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1.
Ear Nose Throat J ; : 1455613241275343, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39305077

ABSTRACT

Sudden idiopathic hearing loss (SIHL) is defined as sensorineural hearing loss at 30 dB or more at 3 consecutive frequencies that begins within 72 hours, and the etiology of the disease is still unclear. Steroid treatment is used as systemic and local (intratympanic) in sudden hearing loss, and different results have been reported for both treatment modalities. This study aimed to compare the results of the treatment in patients who received systemic steroid (SS) therapy and in patients who received systemic and intratympanic steroid (ITS) therapy for SIHL. In all, 169 patients who were admitted to our clinic with the diagnosis of SIHL between January 2007 and June 2018 were randomly divided into 2 treatment groups according to their admittance day, such as patients who received only SSs and patients who received SSs and ITSs. The results of these 2 treatment protocols were investigated. Statistical analysis was performed for all patients by grouping many factors that could be effective in prognosis, such as age, sex, and time of initiation of treatment. No differences were found between the SS group and the combined systemic-ITS group in treatment success. It was determined that being under 15 years of age, over 60 years of age, starting treatment after 7 days, vertigo, high initial hearing loss, descendant type, and total loss type in the audiogram configuration are poor prognostic factors. Being between 16 and 59 years of age, starting treatment within 7 days, having no vertigo, mild hearing loss, and having ascendant and plateau type in audiogram configuration are good prognostic factors. We observed that adding ITS treatment to SS treatment as an initial treatment did not provide any extra benefit. However, prospective, randomized, controlled studies will clarify the topic.

2.
Drug Test Anal ; 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39307175

ABSTRACT

Altrenogest is a synthetic progestin that suppresses reproductive behaviours and assists pregnancy maintenance in female horses. Two formulations are available, a 'weekly' intramuscular injection and a daily oral formulation. Altrenogest administration has returned positive swabs for steroids; consequently, using injectable altrenogest in racing mares is prohibited. Oral administration may be permitted in race mares if there is one clear day between dosing and racing. The only pharmacokinetic data available were generated from geldings. Therefore, to assist veterinarians and analysts in determining accurate dosing and detection intervals, pharmacokinetic analysis using mares is required. Blood samples were taken from 10 mares pretreatment to obtain baseline concentrations. Mares were administered altrenogest, either oral (PO; 0.044 mg/kg; daily for 15 days) or intramuscular (IM; 0.3 mg/kg; twice; Days 0 and 7). On the first and last treatment day, blood samples were taken at designated times post dosing. After a 3-week washout, mares received the alternative treatment with sampling repeated. At the initial dose, for IM administration mean (± SD) plasma altrenogest Cmax was 18.0 ± 6.6 ng/mL at 7.9 ± 3.9 h compared with PO dosing 13.2 ± 5.8 ng/mL at 0.8 ± 0.8 h. Plasma Cmax on the final day was significantly higher (p = 0.002 [IM]; p = 0.006 [PO]). At 24 h post final oral treatment, mean (± SD) plasma altrenogest was 1.0 ± 0.8 ng/mL and at 48 h were 0.65 ± 0.5 ng/mL. Plasma concentrations well exceeding this may indicate that the one clear day rule or dosage recommendations have not been adhered to.

3.
J Mol Cell Cardiol Plus ; 9: 100079, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39309304

ABSTRACT

The electrophysiological properties of the hearts of women and men are different. These differences are at least partly mediated by the actions of circulating estrogens and androgens on the cardiomyocytes. Experimentally, much of our understanding in this field is based on studies focusing on ventricular tissue, with considerably less known in the context of atrial electrophysiology. The aim of this investigation was to compare the electrophysiological properties of male and female atria and assess responses to acute sex steroid exposure. Age-matched adult male and female C57BL/6 mice were anesthetized (4 % isoflurane) and left atria isolated. Atria were loaded with Di-4-ANEPPS voltage sensitive dye and optical mapping performed to assess action potential duration (APD; at 10 %, 20 %, 30 %, 50 %, and 70 % repolarization) and conduction velocity in the presence of 1 nM and 100 nM 17ß-estradiol or testosterone. Male and female left atria demonstrated similar baseline action potential duration and conduction velocity, with significantly greater APD70 spatial heterogeneity evident in females. 17ß-estradiol prolonged action potential duration in both sexes - an effect that was augmented in females. Atrial conduction was slowed in the presence of 100 nM 17ß-estradiol in both males and females. Testosterone prolonged action potential duration in males only and did not modulate conduction velocity in either sex. This study provides novel insights into male and female atrial electrophysiology and its regulation by sex steroids. As systemic sex steroid levels change and intra-cardiac estrogen synthesis capacity increases with aging, these actions may have an increasingly important role in determining atrial arrhythmia vulnerability.

4.
J Intensive Med ; 4(4): 417-432, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39310055

ABSTRACT

Acute respiratory distress syndrome (ARDS), a fatal critical disease, is induced by various insults. ARDS represents a major global public health burden, and the management of ARDS continues to challenge healthcare systems globally, especially during the pandemic of the coronavirus disease 2019 (COVID-19). There remains no confirmed specific pharmacotherapy for ARDS, despite advances in understanding its pathophysiology. Debate continues about the potential role of glucocorticoids (GCs) as a promising ARDS clinical therapy. Questions regarding GC agent, dose, and duration in patients with ARDS need to be answered, because of substantial variations in GC administration regimens across studies. ARDS heterogeneity likely affects the therapeutic actions of exogenous GCs. This review includes progress in determining the GC mechanisms of action and clinical applications in ARDS, especially during the COVID-19 pandemic.

5.
Phytochemistry ; 229: 114286, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39271036

ABSTRACT

Chemical investigations of a methanolic extract of the twigs of Vernonia amygdalina Delile (Asteraceae) resulted in the isolation and identification of three previously undescribed highly oxygenated Δ7,9(11) stigmastane-type steroids namely vernonins U-W (1-3) along with six known compounds (4-9). The structural characterization of all the isolated compounds has been conducted via comprehensive 1D and 2D-NMR spectroscopy as well as HRMS. The seven steroidal derivatives 1-7 were evaluated for their antiplasmodial activity against the chloroquine-resistant strain P. falciparum Dd2 (PfDd2) and their hemolytic effect on human red blood cells (RBCs). Vernonins U (1), A (4) and stigmasterol-3-O-ß-d-glucopyranoside (7) showed the highest activity with IC50 values of (5.47 ± 0.01) µg/mL, (6.02 ± 0.13) µg/mL and (6.34 ± 0.80) µg/mL, respectively, against PfDd2, while vernonin W (3) showed moderate activity of (21.20 ± 0.40) µg/mL. None of the tested compounds displayed hemolytic effects on human RBCs up to 100 µg/mL indicating their safety. These results enrich the known chemistry of V. amygdalina and support its use in folk medicine for the treatment of malaria. This encourages further research towards new antiplasmodial drug candidates from this plant.

6.
Palliat Med ; : 2692163241270945, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264397

ABSTRACT

BACKGROUND: Severe and refractory chronic breathlessness is a common and burdensome symptom in patients with advanced life-limiting disease. Its clinical management is challenging because of the lack of effective interventions. AIM: To provide practice recommendations on the safe use of pharmacological therapies for severe chronic breathlessness. DESIGN: Scoping review of (inter)national guidelines and systematic reviews. We additionally searched for primary studies where no systematic review could be identified. Consensus on the recommendations was reached by 75% approval within an international expert panel. DATA SOURCES: Searches in MEDLINE, Cochrane Library and Guideline International Network until March 2023. Inclusion of publications on the use of antidepressants, benzodiazepines, opioids or corticosteroids for chronic breathlessness in adults with cancer, chronic obstructive pulmonary disease, interstitial lung disease or chronic heart failure. RESULTS: Overall, the evidence from eight guidelines, 14 systematic reviews and 3 randomised controlled trials (RCTs) on antidepressants is limited. There is low quality evidence favouring opioids in patients with chronic obstructive pulmonary disease, cancer and interstitial lung disease. For chronic heart failure, evidence is inconclusive. Benzodiazepines should only be considered for anxiety associated with severe breathlessness. Antidepressants and corticosteroids should not be used. CONCLUSION: Management of breathlessness remains challenging with only few pharmacological options with limited and partially conflicting evidence. Therefore, pharmacological treatment should be reserved for patients with advanced disease under monitoring of side effects, after optimisation of the underlying condition and use of evidence-based non-pharmacological interventions as first-line treatment.

7.
Glob Pediatr Health ; 11: 2333794X241273204, 2024.
Article in English | MEDLINE | ID: mdl-39257635

ABSTRACT

We report a case of a neonate, delivered by C-section, that rapidly developed respiratory compromise and hemodynamic instability prompting admission to critical care. Urgent cardiology assessment with echocardiography revealed severe systolic dysfunction from localized myocardial ischemia and pulmonary hypertension. Their management progressively escalated, eventually requiring inotropic support. Despite intensive treatment and meticulous nursing with demonstrable improvement of cardiac function, they deteriorated suddenly and died on Day 2 post-partum. This case emphasizes the challenge in early recognition of neonatal shock due to often nonspecific presentations, with hemodynamic compromise arising later. We recommend close vigilance for deterioration, awareness of indolent etiology including viral myocarditis, titration of appropriate inotropes and synergistic adjunctive vasodilators, and consideration of immune modulators such as corticosteroids that addresses biochemical deficiencies and support cardiac function. Ultimately, aggressive, targeted, and multi-focal treatment, especially in resource-limited environments, maximizes the chances of survival in challenging clinical situations such as progressive neonatal shock.

8.
Drug Test Anal ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39317641

ABSTRACT

This narrative review explores the concept of muscle memory, focusing on the physiological and biochemical mechanisms underlying information retention in skeletal muscle tissue as it relates to antidoping. The discussion encompasses the role of satellite cells (SCs) in myonuclei recruitment, resulting in increased myonuclear density and heightened muscle protein turnover. The myonuclear domain theory suggests that myonuclei acquired during hypertrophy may persist, contributing to enhanced muscle protein synthesis (MPS) and potential benefits of muscle memory. The impact of sustained training, protein intake, and resistance exercise on muscle memory, especially in elite athletes, is considered. The review also delves into the influence of anabolic androgenic steroids (AAS) on muscle tissue, highlighting their role in elevating the performance threshold and supporting recovery during intense training through increased muscle protein turnover rates. Additionally, genetic and epigenetic modifications, such as DNA methylation, are explored as potential contributors to muscle memory. The complex interplay of continuous training, AAS use, and genetic factors offers avenues for further research, especially in the context of antidoping efforts. The understanding of muscle memory has implications for maintaining performance gains and addressing ethical challenges in sports.

9.
Ann Otol Rhinol Laryngol ; : 34894241282577, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39318089

ABSTRACT

OBJECTIVE: Oral corticosteroids (OCS) are frequently prescribed by otolaryngologists. However, there are limited quantitative data on OCS-related adverse events (AEs) in otolaryngology. We sought to quantify OCS-related AEs in otolaryngology. METHODS: All outpatient otolaryngology encounters in our healthcare system (2018-2023) at which an OCS was prescribed were identified via the electronic medical record. The diagnoses indicating OCS were categorized as sinonasal, otologic, pharyngo-laryngeal, and other. The medical record was subsequently examined to assess for OCS AEs during the 21-day period following the prescription. OCS AEs were grouped into (1) gastrointestinal, (2) metabolic, (3) bone/muscle, (4) ophthalmologic, and/or (5) psychiatric complications. The frequency and types of OCS related AEs were determined. RESULTS: A total of 20 746 otolaryngology encounters with OCS prescribed were examined. Seventy OCS courses had 1 or more AEs, implying a number needed to harm of 296.4 (240.2-386.8). There were 83 total OCS-related AEs, yielding an AE incidence rate of 4.0:1000 (95% CI, 3.0-5.0:1000) OCS prescriptions. The mean age of subjects with AEs (61.5 years) was significantly higher than those without (50.3 years; P < .001). Forty-seven (56.6%) of the complications were metabolic, with hyperglycemia and hypokalemia the most common, followed by gastrointestinal (26.5%), ophthalmologic (3.6%), psychiatric (2.4%), and musculoskeletal (2.4%). CONCLUSION: AEs related to OCS prescribed by otolaryngologists occur at a rate of once per 296 courses of treatment and older populations may be at increased risk for AEs. Otolaryngologists should balance AE rates against anticipated benefits of steroid therapy. LEVEL OF EVIDENCE: 3.

11.
J Clin Med ; 13(17)2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39274242

ABSTRACT

Background/Objectives: Fetal spina bifida (fSB) is the most common neural tube defect, and intrauterine repair has become a valid treatment option for selected cases. If fSB repair is offered, the ideal time for surgery is from 24 to 26 gestational weeks (GWs). The preoperative steroids for lung maturation and preoperative tocolytics that are administered are known to increase the prevalence of gestational diabetes (GD), which normally occurs in about 10-15% of all pregnant women. This study assessed the prevalence, possible influencing factors, and consequences on the course of pregnancy regarding GD in this cohort. Methods: Between 2010 and 2022, 184 fSB cases were operated. Those patients operated on after 24 0/7 GWs received steroids before surgery. All the patients received tocolysis, and an oral glucose tolerance test was performed between 26 and 28 GWs at least 7 days after steroid administration. In 2020, we established an early postoperative mobilization protocol. The perioperative management procedures of those patients with and without GD were compared to each other, and also, the patients treated according to the early mobilization protocol were compared to the remaining cohort. Results: Nineteen percent were diagnosed with GD. Corticosteroids were administered in 92%. Neither the corticoid administration nor the interval between the administration and glucose tolerance test was different in patients with or without GD. Further, 99.5% received postoperative tocolytics for at least 48 h. The women with GD had significantly longer administration of tocolytics. The length of stay (LOS) was higher in those patients with GD. The gestational age (GA) at delivery was significantly lower in the cohort with GD. In the early mobilized group, we found a significantly higher GA at delivery (37.1 GWs vs. 36.2 GWs, p = 0.009) and shorter LOS (p < 0.001), and their GD rate was lower (10% vs. 20%), although not statistically significant. Conclusions: The GD incidence in the women after fSB repair was higher than in the usual pregnant population. Early mobilization, rapid tocolytics decrease, and shorter LOS could benefit the pregnancy course after fSB repair and may decrease the risk for GD in this already high-risk cohort without increasing the risk for preterm delivery.

12.
Environ Sci Technol ; 58(37): 16291-16301, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39226190

ABSTRACT

Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.


Subject(s)
Autism Spectrum Disorder , Fluorocarbons , Prenatal Exposure Delayed Effects , Humans , Female , Autism Spectrum Disorder/epidemiology , Pregnancy , Child, Preschool , Male , Infant, Newborn , Decanoic Acids
13.
Arch Dermatol Res ; 316(9): 644, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39325061

ABSTRACT

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, adverse drug reaction that is notoriously complex in both its presentation and treatment. Although early diagnosis and cessation of the causative agent are universally accepted as the initial interventions for DRESS, the subsequent management lacks a standardized approach. Historically, systemic steroids have been used as first-line treatment, but there is debate about the optimal dosing and route of administration, and evidence persists on the long-term complications associated with steroid use. Novel treatment approaches with targeted therapy, cyclosporine, intravenous immunoglobulin, and plasmapheresis have been gaining interest as alternative mono- and adjuvant therapies, but their use has yet to be supported by clinical trials. This narrative review provides a summary of the current knowledge of DRESS, with a focus on clinical management. The various mono- and adjuvant therapy options are discussed, with literature-supported suggestions for their optimal use in clinical practice. The risks for relapses, viral reactivation, and long-term complications are also considered. The PubMed and Medline databases were searched for articles on DRESS, published between January 1, 2008, and May 1, 2023. 334 articles met the inclusion criteria. Based on the literature, a DRESS management tool with step-by-step guidance is provided. Further suggestions for management are woven throughout this review, giving clinicians a toolbelt of resources with which to approach diagnosis, treatment, and follow-up.


Subject(s)
Drug Hypersensitivity Syndrome , Humans , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/etiology , Drug Hypersensitivity Syndrome/therapy , Practice Guidelines as Topic , Plasmapheresis/methods , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/adverse effects , Cyclosporine/therapeutic use , Cyclosporine/adverse effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use
14.
Steroids ; : 109518, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39322097

ABSTRACT

Anabolic-androgenic steroids (AASs), more correctly termed "steroidal androgens", are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have long been employed as performance-enhancing substances, primarily among recreational athletes and some professionals. While their short-term effects on muscle physiology are well-documented, the long-term health consequences remain inadequately understood. A key finding is the disruption of hormone production, leading to reversible and irreversible changes, particularly with prolonged use. While debate exists over the prevalence of adverse effects, studies suggest a spectrum of somatic and psychiatric consequences highlighting the need for improved understanding and prevention strategies. AASs not only affect muscle structure but also influence mood, behavior, and body image, potentially exacerbating substance dependence and psychological distress. Liver alterations are a prominent concern, with oxidative stress implicated in AAS-induced hepatotoxicity. Reproductive complications, including gonadal atrophy and infertility, are common, alongside virilization and feminization effects in both genders. Cardiovascular effects are particularly worrisome, with AASs implicated in hypertension, dyslipidemia, and increased thrombotic risk, contributing to cardiovascular morbidity and mortality. Moreover, AASs may enhance cancer risks, potentially accelerating carcinogenesis in various tissues, including the prostate. The review emphasizes the need for comprehensive public health initiatives to mitigate harm, including harm minimization strategies, routine health screenings, and targeted interventions for AAS users. Understanding the complex interplay of biological mechanisms and systemic effects is crucial for informing clinical management and preventive measures. This review also examines the biological impact of AASs on human muscles, detailing mechanisms of action, chemistry, and associated health risks such as liver damage, cardiovascular disease, and endocrine dysfunction.

15.
Subst Use Misuse ; : 1-7, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39323067

ABSTRACT

Background: The present study aimed to explore women's perception of men with different addictions in terms of their short- and long-term mate value. Objectives: 2,525 women (age range: 18-40, M = 28.35, SD = 6.39) were randomized to six conditions in a vignette-based experiment where a male of otherwise high mating value was described as suffering from either gambling, gaming, cannabis, anabolic androgenic steroid, and alcohol addiction or as not suffering from addiction (control). Results: Regarding long-term mate value of the target, the control target was rated higher than each of the targets. The gaming target was rated higher than the alcohol, cannabis, and gambling targets. Finally, the AAS target was rated as higher on long-term mate value than the alcohol and gambling addiction targets. Conclusions: Overall, women seem to perceive risk-taking in the face of uncertainty, reflected by gambling addiction, as an attractive behavioral tendency in men in terms of short-term mating. In contrast, potential long-term mates with gaming or chemical addictions are viewed more negatively, probably because it signals inadequate time and resources to be invested in a relationship.

16.
World J Virol ; 13(3): 95709, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39323444

ABSTRACT

BACKGROUND: The severe respiratory manifestations observed in severe coronavirus disease 2019 (COVID-19) cases are often associated with an excessive inflammatory response. Dexamethasone, a synthetic glucocorticoid, exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells. This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases. Early on in the pandemic, the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support. However, the optimal dosage of corticosteroids remains debatable. Several studies that compare different doses of dexamethasone in COVID-19 exist, but the results are conflicting. AIM: To review the latest evidence regarding dosage, safety, and efficacy of dexamethasone in severe COVID-19. METHODS: We followed preferred reporting items for systematic reviews and meta-analysis guidelines. A detailed literature search was conducted across PubMed, Google Scholar, and Medline to include publications up to March 2024. Our keywords included "COVID-19" "SARS-CoV-2" "dexamethasone" "corticosteroid" "steroid" and "glucocorticoid"-along with their combinations. We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies. A meta-analysis was conducted using a random-effects model, assessing pooled odds ratios and mean differences, with heterogeneity gauged by the I 2 statistic and the χ 2 tests. RESULTS: No statistical differences were found in 28-day all-cause mortality [pooled odds ratio (OR) = 1.109, 95%CI: 0.918-1.340], 60-day all-cause mortality (OR = 0.873, 95%CI: 0.744-1.024; I 2 = 47.29%), mean length of hospital stay (mean difference = -0.08 days, 95%CI: -0.001 to 0.161) and adverse events (OR = 0.877, 95%CI: 0.707-1.087). CONCLUSION: Differing doses of corticosteroids have no clinical implications on mortality, mean length of hospital stay, and adverse events in COVID-19 patients. Additional research is required in patients requiring invasive or non-invasive ventilation.

17.
Data Brief ; 57: 110870, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39290430

ABSTRACT

Sex hormones are necessary for the development and functions of the normal prostate as well as for the initiation and progression of prostate tumors. Indeed, androgens and estrogens can activate their respective nuclear receptors to modulate the expression of multiple genes and pathways in prostate cells. Nevertheless, the androgen and estrogen responses in the normal prostate, and the transcriptomic changes occurring after carcinogenesis, remain poorly understood. Here, wildtype mice and transgenic mice that spontaneously develop prostate cancer (C57BL/6J PB-Cre4+/-;Pten fl/fl) were castrated to ensure hormone deprivation. After three days, animals received injections of testosterone and/or estradiol. After one day, the prostates were harvested, and RNA was purified for sequencing. Sequencing data were then analyzed to study transcriptional modulations following hormonal exposures in normal and tumoral murine prostates. New analyses can be carried out with specific fold-change thresholds for gene expression, or with different pair-wise combinations between conditions (treatments and/or mouse models). Together, the data generated herein are a useful tool to study hormonal transcriptional responses in prostate and prostate cancer biology.

18.
J Agric Food Chem ; 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39295137

ABSTRACT

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

19.
Radiol Case Rep ; 19(12): 5589-5594, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39296754

ABSTRACT

Myelin oligodendrocyte glycoprotein antibody-associated disease is a group of central nervous system demyelinating disorders caused by autoantibodies. While myelin oligodendrocyte glycoprotein antibody-associated disease typically presents as optic neuritis and myelitis in adults, this case report details a patient with brainstem lesions. A 45-year-old male presented with episodes of vertigo, nystagmus, and diplopia in left lateral gaze, which had persisted for 2 months, accompanied by headache. Computed tomography showed hyperdensity extending from the left side of the pons to the middle cerebellar peduncle. Magnetic resonance imaging revealed lesions exhibiting heterogeneous diffusion restriction, with enhancement that included granular and linear patterns. 18F-fluorodeoxyglucose positron emission tomography demonstrated increased uptake in these lesions. Following further evaluation, myelin oligodendrocyte glycoprotein antibody-associated disease was diagnosed. Treatment with high-dose corticosteroids initially alleviated symptoms, but symptoms flared upon reduction of the steroids. This case underscores the importance of considering myelin oligodendrocyte glycoprotein antibody-associated disease in the differential diagnosis of brainstem lesions and discusses distinguishing imaging features from similar conditions.

20.
Chempluschem ; : e202400404, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235155

ABSTRACT

The aggregation of ß-amyloid peptide (Aß) is associated with neurodegenerative diseases such as Alzheimer's disease (AD). Several therapies aimed at reducing the aggregation of this peptide have emerged as potential strategies for the treatment of AD. This paper describes the design and preparation of new hybrid molecules based on steroids, selenosugars, and [60]fullerene as potential inhibitors of Aß oligomerization. These moieties were selected based on their antioxidant properties and possible areas of interaction with the Aß. Cyclopropanations between C60 and malonates bearing different steroid and selenosugar moieties using the Bingel-Hirsch protocol have enabled the synthesis of functionalized molecular hybrids. The obtained derivatives were characterized by physical and spectroscopic techniques. Theoretical calculations for all the selenium compounds were performed using the density functional theory DFT/B3LYP-D3(BJ)/6-311G(2d,p) predicting the most stable conformations of the synthesized derivatives. Relevant geometrical parameters were investigated to relate the stereochemical behavior and the spectroscopic data obtained. The affinity of the compounds for Aß-peptide was estimated by molecular docking simulation, which predicted an increase in affinity and interactions for Aß for the hybrids containing the C60 core. In addition, parameters such as lipophilicity, polar surface area, and dipole moment were calculated to predict their potential interaction with membrane cells.

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