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European Heart Journal Jun 2024The spleen serves as an important relay organ that releases cardioprotective factor(s) upon vagal activation during remote ischaemic conditioning (RIC) in rats and pigs....
BACKGROUND AND AIMS
The spleen serves as an important relay organ that releases cardioprotective factor(s) upon vagal activation during remote ischaemic conditioning (RIC) in rats and pigs. The translation of these findings to humans was attempted.
METHODS
Remote ischaemic conditioning or electrical auricular tragus stimulation (ATS) were performed in 10 healthy young volunteers, 10 volunteers with splenectomy, and 20 matched controls. Venous blood samples were taken before and after RIC/ATS or placebo, and a plasma dialysate was infused into isolated perfused rat hearts subjected to global ischaemia/reperfusion.
RESULTS
Neither left nor right RIC or ATS altered heart rate and heart rate variability in the study cohorts. With the plasma dialysate prepared before RIC or ATS, respectively, infarct size (% ventricular mass) in the recipient rat heart was 36 ± 6% (left RIC), 34 ± 3% (right RIC) or 31 ± 5% (left ATS), 35 ± 5% (right ATS), and decreased with the plasma dialysate from healthy volunteers after RIC or ATS to 20 ± 4% (left RIC), 23 ± 6% (right RIC) or to 19 ± 4% (left ATS), 26 ± 9% (right ATS); infarct size was still reduced with plasma dialysate 4 days after ATS and 9 days after RIC. In a subgroup of six healthy volunteers, such infarct size reduction was abrogated by intravenous atropine. Infarct size reduction by RIC or ATS was also abrogated in 10 volunteers with splenectomy, but not in their 20 matched controls.
CONCLUSIONS
In humans, vagal innervation and the spleen as a relay organ are decisive for the cardioprotective signal transduction of RIC and ATS.
PubMed: 38842545
DOI: 10.1093/eurheartj/ehae250 -
Journal of Oral Rehabilitation Jun 2024It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication.
BACKGROUND
It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication.
OBJECTIVES
We aimed to clarify: (1) how hyposalivation affects jaw-closing and hyoid-elevating muscle activities in bolus formation, and (2) if the effect of hyposalivation on muscle activity depends on the fat content of food.
METHODS
Eighteen healthy male volunteers were instructed to freely ingest four test foods: Plain, Fat without seasoning, Fat with seasoning, and Soft rice crackers. Masseter and suprahyoid electromyographic activities were recorded before and 30 min after the administration of atropine sulfate, a muscarinic receptor antagonist that induces hyposalivation.
RESULTS
Hyposalivation extended the masticatory duration significantly in all the test foods except Fat with seasoning. Masticatory cycle time was significantly longer with vs without hyposalivation for the Soft (p = .011). Suprahyoid activity/cycle was significantly greater with vs without hyposalivation (p = .013). Masticatory cycle time was significantly longer at the late stage with vs without hyposalivation for the Soft (p < .001). Suprahyoid activity/cycle was significantly greater at the middle (p = .045) and late stages (p = .002) with vs without hyposalivation for the Soft and greater at the late stage with vs without hyposalivation for the Plain (p = .043). Changes in masticatory cycle time and suprahyoid activity/cycle for these foods had significantly positive relationship (p < .001).
CONCLUSION
Hyposalivation-induced changes in masticatory behaviours resulted from the middle and late stage suprahyoid activity. Fat content and seasoning compensate for salivary flow inhibition.
PubMed: 38840501
DOI: 10.1111/joor.13764 -
Journal of Applied Toxicology : JAT Jun 2024Glyphosate (GLY) is a pesticide that severely alters nigrostriatal dopaminergic neurotransmission, inducing great increases in dopamine release from rat dorsal striatum....
Glyphosate (GLY) is a pesticide that severely alters nigrostriatal dopaminergic neurotransmission, inducing great increases in dopamine release from rat dorsal striatum. This GLY-induced striatal dopamine overflow occurs through mechanisms not yet fully understood, hence the interest in evaluating the role of other neurotransmitter systems in such effects. So, the main objective of this mechanistic study was to evaluate the possible mediation of the glutamatergic, cholinergic, and nitrergic systems in the GLY-induced in vivo dopamine release from rat dorsal striatum. The extracellular dopamine levels were measured by cerebral microdialysis and HPLC with electrochemical detection. Intrastriatal administration of GLY (5 mmol/L) significantly increased the dopamine release (1102%). Pretreatment with MK-801 (50 or 400 μmol/L), a non-competitive antagonist of NMDA receptors, significantly decreased the effect of GLY (by 70% and 74%, respectively), whereas AP-5 (400 μmol/L), a competitive antagonist of NMDA receptors, or CNQX (500 μmol/L), an AMPA/kainate receptor antagonist, had no significant effect. Administration of the nitric oxide synthase inhibitors, L-nitroarginine (L-NAME, 100 μmol/L) or 7-nitroindazole (7-NI, 100 μmol/L), also did not alter the effect of GLY on dopamine release. Finally, pretreatment of the animals with mecamylamine, an antagonist of nicotinic receptors, decreased the effect of GLY on dopamine release by 49%, whereas atropine, a muscarinic antagonist, had no significant effect. These results indicate that GLY-induced dopamine release largely depends on the activation of NMDA and nicotinic receptors in rat dorsal striatum. Future research is needed to determine the effects of this pesticide at environmentally relevant concentrations.
PubMed: 38828527
DOI: 10.1002/jat.4651 -
Cureus May 2024Oculocardiac reflex (OCR), presenting as bradycardia and asystole, is a potential intraoperative complication that may occur during maxillofacial trauma surgery....
Oculocardiac reflex (OCR), presenting as bradycardia and asystole, is a potential intraoperative complication that may occur during maxillofacial trauma surgery. Bradycardia is the most common symptom of this phenomenon. Surgeons should be aware of its long-term effects, such as arrhythmias and even cardiac arrest. We report the case of a 40-year-old male patient with a fracture of the floor of the orbit. During a surgical exploration of the orbital floor, the patient exhibited sudden symptoms of OCR. It was managed by withholding the surgery and administering atropine. The article also highlights the mechanism, types, incidence, and management of OCR in patients with maxillofacial trauma.
PubMed: 38827001
DOI: 10.7759/cureus.59528 -
Food Research International (Ottawa,... Jul 2024Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC)...
Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC) 2023/915 sets maximum levels for atropine and scopolamine in cereal-based foods for infants containing millet, sorghum, buckwheat or their derived products. The aim of this study was to evaluate the effect of pH and temperature on the stability of TAs, as possible parameters in thermal processing to mitigate this chemical hazard in cereal-based infant food. The effect of pH (4 and 7) and temperature (80 °C and 100 °C) was assessed in buffer solutions. Also, treatment at 180 °C was performed in spiked and naturally incurred millet flour to assess the effect of high temperature, simulating cooking or drying, on the stability of TAs in the cereal matrix. The fate of 24 TAs was assessed by UHPLC-MS/MS. TAs showed high thermostability, although it was variable depending on the specific compound, pH, temperature and treatment time. In buffer solutions, higher degradation was found at 100 °C and pH 7. In spiked millet flour at 180 °C for 10 min, scopolamine and atropine contents decreased by 25 % and 22 %, similarly to other TAs which also showed a slow thermal degradation. Atropine, scopolamine, anisodamine, norscopolamine, scopine and scopoline were found in naturally contaminated millet flour. Interestingly, naturally incurred atropine was more thermostable than when spiked, showing a protective effect of the cereal matrix on TAs degradation. The present results highlight the need for an accurate monitorization of TAs in raw materials, as this chemical hazard may remain in infant cereal-based food even after intense thermal processing.
Topics: Edible Grain; Hydrogen-Ion Concentration; Infant Food; Tandem Mass Spectrometry; Food Contamination; Tropanes; Temperature; Alkaloids; Humans; Food Handling; Hot Temperature; Atropine; Infant; Chromatography, High Pressure Liquid
PubMed: 38823829
DOI: 10.1016/j.foodres.2024.114439 -
International Journal of Pharmaceutics May 2024Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and...
Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.
PubMed: 38823467
DOI: 10.1016/j.ijpharm.2024.124294 -
PloS One 2024Poisoning is a significant public health problem globally. Ethiopia is a low-income country undergoing technological and social change that may increase access to drugs... (Observational Study)
Observational Study
BACKGROUND
Poisoning is a significant public health problem globally. Ethiopia is a low-income country undergoing technological and social change that may increase access to drugs and chemicals, potentially increasing the incidence of poisoning. This study describes the epidemiology of hospital admissions due to poisoning in a region of Ethiopia.
METHODS
An institution based prospective observational study was employed, as a study design, in selected hospitals of the region from January to December 2018.
RESULTS
Of 442 poisoning cases, 78 (17.6%) died. Almost all poisoning cases were intentional self-poisonings. The most frequent poisonings were organophosphate compounds, 145 (32.8%), and metal phosphides (majorly aluminum phosphide), 115 (26.0%). The ingested poison was most frequently accessed from the patients' homes, 243 (55.0%), followed by purchases from local shops, 159 (36%). The median duration of admission was 24 hours. Of all the cases, 23 (5.2%) were admitted to intensive care units (ICU) requiring mechanical ventilation. Most of the cases admitted to the ICU were aluminum phosphide-poisoned patients. The majority of deaths (43 of 78) were due to metal phosphides. From the multivariate logistic regression analysis, altered level of consciousness on hospital arrival, metal phosphide poisoning, and no laboratory result as a part of the diagnosis process or investigation of the extent of toxicity were found to be significantly associated with the likelihood of poor treatment outcome.
CONCLUSION
The majority of the poisoning cases were females. The most common reasons for the intent of self-poisoning were dispute-related, mainly family disharmonies, followed by psychiatric conditions. The poisoning agents were mostly obtained from households. Organophosphate compounds and metal phosphides were the first and the second most frequently encountered poisoning agents, respectively, and it was noted that the later ones were responsible for most of the fatal cases. Of the pharmacologic interventions, atropine was the only agent regarded as an antidote. The most commonly employed agent for supportive treatment was cimetidine followed by maintenance fluids, while gastric lavage was the only GI decontamination method used among others. The fatality rate of poisoning in this study was found to be much higher than in other similar studies. Impaired consciousness upon hospital arrival, metal phosphide poisoning, and no involvement of laboratory investigation were found to significantly associate with the likelihood of death. Generally, the results dictate the need for the design and implementation of strategies to create awareness, prevent, and manage poisoning incidences in the community.
Topics: Humans; Ethiopia; Female; Male; Adult; Prospective Studies; Middle Aged; Poisoning; Adolescent; Young Adult; Phosphines; Hospitalization; Child; Aged; Aluminum Compounds; Intensive Care Units; Hospitals; Child, Preschool
PubMed: 38820326
DOI: 10.1371/journal.pone.0303438 -
Clinical Hematology International 2024Cyclosporine A (CSA) is a commonly used immunosuppressive agent for the prophylaxis of graft-versus-host disease following allogeneic hematopoietic stem cell...
Cyclosporine A (CSA) is a commonly used immunosuppressive agent for the prophylaxis of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (alloHSCT). While tachycardia is a known adverse effect of CSA, bradycardia remains a phenomenon rarely described in the literature. We conducted a retrospective evaluation of the incidence of bradycardia in patients after alloHSCT treated with CSA between January 2020 and February 2023 at our center. Out of 206 patients, sinus bradycardia following the administration of CSA was observed in 6 (2.9%), comprising 3 women and 3 men, with the median age of 55 years (range: 20-65). The underlying diseases were myeloid malignancies in 4 and aggressive lymphoma in 2 patients. The patients received grafts from a matched unrelated (n=5) or a haploidentical family donor (n=1) following various conditioning regimens. Coexisting cardiovascular disorders were found in 5 of the 6 patients. All patients experienced symptomatic bradycardia within 1-4 days (median 2 days) after CSA introduction, which persisted until CSA withdrawal. One patient required treatment with atropine. All patients continued their immunosuppressive therapy with tacrolimus, which was well-tolerated Our study indicates CSA as a causative factor of sinus bradycardia in a small percentage of alloHSCT patients receiving CSA as graft-versus host disease (GvHD) prophylaxis. Importantly, these patients did not experience any cardiac complications when switched to tacrolimus. Although further research on the effects of CSA on heart automatation is needed, our single-center experience can help prompt diagnosis and therapeutic intervention in daily clinical practice.
PubMed: 38817698
DOI: 10.46989/001c.94362 -
Journal of AAPOS : the Official... May 2024Hypotony is a rare postoperative complication of strabismus surgery. Resolution has been reported to occur within 1 month of surgery. Here, we describe the case of a...
Hypotony is a rare postoperative complication of strabismus surgery. Resolution has been reported to occur within 1 month of surgery. Here, we describe the case of a 14-year-old boy with prolonged hypotony maculopathy following uneventful bilateral medial rectus recession. The hypotony resolved without long-term sequela after 7 months of treatment with topical steroids and atropine. Ultrasound biomicroscopy revealed a ciliary body effusion, which we hypothesize was the cause of decreased aqueous humor production and hypotony.
PubMed: 38815649
DOI: 10.1016/j.jaapos.2024.103939 -
Journal of Applied Physiology... May 2024Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardio-vagal arms. Since sympathetic post-ganglionic neurons also innervate the...
BACKGROUND
Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardio-vagal arms. Since sympathetic post-ganglionic neurons also innervate the left ventricle (LV), it is oft-assumed that the LV produces a sympathetically-mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine a) whether LV contractility increases in response to baroreceptor unloading, and b) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system.
METHODS
Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/dt)], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol+atropine.
RESULTS
Under control conditions, PAdP/dt increased during baroreceptor unloading (26±6 vs. 31±9 mmHg·s·μL, p=0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11±2 vs. 12±2, p=0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26±6 vs. 31±9, p=0.019). During combined esmolol and atropine, there was a small increase in contractility vs control (13±3 vs. 15±4, p=0.046).
CONCLUSION
Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated.
PubMed: 38813608
DOI: 10.1152/japplphysiol.00722.2023