Search Results (85)

Background/Objectives: Antenatal corticosteroids (ACSs) are widely used to improve outcomes in preterm infants, but their effects in the context of fetal growth restriction (FGR) remain incompletely understood. This study investigated the impact of ACSs on pulmonary and neurodevelopmental outcomes using a rabbit mod (K.Z.el) of FGR. Methods: FGR was induced at a gestational age (GA) of 25 days (term 31.5 days) by partial uteroplacental vessel ligation (UPVL) in one uterine horn, with the contralateral horn serving as a control. Dams received intramuscular betamethasone (0.1 mg/kg) or saline 24 and 12 h before expected delivery. At GA 30 days, offspring were delivered by caesarean section and allocated to four groups for pulmonary function testing or neurobehavioral assessment on postnatal day 1, followed by histological analyses of the brain, lungs, and placenta. Results: ACSs improved respiratory mechanics, particularly static and dynamic compliance, in FGR offspring. PND 1 survival showed a concerning pattern, with numerically lower model-estimated survival in both ACS-exposed groups, although the only statistically significant adjusted comparison was between Control/NoACS and FGR/ACS offspring. Neurobehavioral testing showed lower neurosensory performance after ACS exposure within both control and FGR offspring. Lung morphometry and apoptosis were not significantly altered, while neuronal density and astrogliosis showed isolated regional differences. Placental histology showed a higher junctional zone proportion in untreated FGR placentas than in untreated controls. Conclusions: ACSs improved short-term respiratory mechanics without detectable alveolar structural benefit. The observed PND 1 survival pattern and lower neurobehavioral performance warrant cautious interpretation, and these animal findings should not be directly extrapolated to clinical ACS decision-making in FGR pregnancies. Full article

Background/Objectives: Acute inflammatory episodes demand rapid symptom control while limiting systemic exposure. We assessed whether co-therapy with the selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib and the corticosteroid betamethasone provides antinociceptive and anti-edema activity in a rat model with complete Freund’s adjuvant-induced arthritis (AIA). Methods: Male Wistar rats (n = 10/group) were allocated to seven groups: Intact, AIA disease control, indomethacin 5 mg/kg, etoricoxib 8 mg/kg, betamethasone 0.022 mg/kg, low-dose combination (4 + 0.011 mg/kg), and full-dose combination (8 + 0.022 mg/kg), administered orally once daily from Days 4 to 28. Paw edema, von Frey withdrawal thresholds, and clinical arthritis score were assessed longitudinally as area under the curve (AUC) values. Terminal joint tissues were profiled for cytokines, prostaglandin pathway mediators, and immune cell markers. Results: Both combinations reduced edema and improved mechanical thresholds. The full-dose combination exceeded either monotherapy regarding mechanical sensitivity and the arthritis index, consistent with additive activity. The low-dose combination matched full-dose monotherapies, consistent with a dose-reduction effect. Biomarker shifts indicated attenuated prostaglandin signaling and a pro-resolving cytokine balance. Conclusions: These findings support the further evaluation of etoricoxib–betamethasone co-therapy for acute inflammatory conditions. Full article

Despite the need for immediate treatment during acute allergic reactions (AARs), many patients do not consistently carry medication. A new mouth-dissolving dexamethasone film offers a portable, easily administered alternative to corticosteroid tablets. This non-randomized, open-label, low-interventional real-world trial assessed satisfaction (accessibility and safety/security) with the mouth film versus betamethasone tablets in adults prescribed tablets for moderate to severe AARs at a Swedish primary care center. Over six months, participants had access to both treatments and reported monthly via an electronic diary; qualitative responses were converted to Likert scales where applicable. Of 50 enrolled, 44 provided diary data (mean age 50 years, 74% female, 58% had an epinephrine autoinjector). In total, 189 responses were collected: 98% stated that the participant was satisfied or very satisfied with mouth film accessibility versus 58% for tablets (mean Likert scores 3.5–3.7 vs. 2.5–2.8; p < 0.001). A higher feeling of safety with the mouth film versus tablets was reported in 78% of responses and improved medication carriage compliance in 77%. At six months, 69% preferred the film. Of 18 AARs in total reported by 13 participants, the mouth film was chosen for treatment of 16 (11 participants); in 94%, the mouth film was found immediately accessible, and in 94%, the efficacy was rated as good or very good. In conclusion, the mouth film improved perceived accessibility, safety/security, and medication-carriage compliance compared with tablets for the treatment of AARs. Full article

Pharmaceutical residues are increasingly detected in aquatic environments and are recognized as contaminants of emerging concern. This systematic literature review compiled and evaluated published concentrations of pharmaceutical residues in bottled water, tap water, and surface water in Portugal, applying risk quotient (RQ) and screening-level risk quotient (RQ_screen) approaches to evaluate potential human health risks and prioritize contaminants. Assessment based on the compiled literature data across age groups showed bottled and tap water posed low risk, while surface water presented the highest concern, with compounds spanning the full risk spectrum. Key contributors to potential human health risk included hormones (17-alpha-ethinylestradiol, 17-beta-estradiol, estrone), ramipril, betamethasone, citalopram, and amoxicillin. RQ_screen highlighted compounds relevant for ongoing monitoring even in treated waters, such as carbamazepine, diclofenac, salicylic acid, warfarin, fluoxetine, and erythromycin, due to their persistence and toxicological significance. Both RQ and RQ_screen indicated higher risk values for infants and children, reflecting lower body weight and higher water intake per unit mass, underscoring the need for age-specific evaluations. The RQ_screen method proved useful for contaminant prioritization, identifying substances relevant for monitoring despite low concentrations. Overall, this systematic review highlights pharmaceutical residues as an emerging public and environmental health concern in Portugal and emphasizes the importance of targeted monitoring and risk-based management within a One Health framework. Full article

Objectives: We aimed to investigate the short-term effects of preoperative postauricular glucocorticoid (GC) injection on electrode impedance in cochlear implant (CI) recipients. Methods: A total of 69 participants were enrolled: 44 children (<18 years) and 25 adults (18–85 years). Using a pre-specified non-randomized alternating assignment strategy, they were respectively assigned to either the treatment group (preoperative postauricular methylprednisolone injection and intraoperative intratympanic betamethasone) or the control group (intraoperative intratympanic betamethasone alone). Electrode impedance was measured intraoperatively and at 1, 3, and 6 months postoperatively. Owing to the use of different implant systems in pediatric and adult patients, the two cohorts were analyzed separately. Longitudinal impedance data across cochlear turns (apex, middle, base) were analyzed using linear mixed-effects models adjusted for baseline values. This study was registered on Chictr.org.cn (ChiCTR2400081024). Results: In the pediatric cohort, a significant interaction between group and time was observed (F = 8.34, p < 0.001); however, post hoc analyses did not demonstrate statistically significant differences between groups at individual postoperative time points (all p > 0.05). In the adult cohort, a significant interaction between group and turn was identified (F = 3.07, p = 0.049); post hoc analysis demonstrated statistically significant differences in impedance in the middle turn between groups (intervention effect = 1.355 kΩ; 95% CI, 0.115 to 2.596; p = 0.033). Conclusions: Preoperative postauricular GC administration, when combined with intraoperative intratympanic steroid therapy, may be associated with differences in postoperative electrode impedance dynamics and the electrode–tissue interface. Full article

Objectives: To evaluate the association between antenatal betamethasone exposure and neonatal respiratory morbidity among late-preterm births. We further examined whether gestational age at delivery and the exposure-to-delivery interval modify this association. Methods: We conducted a retrospective cohort study of singleton live births at 34–36 + 6 weeks in a tertiary center (2011–2023). Betamethasone exposure was classified as none, early (<34 weeks), or late (34–36 + 6 weeks). Among exposed pregnancies, the interval from first dose to delivery was categorized as ≤7 or >7 days and evaluated separately at 34, 35, and 36 weeks. Primary outcomes were RDS and composite respiratory morbidity (RDS, TTN, or ≥3 days of respiratory support); neonatal hypoglycemia was secondary. Adjusted odds ratios were estimated using multivariable logistic regression including maternal age, parity, delivery mode, and birthweight. Results: The study included 2668 late-preterm infants, of whom 2356 (88.3%) were unexposed and 312 (11.7%) were exposed to antenatal corticosteroids (ACSs). Among exposed pregnancies, 138 (44.2%) received early ACS and 174 (55.8%) late ACS; 163 (52.2%) delivered ≤7 days and 149 (47.8%) >7 days after administration. Late ACS exposure was associated with lower odds of RDS (aOR 0.37, 95% CI 0.17–0.69) and composite respiratory morbidity (aOR 0.55, 95% CI 0.31–0.92), but with increased odds of neonatal hypoglycemia (aOR 2.72, 95% CI 1.26–5.31). Among pregnancies delivering at 34 weeks, exposure within ≤7 days was associated with a marked reduction in RDS (aOR 0.25, 95% CI 0.07–0.79; NNT ≈ 3), whereas no respiratory benefit was observed at 35 or 36 weeks or when the interval exceeded 7 days. Conclusions: Antenatal betamethasone exposure among late-preterm births was not uniformly associated with neonatal respiratory outcomes, with associations varying by gestational age at delivery and the exposure-to-delivery interval. These findings may be interpreted in the context of potential respiratory benefit alongside accompanying metabolic risk, with exploratory analyses suggesting a more pronounced signal among deliveries at 34 weeks within ≤7 days. Full article

Background: Analgesics are widely used in competitive sports, but their patterns of use and detection in anti-doping controls vary significantly across drug classes. This study examined a decade of Italian anti-doping reports with three aims: to describe trends involving non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and narcotics; to characterize the distribution of specific active ingredients; and to analyze the relative contribution of these classes to anti-doping violations, placing the findings within the regulatory framework. Methods: Data from national anti-doping reporting systems were analyzed from 2013 to the first half of 2023. Yearly data included tested athletes, athlete declarations of NSAID use, and laboratory analytical findings for prohibited substances (glucocorticoids and narcotics). NSAID prevalence was calculated relative to tested athletes, while glucocorticoid and narcotic findings were assessed as absolute counts and proportions of total violations. Temporal trends were assessed using the Cochran–Armitage test. Results: NSAIDs consistently ranked as the most frequently reported medication, with nearly half of the tested athletes reporting their use and no significant linear trend in overall prevalence. However, a significant shift was observed within the NSAID class, with a marked decrease in declarations of COX-2 selective agents over time. Glucocorticoids accounted for a significant portion of prohibited substances, with fluctuating proportions (showing no significant linear trend), betamethasone being the most common active ingredient. Narcotics appeared only sporadically, although the use of non-prohibited opioids such as tramadol and codeine—absent from official reports—remains relevant for understanding analgesic practices. Conclusions: Analgesic use in Italian elite sports shows distinct patterns driven by therapeutic needs and anti-doping regulations. NSAIDs remain the primary choice for routine pain management, though the type of NSAID reported has shifted significantly. Glucocorticoids represent a notable share of prohibited findings with a fluctuating, rather than steadily increasing, pattern. Narcotics appear only sporadically in violation data. Ongoing monitoring will be crucial to understanding how evolving clinical practices and recent regulatory changes influence future detection trends and athlete health. Full article

Background/Objectives: Infantile epileptic spasms syndrome (IESS) is a severe epilepsy of infancy. Corticotropin (ACTH) and vigabatrin are the only FDA-approved therapies. The efficacy of ACTH together with the strong convulsant effects of corticotropin-releasing hormone (CRH) suggests that excess CRH, secondary to impaired ACTH feedback, may contribute to spasms. We therefore hypothesized that CRH receptor 1 (CRHR1) antagonists would suppress spasms in a route- and drug-dependent manner. Methods: Using our validated rat model of IESS, in which prenatal priming with betamethasone was followed by postnatal triggering of spasms with N-methyl-D-aspartic acid (NMDA), we tested two CRHR1 antagonists, CP376395 and SN003, delivered intracranially (via intracerebroventricular or intraparenchymal infusion) or systemically. Results: Intracerebroventricular infusion of both antagonists suppressed spasms, with CP376395 providing more consistent effects. Intraparenchymal administration into the hypothalamic arcuate nucleus also reduced spasms, whereas misses into the mammillary bodies were ineffective, highlighting site specificity. Systemic administration yielded divergent results: SN003 robustly suppressed spasms, whereas CP376395 unexpectedly exacerbated them. No sex differences were observed. Conclusions: These findings demonstrate that CRHR1 blockade modifies experimental spasms in a route- and drug-specific manner and implicates discrete hypothalamic circuits, particularly those including the arcuate nucleus, in spasm generation. The divergent systemic responses between CP376395 and SN003 likely reflect differences in CRHR1 engagement (competitive and non-competitive antagonism, respectively) as well as differences in binding properties that may include differential network interactions beyond local CRH signaling or duration of receptor occupancy. In conclusion, SN003 may be a better option than CP376395 for further development as a CRHR1-targeted therapy pending additional pharmacokinetic/pharmacodynamic studies. Further work should explore dosing paradigms of CP376395 to determine if a therapeutic range for CP376395 exists. Full article

Background/Objectives: Persistent inflammation driven by cytokines/chemokines plays a crucial role in the pathogenesis of numerous chronic inflammatory and autoimmune conditions, including rheumatoid arthritis, atopic dermatitis, and ulcerative colitis. Current therapeutic agents often present limitations due to adverse effects. Thykamine™, a new plant-derived multi-target drug, has demonstrated promising anti-inflammatory effects and a favorable safety profile in clinical settings. This study aimed to compare the in vitro chemokine-inhibitory potency of Thykamine™, a novel plant-derived anti-inflammatory compound, with that of six marketed corticosteroid and non-steroidal agents. Methods: This study compared the in vitro potency of Thykamine™ against widely prescribed anti-inflammatory agents, including corticosteroids (betamethasone, clobetasol, hydrocortisone, prednisone) and non-steroidal therapies (crisaborole, pimecrolimus). Potency was assessed by measuring the inhibition of key pro-inflammatory chemokines: MCP-1, MIP-1α, MIP-1β, and RANTES in lipopolysaccharide-stimulated U937 cells. Results: Area-under-the-curve (AUC) analyses confirmed that Thykamine™ inhibited secretion of the chemokines MCP-1, MIP-1α, and MIP-1β with significantly greater potency than all other agents tested. Thykamine™ also suppressed secretion of RANTES similarly to prednisone and significantly more than betamethasone, clobetasol, hydrocortisone, and pimecrolimus but less than crisaborole due to crisaborole’s elevated potency when administered at high concentration. Conclusions: Overall, Thykamine™ showed significantly greater or comparable inhibitory potency, particularly at lower concentrations, without evidence of cytotoxicity. These findings underscore the potential of Thykamine™ as a potent, multi-target anti-inflammatory therapy, which could offer substantial clinical advantages by effectively controlling chemokine-mediated inflammation with potentially fewer adverse effects. The results of this study support the need for evaluation of the clinical therapeutic efficacy of Thykamine™ in a wide range of autoimmune conditions. Full article

Glucocorticoids are essential for fetal organ maturation and form the basis of antenatal corticosteroid therapy that has significantly reduced preterm-related morbidity such as respiratory distress syndrome (RDS). However, neonatal morbidity remains a clinical challenge regardless of antenatal corticosteroid therapy. Currently, it is thought that adverse intrauterine environments dysregulate glucocorticoid receptor (GR) homeostasis, yet the biological mechanisms remain poorly understood. Therefore, we aimed to study ex vivo glucocorticoid sensitivity in cord blood immune cells from two independent preterm cohorts to identify associations with neonatal morbidity and uncover potential mechanisms of dysregulated glucocorticoid homeostasis. In the first cohort, thawed cord blood mononuclear cells were exposed to betamethasone in the presence of lipopolysaccharides (LPS) for 4 h. In the second cohort, freshly isolated white blood cells were treated with dexamethasone under unstimulated and LPS-stimulated conditions for 48 h. GR isoform expression and regulation of transactivated and transrepressed genes were assessed via qPCR, immunoblotting, flow cytometry, and ELISA. In both cohorts, reduced GR expression, particularly of the GRα isoform, was observed in neonates with morbidity, but only with culture time and not in freshly isolated cells. Ex vivo impaired glucocorticoid-mediated transrepression of proinflammatory genes IL6 and TNF was also observed in the morbidity groups. In contrast, all samples were comparable in basal immune cell distributions and transactivation of glucocorticoid response element (GRE)-dependent genes GILZ and FKBP5, irrespective of neonatal morbidity. These findings suggest that neonates that develop morbidities experience an early postnatal GR dysfunction that is potentially programmed in utero. Moreover, under conditions of decreased GR abundance, classical transactivation functions appear to be preserved at the expense of more complex regulatory mechanisms such as transrepression. Full article

Canine otitis externa (OE) presents a significant challenge in veterinary medicine due to its complex, multifactorial nature and the growing issue of antimicrobial resistance (AMR) associated with conventional antibiotic use. The objective of this study was to compare the efficacy of a novel, antibiotic-free topical ear solution (Therapy A) containing antimicrobial peptides and encapsulated plant extracts (chamomile, calendula, rosemary, and hops) against a standard conventional treatment (Therapy B) composed of gentamicin, betamethasone valerate, and clotrimazole. A longitudinal, randomized study was conducted over four weeks with 40 domestic dogs diagnosed with OE. The dogs were divided into two groups, each receiving one of the therapies. Evaluations were performed weekly, assessing clinical signs using the Otitis Index Scoring System (OTIS-3) and a pruritus visual analog scale (pVAS), as well as ear canal pH and cytology. The results showed that Therapy A provided similar clinical efficacy in OTIS-3 and pVAS scores that were comparable to Therapy B. Cytological analysis also revealed a significant reduction in microbial presence for both groups. Notably, Therapy A was clinically effective in two of the three dogs presenting multi-drug resistant (MDR) bacterial infections. The novel formulation also demonstrated a favorable safety profile, with no adverse drug reactions reported, in contrast to one dog in the conventional treatment group that experienced an adverse reaction. These findings suggest that the plant-based formulation is a safe and effective alternative for managing canine OE, offering a promising solution to reduce the reliance on antibiotics and corticosteroids. Full article

Background/Objectives: Lichen sclerosus is a chronic lymphocyte-mediated inflammatory disorder with a predilection for the anogenital region. It is a common cause of urethral stricture disease in males. The gold standard treatment is considered to be surgical reconstruction; however, there are many patients who are not suitable or not willing to undergo surgery. Cutaneous lichen sclerosus restricted to the foreskin, prepuce or glans is often response to topical corticosteroids; however, the use of intraurethral corticosteroids for urethral involvement has limited research. Methods: We conducted a retrospective cohort study on 18 patients with histologically confirmed lichen sclerosus and associated urethral stricture disease. They were treated with clean intermittent self catheterisation using a hydrophilic catheter coated with 0.05% betamethasone ointment. International Prostate Symptom Score with Quality of Life scores were measured prior to treatment and at follow-up intervals. Results: There was significant improvement in International Prostate Symptom Score and Quality of Life scores at 3 months, 12 months and 24 months, with only 1 patient ceasing treatment due to intolerance. One patient required a single repeat endoscopic dilatation following a period of non-compliance with treatment. Conclusions: Intraurethral corticosteroids with clean-intermittent self-catheterisation is effective and well tolerated for treating lichen sclerosus-associated urethral stricture disease in the short to intermediate term for patients not willing to undergo urethroplasty. Full article

A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article

Calcipotriol, a synthetic vitamin D₃ analogue widely used in psoriasis treatment, requires a detailed stability assessment due to its topical application and potential exposure to UV radiation. As a drug applied directly to the skin, calcipotriol is particularly susceptible to photodegradation, which may affect its therapeutic efficacy and safety profile. The present study focuses on the analysis of calcipotriol photostability. An advanced UHPLC/MS^E method was employed for the precise determination of calcipotriol and its degradation products. Particular attention was given to the effects of commonly used organic UV filters—approved for use in cosmetic products in both Europe and the USA (benzophenone-3, dioxybenzone, meradimate, sulisobenzone, homosalate, and avobenzone)—on the stability of calcipotriol. Unexpected degradation of calcipotriol was observed in the presence of sulisobenzone. Importantly, this effect was consistently detected in methanolic solution and in the pharmaceutical formulation containing calcipotriol and betamethasone, which is particularly significant from a practical perspective. This finding underscores the necessity of evaluating photostability under real-life conditions, as cosmetic ingredients, when co-applied with topical drugs on the skin, may substantially influence the stability profile of the pharmaceutical active ingredient. The research resulted in the first-time characterization of four degradation products of calcipotriol. The degradation process was found to primarily affect the E-4-cyclopropyl-4-hydroxy-1-methylbut-2-en-1-yl moiety, causing its isomerization to the Z isomer and the formation of diastereomers with either the R or S configuration. Computational analyses using the OSIRIS Property Explorer indicated that none of the five degradation products exhibit a toxicity effect, whereas molecular docking studies suggested possible binding of two of the five degradation products of calcipotriol with the VDR. Full article

Background/Objectives: The treatment of atopic dermatitis frequently involves using a topical corticosteroid and a moisturizer. While the sequential application of these products is a common dermatological practice, their influence on drug penetration remains poorly understood. There is no clear evidence on how hydration, application sequence, and massage affect cutaneous drug delivery. Hence, this study aimed to evaluate the effects of formulation type, moisturizer composition, application sequence, and mechanical stimulation on betamethasone dipropionate (BET) cutaneous penetration. Methods: Two commercial formulations (cream and ointment) of BET were evaluated in different experimental conditions, including drug application combined with moisturizers (Cetaphil^®, as an emollient; Nivea^®, as an occlusive) pre- or post-application, with or without a 30 s massage. In vitro skin penetration assays were conducted for 12 h using porcine skin mounted in modified Franz diffusion cells. BET levels were extracted from the skin layers and quantified by HPLC. Results: The cutaneous BET penetration was strongly influenced by the application sequence, type of moisturizer, and mechanical stimuli. Pre-application of an occlusive or emollient moisturizer, followed by 30 s physical stimuli, significantly enhanced drug retention in the stratum corneum. For the cream, pre-application of moisturizers followed by massage notably increased BET levels in both the stratum corneum and viable skin. Conversely, post-application of moisturizers hindered BET absorption. The ointment showed limited penetration across all conditions, with no drug detected in the viable skin. Conclusions: The results showed pre-hydrating the skin, combined with a 30 s massage, was the best strategy for BET diffusion into the skin following cream administration. The formulation type and the order of application directly influence the effectiveness of drug therapy and the topical absorption of BET. Full article