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Journal of Functional Biomaterials Jan 2024This review aimed at searching literature for data regarding the inflammasomes' involvement in the pathogenesis of oral diseases (mainly periodontitis) and general... (Review)
Review
This review aimed at searching literature for data regarding the inflammasomes' involvement in the pathogenesis of oral diseases (mainly periodontitis) and general pathologies, including approaches to control inflammasome-related pathogenic mechanisms. The inflammasomes are part of the innate immune response that activates inflammatory caspases by canonical and noncanonical pathways, to control the activity of Gasdermin D. Once an inflammasome is activated, pro-inflammatory cytokines, such as interleukins, are released. Thus, inflammasomes are involved in inflammatory, autoimmune and autoinflammatory diseases. The review also investigated novel therapies based on the use of phytochemicals and pharmaceutical substances for inhibiting inflammasome activity. Pharmaceutical substances can control the inflammasomes by three mechanisms: inhibiting the intracellular signaling pathways (Allopurinol and SS-31), blocking inflammasome components (VX-765, Emricasan and VX-740), and inhibiting cytokines mediated by the inflammasomes (Canakinumab, Anakinra and Rilonacept). Moreover, phytochemicals inhibit the inflammasomes by neutralizing reactive oxygen species. Biomaterials functionalized by the adsorption of therapeutic agents onto different nanomaterials could represent future research directions to facilitate multimodal and sequential treatment in oral pathologies.
PubMed: 38391885
DOI: 10.3390/jfb15020032 -
BMC Nephrology Feb 2024The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to...
BACKGROUND
The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to compare new organ preservation solution PERLA® with the gold standard preservation solution University of Wisconsin (UW) regarding oxidative stress and early graft injury.
METHODS
In order to assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW solution or PERLA® solution and then assessed for oxidative stress injury (protocol 1). To assess kidney injuries and oxidative stress after reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h at 4 °C and then transplanted heterotopically for 6 h (protocol 2). PERLA® is a high Na/low K solution including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 µM) and tacrolimus (5 µM).
RESULTS
Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. We found a significant decrease in oxidative damage indicators (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreased kidney injury after reperfusion (creatinine, LDH and uric acid).
CONCLUSION
PERLA® solution was more effective than UW storage solution in preserving rat's kidney grafts.
Topics: Humans; Rats; Animals; Kidney Transplantation; Reperfusion Injury; Organ Preservation Solutions; Kidney; Allopurinol; Oxidative Stress; Adenosine; Glutathione; Insulin; Raffinose
PubMed: 38389057
DOI: 10.1186/s12882-024-03488-z -
Indian Journal of Gastroenterology :... Feb 2024Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources. The classical thiopurines face significant challenges due to cessation of therapy in approximately half of patients within one year due to side effects or ineffectiveness. In this article, we highlight innovating thiopurine treatment for IBD patients in downregulating side effects and improving efficacy.
Topics: Humans; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Mercaptopurine; Azathioprine; Immunosuppressive Agents; Purines; Sulfhydryl Compounds
PubMed: 38383877
DOI: 10.1007/s12664-024-01529-x -
Journal of Inflammation Research 2024Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in...
Lipidomics Analysis Deepen Understanding the Molecular Mechanisms in a Gouty Model Induced by Combination of MSU Crystals Injection and High-Fat Diet Feeding and the Intervention Mechanisms of Allopurinol.
BACKGROUND
Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases.
METHODS
Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol. Meanwhile, ELISA kit was used to detect mouse serum levels of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin 1 beta) and HE staining was used to observe the infiltration of inflammatory cells in the foot pad.
RESULTS
A total of 9 types of serum lipids were detected in lipidomics by shotguns, and the result of NMDS' analysis demonstrated significant differences in lipids profiles between the control and model group. It is worth noting that lipid abnormality in GA (such as Ceramide (Cer), sphingomyelin (SM), 4-hydroxyalkenals (HNE), phosphatidylinositol (PI), ethanolamine glycerophospholipid (PE), etc.) is related with phospholipid and energy metabolism, and allopurinol treatment could correct the aberrant metabolism of lipid to some extent.
CONCLUSION
Our results indicated that various aberrant lipid metabolisms were present in the established gouty model, and allopurinol treatment could relief this aberrant metabolism of lipids to some degree.
PubMed: 38370465
DOI: 10.2147/JIR.S443358 -
Cureus Jan 2024Drug-induced hypersensitivity syndrome (DIHS) is a severe type of cutaneous adverse event involving systemic organ failures. In some cases of DIHS, acute renal failure...
Drug-induced hypersensitivity syndrome (DIHS) is a severe type of cutaneous adverse event involving systemic organ failures. In some cases of DIHS, acute renal failure takes place, and it becomes necessary to perform hemodialysis. However, the clinical outcome of renal failure in the course of treatment of DIHS remains unclear. Herein, we report a case of DIHS complicated with acute renal failure, which requires hemodialysis. Furthermore, we also review the DIHS cases accompanied by acute renal failure with hemodialysis in the English case report literature.
PubMed: 38361726
DOI: 10.7759/cureus.52335 -
Journal of Chromatography. B,... Mar 2024Adenine phosphoribosyltransferase (APRT) deficiency is a rare , hereditary disorder characterized by renal excretion of 2,8-dihydroxyadenine (DHA), leading to kidney...
Optimization and validation of a UPLC-MS/MS assay for simultaneous quantification of 2,8-dihydroxyadenine, adenine, allopurinol, oxypurinol and febuxostat in human plasma.
Adenine phosphoribosyltransferase (APRT) deficiency is a rare , hereditary disorder characterized by renal excretion of 2,8-dihydroxyadenine (DHA), leading to kidney stone formation and chronic kidney disease (CKD). Treatment with a xanthine oxidoreductase inhibitor, allopurinol or febuxostat, reduces urinary DHA excretion and slows the progression of CKD. The method currently used for therapeutic monitoring of APRT deficiency lacks specificity and thus, a more reliable measurement technique is needed. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma was optimized and validated. Plasma samples were prepared with protein precipitation using acetonitrile followed by evaporation. The chemometric approach design of experiments was implemented to optimize gradient steepness, amount of organic solvent, flow rate, column temperature, cone voltage, desolvation temperature and desolvation flow rate. Experimental screening was conducted using fractional factorial design with addition of complementary experiments at the axial points for optimization of peak area, peak resolution and peak width. The assay was validated according to the US Food and Drug Administration guidelines for bioanalytical method validation over the concentration range of 50 to 5000 ng/mL for DHA, allopurinol and febuxostat, 100 to 5000 ng/mL for adenine and 50 to 12,000 ng/mL for oxypurinol, with r ≥ 0.99. The analytical assay achieved acceptable performance of accuracy (-10.8 to 8.3 %) and precision (CV < 15 %). DHA, adenine, allopurinol, oxypurinol and febuxostat were stable in plasma samples after five freeze-thaw cycles at -80 °C and after storage at -80 °C for 12 months. The assay was evaluated for quantification of the five analytes in clinical plasma samples from six APRT deficiency patients and proved to be both efficient and accurate. The proposed assay will be valuable for guiding pharmacotherapy and thereby contribute to improved and more personalized care for patients with APRT deficiency.
Topics: Humans; Allopurinol; Oxypurinol; Febuxostat; Chromatography, Liquid; Tandem Mass Spectrometry; Liquid Chromatography-Mass Spectrometry; Adenine; Adenine Phosphoribosyltransferase; Renal Insufficiency, Chronic; Metabolism, Inborn Errors; Urolithiasis
PubMed: 38359644
DOI: 10.1016/j.jchromb.2024.124041 -
Journal of Vector Borne Diseases Feb 2024Amphotericin B, Allopurinol, Glucantime and Beta-Glucan are the main drugs currently used for the treatment of cutaneous leishmaniasis. In present study, we evaluated...
BACKGROUND OBJECTIVES
Amphotericin B, Allopurinol, Glucantime and Beta-Glucan are the main drugs currently used for the treatment of cutaneous leishmaniasis. In present study, we evaluated the effect of medical leeches on BALB/c mice models infected with Leishmania parasites.
METHODS
To create animal models of leishmaniasis, BALB/c mice were inoculated with the standard Leishmania major strain MRHO / IR / 75 / ER. Treatment was performed through blood sampling with leeches. We used medical leech (Hirudo medicinalis) species. This leech is a European medicinal leech, one of several species known used as medicinal leech. 22 mice infected with Leishmania major were used for the tests .The studied mice were divided into two groups which were named with the letters L and D. The duration of blood sampling was 25 min for initial treatment, 20 min for the 2nd blood sampling and 15 min for the third times and onwards. Meglumine antimoniate (Glucantime) is a pentavalent antimony (SbV) that recommended by the World Health Organization as a golden standard treatment for all kind of leishmaniasis, but many side effects are still reported. Criteria for anti-leshmania assessment of Leech were including: Leech saliva has an anti-leishmania effect by acting on the purin pathway. Leech saliva prevents the growth and multiplication of Leishmania by a mechanism of action similar to Glucantim (breaking ATP).
RESULTS
The duration of leech treatment in BALB/c mice infected with L.major parasites was about 6-8 weeks. Out of the 22 leishmaniasis mice models that underwent treatment, 13 survived until the end of the treatment duration. The recovery rate was about 56%; lesions improved in five out of the 13 surviving mice models. Paired t-test showed a significant difference between the mean wound size at the beginning of treatment and the 8th week of treatment (PV <0.0001).
INTERPRETATION CONCLUSION
Considering the fact that the standard drugs for the treatment of leishmaniasis have many side effects, alternative therapies such as leech therapy can be effectively used to treat these chronic wounds. There are about 20 active substances in leech saliva. These substances include antistasin, eglins, guamerin, hirudin, saratin, bdellins, complement, and carboxypeptidase inhibitors. Leech saliva is an anticoagulant, anti-inflammation and prevents the platelet. Leech therapy was effective in treating leishmaniasis wounds in BALB/c mice. In this study, there was complete wound healing in 56% of the mice models.
PubMed: 38358005
DOI: 10.4103/JVBD.JVBD_114_22 -
Haematologica Feb 2024Allopurinol can be used in maintenance therapy (MT) for pediatric acute lymphoblastic leukemia (ALL) to mitigate hepatic toxicity in patients with skewed 6-...
Allopurinol can be used in maintenance therapy (MT) for pediatric acute lymphoblastic leukemia (ALL) to mitigate hepatic toxicity in patients with skewed 6- mercaptopurine metabolism. Allopurinol increases the erythrocyte levels of thioguanine nucleotides (e-TGN), which is the proposed main mediator of the antileukemic effect and decreases methyl mercaptopurine (e-MeMP) levels, associated with hepatotoxicity. We investigated the effects of allopurinol in thiopurine methyltransferase (TPMT) wild-type patients without previous clinical signs of skewed 6MP metabolism. Fifty-one patients from Sweden and Finland were enrolled in this prospective beforeafter trial during ALL MT. Mean e-TGN increased from 280 nmol/mmol Hb after 12 weeks of standard MT to 440 after 12 weeks of MT with addition of allopurinol 50 mg/m2 (p.
PubMed: 38356449
DOI: 10.3324/haematol.2023.284390 -
Cancer Reports (Hoboken, N.J.) Feb 2024Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed...
Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy.
BACKGROUND
Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities.
AIMS
To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation.
METHODS AND RESULTS
The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m /day).
CONCLUSION
Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.
Topics: Humans; Child; Mercaptopurine; Allopurinol; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hypoglycemia; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury; Lymphoma; Pancreatitis
PubMed: 38351548
DOI: 10.1002/cnr2.1987 -
Cureus Jan 2024Toxic epidermal necrolysis (TEN) is a rare and life-threatening cutaneous disease, frequently triggered by drugs. Allopurinol is one of the most frequent drugs...
Toxic epidermal necrolysis (TEN) is a rare and life-threatening cutaneous disease, frequently triggered by drugs. Allopurinol is one of the most frequent drugs associated with TEN, which implies detachment of a significant amount of the body surface area (BSA) and has a high morbidity and mortality associated with it. We present the case of a 68-year-old female with a recent diagnosis of hyperuricemia who started treatment with allopurinol. A week later, she presented to the emergency department with an extensive maculopapular exanthema with blisters and skin detachment. After the exclusion of other etiologies, the diagnosis of allopurinol-induced TEN was made, with 35% of BSA involvement. Due to the severity of the clinical condition, she was admitted to intensive care and treated with corticoids that had no response. So, she was started on immunoglobulins and transferred to a burn unit. She developed sepsis with multiorgan failure and required supportive treatment. She was discharged after a month, and physical rehabilitation was needed. This clinical case highlights the severity of allopurinol hypersensitivity that may happen and the importance of an accurate diagnosis and treatment for this rare disease.
PubMed: 38347997
DOI: 10.7759/cureus.52222