 10.1097/MD.0000000000038384 -
Biomedical Papers of the Medical... Jun 2024To present a new method of dynamic Purkinje-metry and to verify it by comparison with a commercially available anterior segment optical coherence tomography CASIA2.
AIMS
To present a new method of dynamic Purkinje-metry and to verify it by comparison with a commercially available anterior segment optical coherence tomography CASIA2.
PATIENTS AND METHODS
A dynamic Purkinje-meter with a movable fixation target was assembled. A coaxial circular pattern formed by infrared LEDs was projected onto the eye and evoked Purkinje images (1st, 3rd, 4th = P1, P3, P4). The measurement was performed on 29 eyes with an implanted toric IOL (intraocular lens), under mydriatic conditions, with reference to the visual axis. The IOL tilt was calculated from the position of a fixation target at the moment of P3 and P4 superposition. The IOL decentration was determined based on the relative position of P1 during on-axis fixation and of P3 and P4 superposition during off-axis fixation. A custom-developed software was used for distance measurements. Using CASIA2, the IOL position was fully calculated by the device.
RESULTS
The mean absolute difference between CASIA2 and Purkinje-meter values was 0.6° ± 0.4° for the tilt magnitude and 10° ± 10° for the tilt direction, and 0.11 mm ± 0.08 mm for the decentration magnitude and 16° ± 14° for the decentration direction. There was no statistically significant difference between the values determined by the two methods for the tilt and decentration direction. The differences were statistically significant for the tilt and decentration magnitude.
CONCLUSION
The values of IOL tilt and decentration direction are similar for both devices. The values of IOL tilt and decentration magnitude measured by Purkinje-meter are higher than those from CASIA2, but overall, they correspond to the values presented in other published studies.
PubMed: 38868995
DOI: 10.5507/bp.2024.017 -
Pediatric Allergy, Immunology, and... Jun 2024Povidone, a synthetic polymer commonly used in various products such as antiseptics, cosmetics, and medications, has been associated with allergic reactions, including... (Review)
Review
Povidone, a synthetic polymer commonly used in various products such as antiseptics, cosmetics, and medications, has been associated with allergic reactions, including anaphylaxis. Despite its widespread use, cases of povidone-induced anaphylaxis, especially in children, are under-recognized. This case report aims to highlight the importance of considering povidone allergy in pediatric patients presenting with anaphylaxis. We describe a 3-year-old boy who experienced anaphylaxis following the application of povidone-iodine antiseptic solution to a leg wound. He presented with generalized urticaria, angioedema, dyspnea, and cough. Prompt diagnosis and management were initiated in the emergency department. He experienced the second anaphylaxis with povidone-containing eye drops prescribed during an ophthalmology visit. Povidone allergy should be considered in pediatric patients presenting with anaphylaxis, especially those with idiopathic reactions or multiple drug allergies. Clinicians should emphasize patient education on label reading and the provision of adrenaline autoinjectors to prevent life-threatening reactions associated with povidone exposure.
Topics: Humans; Anaphylaxis; Male; Child, Preschool; Povidone-Iodine; Anti-Infective Agents, Local; Drug Hypersensitivity; Epinephrine; Ophthalmic Solutions
PubMed: 38864768
DOI: 10.1089/ped.2024.0036 -
Journal of Medicinal Chemistry Jun 2024Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis....
Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino ester , in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for ) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood-brain barrier, and negligible toxicity on nontumor normal human dermal fibroblasts. Compound represents an important complementary pharmacological tool to study the involvement of adrenoceptor subtypes in pathophysiologic conditions such as inflammation and sepsis and a novel candidate for further preclinical development to treat ADRA2A-mediated pathologies.
Topics: Humans; Receptors, Adrenergic, alpha-2; Yohimbine; Structure-Activity Relationship; Drug Design; Adrenergic alpha-2 Receptor Antagonists; Animals
PubMed: 38857067
DOI: 10.1021/acs.jmedchem.4c00323 -
Phytomedicine : International Journal... Aug 2024Alzheimer's disease (AD) is a serious neurodegenerative disease and brings a serious burden to society and families. Due to lack of effective drugs for the treatment of...
Zexieyin formula alleviates Alzheimer's disease via post-synaptic CaMKII modulating AMPA receptor: Involved in promoting neurogenesis to strengthen synaptic plasticity in mice hippocampus.
BACKGROUND
Alzheimer's disease (AD) is a serious neurodegenerative disease and brings a serious burden to society and families. Due to lack of effective drugs for the treatment of AD, it's urgent to develop new and effective drug for the treatment of AD.
PURPOSE
The study aimed to investigate the potential of Zexieyin formula (ZXYF), a Chinese medicine formula, for the treatment of AD and its potential mechanism of action.
METHODS
We used chronic scopolamine (SCOP) induction mice model and APP/PS1 mice to reveal and confirm ZXYF for the treatment of AD with donepezil (DON) as a positive reference. The learning and memory function were detected by morris water maze test (MWM) and y-maze test. Moreover, western blot and immunofluorescence were used to detect the molecular mechanism of ZXYF for the alleviation of AD in hippocampus. Lastly, pharmacological technology was applied to evaluate AMPA receptor involved in the role of ZXYF in the treatment of AD.
RESULTS
The results showed that ZXYF could improve memory and learning deficits both in two AD models including scopolamine (SCOP)-induced mice model and APP/PS1mice. Moreover, ZXYF or not DON increased expressions of BrdU/DCX and Ki67 positive cells in dentate gyrus (DG), up-regulated the levels of AMPA subunit type (GluA1) and PKA in hippocampus in SCOP-induced mice model, although ZXYF and DON activated CaMKII, CaMKII-phosphorylation, CREB, CREB-phosphorylation and PSD95 in hippocampus in SCOP-induced mice model. ZXYF also activated CaMKII, CaMKII-phosphorylation and GluA1 in HT22 cells. Furthermore, transient inhibiting AMPA receptor was capable of blocking the effects of ZXYF to treat AD in MWM and suppressing the number of BrdU/DCX positive cells increased by ZXYF in DG in SCOP-induced mice model, but had no effect on the alteration of Ki67 positive cells.
CONCLUSION
ZXYF had the therapeutic effects on AD-treatment, which activated CaMKII to promote AMPA receptor (GluA1) and subsequently up-regulated PKA/CREB signaling to facilitate neurogenesis to achieve enhanced postsynaptic protein.
Topics: Animals; Alzheimer Disease; Receptors, AMPA; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Drugs, Chinese Herbal; Hippocampus; Neurogenesis; Disease Models, Animal; Mice; Male; Neuronal Plasticity; Scopolamine; Mice, Transgenic; Maze Learning; Donepezil; Cyclic AMP Response Element-Binding Protein; Memory; Mice, Inbred C57BL
PubMed: 38852473
DOI: 10.1016/j.phymed.2024.155802