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Healthcare (Basel, Switzerland) Jun 2024This article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who does not consent to the implantation of a cardiac...
This article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who does not consent to the implantation of a cardiac pacemaker but was referred by her primary care physician for cardiological evaluation. The conduction disturbance was recognized at the age of 6 and was asymptomatic. The professional disqualification from pacemaker implantation included a detailed history of a patient's symptoms, an echocardiographic assessment of the heart, exercise testing and ECG Holter monitoring. The aid of salbutamol administered orally was also useful.
PubMed: 38921273
DOI: 10.3390/healthcare12121158 -
Journal of Chromatography. B,... Jun 2024Cortex Morin Radicis (CMR) is the dried root bark of Morus alba. L. It has a variety of effects such as antibacterial, anti-tumour, treatment of cardiovascular diseases...
Screening for promising multi-target bioactive components from Cortex Mori Radicis for the treatment of chronic cor pulmonale based on immobilized beta-adrenergic receptor and beta-adrenergic receptor chromatography.
Cortex Morin Radicis (CMR) is the dried root bark of Morus alba. L. It has a variety of effects such as antibacterial, anti-tumour, treatment of cardiovascular diseases or upper respiratory tract disease and so on. The pursuit for drugs selected from Cortex Mori Radicis having improved therapeutic efficacy necessitates increasing research on new assays for screening bioactive compounds with multi-targets. In this work, we applied immobilized β-AR and β-AR as the stationary phase in chromatographic column to screen bioactive compounds from Cortex Morin Radicis. Specific ligands of the two receptors (e.g. esmolol, metoprolol, atenolol, salbutamol, methoxyphenamine, tulobuterol and clorprenaline) were utilized to characterize the specificity and bioactivity of the columns. We used high performance affinity chromatography coupled with ESI-MS to screen targeted compounds of Cortex Morin Radicis. By zonal elution, we identified morin as a bioactive compound simultaneously binding to β-AR and β-AR. The compound exhibited the association constants of 3.10 × 10 and 2.60 × 10 M on the β-AR and β-AR column. On these sites, the dissociation rate constants were calculated to be 0.131 and 0.097 s. Molecular docking indicated that the binding of morin to the two receptors occurred on Asp200, Asp121, and Val122 of β-AR, Asn312, Thr110, Asp113, Tyr316, Gly90, Phe193, Ile309, and Trp109 of β-AR. Likewise, mulberroside C was identified as the bioactive compound binding to β-AR. The association constants and dissociation rate constants were calculated to be 1.08 × 10 M and 0.900 s. Molecular docking also indicated that mulberroside C could bind to β-AR receptor on its agonist site. Taking together, we demonstrated that the chromatographic strategy to identify bioactive natural products based on the β-AR and β-AR immobilization, has potential for screening bioactive compounds with multi-targets from complex matrices including traditional Chinese medicines.
PubMed: 38917653
DOI: 10.1016/j.jchromb.2024.124175 -
Journal of the American Society For... Jun 2024A small ionization needle with an ultrasharp, ultrafine tip is introduced. It is lab-fabricated from tungsten wire and serves as a corona discharge emitter in...
A small ionization needle with an ultrasharp, ultrafine tip is introduced. It is lab-fabricated from tungsten wire and serves as a corona discharge emitter in nanoelectrode atmospheric pressure chemical ionization mass spectrometry (nAPCI-MS). Tip radii ranged from 8 to 44 nm, up to 44× smaller than the sharpest previously reported corona needle. Because of this, nAPCI was able to operate at +1.0 kV with no auxiliary counter electrode. Alternatively, at +1.2 kV, nAPCI could be enclosed in a small plastic assembly for headspace analysis with a sampling tube attachment as long as 15 m. No added heat or gas flow was necessary. The efficacy of nAPCI-MS was demonstrated through needle durability studies and direct analysis of vapors from real-world samples. Provisional identifications include ibuprofen from a pharmaceutical tablet, albuterol aerosol sprayed from a medical inhaler, cocaine from paper currency, caffeine from a fingertip, and bisphenol E from a paper receipt.
PubMed: 38917028
DOI: 10.1021/jasms.4c00117 -
Molecular Medicine (Cambridge, Mass.) Jun 2024Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that is frequently identified with a poor prognosis. Macrophages play an... (Review)
Review
Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that is frequently identified with a poor prognosis. Macrophages play an important role in its pathogenesis. Different macrophage subtypes have different effects on lupus-affected kidneys. Based on their origin, macrophages can be divided into monocyte-derived macrophages (MoMacs) and tissue-resident macrophages (TrMacs). During nephritis, TrMacs develop a hybrid pro-inflammatory and anti-inflammatory functional phenotype, as they do not secrete arginase or nitric oxide (NO) when stimulated by cytokines. The infiltration of these mixed-phenotype macrophages is related to the continuous damage caused by immune complexes and exposure to circulating inflammatory mediators, which is an indication of the failure to resolve inflammation. On the other hand, MoMacs differentiate into M1 or M2 cells under cytokine stimulation. M1 macrophages are pro-inflammatory and secrete pro-inflammatory cytokines, while the M2 main phenotype is essentially anti-inflammatory and promotes tissue repair. Conversely, MoMacs undergo differentiation into M1 or M2 cells in response to cytokine stimulation. M1 macrophages are considered pro-inflammatory cells and secrete pro-inflammatory mediators, whereas the M2 main phenotype is primarily anti-inflammatory and promotes tissue repair. Moreover, based on cytokine expression, M2 macrophages can be further divided into M2a, M2b, and M2c phenotypes. M2a and M2c have anti-inflammatory effects and participate in tissue repair, while M2b cells have immunoregulatory and pro-inflammatory properties. Further, memory macrophages also have a role in the advancement of LN. Studies have demonstrated that the polarization of macrophages is controlled by multiple metabolic pathways, such as glycolysis, the pentose phosphate pathway, fatty acid oxidation, sphingolipid metabolism, the tricarboxylic acid cycle, and arginine metabolism. The changes in these metabolic pathways can be regulated by substances such as fish oil, polyenylphosphatidylcholine, taurine, fumaric acid, metformin, and salbutamol, which inhibit M1 polarization of macrophages and promote M2 polarization, thereby alleviating LN.
Topics: Humans; Lupus Nephritis; Macrophages; Animals; Macrophage Activation; Cytokines; Cell Differentiation; Disease Management; Cellular Reprogramming; Metabolic Reprogramming
PubMed: 38914953
DOI: 10.1186/s10020-024-00866-z -
BMC Neurology Jun 2024Congenital myasthenic syndromes (CMS) are among the most challenging differential diagnoses in the neuromuscular domain, consisting of diverse genotypes and phenotypes.... (Review)
Review
BACKGROUND
Congenital myasthenic syndromes (CMS) are among the most challenging differential diagnoses in the neuromuscular domain, consisting of diverse genotypes and phenotypes. A mutation in the Docking Protein 7 (Dok-7) is a common cause of CMS. DOK7 CMS requires different treatment than other CMS types. Regarding DOK7's special considerations and challenges ahead of neurologists, we describe seven DOK7 patients and evaluate their response to treatment.
METHODS
The authors visited these patients in the neuromuscular clinics of Tehran and Kerman Universities of Medical Sciences Hospitals. They diagnosed these patients based on clinical findings and neurophysiological studies, which Whole Exome Sequencing confirmed. For each patient, we tried unique medications and recorded the clinical response.
RESULTS
The symptoms started from birth to as late as the age of 33, with the mean age of onset being 12.5. Common symptoms were: Limb-girdle weakness in 6, fluctuating symptoms in 5, ptosis in 4, bifacial weakness in 3, reduced extraocular movement in 3, bulbar symptoms in 2 and dyspnea in 2 3-Hz RNS was decremental in 5 out of 6 patients. Salbutamol was the most effective. c.1124_1127dupTGCC is the most common variant; three patients had this variant.
CONCLUSION
We strongly recommend that neurologists consider CMS in patients with these symptoms and a similar familial history. We recommend prescribing salbutamol as the first-choice treatment option for DOK7 patients.
Topics: Humans; Myasthenic Syndromes, Congenital; Male; Female; Muscle Proteins; Adult; Young Adult; Adolescent; Child; Mutation
PubMed: 38907197
DOI: 10.1186/s12883-024-03713-0 -
Cureus May 2024Background Levalbuterol is a short-acting β-agonist (SABA) indicated for treating or preventing asthma exacerbation. It was included in the 2020 Chinese National...
Estimating the Economic Impact of Levalbuterol's Potential Transition From the National Reimbursement Drug List for the Treatment of Pediatric Asthma in China: A Budget Impact Analysis.
Background Levalbuterol is a short-acting β-agonist (SABA) indicated for treating or preventing asthma exacerbation. It was included in the 2020 Chinese National Reimbursement Drug List (NRDL). This study estimates the economic impact of levalbuterol's status change within and withdrawal from the NRDL in treating pediatric asthma from a publicly funded medical insurance perspective. Methodology A prevalence-based budget impact model was developed. The analysis compared a a levalbuterol scenario to a levalbuterol. Epidemiological data were obtained from the existing literature. Cost data were estimated based on the drug dosage in clinical trials, real-world settings, and expert opinions. Scenario analysis considered the same length of stay (LOS) in the two groups. One-way sensitivity analyses were carried out to show the impact of varying individual parameters. Results In the base-case analysis, compared to the scenario, the preservation of levalbuterol resulted in cost savings of ¥82.8 million in China over three years. In the scenario analysis, savings decreased to ¥76.1 million over three years. Sensitivity analysis showed that, for the most part, the results were robust to changes in input parameter values. Conclusions Using levalbuterol may lead to substantial cost savings for Chinese society.
PubMed: 38903381
DOI: 10.7759/cureus.60640 -
The Journal of Allergy and Clinical... Jun 2024Ten % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient...
BACKGROUND
Ten % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient de-labelling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and non-allergist de-labelling.
OBJECTIVE
To assess the safety of de-labelling low-risk adults by means of dDC in primary care.
METHODS
We searched MEDLINE, EMBASE and the Conchrane Library databases, from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal was performed by one reviewer and we pooled the results in a meta-analysis.
RESULTS
Out of 2,138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated de-labelling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely de-labelled. Ten patients (<1%) developed an immediate reaction: three had self-limiting reactions, and seven needed antihistaminics, steroids, epinephrine and/or salbutamol.
CONCLUSION
No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of one recent report, these studies are of low to moderate quality. Non-specialist de-labelling is promising but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.
PubMed: 38901618
DOI: 10.1016/j.jaip.2024.06.017 -
Journal of Oral Rehabilitation Jun 2024Activation of β adrenergic receptors reduces cutaneous mechanical pain thresholds in rats. While β adrenergic receptor activation may contribute to mechanisms that...
BACKGROUND
Activation of β adrenergic receptors reduces cutaneous mechanical pain thresholds in rats. While β adrenergic receptor activation may contribute to mechanisms that underlie temporomandibular joint pain, its effect on masticatory muscle pain sensitivity is uncertain.
OBJECTIVES
The current study sought to determine the extent to which β adrenergic receptors are expressed by masticatory muscle afferent fibres, and to assess the effect of local activation of these receptors on the mechanical sensitivity of masticatory muscle afferent fibres in rats.
METHODS
Trigeminal ganglion neurons that innervate the rat (n = 12) masseter muscle and lower lip were identified by tissue injection of fluorescent dyes and were then stained with antibodies against β or β adrenergic receptors. Extracellular recordings from 60 trigeminal ganglion neurons that innervate the masticatory muscle were undertaken in a second group of anaesthetised rats of both sexes (n = 37) to assess afferent mechanical activation thresholds. Thresholds were assessed before and after injection of the β adrenergic receptor agonists into masticatory muscle.
RESULTS
β and β adrenergic receptor expression was greater in labial skin than in masticatory muscle ganglion neurons (p < .05, one-way ANOVA, Holm-Sidak test). There was a higher expression of β adrenergic receptors in masticatory muscle ganglion neurons in males than in females. The mixed β agonist isoproterenol increased afferent mechanical activation threshold in male but not female rats (p < .05, Mann-Whitney test). In male rats, salbutamol, a β selective agonist, also increased afferent mechanical activation threshold but hydralazine, a vasodilator, did not (p < .05, Mann-Whitney test).
CONCLUSION
Activation of β adrenergic receptors decreases the mechanical sensitivity of masticatory muscle afferent fibres in a sex-related manner.
PubMed: 38894554
DOI: 10.1111/joor.13787 -
Journal of Chromatography. A Jun 2024Protein functionalized surface has the potential to develop new assays for determining the drug-like properties of potential compounds and discovering specific partners...
Protein functionalized surface has the potential to develop new assays for determining the drug-like properties of potential compounds and discovering specific partners of G protein-coupled receptors (GPCRs). However, a universal method for purifying and immobilizing functional GPCRs has remained elusive. To this end, we developed a general and rapid way to purify and immobilize β-adrenergic receptor (βAR) by silicon-specific peptide. We screened CotB1p as a tag from six silica-binding peptides (minTBP-1, CotB1p, SB, Car, and Si) by examining their affinity to macroporous silica gel. We investigated the adsorption and desorption of CotB1p-tagged β-adrenoceptor (βAR-CotB1p) under diverse conditions to propose a protocol for receptor purification and immobilization. Under optimized conditions, βAR immobilization were achieved by directly immersing cell lysates harboring the receptor with silica gel, and the elution of the receptor without demonstratable contaminants was realized by including l-arginine/L-lysine in the elutes. This allows purification of the receptor from Escherichia coli (E.coli) lysates with a purity of 95 %. The immobilized receptor was utilized as a stationary phase to reveal the tag impact on ligand-binding outputs by comparing the CotB1p-strategy with a typical covalent method. The Ks of salbutamol, chlorprenaline, tulobuterol, and terbutaline on βAR-CotB1p column were 1.26 × 10, 6.59 × 10, 7.90 × 10, and 8.97 × 10 M respectively, which were two orders of magnitude higher than those on the Halo-βAR column. The whole immobilization was accomplished within 30 min without the requirement of any special treatment, resulting in enhanced accuracy for determining receptor-ligand binding parameters. Taken together, CotB1p-mediated strategy is simple, rapid, and universal for purification or immobilization of unstable biomolecules like GPCRs for analytical and biological applications.
PubMed: 38889580
DOI: 10.1016/j.chroma.2024.465037 -
Cureus May 2024Background Rituximab, a chimeric monoclonal antibody targeting the CD20 protein on the surface of B cells, is used to treat several rheumatologic and oncologic diseases....
Implementation of an Accelerated Infusion Protocol (90-Minute Infusion) of Rituximab and Its Safety in Patients With Autoimmune Rheumatic Diseases at a Tertiary Veterans Affairs Center.
Background Rituximab, a chimeric monoclonal antibody targeting the CD20 protein on the surface of B cells, is used to treat several rheumatologic and oncologic diseases. The standard infusion duration of rituximab is four hours. Objective Evaluating the safety of administering the accelerated 90-minute protocol at our Veterans Affairs center to patients with rheumatologic diseases and monitoring for any infusion-related reactions. This study is unique as it examines infusion rates faster than those most described (120 minutes). Methods Patients treated with rituximab for autoimmune diseases between June 2020 and June 2022 at our center were included in the study. Our patients were over 18 years of age, met the inclusion criteria, and had received previous rituximab infusions without prior infusion-related reactions. They received the accelerated protocol of 90 minutes over their next cycles and were monitored for any reactions during their infusions. Results A total of 34 patients receiving 76 infusions were included in the analysis. Most of the patients were males (n = 27). The most prevalent indication for rituximab infusion was rheumatoid arthritis (n = 20). Out of 76 infusions, only two infusion-related reactions were recorded (2.6% incidence). The first patient had itching and a sore throat, indicating a grade 1A reaction. The second patient developed chest pain and dyspnea, which resolved with diphenhydramine and albuterol. For both, the infusion was completed after appropriate management. Conclusion The incidence of infusion-related reactions during the accelerated 90-minute rituximab infusion was remarkably low and well-tolerated by our rituximab-experienced patients. Only two infusions were complicated by a reaction, an incidence comparable to or even lower than other reported 120-minute infusion protocols. This protocol is time- and cost-efficient, allowing for more infusions per chair per day at our center.
PubMed: 38887351
DOI: 10.7759/cureus.60558