Search Results (119)

Background: In the last several years, “physiologically based pharmacokinetic (PBPK) modeling” has gathered significant emphasis in the modeling of drug absorption, disposition, and metabolism. This research study aims to elaborate the plasma/serum concentration–time profiles and pharmacokinetics (PK) of ofloxacin by establishing a PBPK model in healthy subjects and those suffering from renal impairment (RI). Methods: A comprehensive literature analysis was conducted to screen out all the systemic PK profiles and parameters specific to ofloxacin, followed by their implementation in PK-Sim^® version 12 software. This model-driven approach begins by developing the model in healthy populations using both intravenous (IV) and per-oral (PO) routes and then extrapolating it to the diseased population. The model evaluation was then strengthened for different PK variables such as the maximal plasma/serum concentration (C_max), the area under the curve from 0 to t (AUC_0–t), and plasma/serum clearance (CL) by employing various metrics such as predicted/observed ratios (R_pre/obs), visual predictive checks, the average fold error (AFE), root mean squared error (RMSE), and mean absolute error (MAE). Results: The AFE, RSME, and MAE for C_max in RI were 1.10, 0.22, and 0.16, respectively, which fell within the acceptable simulated error range. Furthermore, dosage adjustments for individuals with mild, moderate, and severe RI were presented by box-whisker plots to compare their systemic exposure with that of the healthy population. Conclusions: These model predictions have confirmed the PK variations in ofloxacin, which may assist the clinicians in optimizing dosage schedules in healthy and various categories of RI populations. Full article

Background/Objectives: Interleukin-33 (IL-33) is crucial in immune-mediated diseases like asthma. Targeting the IL-33/ST2 pathway holds therapeutic promise. This study characterized the pharmacokinetics (PK) and metabolism of KB-1517 and KB-1518, new oxazolo[4,5-c]quinoline IL-33 inhibitors. Methods: PK studies were conducted in male ICR mice following intravenous (IV) and oral (PO) administration. In vitro metabolic stability and metabolite identification were assessed using human and mouse liver S9 fractions supplemented with cofactors (NADPH, UDPGA, PAPS, GSH). Plasma and incubation samples were analyzed using validated LC-MS/MS methods. Results: KB-1517 exhibited slow absorption/elimination and high apparent oral bioavailability (>100%) post-PO, with an unusually late increase in plasma concentration after IV dosing, hindering terminal parameter calculation. KB-1518 showed low clearance post-IV but suffered from low oral bioavailability (~14%). Both compounds demonstrated high in vitro metabolic stability (t_½ > 60 min) in both human and mouse liver S9 fractions. Primary metabolism involved phase I oxidation (N-oxidation and N-demethylation), yielding several metabolites identified in vitro and confirmed in vivo. Some species differences in metabolite profiles were observed. Conclusions: KB-1517 and KB-1518 are promising, metabolically stable IL-33 inhibitor lead compounds with distinct PK profiles. KB-1517’s complex kinetics suggest potential sustained exposure but require further elucidation. KB-1518’s low oral bioavailability necessitates further optimization. These ADME findings provide a critical foundation for their continued optimization and development. Full article

This study aimed to investigate the effect of gender on the pharmacokinetics of meloxicam in goats following intravenous (IV, 0.5 mg/kg) and oral (PO, 1.0 mg/kg) administration. A crossover design was used with 12 clinically healthy Saanen goats (six females and six males). Plasma samples were collected up to 96 h post-administration and analyzed with an HPLC for meloxicam concentrations. Pharmacokinetic parameters were calculated and statistically compared between genders and administration routes. The results show that male goats exhibited significantly longer terminal half-life (T_1/2λz), a greater mean residence time (MRT_0–∞), and higher systemic exposure (AUC_0–∞) than females, particularly after oral administration. Oral bioavailability was calculated as 77.43% in females and 104.73% in males. These differences may be linked to gender-based variations in hepatic metabolism, enterohepatic recirculation, and the hormone-mediated modulation of cytochrome P450 activity. The findings are consistent with previous research demonstrating that gender can influence drug disposition through hormonal and enzymatic mechanisms. This study underscores the importance of considering gender as a biological variable in pharmacokinetic assessments of veterinary drugs, especially those used in food-producing animals, to optimize dosing strategies and ensure both therapeutic efficacy and food safety. Full article

In this study, phosphogypsum waste collected from a factory dump in Kedainiai, Lithuania, was used for the first time as a starting material in the dissolution–precipitation synthesis of high-quality bioceramic calcium hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂; CHA). The CHA powders were synthesized using the dissolution–precipitation method, employing phosphogypsum in four different conditions: untreated, dried at 100 °C, dried at 150 °C, and annealed at 1000 °C. Various phosphorus sources were used in the CHA synthesis process: Na₂HPO₄; a mixture of Na₂HPO₄ and NaH₂PO₄; or a combination of Na₂HPO₄, NaH₂PO₄, and NaHCO₃. These mixtures were allowed to react at 80 °C for 48 h, 96 h, 144 h, and 192 h. X-ray diffraction (XRD) analysis revealed slight variations in the synthesized products depending on the specific starting materials used. Fourier transform infrared spectroscopy (FTIR) was conducted to confirm the structural characteristics of the synthesized CHA samples. The surface microstructure of the synthesized CHA samples differed notably from that of the raw phosphogypsum. All synthesized CHA samples exhibited Type IV nitrogen adsorption–desorption isotherms with H3-type hysteresis loops, indicating the presence of mesoporous structures, typically associated with slit-like pores or aggregates of plate-like particles. To the best of our knowledge, an almost monophasic CHA has been fabricated from phosphogypsum waste for the first time using a newly developed dissolution–precipitation synthesis method. A key challenge in the high-end market is the development of alternative synthesis technologies that are not only more environmentally friendly but also highly efficient. These findings demonstrate that phosphogypsum is a viable and sustainable raw material for CHA synthesis, with promising applications in the medical field, including the production of artificial bone implants. Full article

This study investigates the potential of low-cost, naturally available porous materials (PoMs), gravel, marble, flint, and sandstone, as thermal management for photovoltaic (PV) panels. Experiments were conducted in a controlled environment at a solar energy laboratory, where variables such as solar irradiance, ambient temperature, air velocity, and water flow were carefully regulated. A solar simulator delivering a constant irradiance of 1250 W/m² was used to replicate solar conditions throughout each 3 h trial. The test setup involved polycrystalline PV panels (30 W rated) fitted with cooling channels filled with PoMs of varying porosities (0.35–0.48), evaluated across water flow rates ranging from 1 to 4 L/min. Experimental results showed that PoM cooling significantly outperformed both water-only and passive cooling. Among all the materials tested, sandstone with a porosity of 0.35 and a flow rate of 2.0 L/min demonstrated the highest cooling performance, reducing the panel surface temperature by 58.08% (from 87.7 °C to 36.77 °C), enhancing electrical efficiency by 57.87% (from 4.13% to 6.52%), and increasing power output by 57.81% (from 12.42 W to 19.6 W) compared to the uncooled panel. The enhanced heat transfer (HT) was attributed to improved conductive and convective interactions facilitated by lower porosity and optimal fluid velocity. Furthermore, the cooling system improved I–V characteristics by stabilizing short-circuit current and enhancing open-circuit voltage. Comparative analysis revealed material-dependent efficacy—sandstone > flint > marble > gravel—attributed to thermal conductivity gradients (sandstone: 5 W/m·K vs. gravel: 1.19 W/m·K). The configuration with 0.35 porosity and a 2.0 L/min flow rate proved to be the most effective, offering an optimal balance between thermal performance and resource usage, with an 8–10% efficiency gain over standard water cooling. This study highlights 2.0 L/min as the ideal flow rate, as higher rates lead to increased water usage without significant cooling improvements. Additionally, lower porosity (0.35) enhances convective heat transfer, contributing to improved thermal performance while maintaining energy efficiency. Full article

Background: Although benzodiazepines are the first-line treatment for alcohol withdrawal syndrome (AWS), their use may pose significant risks, including oversedation and the potential for misuse, particularly in vulnerable populations such as individuals with alcohol use disorder. Valproate has been investigated as a potential adjunctive treatment for AWS. We first conducted a brief narrative review of the existing literature on valproate in AWS, identifying only a few relevant studies. We then performed a retrospective study to evaluate the effectiveness of valproate, administered orally (PO) or intravenously (IV), in combination with benzodiazepines for the treatment of AWS and associated anxiety symptoms. Methods: We retrospectively analyzed 72 inpatients treated for AWS with valproate (IV or PO) combined with benzodiazepines. Dosages of valproate, the type and daily dose of benzodiazepine, and any adverse effects were recorded. Withdrawal symptoms were assessed using the Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised (CIWA-Ar) on days 1, 3, 5, and 7. Anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAM-A) on days 1, 3, and 7. Results: The median daily benzodiazepine dose was 2.5 mg lorazepam-equivalents (IQR: 2.0–3.81 mg). Significant reductions in both CIWA-Ar and HAM-A scores were observed across all time points. Percentage reductions in both anxiety and withdrawal symptoms were significantly higher in the IV group. No serious adverse events occurred. Conclusions: Valproate appears to be an effective adjunctive treatment for AWS, providing symptom relief and enabling reduced benzodiazepine use. IV administration may offer more rapid clinical improvement. Larger prospective trials are warranted to confirm these findings. Full article

Introduction: Prostate cancer has been generally resistant to immunotherapy approaches. Radiation can be immunostimulatory, but the extent to which standard prostate cancer treatments induce immune activation has not been well described. The bone-targeted radiopharmaceutical Radium223 (Ra223) has been proposed to enrich immune function, but clinical studies have not fully delineated whether this is true, or by what mechanisms. Enzalutamide has been shown to increase PD-L1 expression on dendritic cells, which could impact immune activation, though the extent to which this is associated with other evidence of immune activation remains uncertain, and combination strategies remain of interest. We performed a randomized phase II trial to evaluate whether Radium223 (Ra223) added to enzalutamide would induce greater immune activation and clinical responses compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: Eligible patients were randomized 2:1 to Arm A (enzalutamide 160 mg PO daily + Ra223 55 kBq/kg IV q4 weeks × 6 doses) or Arm B (enzalutamide 160 mg PO daily). Blood was collected at treatment start and during treatment to measure soluble immune checkpoint biomarkers (BTLA, TIM3, HVEM, GITR, LAG3, PD-1, CTLA-4, PD-L1, PD-L2, ICOS). Immunophenotyping by mass cytometry time of flight (CyTOF) was performed to measure peripheral blood mononuclear cell populations before and after treatment. CyTOF was used to determine changes in circulating immune cell population subsets before and after treatment. Biopsies were performed of an active bone metastatic lesion prior to study treatment and after at least 3 months. IHC was subsequently performed to examine changes in immune cell population subsets before and after treatment, and changes in pSTAT3 levels. Results: In total, 30 patients were enrolled, with median age 68. The median duration of follow up was 36 months. PSA responses, PFS, and OS were not significantly different between the two arms; however, the study was not powered for clinical endpoints. Peripheral blood and bone biopsy specimens were analyzed for immune correlatives. Soluble receptor concentrations showed significantly increased expression of PDL-2 in the combination arm, but this was not seen on CyTOF. Otherwise, there were no significant differences in markers of immune activation/exhaustion or immune cell population subsets in the combination arm and enzalutamide monotherapy arm. IHC also did not show a significant difference in immune cell population subsets in bone biopsy specimens before and after treatment in both arms. However, treatment with the combination arm did show significantly increased levels of pSTAT3 (p = 0.04), which was not seen in the enzalutamide monotherapy arm. Conclusions: Our study showed an overall lack of evidence for immune activation or cytokine induction with the combination, which does not make a strong case for combinatorial immunotherapy approaches. However, the combination did induce higher levels of pSTAT3, which has been implicated in radio-resistance. Therefore, the addition of a STAT3 inhibitor to the combination may be of interest to improve efficacy. Full article

Herein, we present a comprehensive study on the dissolution behaviour of two sodium–cerium(IV) phosphate phases synthesised hydrothermally from CeO₂ nanoparticles: crystalline Na₂Ce(PO₄)₂ and nanocrystalline NaCe₂(PO₄)₃. For the first time, experimental dissolution data were obtained for both compounds over a wide pH range (1.5–10) under long-term equilibration. The crystalline phase undergoes pH-dependent transformation, including recrystallisation at a near-neutral pH and the formation of secondary CeO₂ nanoparticles above pH 7. In contrast, the nanophase NaCe₂(PO₄)₃ exhibits exceptional structural and chemical stability, showing no signs of recrystallisation, phase transformation, or CeO₂ formation, even after extended ageing. The experimental results help refine the thermodynamic stability conditions for cerium phosphate and oxide phases, providing insights into the reversible transformation pathways between CeO₂ and Ce(IV) phosphates as governed by pH. Full article

Background/Objectives: Previous research indicates that non-surgical periodontal therapy (NSPT) improves glycemic control in individuals with prediabetes and diabetes who have periodontitis. Few studies have demonstrated its effects on mouthrinse active-matrix metalloproteinase-8 (aMMP-8) levels as it relates to glycemic control. We assessed the periodontal treatment response of stage II–IV periodontitis patients with prediabetes, diabetes, and normoglycemia, regarding glycated hemoglobin (HbA1c) and mouthrinse aMMP-8 levels using point-of-care kits (PoC). Materials and Methods: Eighty-eight adults (11 normoglycemic, 32 prediabetic, 45 with type 2 diabetes), aged 25–78, with stage II–IV periodontitis were included. Full-mouth clinical examinations were used to evaluate their periodontal parameters. HbA1c and mouthrinse aMMP-8 levels were assessed using PoC kits before and approximately three months after scaling and root planing. Results: There were positive treatment effects of non-surgical periodontal therapy on periodontal clinical parameters, aMMP-8 and HbA1c levels in the prediabetes and diabetes groups. The aMMP-8 reduction was significant (p < 0.001) in the prediabetes and prediabetes + diabetes groups, while HbA1c decreased significantly in the diabetes and prediabetes + diabetes (p < 0.001) groups. In contrast, a non-significant increase in mean aMMP-8 levels, HbA1c, and CAL was observed in normoglycemia (p > 0.05). Stage III + IV periodontitis showed significant treatment effects for aMMP-8 (p < 0.001) and HbA1c (p < 0.01) compared to stage II, regardless of glycemic status. Conclusions: Non-surgical periodontal therapy significantly improves periodontal health as well as HbA1c and aMMP-8 levels in people living with prediabetes and diabetes. Full article

This study was designed to investigate the immunostimulatory and anticancer efficacies of pectic polysaccharides from ginseng leaves treated using the high-pressure extraction method (HPEM). The isolation of polysaccharides using HPEM resulted in 1.35-fold higher polysaccharide yields than those obtained using the commonly used hot water extraction method. In addition, component sugar analysis of ginseng-leaf-derived polysaccharides (GLHP) showed the presence of nine different types of monosaccharides, including galacturonic acid, galactose, rhamnose, and arabinose, which are characteristic of pectic polysaccharides. In addition, GLHP effectively induced activation of the complement system, and macrophages stimulated with GLHP showed enhanced production of cytokines such as IL-6, IL-12, and TNF-α. Intravenous (i.v.) and oral administration (p.o.) of GLHP significantly increased the cancer-cell-killing ability of spleen-derived NK cells. In a lung-cancer-bearing mouse model using Colon26-M3.1 carcinoma, prophylactic i.v. and p.o. GLHP potently inhibited 95.2% and 33.5% of lung cancer, respectively. Furthermore, GLHP showed significant anticancer effects, even in mice with NK cell dysfunction, via the anti-asialo GM1 antibody. These effects may be related to the cancer-cell-killing effects of cytotoxic T lymphocytes (CTL). Therefore, GLHP, a polysaccharide isolated from ginseng leaves using HPEM, has a potent anticancer effect, and these effects are closely related to the stimulation of various immune factors. Full article

Background: A rapid intervention team is a broad category of special teams used by police and emergency respondents to cover various needs. It is essential to ensure the safety and well-being of people in emergencies, minimising the risk of harm and maximising the chances of survival. Objective: This study aimed (i) to identify the fitness profiles and levels of POs from the EIR of the Lisbon Metropolitan Command (COMETLIS, PSP, Portugal), considering age classes; (ii) to directly compare the observed fitness profiles to previous research and normative data; and (iii) to compare the fitness profile of POs from the EIR with cadets from the Police Academy. Methods: This cross-sectional observational study included the participation of 121 male POs from the EIR of the Lisbon Metropolitan Command (Portugal) and 92 male cadets from the Police Academy (Lisbon, Portugal). The assessment protocol sequence involved the collection of biosocial data (age classes: ≤29 years; 30–39 years; 40–49 years), a body size assessment, and a fitness assessment (horizontal jump, handgrip strength, 60 s sit-ups and 20 m shuttle run). Results: (i) In the ≤29 years age class, POs performed better in all fitness tests (highlighting that the age class had a statistically significant effect on performance in the horizontal jump, sit-ups, 20 m shuttle run, and predicted VO₂max), and they showed significantly better performance than cadets in handgrip (left, right, and sum), and significantly worse performance in sit-ups and predicted VO₂max. (ii) In the 30–39 years age class, POs had significantly worse performance than cadets in the horizontal jump, sit-ups, 20 m shuttle run, and predicted VO₂max, even after controlling for age. Conclusions: (i) The fitness performance decreased as the age class became older; (ii) the handgrip strength and cardiovascular capacity attributes were between the standard and excellent levels according to the ACSM guidelines for the general population; (iii) POs from the EIR were stronger than cadets in terms of handgrip strength but weaker in terms of lower limb power, abdominal muscular endurance, and aerobic capacity; and (iv) the differences observed between POs from the EIR and cadets in the 30–39 years age class emphasise the importance of physical training after the training period and throughout professional life. Full article

The P-V and I-V curves of photovoltaic (PV) strings show multiple peaks when exposed to partial shading conditions (PSCs). The traditional maximum power point tracking (MPPT) method cannot track the global maximum power point (GMPP) due to the multi-peak characteristics, power fluctuation, and tracking speed. In this paper, a multi-peak PV MPPT method based on the honey badger algorithm (HBA) is proposed to track the GMPP in a localized shading environment. The performance of this method is also compared and analyzed with the traditional MPPT methods based on the perturbation observation (P&O) method and Particle Swarm Optimization (PSO) algorithm. The experimental results have proven that, compared with the MPPT methods based on P&O and PSO, the proposed multi-peak MPPT method based on the HBA algorithm has a faster tracking speed, higher tracking accuracy, and fewer iterations. Full article

Primary dental implant stability is critical to enable osseointegration. We assessed the primary stability of our newly designed dental implant. We used the calf rib bone animal model. Our implant has an outside tapered screw with two inside barrettes that deploy with a second screw situated at the implant’s crown. We used ten calf ribs with III/IV bone density and inserted ten implants per rib. We deployed the barrettes in the calf rib’s transversal direction to support against the nearby cortical bone. We measured the primary implant’s stability with resonance frequency analysis and collected the Implant Stability Quota (ISQ) in the transverse and longitudinal calf rib planes before (PRE) and after (POS) deploying the barrette. The mean ISQ was PRE 84.00 ± 3.56 and POS 84.73 ± 4.53 (p = 0.84) in the longitudinal plane and PRE 81.80 ± 2.74 and POS 83.53 ± 4.53 (0.27) in the transverse plane. The barrettes’ insertion increases our dental implant primary stability by 11% in the transverse plane and 2% in the longitudinal plane. Our dental implant ISQ values are in the higher range than those reported in the literature and reflect high primary stability after insertion. The barrette deployment improves the dental implant’s primary stability, particularly in the direction in which it deploys (transverse plane). Full article

Background: Studies have demonstrated that resveratrol exerts several pharmacological effects. However, the pharmacokinetic parameters are not completely established. Objectives: This study describes the plasma pharmacokinetics and tissue distribution of resveratrol after administration by different routes and doses in rats. Methods: A reliable, simple, and sensitive HPLC method using UV detection for the quantification of resveratrol in rat plasma and tissues was developed and validated. In addition, a pharmacokinetic analysis using non-compartmental and population modeling was performed. Results: The pharmacokinetic parameters of resveratrol after the administration of 5 mg/kg via i.v. bolus calculated by non-compartmental analysis were a constant of elimination (ke) of 0.09 h⁻¹ ± 0.04, a half-life (t1/2) of 9.5 h ± 3.7, an apparent volume of distribution (Vd) of 5.8 L/kg ± 4.7, a clearance (Cl) of 0.39 L/h/Kg ± 0.26, and an area under the curve (AUC) of 6076 ng/h/mL ± 2959. The results obtained after the administration of 100 mg/kg p.o. were an elimination constant (ke) of 0.12 ± 0.07 h⁻¹, a half-life (t1/2) of 7.9 ± 4.2 h, the apparent volume distribution (Vd) of 13.3 ± 3.3 L/kg, a clearance (Cl) of 1.76 ± 0.49 L/h/Kg ± 0.26, and an area under the curve (AUC) of 6519 ± 1592 ng/h/mL. For the tissue distribution analysis, 10 mg/kg of resveratrol was intravenously administered to rats and the molecule was quantified in the liver, lung, kidney, heart, stomach, spleen, adipose tissue, and brain of the animals. Conclusions: The population pharmacokinetic modeling showed that resveratrol has a two-compartment model in both routes of administration and has a higher volume of distribution when it is given orally. In addition, resveratrol showed a high brain concentration after iv administration, which indicates that this molecule is capable of crossing the blood–brain barrier of animals, a crucial capacity for its neuroprotective activity. Full article

In the waste oil recycling industry, large amounts of oil-containing sludge are still generated, thus posing a resource depletion issue when disposed of or incinerated without energy recovery or residual oil utilization. In this work, chemical activation experiments using phosphoric acid (H₃PO₄) were performed at a low temperature (600 °C) for 30 min to produce porous carbon products. From the results of the pore property analysis, an increasing trend with an increasing impregnation ratio from 0.5 to 2.0 was observed. Based on the Brunauer–Emmett–Teller (BET) model, the maximal BET surface area was about 70 m²/g, which was indicative of the hysteresis loop and the type IV isotherms in the resulting carbon product. In addition, the enhancement in the pore properties of the carbon products obtained through acid-washing was superior to that achieved through water-washing and without post-washing. From observations made using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), the carbon products featured a porous structure and inherent magnetism due to their richness of iron oxides. In this regard, they can be used as efficient adsorbents or catalyst supports due to their simple recovery (or separation) when exhausted. Full article