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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 -
Anesthesiology May 2024
PubMed: 38810018
DOI: 10.1097/ALN.0000000000005009 -
Klinische Monatsblatter Fur... May 2024Over the past decade, atropine has emerged as an effective intervention for preventing myopia in children. Multiple randomized controlled trials, mainly from Asia, have...
Over the past decade, atropine has emerged as an effective intervention for preventing myopia in children. Multiple randomized controlled trials, mainly from Asia, have demonstrated the safety and efficacy of topical atropine for myopia control. Both efficacy and side effects exhibit a positive dose-response relationship. This review focuses on new data from studies with predominantly white populations, ethnicity-dependent differences in efficacy and side effects, and primary prevention of incident myopia with atropine.
PubMed: 38802078
DOI: 10.1055/a-2307-0363 -
Journal of Ethnopharmacology Oct 2024Rosmarinus officinalis L. (Rosemary) is a popular herb with reported effectiveness against diarrhea, anxiety and constipation, albeit with limited pharmacological...
ETHNOPHARMACOLOGICAL RELEVANCE
Rosmarinus officinalis L. (Rosemary) is a popular herb with reported effectiveness against diarrhea, anxiety and constipation, albeit with limited pharmacological evidence.
AIM OF THE STUDY
The current study was aimed at evaluating the therapeutic potential, possible pharmacological mechanisms of action and active constituents of hydro-ethanolic extract of rosemary (Rs.Cr), as potential anti-diarrheal, laxative and anxiolytic agent.
METHOD
Rs.Cr was analyzed through reverse-phase high pressure liquid chromatography (RP-HPLC). Laxative, antidiarrheal, and anxiolytic activities were assessed using in vivo models. Spasmogenic and spasmolytic mechanisms were studied on isolated guinea pig ileum and rabbit jejunum tissues, respectively. Possible role of diosmetin, one of the active constituents of Rs.Cr was also evaluated.
RESULTS
RP-HPLC analysis revealed presence of diosmetin, rutin and apigenin in Rs.Cr. Laxative effect was seen at low doses, which was partially reversed in atropinized mice. The spasmogenic mechanism was mediated by cholinergic and histaminergic receptors stimulation. At higher doses, antidiarrheal activity was evident, with reduction in gastrointestinal motility and secretions using charcoal meal and enteropooling assays, respectively. Rs.Cr also showed dose-dependent anxiolytic effect. The antispasmodic mechanisms were mediated by anti-muscarinic and K channel opening-like effect (predominant K-dependent). Diosmetin exhibited antidiarrheal and antispasmodic activities, but spasmogenic effect was not seen.
CONCLUSION
Rosemary leaves have dual antidiarrheal and laxative effects, and as well as anxiolytic activity. In addition, the possible modulation of muscarinic and histaminergic receptors, and K channels show it as potential herb to be explored for irritable bowel syndrome. Diosmetin is possibly one of its constituents that contributes to its antidiarrheal activity.
Topics: Animals; Guinea Pigs; Rosmarinus; Plant Extracts; Mice; Male; Gastrointestinal Motility; Rabbits; Anti-Anxiety Agents; Ileum; Antidiarrheals; Flavonoids; Parasympatholytics; Laxatives; Jejunum; Diarrhea; Female
PubMed: 38801915
DOI: 10.1016/j.jep.2024.118395 -
American Journal of Health-system... May 2024In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been...
DISCLAIMER
In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
PURPOSE
In high-acuity situations such as cardiac arrest, clinicians rely on prepared medications stocked in code carts to provide timely and accurate pharmacotherapy. We examined shortage trends for medications commonly used in code carts.
METHODS
Drug shortage data from 2001 to 2022 were retrieved from the University of Utah Drug Information Service (UUDIS) to characterize shortages reported for commonly used code cart medications. Data extracted included the number of shortages, shortage duration, drug characteristics, and reason for the shortage.
RESULTS
From 2001 to 2022, 71 drug shortages for code cart medications were reported. The number of new shortages peaked in 2010, and the number of total shortages peaked in 2010. At the end of the study period, 61 (84.7%) shortages had been resolved. For resolved shortages, the mean shortage duration was 18.2 months. The drug with the greatest number of reported shortages was dextrose (10 total), the drug with the longest resolved shortage was calcium chloride injection (116 months), and the drug with the longest active shortage was atropine injection (165 months at the end of the study period). Throughout the entire study period, only 2 suppliers provided commercially available prefilled syringes of dextrose for stocking on code carts. The most common reason for shortages, when reported, was manufacturing delays.
CONCLUSION
Medications commonly used in code carts were frequently impacted by drug shortages, which have the potential to impact patient care. Institutional protocols for mitigation and larger efforts to promote a more resilient drug supply chain are critical to ensure patient safety and quality care.
PubMed: 38800925
DOI: 10.1093/ajhp/zxae150 -
Cureus Apr 2024Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by...
Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by medications used in intensive care settings, such as atropine and pralidoxime methyl (PAM). Because of this, there are no established methods for assessing the duration of OP while receiving antidotal treatment. In the present case, we used the Neurological Pupil Index (NPi) to evaluate the duration of OP in an 82-year-old woman who attempted suicide by ingesting up to 100 mL of fenitrothion. Until hospitalization day (HD) 20, discontinuation of atropine led to the recurrence of altered consciousness, while its reinstatement resulted in improvement; this made it difficult to assess the prolongation of OP based on signs and symptoms. Until HD 20, the NPi remained at 0/0, and subsequently, it increased. Additionally, even after discontinuing atropine, consciousness, tearing, and salivation did not worsen, indicating recovery from OP. On HD 26, serum acetylcholinesterase (AChE) levels were elevated above the measurable level for the first time, following an increase in the NPi. In this case, assessing the persistence of OP based on signs was challenging because these signs improved with atropine and PAM treatment. The improvement in NPi levels coincided with an improvement in poisoning, suggesting that NPi is useful for evaluating the duration of OP. NPi is noninvasive and sensitive compared to AChE, which is used to gauge the persistence of OP and could be used to allow earlier cessation of medication and guide appropriate treatment durations.
PubMed: 38800312
DOI: 10.7759/cureus.58872 -
JFMS Open Reports 2024A 1-year-old male neutered domestic shorthair cat presented on an emergency basis with clinical signs suspected to be secondary to organophosphate (OP) toxicity. The...
CASE SUMMARY
A 1-year-old male neutered domestic shorthair cat presented on an emergency basis with clinical signs suspected to be secondary to organophosphate (OP) toxicity. The control of clinical abnormalities (bradycardia, obtundation, tachypnea, anorexia) was achieved using high-dose continuous rate intravenous infusion (CRI) of atropine sulfate (maximum rate 0.1 mg/kg/h). After 5 days of hospitalization, the patient made a full clinical recovery without the development of atropine toxicity, intermediate syndrome or delayed polyneuropathy at 4 weeks after discharge.
RELEVANCE AND NOVEL INFORMATION
Treatment of OP toxicity in cats is sparsely reported in veterinary literature. Current standards of treatment and published protocols recommend the use of atropine sulfate as intermittent boluses for the treatment of muscarinic signs of toxicity; however, there is a paucity of information regarding the safety and efficacy of atropine sulfate as a CRI for severe toxicosis as described in humans. This report includes the first published case using such a treatment protocol in a cat.
PubMed: 38799116
DOI: 10.1177/20551169241249637 -
Current Reviews in Clinical and... May 2024There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and...
OBJECTIVE
There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.
METHODOLOGY
Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.
RESULTS
A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.
CONCLUSION
Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.
PubMed: 38797902
DOI: 10.2174/0127724328290595240509051331 -
Pharmaceuticals (Basel, Switzerland) May 2024Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative...
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
PubMed: 38794204
DOI: 10.3390/ph17050633 -
Life (Basel, Switzerland) May 2024Scopolamine and atropine are two medicinal alkaloids derived from L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth...
Modulation of Tropane Alkaloids' Biosynthesis and Gene Expression by Methyl Jasmonate in L.: A Comparative Analysis of Scopolamine, Atropine, and Hyoscyamine Accumulation.
Scopolamine and atropine are two medicinal alkaloids derived from L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth regulator, affects the biosynthesis and accumulation of these alkaloids in different plant tissues. The expression levels of putrescine N-methyltransferase (), tropinone reductase I (), and hyoscyamine 6β-hydroxylase (), three critical enzymes in the biosynthetic pathway, were also analyzed. The results indicated that MJ at 150 µM increased the production of scopolamine and atropine in both leaves and roots, while MJ at 300 µM had an adverse effect. Furthermore, MJ enhanced the expression of , and genes in the roots, the primary site of alkaloid synthesis, but not in the leaves, the primary site of alkaloid storage. These results imply that MJ can be applied to regulate the biosynthesis and accumulation of scopolamine and atropine in , thereby improving their production efficiency.
PubMed: 38792639
DOI: 10.3390/life14050618