Análise dos mecanismos pró-inflamatórios do ácido úrico solúvel: efeito sobre proteínas sensíveis à modulação redox e sobre a polarização de células THP-1 / Analysis of the pro-inflammatory mechanisms of soluble uric acid: effect on redox sensitive proteins and THP-1 cell polarization

Vários estudos epidemiológicos estabelecem correlação positiva entre os níveis de ácido úrico sérico e o aumento do risco para doenças cardiovasculares. Fatores dietéticos e socioeconômicos, além da presença de comorbidades estão diretamente associados aos níveis séricos de ácido úrico. Países desenvolvidos apresentam maior incidência e prevalência da gota e alguns grupos étnicos são particularmente susceptíveis à hiperuricemia. Cristais de ácido úrico são descritos por iniciar e perpetuar resposta inflamatória, e sinalizar um padrão de resposta molecular associado ao dano (DAMP), permitindo a diferenciação de macrófagos para perfis pró-inflamatórios. Por outro lado, os efeitos do ácido úrico em sua forma solúvel ainda carecem de estudos. Macrófagos derivados de precursores monocíticos apresentam diferenciação específica e respondem a um conjunto de fatores extrínsecos, resultando em perfis distintos, um fenômeno conhecido como polarização. Assim, os macrófagos podem ser classicamente ativados para uma resposta Th1 (T helper 1) e polarizados a um perfil pró- inflamatório (M1, resposta Th1) ou a um perfil alternativo e oposto, um perfil de resolução da inflamação (M2, resposta Th2, T helper 2). Nesse sentindo, buscamos analisar os efeitos do ácido úrico solúvel sobre vias de modulação da polarização fenotípica de macrófagos e modificação redox. Utilizamos a linhagem monocítica humana THP-1, a qual foi diferenciada em macrófagossímile por acetato miristato de forbol (PMA; 5 ng.mL-1) por 48 h, seguidas da incubação com ácido úrico em meio ausente de tióis e soro fetal bovino por 8h ou 24h (0-1000 µM). A expressão de fatores de transcrição e marcadores de polarização foi realizada através de citometria de fluxo, western-blotting e por microscopia de fluorescência com alto conteúdo de imagens (HCI). Em concentrações fisiológicas, verificamos que o ácido úrico solúvel regulou positivamente a frequência de células para receptor manose CD206, um marcador clássico de perfil alternativo/M2 e regulou negativamente a expressão óxido nítrico sintase induzível (iNOS), um marcador M1, sugerindo inicialmente uma modulação para o perfil de polarização M2. Além disso, as proteínas redoxsensíveis, heme oxigenase-1 (HO-1) e tiorredoxina (Trx) tiveram sua expressão reduzida e aumentada, respectivamente, pelo tratamento com ácido úrico. Os fatores de transcrição Nrf2 e STAT3 tiveram regulação negativa após a exposição ao ácido úrico solúvel. Os resultados apresentados nesta tese sugerem uma função do urato no priming de macrófagos através da alteração da polarização destas células

Several epidemiological studies have established a positive correlation between high serum uric acid levels and increased risk for cardiovascular diseases. Developed countries have a higher incidence and prevalence of gout and some ethnic groups are particularly susceptible to hyperuricemia. Although hyperuricemia is a prevalent condition, it has still controversy biological consequences. Uric acid crystals are described as capable of initiating and perpetuating inflammatory responses, by activating the damage-associated molecular response pattern (DAMP) cascade, allowing macrophage differentiation to inflammatory profiles. In spite of that, biological response to soluble uric acid are not completely understood. Monocyte-derived macrophages respond to a set of extrinsic factors that result in different profiles and can be polarized to a proinflammatory (M1) or anti-inflammatory (M2) profile. In this thesis, we analyzed the effects of soluble uric acid on redox-modulated pathways and the phenotypic polarization of macrophages. We used human monocytic THP-1 cell line, differentiated into macrophage by phorbol myristate acetate (PMA; 5 ng.mL-1) for 48 h. After differentiation, cells were incubated with soluble uric acid in medium without thiols and fetal bovine serum for 8 h and 24 h (0-1000 µM). The expression of transcription factors and polarization markers were assessed by flow cytometry, western-blotting and fluorescence microscopy with high content imaging (HCI). At physiological concentrations, soluble uric acid positively regulated the frequency of cells for mannose receptor CD206, a classic marker of the anti-inflammatory M2 profile and negatively regulated the inducible nitric oxide synthase (iNOS) expression, a proinflammatory M1 marker, suggesting that the soluble uric acid changes the polarization profile to M2 profile. In addition, the redox-sensitive proteins heme oxygenase-1 (HO-1) and thioredoxin (Trx) had their expression decreased and increased, respectively, after exposure to urate. STAT3 and Nrf2 transcription factors were downregulated upon soluble uric acid exposure. The results presented in this thesis suggest a role of uric acid in macrophage priming through the alteration of cell polarization

Development and validation of a simple and noninvasive method for salivary uric acid: potential applications for monitoring the salivary uric acid level in healthy volunteers and gout patients

Abstract Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future

Ácido úrico y gamma-glutamiltransferasa como biomarcadores de enfermedad cardiovascular a través del estrés oxidativo / Uric acid and gamma-glutamyltransferase as biomarkers of cardiovascular disease via oxidative stress

Introducción: Las enfermedades cardiovasculares constituyen la principal causa de mortalidad y morbilidad a nivel mundial. Reconocidas como problemas de salud de impacto social, han motivado a muchos científicos a tratar de explicar su patogénesis. Actualmente se plantea de la existencia de otros factores de riesgo, independientemente de los clásicos. Entre estos factores se describen el papel de las altas concentraciones de ácido úrico y la actividad de la enzima gamma-glutamiltransferasa en sangre, biomarcadores de estrés oxidativo. Estos elementos que de manera individual pudieran contribuir a las enfermedades cardiovasculares, parecen tener un efecto sinérgico. Objetivo: Revisar las evidencias que sostienen que altas concentraciones de ácido úrico y la actividad de la enzima gamma-glutamiltransferasa en sangre pueden constituir factores de riesgo que desde el estrés oxidativo contribuyan a las enfermedades cardiovasculares. Métodos: Se recopiló la información a partir de las bases de datos de diferentes buscadores (Medline-Pubmed, Cochrane, Scopus y SciELO) entre el 1 de marzo del 2019 y el 23 de mayo 2020. Conclusiones: Se encontró que, tanto el ácido úrico como la gamma-glutamiltransferasa son productos horméticos que a bajas concentraciones tienen efecto antioxidante en el organismo, pero al elevarse involucran la ocurrencia de procesos oxidativos que conducen a la disfunción endotelial y las enfermedades cardiovasculares(AU)

Introduction: Cardiovascular diseases are the leading cause of mortality and morbidity worldwide. Recognized as a health problem of social impact; they have prompted many scientists to try to explain their pathogenesis. New risk factors are currently acknowledged alongside the classic ones. These factors include the role of high uric acid concentrations and the activity of the enzyme gamma-glutamyltransferase in blood, both of which are biomarkers of oxidative stress. These elements may individually contribute to the development of cardiovascular diseases, and seem to have a synergistic effect. Objective: Review the evidence supporting the idea that high uric acid concentrations and the activity of the enzyme gamma-glutamyltransferase in blood may be risk factors contributing to the development of cardiovascular diseases via oxidative stress. Methods: Data were collected from the databases of various search engines (Medline-Pubmed, Cochrane, Scopus and SciELO) from 1 March 2019 to 23 May 2020. Conclusions: It was found that uric acid and gamma-glutamyltransferase are hormetic products causing an antioxidant effect on the organism at low concentrations. However, when concentrations rise, they are involved in the occurrence of oxidative processes leading to endothelial dysfunction and cardiovascular diseases(AU)

Upper urinary tract stone compositions: the role of age and gender

ABSTRACT Objective: To analyze the compositions of upper urinary tract stones and investigate their distributions in different gender and age groups. Materials and Methods: Patients diagnosed with upper urinary tract stone disease between December 2014 and March 2018 were retrospectively reviewed. Patient's age, gender, BMI, comorbidities, stone event characteristics, and compositions were collected, and proportions of stone components in different gender and age groups were analyzed. Results: A total of 1532 stone analyses were performed (992 from males and 540 from females). The mean age was younger in males (p <0.001). Males included more cases with larger BMI, hyperuricemia, and obesity, while females had more urinary tract infections. Multiple components were present in 61.8% of stones. Calcium oxalate (CaOx) (67.0%) was the most common component, followed by uric acid (UA) (11.8%), infection stone (11.4%), calcium phosphate (CaP) (8.0%), cystine (1.1%), brushite (0.4%), and 2, 8-dihydroxyadenine (0.2%). Men contributed with more CaOx stones than women at age 30-49 years (all p <0.01) and more UA stones at 30-59 years (all p <0.05). Women contributed with more infection stones than men in age groups 30-49 and 60-69 years (all p <0.05), and more CaP stones at 30-49 years. The prevalence peak was 50-59 years in men and 60-69 years in women. Both genders had the lowest prevalence in adolescence. Prevalence of UA stones increased while that of infection stones decreased with aging in both genders. Conclusions: Age and sex had a strong association with distribution of stone compositions in this Chinese cohort.

Effects of hyperuricemia on incident renal replacement therapy and all-cause mortality among patients with chronic kidney disease stages 3-5: a retrospective cohort study

ABSTRACT BACKGROUND: Findings regarding the effects of hyperuricemia on renal function and mortality have been inconsistent. OBJECTIVES: To investigate the effects of hyperuricemia on incident renal replacement therapy and all-cause mortality among patients with chronic kidney disease (CKD). DESIGN AND SETTING: Retrospective cohort study conducted in a medical center in Taiwan. METHODS: Patients with CKD in stages 3-5, without histories of renal replacement therapy, were consecutively recruited from 2007 to 2013. Their medical history, laboratory and medication data were collected from hospital records. The mean uric acid level in the first year of follow-up was used for analyses. Hyperuricemia was defined as mean uric acid level ≥ 7.0 mg/dl in men or ≥ 6.0 mg/dl in women. The primary outcomes were incident renal replacement therapy and all-cause mortality, and these data were retrospectively collected from hospital records until the end of 2015. RESULTS: A total of 4,381 patients were analyzed (mean age 71.0 ± 14.8 years; males 62.7%), and the median follow-up period was 2.5 years. Patients with hyperuricemia were at increased risk of incident renal replacement therapy and all-cause mortality, especially those with CKD in stages 4 or 5. Compared with patients with CKD in stage 3 and normouricemia, patients with CKD in stages 4 or 5 presented significantly higher risk of all-cause mortality only if they had hyperuricemia. CONCLUSIONS: In patients with CKD in stages 3-5, hyperuricemia was associated with higher risk of incident renal replacement therapy and all-cause mortality. Whether treatment with uric acid-lowering drugs in these patients would improve their outcomes merits further investigation.

Relación del riesgo cardiovascular global con el ácido úrico y algunos componentes del síndrome metabólico / Relation of overall cardiovascular risk with uric acid and some components of the metabolic syndrome

Antecedentes: en los últimos años se ha debatido en cuanto al papel de ácido úrico como marcador independiente del riesgo cardiovascular y como posible componente del síndrome metabólico en personas con sobrepeso y obesidad. Objetivo: demostrar la asociación entre las concentraciones de ácido úrico con el riesgo cardiovascular global, y su nexo con algunos componentes del síndrome metabólico en personas con sobrepeso y obesidad. Métodos: se realizó un estudio observacional descriptivo transversal basado en 350 sujetos con edades comprendidas entre 19 y 70 años que fueron reclutados consecutivamente de una consulta para personas con sobrepeso y obesidad. Se estudiaron variables sociodemográficas, antecedentes patológicos personales, mediciones antropométricas y tensión arterial, así como las concentraciones de glucosa, insulina, lípidos, creatinina y ácido úrico. El riesgo cardiovascular global fue evaluado mediante las tablas de Gaziano, que no emplea análisis de laboratorio. Resultados: la frecuencia de riesgo cardiovascular global moderado/alto fue de 20,6 por ciento (72/350). Los individuos con riesgo cardiovascular global moderado/alto presentaron edades superiores, incremento en el índice de conicidad y de la tensión arterial sistólica, así como concentraciones elevadas de glucosa, colesterol, triglicéridos, creatinina y ácido úrico, que los individuos con riesgo cardiovascular global bajo. La frecuencia de personas con concentraciones de ácido úrico superior o igual al percentil 50 (296,5 mujeres y 365,0 hombres) fue superior en los individuos con riesgo cardiovascular global moderado/alto (62,5 por ciento [45/72]) que en aquellos con riesgo cardiovascular global bajo (47,12 por ciento [131/278], p= 0,014). De los sujetos con hiperuricemia, el 31,5 por ciento (23/73) presentó riesgo cardiovascular global moderado/alto, en cambio, en los individuos sin hiperuricemia, la frecuencia de riesgo cardiovascular global moderado/alto fue baja (17,7 por ciento [49/277], p= 0,014). Conclusiones: el incremento de las concentraciones de ácido úrico se relacionó con un mayor riesgo cardiovascular global. Los sujetos con riesgo cardiovascular global moderado/alto mostraron niveles elevados de la mayoría de los componentes del síndrome metabólico, así como de colesterol y ácido úrico. Este último podría utilizarse como un factor de riesgo potencial de enfermedad cardiovascular a nivel de la atención primaria de salud(AU)

Background: in recent years there has been a debate about the role of uric acid as an independent marker of cardiovascular risk and as a possible component of the metabolic syndrome in overweight and obese people. Objective: to demonstrate the association between uric acid concentrations and overall cardiovascular risk, and its connection with some components of the metabolic syndrome in overweight and obese people. Methods: a transversal descriptive, observational study was carried out based on 350 subjects aged from 19 to 70 years who were consecutively recruited from a consultation for overweight and obese people. Sociodemographic variables, personal pathological history, anthropometric measurements and blood pressure were studied, as well as glucose, insulin, lipids, creatinine and uric acid concentrations. The overall cardiovascular risk was assessed using Gaziano tables, which do not use laboratory analysis. Results: the frequency of moderate/high overall cardiovascular risk was 20.6 percent (72/350). Individuals with moderate/high overall cardiovascular risk were older, had increased conicity and systolic blood pressure, as well as higher glucose, cholesterol, triglycerides, creatinine and uric acid levels than individuals with low overall cardiovascular risk. The frequency of people with uric acid concentrations greater than or equal to the 50th percentile (296.5 women and 365.0 men) was higher in individuals with moderate/high overall cardiovascular risk (62.5 percent [45/72]) than in those with low global cardiovascular risk (47.12 percent [131/278], p= 0.014). Of the subjects with hyperuricemia, 31.5 percent (23/73) presented moderate/high overall cardiovascular risk, whereas, in individuals without hyperuricemia, the frequency of moderate/high overall cardiovascular risk was low (17.7 percent [ 49/277], p= 0.014). Conclusions: the increase in uric acid concentrations was associated with an increased overall cardiovascular risk. Subjects with moderate/high overall cardiovascular risk showed elevated levels of most components of the metabolic syndrome, as well as cholesterol and uric acid. The latter could be used as a potential risk factor for cardiovascular disease at the primary health care level(AU)

The effect of gentamicin nephrotoxicity in newborn mice at breastfeeding / El efecto de la nefrotoxicidad por gentamicina en ratones recién nacidos durante la lactancia

Gentamicin can pass through the placenta. This antibiotic also enters breast milk, but its absorption in the intestine is insignificant, so that it could be only found in half of the infants' blood. In the present study, it is attempted to experimentally evaluate the toxic effect of gentamicin on the kidneys of newborn mice in breastfeeding. This study was performed on 20 female Balb/c pregnant mice weighing 30 to 35 g. The female pregnant mice were randomly divided to two groups of 10. The lactating mothers were intraperitoneally injected with gentamicin at 200 mg/kg every other day sequentially, and the normal group was injected with normal saline at the same volume. Blod samples were collected from the heart of the newborns for the evaluation of renal function. The samples were passing paraffin blocks and were staining with hematoxylin and eosin. The data were expressed as mean±SE and T-test was used. In the observations of kidney tissues of the newborns treated with gentamicin, there were several tissue injuries in comparison with the normal group such as lytic necrosis with picnotic nucleus occurred in the epithelium cells of kidney tubules. Moreover, in some epithelium cells of tubules, degeneration changes of the kind of hydropic and cytoplasmic vacuolation were observed. In the current study, though gentamicin had no significant effect on anomalies in newborns. it indicated however, that the intervention breastfeeding could have pathological effects and consequently, cause changes in the function factors of the kidneys of newborns.

La gentamicina puede pasar a través de la placenta. Este antibiótico también ingresa en la leche materna, pero su absorción en el intestino es insignificante, por lo que solo se puede encontrar en la mitad de la sangre de los recién nacidos. En el presente estudio, se intentó evaluar experimentalmente el efecto tóxico de gentamicina en los riñones de ratones recién nacidos durante la lactancia. Este estudio se realizó en 20 hembras preñadas con un peso entre 30 y 35 g. Las hembras lactantes se dividieron aleatoriamente en dos grupos de 10 animales. Las madres que amamantaron fueron tratadas con gentamicina (200 mg/kg, vía intraperitoneal), cada dos días secuencialmente, y al grupo normal se le inyectó solución salina normal en el mismo volumen. Se tomaron muestras de sangre del corazón de los recién nacidos para la evaluación de la función renal. Las muestras pasaron por bloques de parafina y se tiñeron con hematoxilina y eosina. Los datos se expresaron como media ± DE y t-test. En comparación con el grupo normal, se observaron varias lesiones en los tejidos del riñón de los ratones recién nacidos tratados con gentamicina, tal como como necrosis lítica con núcleo picnótico en las células del epitelio de los túbulos renales. Además, en algunas células del epitelio de los túbulos renales, se observaron cambios degenerativos del tipo de vacuolación hidrópica y citoplásmica. En el estudio actual, la gentamicina no tuvo un efecto significativo sobre las anomalías en los recién nacidos. Sin embargo, observamos que la intervención de amamantamiento podría tener efectos patológicos y, en consecuencia, causar cambios en los factores funcionales de los riñones en recién nacidos.

Gota úrica visceral em bobo-pequeno (Puffinus puffinus) no sul do Brasil / Visceral gout uric in manx shearwater (Puffinus puffinus) in Southern of Brazil

A gota úrica visceral é uma doença que acomete répteis, aves e mamíferos. Caracteriza-se por depósitos de cristais de urato e ácido úrico em diferentes órgãos da região visceral. O objetivo deste trabalho foi relatar um caso de gota úrica visceral em um indivíduo de bobo-pequeno (Puffinus puffinus) encontrado morto no litoral norte de Santa Catarina, sul do Brasil. No período de 20 de agosto de 2015 a 20 de abril de 2016, as praias dos municípios de Araquari, Barra do Sul, São Francisco do Sul e Itapoá foram monitoradas diariamente para o registro e a recuperação de tetrápodes marinhos mortos, incluindo aves marinhas. Foram encontrados e necropsiados 84 indivíduos. Um deles apresentou o pericárdio aderido ao miocárdio e com a coloração esbranquiçada. Os rins, o fígado e os pulmões continham inúmeros pontos esbranquiçados. A ocorrência dessa patologia na espécie foi de 1,19%. Trata-se do primeiro relato de bobo-pequeno com gota úrica visceral encontrado no Brasil.(AU)

Visceral gout uric is a disease that affects reptiles, birds and mammals. It is characterized by urate crystal deposits and uric acid in different organs of visceral region. The objective of this study was to report a case of visceral urica drop in a manx shearwater individual (Puffinus puffinus) found dead on the north coast of Santa Catarina, Southern Brazil. In the period from 20 August 2015 and 20 April 2016, beaches in the municipalities of Araquari, Barra do Sul, São Francisco do Sul and Itapoá, were monitored daily for the registration and recovery of dead marine tetrapods, including seabirds. Eighty-four were found and necropsied. One of them was whitish in color and had the pericardium adhered to the myocardium. The kidneys, liver and lungs contained numerous whitish dots. The occurrence of this disease in the species was 1.19%. This is the first manx shearwater report with visceral urica drop found in Brazil.(AU)

Evaluation of salivary oxidative parameters in overweight and obese young adults

ABSTRACT Background Obesity is characterized by a deposition of abnormal or excessive fat in adipose tissue, and is linked with a risk of damage to several metabolic and pathological processes associated with oxidative stress. To date, salivary oxidative biomarkers have been minimally explored in obese individuals. Thus, the aim of this study was to assess the concentrations of salivary oxidative biomarkers (ferric-reducing antioxidant power, uric acid, sulfhydryl groups) and lipid peroxidation in obese and overweight young subjects. Materials and methods Levels of lipid peroxidation, ferric-reducing antioxidant power, uric acid, and SH groups were determined in the saliva and serum of 149 young adults, including 54 normal weight, 27 overweight, and 68 obese individuals. Anthropometric measurements were also evaluated. Results Salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, as well as serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation were higher in obese patients when compared with individuals with normal weight. There were correlations between salivary and serum ferric-reducing antioxidant power and salivary and serum uric acid in the obese and normal-weight groups. Conclusions Our results indicate that the increase in salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, and serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation could be related to the regulation of various processes in the adipose tissue. These findings may hold promise in identifying new oxidative markers to assist in diagnosing and monitoring overweight and obese patients.

Relationship between oxidative stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats

To study what kind of role uric acid play on the relationship between oxidative Stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats. Twenty-six eight male Wistar rats were divided into two groups randomly. Potassium oxonate was used to establish hyperuricemic model for four weeks. In 2nd and 4th week, uric acid (UA) level, total superoxide dismutase (T-SOD), Gu,Zn-SOD activity and interleukin-1beta (IL-1ß) concentration in serum were determined respectively. In 4th week, one hour after last PO treatment, five rats of every group were given Evans Blue to test blood-brain barrier (BBB) permeability. Other brains were obtained to analysis T-SOD, Gu,Zn-SOD activity and IL-1ß concentration in cerebral system. Meanwhile, brain and kidney were stained with hematoxylin and eosin (H&E) to observe pathological change. In 2nd week, both of T-SOD and Gu,Zn-SOD activity in serum increased obviously (P<0.05) in hyperuricemia rats. However, IL-1ß content didn't change remarkably. In the 4th week, T-SOD activity in model group had become similar with control group, and at the same time IL-1ß content in serum increased significantly (P<0.05). Pathological section showed the structural and functional unit of the kidney had been damaged. On the contrary, both of T-SOD and Gu,Zn-SOD activity in brain increased obviously (P<0.05), but IL-1ß concentration was no significant difference between two groups. In addition, the results of Evans Blue and H&E suggested the integrity of BBB and structure of brain were not changed after PO treatment. The permeability of BBB and form of UA would be potential factors to decide what kind role UA play on keeping balance between anti-oxidative stress and induction of inflammatory response.

Can a dual-energy computed tomography predict unsuitable stone components for extracorporeal shock wave lithotripsy?

PURPOSE: To assess the potential of dual-energy computed tomography (DECT) to identify urinary stone components, particularly uric acid and calcium oxalate monohydrate, which are unsuitable for extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: This clinical study included 246 patients who underwent removal of urinary stones and an analysis of stone components between November 2009 and August 2013. All patients received preoperative DECT using two energy values (80 kVp and 140 kVp). Hounsfield units (HU) were measured and matched to the stone component. RESULTS: Significant differences in HU values were observed between uric acid and nonuric acid stones at the 80 and 140 kVp energy values (p or =90%, calcium oxalate dihydrate group: monohydrate<90%). Significant differences in HU values were detected between the two groups at both energy values (p<0.001). CONCLUSIONS: DECT improved the characterization of urinary stone components and was a useful method for identifying uric acid and calcium oxalate monohydrate stones, which are unsuitable for ESWL.

Evaluation of low-dose dual energy computed tomography for in vivo assessment of renal/ureteric calculus composition

PURPOSE: This study aimed to assess the accuracy of low-dose dual-energy computed tomography (DECT) in predicting the composition of urinary calculi. MATERIALS AND METHODS: A total of 52 patients with urinary calculi were scanned with a 128-slice dual-source DECT scanner by use of a low-dose protocol. Dual-energy (DE) ratio, weighted average Hounsfield unit (HU) of calculi, radiation dose, and image noise levels were recorded. Two radiologists independently rated study quality. Stone composition was assessed after extraction by Fourier transform infrared spectroscopy (FTIRS). Analysis of variance was used to determine if the differences in HU values and DE ratios between the various calculus groups were significant. Threshold cutoff values to classify the calculi into separate groups were identified by receiver operating characteristic curve analysis. RESULTS: A total of 137 calculi were detected. FTIRS analysis differentiated the calculi into five groups: uric acid (n=17), struvite (n=3), calcium oxalate monohydrate and dihydrate (COM-COD, n=84), calcium oxalate monohydrate (COM, n=28), and carbonate apatite (n=5). The HU value could differentiate only uric acid calculi from calcified calculi (p80% sensitivity and specificity to differentiate them. The DE ratio could not differentiate COM from COM-COD calculi. No study was rated poor in quality by either of the observers. The mean radiation dose was 1.8 mSv. CONCLUSIONS: Low-dose DECT accurately predicts urinary calculus composition in vivo while simultaneously reducing radiation exposure without compromising study quality.

Gestational hypertension; maternal and fetal outcome in women with role of hyperurecemia

Aim of the study was to ascertain prospectively the prognostic value of serum uric acid for fetal and maternal outcomes in women with gestational hypertension. This prospective study was conducted at department of Gynae and Obs, Maternal and Child Health Center, PIMS Islamabad, from January to December 2003. A total of 200 women with a gestational age >20 weeks, and blood pressure >130/90 mmHg were inducted in the study. At presentation serum uric acid, creatinine, hemoglobin, and platelets were measured along with blood pressure. All patients were divided into group A [uric acid <4.5 mg/dl] and group B [>4.5 mg/dl] and were followed for one month after the delivery to record pregnancy and neonatal outcome. A significant difference [p<0.05] in the levels of uric acid, hemoglobin, platelet count, creatinine and blood pressure was noted between patients of group A and B. A significant decrease [p<0.05] in preterm delivery, baby birth weight and increase in fetal mortality was noted in patients of group B as compared to those of group A. Regarding maternal outcome preeclampsia [p=0.005, CI: 0.143-0.689], deranged liver functions [p=0.000, CI: 0.062-0.397], and disseminated intravascular coagulation [p=0.005; CI: 0.049-0.626] was noted in patients of group B as compared to group A. The patients of Group B showed a significant low birth weight, increased fetal mortality rate [p=0.005, CI: 0.030-0.622] and more chances of shifting neonates to NICU [p=0.002, CI: 0.164-0.667] as compared to those of group A. Hyperuricaemia in setting of gestational hypertension was associated with adverse fetal and maternal outcome

Medical and Dietary Therapy for Kidney Stone Prevention

The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention.

Caspase-1 Level in Synovial Fluid Is High in Patients with Spondyloarthropathy but Not in Patients with Gout

Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis. The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to elucidate the clinical significance of caspase-1 levels in synovial fluid. Caspase-1, IL-1beta, IL-18, and uric acid were measured in synovial fluid from 112 patients with gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondyloarthropathy was 35.9 +/- 86.7, 49.7 +/- 107.7, 2.1 +/- 7.0, and 152.6 +/- 155.7 pg/mL, respectively. The mean level and the frequency of high levels (> or =125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than those in the other arthritides including gout. Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis, the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.

Associação entre ácido úrico e variáveis de risco cardiovascular em uma população não hospitalar / Association between uric acid and cardiovascular risk variables in a non-hospitalized population / Asociación entre ácido úrico y variables de riesgo cardiovascular en una población no hospitalaria

FUNDAMENTO: A associação entre ácido úrico (AU) e as variáveis de risco cardiovascular permanece controversa em estudos epidemiológicos. OBJETIVO: Avaliar a associação entre o AU, pressão arterial (PA), índices antropométricos e variáveis metabólicas em população não hospitalar estratificada por quintis de AU. MÉTODOS: Em estudo observacional transversal, foram avaliados 756 indivíduos (369M), com idade de 50,3 ± 16,12 anos, divididos em quintis de AU. Foram obtidos PA, índice de massa corporal (IMC), circunferência abdominal (CA), AU, glicose, insulina, HOMA-IR, colesterol (CT), LDL-c, HDL-c, triglicerídeos (TG), creatinina (C). Foi calculada a taxa de filtração glomerular estimada (TFGE) e considerada hipertensão arterial (HA) quando a PA > 140x90 mmHg, sobrepeso/obesidade (S/O) quando IMC > 25 kg/m² e síndrome metabólica (SM) de acordo com a I Diretriz Brasileira de SM. RESULTADOS: 1) Não houve diferença entre os grupos na distribuição por sexo e faixa etária; 2) Os maiores quintis de AU apresentaram maiores médias de idade (p < 0,01), IMC, CA (p < 0,01), PAS, PAD (p < 0,001), CT, LDL-c, TG (p < 0,01), C e TFGE (p < 0,001) e menor média de HDL-c (p < 0,001); 3) O grupo com maior quintil de AU mostrou maiores prevalências de HA, S/O e SM (p < 0,001); 4) Maiores percentuais dos menores quintis de insulina (p < 0,02) e de HOMA-IR (p < 0,01) foram encontrados nos menores quintis de AU; 5) Em análise de regressão logística, o AU e as variáveis que compõem a SM apresentaram-se associados à ocorrência de SM (p < 0,01). CONCLUSÃO: Maiores quintis de ácido úrico associaram-se a pior perfil de risco cardiovascular e a pior perfil de função renal na amostra populacional não hospitalar estudada.

BACKGROUND: The association between uric acid (UA) and cardiovascular risk variables remains a controversial issue in epidemiological studies. OBJECTIVE: To evaluate the association between UA, blood pressure (BP), anthropometric indices and metabolic variables in a non-hospitalized population stratified by UA quintiles. METHODS: A cross-sectional observational study evaluated 756 individuals (369 males), aged 50.3 ± 16.12 years, divided in UA quintiles. BP, body mass index (BMI), abdominal circumference (AC), UA, glucose, insulin, HOMA-IR, total cholesterol (TC), LDL-c, HDL-c, triglycerides (TG) and creatinine (C) levels were obtained. The estimated glomerular filtration rate (eGFR) was calculated and arterial hypertension (AH) was considered when BP > 140x90 mmHg, overweight/obesity (OW/O) was considered when BMI > 25 kg/m² and metabolic syndrome (MS) was established according to the I Brazilian Guideline of MS. RESULTS: 1) There was no difference between the groups regarding the distribution by sex and age range; 2) The highest UA quintiles presented higher mean age (p < 0.01), BMI, AC (p < 0.01), SBP, DBP (p < 0.001), TC, LDL-c, TG (p < 0.01), C and eGFR (p < 0.001) and lower mean HDL-c (p < 0.001); 3) The group with the highest UA quintile showed higher prevalence of AH, OW/O and MS (p < 0.001); 4) Higher percentages of the lowest quintiles of insulin (p < 0.02) and HOMA-IR (p < 0.01) were observed with the lowest quintiles of UA; 5) A logistic regression analysis showed that UA and the variables that compose MS were associated with the occurrence of MS (p < 0.01). CONCLUSION: Higher quintiles of uric acid were associated with a worse cardiovascular risk profile and a worse kidney function profile in the non-hospitalized population sample studied.

FUNDAMENTO: La asociación entre ácido úrico (AU) y las variables de riesgo cardiovascular permanece controvertida en estudios epidemiológicos. OBJETIVO: Evaluar la asociación entre el AU, presión arterial (PA), índices antropométricos y variables metabólicas en población no hospitalaria estratificada por quintiles de AU. MÉTODOS: En estudio observacional transversal, se evaluaron a 756 individuos (369 hombres), con promedio de edad de 50,3 ± 16,12 años, divididos en quintiles de AU. Se obtuvieron PA, índice de masa corporal (IMC), circunferencia abdominal (CA), dosis de AU, glucosa, insulina, HOMA-IR, colesterol (CT), LDL-c, HDL-c, triglicéridos (TG), creatinina (C). Se calculó la tasa de filtración glomerular estimada (TFGE) y considerada como hipertensión arterial (HA) cuando la PA > 140 x 90 mmHg, sobrepeso/obesidad (S/O) cuando IMC > 25 kg/m² y síndrome metabólico (SM) de acuerdo con la I Directriz Brasileña de SM. RESULTADOS: 1) no hubo diferencia entre los grupos en la distribución por sexo y grupo de edad; 2) los mayores quintiles de AU presentaron mayores promedios de edad (p < 0,01), IMC, CA (p < 0,01), PAS, PAD (p < 0,001), CT, LDL-c, TG (p < 0,01), C y TFGE (p < 0,001) y menor promedio de HDL-c (p < 0,001); 3) el grupo con mayor quintil de AU reveló mayores prevalencias de HA, S/O y SM (p < 0,001); 4) mayores porcentuales de los menores quintiles de insulina (p < 0,02) y de HOMA-IR (p < 0,01) fueron encontrados en los menores quintiles de AU; 5) en análisis de regresión logística, el AU y las variables que componen la SM se presentaron asociados a la ocurrencia de SM (p < 0,01). CONCLUSIÓN: Mayores quintiles de ácido úrico se asociaron a un peor perfil de riesgo cardiovascular y a un peor perfil de función renal en la muestra poblacional no hospitalaria estudiada.

Metabolic factors associated with urinary calculi in children

We aimed to identify metabolic and anatomical abnormalities present in children with urinary calculi. Metabolic evaluation was done in 142 pediatric calculus formers. Evaluation included serum biochemistry; measurement of daily excretion of urinary calcium, uric acid, oxalate, citrate, and magnesium [in older children]; and measurement of calcium, uric acid, oxalate, and creatinine in random urine samples in nontoilet-trained patients. Urinary tests for cystinuria were also performed. All of the patients underwent renal ultrasonography. Sixty-one patients [42.7%] had metabolic abnormalities. Anatomical abnormalities were found in 12 patients [8.4%]. Three children [2.1%] had infectious calculi, and 3[2.1%] had a combination of metabolic and anatomic abnormalities. In 66 children [46.2%] we did not find any reasons for calculus formation [idiopathic]. Urinalysis revealed hypercalciuria in 25 [17.6%], hyperuricosuria in 23 [16.1%], hyperoxaluria in 17 [11.9%], cystinuria in 9 [6.3%], hypocitraturia in 3 [2.1%], and low urinary magnesium level in 1 [0.7%] patients. Sixteen patients [11.2%] had mixed metabolic abnormalities. Metabolic abnormalities are common in pediatric patients with urinary calculi. In our study, calcium and uric acid abnormalities were the most common, and vesicoureteral reflux seemed to be the most common urological abnormality which led to urinary stasis and calculus formation

El tratamiento con atorvastatina reduce la actividad de xantina-oxidasa unida al endotelio en pacientes con insuficiencia cardíaca crónica: ¿un posible nuevo efecto pleiotrópico? / Treatment with atorvastatin reduces the activity of xanthine oxydase bound to endothelium in patients with chronic heart failure

El aumento en la actividad de la xantina-oxidasa unida al endotelio (XOec) puedeparticipar como un importante mediador de la disfunción endotelial en la insuficiencia cardíaca crónica (IC). Las estatinas son capaces de reducir el estrés oxidativo y restaurar la disfunción endotelial a través de mecanismos independientes de la reducción del colesterol. Sin embargo, el efecto de estos fármacos en la actividad de XOec es completamente desconocido. Nosotros estudiamos la hipótesis que atorvastatina durante 8 semanas reduce la actividad de XOec de manera independiente de los cambios en el colesterol. Metodología: Un total de 25 pacientes con IC (Fracción de eyección < 40 por ciento y Clase funcional NYHA II-III) recibieron placebo por 4 semanas, seguido por 8 semanas de atorvastatina 20 mg por día. Muestras desangre fueron recolectadas basalmente, 4 semanas y 12 semanas. La actividad de XOec y los niveles de ácido úrico fueron medidos por espectrofotometría.Resultados: El tratamiento con atorvastatina, pero no el placebo, redujo la actividad de ecXO (p<0.01), los niveles de ácido úrico (p<0.05), colesterol total (p<0.01), LDL-colesterol (p<0.01) y triglicéridos (p<0.05) sin cambios en los niveles de HDL-colesterol y creatinina. Además, no se encontraron correlaciones estadísticas entre la fracción de cambio de XOec y las fracciones de cambio de parámetros lipídicos. Conclusión: El efecto beneficioso a corto plazo de la atorvastatina en relación a la mejoría de la función endotelial demostrado en estudios previos, estaría asociado a una disminución en la actividad de XOec de una manera independiente a los cambios en el colesterol, lo que sugiere la presencia de un nuevo efecto pleiotrópico de las estatinas.

An increased activity of endothelium bound xanthine oxydase (XOeb) may play an important role as a mediator of endothelial dysfunction in chronic heart failure (CHF). Statins reduce oxydative stress and improve endothelial dysfunction through mechanisms unrelated to cholesterol lowering. However, the effect of statins on XOeb activity is unknown. We hypothesized that atorvastatin administered for 6 weeks would reduce XOeb independently of changes in serum cholesterol levels. Methods: 25 patients with CHF (NYHA class II or III with ejection fraction <40 percent received placebo for 4 weeks followed by atorvastatin, 20mg per day, for 8 weeks. Blood samples were obtained before statin administration and 4 and 12 weeks later. Spectrophotometry was used to determine XOeb and uric aced levels. Results: Atorvastatin, but not placebo, reduced XOeb activity (p<0.01), and uric acid (p<0.05), total cholesterol (p<0.01), LDL-cholesterol (p<0.01) and triglyceride levels (p<0.05). No changes were observed inHDL and creatinine levels. There was no correlation between XOeb changes and changes in the other lipid parameters. Conclusion: The known improvement in endothelial dysfuncion related to statin use previously reported is associated to a decrease in XOec activity independently of changes in cholesterol levels, suggesting a new pleiotropic effect of statins.

Efeito do exercício de ultrarresistência sobre parâmetros de estresse oxidativo / Effect of the ultra-endurance exercise on oxidative stress parameters

INTRODUÇÃO: Exercícios de longa duração podem levar ao desequilíbrio entre os sistemas pró e antioxidante, acarretando dano a lipídeos, proteínas e DNA. Entretanto, alguns estudos avaliando triatlo Ironman observaram proteção aos lipídeos. OBJETIVO: Avaliar parâmetros de estresse oxidativo após uma competição de meio Ironman. MÉTODOS: Participaram 11 sujeitos com idade de 31,1 ± 3,3 anos, massa corporal de 72,4 ± 5,4kg, estatura de 176,2 ± 4,8cm, gordura corporal de 9,8 ± 3,3%, VO2máx na corrida de 60,7 ± 6,0mL/kg/min. Foram mensurados: dano a lipídeos através da quimiluminescência nos eritrócitos e TBARS no plasma, dano a proteínas através das carbonilas plasmáticas, ácido úrico e compostos fenólicos plasmáticos, assim como a atividade antioxidante enzimática da catalase, superóxido dismutase e glutationa peroxidase nos eritrócitos. RESULTADOS: Houve redução na atividade da enzima superóxido dismutase (23,24 ± 1,49 para 20,77 ± 2,69U SOD/mg proteína, p = 0,045), e aumento no ácido úrico (40,81 ± 10,68 para 60,33 ± 6,71mg/L, p < 0,001) logo após a competição. Não houve diferença estatisticamente significativa na atividade das enzimas antioxidantes catalase e glutationa peroxidase e nos compostos fenólicos totais, assim como não foi observado dano a lipídeos (TBARS e quimiluminescência) e proteínas (carbonilas). CONCLUSÃO: Esse grupo de atletas não sofreu estresse oxidativo, provavelmente devido à liberação de ácido úrico e outros antioxidantes no plasma.

Ultra-endurance exercises can cause imbalance between the pro and antioxidant systems, leading to lipid, protein and DNA damage. Nevertheless, some studies evaluating Ironman triathlon found protection to lipids. PURPOSE: To evaluate oxidative stress parameters after a half-Ironman competition. METHODS: Eleven subjects aged 31.1 ± 3.3 yr, body weight 72.4 ± 5.4 kg, height 176.2 ± 4.8 cm, body fat 9.8 ± 3.3%, VO2máx on run 60.7 ± 6.0 mL/kg/min, participated in this study. The following data were measured: lipid damage by chemoluminescence in erythrocyte and TBARS in plasma, protein damage by plasmatic carbonyls, uric acid and phenolic compounds, as well as the antioxidant enzymatic activity of catalase, superoxide dismutase and glutathione peroxidase in erythrocytes. RESULTS: Reduction in superoxide dismutase (23.24 ± 1.49 to 20.77 ± 2.69 U SOD/mg protein, p = 0.045), and increase in uric acid (40.81 ± 10.68 to 60.33 ± 6.71 mg/L, p < 0.001) were found immediately after the competition. No statistically significant differences were found in catalase and glutathione peroxidase or phenolic compounds. Lipid (TBARS and chemoluminescence) or protein (carbonyl) damage was not observed either. CONCLUSION: These athletes did not suffer oxidative stress, probably due to uric acid and other plasmatic antioxidants release in the plasma.

Valores de referência de parâmetros bioquímicos no sangue de duas linhagens de camundongos / Reference values for blood-based biochemical parameters in BALB/C and C57BL/6 wild-type mice

INTRODUÇÃO: Conhecer os parâmetros bioquímicos individuais de animais de laboratório utilizados na experimentação é importante, pois eles servirão como parâmetros para avaliar alterações funcionais em órgãos e como base para estabelecer valores de referência. OBJETIVO:Estabelecer valores de referência bioquímicos do sangue em camundongos das linhagens BALB/c e C57BL/6 selvagens do Biotério da Disciplina de Biologia Celular da Universidade Federal do Triângulo Mineiro (UFTM). Materiais e métodos: Foram utilizados 30 camundongos (BALB/c e C57BL/6 selvagem). Os exames realizados foram glicose, triglicérides, colesterol, proteínas totais, albumina, amilase, ácido úrico, uréia, fosfatase alcalina (kits Wiener), e as determinações foram realizadas no equipamento BIOPLUS-2000. RESULTADOS:Entre os nove analitos observou-se que quatro (albumina, glicose, proteínas totais e colesterol) apresentaram diferenças estatisticamente significativas entre as linhagens. Padronizamos como valores de referência para os camundongos os valores do intervalo de confiança (IC). Nos analitos em que houve diferença significativa entre as linhagens (p < 0,05) adotamos os valores do IC de cada linhagem; para os que não apresentaram diferenças foram utilizados os valores mínimos e máximos do IC entre as duas linhagens. CONCLUSÃO:Ao final da análise, acreditamos que os resultados obtidos sugerem a padronização de intervalos de referência próprios de cada biotério, pois refletem a condição da população para os quais os testes serão aplicados no dia-a-dia.

INTRODUCTION: Identifying individual biochemical parameters of laboratory animal species is important inasmuch as they may be used in the evaluation of functional changes in organs and in the establishment of reference values. OBJECTIVE: To establish biochemical reference values for blood tests in BALB/c and C57BL/6 wild-type mice from the Vivarium of the Department of Cellular Biology at the Federal University of "Triângulo Mineiro". MATERIALS AND METHODS: Thirty wild-type mice of the lineages BALB/c and C57BL/6 were used to evaluate the serum levels of glucose, triglycerides, cholesterol, total protein, albumin, amylase, uric acid, urea and alkaline phosphatase. The determinations were performed in a BIOPLUS-2000 analyzer. Results: Four out of the nine analytes (albumin, glucose, total proteins and cholesterol) showed significant statistical differences between the strains. Confidence interval (CI) values were standardized as reference values. In those analytes in which there was significant difference between strains (p < 0.05), confidence interval values of each lineage were adopted, whereas in those ones in which there were no differences, the minimum and maximum values of confidence interval from both lineages were applied. CONCLUSION: The results show the need for reference interval standardization of each Vivarium inasmuch as it reflects the conditions of the population in which the tests will be routinely performed.