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Discovery Medicine Apr 2024Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for...
BACKGROUND
Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom.
METHODS
The biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, ), Lithom (43 mg/kg, ), and Lithom (129 mg/kg, ). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom.
RESULTS
The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 μg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups.
CONCLUSION
Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.
Topics: Animals; Calcium Oxalate; Hyperoxaluria; Oxidative Stress; Rats, Sprague-Dawley; Rats; Disease Models, Animal; Nephrolithiasis; Male; Crystallization; Ethylene Glycol; Plant Extracts
PubMed: 38665028
DOI: 10.24976/Discov.Med.202436183.75 -
RMD Open Apr 2024Currently, gout management, particularly urate-lowering therapy (ULT), is often suboptimal. Nurses successfully manage various diseases including gout. As gout...
OBJECTIVES
Currently, gout management, particularly urate-lowering therapy (ULT), is often suboptimal. Nurses successfully manage various diseases including gout. As gout prevalence is rising, and rheumatologists and general practitioners face shortages, a new approach is imperative. This real-life prospective cohort study evaluated the effectiveness of nurse-led care employing a treat-to-target strategy for gout management over a 2-year period.
METHODS
All consecutively confirmed gout patients were included. The nurse-led clinic provided a structured treatment plan with consultations, patient leaflets, telephone contacts and laboratory monitoring. After a year of nurse-led care, patients transitioned to continued care in general practice. Follow-up data were complete through registries. The primary outcome was achieving target p-urate levels (<0.36 mmol/L) at 2 years after diagnosis. Secondary outcomes included treatment continuation and achievement of target p-urate levels in specific subgroups. The results were compared with patients diagnosed in the same clinic but followed up in 'usual care'.
RESULTS
In the nurse-led group (n=114), 83% achieved target p-urate levels and ULT was continued by 98%. This trend persisted across various patient subgroups. Only 44% of patients in usual care achieved target p-urate and with insufficient doses of allopurinol . Nurse-led care involved an average of two visits and three telephone contacts over 336 days. The 2-year mortality rate was 15%.
CONCLUSIONS
Nurse-led gout care, employing a targeted approach, was associated with a very high uptake of and adherence to ULT. The encouraging results were not achieved in usual care although a direct comparison might be influenced by selection bias.
Topics: Humans; Gout; Male; Female; Middle Aged; Aged; Uric Acid; Prospective Studies; Gout Suppressants; Treatment Outcome; Practice Patterns, Nurses'; Allopurinol; Disease Management
PubMed: 38663881
DOI: 10.1136/rmdopen-2024-004179 -
Frontiers in Chemistry 2024This study investigates the biological activities of essential oil (LPEO), an endemic lavender species from the Canary Islands, traditionally used in treating various...
This study investigates the biological activities of essential oil (LPEO), an endemic lavender species from the Canary Islands, traditionally used in treating various ailments. LPEO was extracted by hydrodistillation and analyzed using GC-MS. Antioxidant activity was assessed by DPPH radical scavenging and total antioxidant capacity assays. Antimicrobial activity was evaluated by disc diffusion, MIC, MBC, and MFC determination against bacterial () and fungal () strains. Antidiabetic and anti-gout potential were investigated through α-amylase, α-glucosidase, and xanthine oxidase inhibition assays. Antityrosinase activity was determined using a modified dopachrome method. Cytotoxicity was assessed by MTT assay against breast (MCF-7, MDA-MB-468), liver (HepG2), colon (HCT-15) cancer cells, and normal cells (PBMCs). LPEO exhibits potent antiradical activity (IC50 = 148.33 ± 2.48 μg/mL) and significant antioxidant capacity (TAC = 171.56 ± 2.34 μg AA/mg of EO). It demonstrates notable antibacterial activity against four strains ( and ) with inhibition zones ranging from 18.70 ± 0.30 mm to 29.20 ± 0.30 mm, along with relatively low MIC and MBC values. LPEO displays significant antifungal activity against four strains ( and ) with a fungicidal effect at 1 mg/mL, surpassing the positive control (cycloheximide), and MIC and MFC values indicating a fungicidal effect. It exhibits substantial inhibition of xanthine oxidase enzyme (IC50 = 26.48 ± 0.90 μg/mL), comparable to allopurinol, and marked inhibitory effects on α-amylase (IC50 = 31.56 ± 0.46 μg/mL) and α-glucosidase (IC50 = 58.47 ± 2.35 μg/mL) enzymes.The enzyme tyrosinase is inhibited by LPEO (IC50 = 29.11 ± 0.08 mg/mL). LPEO displays moderate cytotoxic activity against breast, liver, and colon cancer cells, with low toxicity towards normal cells (PBMC). LPEO exhibits greater selectivity than cisplatin for breast (MCF-7) and colon (HCT-15) cancer cells but lower selectivity for liver (HepG2) and metastatic breast (MDA-MB-468) cancer cells. These findings suggest the potential of LPEO as an antioxidant, antimicrobial, anti-gout, antidiabetic, and anticancer agent.
PubMed: 38660570
DOI: 10.3389/fchem.2024.1383731 -
Phytotherapy Research : PTR Apr 2024Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as... (Review)
Review
Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.
PubMed: 38655878
DOI: 10.1002/ptr.8211 -
Internal Medicine Journal May 2024Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact...
Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact all aspects of the person's life. This Clinical Perspectives article provides an update on gout diagnosis, medications and strategies to improve the quality of gout care.
Topics: Humans; Disease Management; Gout; Gout Suppressants; Uric Acid
PubMed: 38654576
DOI: 10.1111/imj.16382 -
BMC Medical Genomics Apr 2024Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless,...
BACKGROUND
Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients.
METHODS
We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls.
RESULTS
Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2-266.8; P = 1.9 × 10). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3-670.5 and p-value = 1.7 × 10).
CONCLUSIONS
Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.
Topics: Humans; Allopurinol; Polymorphism, Single Nucleotide; Male; Female; Thailand; Middle Aged; Case-Control Studies; Aged; Adult; Pharmacogenetics; HLA-B Antigens; Genetic Predisposition to Disease; Pharmacogenomic Variants; Southeast Asian People
PubMed: 38654296
DOI: 10.1186/s12920-024-01874-y -
European Journal of Pharmaceutical... Jul 2024Uric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and...
Uric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and gout. Currently, treatment options remain limited for gout patients. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a derivative of the natural product protocatechualdehyde with good biological activity. In this work, we identify a DHNB thiosemicarbazide class of compounds that targets XOD. 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazone can effectively inhibit XOD activity (IC50 value: 0.0437 μM) and exhibits a mixed inhibitory effect. In a mouse model of acute hyperuricemia, a moderate dose (10 mg/kg.w) of 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide effectively controlled the serum uric acid content and significantly inhibited serum XOD activity. In addition, 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide showed favorable safety profiles, and mice treated with the target compound did not show any symptoms of general toxicity following a single dose of 500 mg/kg. In the allopurinol group, 50 % of the mice died. These results provide a structural framework and mechanism of XOD inhibition that may facilitate the design of hyperuricemia and gout treatments.
Topics: Animals; Hyperuricemia; Male; Semicarbazides; Mice; Benzaldehydes; Gout; Xanthine Oxidase; Uric Acid; Humans
PubMed: 38653341
DOI: 10.1016/j.ejps.2024.106778 -
Frontiers in Pharmacology 2024The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND...
The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with N-nitro-L-arginine methyl ester (L-NAME). In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). Pre-incubation (30 min) of the tissues with GKT137831 (1 μM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 μM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (HO) (100 μM) increased 6-ND basal release, whereas pre-incubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30 min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 μM) or uric acid (1 mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUA with L-NAME (100 μM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and HO. The results obtained indicate a major role of endogenous H2O2 and peroxidases as modulators of 6- ND biosynthesis/release and a lack of peroxynitrite contribution.
PubMed: 38645555
DOI: 10.3389/fphar.2024.1348876 -
Rheumatology (Oxford, England) Apr 2024Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications...
OBJECTIVES
Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol.
METHODS
We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated.
RESULTS
From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD.
CONCLUSION
People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.
PubMed: 38636489
DOI: 10.1093/rheumatology/keae229 -
Natural Product Research Apr 2024Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of resulted in the isolation of two new triterpenoids (), designated...
Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of resulted in the isolation of two new triterpenoids (), designated Ampejaponoside A and B, along with sixteen known compounds (). The structures of Ampejaposide A and B were elucidated by comprehensive analysis of spectroscopic data with the structures of the known compounds confirmed by comparison the spectral data with corresponding values reported in literatures. All the isolates were evaluated for their XOD inhibitory activity . As a result, compounds , , and displayed significant XOD inhibitory effect, particularly being the most potent with an IC value of 0.21 M, superior to positive substance allopurinol (IC 1.95 M). Molecular docking uncovered a unique interaction mode of with the active site of XOD. The current study showed that the triterpenoids and polyphenols from could serve as new lead compounds with the potential to speed up the development of novel XOD inhibitors with clinical potential to treat hyperuricaemia and gout.
PubMed: 38635344
DOI: 10.1080/14786419.2024.2341308