Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 879
Filtrar
1.
Cochrane Database Syst Rev ; 1: CD009497, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507555

RESUMO

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are two of the most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the people with metastatic liver disease will die from metastatic complications. Electrocoagulation by diathermy is a method used to destroy tumour tissue, using a high-frequency electric current generating high temperatures, applied locally with an electrode (needle, blade, or ball). The objective of this method is to destroy the tumour completely, if possible, in a single session. With the time, electrocoagulation by diathermy has been replaced by other techniques, but the evidence is unclear. OBJECTIVES: To assess the beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, CINAHL, ClinicalTrials.gov, ICTRP, and FDA to October 2020. SELECTION CRITERIA: We considered all randomised trials that assessed beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus comparators, in people with liver metastases, regardless of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed risk of bias of the included trial using predefined risk of bias domains, and presented the review results incorporating the certainty of the evidence using GRADE. MAIN RESULTS: We included one randomised clinical trial with 306 participants (175 males; 131 females) who had undergone resection of the sigmoid colon, and who had five or more visible and palpable hepatic metastases. The diagnosis was confirmed by histological assessment (biopsy) and by carcinoembryonic antigen (CEA) level. The trial was conducted in Iraq. The age of participants ranged between 38 and 79 years. The participants were randomised to four different study groups. The liver metastases were biopsied and treated (only once) in three of the groups: 75 received electrocoagulation by diathermy alone, 76 received electrocoagulation plus allopurinol, 78 received electrocoagulation plus dimethyl sulphoxide. In the fourth intervention group, 77 participants functioning as controls received a vehicle solution of allopurinol 5 mL 4 x a day by mouth; the metastases were left untouched. The status of the liver and lungs was followed by ultrasound investigations, without the use of a contrast agent. Participants were followed for five years. The analyses are based on per-protocol data only analysing 223 participants. We judged the trial to be at high risk of bias. After excluding 'nonevaluable patients', the groups seemed comparable for baseline characteristics. Mortality due to disease spread at five-year follow-up was 98% in the electrocoagulation group (57/58 evaluable people); 87% in the electrocoagulation plus allopurinol group (46/53 evaluable people); 86% in the electrocoagulation plus dimethyl sulphoxide group (49/57 evaluable people); and 100% in the control group (55/55 evaluable people). We observed no difference in mortality between the electrocoagulation alone group versus the control group (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.94 to 1.03; 113 participants; very low-certainty evidence). We observed lower mortality in the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus the control group (RR 0.87, 95% CI 0.80 to 0.95; 165 participants; low-certainty evidence). We are very uncertain regarding post-operative deaths between the electrocoagulation alone group versus the control group (RR 1.03, 95% CI 0.07 to 16.12; 152 participants; very low-certainty evidence) and between the electrocoagulation combined with allopurinol or dimethyl sulphoxide groups versus the control group (RR 1.00, 95% CI 0.09 to 10.86; 231 participants; very low-certainty evidence). The trial authors did not report data on number of participants with other adverse events and complications, recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life. Data on failure to clear liver metastases were not provided for the control group. There was no information on funding or conflict of interest. We identified no ongoing trials. AUTHORS' CONCLUSIONS: The evidence on the beneficial and harmful effects of electrocoagulation alone or in combination with allopurinol or dimethyl sulphoxide in people with liver metastases is insufficient, as it is based on one randomised clinical trial at low to very low certainty. It is very uncertain if there is a difference in all-cause mortality and post-operative mortality between electrocoagulation alone versus control. It is also uncertain if electrocoagulation in combination with allopurinol or dimethyl sulphoxide may result in a slight reduction of all-cause mortality in comparison with a vehicle solution of allopurinol (control). It is very uncertain if there is a difference in post-operative mortality between the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus control. Data on other adverse events and complications, failure to clear liver metastases or recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life were most lacking or insufficiently reported for analysis. Electrocoagulation by diathermy is no longer used in the described way, and this may explain the lack of further trials.


Assuntos
Neoplasias do Colo , Eletrocoagulação/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Alopurinol/administração & dosagem , Causas de Morte , Dimetil Sulfóxido/administração & dosagem , Eletrocoagulação/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Solventes/administração & dosagem
2.
Medicine (Baltimore) ; 99(35): e21675, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871882

RESUMO

To assess the impact of allopurinol on diabetes in a retrospective cohort of Veterans' Affairs patients with gout.The New York Harbor VA computerized patient record system was searched to identify patients with an ICD-9 code for gout meeting at least 4 modified 1977 American Rheumatology Association gout diagnostic criteria. Patients were divided into subgroups based on >30 continuous days of allopurinol, versus no allopurinol. New diagnoses of diabetes, defined according to American Diabetes Association diagnostic criteria or clinical documentation explicitly stating a new diagnosis of diabetes, were identified during an observation period from January 1, 2000 through December 31, 2015.Six hundred six gout patients used allopurinol >30 continuous days, and 478 patients never used allopurinol. Over an average 7.9 ±â€Š4.8 years of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (11.7/1000 person-years vs 10.0/1000 person-years, P = .27). A lower diabetes incidence in the longest versus shortest quartiles of allopurinol use (6.3 per 1000 person-years vs 19.4 per 1000 person-years, P<.0001) was attributable to longer duration of medical follow-up.In this study, allopurinol use was not associated with decreased diabetes incidence. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity, and diabetes, and the potential impact of gout treatments on diabetes incidence.


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 2/epidemiologia , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alopurinol/administração & dosagem , Colchicina/uso terapêutico , Feminino , Seguimentos , Supressores da Gota/administração & dosagem , Humanos , Incidência , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , Ácido Úrico/sangue
3.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1321-1328, July-Aug. 2020. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1131480

RESUMO

Fifteen New Zealand adult rabbits were randomly allocated into three groups: Sham-operated (group A), Ischemia and Reperfusion (group B) and Carolina Rinse Solution (CRS) (group C). Groups B and C were subjected to one hour of ischemia and two hours of reperfusion. In group C, ten minutes before reperfusion, the bowel lumen was filled with CRS, and the segment immersed in CRS. Necrosis and loss of integrity of the villi were visible in groups B and C. Edema of the submucosa and circular muscle was observed in all groups. Hemorrhage was observed in different layers for groups B and C, but group C showed more severe hemorrhage in different layers during reperfusion. All groups showed polymorphonuclear leukocyte infiltration on the base of the mucosa, submucosa, and longitudinal muscle, in addition to polymorphonuclear leukocytes margination in the mucosal and submucosal vessels. Necrosis of enterocytes, muscles, crypts of Lieberkühn and myenteric plexus was observed in groups B and C during reperfusion. Topical and intraluminal Carolina Rinse Solution did not attenuate the effects of ischemia and reperfusion in the small intestine of rabbits.(AU)


Quinze coelhos da raça Nova Zelândia foram alocados em três grupos: instrumentado (grupo A), isquemia e reperfusão (grupo B) e solução de Carolina rinse (CRS) (grupo C). Os grupos B e C foram submetidos a uma hora de isquemia e a duas horas de reperfusão. No grupo C, 10 minutos antes da reperfusão, o segmento isolado foi imerso e teve seu lúmen preenchido com CRS. Os grupos B e C apresentaram necrose e perda progressiva da integridade das vilosidades. Foi observado edema na submucosa e na camada muscular circular em todos os grupos. Nos grupos B e C, foi observada hemorragia em diferentes camadas, mas, no grupo C, a hemorragia foi mais intensa durante a reperfusão. Todos os grupos apresentaram infiltrado de PMN na base da mucosa, na submucosa e na camada muscular longitudinal e marginação de PMN nos vasos da mucosa e da submucosa. Durante a reperfusão, foi observada necrose dos enterócitos, das camadas musculares, das criptas de Lieberkühn e do plexo mioentérico nos grupos B e C. O uso tópico e intraluminal de CRS não atenuou os efeitos da isquemia e da reperfusão no intestino delgado de coelhos.(AU)


Assuntos
Animais , Coelhos , Reperfusão/veterinária , Alopurinol/administração & dosagem , Desferroxamina/administração & dosagem , Glutationa/administração & dosagem , Isquemia/veterinária , Jejuno/cirurgia
4.
AAPS PharmSciTech ; 21(5): 164, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488630

RESUMO

The aim of present research work was to design, fabricate, optimize, and evaluate allopurinol (ALLO)-loaded bovine serum albumin nanoparticles (ABNPs) for kidney targeting of the drug and exploring the potential of fabricated ABNPs for management of hyperuricemia-related nephrolithiasis. ABNP formulation was prepared by employing desolvation technique, and its optimization was conducted by 2-factor-3-level central composite design (CCD) in order to achieve minimum particle size (PSA) and polydispersity index (PDI), maximum entrapment efficiency (EE), and zeta potential (ZP). Further, the optimized formulation (ABNPsopt) was also assessed for in vitro drug release study, TEM, DSC, XRD analysis, FTIR spectroscopy, and in vivo animal study. The in vivo study revealed that after 2 h of ABNPsopt administration, a significant concentration of ALLO was present in kidney (21.26-fold) as compared with serum while in case of standard pure drug group; no drug was seen in mice kidney and serum post 2 h administration, which indicates successful targeting of ALLO by formulating its albumin nanoparticles. Also, uric acid and pH levels were measured in serum and urine samples of mice which showed significant (P < 0.01) efficacy of ABNPsopt formulation in management of hyperuricemia-related nephrolithiasis. Histological studies on kidney samples also confirmed these outcomes. Findings of present study indicate higher kidney uptake of allopurinol from formulated ABNPsopt, which could be due to the specificity of albumin polymer for cubilin and megalin receptors, and it also serves as effective strategy in management of hyperuricemic-related nephrolithiasis.


Assuntos
Alopurinol/administração & dosagem , Supressores da Gota/administração & dosagem , Hiperuricemia/tratamento farmacológico , Nefrolitíase/tratamento farmacológico , Soroalbumina Bovina/química , Alopurinol/uso terapêutico , Animais , Portadores de Fármacos/química , Composição de Medicamentos , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/complicações , Rim , Camundongos , Nanopartículas/química , Nefrolitíase/complicações , Tamanho da Partícula
6.
Aliment Pharmacol Ther ; 51(11): 1076-1086, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32339331

RESUMO

BACKGROUND: Both tioguanine and low-dose thiopurines combined with allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail due to adverse events. AIM: To compare the safety of tioguanine and LDTA in IBD patients. METHODS: Inflammatory bowel disease patients who failed conventional thiopurines due to adverse events and initiated LDTA in standard care were identified in the prospective ICC Registry. IBD patients who failed conventional thiopurines due to adverse events and initiated tioguanine were enrolled in three university hospitals. Patients on concomitant biologicals were excluded. The primary outcome was discontinuation of therapy due to adverse events. Secondary outcomes included: safety outcomes and surgery-, biological- and corticosteroid-free clinical remission (physician global assessment = 0) after 104 weeks. Both multiple logistic regression and propensity score matching were used to correct for confounders. RESULTS: In total, 182 IBD patients treated with tioguanine (n = 94) or LDTA (n = 88) were included with a median follow-up of 104 weeks (IQR 91-104). Of these, 19% (tioguanine: 20%, LDTA: 18%) of patients discontinued therapy due to adverse events. After adjusting for confounders, there were no differences in terms of discontinuation rate due to adverse events (OR 0.50, 95% CI 0.15-1.68, P = 0.26), adverse events (OR 0.89, 95% CI 0.44-1.81, P = 0.75), infections (OR 1.05, 95% CI 0.40-2.73, P = 0.93), hospitalisations (OR 2.00, 95% CI 0.64-6.23, P = 0.23) or clinical remission (OR 0.74, 95%CI 0.33-1.68, P = 0.48). All results are comparable with the propensity score matched cohort. CONCLUSION: Nineteen percent of IBD patients with prior failure to conventional thiopurines due to adverse events discontinued therapy with tioguanine or LDTA due to adverse events. Either therapy may be considered before escalating to biological therapy.


Assuntos
Alopurinol/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Purinas/administração & dosagem , Tioguanina/administração & dosagem , Adulto , Alopurinol/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Purinas/efeitos adversos , Sistema de Registros , Tioguanina/efeitos adversos , Resultado do Tratamento
7.
Leuk Res ; 89: 106298, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31945598

RESUMO

While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes, such as acute kidney injury (AKI), in tumor lysis syndrome (TLS) is unknown. In this retrospective cohort study, we included all hospitalized cancer patients with hyperuricemia and AKI who received rasburicase +/- allopurinol or allopurinol alone from 2009 to 2015. Inverse probability of treatment weighting using propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. 150 patients met inclusion criteria; 89 received rasburicase +/- allopurinol and 61 received allopurinol alone. Weighted outcome regression analysis demonstrated that rasburicase was associated with significantly lower mean uric acid nadir at 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p < 0.01). However, likelihood of renal function recovery (OR = 0.90, p = 0.79), creatinine nadir by 7 days (1.80 versus 1.66 mg/dL, p = 0.51), and final creatinine by 30 days (2.08 versus 2.07 mg/dL, p = 0.98) did not significantly differ. In conclusion, the clinical benefit of rasburicase in promoting renal function recovery in cancer patietns with concurrent hyperuricemia and renal failure remains inconclusive. Our results suggest that correction of hyperuricemia as a surrogate endpoint may not be associated with significant renal function improvement, particularly if renal dysfunction is unrelated to TLS.


Assuntos
Alopurinol/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etiologia , Neoplasias/complicações , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/etiologia , Urato Oxidase/uso terapêutico , Adulto , Alopurinol/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Razão de Chances , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Síndrome de Lise Tumoral/etiologia , Ácido Úrico/urina
8.
Eur J Pharm Sci ; 141: 105116, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654756

RESUMO

Ulcerative colitis is a chronic auto-inflammatory disorder confined to the colorectal region. It is challenging to find an absolute treatment and current therapy aims to ameliorate symptoms, decrease relapses and prevent prognosis of colorectal cancer. In the present study, we investigated the possible action of xanthine oxidase inhibitors in murine colitis model by measuring different indicative parameters and comparing the results to those of the reference sulfasalazine. Also, we compared the effects of combining sulfasalazine and allopurinol to each drug alone. Dextran Sodium Sulfate (DSS) is used in this study to induce ulcerative colitis in male wistar rats as it is known to be the closest model that mimics human ulcerative colitis. Allopurinol was given prior to colitis induction by four days and febuxostat for six days before induction with DSS (5% w/v) and continue to give them concomitantly during the induction.Il-1ß, malondialdehyde, reduced glutathione (GSH), xanthine oxidase, and superoxide dismutase were measured in colonic tissue. We also measured concentrations of IL-1ß, Il-6 and uric acid in serum. Allopurinol dose-dependently ameliorated biochemical injuries. Febuxostat has shown better results than allopurinol and sulfasalazine, and this is the first study to demonstrate this.


Assuntos
Alopurinol/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Febuxostat/administração & dosagem , Xantina Oxidase/antagonistas & inibidores , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Quimioterapia Combinada , Glutationa/metabolismo , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Malondialdeído/metabolismo , Ratos Wistar , Sulfassalazina/administração & dosagem , Superóxido Dismutase/metabolismo , Ácido Úrico/sangue , Xantina Oxidase/metabolismo
9.
Expert Opin Pharmacother ; 21(1): 85-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31714803

RESUMO

Introduction: Urolithiasis is a common, highly recurrent disease with increasing prevalence worldwide. There are many dietary and pharmacological measures to prevent kidney stones.Areas covered: Herein, the authors explore medical expulsive therapy as well as pharmacological therapies to prevent/treat urolithiasis.Expert opinion: All stone formers should be advised to increase their fluid intake sufficiently to achieve a urine volume of at least 2.5 L/day. In the case of hypercalciuria, a thiazide diuretic should be prescribed while in cases of hypocitraturia, potassium citrate should be given. In the case of hyperoxaluria, the treatment depends on the type of hyperoxaluria. Pyridoxine or calcium supplements with a meal can be offered. For uric acid stone formers, alkali therapy is the standard of care whereas allopurinol can be beneficial in hyperuricosuric stone formers. For cystine stone formers, increased fluid intake, restriction of sodium and animal protein ingestion, and urinary alkalinization are the standard therapies used. Cystine binding thiol drugs such as tiopronin and D-penicillamine are reserved for patients where a conservative approach fails. For struvite stone formers, optimal management is the complete stone removal. Acetohydroxamic acid may be offered only after surgical options have been exhausted, for patients with residual stones but it has many side effects.


Assuntos
Cálculos Renais/prevenção & controle , Urolitíase/tratamento farmacológico , Alopurinol/administração & dosagem , Cálcio/administração & dosagem , Suplementos Nutricionais , Diuréticos/administração & dosagem , Humanos , Fatores de Risco
11.
Daru ; 27(2): 661-671, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31686374

RESUMO

PURPOSE: The major short coming of conventional therapy system is that they can't deliver the therapeutics specifically to a site within the body without producing nonspecific toxicity. Present research aimed at developing kidney targeted allopurinol (AP) loaded chitosan coated magnetic nanoparticles (A-MNPs) for the management of hyperuricemic nephropathy manifested in the form of nephrolithiasis. METHODS: The work includes preparation of magnetic nanoparticles by chemical co-precipitation method and evaluation of the prepared batches for particle size analysis, Transmission electron microscopy, entrapment efficiency, in-vitro release study etc. Further, FTIR spectroscopy, X-ray diffraction, Differential Scanning Calorimetry, Vibrational sample magnetometer (VSM) and in-vivo animal studies were also performed. RESULTS: VSM analysis demonstrates that the prepared nanoparticles exhibit superparamagnetic magnetic behaviour which was retained even after coating by chitosan. In-vivo studies of A-MNPs showed 19.07-fold increase in kidney uptake of AP as compared to serum post 2 h of administration in mice whereas no drug was detected in kidney and serum post 2 h administration of pure drug (free-form) indicating successful targeting to kidney as well as sustained release of AP from the formulated A-MNPs. The significant (p < 0.01) effectiveness of A-MNPs in management of hyperuricemic nephrolithiasis was observed through estimating pH and uric acid levels in urine and serum samples of mice. These findings were also confirmed by histological examination of isolated kidney samples. CONCLUSION: Present investigation signifies that a simple external magnetic field is enough for targeting allopurinol to kidneys by formulating A-MNPs which further offers an effective approach for management of hyperuricemic nephrolithiasis. Graphical Abstract.


Assuntos
Alopurinol/administração & dosagem , Quitosana/química , Rim/química , Nefrolitíase/tratamento farmacológico , Administração Oral , Alopurinol/química , Alopurinol/farmacocinética , Animais , Precipitação Química , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Nanopartículas de Magnetita , Camundongos , Nanopartículas , Nefrolitíase/sangue , Nefrolitíase/induzido quimicamente , Nefrolitíase/urina , Ácido Oxônico/efeitos adversos , Ácido Úrico/sangue , Ácido Úrico/urina
13.
Biomolecules ; 9(10)2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614639

RESUMO

We investigated whether short term high fructose intake may induce early hepatic dysfunction in rats and to test whether allopurinol treatment may have beneficial effects. Twenty male Sprague-Dawley rats received 20% fructose in drinking water (10 treated with allopurinol and 10 received vehicle) and 10 control rats received tap water. After 14 days, the hepatic response to an acute fructose load was evaluated, and in fasted animals, respirometry studies in freshly isolated mitochondria were performed. In fasting rats, we did not find differences in systemic or hepatic uric acid and triglyceride concentrations among the groups, but mitochondrial respiratory control rate was significantly decreased by high fructose feeding and correlated with a reduced expression of Complex I, as well as decreased aconitase-2 activity. On the other hand, in fructose fed rats, an acute fructose load increased systemic and hepatic uric acid, triglycerides and oxidative stress. Fructose feeding was also associated with fructokinase and xanthine oxidase overexpression and increased liver de novo lipogenesis program (fatty acid synthase (FAS) and cell death-inducing DFFA-like effector C (CIDEC) overexpression, ATP citrate lyase (ACL) and acetyl coA carboxylase (ACC) overactivity and decreased AMP-activated protein kinase (AMPk) and endothelial nitric oxide synthase (eNOS) activation). Allopurinol treatment prevented hepatic and systemic alterations. These data suggest that early treatment with xanthine oxidase inhibitors might provide a therapeutic advantage by delaying or even halting the progression of non-alcoholic fatty liver disease (NAFLD).


Assuntos
Alopurinol/farmacologia , Frutose/antagonistas & inibidores , Lipogênese/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Administração Oral , Alopurinol/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Frutose/administração & dosagem , Frutose/farmacologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Ratos Sprague-Dawley
14.
Eur J Clin Pharmacol ; 75(12): 1669-1674, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31587102

RESUMO

PURPOSE: Many patients with Crohn's disease (CD) and ulcerative colitis (UC) who have a high 6-methylmercaptopurine/6-thioguanine (6-MMP/6-TGN) ratio receive allopurinol 100 mg in addition to thiopurines to optimize metabolite concentrations. However, some patients do not tolerate allopurinol at this dosage. The aim of this study was to determine the intra-patient effect of reducing the allopurinol dosage from 100 to 50 mg, in terms of metabolite concentrations, enzyme activities, efficacy, and tolerability. METHODS: A prospective non-inferiority one-way crossover study was performed. CD and UC patients with stable disease using a thiopurine and allopurinol 100 mg were switched to 50 mg for 1 month. Primary outcomes were thiopurine metabolite concentrations. Secondary outcomes were enzyme activities of xanthine oxidase, thiopurine methyltransferase and hypoxanthine-guanine phosphoribosyltransferase, disease activity, and tolerability. RESULTS: Twenty-two patients were included. Treatment with allopurinol 50 mg compared with 100 mg resulted in a significant decrease in mean 6-TGN levels (761 to 625 pmol/8 × 108 RBC; p = 0.005) and a significant increase in mean 6-MMP levels (451 to 665 pmol/8 × 108 RBC; p = 0.01). However, the mean metabolite concentrations were still therapeutic. Enzyme activities, disease activity scores, and patient experiences did not alter significantly. Generally, UC patients were more positive about their improved treatment than CD patients. CONCLUSION: Combination therapy with 50 mg allopurinol led to a decrease of 6-TGN levels compared with 100 mg allopurinol. Disease activity, side effects, and patient experience, however, were similar between allopurinol 100 and 50 mg. UC patients seem to benefit and prefer lower doses whereas the contrary is seen in CD patients. TRIAL REGISTRATION: EudraCT trial registry - number 2016-001638-84.


Assuntos
Alopurinol/administração & dosagem , Azatioprina/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Mercaptopurina/análogos & derivados , Adulto , Idoso , Alopurinol/efeitos adversos , Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Masculino , Mercaptopurina/administração & dosagem , Mercaptopurina/metabolismo , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Tioguanina/metabolismo
15.
Int J Pharm ; 571: 118700, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31526838

RESUMO

Several diseases would benefit from prolonged drug release provided by systems retained in the stomach for extended time periods. Expandable gastroretentive devices are administered in a collapsed configuration enabling swallowing and regain in situ their native shape having larger spatial encumbrance, thus hindering voidance through the wide open pylorus. An expandable system for gastric retention was here proposed relying on the shape memory behavior of pharmaceutical-grade poly(vinyl alcohol). Different original configurations to be recovered upon exposure to aqueous fluids at 37 °C, potentially enabling gastric retention, were conceived. Prototypes containing allopurinol were directly manufactured by fused deposition modeling or shaped by purposely-designed templates from hot melt extruded rods immediately after production. Various temporary shapes, in principle suitable for administration, were programmed by manual deformation of samples by means of specific templates, under defined temperature conditions. In 0.1 N hydrochloric solution at 37 °C, the prototypes recovered their original shape, reaching the desired spatial encumbrance within few minutes. Release from the samples, although of relatively short duration, was independent of the original shape and processing undergone, and was noticeably slowed down by application of Eudragit® RS/RL-based coatings.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Impressão Tridimensional , Materiais Inteligentes/química , Resinas Acrílicas/química , Administração Oral , Alopurinol/administração & dosagem , Alopurinol/farmacocinética , Cápsulas , Química Farmacêutica , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Estudos de Viabilidade , Mucosa Gástrica/metabolismo , Modelos Químicos , Polímeros/química , Fatores de Tempo
16.
Aust J Gen Pract ; 48(9): 631-637, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31476837

RESUMO

BACKGROUND AND OBJECTIVES: The aim of this project was to determine the effects of a package of care for gout in primary care. METHOD: An audit of gout management in a single rural medical practice was undertaken before (in 2012) and after (in 2015) the introduction of the package of care reflecting guidelines in gout management. RESULTS: There was a statistically significant increase in the number of individuals commenced on allopurinol ≤100 mg/d and a decrease in the number commenced on allopurinol ≥200 mg/d (P <0.001). The number of times each patient had serum urate tested between 2012 and 2015 (median [range] 1 [0-3] versus 2 [0-10], respectively; P <0.001). Of those individuals who had at least one serum urate measurement, the number of individuals who were never at target urate was 43 out of 67 (64.2%) in 2012, compared with 52 out of 133 (39.1%) in 2015 (P = 0.001). DISCUSSION: A package of care can improve adherence to gout management guidelines in primary care.


Assuntos
Alopurinol/administração & dosagem , Colchicina/uso terapêutico , Supressores da Gota/administração & dosagem , Gota/tratamento farmacológico , Fidelidade a Diretrizes , Hiperuricemia/tratamento farmacológico , Atenção Primária à Saúde , Idoso , Alopurinol/uso terapêutico , Auditoria Clínica , Testes de Química Clínica , Protocolos Clínicos , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Gerenciamento Clínico , Feminino , Gota/sangue , Supressores da Gota/uso terapêutico , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Hiperlipidemias/terapia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/terapia , Hiperuricemia/sangue , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/terapia , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Reumatologia , População Rural , Ácido Úrico/sangue
17.
Res Vet Sci ; 126: 131-138, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491669

RESUMO

This study examines correlations among serum proteins, clinical score, body weight and kidney function biomarkers after a standard treatment course (meglumine antimoniate plus allopurinol) in twelve Canine leishmaniosis (CanL) patients at the three times points pre treatment, after treatment and after the end of treatment. The laboratory variables measured were those used for the follow-up of sick dogs along with biomarkers of kidney function: glomerular filtration rate (GFR), creatinine (Cr), urea, calcium, inorganic phosphorus, urine specific gravity (USG) and urine protein to creatinine ratio (UPC). Arterial blood pressure (systolic blood pressure, SBP), clinical score (CS) and weight were also monitored over the study period. At Tp0, GFR was within the normal range in most dogs. Hyperfiltration was detected in three patients and hypofiltration in one. In dogs showing hyperfiltration, this factor remained in the non-azotemic range over the whole study period. After treatment normal filtration values were recovered. Meglumine antimoniate did not modify GFR or USG. A significant reduction in UPC was recorded. In all dogs, clinical scores improved. Negative correlation was found between GFR and Cr, UPC and albumin (Alb) and CS and Alb, while positive correlation was detected between UPC and total globulins (GlobT), CS and GlobT, UPC and total solids (TS), SBP and CS and SBP and UPC. Our findings indicate no impacts on kidney function of the treatment of CanL with meglumine antimoniate, as no effects were produced on GFR or USG. Treatment was effective and found to reduce UPC which could suggest improved glomerular injury.


Assuntos
Antiprotozoários/uso terapêutico , Doenças do Cão/tratamento farmacológico , Nefropatias/veterinária , Leishmaniose Visceral/veterinária , Antimoniato de Meglumina/uso terapêutico , Alopurinol/administração & dosagem , Animais , Antiprotozoários/efeitos adversos , Biomarcadores , Creatinina/urina , Cães , Feminino , Taxa de Filtração Glomerular , Nefropatias/induzido quimicamente , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem
18.
Exp Parasitol ; 206: 107768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539540

RESUMO

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.


Assuntos
Alopurinol/efeitos adversos , Doenças do Cão/tratamento farmacológico , Audição/efeitos dos fármacos , Rim/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Paromomicina/efeitos adversos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Animais , Cóclea/efeitos dos fármacos , Creatinina/sangue , Doenças do Cão/parasitologia , Cães , Método Duplo-Cego , Combinação de Medicamentos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/veterinária , Injeções Subcutâneas/veterinária , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Antimoniato de Meglumina/uso terapêutico , Exame Neurológico/veterinária , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Distribuição Aleatória , Vestíbulo do Labirinto/efeitos dos fármacos
19.
Cardiol Young ; 29(9): 1160-1164, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31451121

RESUMO

OBJECTIVES: Limited data exist for management of hyperuricemia in non-oncologic patients, particularly in paediatric cardiac patients. Hyperuricemia is a risk factor for acute kidney injury and may prompt treatment in critically ill patients. The primary objective was to determine if rasburicase use was associated with greater probability normalisation of serum uric acid compared to allopurinol. Secondary outcomes included percent reduction in uric acid, changes in serum creatinine, and cost of therapy. DESIGN: A single-centre retrospective chart review. SETTING: A 20-bed quaternary cardiovascular ICU in a university-based paediatric hospital in California. PATIENTS: Patients admitted to cardiovascular ICU who received rasburicase or intravenous allopurinol between 2015 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from a cohort of 14 patients receiving rasburicase were compared to 7 patients receiving IV allopurinol. Patients who were administered rasburicase for hyperuricemia were more likely to have a post-treatment uric acid level less than 8 mg/dl as compared to IV allopurinol (100 versus 43%; p = 0.0058). Patients who received rasburicase had a greater absolute reduction in post-treatment day 1 uric acid (-9 mg/dl versus -1.9 mg/dl; p = 0.002). There were no differences in post-treatment day 3 or day 7 serum creatinine or time to normalisation of serum creatinine. The cost of therapy normalised to a 20 kg patient was greater in the allopurinol group ($18,720 versus $1928; p = 0.001). CONCLUSION: In a limited paediatric cardiac cohort, the use of rasburicase was associated with a greater reduction in uric acid levels and associated with a lower cost compared to IV allopurinol.


Assuntos
Alopurinol/administração & dosagem , Cardiopatias/complicações , Hiperuricemia/tratamento farmacológico , Urato Oxidase/administração & dosagem , Adolescente , Criança , Pré-Escolar , Creatinina/sangue , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Cardiopatias/sangue , Humanos , Hiperuricemia/sangue , Hiperuricemia/complicações , Injeções Intravenosas , Unidades de Terapia Intensiva , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...