Passive leg movement (PLM) offers a robust method for assessing vascular function; however, the interactions among age, endothelial-mediated vasodilatory mechanisms, and exercise training-induced PLM modulation remain poorly understood. To address these gaps, the vasodilatory responses to PLM, quantified as leg vascular conductance (LVC) dynamics, were measured in younger (n=9, 25±4 yr) and older males (n=9, 69±5 yr) before and after 8 weeks of single-leg knee-extension exercise training. Femoral arterial drug infusions pharmacologically dissected the contribution of the prostaglandin (PG) and epoxyeicosatrienoic acids (EETs) pathways to the residual, nitric oxide (NO)-independent component of the PLM vasodilatory response. Interrogation of these vasodilatory pathways were assessed by PLM under three conditions: control (CON), inhibition of NOS alone (N[G]-monomethyl-l-arginine; L-NMMA), and combined inhibition of NOS, cyclooxygenase (ketorolac tromethamine; KET) and cytochrome P450 (fluconazole; FLUC) (L-NMMA+KET+FLUC). Exercise training improved the PLM vasodilatory (LVC area under the curve) response in younger (4.3±1.4 to 7.1±4.3 mL·mmHg[-1], P<0.05) but not older (2.2±1.4 to 2.4±1.2 mL·mmHg[-1], P=0.97) males. In younger males, both L-NMMA and L-NMMA+KET+FLUC elicited significant (both P<0.05) and similar (P=0.99) reductions in the PLM vasodilatory response, with no effect of exercise training (P=0.90). Neither L-NMMA nor L-NMMA+KET+FLUC attenuated the PLM vasodilatory response in older males before or after exercise training (P=0.68 and P=0.51, respectively). Together, these results indicate 8 weeks of single-leg knee-extension exercise training improves the vasodilatory response to PLM in younger, but not older males, and does not alter the contribution of NO or the combined contribution of PG and EETs to PLM-induced vasodilation.

Ketorolac tromethamine (KT) is a potent nonsteroidal anti-inflammatory drug (NSAID) used for moderate to severe pain management. Its short elimination half-life necessitates frequent dosing, which can reduce patient compliance. The objective of this study was to formulate, develop, and optimize a novel biphasic-release tablet-in-tablet (TIT) system for KT to provide immediate pain relief followed by extended drug release. A TIT system was designed, comprising an immediate-release (IR) outer layer and an extended-release (ER) core matrix. The ER core was optimized using a 32 full factorial design, with the amounts of HPMC K100M and HPMC K4M as independent variables. Formulations were evaluated for pre- and post-compression parameters, drug-excipient compatibility, and in vitro drug release. The drug release kinetics and mechanism were analyzed using various mathematical models. The optimal ER core formulation (F1) exhibited a drug release of 4.6% at 0.5 h and 66.1% at 12 h, closely matching the theoretical profile (similarity factor f2 = 51). Release kinetics followed the first-order model and the Korsmeyer-Peppas model indicated an anomalous (non-Fickian) release mechanism (n = 0.831). The corresponding TIT formulation (F11) demonstrated desired physicochemical properties: hardness of 75 N, friability of 0.59%, and rapid outer layer disintegration (<50 s). The TIT provided an initial burst release (~30%) within 30 minutes, followed by sustained release exceeding 90% over 24 hours. This TIT system represents a promising alternative to conventional KT tablets for effective pain management.

In obstetrics, an amniotic fluid embolism (AFE) is a rare and highly devastating event. This case highlights the presentation of an amniotic fluid embolism and its treatments. A 35-year-old G1P0 became pulseless shortly after her cesarean section and was successfully resuscitated with high-quality CPR, fluid administration, and a regimen of atropine, ondansetron, and ketorolac. She was under general anesthesia for her cesarean due to non-reassuring heart tones and remained intubated when transferred to the intensive care unit. Due to the rapid responsiveness of treatment, she had a favorable outcome unlike a majority of AFEs. This case highlights the presentation of AFE and importance of prompt treatment. While there are specific diagnostic criteria atypical AFEs are not uncommon, and the threshold should be low for the initiation of treatment. The article reviews the most recent standards of care put forth by the Society for Maternal Fetal Medicine. It also adds to the data that supports the use of various experimental treatments to prevent morbidity and mortality.

Acute interstitial nephritis (AIN) is an immunologically mediated cause of acute kidney injury (AKI), most often drug-induced, with NSAIDs being a leading culprit. We present a 39-year-old woman who developed biopsy- proven AIN following a single intramuscular dose of ketorolac, an exceptionally short latency likely due to prior sensitization. Despite lacking classic systemic features, she exhibited non-oliguric AKI that improved rapidly with corticosteroids. This case underscores that NSAID-induced AIN can occur even after minimal exposure, highlighting the importance of early recognition, drug withdrawal, and timely steroid therapy to optimize renal recovery.

Background:Staphylococcus aureus is a major cause of life-threatening infections, and increasing antimicrobial resistance necessitates alternative therapeutic strategies. This study evaluated the antiquorum sensing and antivirulence activities of selected nonsteroidal anti-inflammatory drugs (NSAIDs) against S. aureus clinical isolates by targeting the accessory gene regulator (agr). Methods: Antimicrobial susceptibility and virulence factor production were evaluated in 56 S. aureus clinical isolates. The MICs of six NSAIDs (Diclofenac, ketoprofen, ketorolac, meloxicam, indomethacin and celecoxib) were determined by broth microdilution, and the effects of sub-MICs (½ and ¼ MIC) on virulence factors were assessed. The expression of agrA, hlb, and hld was analyzed by qRT-PCR, and molecular docking was performed to evaluate interactions with AgrA receptor. Results: Among the isolates, high resistance rates were accompanied with cefoxitin, ceftazidime, and cefepime. Hemolysin, protease, and lipase production were detected in 42.86%, 89.28%, and 94.64% of isolates, respectively. Meloxicam and celecoxib at sub-MIC levels significantly reduced hemolysin, protease, and lipase activities. Additionally, both drugs markedly downregulated agrA expression by 88.9-95.3% and significantly reduced hlb and hld expression by 90.5-99.9% without affecting bacterial growth. Molecular docking demonstrated favorable binding interactions with AgrA. Conclusions: Meloxicam and celecoxib could be promising adjunctive therapies against S. aureus through suppression of the Agr-regulated virulence traits.