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Frontiers in Pharmacology 2024Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases. Roflumilast, apremilast, and crisaborole have been developed... (Review)
Review
Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases. Roflumilast, apremilast, and crisaborole have been developed and approved for the treatment of chronic obstructive pulmonary disease psoriatic arthritis, and atopic dermatitis. Inflammation underlies many vascular diseases, yet the role of PDE4 inhibitors in these diseases remains inadequately explored. This review elucidates the clinical applications and anti-inflammatory mechanisms of PDE4 inhibitors, as well as their potential protective effects on vascular diseases. Additionally, strategies to mitigate the adverse reactions of PDE4 inhibitors are discussed. This article emphasizes the need for further exploration of the therapeutic potential and clinical applications of PDE4 inhibitors in vascular diseases.
PubMed: 38915460
DOI: 10.3389/fphar.2024.1407871 -
Scientific Reports Jun 2024The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological,...
The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological, biochemical, and antioxidant parameters, along with immunohistochemical and histological indications in tilapia (Oreochromis niloticus) after being exposed to tadalafil, polyethylene microplastics (PE-MPs), and their mixtures for 15 days. The fish were distributed into 1st group control group (The fish was maintained in untreated water without any supplements); 2nd group exposed to 10 mg/L PE-MPs;3rd group exposed to 20 mg/l tadalafil (Cilais); 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs (in triplicate). The levels of creatinine, uric acid, glucose, AST, ALT, and albumin in fish treated with tadalafil alone or in combination with PE-MPs were significantly higher than those in the control group. Fish exposed to PE-MPs, tadalafil, and tadalafil plus PE-MPs showed significantly lower levels of RBCs, Hb, Ht, neutrophils, and lymphocytes compared to the control group. Serum levels of total antioxidant capacity and reduced glutathione (GSH) were notably lowered in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations in comparison to the control group. Malondialdehyde (MDA) serum levels were notably elevated in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations compared to the control group. The most severe impact was observed in the tadalafil + PE-MPs combination group. Interleukin-6 (IL-6) levels were significantly increased in liver tissues following exposure to both tadalafil and microplastics compared to tissues exposed to only one substance or the control group. Changes in the gills, liver, and renal tissues were seen following exposure to PE-MPs, tadalafil, and tadalafil + PE-MPs combination in comparison to the control group of fish. Ultimately, the mixture of tadalafil and PE-MPs resulted in the most detrimental outcomes. Tadalafil and PE-MPs exhibited showed greater adverse effects, likely due to tadalafil being absorbed onto PE-MPs.
Topics: Animals; Tadalafil; Cichlids; Water Pollutants, Chemical; Microplastics; Antioxidants; Tilapia; Glutathione; Gills; Oxidative Stress
PubMed: 38914580
DOI: 10.1038/s41598-024-64282-3 -
The Journal of Dermatological Treatment Dec 2024Understanding the economic value of deucravacitinib and apremilast could assist treatment decision-making for patients with moderate to severe plaque psoriasis. (Comparative Study)
Comparative Study
BACKGROUND
Understanding the economic value of deucravacitinib and apremilast could assist treatment decision-making for patients with moderate to severe plaque psoriasis.
OBJECTIVE
This study compared the cost per response (CPR) for US patients initiating deucravacitinib versus apremilast for moderate to severe plaque psoriasis.
METHODS
A CPR model using pharmacy and administration costs was developed from a US payer perspective. Response was defined as a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at weeks 16 and 24. Long-term response was defined as the cumulative benefit over 52 weeks, measured as area under the curve; subsequent treatment was included. Scenario analyses explored varying the efficacy measure or choices of subsequent treatments and limiting discontinuation.
RESULTS
The CPR for deucravacitinib versus apremilast was lower at 16 weeks (difference: -$3796 [95% confidence interval (CI): -$6140 to -$1659]) and 24 weeks (difference: -$12,784 [95% CI: -$16,674 to -$9369]). At 52 weeks, the cost per cumulative benefit was lower for patients who initiated deucravacitinib, regardless of initial treatment period duration (16 or 24 weeks).
CONCLUSIONS
Scenario analyses found mainly consistent results. This study showed that the CPR is lower when initiating deucravacitinib versus apremilast in moderate to severe plaque psoriasis.
Topics: Humans; Psoriasis; United States; Thalidomide; Severity of Illness Index; Cost-Benefit Analysis; Biological Products; Treatment Outcome; Drug Costs; Male; Female
PubMed: 38914425
DOI: 10.1080/09546634.2024.2366503 -
The Journal of Dermatological Treatment Dec 2024This noninterventional, cross-sectional survey estimated the prevalence and consequences of residual disease in apremilast-treated US adults with moderate to severe...
This noninterventional, cross-sectional survey estimated the prevalence and consequences of residual disease in apremilast-treated US adults with moderate to severe psoriasis. Residual disease was defined as experiencing moderate, severe, or very severe psoriasis over the past week or having ≥3% body surface area affected, despite treatment. Factors associated with residual disease and its effects on flare-ups, humanistic burden, and health care resource utilization (HCRU) were evaluated. Of the 344 apremilast users (mean age, 44.9 years; female, 65.4%), 174 (50.6%) had residual disease. It was more prevalent in Black versus White participants (OR, 4.5; 95% CI, 1.6-12.2), those receiving apremilast for ≥1 versus <1 year (OR, 16.5; 95% CI, 7.9-34.4), those reporting ≥2 versus 0 to 1 flare-ups during the past 3 months (OR, 10.0; 95% CI, 5.0-20.1), and those with ≥4 versus 1 to 3 body regions affected at time of survey (OR, 8.6; 95% CI, 3.8-19.8). Participants with versus without residual disease self-reported more psoriasis flare-ups over the past 3 months (mean, 4.7 vs 0.9; < .001) and more anxiety (89.7% vs 50.0%; < .001) and depression (69.0% vs 23.6%; < .001) over the past 30 days. Generally, participants with versus without residual disease also had significantly more comorbidities and greater HCRU.
Topics: Humans; Psoriasis; Thalidomide; Female; Male; Cross-Sectional Studies; Adult; Middle Aged; United States; Prevalence; Severity of Illness Index; Anti-Inflammatory Agents, Non-Steroidal; Surveys and Questionnaires; Symptom Flare Up
PubMed: 38914422
DOI: 10.1080/09546634.2024.2366532 -
Scientific Reports Jun 2024To assess the effects of warm-up music and low dose (3 mg·kg) of caffeine (CAF) on female taekwondo athlete's activity profile and psychophysiological responses during... (Randomized Controlled Trial)
Randomized Controlled Trial
To assess the effects of warm-up music and low dose (3 mg·kg) of caffeine (CAF) on female taekwondo athlete's activity profile and psychophysiological responses during simulated combat. In a double-blinded, randomized, crossover study, 16 female athletes participated in simulated combats under one control and 5 experimental conditions [i.e., CAF alone (CAF), placebo alone (PL), CAF with music (CAF + M), PL with music (PL + M), and no supplement with music (M)]. After warming-up, athletes rated their felt arousal (FAS). Mean (HR) and peak (HR) heart rate values were determined for each combat. After fighting, athletes rated their perceived exertion (RPE), feeling scale (FS), FAS, and physical enjoyment (PACES). Time-motion and technical-tactical variables were analyzed. CAF + M induced shorter skip and pause time, while attack time increased compared to other conditions (p < 0.05). Moreover, CAF + M increased single attacks, combined attacks, counter-attacks (p < 0.001), and defensive actions (p < 0.05) than other conditions. HR and HR were lower under CAF + M than other conditions (p < 0.05). Additionally, higher FAS post-combat, FS, and PACES were observed under CAF + M, while RPE was lower (except CAF condition) compared to the other conditions (p < 0.05.Using CAF with warm-up music may increase combat cadence and improve the psychological state in female athletes more effectively than either strategy alone.
Topics: Humans; Female; Caffeine; Music; Athletes; Martial Arts; Young Adult; Cross-Over Studies; Double-Blind Method; Heart Rate; Warm-Up Exercise; Adult; Athletic Performance; Arousal
PubMed: 38906894
DOI: 10.1038/s41598-024-64880-1 -
BMC Pediatrics Jun 2024With a wide therapeutic index, efficacy, ease of use, and other neuroprotective and respiratory benefits, caffeine citrate(CC) is currently the drug of choice for...
BACKGROUND
With a wide therapeutic index, efficacy, ease of use, and other neuroprotective and respiratory benefits, caffeine citrate(CC) is currently the drug of choice for preterm neonates (PTNs). Caffeine-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side-effects (CC-APSEs) result in lower daily-weight gain (WG) in premature neonates. This study aimed to evaluate the risk factors for daily-WG in neonates exposed to different dose regimens of caffeine in ICU.
METHOD
This retrospective cohort study included neonates of ≤ 36weeks gestational age (GA) and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I (received; standard-doses = 5 mg/kg/day), group-II (received;>5-7 mg/kg/day), and group-III (received;>7 mg/kg/day). Prenatal and postnatal clinical characteristics, CC-regimen, daily-WG, CC-APSEs, and concomitant risk-factors, including daily-caloric intake, Parenteral-Nutrition duration, steroids, diuretics, and ibuprofen exposure, were analyzed separately for group-II and group-III using group-I as standard. Regression analysis was performed to evaluate the risk factors for daily-WG.
RESULTS
Included 314 PTNs. During 15-28 DOL, the mean-daily-WG(MD-WG) was significantly higher in group-I than group-II [19.9 ± 0.70 g/kg/d vs. 17.7 ± 0.52 p = 0.036] and group-III [19.9 ± 0.70 g/kg/d vs. 16.8 ± 0.73 p < 0.001]. During 29-42 DOL the MD-WG of group-I was only significantly higher than group-III [21.7 ± 0.44 g/kg/d vs. 18.3 ± 0.41 g/kg/d p = 0.003] and comparable with group-II. During 15-28 DOL, observed CC-APSEs was significantly higher in group-II and III but during 29-42 DOL it was only significant in group-III. In the adjusted regression analysis for daily-WG during 15-28DOL, with respect to standard-dose, 5-7 mg/kg/day (β=-1.04; 95%CI:-1.62,-0.93) and > 7-10 mg/kg/day (β=-1.36; 95%CI:-1.56,-1.02) were associated with a lower daily-WG. However, during 29-42DOL, this association was present only for > 7-10 mg/kg/day (β=-1.54; 95%CI:-1.66,-1.42). The GA ≤ 27weeks (β=-1.03 95%CI:-1.24, -0.88) was associated with lower daily-WG only during 15-28DOL. During both periods of therapy, higher cumulative-caffeine dose and presence of culture proven sepsis, tachypnea, hyponatremia, and feeding intolerance were significantly associated with lower daily-WG. Conversely, daily kcal intake was found to be linked with an increase in daily-WG in both periods.
CONCLUSION
In this study cohort exposure to higher caffeine daily and cumulative doses is associated with lower postnatal daily-WG in PTNs than standard-daily doses, which may be due to its catabolic effects and CC-APSEs.
Topics: Humans; Caffeine; Retrospective Studies; Infant, Newborn; Female; Male; Infant, Premature; Weight Gain; Dose-Response Relationship, Drug; Risk Factors; Intensive Care Units, Neonatal; Citrates; Central Nervous System Stimulants
PubMed: 38898410
DOI: 10.1186/s12887-024-04850-8 -
Brazilian Journal of Medical and... 2024The purpose of this study was to verify the association between angiotensin-converting enzyme (ACE) genotypes DD, DI, and II and caffeine (CAF) ingestion on endurance... (Randomized Controlled Trial)
Randomized Controlled Trial
ACE gene polymorphisms (rs4340) II and DI are more responsive to the ergogenic effect of caffeine than DD on aerobic power, heart rate, and perceived exertion in a homogeneous Brazilian group of adolescent athletes.
The purpose of this study was to verify the association between angiotensin-converting enzyme (ACE) genotypes DD, DI, and II and caffeine (CAF) ingestion on endurance performance, heart rate, ratio of perceived exertion (RPE), and habitual caffeine intake (HCI) of adolescent athletes. Seventy-four male adolescent athletes (age: DD=16±1.7; DI=16±2.0; II=15±1.7 years) ingested CAF (6 mg/kg) or placebo (PLA) one hour before performing the Yo-Yo Intermittent Recovery level 1 (Yo-Yo IR1) test. No difference was found among groups for HCI. However, CAF increased the maximal distance covered and VO2max in DI and II genotype carriers compared to PLA (DD: Δ=31 m and 0.3 mL·kg-1·min-1; DI: Δ=286 m and 1.1 mL·kg-1·min-1; II: Δ=160 m and 1.4 mL·kg-1·min-1). Heart rate of DI and II genotype carriers increased with CAF compared to PLA, while RPE was higher in the II and lower in the DD genotypes. The correlations between HCI and maximal distance covered or VO2max were significant in the II genotype carriers with CAF. CAF increased endurance capacity, heart rate, and RPE in adolescent athletes with allele I, while endurance performance and aerobic power had a positive correlation to HCI in the II genotype group. These findings suggested that DD genotype were less responsive to CAF and that genetic variations should be taken into account when using CAF supplementation to enhance exercise performance.
Topics: Humans; Adolescent; Male; Heart Rate; Caffeine; Genotype; Athletes; Physical Exertion; Peptidyl-Dipeptidase A; Athletic Performance; Physical Endurance; Polymorphism, Genetic; Brazil; Oxygen Consumption; Performance-Enhancing Substances
PubMed: 38896643
DOI: 10.1590/1414-431X2024e13217 -
Drug Design, Development and Therapy 2024This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
OBJECTIVE
This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application.
METHODS
A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (C), the areas under the plasma concentration-time curve (AUC, AUC), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.
RESULTS
Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09-103.44% for C, 94.05-103.51% for AUC, and 94.56-103.86% for AUC under fasting conditions, and 99.18-112.48% for C, 98.79-106.02% for AUC, and 98.95-105.89% for AUC under postprandial conditions, all of which were within the bioequivalence range of 80.00-125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study.
CONCLUSION
The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated.
CLINICAL TRIAL REGISTRATION
chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).
Topics: Humans; Therapeutic Equivalency; Thalidomide; Fasting; Postprandial Period; Adult; Male; Cross-Over Studies; Healthy Volunteers; Tablets; Young Adult; Female; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Area Under Curve; Administration, Oral
PubMed: 38895175
DOI: 10.2147/DDDT.S461771 -
Molecules (Basel, Switzerland) May 2024Yerba Mate drink made from dried and crushed leaves and twigs of Paraguayan holly ( A. St.-Hil.), which is a valuable source of bioactive substances, in particular...
Yerba Mate drink made from dried and crushed leaves and twigs of Paraguayan holly ( A. St.-Hil.), which is a valuable source of bioactive substances, in particular antioxidants. The available literature lacks data on changes in the content and profile of bioactive compounds such as tannins, caffeine, the phenolic acid profile of flavonoids and carotenoids, as well as total polyphenol content and antioxidant activity in Yerba Mate infusions depending on different brewing conditions, and how different brewing conditions affect the physicochemical properties of these infusions. Therefore, this study evaluated the physicochemical properties of dried and Yerba Mate infusions prepared via single and double brewing processes at 70 °C and 100 °C. The organoleptic evaluation, as well as the instrumental color measurement, showed significant changes in the total color difference (Δ) and the *** chromatic coordinates of dried Yerba Mate samples and their infusions. Moreover, the research showed higher contents of tannins (mean 1.36 ± 0.14 g/100 g d.m.), caffeine (mean 17.79 ± 3.49 mg/g d.m.), carotenoids (mean 12.90 ± 0.44 μg/g d.m.), phenolic acids (mean 69.97 ± 7.10 mg/g d.m.), flavonoids (mean 5.47 ± 1.78 mg/g d.m.), total polyphenols (mean 55.26 ± 8.51 mg GAE/g d.m.), and antioxidant activity (mean 2031.98 ± 146.47 μM TEAC/g d.m.) in single-brewed Yerba Mate infusions compared to double-brewed (0.77 ± 0.12 g/100 g d.m., 14.28 ± 5.80 mg/g d.m., 12.67 ± 0.62 μg/g d.m., 57.75 ± 8.73 mg/g d.m., 3.64 ± 0.76 mg/g d.m., 33.44 ± 6.48 mg GAE/g d.m. and 1683.09 ± 155.34 μM TEAC/g d.m., respectively). In addition, infusions prepared at a lower temperature (70 °C) were characterized by a higher content of total polyphenols and higher antioxidant activity, in contrast to the tannin and carotenoid contents, the levels of which were higher at 100 °C than at 70 °C. Considering the high amount of bioactive ingredients, in particular antioxidants, and a wide range of health benefits, it is worth including Yerba Mate in the daily diet.
Topics: Ilex paraguariensis; Antioxidants; Polyphenols; Tannins; Flavonoids; Carotenoids; Plant Extracts; Plant Leaves; Caffeine; Hydroxybenzoates; Beverages
PubMed: 38893465
DOI: 10.3390/molecules29112590 -
Nutrients Jun 2024This systematic review aimed to evaluate the effectiveness of the independent or combined use of nutritional ergogenic aids belonging to Group A of the ABCD... (Review)
Review
This systematic review aimed to evaluate the effectiveness of the independent or combined use of nutritional ergogenic aids belonging to Group A of the ABCD classification by the Australian Institute of Sport (AIS) in the context of cycling (caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates, and glycerol). A comprehensive search was carried out using three databases: PubMed, Scopus, and Web of Science. All the databases were searched for Randomized Controlled Trials or crossover design studies assessing the effects of supplementation on cycling performance in comparison with placebos in healthy adults. The methodological quality of each study was evaluated using the Physiotherapy Evidence Database scale. Thirty-six articles involving 701 participants were included in this review, examining supplementation with caffeine (n = 5), creatine (n = 2), sodium bicarbonate (n = 6), beta-alanine (n = 3), and nitrates (n = 8). Additionally, supplemental combinations of caffeine and creatine (n = 3), caffeine and sodium bicarbonate (n = 3), caffeine and nitrates (n = 1), creatine and sodium bicarbonate (n = 1), and sodium bicarbonate and beta-alanine (n = 4) were analyzed. A benefit for cyclists' athletic performnce was found when consuming a caffeine supplement, and a potential positive effect was noted after the consumption of sodium bicarbonate, as well as after the combination of caffeine and creatine. However, no statistically significant effects were identified for the remaining supplements, whether administered individually or in combination.
Topics: Humans; Dietary Supplements; Bicycling; Athletic Performance; Nitrates; Performance-Enhancing Substances; Caffeine; Creatine; Sodium Bicarbonate; beta-Alanine; Adult; Male; Female; Randomized Controlled Trials as Topic
PubMed: 38892701
DOI: 10.3390/nu16111768