Search Results (167)

Advanced cell-based therapies, including immunotherapy, regenerative medicine, and other biotechnological applications, require large quantities of viable mammalian cells for research and clinical use. Conventional enzymatic harvesting methods, such as trypsini-zation, can compromise cell integrity and reduce viability. This study investigates an al-ternative temperature-responsive approach using alginate beads incorporated with poly(N-isopropylacrylamide) (PNIPAAm), a polymer exhibiting a lower critical solution temperature (LCST) of approximately 32 °C. This system enables temperature-controlled cell detachment while preserving cellular structure and extracellular matrix components, thereby potentially improving post-harvest viability compared to trypsin treatment. Ho-mogeneous alginate hydrogel beads were synthesized using a standard infusion pump and ionically crosslinked with calcium cations. The beads were characterized by scanning electron microscopy (SEM) for morphology and by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and micro-computed tomography (µ-CT) for compositional and thermal analysis. Mouse fibroblast cells (L929 cell line) were cultured on the beads, and their proliferation and viability were assessed using CCK-8 and Live/Dead assays, demonstrating significant cell growth over seven days. The results suggest that PNIPAAm-modified alginate beads provide a promising, enzyme-free platform for efficient mammalian cell harvesting and delivery, with potential applications across advanced cell manufacturing and therapeutic technologies. Full article

Background: Intraoperative high-volume diuresis is a frequent but underrecognized complication in cardiac surgery, potentially leading to hypovolemia, electrolyte imbalances, and hemodynamic instability. Its mechanisms remain poorly defined. This study investigated the hormonal and biochemical regulation of urine output during off-pump coronary artery bypass grafting (OPCABG). Methods: For this single-center observational cohort study, 70 patients undergoing OPCABG were enrolled (diuresis: urine output > 5 mL/kg/h, n = 38; normal, n = 32). Hormonal markers and osmolality parameters were measured perioperatively. Logistic regression was used to identify independent predictors, and receiver operating characteristic (ROC) curves was used to assess model performance. Results: Intraoperative high-volume diuresis occurred in 54.2% of patients. Logistic regression identified a low Body Mass Index (BMI) (OR 0.72, p = 0.002), reduced albumin (OR 0.75, p = 0.014), and lower copeptin (OR 0.43, p = 0.037) as independent predictors (AUC 0.855). Perioperatively, NT-proBNPT0 rose in both groups, aldosterone increased only in the diuresis group, and copeptin showed a slight nonsignificant rise. Plasma sodium was higher in cases of diuresis at the end of surgery (148.4 vs. 144.9 mmol/L, p < 0.001). Despite greater urine output and fluid infusion, the rates of intensive care unit (ICU) admission and hospital stays were similar. Conclusions: Intraoperative high-volume diuresis in OPCABG is strongly associated with reduced antidiuretic hormone activity, suggesting a partial central diabetes insipidus-like mechanism. Although not affecting short-term outcomes, it posed challenges for intraoperative fluid and electrolyte management. Larger multicenter studies are needed for validation. Full article

Background: Elastomeric infusion pumps (EMPs) are safe and effective for administering outpatient intravenous (IV) antibiotics. We hypothesized that EMPs may provide benefits in the inpatient setting. This study aimed to assess the feasibility of giving IV antibiotics using EMPs to adult inpatients and to identify barriers and facilitators for their implementation. Methods and Objectives: Patients who were 18 years of age and over requiring at least seven days of IV flucloxacillin, benzylpenicillin or piperacillin/tazobactam and who were clinically stable were eligible. We collected quantitative data for feasibility, clinical outcomes and intervention acceptability. We applied an implementation research framework to help triangulate the data. Analyses were descriptive, with the intent of preparing for future studies. Results: IV antibiotics from 94 EMPs were administered to nine patients, with five patients completing treatment with an EMP. Five of the six patients surveyed said they would use EMPs again. Nurses felt EMPs were safer, less time consuming and improved working conditions. IV antibiotics via EMPs cost GBP 32.50 (GBP 3.35–GBP 83.44) more per day than intermittent infusions. Residual volume in EMPs was an issue which resulted in reduced antibiotic doses being delivered. The main facilitators to use of EMPs in the inpatient setting were adaptability, tension for change, recipient centeredness and needs of the deliverers. The barriers were lack of advantage, critical incidents and cost. Conclusion: This proof of concept feasibility study shows that it may be feasible to use EMPs in the inpatient setting. There is potential to improve patient and staff experience; however, cost and residual volume are potential barriers to implementation, with further studies required. Full article

Background: There are multiple treatments and approaches available to manage pain. However, when these interventions fail to achieve adequate relief, pain management may involve the implantation of intrathecal infusion pumps. The use of ultrasound guidance may enhance nursing practice by improving procedural efficiency and patient comfort. This technique offers a more precise, safer, and less painful approach, potentially increasing patient satisfaction and reducing procedural complications. Aim: To evaluate patient pain levels during intrathecal infusion pump refills under ultrasound guidance compared to the traditional approach, also aiming to determine the time taken per technique and to assess related intra-procedural complications. Design: A prospective quasi-experimental pre-post study. Methods: The study population included individuals with intrathecal infusion pumps. Each participant underwent two refill visits: one using the traditional method and the subsequent refill using ultrasound guidance. The time required to complete the procedure, any complications, and pain related to the procedure were measured for both techniques. Time was measured using a stopwatch, and pain was assessed at the end of each procedure using a Visual Analogue Scale (VAS). Results: A total of 45 patients (25 men and 20 women), with a median age of 56.0 years were included. The estimated mean refill duration was 13.67 min for the traditional method versus 7.26 min for ultrasound-guided refills, representing a 53.2% reduction. The adjusted mean VAS was 2.76 (2.27–3.24) with ultrasound versus 5.91 (5.20–6.62) with the traditional method, yielding an adjusted mean difference of −3.16 (−4.02 to −2.30; p < 0.001). Reductions were consistent across subgroups defined by sex, refill duration, inter-procedural interval, intrathecal medication, and medical history. Complications occurred in 20.0% of traditional refills but in none of the ultrasound-guided procedures. Conclusions: Ultrasound guidance significantly reduces pain, complications, and procedure time, positioning it as the new standard of care for intrathecal pump refills. This mandates its immediate integration into nursing protocols and health management policies. Full article

Measuring RBC aggregation can be considered as a valuable tool for detecting pathological diseases. Most previous methods need to stop and run blood flows periodically. Thus, it is impossible to probe RBC aggregation in continuously varying infusion flow. To resolve the issues, a novel bifurcated continuous-flow mechanism is suggested to probe RBC aggregation without periodic interruption of blood flow. A microfluidic chip is then designed to split single flow into two branches (low flow rate and high flow rate). RBC aggregation occurs in the low flow-rate channel, whereas it is dispersed fully in the high flow-rate channel. Using a syringe pump, blood is infused into a microfluidic chip at constant and sinusoidal pattern. RBC aggregation index (AI) is calculated from time-lapse imaging intensity within each channel. From fluidic circuit analysis and experimental results, the optimal infusion flow rate is determined as Q_sp = 0.5~2 mL/h. The AI is higher at Hct = 30% than at Hct = 50%. The high concentration of dextran solution increases AI considerably. The period of pulsatile infusion flow rate has a strong influence on time-lapse AI. In conclusion, the present method can be capable of measuring time-lapse AI consistently, without interrupting infusion flow. Full article

The blood–brain barrier (BBB) restricts the entry of therapeutic agents into the brain cardiovascular regulatory region, potentially contributing to drug-resistant hypertension. Objective: The objective of this study was to overcome this limitation by modifying PEGylated liposomes with transferrin (Tf) to facilitate Tf receptor binding at the BBB and penetratin (Pen), a cell-penetrating peptide, to enhance neuronal uptake. Methods: This study evaluated the efficacy of Tf-Pen-liposomes in delivering angiotensin-converting enzyme 2 (ACE2) or EGFP (control) genes across the BBB in rats. In addition, the therapeutic effect of intravenous administration of Tf-Pen-Lip carrying plasmid DNA encoding ACE2 (Tf-Pen-Lip-pACE2) was tested in a neurogenic hypertension model induced by intracerebroventricular (ICV) infusion of angiotensin II (Ang II) via osmotic pump implantation and brain cannulation. Results: Conjugation with Tf and Pen significantly enhanced liposome-mediated gene transfection in cultured cells and increased transport across an in vitro BBB model. In vivo, intravenous administration of Tf-Pen-Lip-pACE2 or Tf-Pen-Lip-pGFP successfully elevated ACE2 or EGFP expression, respectively, in the hypothalamic paraventricular nucleus (PVN). Chronic ICV infusion of Ang II produced a sustained increase in blood pressure and heart rate, accompanied by sympathetic overactivation and elevated arginine vasopressin (AVP) secretion, hallmarks of neurogenic hypertension. Notably, intravenous Tf-Pen-Lip-pACE2 treatment dramatically attenuated Ang II–induced neurogenic hypertension, whereas Tf-Pen-Lip-pGFP had no effect on pressor responses, sympathetic activity, or AVP secretion. Conclusions: This dual-functionalized liposomal delivery system effectively transported the ACE2 gene across the BBB into the brain, increased ACE2 expression, and markedly attenuated neurogenic hypertension following systemic administration. Full article

Background/Objectives: General anesthesia is occasionally required for cesarean delivery (CD). Propofol target-controlled infusion (TCI) enables dosing based on pharmacokinetic modeling. During the transition from induction to maintenance, infusion pauses. This simulation study assessed propofol from induction to delivery and the proportion of deliveries estimated during this pause. Methods: Surgical data from women undergoing CD were compiled, and the demographics were entered into a TCI pump using the Schnider model. Effect-site targets (6 and 8 mcg/mL) were simulated for induction, followed by 2.5 mcg/mL for maintenance. Outcomes were estimated propofol dose from induction to delivery and timing of delivery relative to infusion pause. Results: Among 50 women, the estimated mean propofol dose from induction to delivery was 19 ± 22 mg (0.2 ± 0.3 mg/kg) at 6 mcg/mL and 13 ± 17 mg (0.2 ± 0.2 mg/kg) at 8 mcg/mL. Delivery occurred during the infusion pause in 40% and 50% of cases, and it was more often in emergency than elective procedures. Emergency status, but not age or body mass index, predicted delivery during the pause. Conclusions: Standardized TCI with reduced effect-site targets for maintenance resulted in modest propofol administration between induction and delivery. These findings require confirmation in clinical studies, where dosing should be guided by depth-of-anesthesia monitoring. Full article

Background: Managing pain with intrathecal infusion pumps has significantly improved the treatment of individuals whose pain is uncontrollable by other methods. Using ultrasound to locate the refill port of these infusion pumps may offer an improvement over traditional methods. Objective: The objective of this systematic review is to update existing knowledge on the use of ultrasound for locating the refill port in intrathecal infusion pumps. Methods: The PRISMA review protocol was followed, and the review was registered in PROSPERO under registration number CRD 42024595671. Results: The main findings indicate that this technique is primarily used only in complex cases where access is difficult. Pain assessment, patient satisfaction, and recharge time compared to the traditional method are crucial factors for selecting the type of process to implement. Conclusions: No conclusive data are presented regarding the technique’s effect on pain reduction, patient satisfaction, reduction in time spent refilling the pump, or the prior experience level of the professional performing it, but notable improvements in these aspects are observed in certain situations. Full article

Objective: Morphine is a widely used analgesic for severe pain, but tolerance is a major challenge in long-term pain management. This study examined the potential of Daflon^® to enhance morphine’s pain-relieving effects and to reduce tolerance in a rat model with neuropathic pain induced by partial sciatic nerve transection (PSNT). Methods: Male Wistar rats were divided into five groups: (1) Sham + Saline, (2) PSNT + Saline, (3) PSNT + morphine, (4) PSNT + Daflon, and (5) PSNT + morphine + Daflon. Morphine tolerance was induced through continuous intrathecal infusion (15 µg/µL/h, i.t.) for 7 days, starting on day 7 post-PSNT, while Daflon was administered orally (50 mg/kg/day, oral) for 7 days. Pain relief was assessed using tail-flick and paw withdrawal on days 1, 4, and 7 after osmotic pump implantation. Spinal cords were collected for immunohistochemistry to analyze glial expression, and serum biomarkers (TNF-α, IL-1β, IL-6, and IL-10) were measured to evaluate neuroinflammation. Results: The results showed that oral Daflon significantly enhanced morphine’s analgesic effects, evidenced by improved pain thresholds in all behavioral tests. Moreover, Daflon reduced morphine tolerance. Mechanistically, Daflon upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and activated heme oxygenase-1 (HO-1), reducing oxidative stress and modulating neuroinflammation through glial regulation. Combining morphine and Daflon reduces pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhances anti-inflammatory IL-10 serum level, showing a synergistic effect in managing neuropathic pain with greater efficacy and lower drug dependence. Histology and immunohistochemistry evaluations further confirmed that morphine and Daflon co-treatment substantially reduced mononuclear cell infiltration, astrocyte activation (as indicated by GFAP expression), and microglial activation (as indicated by Iba-1 expression) compared to single treatment. Conclusions: Our findings suggest that dual therapy synergistically targets both oxidative stress and inflammatory pathways, leading to stronger neuroprotection and pain relief. Importantly, the combination approach may allow for lower opioid dosages, minimizing the risks of opioid-related side effects. Overall, morphine and Daflon co-administration offers a promising and safer strategy for managing neuropathic pain and preserving spinal cord integrity. Full article

Hypertension is a major risk factor for heart failure. Acetylation of p53 is known to regulate its activities. We have previously identified that p53 acetylation is required for cardiac remodeling in a mouse model of pressure overload-induced heart failure. Acetylation mutant p53 (p53aceKO) mice have been shown to have the ability to regulate SIRT3 KO-induced cardiac fibrosis. In the present study, we hypothesized that p53aceKO mice would exhibit cardiac protection and blunt cardiac fibrosis when subjected to Ang-II-induced hypertension. Control and p53aceKO mice received either a micro-osmotic pump implant administering Ang-II for 28 days or a sham procedure. Blood pressure was measured weekly, and echocardiography was performed every two weeks. Mice were euthanized and hearts were processed for histological analysis. While both control and p53aceKO mice receiving Ang-II exhibit increased systolic and diastolic blood pressures, control mice also demonstrate increases in ejection fraction and fractional shortening compared to the sham, while p53aceKO mice do not. Furthermore, control mice receiving Ang-II exhibit decreased left ventricular diameter and volume at end-systole and end-diastole, as well as thickening of both the anterior and posterior walls, while p53aceKO mice exhibit no significant changes in any of these parameters. Additionally, p53aceKO mice do not exhibit the Ang-II infusion-induced cardiac fibrosis seen in control mice treated with Ang-II. Mutation of p53 acetylation is protective against Ang-II infusion-induced cardiac fibrosis and dysfunction in mice. Acetylated p53 may, therefore, be a novel therapeutic target to address complications in the heart associated with hypertension. Full article

Background: Patient satisfaction with diabetes technology is increasingly recognized as a key factor in therapeutic success. Patient-reported outcomes (PROs) are gaining importance in diabetes care and in the evaluation of advanced insulin delivery systems. Objectives: This study aimed to design and validate a new questionnaire, the Insulin Pump Infusion Sets Satisfaction Scale (IPISS), to assess satisfaction with insulin infusion sets among individuals with type 1 diabetes. Methods: The questionnaire was developed by our Diabetology Unit in two versions: one for patient self-reporting and one for caregivers when the patient is too young to complete it autonomously. Content validity was assessed by six healthcare professionals (three diabetologists and three nurses) based on Polit and Beck’s methodology. The Item Content Validity Index (I-CVI) was calculated for both relevance and comprehensibility and was considered satisfactory if expert agreement reached ≥83%. The Scale Content Validity Index (S-CVI) was computed as the average of I-CVIs, with a cut-off value > 90% deemed acceptable. Results: Almost all items achieved 100% positive agreement for both relevance and comprehensibility, except one item in the caregiver version, for which one rater did not provide a rating for comprehensibility (I-CVI = 83.3%). The S-CVI was 100% for relevance in both versions, 99.24% for comprehensibility in the caregiver version, and 100% in the patient version. Conclusions: The IPISS is a content-validated, self-reported tool, suitable for evaluating satisfaction with infusion sets in individuals using insulin pumps, with versions adapted for both patients and caregivers. Full article

Background: Doxorubicin, a widely used chemotherapeutic agent, has been shown to increase reactive oxygen species (ROS) levels, disrupting cellular homeostasis not only in cancer cells but also in healthy tissues, particularly in cardiomyocytes, which leads to chemotherapy-induced cardiotoxicity. Therefore, new strategies are continually being explored to mitigate these adverse effects. One such approach is the use of additional substances with cardioprotective properties during doxorubicin therapy. A promising candidate is elabela, a peptide of the apelinergic system, which may exert protective effects against doxorubicin-induced oxidative stress in cardiomyocytes. Objectives: This study aims to evaluate the modulatory effects of elabela on oxidative stress markers, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the left ventricle of the myocardium following chronic doxorubicin administration in rats. Material and Methods: 32 male, 12-week-old Sprague-Dawley rats (SPRD) were randomly assigned to four experimental groups. For 28 days, all animals received continuous infusions (2.5 μL/h) via subcutaneously implanted osmotic pumps of 0.9% NaCl or elabela (40 μg/kg body weight/day or 200 μg/kg body weight/day). Simultaneously, animals were injected intraperitoneally 4 times at weekly intervals with 0.9% NaCl or DOX (3.5 mg/kg body weight). Next, the animals were sacrificed, and left ventricular (LV) cardiac tissue was collected for further analysis. MDA and 8-OHdG and elabela level in LV lysate were assessed by ELISA. The Ela expression in LV was quantified by Real-Time PCR. The TUNEL assay, labeled with a 5′-triphosphate strand, was used to assess the degree of apoptosis. Results: DOX treatment decreased both the Ela expression and elabela levels in the LV. Elabela administration at a dose of 200 µg/kg body weight/day significantly decreased ELA levels and Ela expression compared to the control group. The level of 8-OhdG was unexpectedly decreased in the DOX group compared to controls, while elabela treatment at both doses restored 8-OHdG levels observed in the control group. However, TUNEL staining demonstrated that elabela administration at 200 µg/kg body weight/day reduced the number of apoptotic cardiomyocytes compared to the DOX-only group, indicating a protective effect against DOX-induced apoptosis. The lower dose of 40 µg/kg body weight/day showed a moderate, non-significant attenuation of apoptosis. Conclusions: Elabela showed a protective effect against DOX-induced cardiomyocyte apoptosis in the LV by promoting processes that reduce oxidative stress in cardiac cells. Full article

Background/Objectives: Parenteral antibiotic therapy is indispensable in the treatment of several infections. The parenteral administration often leads to the need for prolonged hospitalization. Therefore, interest in outpatient parenteral antimicrobial therapy (OPAT) is growing. OPAT is typically administered in elastomeric devices, which release an infusion solution over a 24 h period and are meanwhile worn close to the body. This work aimed to evaluate the stability of the reserve antibiotics ceftazidime-avibactam and ceftolozane-tazobactam for OPAT use. Methods: Elastomeric pumps were prepared in triplicate at the dosages 3.75 and 7.5 g of ceftazidime-avibactam and 2.25, 4.5, and 9.0 g of ceftolozane-tazobactam in 240 mL 0.9% saline each. The pumps were first stored at 2–8 °C for 7 days and subsequently incubated for 48 h at 25 °C. To determine actual concentrations of ceftazidime, avibactam, ceftolozane, tazobactam, and pyridine, samples were taken at nine different time points during storage and incubation. High-performance liquid chromatography coupled to tandem mass spectrometry was used for quantification. Results: Although concentrations of ceftazidime and avibactam stayed above 90% during a 24 h incubation period at 25 °C, the pyridine limit of the European Pharmacopeia was already exceeded in the ceftazidime-avibactam pumps after the storage time at 2–8 °C. In the ceftolozane-tazobactam pumps, the ceftolozane concentration was stable for 24 h incubation, but tazobactam concentrations decreased below 90% within 12 h in the two higher dosages. Conclusions: Accordingly, stability cannot be guaranteed for both tested preparations and their use for OPAT should be thoroughly considered. Full article

Background/Objectives: Cinnamon leaves, an important source of the functional compound cinnamaldehyde (CA), have been shown to be effective in improving type II diabetes and Parkinson’s disease (PD) in rats following the incorporation of cinnamon leaf extract into a nanoemulsion. However, the effect of a cinnamon leaf extract nanoemulsion (CLEN) on improving Alzheimer’s disease (AD), the most prevalent type of dementia, remains unexplored. The objectives of this study were to determine functional compounds in cinnamon leaves by UPLC-MS/MS, followed by the preparation of a nanoemulsion and its byproducts to study their effects on AD and PD in rats. Methods: Oven-dried (60 °C for 2 h) cinnamon leaf powder and hydrosol, obtained by steam distillation of cinnamon leaf powder, were stored at 4 °C. After determination of basic composition (crude protein, crude fat, carbohydrate, moisture and ash) of cinnamon leaf powder, it was extracted with 80% ethanol with sonication at 60 °C for 2 h and analyzed for bioactive compounds by UPLC-MS/MS. Then, the CLEN was prepared by mixing cinnamon leaf extract rich in CA with lecithin, soybean oil, tween 80 and ethanol in an optimal ratio, followed by evaporation to form thin-film and redissolving in deionized water. For characterization, mean particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and surface morphology were determined. Animal experiments were done by dividing 90 male rats into 10 groups (n = 9), with groups 2–8 being subjected to mini-osmotic pump implantation surgery in brain to infuse Amyloid-beta 40 (Aβ40) solution in groups 2–8 for induction of AD, while groups 9 and 10 were pre-fed respectively with cinnamon powder in water (0.5 g/10 mL) and in hydrosol for 4 weeks, followed by induction of AD as shown above. Different treatments for a period of 4 weeks included groups 1–9, with group 1 (control) and group 2 feeding with sterilized water, while groups 3, 4 and 5 were fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of cinnamon leaf extracts, groups 6, 7 and 8 fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of nanoemulsions, groups 9 and 10 fed respectively with 10 mL/kg of cinnamon powder in water and hydrosol (0.5 g/10 mL). Morris water maze test was conducted to determine short-term memory, long-term memory and space probing of rats. After sacrificing of rats, brain and liver tissues were collected for determination of Aβ40, BACE1 and 8-oxodG in hippocampi, and AchE and malondialdehyde (MDA) in cortices, antioxidant enzymes (SOD, CAT, GSH-Px) and MDA in both cortices and livers, and dopamine in brain striata by using commercial kits. Results: The results showed that the highest level of CA (18,250.7 μg/g) was in the cinnamon leaf powder. The CLEN was prepared successfully, with an average particle size of 17.1 nm, a polydispersity index of 0.236, a zeta potential of −42.68 mV, and high stability over a 90-day storage period at 4 °C. The Morris water maze test revealed that the CLEN treatment was the most effective in improving short-term memory, long-term memory, and spatial probe test results in AD rats, followed by the cinnamon leaf extract (CLE), powder in hydrosol (PH), and powder in water (PW). Additionally, both CLEN and CLE treatments indicated a dose-dependent improvement in AD rats, while PH and PW were effective in preventing AD occurrence. Furthermore, AD occurrence accompanied by PD development was demonstrated in this study. With the exception of the induction group, declines in Aβ40, BACE1, and 8-oxodG in the hippocampi and AchE and MDA in the cortices of rats were observed for all the treatments, with the high-dose CLEN (90 mg/kg bw) exhibiting the highest efficiency. The antioxidant enzyme activity, including that of SOD, CAT, and GSH-Px, in the cortices of rats increased. In addition, dopamine content, a vital index of PD, was increased in the striata of rats, accompanied by elevations in SOD, CAT, and GSH-Px and decreased MDA in rat livers. Conclusions: These outcomes suggest that the CLEN possesses significant potential for formulation into a functional food or botanical drug for the prevention and treatment of AD and/or PD in the future. Full article

In addition to its role in angiotensin II (Ang II) production, chymase exhibits various functions, including activation of latent transforming growth factor beta 1 (TGF-β1) and pro-matrix metalloproteinases (MMPs). However, the extent to which these Ang II-independent functions contribute to pathological conditions remains unclear. In this study, we investigated the Ang II-independent roles of chymase in cardiac remodeling and dysfunction. Eighteen male Syrian hamsters, aged 6 weeks and weighing 90–110 g, were used. Exogenous Ang II was administered to a hamster model that mirrors the human chymase-dependent Ang II production pathway, via subcutaneous osmotic mini pumps (2 mg/kg/day) for 4 weeks. A chymase-specific inhibitor, TY-51469 (10 mg/kg/day), was given daily starting 1 day after commencement of Ang II infusion. Evaluation showed that while systolic blood pressure increased significantly, only diastolic dysfunction developed over time. Ang II treatment led to elevated cardiac expression of chymase, TGF-β1, and MMP-2, and increased the number of chymase-positive mast cells, resulting in notable cardiac hypertrophy and fibrosis. TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2. Full article