RESUMEN
BACKGROUND: Recently, it was demonstrated that allopurinol, a xanthine oxidase inhibitor, has cardiovascular and anti-ischaemic properties and may be a metabolic antianginal agent option.Objective: The objective of this study was to evaluate the antianginal effect of allopurinol as a third drug for patients with stable coronary artery disease (CAD). METHODS: This was a randomized clinical trial between 2018 and 2020 including patients with CAD who maintained angina despite initial optimization with beta-blockers and calcium channel blockers. The individuals were randomized 1:1 to 300 mg of allopurinol twice daily or 35 mg of trimetazidine twice daily. The main outcome was the difference in the angina frequency domain of the Seattle Angina Questionnaire (SAQ-AF). A probability (p) value < 0.05 was considered statistically significant. RESULTS: A hundred and eight patients were included in the randomization phase, with 54 (50%) in the allopurinol group and 54 (50%) in the trimetazidine group. Six (5.6%) individuals, 3 from each group, were lost to follow-up for the primary outcome. In the allopurinol and trimetazidine groups, the median SAQ-AF scores were 50 (30.0 to 70.0) and 50 (21.3 to 78.3), respectively. In both groups, the SAQ-AF score improved, but the median of the difference compared to baseline was lower in the allopurinol group (10 [0 to 30] versus 20 [10 to 40]; p < 0.001), as was the mean of the difference in the total SAQ score (12.8 ± 17.8 versus 21.2 ± 15.9; p = 0.014). CONCLUSION: Both allopurinol and trimetazidine improved the control of angina symptoms; however, trimetazidine presented a greater gain compared to baseline. Brazilian Registry of Clinical Trials - Registration Number RBR-5kh98y.
FUNDAMENTO: Recentemente, foi demonstrado que o alopurinol, um inibidor da xantina oxidase, possui propriedades cardiovasculares e anti-isquêmicas e pode ser uma opção de agente antianginoso metabólico. OBJETIVO: O objetivo do presente estudo foi avaliar o efeito antianginoso do alopurinol como terceiro medicamento para pacientes com doença arterial coronariana (DAC) estável. MÉTODOS: Trata-se de um ensaio clínico randomizado entre 2018 e 2020 incluindo pacientes com DAC que mantiveram angina apesar da otimização inicial com betabloqueadores e bloqueadores dos canais de cálcio. Os indivíduos foram randomizados 1:1 para 300 mg de alopurinol 2 vezes ao dia ou 35 mg de trimetazidina 2 vezes ao dia. O desfecho principal foi a diferença no domínio da frequência da angina do Questionário de Angina de Seattle (QAS-FA). Foram considerados estatisticamente significativos valores de probabilidade (p) < 0,05. RESULTADOS: Foram incluídos 108 pacientes na fase de randomização, com 54 (50%) no grupo alopurinol e 54 (50%) no grupo trimetazidina. Seis (5,6%) indivíduos, 3 de cada grupo, foram perdidos no seguimento para o desfecho primário. Nos grupos de alopurinol e trimetazidina, as pontuações medianas do QAS-FA foram 50 (30,0 a 70,0) e 50 (21,3 a 78,3), respectivamente. Em ambos os grupos, a pontuação do QAS-FA melhorou, mas a mediana da diferença em relação à linha de base foi menor no grupo alopurinol (10 [0 a 30] versus 20 [10 a 40]; p < 0,001), assim como a média da diferença na pontuação total do QAS (12,8 ± 17,8 versus 21,2 ± 15,9; p = 0,014). CONCLUSÃO: Tanto o alopurinol quanto a trimetazidina melhoraram o controle dos sintomas de angina; no entanto, a trimetazidina apresentou um ganho maior em relação à linha de base. Registro Brasileiro de Ensaios Clínicos Número de Registro RBR-5kh98y.
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Alopurinol , Trimetazidina , Vasodilatadores , Humanos , Alopurinol/uso terapéutico , Trimetazidina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Vasodilatadores/uso terapéutico , Resultado del Tratamiento , Anciano , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Angina de Pecho/tratamiento farmacológicoRESUMEN
BACKGROUND: In response to inflammation and other stressors, tryptophan is catalyzed by Tryptophan 2,3-Dioxygenase (TDO), which leads to activation of the kynurenine pathway. Sepsis is a serious condition in which the body responds improperly to an infection, and the brain is the inflammation target in this condition. OBJECTIVE: This study aimed to determine if the induction of TDO contributes to the permeability of the Blood-Brain Barrier (BBB), mortality, neuroinflammation, oxidative stress, and mitochondrial dysfunction, besides long-term behavioral alterations in a preclinical model of sepsis. METHODS: Male Wistar rats with two months of age were submitted to the sepsis model using Cecal Ligation and Perforation (CLP). The rats received allopurinol (Allo, 20 mg/kg, gavage), a TDO inhibitor, or a vehicle once a day for seven days. RESULTS: Sepsis induction increased BBB permeability, IL-6 level, neutrophil infiltrate, nitric oxide formation, and oxidative stress, resulting in energy impairment in 24h after CLP and Allo administration restored these parameters. Regarding memory, Allo restored short-term memory impairment and decreased depressive behavior. However, no change in survival rate was verified. CONCLUSION: In summary, TDO inhibition effectively prevented depressive behavior and memory impairment 10 days after CLP by reducing acute BBB permeability, neuroinflammation, oxidative stress, and mitochondrial alteration.
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Alopurinol , Barrera Hematoencefálica , Depresión , Estrés Oxidativo , Sepsis , Triptófano Oxigenasa , Animales , Masculino , Ratas , Alopurinol/farmacología , Alopurinol/uso terapéutico , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Memoria/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo , Triptófano Oxigenasa/metabolismo , Triptófano Oxigenasa/antagonistas & inhibidoresRESUMEN
Canine visceral leishmaniasis is a parasitic zoonosis that has a profound impact on public health in countries where it is endemic. Chemotherapeutic treatments cannot keep dogs stable for long periods, and the risk of generating parasitic resistance must be considered. Forty-four symptomatic and naturally infected dogs with Leishmania infantum were tested with two treatment protocols (i) immunotherapy with LaSap vaccine and (ii) immunochemotherapy with LaSap vaccine plus allopurinol. At 90 days after the end of the treatment, it was verified that, although both protocols had generated significant clinical improvements with a greater production of IFN-γ/IL-10, in relation to the parasite load, mainly in the skin, the dogs treated only with immunotherapy maintained the same profile. These results indicate that LaSap is a good strategy to control dog parasitism.
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Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Vacunas , Animales , Perros , Alopurinol/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/veterinaria , Inmunoterapia/métodos , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/prevención & controlRESUMEN
BACKGROUND: Leishmania spp., a protozoan transmitted by sandflies, widely affects humans and dogs in Colombia, nevertheless feline leishmaniasis (FeL) remains understudied. OBJECTIVE: This study reports a case of feline leishmaniasis in Colombia and its therapeutic management. METHODS: Complete blood count, renal and hepatic serum biochemistry, nodular lesion cytology, FeLV/FIV snap test, abdominal ultrasound, and molecular diagnosis of Leishmania spp. 16 s rRNA gene amplification by real-time-PCR (qPCR), ITS-1 and hsp70 gene by endpoint-PCR and Sanger sequencing were performed. RESULTS: The patient was negative for FIV/FeLV and showed leukocytosis, lymphocytosis, thrombocytopenia, neutrophilia, monocytosis, hypergammaglobulinemia, increased gamma-glutamyl-transferase, cortical nephrocalcinosis, diffuse heterogeneous splenic parenchyma, and cholangitis. Nodular lesion cytology, qPCR and Sanger sequencing confirmed the diagnosis of Leishmania spp. The patient was treated with allopurinol and miltefosine. After treatment, clinical signs disappeared. CONCLUSION: Clinical examination, cytology, and molecular tests allowed a rapid and sensitive FeL diagnosis. Allopurinol and miltefosine improved the clinical condition of the cat.
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Enfermedades de los Gatos , Enfermedades de los Perros , Leishmania , Leishmaniasis , Fosforilcolina/análogos & derivados , Gatos , Animales , Humanos , Perros , Colombia , Alopurinol/uso terapéutico , Virus de la Leucemia Felina , Leishmaniasis/diagnóstico , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/veterinaria , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/tratamiento farmacológicoRESUMEN
To characterize CD4+CD28null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4+CD28null/CD4+ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet+ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt+ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4+ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4+CD28null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4+CD28nullT-bet+ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4+CD28nullGATA-3+ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4+CD28nullRORγt+ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4+CD28null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4+ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.
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Antígenos CD28 , Hiperuricemia , Humanos , Alopurinol/uso terapéutico , Antígenos CD28/metabolismo , Linfocitos T CD4-Positivos , Hiperuricemia/tratamiento farmacológico , Leucocitos Mononucleares/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Fenotipo , Proyectos Piloto , Ácido Úrico/metabolismo , Prueba de Estudio ConceptualRESUMEN
INTRODUCTION: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. METHODS: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). RESULTS: The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs. CONCLUSION: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.
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Alopurinol , Gota , Humanos , Masculino , Alopurinol/uso terapéutico , Alopurinol/efectos adversos , Febuxostat/uso terapéutico , Supresores de la Gota/uso terapéutico , Prevalencia , Calidad de Vida , Diálisis Renal , Gota/tratamiento farmacológico , Gota/epidemiología , Gota/complicaciones , Colchicina/uso terapéuticoRESUMEN
Background: Canine visceral leishmaniasis causes several clinical signs, such as lymphadenomegaly, exfoliative dermatitis, ulcerative skin lesions, and lameness. The most commonly reported locomotor changes are claudication, edema, arthralgia, joint stiffness, and muscle atrophy. Radiographic exam revealed cortical and medullary destruction, increase, or decrease in medullary opacity, proliferative periosteal reaction, osteolysis, collapse of joint spaces and soft tissue edema are observed. The aim of this report is to describe the clinical and radiographic evolution of a case of erosive polyarthritis associated with leishmaniasis in a dog before, during and after treatment with miltefosine. Case: A 7-month-old mixed-breed dog was attended due pain and limited mobility. In the orthopedic evaluation, joint swelling, stiffness, and increased pain sensitivity of the four limbs, as well as neck stiffness, were noted. Radiographic examination showed joint changes compatible with edema, with increased volume and radiopacity of the soft tissues adjacent to the joints. The segments of the patient's spine showed more severe bone alterations, the cervical spine being one of the most affected regions, with multiple bone proliferations throughout the vertebral body, especially in the ventral portion (spondylosis), compatible with polyarthritis due to leishmaniasis. Due to the suspicion, lymph node and spleen cytology was performed, confirming the diagnosis. Hematological examination revealed anemia, leukopenia due to lymphopenia and thrombocytopenia in addition to increased AST (79,4 U/L; reference: 6,2 - 13 U/L), creatine kinase (517,6 U/L; reference: 1,5 - 28,4 U/L), lactate dehydrogenase (688,4 IU/L; reference: 45 - 233 IU/L) and hyperproteinemia (7,34 g/dL; reference: 5,4 - 7,1 g/dL). Treatment with miltefosine, allopurinol, domperidone, prednisone, gabapentin and dipyrone was started. Reassessments were performed monthly for 3 consecutive months. Hematological examinations showed improvement, with resolution of anemia and thrombocytopenia, and a marked decrease in creatine kinase values. Thus, it is evident that the dog did not develop liver or kidney changes during treatment. During the treatment and monitoring in this period, the dog had a clinical improvement, which started to walk without pain. In addition, joint swellings were no longer present, however, there was no improvement in the radiographic evaluation of the joints. Discussion: Clinical signs of the locomotor system are compatible with those described in animals that had osteoarticular manifestations associated with leishmaniasis, such as arthralgia, edema, and joint stiffness. In the present report, treatment with miltefosine associated with allopurinol resulted in an improvement in the clinical picture, and this therapy is therefore promising in dogs with polyarthritis due to leishmaniasis. A case published in human medicine demonstrated the intra-articular absorption capacity of this drug. There is only one study to date that describes the radiographic evolution of a dog with arthritis due to leishmaniasis after treatment with miltefosine and allopurinol. In this case described, the dog reported remained with the osteoarticular lesions after treatment, although clinical improvement was observed, as in our report. The use of miltefosine and allopurinol are in accordance with stage II staging for leishmaniasis. In this study, although there was no improvement in the radiographic examinations, the treatment was effective in the remission of the animal's clinical condition.
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Animales , Perros , Artritis/terapia , Artritis/veterinaria , Leishmania , Leishmaniasis Visceral/tratamiento farmacológico , Alopurinol/uso terapéutico , Domperidona/uso terapéuticoRESUMEN
Perforating dermatoses are papulonodular cutaneous pathologies characterized by transepithelial extrusion of components of the extracellular matrix of the dermis, by inflammation or degeneration. When secondary, the systemic diseases are called Acquired Perforating Diseases. Our letter aims to report a case of acquired perforating dermatoses secondary to chronic renal dialysis. The treatment with Allopurinol proved to be effective in this case. Allopurinol would act as an antioxidant, reducing the inflammatory reaction in tissues and consequent damage to the collagen fibers (AU)
Dermatoses perfurantes são patologias cutâneas papulonodulares que se caracterizam pela extrusão transepitelial de componentes da matriz extracelular da derme, por inflamação ou degeneração. Quando são secundárias as doenças sistêmicas são chamadas Doenças Perfurantes Adquiridas. Nossa carta tem como objetivo relatar caso de dermatose perfurante adquirida secundária a insuficiência renal crônica dialítica. O tratamento com Alopurinol se mostrou eficaz neste caso. O Alopurinol atuaria como antioxidante, reduzindo a reação inflamatória nos tecidos e consequentes danos nas fibras colágenas (AU)
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Humanos , Prurigo , Enfermedades de la Piel/terapia , Alopurinol/uso terapéutico , Vía Perforante , Insuficiencia Renal CrónicaRESUMEN
The purpose of the present study was to evaluate the efficacy of the treatment with a recombinant cysteine proteinase from Leishmania, rldccys1, associated with allopurinol or miltefosine on Leishmania (Leishmania) infantum chagasi-infected hamsters. Golden Syrian hamsters infected with L. (L.) infantum chagasi were treated with either miltefosine (46 mg/kg) or allopurinol (460 mg/kg) alone by oral route or associated with rldccys1 (150 µg/hamster) by subcutaneous route for 30 days. Infected hamsters were also treated with miltefosine (46 mg/kg) plus rldccys1 (150 µg/hamster) for 30 days (phase 1) followed by two additional doses of rldccys1 (250 µg/hamster) (phase 2). After the end of treatment, the animals were analyzed for parasite load, body weight, serum levels of immunoglobulins, cytokine expression, and drug toxicity. The data showed a significant decrease of parasite load in infected hamsters treated with allopurinol or miltefosine alone or associated with rldccys1, as well as in those treated with rldccys1 alone. Significantly lower levels of serum IgG were detected in hamsters treated with allopurinol plus rldccys1. The treatment with miltefosine associated with rldccys1 prevented relapse observed in animals treated with miltefosine alone. A significant loss of body weight was detected only in some hamsters treated with miltefosine for 1 month and deprived of this treatment for 15 days. There were no significant differences in transcript expression of IFN-γ and IL-10 in any of treated groups. Neither hepatotoxicity nor nephrotoxicity was observed among controls and treated groups. These findings open perspectives to further explore this immunochemotherapeutic schedule as an alternative for treatment of visceral leishmaniasis.
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Antiprotozoarios , Leishmania infantum , Leishmaniasis Visceral , Alopurinol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Peso Corporal , Cricetinae , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/parasitología , Mesocricetus , Fosforilcolina/uso terapéuticoRESUMEN
Canine visceral leishmaniasis is an endemic zoonosis in Brazil. Dogs are the main hosts in urban environments. The treatment has gained popularity since the Brazilian government authorized miltefosine for canine treatment. The aim of this study was to investigate the clinical and parasitological impact of short-term treatment with miltefosine and allopurinol, alone and in combination. We evaluated the ability of pharmacotherapy to reduce clinical signs of disease, antibody levels using the indirect fluorescence antibody test (IFAT) and skin parasite load via qPCR after 28 days of treatment. The therapeutic protocols promoted a significant decline in clinical signs and in the skin parasite load in dogs (p < 0.01). We observed a moderate correlation between the skin parasite load and the clinical score in all three treatment groups (r > 0.5) Antibody levels did not decrease in this short period. It was concluded that the treatment with allopurinol reduced the number of parasites in the skin of dogs with visceral leishmaniasis in the short term. However, its efficiency is potentiated when associated with miltefosine.
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Antiprotozoarios , Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Alopurinol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/parasitología , Perros , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/veterinaria , Fosforilcolina/análogos & derivadosRESUMEN
PURPOSE: Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism. METHODS: This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml. RESULTS: Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol. CONCLUSION: Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.
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Hiperparatiroidismo Secundario , Hiperuricemia , Insuficiencia Renal Crónica , Deficiencia de Vitamina D , Adulto , Anciano , Anciano de 80 o más Años , Alopurinol/uso terapéutico , Calcio/uso terapéutico , Colecalciferol/uso terapéutico , Femenino , Furosemida/uso terapéutico , Humanos , Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/epidemiología , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea , Fosfatos , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Ácido Úrico , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/complicacionesRESUMEN
INTRODUCTION: Gout is the most common inflammatory arthritis, but was not considered in most COVID-19 and rheumatic diseases reports. Our aim was to describe changes in clinical data, treatment, function and quality of life for gout patients during COVID-19 pandemic. METHODS: Prospective, descriptive and analytical study of 101 consecutive gout (ACR/EULAR 2015) patients from our clinic evaluated during pandemic by phone call (n=52) or phone call + face-to-face (n=68) that accepted to participate. Variables are demographics, clinical and treatment data, HAQ, EQ5D questionnaires and COVID-19-related data. Patients were divided in two groups: flare (n=36) or intercritical gout (n=65) also; available pre-pandemic data was obtained from 71 patients. Statistical analyses are X2, paired t-test and Wilcoxon test. RESULTS: Included gout patients were males (95.8%), mean (SD) age 54.7 (10.7) years and disease duration 16.4 (9.8) years; 90% received allopurinol, 50% colchicine as prophylaxis and 25% suspended ≥ 1 medication. Comparison of pre-pandemic vs pandemic data showed > flares (4.4% vs 36%, p=0.01), more flares in the last 6 months: 0.31 (0.75) vs 1.71 (3.1), (p=0.004 and > urate levels: 5.6 (1.7)vs 6.7 (2.2) mg/dL, p=0.016. Unexpectedly, function and quality-of-life scores improved: HAQ score 0.65 (2.16) vs 0.12 (0.17), p= 0.001. Seven patients were COVID-19-confirmed cases; they had significantly more flares, higher urate levels and lower allopurinol doses and two died. CONCLUSIONS: In gout patients, flares were 9 times more frequent during pandemic also, they had increased urate levels but led to an unexpected improvement in HAQ and functionality scores. Resilience and lifestyle changes in gout during COVID-19 pandemic require further studies. Key Points ⢠COVID-19 pandemic is associated with 4 times more flares in gout patients. ⢠Increased flares were also seen in previously well-controlled gout patients. ⢠Increased serum urate levels were also found in gout patients during pandemic. ⢠In our gout clinic, 8/101 patients were diagnosed as COVID-19+, and two of them died.
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COVID-19 , Gota , Alopurinol/uso terapéutico , Gota/tratamiento farmacológico , Gota/epidemiología , Supresores de la Gota/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , Calidad de Vida , SARS-CoV-2 , Ácido ÚricoRESUMEN
BACKGROUND: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia. METHODS: This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 31) or placebo (n = 29) twice daily during 30 days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30 days thereafter. RESULTS: Oral administration of allopurinol 300 mg twice daily was ineffective in improving pain scores measured by several tools up to 30 days of treatment (P > 0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study. CONCLUSIONS: Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30 days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.
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Alopurinol , Fibromialgia , Alopurinol/uso terapéutico , Animales , Método Doble Ciego , Femenino , Fibromialgia/tratamiento farmacológico , Supresores de la Gota/uso terapéutico , Humanos , Dolor/tratamiento farmacológico , Estudios Prospectivos , Resultado del Tratamiento , Ácido Úrico/uso terapéuticoRESUMEN
BACKGROUND: Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate. METHODS: In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated. RESULTS: The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. CONCLUSION: The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated.
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Anfotericina B/farmacología , Antiprotozoarios/farmacología , Enfermedades de los Perros/parasitología , Leishmania infantum/efectos de los fármacos , Leishmaniasis Visceral/parasitología , Fosforilcolina/análogos & derivados , Alopurinol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Resistencia a Medicamentos , Femenino , Leishmaniasis Visceral/tratamiento farmacológico , Antimoniato de Meglumina/uso terapéutico , Fosforilcolina/farmacología , Fosforilcolina/uso terapéuticoRESUMEN
Background: Canine visceral leishmaniasis is a worldwide zoonosis, with dogs being the main urban reservoirs. It is caused by a protozoan of the genus Leishmania spp. and is transmitted to mammals through a vector belonging to the phlebotomines family. Its treatment aims to reduce the parasitic load preventing these animals from being transmitters. Immunotherapy has been shown to be efficient in stimulating the patients immune response, improving the general condition and preventing recurrence. This report describes the case of a dog diagnosed with canine visceral leishmaniasis submitted to immunotherapy and drug protocol, noting significant general improvement. Case: An 8-year-old female dog was treated with ulcerated lesions on the paw pads, nasal plane and lip region, onychogryphosis and ungeitis, in addition, hypertrophied popliteal lymph nodes and erosive lesions in the elbows, without improvement with previous treatments. Serological examination was then performed to diagnose leishmaniasis by the immunosorbent assay (ELISA) technique with negative results. In addition, was performed puncture of the popliteal lymph node, sample in which amastigote forms of Leishmania were observed and blood sample analysis by immunochromatographic rapid test showing reagent result, confirming the diagnosis of canine visceral leishmaniasis. The treatment protocol with marbofloxacin, allopurinol, prednisolone and domperidone was initiated. Thirty days later, there was a total improvement of the lesions and healing of the paw pads. Immunotherapy was then initiated by applying three double doses of recombinant vaccine against canine visceral leishmaniasis. The applications were made subcutaneously, with an interval of 21 days between them, still maintaining allopurinol. After six months a...(AU)
Asunto(s)
Animales , Femenino , Perros , Inmunoterapia Activa/métodos , Inmunoterapia Activa/veterinaria , Leishmaniasis Visceral/terapia , Leishmaniasis Visceral/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Alopurinol/uso terapéutico , Prednisolona/uso terapéutico , Domperidona/uso terapéuticoRESUMEN
INTRODUCTION: Essential amino acid α-keto acid analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid α-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion. OBJECTIVE: To evaluate the effect of essential amino acid α-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats. MATERIALS AND METHODS: Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid α-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid α-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity. RESULTS: The essential amino acid α-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid α-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid α-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups. CONCLUSIONS: This is a new report on the nephroprotective effects of essential amino acid α-keto acid analogs against ischemia-reperfusion injury. Essential amino acid α-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.
Introducción. Los α-cetoanálogos de aminoácidos esenciales se utilizan en el tratamiento de la enfermedad renal crónica para retrasar los síntomas de la uremia. Sin embargo, se desconoce si los α-cetoanálogos de aminoácidos esenciales afectan el estrés oxidativo y la inflamación en la lesión renal aguda tal como en la producida por la isquemia-reperfusión. Objetivo. Evaluar el efecto de las α-cetoanálogos de aminoácidos esenciales sobre la lesión renal por isquemia-reperfusión en ratas Wistar. Materiales y métodos. Se emplearon 11 grupos de ratas (n=6): dos grupos recibieron solución salina fisiológica con lesión isquemia-reperfusión o sin ella (45 min/24 h), seis grupos recibieron α-cetoanálogos de aminoácidos esenciales (400, 800 o 1.200 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella (α-cetoanálogos de aminoácidos esenciales + isquemia-reperfusión), y dos grupos recibieron (50 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella. Los marcadores bioquímicos incluyeron creatinina y nitrógeno ureico en sangre (BUN), citocinas proinflamatorias (IL-1ß, IL-6 y TNF-α), marcadores de daño renal (cistatina C, KIM-1 y NGAL) y marcadores del estrés oxidativo como el malondialdehído (MDA) y la actividad antioxidante total. Resultados. Los grupos tratados con α-cetoanálogos de aminoácidos esenciales y alopurinol tuvieron niveles inferiores de creatinina, BUN, marcadores de daño renal, citocinas proinflamatorias, actividad antioxidante total y MDA que los grupos isquemia-reperfusión correspondientes. Estos cambios se asociaron con la dosis. La actividad antioxidante total fue menor en los grupos tratados con α-cetoanálogos de aminoácidos esenciales que en los grupos isquemia-reperfusión correspondientes. Conclusiones. Este es un nuevo informe de los efectos nefroprotectores de las α-cetoanálogos de aminoácidos esenciales contra la lesión isquemia-reperfusión. Los α-cetoanálogos de aminoácidos esenciales disminuyeron los niveles de los marcadores bioquímicos, de los de lesión renal, de las citocinas proinflamatorias y el MDA, a la vez que minimizaron el consumo total de antioxidantes.
Asunto(s)
Aminoácidos Esenciales/uso terapéutico , Antioxidantes/uso terapéutico , Cetoácidos/uso terapéutico , Riñón/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Alopurinol/uso terapéutico , Aminoácidos Esenciales/administración & dosificación , Animales , Antioxidantes/análisis , Biomarcadores , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Cistatina C/sangre , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Cetoácidos/administración & dosificación , Riñón/patología , Lipocalina 2/sangre , Masculino , Malondialdehído/sangre , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Wistar , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Daño por Reperfusión/prevención & controlRESUMEN
The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.
Asunto(s)
Antiprotozoarios , Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Compuestos Organometálicos , Alopurinol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/veterinaria , Liposomas/uso terapéutico , Meglumina/uso terapéutico , Antimoniato de Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Polietilenglicoles/uso terapéuticoRESUMEN
In the present study, we reported the natural infection by Leishmania sp. in a domestic cat, in which the amastigote forms of the parasite were observed within a lesion on its ear-tip. Fragment of the lesion was obtained and cultured in NNN medium, and PCR-RFLP analysis of the isolated sample was performed, which revealed that the profile was compatible with Leishmania (L.) amazonensis. This is the first proven case of a cat infected by L. (L.) amazonensis reported in Belém city, Pará state, northern Brazil.