Search Results (202)

A male castrated Shih Tzu was evaluated for recurrent nocturnal episodes of acute respiratory distress accompanied by hemoptysis and transient erythrocytosis. The dog was clinically normal between episodes, but each nighttime event was severe and prompted repeated emergency visits. During each emergency presentation, thoracic radiographs revealed severe diffuse interstitial-to-alveolar pulmonary infiltrates, and packed cell volume showed marked but reversible increases. A stepwise diagnostic evaluation, including serial indirect blood pressure measurement, coagulation assessment, echocardiography, and bronchoscopy with bronchoalveolar lavage, progressively excluded typical infectious, cardiac, structural, and coagulopathic causes of hemoptysis and acute respiratory distress. Given the stereotyped pattern of near-acute crises with diffuse pulmonary infiltrates and hemoptysis, mechanisms analogous to noncardiogenic pulmonary edema or exercise-induced pulmonary hemorrhage were considered. Therapeutic trials with sildenafil and furosemide failed to prevent further nocturnal recurrences. Considering concurrent transient PCV surges and the proposed role of catecholamine-driven splenic contraction as a rapidly mobilizable erythrocyte reservoir, a sympathetically mediated process was suspected, and α₁-adrenergic blockade with prazosin was initiated. Following prazosin therapy, sustained clinical remission was achieved, with no further emergency episodes over a 15-month follow-up period. The response may have reflected multiple pharmacological effects of prazosin, including attenuation of sympathetically mediated splenic α₁-adrenergic activity, systemic vasodilation, and reduction in venous return. This unique case suggests that dysregulation of the sympathetic nervous system may have contributed to the recurrent hemoptysis and acute respiratory distress and highlights adrenergic modulation as a potential therapeutic consideration in similar cases. Full article

Background/Objectives: Since 2015, pulmonary arterial hypertension (PAH)-specific medications have been fully reimbursed in Lithuania. To describe the current situation of PAH treatment in the country and to determine survival during different PAH treatment regimens. Methods: The data from the Institute of Hygiene and the State Data Agency of Lithuania cases with administrative codes I27.0 and I27.8 have been evaluated. Results: In 2025, 225 confirmed cases of PAH were treated with PAH-specific medications in two PH centers. At least one PAH-specific medication was prescribed to 163 (72.4%) female and 62 (27.6%) male patients. Among these, 96 (42.7%) received sildenafil monotherapy, 82 (36.4%) received a combination of sildenafil and an ERA, 36 (16.0%) were on triple PAH-specific therapy (including selexipag or treprostinil), and 11 (4.9%) received other regimens due to specific medical considerations. The age of adults treated with sildenafil monotherapy vs. other therapies was 63.9 ± 14.8 (n = 117) and 51.5 ± 17.3 (n = 116) years, respectively (p < 0.05). A total of 191 PAH patients who received targeted therapy died during the observational period 2017–2025. Of these, 105 received monotherapy, 57 sildenafil and endothelin receptor antagonist and 29 triple therapies (treprostinil [n = 19], selexipag [n = 6], or inhaled iloprost [n = 4] were prescribed as the third drug). Patients who died and received triple therapy were younger than those on mono- and dual therapy (age at diagnosis 45.0 ± 21.6, 67.2 ± 14.7 and 61.6 ± 16.3 years, respectively, p < 0.01). Survival was longer in patients on dual therapy compared with monotherapy (43.1 ± 28.1 vs. 31.7 ± 25.0 months, p = 0.04), and the longest was in those receiving triple therapy (59.9 ± 29.4 months; p < 0.05). Conclusions: The availability of reimbursed medications dramatically increased the number of treated PAH cases in Lithuania. In 2025, most of the PAH patients received sildenafil monotherapy. Patients treated with sildenafil only were significantly older than the rest of cohort. In the survival analysis, combination PAH therapies were more often prescribed to younger patients and were associated with longer duration of life than monotherapy. Full article

Background: Contrast-induced encephalopathy (CIE) is an uncommon yet clinically significant complication associated with iodinated contrast media, with its mechanisms remaining unclear. Objective: The aims of this study are to examine the neurotoxic effects of contrast media and assess the neuroprotective roles of N-Acetylcysteine (NAC) and sildenafil with regard to HIF-1α expression. Methods: Thirty-six female Wistar albino rats (n = 36) were allocated into four experimental groups (n = 9 each): control, contrast media + saline (CMA + Saline), contrast media + NAC (CMA + NAC), and contrast media + sildenafil (CMA + Sildenafil). NAC (150 mg/kg) and sildenafil (50 mg/kg/day) were administered intragastrically for 48 h before exposure to contrast media. Biochemical, histopathological, and immunohistochemical evaluations were conducted 48 h post-contrast administration. Results: Exposure to contrast media resulted in neuronal death, vascular obstruction, and increased hypoxia-inducible factor-1 alpha (HIF-1α) immunoreactivity. The primary outcome measure, tissue HIF-1α concentration by ELISA, did not differ significantly among groups (p = 0.119). Semi-quantitative immunohistochemical analysis revealed significant group differences in HIF-1α immunoreactivity (p < 0.001), with all injury/treatment groups differing significantly from control. The difference between the contrast media group and the sildenafil-treated group approached but did not reach statistical significance after correction for multiple comparisons (Dunn’s test, p = 0.050). Conclusions: The primary biochemical endpoint did not demonstrate significant group differences. Secondary IHC analysis suggests a potential attenuation of HIF-1α immunoreactivity by sildenafil, though this did not reach statistical significance and requires confirmation in adequately powered studies. HIF-1α immunoreactivity warrants further investigation as a potential biomarker for contrast-induced neural injury. Full article

Background and Clinical Significance: Pulmonary hypertension (PH) is a recognized complication of chronic liver disease, most commonly manifesting as portopulmonary hypertension (POHP) prior to liver transplantation. While the natural history and management of pre-transplant PH are well described, the development of de novo pulmonary arterial hypertension (PAH) following liver transplantation remains exceedingly rare and poorly understood. In such cases, establishing true causality is challenging, and alternative explanations—including previously unrecognized or masked disease—must be carefully considered. This entity poses significant diagnostic and therapeutic challenges and may adversely affect post-transplant outcomes if not promptly recognized and treated. Case Presentation: We report the case of a 46-year-old man with end-stage liver disease secondary to alcohol use who underwent deceased donor liver transplantation without preoperative evidence of PH. His pre-transplant evaluation revealed preserved biventricular function and no measurable PH. Eight days postoperatively, he was readmitted with acute dyspnea, hypoxemia, and signs of right ventricular failure. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction with markedly elevated pulmonary artery systolic pressure. Right heart catheterization confirmed severe PAH. Secondary causes of PH were excluded. The patient was initiated on sildenafil and continuous intravenous epoprostenol, resulting in clinical, echocardiographic, and hemodynamic improvement. Subsequent follow-up demonstrated sustained response to therapy despite concurrent progression of coronary artery disease requiring complex percutaneous intervention. Conclusions: This case highlights a rare presentation of severe PAH occurring shortly after liver transplantation, in the absence of documented pre-transplant PH. While a causal relationship cannot be definitively established, the temporal association raises important clinical considerations. It underscores the need for heightened clinical vigilance for pulmonary vascular disease in post-transplant patients presenting with cardiopulmonary symptoms. Further research is warranted to elucidate the underlying mechanisms, risk factors, and optimal management strategies for PAH diagnosed after liver transplantation. Full article

Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor, supports vascular remodeling, but its effects on angiogenesis and regeneration of ischemic muscle tissue are not fully understood. We investigated the function of sildenafil by employing a murine hindlimb model of ischemia, in which ischemia and angiogenesis is induced by femoral artery ligation (FAL) in the lower leg of mice. Then, 7 days after FAL or sham operation, gastrocnemius muscles of sildenafil-treated and control mice were isolated and processed for histological and immunofluorescence analyses. Sildenafil treatment led to reduced apoptotic areas within the ischemic tissue (ascertained via TUNEL assay) and increased angiogenesis, evidenced by a higher capillary-to-muscle fiber ratio and an augmented number of proliferating capillary cells (CD31⁺/CD45⁻/BrdU⁺), compared to controls. We observed a decrease in the total count of leukocytes (CD45⁺) in sildenafil-treated mice. Regarding macrophage infiltration, we found a reduced total number of macrophages (CD68⁺), along with a shift in macrophage polarization toward the pro-angiogenic and anti-inflammatory M2-like phenotype (CD68⁺/MRC1⁺). In summary, we show that sildenafil treatment contributes to angiogenesis and the regeneration of ischemic muscle tissue, most likely by attenuating inflammatory responses and influencing macrophage polarization in direction to regenerative M2-like polarized macrophages. Full article

Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and right ventricular (RV) dysfunction, processes that are increasingly associated with disturbances in cellular metabolism. We investigated whether transplantation of exogenous mitochondria derived from bone marrow mesenchymal stromal cells, alone or combined with sildenafil, could improve mitochondrial homeostasis and attenuate cardiopulmonary remodeling in monocrotaline-induced PAH. Male Wistar rats were assigned to control (CTRL, n = 8) or PAH (n = 32) groups. Fourteen days after induction of PAH, animals were randomized to receive saline, sildenafil (20 mg/kg/day for 14 days), intravenous mitochondrial transplantation (100 μg, days 14 and 21), or combined therapy. On day 28, echocardiography, invasive measurement of RV systolic pressure (RVSP), pulmonary vascular histology, gene expression analyses (vimentin, VE-cadherin, and mitochondrial metabolism–related genes), and high-resolution respirometry were performed. All treatments significantly reduced RVSP compared with untreated PAH. Mitochondrial therapy, alone or combined with sildenafil, decreased arteriolar α-smooth muscle actin content, whereas endothelial–mesenchymal transition was attenuated only with combined treatment. Mitochondrial transplantation and sildenafil increased Complex I–dependent respiration, whereas Complex IV activity improved exclusively with mitochondrial therapy. Combined treatment reduced plasma IL-6 and IL-1β levels compared with PAH. Thus, mitochondrial transplantation, particularly when combined with sildenafil, improved RV function, limited pulmonary vascular remodeling, reduced plasma inflammatory markers, and changed key mitochondrial pathways in experimental PAH. Full article

Background: Pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs), a life-threatening congenital heart defect (CHD), is frequently associated with abnormal pulmonary blood flow and vascular remodeling, causing hypoxia and heart failure. Segmental pulmonary hypertension (PH), a distinct PH type, may exist in some patients. Pulmonary vasodilators have been considered for treatment; however, evidence of their efficacy and safety remains lacking. Methods: A systematic review was conducted using PubMed, MEDLINE, The Cochrane Library, and Ichushi Web, encompassing studies from inception to May 2023. Inclusion criteria focused on patients with PA/VSD/MAPCAs treated with PH medications. Results: Of 86 studies screened, 6 met the inclusion criteria, including 1 cohort study and 5 case reports, comprising 22 patients. The most frequently administered medications were sildenafil (14 cases) and bosentan (12 cases), with 16 patients receiving monotherapy. Clinical improvements were observed in pulmonary vascular resistance (8/8 patients), oxygen saturation (8/19 patients), and symptoms (19/21 patients). Adverse effects were noted in five patients, including treatment discontinuation in two. Conclusions: PH medications may benefit some patients with PA/VSD/MAPCAs; however, the extremely limited sample size (n = 22) and substantial heterogeneity in anatomy, age, surgical status, and treatment regimens severely limit interpretability and clinical applicability. Considering the potential benefits and risks associated with these medications, their use should be considered cautiously and restricted to specialized centers with expertise in CHD and PH management. Full article

Arteriogenesis, the growth of pre-existing arterioles into functional collateral arteries, represents a key adaptive response to severe arterial stenosis. This process is driven by hemodynamic forces and a tightly coordinated inflammatory cascade. Here, we investigated the effects of pharmacological stimulation of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway using the phosphodiesterase-5 (PDE5) inhibitor Sildenafil on collateral vessel growth in a murine model of femoral artery ligation (FAL). Flow cytometric analyses revealed that Sildenafil treatment significantly enhanced platelet–leukocyte aggregate formation, a prerequisite for the subsequent initiation of a localized perivascular inflammation. Histological and immunofluorescence analyses further demonstrated a marked increase in mast cell recruitment and degranulation at early time points (days 1 and 3 post-FAL). In addition, Sildenafil promoted perivascular macrophage accumulation on days 3 and 7, with a pronounced shift toward an M2-like pro-regenerative polarization state, ultimately resulting in the enhanced proliferation of vascular cells and the enlargement of collateral diameters. Together, these findings identify Sildenafil as a potent enhancer of arteriogenesis through coordinated immune cell activation, stimulating vascular cell proliferation along with positive collateral outward remodeling. Thus, Sildenafil emerges as a promising therapeutic candidate to promote collateral artery growth in cardiovascular occlusive diseases. Full article

Pulmonary drug delivery represents a promising approach in the treatment of respiratory diseases, allowing for passive targeting and enhanced drug efficacy. Background/Objectives: The aim of the present study was to develop inhalable dry powders from lyophilized sildenafil citrate (SC)-loaded liposomes made from phosphatidylcholine and either cholesterol (CH) or resveratrol (RSV). Methods: Liposomes were prepared via a pH gradient method to increase drug entrapment efficiency and drug loading, and then the liposomes were lyophilized using different proportions of ethanol, mannitol, and lactose as excipients. The resulting dry cakes were converted into powders and evaluated for aerodynamic performance using a custom-designed air-blowing device. Notably, this is the first time that resveratrol has been used as a substitute for cholesterol in SC-loaded liposomes. Results: Our results demonstrate that RSV is a suitable liposome bilayer component and improves drug loading. Our findings prove that lyophilized cakes containing liposomes produce a dry powder that is suitable for aerosolization with potential application to pulmonary delivery of sildenafil citrate. The results suggest that RSV represents a potential alternative to traditional cholesterol-based liposomal formulations. Conclusions: This work presents a novel strategy for the pulmonary delivery of sildenafil, using biocompatible and FDA-approved mannitol and lactose for this administration route. Full article

TiO₂ shows improved photocatalytic properties when combined with other oxides, such as ZrO₂. Unfortunately, this material does not exhibit a spectral response in the visible range, but this can be improved by adding WO₃. Here, the effect of the amount of WO₃ and the treatment temperature on TiO₂-ZrO₂-WO₃ materials applied in the solar photocatalytic oxidation of sildenafil was evaluated. The materials were synthesized using the sol–gel method and were characterized by N₂, XRD, UV-Vis RDS, SEM, PL, and XPS. Photocatalytic activity was determined by the degradation and mineralization of sildenafil. The most active photocatalysts were selected for stability testing and to determine the oxidizing species that dominate the reaction mechanism. The optimal amount of WO₃ that improves solar photocatalytic activity at both treatment temperatures was found to be 1% with a reaction mechanism based on OH· and h⁺. WO₃ reduces electron–hole pair recombination. At 500 °C, the crystallinity of the anatase phase is improved, while at 800 °C, the transformation to rutile is suppressed at low WO₃ concentrations. XPS observed the reduction in Ti⁴⁺ to Ti³⁺ and W⁶⁺ to W⁵⁺ in TiO₂–ZrO₂–WO₃ materials, which were found to be photoactive under sunlight with potential for use in industrial-scale reaction systems. Full article

Background/Objectives: This study aimed to perform a comparative analysis of the original Viagra^® product and sildenafil-containing tablets obtained from illegal sources (the darknet). Specifically, the analyzed material consisted of samples seized by Polish law enforcement authorities from unverified vendors operating within the Central European darknet market. The study utilized thermal methods, specifically Thermogravimetry (TG), Derivative Thermogravimetry (DTG), and calculated Differential Thermal Analysis (c-DTA), as well as colorimetric analysis based on the International Commission on Illumination (CIE) L*a*b* system. Methods: Thermal analyses enabled the assessment of the thermal stability of the tested samples, identification of characteristic stages of thermal decomposition, and determination of differences in thermal behavior between the pure substance, the original preparation, and darknet samples. In turn, color measurements in the CIE L*a*b* space allowed for an objective comparison of tablet appearance and determination of the degree of color similarity to the original product. Results: The obtained results showed that only a few samples (V1, V3, V4, V6, V8) exhibited features similar to the original Viagra^®, both in terms of thermal profile and color. Most of the tested tablets were characterized by significant variability in physicochemical properties, indicating a lack of quality control and inconsistency in formulation. Samples V2 and V7 deviated particularly strongly—both thermally and visually—suggesting that they might not contain the original active substance or contained it in a different chemical form. Conclusions: The use of combined thermal and colorimetric methods proved to be an effective tool in the identification of counterfeit pharmaceutical products, enabling simultaneous evaluation of their composition and authenticity. The results confirm the validity of employing integrated physicochemical analyses for the detection of falsified medicines present on the illegal market. Full article

Neonatal pulmonary hypertension (PH) is a major cause of illness and death in newborns. Neonatologist-performed echocardiography (NPE) is increasingly used as a bedside tool to assess heart function, shunt patterns, and pulmonary blood flow in real time, helping clinicians better understand the severity and type of PH. This narrative review summarizes current evidence on the use of NPE in diagnosing, monitoring, and treating neonatal PH, drawing on clinical studies, guidelines, and expert recommendations. NPE provides key diagnostic and therapeutic information, including evaluation of ventricular function, estimation of pulmonary pressures, and assessment of shunt direction. Advanced measures—such as tricuspid annular plane systolic excursion (TAPSE), myocardial performance index, pulmonary artery acceleration time (PAAT), and deformation imaging—improve accuracy and help guide therapies like inhaled nitric oxide, milrinone, and sildenafil. NPE is also useful in chronic conditions such as bronchopulmonary dysplasia (BPD)- and congenital diaphragmatic hernia (CDH)-associated PH. Despite its clear clinical value, NPE use remains limited by variations in training, protocols, and resource availability. Standardized curricula, accreditation, and unified reporting practices are needed to ensure safe, consistent integration of NPE into neonatal care pathways. Full article

Background: In patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (summarized as pulmonary vascular disease; PVD), it is unclear whether the brain is protected against acute hypoxia and whether acute pulmonary vascular dilatation by sildenafil would influence cerebral and muscle tissue oxygenation whilst breathing normoxia or hypoxia. Methods: Adult patients with PVD underwent right heart catheterization, while cerebral and muscular tissue oxygenation and tissue hemoglobin index were measured using near-infrared spectroscopy along with arterial and mixed-venous blood gases. Participants underwent a four-stage protocol in which they were blinded to breathing either normoxia (FiO₂ 0.21) or normobaric hypoxia (FiO₂ 0.15), both before and after a single oral dose of sildenafil (50 mg) according to a randomized, cross-over design. Results: In 22 PVD patients (9 women, age 54 ± 14 y) under hypoxia, mean cerebral tissue oxygenation decreased by −2% (95% CI −4 to 0%, p = 0.046), muscular tissue oxygenation by −1% (95% CI −3 to 0%, p = 0.011) and mean arterial partial pressure of oxygen by −2.3 kPa (95% CI −2.7 to −1.8 kPa, p < 0.0001). Sildenafil improved the cerebral tissue hemoglobin index under hypoxia compared to hypoxia without sildenafil by 0.12 (95% CI 0.00 to 0.23, p = 0.049), but not the muscular tissue hemoglobin index. Conclusions: In PVD patients, acute exposure to normobaric hypoxia leads to a reduction in arterial oxygenation as well as cerebral and muscular tissue oxygenation. Sildenafil improves cerebral blood flow but has no effect on arterial, cerebral or muscular oxygenation. Full article

Health wines are alcoholic beverages produced by infusing traditional liquors or rice wines with natural, medicinal, and food-safe ingredients. However, to accelerate efficacy, some manufacturers illegally adulterate health wines with phosphodiesterase type 5 (PDE-5) inhibitors, which may cause severe adverse effects. This study developed a method based on ultra-high-performance liquid chromatography–time-of-flight mass spectrometry (UPLC–TOF/MS) for the rapid screening and identification of 68 PDE-5 inhibitors illegally added to health wines. After optimizing the sample preparation procedure, chromatographic conditions, mass spectrometric parameters, and primary and secondary mass spectra of the 68 PDE-5 inhibitors were acquired as reference standards. Retention times and mass spectral data were imported into the Personal Compound Database and Library, establishing a high-resolution screening database with matched drug names, molecular formulas, and accurate molecular weights. A quantitative method was validated using 11 commonly adulterated compounds, including sildenafil. The response was highly linear (r ≥ 0.9988; 0.8–400 μg/L) with low detection limits (0.2–1.0 μg/L). The average spiked recoveries were 71.2–104.1%, with relative standard deviations of ≤10.1%. Among 59 commercial health wine samples, three batches tested positive for PDE-5 inhibitors (detection rate: 5.1%). The proposed method can assist market surveillance even when reference standards are unavailable for all compounds. Full article

Background/Objectives: Molnupiravir (MOV) and nirmatrelvir (NMV) are antiviral drugs that were FDA-approved under the emergency use authorization (EUA) for coronavirus disease-2019 (COVID-19) treatment. MOV and NMV target the viral RNA-dependent RNA polymerase and main protease, respectively. Paxlovid is a combination of NMV and ritonavir (RTV), an inhibitor of the human cytochrome P450-3A4 (hCYP3A4). In this study, the structural consequences in the hCYP3A4 caused by MOV-induced mutations (MIM) were evaluated using in silico tools. Methods: MOV-induced mutations (MIM) were inserted into all the possible hotspots in the active site region of the hCYP3A4 gene, and mutant protein models were built. Structural changes in the heme-porphyrin ring of hCYP3A4 were analyzed in the presence and absence of substrates/inhibitors, including RTV. Molecular dynamics (MD) simulations were performed to analyze the effect of MIM-induced structural changes in hCYP3A4 on drug binding. Results: MD simulations confirm that MIMs, R375G and R440G in hCYP3A4 severely affect the heme-porphyrin ring stability by causing a tilt that in turn affects RTV binding, suggesting a possible inefficiency in the function of hCYP3A4. Similar results were seen for amlodipine, atorvastatin, sildenafil and warfarin, which are substrates of hCYP3A4. Conclusions: The current in silico studies indicate that hCYP3A4 containing MIMs can create complications in the treatment of COVID-19 patients, particularly with co-morbidities due to its functional inefficiency. Hence, clinicians must be vigilant when using MOV in combination with other drugs. Further in vitro studies focused on hCYP3A4 containing MIMs are currently in progress to support our current in silico findings. Full article