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Frontiers in Neurology 2024Current literature extensively covers the use of sphenopalatine ganglion stimulation (SPGs) in treating a broad spectrum of medical conditions, such as allergic...
BACKGROUND
Current literature extensively covers the use of sphenopalatine ganglion stimulation (SPGs) in treating a broad spectrum of medical conditions, such as allergic rhinitis, cluster headaches, and strokes. Nevertheless, a discernible gap in the systematic organization and analysis of these studies is evident. This paper aims to bridge this gap by conducting a comprehensive review and analysis of existing literature on SPGs across various medical conditions.
METHODS
This study meticulously constructed a comprehensive database through systematic computerized searches conducted on PubMed, Embase, CNKI, Wanfang, VIP, and CBM up to May 2022. The inclusion criteria encompassed randomized controlled trials (RCTs) published in either Chinese or English, focusing on the therapeutic applications of SPGs for various medical conditions. Both qualitative and quantitative outcome indicators were considered eligible for inclusion.
RESULTS
This comprehensive study reviewed 36 publications, comprising 10 high-quality, 23 medium-quality, and three low-quality articles. The study investigated various diseases, including allergic rhinitis (AR), ischemic strokes (IS), cluster headache (CH), primary trigeminal neuralgia (PTN), pediatric chronic secretory otitis (PCSO), refractory facial paralysis (RFP), chronic tension-type headache (CTTH), as well as the analysis of low-frequency sphenopalatine ganglion stimulation (LF-SPGs) in chronic cluster headache (CCH) and the impact of SPGs on Normal nasal cavity function (NNCF). SPGs demonstrate efficacy in the treatment of AR. Regarding the improvement of rhinoconjunctivitis quality of life questionnaire (RQLQ) scores, SPGs are considered the optimal intervention according to the SUCRA ranking. Concerning the improvement in Total Nasal Symptom Score (TNSS), Conventional Acupuncture Combined with Tradiational Chinese Medicine (CA-TCM) holds a significant advantage in the SUCRA ranking and is deemed the best intervention. In terms of increasing Effective Rate (ER), SPGs outperformed both conventional acupuncture (CA) and Western Medicine (WM; < 0.05). In the context of SPGs treatment for IS, the results indicate a significant improvement in the 3-month outcomes, as evaluated by the modified Rankin Scale (mRS) in the context of Cerebral Cortical Infarction (CCI; < 0.05). In the treatment of CH with SPGs, the treatment has been shown to have a statistically significant effect on the relief and disappearance of headaches ( < 0.05). The impact of SPGs on NNCF reveals statistically significant improvements ( < 0.05) in nasal airway resistance (NAR), nasal cavity volume (NCV), exhaled nitric oxide (eNO), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). SPGs treatments for PCSO, RFP, and CTTH, when compared to control groups, yielded statistically significant results ( < 0.05).
CONCLUSION
SPGs demonstrate significant effectiveness in the treatment of AR, IS, and CH. Effective management of CCH may require addressing both autonomic dysregulation and deeper neural pathways. However, additional high-quality research is essential to clarify its effects on NNCF, PTN, PCSO, RFP, and CTTH.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42021252073, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=312429.
PubMed: 38813242
DOI: 10.3389/fneur.2024.1352145 -
Bioorganic Chemistry Aug 2024While cross-linked hemoglobin tetramers are functional acellular oxygen carriers, their ability to scavenge endogenous nitric oxide (NO) by endothelial pore penetration...
Efficient conversion of hemoglobin to a non-vasoactive oxygen carrier by site-specific cross-linking with azido acyl methyl phosphates followed by bio-orthogonal CuAAC with a bis-alkyne.
While cross-linked hemoglobin tetramers are functional acellular oxygen carriers, their ability to scavenge endogenous nitric oxide (NO) by endothelial pore penetration results in adverse cardiovascular effects. Animal studies established that cross-linked human hemoglobins, chemically joined into a double protein, avoid NO scavenging, presumably due to their larger size preventing penetration into endothelial regions that produce NO. In the present report, we utilize azide-containing acyl phosphate reagents to form cross-linked hemoglobins then bio-orthogonally click-couple them with a bis-alkyne (CuAAC). The production of these larger oxygen-carrying hemoglobin conjugates is obtained in high yields through subunit-specific cross-linking between each βLys82 ε-amino group. The methyl phosphate leaving groups provide electrostatically induced β-subunit site-selectivity, producing azido-cross-linked hemoglobin that undergoes highly efficient CuAAC compared with previous cross-linkers. The acyl phosphates also efficiently cross-link both T-state and R-state hemoglobin. The resulting bis- and tris-tetrameric hemoglobin conjugates exhibit oxygen affinity and cooperativity that are comparable to those of the native protein. The hemoglobin derivatives from the process we describe can function as sources of oxygen in biomedical applications, such as in ex-vivo donor organ perfusion.
Topics: Alkynes; Hemoglobins; Azides; Cross-Linking Reagents; Humans; Oxygen; Molecular Structure; Click Chemistry; Copper
PubMed: 38810483
DOI: 10.1016/j.bioorg.2024.107464 -
Drug Design, Development and Therapy 2024Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Clinical Trial
Comparison of Remimazolam Tosilate and Propofol Sedation on the Early Postoperative Quality of Recovery in Patients Undergoing Day Surgery: A Prospective Randomized Controlled Trial.
PURPOSE
Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few articles are still focusing on the quality of recovery after general anesthesia with remimazolam, especially in day surgery. This study aimed to compare the early postoperative quality of recovery of remimazolam tosilate with flumazenil and propofol in patients undergoing day surgery.
PATIENTS AND METHODS
137 patients scheduled for day surgery were randomly divided into the remimazolam tosilate or propofol group. The primary endpoint was the incidence of overall recovery assessed with the early postoperative quality of recovery scale (PostopQRS) on postoperative day 1 (POD 1). The Richmond Agitation-Sedation Scale (RASS) scores in the post-anesthesia care unit (PACU), extubation time, postoperative recovery profiles, and perioperative data were documented. Any adverse events were recorded.
RESULTS
The incidence of overall recovery on POD1 was 47.7% in the remimazolam tosilate group and 65.1% in the propofol group (odds ratio, 0.52; 95% confidence interval (CI) 0.26 to 1.06; P = 0.072). In general, the overall recovery of the PostopQRS increased over time, and its interaction between time and group was significant (P = 0.003). Among the five dimensions of PostopQRS, there exist statistical differences between groups including emotional state and cognitive recovery. Upon arrival at the PACU, the remimazolam group was more sedated and took longer to recover to a RASS score similar to propofol. The frequency of application of vasoactive drugs during anesthesia was similar in both groups (P = 0.119). Despite rapid emergence with remimazolam after flumazenil reversal, re-sedation (10.8%) or somnolence (60%) in the PACU was observed, and the length of PACU stay in patients treated with remimazolam tosilate was longer than that of the propofol (35 min vs 30 min, P<0.001).
CONCLUSION
General anesthesia with remimazolam tosilate in conjunction with flumazenil reversal permits rapid recovery of consciousness in day surgery, but there was a notable occurrence of re-sedation or somnolence observed in PACU.
Topics: Humans; Propofol; Female; Male; Prospective Studies; Middle Aged; Benzodiazepines; Hypnotics and Sedatives; Adult; Ambulatory Surgical Procedures; Anesthesia Recovery Period; Aged; Flumazenil
PubMed: 38803562
DOI: 10.2147/DDDT.S456675 -
ACS Omega May 2024Autoimmune disorders include vast and distinct illnesses and are characterized by an immune system-mediated attack on the body's own tissues. Because of their ability to...
-Chalcone (1-3-diphenyl-2-propen-1-one) as a Therapeutic Candidate in Joint Inflammation via Reduction of TNF-α, IL-1β, IL-6, and IL-17 in Rodents: An Study by RT-PCR and ELISA analysis.
Autoimmune disorders include vast and distinct illnesses and are characterized by an immune system-mediated attack on the body's own tissues. Because of their ability to impact any portion of the body, their clinical symptoms are incredibly varied. The variations in symptoms are normally linked with the release and activation of vasoactive, chemotactic substances and cytokines. Cytokines perform a multitude of vital biological tasks, such as immune response control, inflammation, proliferation, and tissue repair. The reversal of inflammatory cytokines and leukocyte infiltration into the inflamed tissue by natural compounds provides an effective remedy for autoimmune diseases. Here, the oral administration of -chalcone (TC) for 28 days was tested with gradually increasing doses (30, 60, and 120 mg/kg) in complete Freund's adjuvant (CFA)-provoked joint tissue stiffness in rats. Paw edema, arthritic index, joint stiffness, thermal and flexion pain, C-reactive protein, and rheumatoid factor (RF) levels were determined to check the tested drug effectiveness in a chronic inflammatory model. Molecular docking studies revealed strong binding affinity with inflammatory cytokines and mediators such as TNF-α, IL-17, COX-2, and iNOS; further, they were quantified at the mRNA level by RT-PCR and ELISA analysis. Oral administration of TC significantly ameliorated paw edema, thymus and spleen indices, joint stiffness, thermal and flexion pain, C-reactive protein, RF, mobility, and stance of the treated animals. This therapeutic effectiveness was linked with a reduction in the mRNA expression of proinflammatory cytokines such as IL-1β, IL-6, and IL-17. The findings of the reported research confirmed the effectiveness of TC in ameliorating joint stiffness and flexion pain by prominently lowering the inflammatory cytokines.
PubMed: 38799342
DOI: 10.1021/acsomega.4c00368 -
Biomedicines May 2024The vasoactive peptide bradykinin (BK) is an important member of the renin-angiotensin system. Its discovery is tightly interwoven with snake venom research, because it...
The vasoactive peptide bradykinin (BK) is an important member of the renin-angiotensin system. Its discovery is tightly interwoven with snake venom research, because it was first detected in plasma following the addition of viper venom. While the fact that venoms liberate BK from a serum globulin fraction is well described, its destruction by the venom has largely gone unnoticed. Here, BK was found to be cleaved by snake venom metalloproteinases in the venom of , one of the deadliest snakes, which degraded its dabsylated form (DBK) in a few minutes after Pro7 (RPPGFSP↓FR). This is a common cleavage site for several mammalian proteases such as ACE, but is not typical for matrix metalloproteinases. Residual protease activity < 5% after addition of EDTA indicated that DBK is also cleaved by serine proteases to a minor extent. Mass spectrometry-based protein analysis provided spectral proof for several peptides of zinc metalloproteinase-disintegrin-like Eoc1, disintegrin EO4A, and three serine proteases in the venom.
PubMed: 38790989
DOI: 10.3390/biomedicines12051027 -
Children (Basel, Switzerland) May 2024(1) Background: Sepsis management in children is crucial, especially in emergency services. This study aims to evaluate Thai physicians' knowledge gaps in the emergency...
(1) Background: Sepsis management in children is crucial, especially in emergency services. This study aims to evaluate Thai physicians' knowledge gaps in the emergency management of sepsis in children and to evaluate their adherence to the current sepsis clinical practice guidelines. (2) Methods: This is a cross-sectional survey of Thai physicians' management of septic shock in children. The survey was conducted through online questionnaires from March 2019-April 2019. (3) Results: Of the 366 responders, 362 (98.9%) were completed. Most of the responders were general practitioners (89.2%) and pediatricians (10.8%). The time from positive sepsis screening to being evaluated by physicians within 15 min was reported by 83.9%. The most common choice of fluid resuscitation was normal saline solution (77.3%). The practice of a fluid loading dose (20 mL/kg) consistent with the guidelines was 56.3%. The selection of the first vasoactive agent in warm shock (norepinephrine) and cold shock (epinephrine) according to recommendations in the guidelines was 74.3% and 36.2%, respectively. There was a significant difference between general practitioners and pediatricians in terms of knowledge about initial fluid resuscitation and the optimal vasoactive agent in cold shock (value < 0.001). In the multivariate model, factors associated with the guideline-based decision-making of vasoactive agent choice for cold shock were specialist training (pediatrician) and the completion of sepsis management training certification, with adjusted odds ratios (AORs) of 7.81 and 2.96, but working experience greater than ten years was inconsistent with the guideline-based decision-making (AOR 0.14). (4) Conclusions: Thai clinicians were unfamiliar with pediatric sepsis therapy standards, specifically the quantity of early fluid resuscitation and the appropriate vasoactive medications for cold shock. To encourage adherence to the guidelines, we propose a regularly required training course on pediatric sepsis management.
PubMed: 38790592
DOI: 10.3390/children11050597 -
Children (Basel, Switzerland) May 2024Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD)....
OBJECTIVES
Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates.
METHODOLOGY
In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B).
RESULTS
The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 ( = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 ( = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVIS) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], = 0.011).
CONCLUSION
Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.
PubMed: 38790543
DOI: 10.3390/children11050548 -
Cells May 2024Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably... (Review)
Review
Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac hypertrophy and progression to heart failure. One of these includes the activation of different neuroendocrine systems for elevating the circulating levels of different vasoactive hormones such as catecholamines, angiotensin II, vasopressin, serotonin and endothelins. All these hormones are released in the circulation and stimulate different signal transduction systems by acting on their respective receptors on the cell membrane to promote protein synthesis in cardiomyocytes and induce cardiac hypertrophy. The elevated levels of these vasoactive hormones induce hemodynamic overload, increase ventricular wall tension, increase protein synthesis and the occurrence of cardiac remodeling. In addition, there occurs an increase in proinflammatory cytokines and collagen synthesis for the induction of myocardial fibrosis and the transition of adaptive to maladaptive hypertrophy. The prolonged exposure of the hypertrophied heart to these vasoactive hormones has been reported to result in the oxidation of catecholamines and serotonin via monoamine oxidase as well as the activation of NADPH oxidase via angiotensin II and endothelins to promote oxidative stress. The development of oxidative stress produces subcellular defects, Ca-handling abnormalities, mitochondrial Ca-overload and cardiac dysfunction by activating different proteases and depressing cardiac gene expression, in addition to destabilizing the extracellular matrix upon activating some metalloproteinases. These observations support the view that elevated levels of various vasoactive hormones, by producing hemodynamic overload and activating their respective receptor-mediated signal transduction mechanisms, induce cardiac hypertrophy. Furthermore, the occurrence of oxidative stress due to the prolonged exposure of the hypertrophied heart to these hormones plays a critical role in the progression of heart failure.
Topics: Heart Failure; Humans; Cardiomegaly; Signal Transduction; Animals; Angiotensin II; Oxidative Stress
PubMed: 38786079
DOI: 10.3390/cells13100856 -
Cells May 2024This review addresses the need for innovative co-culture systems integrating the enteric nervous system (ENS) with intestinal organoids. The breakthroughs achieved... (Review)
Review
This review addresses the need for innovative co-culture systems integrating the enteric nervous system (ENS) with intestinal organoids. The breakthroughs achieved through these techniques will pave the way for a transformative era in gastrointestinal (GI) disease modeling and treatment strategies. This review serves as an introduction to the companion protocol paper featured in this journal. The protocol outlines the isolation and co-culture of myenteric and submucosal neurons with small intestinal organoids. This review provides an overview of the intestinal organoid culture field to establish a solid foundation for effective protocol application. Remarkably, the ENS surpasses the number of neurons in the spinal cord. Referred to as the "second brain", the ENS orchestrates pivotal roles in GI functions, including motility, blood flow, and secretion. The ENS is organized into myenteric and submucosal plexuses. These plexuses house diverse subtypes of neurons. Due to its proximity to the gut musculature and its cell type complexity, there are methodological intricacies in studying the ENS. Diverse approaches such as primary cell cultures, three-dimensional (3D) neurospheres, and induced ENS cells offer diverse insights into the multifaceted functionality of the ENS. The ENS exhibits dynamic interactions with the intestinal epithelium, the muscle layer, and the immune system, influencing epithelial physiology, motility, immune responses, and the microbiome. Neurotransmitters, including acetylcholine (ACh), serotonin (5-HT), and vasoactive intestinal peptide (VIP), play pivotal roles in these intricate interactions. Understanding these dynamics is imperative, as the ENS is implicated in various diseases, ranging from neuropathies to GI disorders and neurodegenerative diseases. The emergence of organoid technology presents an unprecedented opportunity to study ENS interactions within the complex milieu of the small and large intestines. This manuscript underscores the urgent need for standardized protocols and advanced techniques to unravel the complexities of the ENS and its dynamic relationship with the gut ecosystem. The insights gleaned from such endeavors hold the potential to revolutionize GI disease modeling and treatment paradigms.
Topics: Enteric Nervous System; Organoids; Humans; Coculture Techniques; Gastrointestinal Diseases; Animals; Models, Biological; Neurons; Intestines
PubMed: 38786042
DOI: 10.3390/cells13100820 -
Current Research in Physiology 2024Chronic kidney disease (CKD) is a progressive and long-term condition marked by a gradual decline in kidney function. CKD is prevalent among those with conditions such... (Review)
Review
Chronic kidney disease (CKD) is a progressive and long-term condition marked by a gradual decline in kidney function. CKD is prevalent among those with conditions such as diabetes mellitus, hypertension, and glomerulonephritis. Affecting over 10% of the global population, CKD stands as a significant cause of morbidity and mortality. Despite substantial advances in understanding CKD pathophysiology and management, there is still a need to explore novel mechanisms and potential therapeutic targets. Urotensin II (UII), a potent vasoactive peptide, has garnered attention for its possible role in the development and progression of CKD. The UII system consists of endogenous ligands UII and UII-related peptide (URP) and their receptor, UT. URP pathophysiology is understudied, but alterations in tissue expression levels of UII and UT and blood or urinary UII concentrations have been linked to cardiovascular and kidney dysfunctions, including systemic hypertension, chronic heart failure, glomerulonephritis, and diabetes. UII gene polymorphisms are associated with increased risk of diabetes. Pharmacological inhibition or genetic ablation of UT mitigated kidney and cardiovascular disease in rodents, making the UII system a potential target for slowing CKD progression. However, a deeper understanding of the UII system's cellular mechanisms in renal and extrarenal organs is essential for comprehending its role in CKD pathophysiology. This review explores the evolving connections between the UII system and CKD, addressing potential mechanisms, therapeutic implications, controversies, and unexplored concepts.
PubMed: 38779598
DOI: 10.1016/j.crphys.2024.100126