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Acta Endocrinologica (Bucharest,... 2023Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD).
BACKGROUND
Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD).
AIM
We therefore aimed at evaluating the influence of allopurinol on the course of NAFLD in rats.
STUDY DESIGN
We divided 21 mature albino Sprague Dawley rats into three groups: controls (n = 7, normal diet for 12 weeks); NAFLD rat models (by feeding water containing 30% fructose for first 8 weeks) treated with allopurinol subsequently for the next 4 weeks (n = 7); and similar case treated with placebo (saline) subsequently for the next 4 weeks (n = 7).
METHODS
We compared the histopathological scores, IL-1 and IL-2 immunoexpression levels across the groups. Liver histopathological score was determined by observing the steatosis (the percentage of liver cells containing fat): <25% = 1+, 25% - 50% = 2+, 51% - 75% = 3+, >75% = 4+; inflammation and necrosis: 1 focus per low-power field = 1+; and 2 or more foci = 2+. The number of liver IL-1 and IL-2 positive cells was measured by systematically scoring at least 100 hepatocyte cells per field in 10 fields of tissue sections by a magnification of 100.
RESULTS
Xanthine oxidase (XO) activity and lipid peroxidation was significantly different in the allopurinol group compared to the saline group (XO; 0.098 ± 0.006 mU/mg . 0.162 ± 0.008 mU/mg, p = 0.01, 0.116 ± 0.040 nmol malondialdehyde/mg 0.246 ± 0.040 nmol malondialdehyde /mg, p = 0.01). The allopurinol group had lower histopathological scores, IL-1 and IL-2 immunoexpression levels in the liver compared to the saline group (2.13 ± 0.35 against 5.45 ± 0.24, p = 0.003, IL-1; 5.76 ± 0.43 against 12.85 ± 3.26, p = 0.023, IL-2; 8.55 ± 1.14 against 56.23 ± 7.12, p = 0.002).
CONCLUSIONS
Allopurinol has a therapeutic role against the progression of NAFLD of the rats.
PubMed: 37908883
DOI: 10.4183/aeb.2023.155 -
Frontiers in Genetics 2023Specific alleles in human leukocyte antigens (HLAs) are associated with an increased risk of developing drug hypersensitivity reactions induced by abacavir,...
Specific alleles in human leukocyte antigens (HLAs) are associated with an increased risk of developing drug hypersensitivity reactions induced by abacavir, allopurinol, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, or flucloxacillin. Transplant patients are genotyped for HLA as a routine practice to match a potential donor to a recipient. This study aims to investigate the feasibility and potential impact of repurposing these HLA genotype data from kidney transplant patients to prevent drug hypersensitivity reactions. A cohort of 1347 kidney transplant recipients has been genotyped in the Leiden University Medical Center (LUMC) using next-generation sequencing (NGS). The risk alleles and were retrieved from the NGS data. Medical history, medication use, and allergic reactions were obtained from the patient's medical records. Carrier frequencies found were compared to a LUMC blood donor population. A total of 13.1% of transplant cohort patients carried at least one of the five risk alleles and therefore had an increased risk of drug-induced hypersensitivity for specific drugs. , were found in carrier frequencies of 4.61%, 1.19%, 4.46%, and 3.35% respectively. No carrier was found. In total nine carriers received flucloxacillin and seven carriers within our cohort received allopurinol. Our study shows that repurposing HLA genotype data from transplantation patients for the assignment of HLA risk alleles associated with drug hypersensitivity is feasible. The use of these data by physicians while prescribing drugs or by the pharmacist when dispensing drugs holds the potential to prevent drug hypersensitivity reactions. The utility of this method was highlighted by 13.1% of the transplant cohort patients carrying an actionable HLA allele.
PubMed: 37908589
DOI: 10.3389/fgene.2023.1289015 -
Journal of Pharmaceutical Policy and... Oct 2023Drug-drug interactions (DDI) are known to increase the risk of morbidity and mortality, and adversely affect the patient's quality of life. The study was to assess...
BACKGROUND AND OBJECTIVE
Drug-drug interactions (DDI) are known to increase the risk of morbidity and mortality, and adversely affect the patient's quality of life. The study was to assess healthcare professional's (HCP) knowledge of DDIs in general hospitals of Buraydah.
METHODS
A cross-sectional survey using convenience sampling methods was conducted among 135 healthcare professionals in general hospitals of Buraydah between November and December 2016. The study was carried out after approval and permission from the Regional Research Ethics Committee (November 2016). Respondents were asked to classify 15 drug pairs as 'contraindicated', 'could be used with monitoring', or 'no interaction'. A response option of 'not sure' was also provided. Data were collected using a self-administered questionnaire. The descriptive analysis was done using frequency distribution and percentage for demographic data and other responses to questions. Data were collected, tabulated, and analyzed using Statistical Package for Social Sciences (SPSS) software (version 23). Logistic regression analysis was used to assess the independent variables that affect the HCP knowledge, the significant levels were set at p-value < 0.05.
RESULTS
A total of 135 healthcare professionals were included in the study. The percentage of HCPs who correctly classified the drug pairs ranged from 15 (11.1%) for "Allopurinol + Pyrazinamide" to 90 (66.7%) for "acetaminophen with codeine + amoxicillin". The average number of correctly categorized drug pairs was 5. About one-half of the respondents 73 (54.1%) answered correctly. The level of education was found to be an independent predictor of DDI knowledge. The results from the multivariate analysis indicated that a higher potential DDI knowledge level was associated with pharmacists. Pharmacists had 8.27 times higher DDI knowledge tests than nurses, P value = 0.001. Pharmacists 43(31.9%) were the most cited information source.
CONCLUSIONS
The present study revealed that health care professional's DDI knowledge was inadequate. Level of education was significantly associated with healthcare professionals' DDI knowledge. Pharmacists were the most cited DDI information source. Healthcare professionals should update their DDI knowledge through continuing education and should improve their familiarity with DDI information sources. These updated educations help to provide the appropriate therapeutic outcomes.
PubMed: 37908021
DOI: 10.1186/s40545-023-00642-0 -
International Journal of Molecular... Oct 2023Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free...
Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 cells and primary human monocytes by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of the ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor ()- and markers of ER/oxidative stress were determined by qRT-PCR, TNF-α protein by ELISA, reactive oxygen species (ROS) by DCFH-DA assay, hypoxia-inducible factor 1-alpha (HIF-1α), p38, extracellular signal-regulated kinase (ERK)-1,2, and nuclear factor kappa B (NF-κB) phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed using qRT-PCR/IHC and plasma TNF-α, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and oxidized low-density lipoprotein (OX-LDL) via ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CCAAT-enhancer-binding protein homologous protein (), activating transcription factor 6 (), superoxide dismutase 2 (), and nuclear factor erythroid 2-related factor 2 () expression ( ≤ 0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α stabilization and p38 MAPK/p65 NF-κB phosphorylation, while the MAPK/NF-κB pathway inhibitors and antioxidants/ROS scavengers such as curcumin, allopurinol, and apocynin attenuated the TNF-α production ( ≤ 0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL ( ≤ 0.05). Our findings support a metabolic-ER stress cooperativity model, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also highlights the therapeutic potential of antioxidants in inflammatory conditions involving metabolic/ER stresses.
Topics: Humans; Endoplasmic Reticulum Stress; Glucose; Inflammation; NF-kappa B; Obesity; Reactive Oxygen Species; THP-1 Cells; Tumor Necrosis Factor-alpha
PubMed: 37894865
DOI: 10.3390/ijms242015186 -
Tropical Medicine and Infectious Disease Oct 2023Canine visceral leishmaniasis (CVL) remains a significant disease worldwide. In Brazil, its treatment is performed using miltefosine, which has demonstrated promising...
Canine visceral leishmaniasis (CVL) remains a significant disease worldwide. In Brazil, its treatment is performed using miltefosine, which has demonstrated promising outcomes in dogs. This study represents the first attempt to treat and monitor dogs with CVL in natural conditions over the course of one year. The dogs were divided into two groups: G1 received miltefosine and allopurinol for 28 days, while G2 received miltefosine for 28 days, followed by allopurinol for one year. The follow-up involved clinical, hematological, and biochemical evaluations, as well as the detection of DNA in skin and bone marrow samples. By the end of the follow-up, dogs in G2 exhibited improved staging compared to their initial conditions, whereas those in G1 showed worsened staging. DNA in skin and bone marrow decreased between 6 and 12 months after treatment. Our observations indicate that the treatment using miltefosine reduces the detection of the parasite in the skin and bone marrow for up to one year following its administration. The continuous use of allopurinol contributes to control of the disease in dogs. These findings provide valuable insights into the response of dogs treated in natural conditions, offering essential information for veterinarians and public health authorities.
PubMed: 37888600
DOI: 10.3390/tropicalmed8100472 -
Animals : An Open Access Journal From... Sep 2023Reducing the alimentary purine intake contributes to the prevention of purine (especially xanthine) urolith formation, a common adverse effect of allopurinol treatment...
Reducing the alimentary purine intake contributes to the prevention of purine (especially xanthine) urolith formation, a common adverse effect of allopurinol treatment in dogs with infections. Analyses of the purine content are not required in order to advertise a diet as low in purine. Due to different analytical methods, data provided on purine content are barely comparable. The aim of this study was to investigate the total purine content of 12 different dog diets. For this, the purine bases adenine, guanine, xanthine, and hypoxanthine were determined by standardised high performance liquid chromatography in commercially available urinary diets (n = 4), kidney diets (n = 2), low protein diets (n = 3), 1 vegan diet, 1 regular diet for healthy adult dogs, and 1 homemade low purine diet. Total purine amounts ranged between 10.2 and 90.9 mg/100 g of dry matter. The daily purine intake calculated for a 20 kg standard dog with the analysed diets ranged between 21.9 and 174.7 mg. The lowest daily purine intakes were achieved by 2 urinary urate diets, followed by the homemade diet. Differences in the purine content of commercially available diets need to be considered. Awareness has to be raised when selecting diets for dogs with infections during allopurinol treatment in order to minimise the risk of urolith formation.
PubMed: 37835666
DOI: 10.3390/ani13193060 -
Doklady. Biochemistry and Biophysics Aug 2023It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related...
It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related to gout. The aim of the study was to evaluate the impact of various risk factors for T2DM in patients with gout. A total of 444 patients (49 women, 395 men) ≥18 years old with gout and without DM were included. The duration of observation was 5.66 [2.69; 7.64] years. To identify the factors associated with the risk of developing T2DM, multivariate logistic regression was used, which included sex; T2DM in relatives; insufficient physical activity; unbalanced diet; age ≥ 45 years; ≥4 attacks per year; presence of tophi; BMI ≥30 kg/m; allopurinol, febuxostat, glucocorticoids, diuretics, metformin, colchicine; GFR < 60 mL/min/1.73 m; serum uric acid level (sUA) ≥ 420 µmol/L and ≥ 480 µmol/L. T2DM developed in 108 (24.3%) patients. According to the multivariate model, the presence of ≥4 attacks of arthritis per year increased the risk of T2DM (OR = 5.23; 95% CI: 2.98-9.19; p = 0.0001); presence of tophi (OR = 2.61; 95% CI: 1.50-4.54; p = 0.001); sUA ≥ 480 µmol/L (OR = 2.26; 95% CI: 1.02-5.00; p = 0.144); diuretics (OR = 2.35; 95% CI: 1.19-4.64; p = 0.014). Febuxostat (OR = 0.31; 95% CI: 0.11-0.84; p = 0.022) and metformin (OR = 0.49; 95% CI: 0.21-1.16; p = 0.107) reduced the risk of developing T2DM. Risk of T2DM in patients with gout is associated with high incidence of arthritis attacks, MK ≥ 480 μmol/L, hypertension, diuretic use, and febuxostat and metformin reduces risk.
Topics: Male; Humans; Female; Middle Aged; Adolescent; Febuxostat; Gout Suppressants; Prospective Studies; Uric Acid; Diabetes Mellitus, Type 2; Gout; Diuretics; Metformin
PubMed: 37833606
DOI: 10.1134/S1607672923700321 -
Clinical Pharmacology : Advances and... 2023Allopurinol is a commonly used medication that lowers uric acid production which is essential for gout treatment and prevention. Although many patients tolerate...
Allopurinol is a commonly used medication that lowers uric acid production which is essential for gout treatment and prevention. Although many patients tolerate allopurinol therapy without severe complications; Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening delayed hypersensitivity reactions that have been reported especially among Asian and African American patients. We describe a case of allopurinol-induced SJS in a 95-year-old Asian female. The patient started allopurinol 13 days prior to presenting to the emergency room (ER). On day 10 of therapy, the patient developed a diffuse erythematous desquamating rash which prompted her to visit the ER after 3 days from the rash onset. This case report describes a rare fatal hypersensitivity reaction that requires rapid identification and treatment in a multi-disciplinary setting.
PubMed: 37811521
DOI: 10.2147/CPAA.S427714 -
Cureus Sep 2023Toxic epidermal necrolysis (TEN) is a life-threatening, blistering dermatitis. It is characterized by fever and the development of mucocutaneous lesions, which lead to...
Toxic epidermal necrolysis (TEN) is a life-threatening, blistering dermatitis. It is characterized by fever and the development of mucocutaneous lesions, which lead to necrosis and sloughing of the epidermis. It is commonly triggered by medications and infections. We present the case of a 75-year-old male who presented to the hospital with a fever and widespread exfoliating skin rash involving 41% of his body surface area (BSA). He has a past medical history of gout, hypertension, asthma, and depression. He was recently started on allopurinol by his general practitioner (GP) for hyperuricemia. The condition also involved oral, eye, and pharynx mucosae. He was diagnosed with toxic epidermal necrolysis and was managed with intravenous (IV) hydrocortisone, steroid and antibiotic eye drops, and steroid and antibiotic topical creams. Due to the weak available evidence supporting the use of ciclosporin and intravenous immunoglobulins, this patient was managed with steroid use only. His rash initially worsened, but ultimately, he made a full recovery without any sequelae. The patient was reviewed in the dermatology clinic four weeks post-discharge, and he did not have any residual disease.
PubMed: 37809172
DOI: 10.7759/cureus.44812 -
Frontiers in Bioscience (Landmark... Sep 2023Disorders of purine metabolism are the main cause of hyperuricemia. Current drugs for the treatment of hyperuricemia usually cause a degree of cardiovascular damage.
BACKGROUND
Disorders of purine metabolism are the main cause of hyperuricemia. Current drugs for the treatment of hyperuricemia usually cause a degree of cardiovascular damage.
METHODS
This study aimed to investigate the therapeutic effects of fruiting body (AFB), rhizomorph (AR) and fermentation product (after rhizomorphs removal) (AFP) on hyperuricemic mice. The hyperuricemia mouse model was established by oral administration of potassium oxonate 0.9 g⋅kg-1 and hypoxanthine 0.5 g⋅kg-1 for two weeks. Starting from the third week, the intragastric administration of the intervention drug group was as follows: Allopurinol 0.013 g⋅kg-1, AFB (3.9 and 7.8 g⋅kg-1), AR (3.9 and 7.8 g⋅kg-1), AFP (1.95 and 3.9 g⋅kg-1) once daily for 14 days.
RESULTS
Results showed that AFB, AR, and AFP reduced the contents of serum uric acid, serum creatinine, and blood urea nitrogen in hyperuricemic mice and the mechanism of action might be through up-regulation of the expression levels of organic anion transporter 1/organic anion transporter 3 proteins in kidney tissue. AR and AFP both exhibited better uric acid-lowering effects than AFB, which may be due to the higher purine content of AFB.
CONCLUSIONS
and its fermentation products can treat hyperuricemia by up-regulating OAT1 protein and OAT3 protein, reducing uric acid content in mice.
Topics: Mice; Animals; Hyperuricemia; Organic Anion Transport Protein 1; Armillaria; Kidney; Uric Acid; Fermentation; Honey; alpha-Fetoproteins; Organic Anion Transporters; Purines
PubMed: 37796687
DOI: 10.31083/j.fbl2809228