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Journal of Cerebral Blood Flow and... May 2024Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is...
Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.
PubMed: 38820436
DOI: 10.1177/0271678X241258576 -
PeerJ 2024Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system,...
BACKGROUND
Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects.
METHODS
A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL).
RESULTS
The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score.
CONCLUSIONS
Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases.
Topics: Humans; Female; Migraine Disorders; Male; Adult; Case-Control Studies; Tomography, Optical Coherence; Retina; Middle Aged; Retinal Ganglion Cells
PubMed: 38818459
DOI: 10.7717/peerj.17454 -
The Turkish Journal of Pediatrics May 2024The objectives of this study were to assess the preoperative and postoperative serum brain- derived neurotrophic factor (BDNF) levels in neonates undergoing surgery for...
BACKGROUND
The objectives of this study were to assess the preoperative and postoperative serum brain- derived neurotrophic factor (BDNF) levels in neonates undergoing surgery for congenital heart defects (CHD). Also to explore the relationship between changes in BDNF levels and the impact of perioperative factors including intraoperative body temperature, aortic cross-clamp time, perfusion time, operation time, inotropic score, vasoactive inotropic score and lactate levels.
METHODS
Forty-four patients with CHD and 36 healthy neonates were included in the study. Blood samples for serum BDNF levels were collected three times: preoperatively, and at 24 and 72 hours postoperatively from each patient in the operated group. Additionally, samples were collected once from each individual in the non-operated case group and the control group. Serum BDNF levels were analyzed using the Elabscience ELISA (Enzyme-Linked Immunosorbent Assay) commercial kit. Cranial ultrasonography (USG) was performed on all infants with CHD. Following cardiac surgery, patients underwent second and third cranial USG examinations at 24 and 72 hours postoperatively, respectively.
RESULTS
Forty-four consecutive patients with CHD were divided into two groups as follows: the operated group (n=30) and the non-operated group (n=14). Although there were no differences in the baseline serum BDNF levels between the case and control groups, the preoperative serum BDNF levels were significantly lower in the patients operated compared to the non-operated patients. The serum BDNF levels at the 24th hour postoperatively were higher than the preoperative levels. However, no significant correlation was found between the serum BDNF levels at 24 and 72 hours postoperatively as well as the cranial USG findings at corresponding times.
CONCLUSIONS
Serum BDNF levels were initially lower in neonates with CHD who underwent surgery, but increased during the early postoperative period. These results suggest that serum BDNF levels are influenced by CHD and the postoperative period.
Topics: Humans; Brain-Derived Neurotrophic Factor; Infant, Newborn; Heart Defects, Congenital; Male; Female; Postoperative Period; Case-Control Studies; Preoperative Period; Cardiac Surgical Procedures; Enzyme-Linked Immunosorbent Assay; Biomarkers
PubMed: 38814304
DOI: 10.24953/turkjpediatr.2024.4562 -
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