Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study / 中国结合医学杂志

OBJECTIVE@#To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.@*METHODS@#M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.@*RESULTS@#TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).@*CONCLUSION@#TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.

Gota tofácea crónica en un adulto / Chronic tophaceous gout in an adult

Se presenta el caso clínico de un paciente de 57 años de edad, mestizo, con antecedentes de artritis reumatoidea y gota, quien acude a la consulta especializada de Dermatología del Hospital Clinicoquirúrgico Docente Celia Sánchez Manduley de Manzanillo, provincia de Granma, por presentar lesiones nodulares dolorosas diseminadas. Se realizaron estudios complementarios y biopsia de piel, cuyos resultados permitieron diagnosticar una gota tofácea crónica. El paciente llevaba tratamiento medicamentoso con prednisona, colchicina y metrotexate, pero luego de discutir el caso con los especialistas en medicina interna y reumatología se decidió sustituir la colchicina por el alopurinol.

The case report of a 57 year-old mestizo patient, is presented with a history of rheumatoid arthritis and gout who visited the specialized Dermatology department of Celia Sánchez Manduley Teaching Clinical-Surgical Hospital in Manzanillo, Granma province, for presenting disseminated painful nodular lesions. Complementary studies and skin biopsy were carried out which results allowed to diagnose a chronic . The patient was under drugs treatment with prednisona, colchicina and metrotexate, but after discussing the case with the specialists in internal medicine and rheumatology it was decided to sustitute colchicina by alopurinol.

Efectos de la ingesta de los edulcorantes estevia y D-tagatosa sobre el metabolismo de la glucosa, ácido úrico y apetito-saciedad / Effects of stevia and D-tagatose sweeteners intake om glucose, uric acid metabolism and appetite-satiety

INTRODUCCIÓN: Si bien, los edulcorantes no nutritivos (ENN) estevia y D-tagatosa han sido reportados como seguros, han demostrado tener algunos efectos metabólicos tras su ingesta. OBJETIVO: Describir los efectos de la ingesta de estevia y D-tagatosa sobre el metabolismo de la glucosa y ácido úrico, y del apetito-saciedad, a partir de la evidencia disponible. MÉTODOS: Revisión descriptiva. Se realizó búsqueda en PubMed utilizando los siguientes términos y palabras clave: "stevia rebaudiana", "tagatose", "D-tagatose", "blood glucose", "insulin", "metabolic processes", "uric acid", "hyperuricemia", "appetite" o "satiety". El análisis de los estudios seleccionados fue discrecional. RESULTADOS: Existen estudios que demuestran efectos beneficiosos tras el consumo de estevia o D-tagatosa sobre el control glicémico, apetito y saciedad tanto en sujetos sanos como con alteraciones en el metabolismo de la glucosa. Por otra parte, un número importante de estudios que evalúan la ingesta de estevia reportan efectos nulos sobre dichos parámetros. En relación al ácido úrico, solo un estudio en sujetos con enfermedad renal crónica reporta aumento en la concentración de ácido úrico plasmático tras la ingesta de 500 mg/día de estevia. Pocos estudios han evaluado el efecto de la ingesta de D-tagatosa sobre uricemia, en sujetos sanos y diabéticos, reportando un aumento transitorio y significativo en los niveles de ácido úrico sérico, sin embargo, no se ha logrado demostrar un efecto hiperuricémico asociado. Es importante destacar que la metodología de los estudios revisados es heterogénea, especialmente en relación al tamaño muestral, tiempo, dosis y vía de adminitración del edulcorante. CONCLUSIÓN: La ingesta de estevia y D-tagatosa ha demostrado efectos beneficiosos sobre el metabolismo de la glucosa, el apetito y la saciedad. El efecto del consumo de D-tagatosa sobre ácido úrico sérico requiere mayor evidencia para demostrar su significancia clínica.

INTRODUCTION: No-nutritive sweeteners stevia and D-tagatose have been reported as safe according to their acceptable daily intake, however, they have been shown to have metabolic effects after their ingestion. OBJECTIVE: To describe the effects of stevia and D-tagatose intake on parameters associated to glucose, uric acid metabolism and on appetite-satiety, considering the available evidence. METHODS: Descriptive review. PubMed search was carried out to identify the totality of the published articles. The following terms and key words were used: "stevia rebaudiana", "tagatose", "D-tagatose", "blood glucose", "insulin", "metabolic processes", "uric acid", "hyperuricemia", "appetite" o "satiety". The analysis of the selected studies was discretionary. RESULTS: studies have shown beneficial effects of stevia and D-tagatose consumption on glycemic control, appetite and satiety in healthy subjects as well as subjects with impairment glucose metabolism. On the other hand, a significant number of studies evaluating estevia intake report null effects on these parameters. In relation to uric acid, only one study in subjects with chronic kidney disease reported an increase in plasmatic uric acid concentration after the intake of 500 mg/day of stevia. Several studies have evaluated the effect of D-tagatose intake on plasmatic uric acid, in healthy and diabetic subjects, reporting a transient and significant increase in serum uric acid levels, however, has not been able to demonstrate an associated hyperuricemic effect. It is important to highlight that the methodology of the studies reviewed is heterogeneous, especially in relation to sample size, dose administered, time and route of exposure to the sweetener. CONCLUSION: Stevia and D-tagatose intake has shown beneficial effects on glucose metabolism, appetite and satiety. The effects of the consumption of both sweeteners on uric acid require further study to demonstrate their clinic significance.

Valores de referencia de oxalato, calcio, citrato, ácido úrico, fósforo, magnesio, sulfato y sodio urinarios en alumnos de la carrera de bioquímica de la Universidad Nacional del Litoral, Argentina / Reference values for urinary oxalate, calcium, citrate, uric acid, phosphate, magnesium, sulphate and sodium in biochemistry students at Universidad Nacional del Litoral, Argentina

INTRODUCCIÓN: La urolitiasis (UL) es una alteración frecuente, cuya incidencia ha aumentado en el último cuarto del siglo XX. Para su diagnóstico se realizan estudios metabólicos para lo cual es necesario contar con valores de referencia (VR) establecidos para la población en cuestión. OBJETIVO: El objetivo del trabajo fue determinar VR de calcio, oxalato, citrato, úrico, fósforo, magnesio, sulfato y sodio en orina de 24 horas de alumnos de la Facultad de Bioquímica y Ciencias Biológicas de la Universidad Nacional del Litoral, Santa Fe, Argentina. Con los VR hallados se determinó la frecuencia de alteraciones y se la comparó con datos bibliográficos. MATERIAL Y MÉTODOS: Se utilizó la guía NCCLSC28-A3, 2008. La muestra de referencia fue de 69 alumnos. Se utilizaron métodos enzimáticos-colorimétricos, espectrofotómetro Metrolab 1600 plus, electrodos ion selectivo DIESTRO. RESULTADOS: Los VR hallados (IC 95%) fueron para el oxalato: 1,96-45,08; calcio: 20,65-250,74; citrato: 112,78-666,01; ácido úrico 58,73-782,17; fósforo 238,37-1051,44; magnesio 28,7-146,67 todos en mg/24h; sulfato 3,15-25,18 mmol/24h y sodio 42,81-285,3 mEq/24h. Se encontró un 3% hiperoxaluria, 12% hipercalciuria, 3% hipocitraturia y 6% hiperuricosuria, 6% hiperfosfaturia, 6% hipomagnesuria, 7% hipernatriuria, 0% hipersulfaturia. Los VR comparados mostraron coincidencias para algunos analitos y para otros amplias diferencias. CONCLUSIONES: El diagnóstico de la alteración metabólica para el estudio de UL varía según el valor de referencia utilizado. Adoptar valores establecidos para otras poblaciones, incluidos los de los fabricantes de los kits comerciales, conducen a un diagnóstico que puede no ser acorde a la situación clínica del paciente

INTRODUCTION: Urolithiasis (UL) is a common disease whose incidence increased in the last quarter of the twentieth century. Metabolic evaluation is necessary for diagnosis, which requires the establishment of reference values (RV) for the population in question. OBJECTIVE: To determine the RV for calcium, oxalate, citrate, uric acid, phosphate, magnesium, sulphate and sodium in 24-hour urine belonging to students from the School of Biochemistry and Biological Sciences at Universidad Nacional del Litoral, province of Santa Fe, Argentina. Once RV were established, a frequency of alterations was determined and then compared with literature data. METHODS: The NCCLSC28-A3 guideline (2008) was used. The study group included 69 students. The enzymatic colorimetric method, a Metrolab 1600 plus spectrophotometer and a DIESTRO ion-selective electrode were also employed. Results: The RV found (95 % CI) were the following: oxalate, 1.96-45.08; calcium, 20.65-250.74; citrate, 112.78-666.01; uric acid, 58.73-782.17; phosphate, 238.37-1051.44; magnesium, 28.7-146.67, all these values expressed as mg/24h; sulphate, 3.15-25.18 mmol/24h, and sodium, 42.81-285.3 mEq/24h. These findings emerged as well: hyperoxaluria, 3%; hypercalciuria 12%; hypocitraturia, 3%; hyperuricosuria, 6%; hyperphosphaturia, 6%; hypomagnesuria, 6%; hypernatriuria, 7%, and hypersulphaturia, 0%. When RV were compared, some analyte levels were similar and others showed a considerable difference. CONCLUSIONS: The diagnosis of UL through the study of metabolic changes is different according to the reference value used. Applying reference values established for other populations, including those of commercial kits manufacturers, may lead to a diagnosis which does not match the clinical condition of the patient

Kidney stones: composition, frequency and relation to metabolic diagnosis

Nephrolithiasis is one of the most frequent urologic diseases. The aim of this paper is to study the composition and frequency of 8854 patient kidney stones and in a subset of them their metabolic risk factors to be related to their type of calculi. Physicochemical and crystallographic methods were used to assess kidney stone composition. In a subset of 715 patients, we performed an ambulatory metabolic protocol with diagnostic purposes. From the total sample 79% of stones were made of calcium salts (oxalate and phosphate), followed by uric acid stones in 16.5%, calcium salts and uric acid in 2%, other salts in 1.9% and cystine in 0.6%. Male to female ratio was almost three times higher in calcium salts and other types of stones, reaching a marked male predominance in uric acid stones, M/F 18.8 /1.0. The major risk factors for calcium stones are idiopathic hypercalciuria, followed by unduly acidic urine pH and hyperuricosuria. In uric acid stones unduly acidic urine pH and less commonly hyperuricosuria are the most frequent biochemical diagnosis. Our results show that analysis of kidney stones composition and the corresponding metabolic diagnosis may provide a scientific basis for the best management and prevention of kidney stone formation, as well as it may help us to study the mechanisms of urine stone formation.

La litiasis renal es una de las enfermedades urológicas más frecuentes. El objetivo de este trabajo fue estudiar la composición y frecuencia de 8854 cálculos renales y evaluar en un subgrupo de ellos la relación de los factores de riesgo metabólicos con el tipo de cálculo hallado. Se utilizaron métodos fisicoquímicos y cristalográficos para evaluar la composición de los cálculos renales. En un subgrupo de 715 pacientes, se pudo realizar un protocolo metabólico ambulatorio con fines diagnóstico. De la muestra total, 79.0% de los cálculos fueron de sales de calcio (oxalato y fosfato), seguido por cálculos de ácido úrico en 16.5%, sales de calcio y ácido úrico en 2.0%, otras sales en 1.9% y cistina en 0.6%. La relación hombre/mujer fue casi tres veces mayor en las sales de calcio y otros tipos de cálculos, alcanzando un marcado predominio en varones con cálculos de ácido úrico, M/F 18.8/1.0. Los principales factores de riesgo para los cálculos de calcio fueron la hipercalciuria idiopática, seguida del pH urinario excesivamente ácido y la hiperuricosuria. En los cálculos de ácido úrico el pH urinario excesivamente ácido y con menor frecuencia la hiperuricosuria fueron los diagnósticos más frecuentes. Nuestros resultados muestran que el análisis de la composición de los cálculos renales y el correspondiente diagnóstico metabólico pueden proporcionar una base científica para el mejor manejo y prevención en la formación de cálculos renales, así como que nos puede ayudar a estudiar los mecanismos de formación de los mismos.

Artritis seudoséptica presenta sinovitis por cuerpo extraño en un paciente con gota / Pseudoseptic arthritis with foreign body synovitis in a patient with gout

La monoartritis es un reto diagnóstico para el clínico, ya que es extensa la lista de patologías asociadas. En pacientes con diagnóstico establecido de enfermedad articular inflamatoria, se acepta que la monoartritis corresponde a la exacerbación de la enfermedad de base; sin embargo, ignorar el abordaje sistematizado de las monoartritis puede generar omisiones e implicaciones diagnósticas erróneas. En este reporte se analiza el abordaje de un caso de artritis seudoséptica, simulando un ataque agudo de artritis por urato monosódico recurrente en un paciente con retención de cuerpo extraño intraarticular.

Monoarthritis is a diagnostic challenge for the clinician, as the list of associated conditions is quite long. It is accepted that in patients with a diagnosis of inflammatory joint disease monoarthritis represents exacerbation of the underlying disease. However, ignoring the systematized approach to monoarthritides may lead to omissions and mistaken diagnostic implications. This report describes the approach to a case of pseudoseptic arthritis that mimicked an acute episode of recurrent arthritis due to monosodium urate in a patient with retention of an intraarticular foreign body.

Oxidative stress in patients with differentiated thyroid cancer: Early effects of radioiodine therapy.

Ionizing radiation in differentiated thyroid cancer (DTC) patients treated with radioiodine (131-I) produces reactive oxygen species (ROS), which could induce oxidative stress with disturbance of redox balance. The aim of this study was to evaluate oxidative stress in DTC patients treated with 3.7 or 5.5 GBq of 131-I using values for serum malondialdehyde (MDA, a marker of oxidative stress), uric acid (to determine antioxidant status) and total antioxidative status (TAS). The study population included 20 DTC patients and 20 healthy controls. Significant differences in MDA concentrations were found between DTC patients before 131-I therapy and control subjects (p = 0.001), while TAS values were similar in both populations (p>0.05). There was a negative correlation between MDA concentrations and TAS in the DTC group before therapy (R2 = 0.2973, p = 0.013). Three days after 131-I therapy, MDA concentrations were higher than the pretreatment values (3.36 ± 1.69 nmol/mL vs. 2.93 ± 1.31 nmol/mL; p = 0.006), while serum uric acid concentrations declined progressively from 341.0 ± 80.39 μmol/L to 304.25 ± 77.25 μmol/L (p = 0.026) in 3 days and 291.2 ± 88.86 μmol/L (p = 0.009) in 7 days after 131-I therapy. There was no dose-dependent effect on MDA, or uric acid concentrations and TAS. Thus, 131-I therapy in DTC patients induced oxidative stress, which was accompanied by a simultaneous and extended reduction in uric acid concentration, but without significant disturbances in TAS. This is the first study that evaluated TAS capacity in DTC patients before and 7 days after 131-I therapy. The relatively stabile TAS values in these patients indicated a good protection from oxidative stress induced by high doses of ionizing radiation.

Clinical factors and treatment outcomes associated with failure in the detection of urate crystal in patients with acute gouty arthritis

BACKGROUND/AIMS: To investigate the rate of detection of monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with acute gouty arthritis and factors associated with false-negative results. METHODS: A total of 179 patients with acute gouty arthritis who had undergone SF crystal examination were identified from the data warehouse of two university hospitals. Clinical and laboratory data were obtained from the medical records. RESULTS: The overall rate of detection of MSU crystals was 78.8%. In univariate analyses, the only significant differences between the variables of crystal-negative and crystal-positive patients were a lower C-reactive protein level (p = 0.040) and fewer patients undergoing emergent surgery in the crystal-positive group (p = 4.5 x 10(-6)). In logistic regression analyses, MSU crystal-negative results were significantly associated with the interval from arthritis onset to crystal examination (p = 0.042), and this was the most significant risk factor for arthroscopic surgery (p = 2.1 x 10(-4)). Seventeen patients who underwent arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a significant delay in gout treatment (p = 8.74 x 10(-5)). The distribution of crystal-negative patients differed significantly between the SF samples that were evaluated by both the laboratory medicine and the rheumatology departments (p = 1.2 x 10(-14)), and the kappa value was 0.108. CONCLUSIONS: Although several clinical features were associated with detection failure, SF MSU crystal identification was critically dependent on the observer. Considering the impact on the treatment outcomes, implementation of a quality control program is essential.

Uric acid metabolism in a sample of Egyptian hypertensive patients with normal kidney function

Hyperuricemia is commonly associated with hypertension. Also, it is well known to coincide with the metabolic syndrome but is still not recognized as a risk factor. So, we aimed to evaluate hyperuricemia among a sample of hypertensive Egyptians with normal renal function. This study was performed on 303 hypertensive patients aged 30-69 years. Patients were divided into 2 groups according to the level of uric acid: group 1 composed of 168 hypertensive hyperuricemic patient sand group 2 composed of 135 hypertensive normouricemic patients. All patients were subjected to complete medical history and detailed clinical examination including body mass index [BMI], complete blood count [CBC], serum creatinine, BUN, FBS, cholesterol, triglycerides, uric acid, sodium, potassium, urinary uric acid, urinary creatinine, urinary uric acid to creatinine ratio and fractional excretion of uric acid[FEUA]. The overall prevalence of hyperuricemia was 55.4%. Uric acid correlated significantly with age [p<0.05]. BMI was significantly higher in group1 than in group 2 [p<0.05], and there was a significant positive correlation between serum uric acid and BMI [p<0.01].Serum triglycerides and cholesterol were significantly higher in group 1 than in group 2 [p<0.05for both] denoting risky metabolic effects. Serum uric acid correlated significantly with systolic blood pressure [p<0.05], but not with diastolic blood pressure. No significant difference found between group 1 and group 2 as regards SBP, DBP or blood pressure control [all p values > 0.05]. Serum uric acid found to correlate significantly [p<0.001] with urinary uric acid, urinary creatinine and negatively with FEUA denoting early tubular defect of the kidney. Also, Urinary uric acid, urinary creatinine and urinary uric acid/creatinine ratio were higher in group 1than in group 2 [p values were<0.001, <0.001 and <0.05 respectively]. FEUA was found to be significantly lower in group 1 than in group 2 [p<0.01]. We found, also, that serum sodium level was significantly higher in the hyperuricemic group than in the normouricemic group [p<0.001] denoting the role of Na[+] in the development of hypertension and defective renal excretion of uric acid. We conclude that the incidence hyperuricemia in our sample of Egyptian hypertensive patients was [55.4%]. Impaired renal clearance of uric acid occurs before deterioration of GFR. Serum uric acid should be measured in all cases of hypertension together with BMI, total cholesterol, triglycerides and should be treated to avoid consequent metabolic complications. Hypertensive patients with hyperuricemia should be warned strictly of high sodium diet

The effects of pycnogenol on antioxidant enzymes in a mouse model of ozone exposure

BACKGROUND/AIMS: Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone. METHODS: Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction. RESULTS: Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas gamma-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and gamma-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment. CONCLUSIONS: Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.

Fructose and cardiometabolic disorders: the controversy will, and must, continue: [review]

The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit. Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.

Estimation of amino acids, urea and uric acid in tasar silkworm, Antheraea mylitta Drury.

The tasar silkworm, Antheraea mylitta Drury, Andhra local ecorace is an exclusive race of Andhra Pradesh. It is on the verge of extinction due to difficulty of acclimatisation at breeding and rearing stages. As an attempt to protect this race, a method of total indoor rearing has been done. In this context, the estimation of free amino acids, excretory products- urea and uric acid were compared during the fourth and fifth instars of tasar silkworm, reared under outdoor and indoor conditions. The study has revealed that amino acids decreased in the fat body in outdoor and indoor reared larvae in contrast to that in the haemolymph where it has gradually increased from first to third crops. This is an important finding as it reveals that indoor worms seem to adopt proteolytic activity in the haemolymph. Secondly, in the fifth instar the excretory products are more compared to fourth instar in the indoor reared worms. During fifth instar, formation of nitrogenous products lessens as silk synthesis enhances. The present study reveals that decrease in uric acid in fifth instar implies increase in growth rate and silk synthesis in both outdoor and indoor worms. The findings of the present investigation is helpful in the conservation and protection of the A. mylitta, Andhra local ecorace.

Síndrome de lise tumoral: uma revisão abrangente da literatura / Acute tumor lysis syndrome: a comprehensive review

A síndrome de lise tumoral é caracterizada pela destruição maciça de células malignas e conseqüente liberação do seu conteúdo no espaço extracelular. Embora possa ocorrer de modo espontâneo, a síndrome de lise tumoral aparece em geral, logo após o início do tratamento com agentes quimioterápicos citotóxicos. Uma vez liberados, estes metabólitos podem subjugar os mecanismos homeostáticos resultando em hiperuricemia, hipercalemia, hiperfosfatemia, e hipocalcemia. Estas alterações biológicas podem levar à ocorrência de diversas manifestações clínicas, incluindo lesão renal aguda, convulsões e morte súbita, que podem requerer cuidados intensivos. Como a síndrome de lise tumoral está associada a um prognóstico reservado, prevenção de sua ocorrência per se e também de suas conseqüências é obrigatória. O objetivo desta revisão foi descrever os mecanismos fisiopatológicos, e as manifestações clínicas e biológicas da síndrome de lise tumoral aguda, e fornecer recomendações atualizadas para sua prevenção. Foram selecionados artigos sobre síndrome de lise tumoral publicados nos últimos 20 anos no PubMed www.pubmed.gov. Estudos referenciados nos artigos selecionados na busca, também foram utilizados. Resultados: A síndrome de lise tumoral é uma complicação grave e freqüente em pacientes com neoplasias de diagnóstico recente. Estratégias de prevenção incluem hidratação vigorosa, agentes uricolíticos, identificação dos fatores que predispõem à lesão renal aguda e, nos pacientes críticos, a indicação profilática de métodos de substituição da função renal necessários para prevenir ou limitar suas conseqüências. Entretanto, o momento adequado assim como as modalidades de prevenção a serem oferecidas ainda são desconhecidos e podem ser inclusive modificadas por alterações no espectro de pacientes em risco de desenvolvê-la. O desenvolvimento e a validação de estratégias baseadas no risco dos pacientes são necessários para limitar a alta morbidade e mortalidade...

Tumor lysis syndrome is characterized by the massive destruction of malignant cells and the release in the extra-cellular space of their content. While Tumor lysis syndrome may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms with development of hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia. These biological manifestations may lead to clinical manifestations including, acute kidney injury, seizure, or sudden death that require intensive care. Since clinical tumor lysis syndrome is associated with a poor prognosis both prevention of tumor lysis syndrome and prevention of clinical consequences of tumor lysis syndrome are mandatory. The objective of this review is to describe pathophysiological mechanisms, biological and clinical manifestations of tumor Lysis syndrome, and to provide upto-date guidelines to ensure prevention of tumor lysis syndrome. Review of selected studies on tumor lysis syndrome published at the PubMed database www.pubmed.gov during the last 20 years. Additional references were retrieved from the studies initially selected. Tumor lysis syndrome is a frequent and life-threatening complication of the newly diagnosed malignancies. Preventive measures, including hydration, uricolytic agents, eviction of factors predisposing to acute kidney injury and, in the more severe patients, on prophylactic renal replacement therapy, are required to prevent or limit clinical consequences of Tumor lysis syndrome. However optimal timing and modalities of prevention remains unknown and may be modified by the changing spectrum of patients at risk of tumor lysis syndrome. Development and validation of risk based strategies is required to limit the high morbidity and mortality of this complication.

Inmunopatogenia de la gota / Immunopathogenesis of gout

La gota es un tipo de artritis gatillada por la cristalización de ácido úrico dentro de las articulaciones. Múltiples factores están involucrados en su desarrollo, constituyendo actualmente la hiperuricemia una condición estrechamente relacionada con el síndrome metabólico. Los humanos carecen de una enzima que degrada el ácido úrico llamada uricasa, lo que les confiere niveles de urato más elevados que otras especies animales. Se cree que esto sería un mecanismo adaptativo que entrega protección contra diversas noxas, dadas sus propiedades antioxidantes. Los cristales de urato monosódico pueden directamente iniciar la cascada inflamatoria a través de la activación del complemento y de diversos tipos celulares. Esto genera a nivel intracelular una cascada de transducción de señales que activarán un complejo catalítico multiproteico llamado inflamasoma, el cual es clave en la activación de caspasas inflamatorias, con el consecuente clivaje proteolítico de la pro-ILl en ILl , que junto a otras citoquinas y mediadores tendrán un rol fundamental en la patogénesis de esta enfermedad. Avances en el conocimiento de esta patología han permitido identificar nuevos targets terapéuticos y desarrollar nuevas terapias que han mostrado resultados favorables en pacientes con fracaso a los tratamientos convencionales.

Gout is a type of arthritis triggered by the crystallization of uric acid in the joints. Multiple factors are involved in its development, hyperuricemia currently constitutes a condition which is closely related to the metabolic syndrome. Humans lack an enzyme that degrades uric acid called uricase, which gives us urate levels higher than other animal species. It is believed that this is an adaptive mechanism that confers protection against various noxa, given its antioxidant properties. Monosodium urate crystals can directly start the infiammatory cascade through the activation of the complement and of various cell types. This leads to a cascade of intracellular signal transduction that will activate a multiprotein catalytic complex called infiammasome, which is key in the activation of infiamatory caspases and the consequent proteolytic cleavaje of the pro-ILl in ILl, which together with other cytokines and mediators have a fundamental role in the pathogenesis of this disease. Advances in the understanding of this condition have allowed us to identify new therapeutic targets and develop new therapies that have shown favorable results in patients that do not respond to conventional treatments.

Mineralized bodies in the fat body of rhinocricus padbergi (Diplopoda)

The fat body is a loosely packed tissue distributed throughout the body cavities of millipedes. The mainfunction of this tissue is the storage of lipids, glycogen, proteins and uric acid and also serves as a site forthe permanent storage for excretion products. In this work, we examined the ultrastructure of the mineralizedbodies found in the fat body of the millipede Rhinocricus padbergi. The mineralized bodies were sphericalbodies that varied in structural organization within a single cell: some consisted of several concentric layers ofamorphous material while others were surrounded by a layer of electron-dense material intimately associatedwith the surrounding membrane. The histochemical and ultrastructural results suggested that these mineralizedbodies are involved in the accumulation of calcium and uric acid. The large number of these structures foundin the fat body of millipedes may be a consequence of these animals´ diet since they overturn soil rich in largeamounts and/or variety of minerals. As in other organisms, uric acid probably accumulates as the metabolicproduct of the degradation of nucleic acids derived from autophagy of the rough endoplasmic reticulum duean earlier massive protein synthesis, but may also be extracted from the hemolymph.

Metabolic assessment in patients with urinary lithiasis

INTRODUCTION: Metabolic investigation in patients with urinary lithiasis is very important for preventing recurrence of disease. The objective of this work was to diagnose and to determine the prevalence of metabolic disorders, to assess the quality of the water consumed and volume of diuresis as potential risk factors for this pathology. PATIENTS AND METHODS: We studied 182 patients older than 12 years. We included patients with history and/or imaging tests confirming at least 2 stones, with creatinine clearance > 60 mL/min and negative urine culture. The protocol consisted in the collection of 2, 24-hour urine samples, for dosing Ca, P, uric acid, Na, K, Mg, Ox and Ci, glycemia and serum levels of Ca, P, Uric acid, Na, K, Cl, Mg, U and Cr, urinary pH and urinary acidification test. RESULTS: 158 patients fulfilled the inclusion criteria. Among these, 151 (95.5 percent) presented metabolic changes, with 94 (62.2 percent) presenting isolated metabolic change and 57 (37.8 percent) had mixed changes. The main disorders detected were hypercalciuria (74 percent), hypocitraturia (37.3 percent), hyperoxaluria (24.1 percent), hypomagnesuria (21 percent), hyperuricosuria (20.2 percent), primary hyperparathyroidism (1.8 percent) secondary hyperparathyroidism (0.6 percent) and renal tubular acidosis (0.6). CONCLUSION: Metabolic change was diagnosed in 95.5 percent of patients. These results warrant the metabolic study and follow-up in patients with recurrent lithiasis in order to decrease the recurrence rate through specific treatments, modification in alimentary and behavioral habits.

Hiperuricemia em obesas sob dieta altamente restritiva / Hyperuricemia on obese women with restrictive highly diet

O trabalho verifica e analisa hiperuricemia em nove mulheres obesas, com índice de massa corporal (IMC) >35kg/m2, sob dieta altamente restritiva (DAR, 400-600kcal/dia) durante 6 semanas. As primeiras duas semanas foram para o diagnóstico clínico e adaptação dietética. Semanalmente foram medidas cetonúria e uricemia e na 4ª. semana foi também determinada a excreção urinária de ácido úrico. A média (ñdp) do IMC foi de 54ñ12 e 49ñ11 kg/m2, respectivamente na admissão e alta hospitalar, correspondendo a uma perda de peso de 14ñ2kg (p<0,05). Das pacientes, 78 por cento apresentavam hiperuricemia assintomática, com níveis >5,7mg/dl, atingindo, durante o estudo, o valor máximo de 12mg/dl. Duas pacientes, com níveis de uricemia >l0mg/dl, receberam alopurinol. A uricosúria, na 4ª. semana, foi de 770ñ262mg/24 hs. 33 por cento das pacientes excretaram entre 300-700mg, considerados valores normais, e 67 por cento excretaram mais do que 700mg. Nenhuma foi considerada hipoexcretora. Sugere-se que pacientes obesos submetidos à DAR tenham, além de uricemia, os valores de uricosúria monitorizados. Quando ocorrer hiperuricemia, a introdução de fármacos que inibem a síntese de ácido úrico estaria indicada.

[Metabolic effects of Ramadan fasting on type 2 diabetes]

We assessed the effects of Ramadan fasting on metabolic control, particularly change of HDL-cholesterol in 25 type 2 diabetic patients treated with diet or oral agents, with good metabolic control. Clinical and biochemical parameters and food intake were evaluated 3 weeks before Ramadan, in the fourth week of Ramadan and 3 weeks after Ramadan.There were no changes in body weight and blood pressure nor any metabolic complications. The mean plasma fasting glucose, serum fructosamin and haemoglobin A1c did not change. We found a negative relation between cholesterol intake during Ramadan and the change of HDL-cholesterol. When cholesterol intake was lower than 400 mg/day, plasma HDL-cholesterol increased by 13% at the end of Ramadan and by 23% 3 weeks after Ramadan