Inflammatory myocardial involvement has been reported in canine leishmaniosis (CanL); however, studies evaluating the degree of myocardial dysfunction in affected dogs are limited. This prospective study aimed to investigate myocardial involvement in dogs with CanL using conventional and speckle-tracking echocardiography (STE), focusing on the assessment of left ventricular systolic function and myocardial strain. Symptomatic, initially untreated dogs with a diagnosis of leishmaniosis and free from other vector-borne diseases or underlying heart diseases were enrolled (Leish group). Healthy dogs matched for age, body weight, breed, and sex were selected for the control group (C group). At the time of inclusion (T0) and at each follow-up, laboratory tests as well as conventional echocardiographic examination and STE were performed. For strain analysis, apical longitudinal long-axis 4-chamber, 3-chamber, and 2-chamber views were used (2C, 3C, 4C, respectively) to obtain the average global longitudinal strain (GLSAV), which is recognised to have the maximum reliability as an indicator of left ventricular dysfunction in humans. The software obtains GLSAV by averaging the longitudinal strain values from all left-ventricular segments derived from the multiple apical views. After enrolment, dogs were treated with a combination of meglumine and allopurinol and were monitored for six months. Clinical-pathological and echocardiographic data were collected at follow-up at 1, 3, and 6 months after the start of treatment (T1, T2, T3) and compared between the two study groups using appropriate statistical tests. Sixteen dogs composed the C group and nine dogs the Leish group. At T0, none of these dogs had abnormalities in cardiac auscultation, plasma cardiac troponin concentration was within the reference range, and standard echocardiographic examination excluded underlying cardiac diseases. The comparison between C and Leish groups did not show a statistically significant difference in any of the strain parameters analysed (GLSAV, GLS4C, GLS3C, GLS2C). Moreover, strain values in the Leish group did not change significantly over time. In conclusion, in this preliminary study on a limited population of dogs with leishmaniosis, both conventional echocardiography and STE failed to reveal clear changes suggestive of left ventricular systolic dysfunction secondary to possible myocarditis or as a consequence of the systemic disease in dogs with active leishmaniosis. However, further STE studies in larger cohorts of dogs with leishmaniosis are needed to confirm and expand our findings.

Achillea santolina is traditionally utilized in herbal therapy; nonetheless, its xanthine oxidase inhibitory and cellular antioxidant properties are not extensively investigated. This work aimed to identify the phytochemical composition of the methanolic extract of A. santolina aerial parts via LC-MS and to assess its xanthine oxidase (XO) inhibitory activity and its modulatory effects on intracellular reactive oxygen species (ROS) in HepG2 cells. The methanolic extract underwent LC-MS analysis for phytochemical identification, and XO inhibitory activity was assessed spectrophotometrically using allopurinol as the reference medication. Intracellular ROS levels were determined using the DCFH-DA fluorescent assay following xanthine-induced oxidative stress. LC-MS profiling identified ten compounds representing 95.1% of the extract, with flavonoid glycosides (44.1%) as the predominant class. Rutin (18.6%) and luteolin-7-O-glucoside (15.2%) were the major constituents. The extract demonstrated concentration-dependent inhibition of XO, with an IC50 value of 29.3 ± 0.4 µg/mL, compared to 2.1 ± 0.3 µg/mL for allopurinol. In HepG2 cells, xanthine significantly increased ROS production, while pre-treatment with the extract greatly diminished ROS levels in a dose-dependent manner, reaching approximately 75% inhibition at 50 µg/mL. The results demonstrate that the methanolic extract of A. santolina exhibits significant xanthine oxidase inhibitory and antioxidant properties, possibly due to its elevated flavonoid concentration, indicating its potential utility in addressing oxidative stress-related disorders. To the best of our knowledge, this study provides the first report on the combined xanthine oxidase inhibitory and intracellular ROS-modulating activities of A. santolina methanolic extract.

Thousands of patients share their testimonials of kidney stone treatment efficacy online routinely, often with the hope of helping other patients understand what may help alleviate the severe suffering inflicted by the condition. Such testimonials generate vast data with potential hypothesis-generating insights that remain largely untapped. For this study, 4,899 publicly available online testimonials of nine different kidney stone products were collected across three different platforms: WebMD, Amazon, and Reddit. Using a state-of-the-art Large Language Model, these subjective reports were classified along multiple dimensions, focusing on reported effectiveness and rate of adverse effects. A methodology to minimize biases and extract statistically significant data from online testimonials is presented. Odds ratios and p-values were calculated using Phyllanthus niruri as the baseline. Phyllanthus niruri demonstrated significantly higher reported effectiveness across all platforms (27.6%-87.4%) compared to most other treatments, including allopurinol, tamsulosin, hydrochlorothiazide, and potassium citrate. On Amazon, Rowatinex showed the highest effectiveness rate (90.0%). Both Phyllanthus niruri and Rowatinex exhibited remarkably low adverse effect profiles across all platforms (3.9% and 4.5% weighted average, respectively), with Rowatinex notably reporting no severe adverse effects. The consistency of these findings across different platforms suggests that patient-reported outcomes for Phyllanthus niruri and Rowatinex may warrant further clinical investigation. The rising incidence and debilitating nature of kidney stones underscore the need for research into additional prophylactic and metaphylactic treatments beyond lifestyle interventions.

The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 has been recognised as an important contributor to interindividual variability in drug response, especially in terms of efficacy and toxicity. This narrative review summarises current knowledge on the clinical relevance of ABCG2 genetic variants, with a focus on their effects on pharmacokinetics, adverse drug reactions and drug-drug-gene interactions, as well as their potential implementation in personalised therapy. A literature search was performed in PubMed, Scopus and the Clinical Pharmacogenomics Database (ClinPGx), with an emphasis on clinically relevant studies and available pharmacogenomic guidelines. The most investigated ABCG2 variant, c.421C>A (rs2231142; p.Gln141Lys), is consistently associated with reduced transporter activity and increased systemic exposure to several substrate drugs, including statins, allopurinol and anticancer agents, which may influence both treatment response and the risk of toxicity. Although growing evidence supports the clinical relevance of ABCG2 genotyping, its routine implementation remains limited. Integration of ABCG2 variability into polygenic models and clinical decision-support tools may further improve individualised treatment, particularly in patients with multimorbidity and polypharmacy.

In the present study, a chemical library of novel lophine clubbed acylthioureas (8a-l) was designed and synthesized through a multistep sequence. 2-(4-Nitrophenyl)-4,5-diphenyl-1H-imidazole (3) was synthesized from benzil, 4-nitrobenzaldehyde, and ammonium acetate via multicomponent reaction. Then the nitro group of the synthesized compound was reduced using zinc and hydrochloric acid to furnish 4-(4,5-diphenyl-1H-imidazol-2-yl) aniline (4). On the other hand, the acid chloride (6a-l) of substituted benzoic acids was prepared by reacting acids (5a-l) with thionyl chloride, followed by their reaction with potassium thiocyanate to afford corresponding acyl isothiocyanates (7a-l), which were further reacted with 4-(4,5-diphenyl-1H-imidazol-2-yl)aniline (4) to produce acylthioureas (8a-l) in good yield. The synthesized series (8a-l) was characterized by using a combination of spectroscopic techniques, including FT-IR, [1]H NMR, and [13]C NMR. Moreover, the synthesized acylthiourea derivatives were assayed for their in vitro and in silico xanthine oxidase and thymidine phosphorylase inhibitory activities. In the tested series, compounds 8j, 8d, and 8i showed robust dual inhibition profiles in low micromolar ranges. Among them, compound 8j revealed the most potent activity, with IC50 values of 1.87 ± 0.26 µM against xanthine oxidase and 1.62 ± 0.27 µM against thymidine phosphorylase. Compound 8d sits in the next position, with an IC50 value of 3.34 ± 0.37 µM (xanthine oxidase) and 3.31 ± 0.06 µM (thymidine phosphorylase), while compound 8i demonstrated considerable xanthine oxidase inhibition with an IC50 of 2.06 ± 0.36 µM. These values have outperformed the standard drug allopurinol (IC50 = 7.4 ± 0.07 µM), which was found to be less potent against xanthine oxidase. Considering the established involvement of these enzymes in oxidative stress, hyperuricemia, and inflammation-based disorders, the results endorse the idea of these derivatives being promising multifunctional therapeutic agents in the treatment of metabolic, inflammatory, and neoplastic diseases.

Buddleja officinalis Maxim. is rich in flavonoids and polyphenols, which exhibits pronounced antioxidant activity. Given that B. asiatica, a related species, has been noted to inhibit xanthine oxidase (XO) in vitro, the urate-lowering effects of B. officinalis have not been confirmed. Thus, this study aimed to screen the XO inhibition of extracts in vitro and to confirm the most active urate-lowering fraction of B. officinalis in vivo. Ethanol extracts were partitioned into n-hexane (HEX), ethyl acetate (EA), n-butanol (BuOH), and aqueous fractions. The EA fraction of B. officinalis extracts exhibited the highest XO inhibitory activity, with it significantly surpassing that of the other fractions (P<0.05). Consequently, the EA fraction was selected for further in vivo evaluation in a mouse model of hyperuricemia, which was induced through intraperitoneal injection of potassium oxonate (PO, 250 mg/kg/day for 7 days). Mice were divided into six groups, including not treated, PO, PO + allopurinol, and low (PO + EA-L), medium (PO + EA-M), and high (PO + EA-H) EA dose groups. EA fractions of B. officinalis extracts were orally administered 1 hr after PO injection. Compared with in the PO group, the serum uric acid levels were significantly reduced in the PO + EA-M, PO + EA-H, and PO + allopurinol groups (P<0.05). These findings support the potential of B. officinalis as a natural XO inhibitor and an adjunctive supplement for hyperuricemia.

A man in his early 30s presented with fever, widespread pruritic rash and deranged liver function tests shortly after returning from a religious pilgrimage. Initial assessment focused on infectious and travel-related causes given recent international travel. Investigations revealed marked eosinophilia, lymphocytosis and a mixed hepatocellular-cholestatic liver injury. Extensive viral, parasitic and autoimmune testing was negative. Despite partial symptomatic improvement following cessation of recently initiated allopurinol, the patient developed progressive eosinophilia and new lymphadenopathy. Multidisciplinary review supported a diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS), with allopurinol identified as the most likely culprit. Oral corticosteroid therapy led to rapid clinical and biochemical improvement, with normalisation of eosinophil count and liver function prior to discharge. This case highlights the diagnostic challenge of drug hypersensitivity reactions in the context of recent travel and emphasises the importance of early medication review in patients presenting with fever, rash and organ dysfunction.

Background: Hyperuricemia frequently coexists with type 2 diabetes mellitus (T2DM), contributing to a heterogeneous patient population. While previous analyses compared the overall longitudinal effects of allopurinol and SGLT2 inhibitors in this cohort, it remains unclear whether baseline metabolic heterogeneity modifies treatment response. This study aimed to determine whether data-driven metabolic clustering identifies phenotypic subgroups with prognostic or predictive relevance in hyperuricemic T2DM. Methods: In a retrospective cohort of 224 patients with T2DM and hyperuricemia, model-based clustering was applied to age, diabetes duration, body mass index (BMI), serum uric acid (sUA), HbA1c, eGFR, and sex. A sensitivity analysis excluded outliers, yielding 207 patients. Longitudinal trajectories of eGFR and sUA were assessed using linear mixed-effects models and individual slopes. Effect modification by cluster was tested via three-way interactions and analysis of covariance. Results: Clustering identified two groups with weak separation: an adipose-metabolic cluster (n = 116; exclusively male, BMI 33.1 ± 5.7 kg/m2, sUA 478 ± 62 µmol/L) and a lean-metabolic cluster (n = 91; exclusively female, BMI 31.3 ± 6.0 kg/m2, sUA 426 ± 67 µmol/L). Treatment-agnostic analyses showed no differences in eGFR and sUA slopes or in all-cause mortality across clusters. In both clusters, SGLT2 inhibitors yielded significantly more favourable eGFR slopes than allopurinol, while sUA reductions were comparable across treatments. No significant three-way interactions were detected. Conclusions: In this cohort, although baseline metabolic characteristics differ among patients, using the selected baseline variables, no clinically actionable treatment-relevant phenotypes were identified.

Effective management of gout in patients with chronic kidney disease (CKD) is frequently complicated by medication intolerance. Although allopurinol remains the preferred first-line urate-lowering therapy, cutaneous hypersensitivity reactions often necessitate drug discontinuation. Febuxostat is commonly used as an alternative, but intolerance or adverse effects may limit its use in certain patients. We describe a therapeutic solution for a patient who failed both standard agents. An 82-year-old woman with CKD and tophaceous gout presented with a benign maculopapular eruption following allopurinol initiation. After discontinuation of the drug, febuxostat was initiated, but this trial was aborted due to idiosyncratic symptomatic hypotension (94/64 mmHg). With no other oral options available, the patient underwent a conservative, 28-day oral allopurinol desensitization protocol under corticosteroid coverage. She successfully completed the desensitization and was titrated to a maintenance dose of 150 mg daily, achieving target serum uric acid levels without recurrence of skin manifestations. This case illustrates that a prolonged "start low, go slow" desensitization protocol can be safely employed in elderly patients with CKD who have experienced benign cutaneous reactions to allopurinol. This approach is particularly valuable when alternative agents like febuxostat are contraindicated or poorly tolerated, ensuring that patients are not left without effective treatment for progressive gout.

Hyperuricemia (HUA), characterized by persistently elevated serum uric acid (UA), represents a growing global public-health concern. Current urate-lowering medications are often associated with hepatotoxicity and nephrotoxicity, highlighting the urgent need for safer, food-derived alternatives.