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Chinese Medicine May 2024The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke....
BACKGROUND
The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved.
METHODS
Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels.
RESULTS
AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP.
CONCLUSIONS
AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.
PubMed: 38778375
DOI: 10.1186/s13020-024-00945-7 -
Journal of the American Board of Family... 2024Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure..
Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure..
Topics: Humans; Acetazolamide; Heart Failure; Acute Disease; Sodium Potassium Chloride Symporter Inhibitors; Diuretics; Carbonic Anhydrase Inhibitors
PubMed: 38740482
DOI: 10.3122/jabfm.2023.230379R0 -
ACS Omega May 2024The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and...
The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are linked with various disorders including Alzheimer's disease. In this study, six new nicotinic hydrazide derivatives (-) were designed and synthesized for the first time, and their inhibitory profiles against hCA I, hCA II, AChE, and BChE were investigated by assays and studies. The structures of novel molecules were elucidated by using spectroscopic techniques and elemental analysis. These molecules showed inhibitory activities against hCA I and II with IC values ranging from 7.12 to 45.12 nM. Compared to reference drug acetazolamide (AZA), compound was the most active inhibitor against hCA I and II. On the other hand, it was determined that IC values of the tested molecules ranged between 21.45 and 61.37 nM for AChE and between 18.42 and 54.74 nM for BChE. Among them, compound was the most potent inhibitor of AChE and BChE, with IC values of 21.45 and 18.42 nM, respectively. In order to better understand the mode of action of these new compounds, state-of-the-art molecular modeling techniques were also conducted.
PubMed: 38737075
DOI: 10.1021/acsomega.3c10182 -
International Journal of Molecular... Apr 2024In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is...
In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca entry triggers a transepithelial Ca flux to regulate proximal tubular (PT) luminal [Ca], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca entry compared to the WT counterparts because of significant inhibition by the store-operated Ca entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca entry) inhibitors (Pyr10), Ca entry by WTT cells was moderately inhibited, suggesting that the Ca and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.
Topics: Animals; Hypercalciuria; Hydrogen-Ion Concentration; Mice; Mice, Knockout; Calcium Oxalate; Kidney Calculi; Calcium Phosphates; Nephrolithiasis; Calcium; TRPC Cation Channels; Kidney Tubules, Proximal; Male; Disease Models, Animal; Mice, Inbred C57BL; Acetazolamide
PubMed: 38732005
DOI: 10.3390/ijms25094787 -
Mikrochimica Acta May 2024The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1...
The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1 inhibitor abrocitinib (ABR). ABR is approved by the U.S. Food and Drug Administration (FDA) for the treatment of atopic dermatitis. The molecularly imprinted polymer (MIP)-based sensor was designed to incorporate zinc nanoflower (ZnNFs)-graphene oxide (GO) conjugate (ZnNFs@GO), synthesized from the root methanolic extract (RME) of the species Alkanna cappadocica Boiss. et Bal. to improve the porosity and effective surface area of the glassy carbon electrode (GCE). Furthermore, the MIP structure was prepared using ABR as a template molecule, 4-aminobenzoic acid (4-ABA) as a functional monomer, and other additional components. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the surface and structure of the synthesized nanomaterial and MIP-based surface. Among the electrochemical methods, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were preferred for detailed electrochemical characterization, and differential pulse voltammetry (DPV) was preferred for all other electrochemical measurements using 5.0 mM [Fe(CN)] solution as the redox probe. The MIP-based sensor, which was the result of a detailed optimization phase, gave a linear response in the 1.0 × 10 - 1.0 × 10 M range in standard solution and serum sample. The obtained limit of detection (LOD) and limit of quantification (LOQ) values and recovery studies demonstrated the sensitivity, accuracy, and applicability of the sensor. Selectivity, the most important feature of the MIP-based sensor, was verified by imprinting factor calculations using ibrutinib, ruxolitinib, tofacitinib, zonisamide, and acetazolamide.
Topics: Molecularly Imprinted Polymers; Electrochemical Techniques; Limit of Detection; Zinc; Graphite; Humans; Aminoimidazole Carboxamide; Nanostructures; Electrodes
PubMed: 38730044
DOI: 10.1007/s00604-024-06404-2 -
Cureus Apr 2024The morning glory (MG) disc anomaly is a congenital excavation of the posterior globe involving the optic disc, with a distinct appearance reminiscent of the MG flower....
The morning glory (MG) disc anomaly is a congenital excavation of the posterior globe involving the optic disc, with a distinct appearance reminiscent of the MG flower. Various intracranial and ocular associations with MG have been documented. Conditions such as trans-sphenoidal encephalocele and hypoplasia of the intracranial vasculature have been observed in association with this anomaly. In this report, we present a case of MG optic disc anomaly accompanied by serous macular detachment.
PubMed: 38721220
DOI: 10.7759/cureus.57817 -
ACG Case Reports Journal May 2024Cerebrospinal fluid (CSF) ascites is a rare cause of ascites that presents in patients with ventriculoperitoneal (VP) shunts, treated by conversion to a ventriculoatrial...
Cerebrospinal fluid (CSF) ascites is a rare cause of ascites that presents in patients with ventriculoperitoneal (VP) shunts, treated by conversion to a ventriculoatrial shunt. Our case describes a patient presenting with CSF ascites almost 40 years after VP shunt placement, with fluid analysis showing elevated serum ascites albumin gradient, and response to acetazolamide therapy. As shown in this case, CSF ascites can present with elevated serum ascites albumin gradient and should be kept a differential diagnosis. Acetazolamide can be considered as a potential alternative treatment in patients who are not candidates for a VP to ventriculoatrial shunt conversion.
PubMed: 38716358
DOI: 10.14309/crj.0000000000001361 -
Neurology India Mar 2024Acute glaucoma following carotid artery recanalization is a rare but severe complication of underlying ocular ischemic syndrome. We present a case of a 71-year-old woman...
Acute glaucoma following carotid artery recanalization is a rare but severe complication of underlying ocular ischemic syndrome. We present a case of a 71-year-old woman with ocular ischemic syndrome and severe stenosis of the right internal and external carotid artery undergoing carotid artery stenting. Immediate postprocedural angiography showed pronounced reperfusion of the ophthalmic artery. Subsequently, the patient developed vision-threatening acute glaucoma despite treatment with acetazolamide. Monitoring of intraocular pressure is important in patients who are at risk of developing ocular ischemic syndrome because of internal carotid artery stenosis. Interventionalists should also assess the degree of vascular collateralization from the external carotid artery.
Topics: Humans; Female; Aged; Carotid Stenosis; Stents; Glaucoma; Carotid Artery, Internal; Ischemia
PubMed: 38691486
DOI: 10.4103/neuroindia.NI_1800_20 -
Ophthalmology. Glaucoma Apr 2024To identify and quantify medications causing angle-closure glaucoma through the FDA Adverse Event Reporting System (FAERS).
OBJECTIVE
To identify and quantify medications causing angle-closure glaucoma through the FDA Adverse Event Reporting System (FAERS).
DESIGN
National retrospective database analysis.
SUBJECTS
There were 11 737 133 total adverse event reports from the FDA Federal Adverse Event Reporting System (FAERS) database 2004 to third quarter of 2023 (2023Q3), which included 1629 reports of angle-closure glaucoma.
METHODS
Drugs associated with reports of angle-closure glaucoma were identified in FAERS through disproportionality analysis MAIN OUTCOME MEASURES: To ascertain if these reports yielded statistically significant signals, we used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC). We considered a signal to be detected when all 4 disproportionality analysis metrics were positive.
RESULTS
We identified a total of 1629 adverse event reports linked to 611 suspected drugs over the course of 20 years (2004-2023Q3). Frequently reported drugs included topiramate (520 reports) and citalopram (69 reports), amongst many others. Eighteen medications yielded a positive signal, including lesser-known medications like olanzapine, phentermine, and ranibizumab. Tropicamide exhibited the most robust statistical significance (n = 18; PRR: 164.263; ROR [95% confidence interval {CI}]: 167.95 [104.994-268.655]; EBGM [EBGM05]: 162.421 [109.5]; IC [IC05]: 7.344 [4.591]), while acetazolamide was the second strongest (n = 51; PRR: 113.088; ROR 95% CI: 114.782 [86.665-152.021]; EBGM [EBGM05]: 109.506 [86.501]; IC [IC05]: 6.775 [5.115]).
CONCLUSIONS
Drug-induced glaucoma included both well-known medications such as topiramate as well as lesser-known medications such as olanzapine, phentermine, and ranibizumab. Clinician awareness of these findings is important.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38679326
DOI: 10.1016/j.ogla.2024.04.006 -
Biomolecules Apr 2024Andersen-Tawil syndrome (ATS) is a multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, prolonged QT interval, and facial dysmorphisms...
Andersen-Tawil syndrome (ATS) is a multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, prolonged QT interval, and facial dysmorphisms occurring in the first/second decade of life. High phenotypic variability and incomplete penetrance of the genes causing the disease make its diagnosis still a challenge. We describe a three-generation family with six living individuals affected by ATS. The proband is a 37-year-old woman presenting since age 16, with episodes of muscle weakness and cramps in the pre-menstrual period. The father, two brothers, one paternal uncle and one cousin also complained of cramps, muscle stiffness, and weakness. Despite normal serum potassium concentration, treatment with potassium, magnesium, and acetazolamide alleviated paralysis attacks suggesting a dyskalemic syndrome. Dysmorphic features were noted in the proband, only later. On the ECG, all but one had normal QT intervals. The affected males developed metabolic syndrome or obesity. The father had two myocardial infarctions and was implanted with an intracardiac cardioverter defibrillator (ICD). A genetic investigation by WES analysis detected the heterozygous pathogenic variant (NM_000891.2: c.652C>T, p. Arg218Trp) in the gene related to ATS, confirmed by segregation studies in all affected members. Furthermore, we performed a review of cases with the same mutation in the literature, looking for similarities and divergences with our family case.
Topics: Adult; Female; Humans; Male; Alleles; Andersen Syndrome; Mutation; Pedigree; Phenotype; Potassium Channels, Inwardly Rectifying
PubMed: 38672523
DOI: 10.3390/biom14040507