Longitudinal analysis of immune reconstitution and metabolic changes in women living with HIV: A real-world observational study / 中华医学杂志(英文版)

BACKGROUND@#Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally.@*METHODS@#HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia.@*RESULTS@#A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C.@*CONCLUSIONS@#This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.

Anti-hyperuricemia activity and its mechanism of flavonoid extract from saffron floral bio-residues / 中国中药杂志

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.

Diacylated anthocyanins from purple sweet potato (Ipomoeabatatas L.) attenuate hyperglycemia and hyperuricemia in mice induced by a high-fructose/high-fat diet / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.

Effects of liquid extract from Plinia cauliflora fruits residues on Chinese hamsters biochemical parameters / Efeitos do extrato líquido de resíduos de frutos de Plinia cauliflora sobre os parâmetros bioquímicos de hamsters chineses

Plinia cauliflora (Mart.) Kausel, popularly known as jabuticaba, is rich in polyphenols. Phenolic compounds exhibit several biological properties, which reflect on biomarkers such as biochemical parameters. In the present study, we evaluated the plasmatic levels of glucose, total cholesterol, HDL-cholesterol, triglycerides, and uric acid of Chinese hamsters fed for 45 days with a regular diet or cholesterol-enriched diet supplemented with a liquid extract obtained from P. cauliflora fruits residues standardized in ellagic acid and total phenolic compounds. The results showed that the concentrated extract obtained from jabuticaba residues increased the glycemia of animals fed with a regular diet and reduced the plasmatic uric acid levels of animals fed with a cholesterol-enriched diet. Since hyperuricemia is considered to be a significant risk factor of metabolic disorders and the principal pathological basis of gout, the liquid extract from P. cauliflora fruits residues would be a promising candidate as a novel hypouricaemic agent for further investigation.

Plinia cauliflora (Mart.) Kausel, popularmente conhecida como jabuticaba, é rica em polifenois. Os compostos fenólicos apresentam diversas propriedades biológicas, que refletem em biomarcadores, como os parâmetros bioquímicos. No presente estudo, avaliamos os níveis plasmáticos de glicose, colesterol total, HDL-colesterol, triglicerídeos e ácido úrico em hamsters chineses alimentados por 45 dias com dieta regular ou dieta enriquecida com colesterol suplementada com extrato líquido obtido de resíduos de frutos de P. cauliflora padronizado em ácido elágico e compostos fenólicos totais. Os resultados mostraram que o extrato concentrado obtido dos resíduos de jabuticaba aumentou a glicemia dos animais alimentados com dieta regular e reduziu os níveis plasmáticos de ácido úrico dos animais alimentados com dieta rica em colesterol. Uma vez que a hiperuricemia é considerada um fator de risco significativo de distúrbios metabólicos e a principal base patológica da gota, o extrato líquido dos resíduos de frutas de P. cauliflora seria um candidato promissor como um novo agente hipouricêmico para investigação posterior.

Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy / 中华肝脏病杂志

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.

Evaluation of methodological and reporting quality of domestic clinical guidelines for hyperuricemia / 中国中药杂志

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.

Research progress on anti-hyperuricemia effects and mechanisms of Chinese medicines based on regulation of intestinal flora and metabolites / 中国中药杂志

Chronical hyperuricemia, a severe metabolic disease characterized by increased serum uric acid, urea nitrogen, and creatinine, has a positive correlation with the risks of gouty arthritis, diabetes, hypertension, and kidney damage. Abnormal purine metabolism and reduced uric acid excretion are the major causes of hyperuricemia, which, thus, points to a potential strategy of preventing from or delaying the progress of hyperuricemia-related diseases and its complications by effectively controlling the serum uric acid level. Increasing evidence has revealed that Chinese medicines alleviate hyperuricemia through regulating intestinal flora, which plays a pivotal role in regulating metabolites, including uric acid level. The disease treatment with traditional Chinese medicine is based on syndrome differentiation, and Chinese medicines often have multiple effects and a wide range of targets. In this review, we summarized the anti-hyperuricemia effects and mechanisms of active compounds in Chinese medicines, single Chinese medicinal herbs, and Chinese medicinal prescriptions in regulating the uric acid level via intestinal flora and metabolites, which will be helpful for further study and application of Chinese medicines in hyperuricemia treatment.

Recomendaciones para el manejo de la lisis tumoral / Recommendations for tumor lysis syndrome management

El síndrome de lisis tumoral representa una complicación potencialmente letal provocada por la liberación masiva de ácidos nucleicos, potasio y fosfato hacia la circulación como resultado de la lisis de células neoplásicas, las cuales se caracterizan por una rápida capacidad de proliferación y alta sensibilidad a fármacos. Esto puede ocurrir de forma espontánea antes del inicio del tratamiento y agravarse luego de haberse iniciado la quimioterapia. Presenta una alta mortalidad. Su prevención continúa siendo la medida terapéutica más importante. El cuadro clínico se caracteriza por la existencia de trastornos del metabolismo hidroelectrolítico, en particular, hipercalemia, hiperfosfatemia e hiperuricemia y por la aparición de una lesión renal aguda. Una adecuada intervención terapéutica implica hidratación intravenosa y medidas para prevenir o corregir las alteraciones metabólicas. En este artículo, se proponen lineamientos para seguir tanto en la etapa diagnóstica como en el tratamiento de esta complicación.

The tumor lysis syndrome represents a potentially lethal complication caused by the massive release of nucleic acids, potassium and phosphate into the circulation as a result of the lysis of neoplastic cells, which are characterized by a rapid proliferation capacity and high sensitivity to drugs. This may occur spontaneously prior to the start of treatment, becoming worse after the initiation of chemotherapy. It presents a high mortality; its prevention continues being the most important therapeutic measure. The clinical picture is characterized by the existence of hydroelectrolytic metabolism disorders, in particular hyperkalemia, hyperphosphatemia and hyperuricemia and by the appearance of an acute renal lesion. Adequate therapeutic intervention involves intravenous hydration and measures to prevent or correct metabolic alterations. This article proposes guidelines to follow both in the diagnostic stage and in the treatment of this complication.

Study on mechanism of Fangji Huangqi Decoction on hypouricemic effect and renal protection in hyperuricemia mice / 中国中药杂志

The aim of this paper was to study the specific mechanism of Fangji Huangqi Decoction(FHT) in decreasing uric acid and improving renal function in mice with hyperuricemia(HUA) induced by potassium oxonate, so as to provide theoretical basis for the research and development of drugs for clinical prevention and treatment of HUA and the modernization of traditional Chinese medicine. Sixty Kunming male mice were randomly divided into 6 groups, with 10 mice in each group, namely normal group, model group(250 mg·kg~(-1) potassium oxonate), FHT high, medium and low-dose groups(10 920, 5 460, and 2 730 mg·kg~(-1)) and positive drug allopurinol group(5 mg·kg~(-1)). Drug administration was given once a day for 7 days. On the 6 th day, mice of each group were kept in metabolic cages, and their urine was collected for 24 hours for determination of uric acid, creatinine, and β2-microglobulin(β2-MG) levels. After 7 days, the animals were sacrificed to determine serum uric acid, creatinine β2-MG and interleukin-1β(IL-1β) levels, and their liver and kidney tissues were collected. The liver tissues were used for subsequent determination of xanthine oxidase(XOD) activity, and the kidney tissues were used for subsequent determination of IL-1β levels, pathological tests and related Western blot experiments. In the cell transfection experiment, the cells were divided into blank group, model group(4.8 mmol·L~(-1) uric acid treatment), FHT administration group(4.8 mmol·L~(-1) uric acid+200 μg·mL~(-1) FHT), leucine-rich repeat kinase 1(LRRK1)-small interfering RNA(siRNA) group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection) and LRRK1-siRNA+FHT group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection+200 μg·mL~(-1) FHT). After 24 h incubation, the level of IL-1β in the cell supernatant was detected, and the cellular proteins were extracted and used to determine LRRK1, epidermal growth factor receptor(EGFR), PDZ kinase 1(PDZK1) and nuclear factor-kappa B(NF-κB) protein expression levels. The results showed that, FHT could significantly reduce the uric acid, creatinine and β2-MG levels in serum and β2-MG levels in urine, increase the uric acid and creatinine levels in urine, and improve the renal pathological results of the HUA mice, but showed no effect on liver XOD activity; at the same time, we found that the expression level of IL-1β in serum and kidney, NF-κB, LRRK1 and EGFR protein levels in kidney of HUA mice were significantly increased, and the expression level of PDZK1 protein was significantly decreased, while FHT could significantly improve the abnormal expression of these proteins, and FHT increased protein expression of renal organic anion transporter 1(OAT1), OAT3 and ATP bin-ding transporter G2(ABCG2) in HUA mice, but FHT had no effect on the expression of urate transporter 1(URAT1). In the cell transfection experiment, after transfection of LRRK1-siRNA, the levels of IL-1β, EGFR and NF-κB in supernatant were significantly reduced, and the expression of PDZK1 protein was significantly increased. As compared with the LRRK1-siRNA group, the levels of IL-1β, EGFR, PDZK1 and NF-κB did not change significantly with the additional FHT. This study showed that FHT may regulate the renal uric acid transport system through LRRK1 gene, improve the capacity of uric acid excretion, so as to reduce the level of serum uric acid. At the same time, FHT can not only protect the kidney directly, but also in an indirect manner by reducing the level of uric acid.

Critical revision of the medical treatment of gout in Brazil / Revisão crítica do tratamento medicamentoso da gota no Brasil

ABSTRACT Gout is considered the most common form of inflammatory arthritis in men over 40 years. The authors present a brief review of the current treatment of gout and discuss the existing pharmacological limitations in Brazil for the treatment of this disease. Although allopurinol is still the main drug administered for decreasing serum levels of uric acid in gout patients in this country, the authors also present data that show a great opportunity for the Brazilian drug market for the treatment of hyperuricemia and gout and especially for patients using private and public (SUS) health care systems.

RESUMO A gota é considerada a forma mais comum de artrite inflamatória em homens acima de 40 anos. Os autores apresentam uma breve revisão sobre o tratamento atual da gota e discutem as limitações farmacológicas existentes no Brasil para o tratamento dessa enfermidade. Apesar de o alopurinol ainda ser a principal medicação para a redução dos níveis de uricemia de pacientes com gota no país, os autores também apresentam dados que apontam para uma grande oportunidade para o mercado farmacológico brasileiro em relação ao tratamento da hiperuricemia e da artrite gotosa e especialmente para pacientes usuários de sistemas privados de saúde e do SUS (Sistema Único de Saúde).

Prevention of renal damage by treating hyperuricemia

Nephrolithiasis, obstructive renal failure, essential hypertension, and chronic tubulointerstitial nephritis have been considered as the renal complications of hyperuricemia. Massive proteinuria has been rarely reported as the primary manifestation of increased serum uric acid. This is the report of a child presented with proteinuira, hypertension, and glomerular scelrosis secondary to hypouricosuric hyperuricemia, who was treated by uric acid lowering management.

role of allopurinol and angiotensin receptor blockers in serum uric acid reduction in gouty and hypertensive patients

To evaluate the effect of Allopurinol in combination with angiotensin receptor blockers on hyperuricemia in gouty and hypertensive patients. Randomized, open label, prospective, comparative trial. This study was conducted in the Department of Pharmacology and Therapeutics; BMSI/JPMC, Karachi from April 2010 to November 2010. 80 hypertensive and hyperuricemic patients were enrolled from OPD and medical wards and were divided into two groups. Group DR-1[40 Patients] were given allopurinol 300mg plus candisartan 8mg daily and group DR-2 [40 patients] were given allopurinol 200mg Plus Losartan 50mg, daily four 4 months. 6 patients were unable to continue the follow-up 3 patients in each group. DR-1 combination therapy decreased serum uric acid level from 8.92 +/- 0.19mg/dl at day 0 to 5.33 +/- 0.11 mg/dl at day120. DR-2 group also showed a significant reduction in serum uric acid level from 9.14 +/- 0.19mg/dl at day 0 to 4.74 +/- 0.09mg/dl at day 120 [p<0.001]. When effects were compared in both treatment groups, the effect of group 2 regimens on serum uric acid level was more marked due to Losartan combination which also have uricosuric effects than in group 1 regimen, with average percentage decrease in serum uric acid - 40.35% in group DR-1 and -48.24% in group DR-2. The allopurinol 200mg and Losartan 50mg is more effective than allopurinol 300mg+ candesartan 8mg, to decrease serum uric acid level and group DR-2 drugs combination useful in those hyperuricemic patients who cannot tolerate high doses of uric acid lowering drugschromatogram obtained indicated the quantity of pesticide residues. Milk samples and serum samples were analyzed using HPLC technique. Pesticides such as malathion, permethrin, deltamethrin and Polytrin-C were detected in different concentrations. The levels were significantly higher than the maximum residual limit. It is concluded that the presence of pesticides in the human body is a major concern in the development of various ailments because of possible immunotoxic, mutagenic and carcinogenic potential of pesticides

Effect of uric acid on vitamin C and E in induced hyperuricemic model

To measure the level of uric acids and find out the effect of uric acid on vit C and E in induced hyperuricemic model. Comparative study. This study was conducted at Baqai Medical University, Karachi from June 2010 to January 2011. Forty male albino rats with an average weight of 180 +/- 2 g were selected. The rats were grouped. The animals were fed on standards diet and given tap water ad libitum untril treatment. The protocols for experiment was according to institute of laboratory animal resources on life sciences, US National research council, 1996 and institutional animal ethical committee [IAEC] of baqai medical university, Karachi. Albino rats were divided into four groups. Group [A] 10 - control given only standard diet, group B[10] fed on 60% fructose with standard diet, group C[10] fed on fructose, standard diet and intraperitonially oxonic acid 250 mg/kg and group D[10] only on injection intraperotonially oxonic acid 250mg/kg. at the end of study 10 ml of blood was drawn from heart of rats. Then blood was estimated for vitamin C,E and uric acids done by kit methods randox-manual /Rx monza UA230/UA233. The concentration of vitamin C and E were significantly lowered as compared to uric acid concentration in the group B, C and D. Decrease level of vit C and E increase the level uric acids were observed. Therefore, it may be suggested that increase intake of vitamin C may be helpful in lowering uric acid concentration

Síndrome de lisis tumoral en pediatría / Tumoral lysis syndrome in pediatrics

Tumor lysis syndrome is a metabolic emergency resulting from the rapid and massive destruction of tumor cells, spontaneously or secondary to cytolytic therapy for cancer. This results in a huge imbalance of internal environment by releasing large amounts of intracellular contents into the interstitial and intravascular space, with serious clinical consequences or even death. The pediatric population is especially at risk of tumor lysis syndrome because it has a high rate of fast-growing tumors, such as those of hematologic origin. Proper recognition of the risk factors that can cause this syndrome, as well as specific prevention and treatment has substantially decreased complications and improved survival in these patients.

El síndrome de lisis tumoral es una emergencia metabólica derivada de la rápida y masiva destrucción de células tumorales en forma espontánea o secundaria a terapia citolítica del cáncer. Esta situación produce un enorme desequilibrio del medio interno al liberarse grandes cantidades de contenido intracelular al espacio intersticial e intravascular, con consecuencias clínicas serias e incluso mortales. La población pediátrica está especialmente expuesta a sufrir síndrome de lisis tumoral ya que presenta una tasa elevada de tumores de rápido crecimiento, como son los de orígenes hematológicos. El adecuado reconocimiento de los factores de riesgo que pueden causar este síndrome, así como su prevención y tratamiento específicos han disminuido sustancialmente las complicaciones y mejorado la sobrevida de estos pacientes.

To study the efficacy of losartan on urinary uric acid excretion in thiazide induced hyperuricemic and hypertensive patients

The precise relationship of Hyperuricemia found in hypertensive patients is still obscure; this study is a urinary uric acid lowering intervention with Losartan in hypertensive patients induced by Thiazide diuretics. A number of pharmacological agents like loop diuretics, similarly low doses of aspirin [<3g daily] aggravate Hyperuricemia. The effect of Losartan on urinary uric acid excretion In Hypertensive patients with Thiazide induced Hyperuricemia were investigated in the Department of pharmacology and therapeutics, Basic Medical Sciences Institute Jinnah Postgraduate Medical Centre Karachi. It was randomized, open label, prospective, comparative study. Total 60 hypertensive Hyperuricemic patients were enrolled one by one in this study, selected from medical OPD and wards of Jinnah Postgraduate Medical Centre, Karachi. Patients were divided in three groups. Group-1 patients were treated with Thiazide 50 mg/day, Group-2 with Losartan + Thiazide 50 mg/day, and Group-3 with Losartan 50 mg/day. The effect on urinary uric acid level was measured, after every fortnightly. Treatment with Thiazide + Losartan group and Losartan group showed significantly increase in urinary uric acid excretion. Whereas, Thiazide group decrease in urinary uric acid level. In contrast to Thiazide and Losartan alone Thiazide + Losartan led to a greater increased in urinary uric acid excretion. The average percentage increase in urinary uric acid excretion in Thiazide + Losartan group was -13.27% and the average percentage increased in urinary uric acid excretion was 6.7% in Losartan group. Thus it can be concluded from the present study that urinary uric acid excretion was more increased in combination therapies. Ultimately Losartan decrease serum uric acid level and uricosuric effect of Losartan might be particularly useful in Hyperuricemic patients those on Thiazide diuretic [for hypertension and heart failure]

Antihyperuricemic and diuretic effects of procyanidins extracted from Crataegus monogyna

Data indicated that procyanidins extracted from grape seeds has uric acid lowering effects in mice, however the hypouricaemic effect of procyanidins was accompanied with changes in enzymatic activities of xanthine dehydrogenase and xanthine oxidase. This study was designed to investigate the effect of procyanidins extracted from Crataegus monogyna on serum uric acid, adenosine deaminase [ADA], 5-nucleotidase, xanthine oxidase, and renal function on normal and potassium oxonate induced hyperuricemic rats. Thirty female albino rats were divided into three groups. The first group included 18 rats pretreated with the uricase inhibitor potassium oxonate [250 mg/kg, i.p.], served as an animal model for hyperuricemia. The rat models were divided into three subgroups, each subgroup having six rats. The first subgroup served as a normal control. Subgroup 2 received a single daily dose [100 mg/kg p.o] of procyanidins for 7 days. The third subgroup received daily dose [50 mg/kg p.o] of allopurinol for 7 days as positive control. The second group included six rats received only water as a vehicle. The serum uric acid, xanthine oxidase, adenosine deaminase [ADA] and 5-nucleotidase levels were measured and com-pared to those in normal untreated control group. The Third group included six normal rats received a single dose of Procyanidins [50 mg/kg body weight; i.v.] to study the renal ef-fects of procyanidins.. A single daily dose [100 mg/kg PO] of procyanidins for 7 days significantly reduced serum levels of uric acid, ADA and 5'-nucleotidase, without detectable effects on the level of xanthine oxidase in hyperuricemic rats. Intravenous infusion of a single dose of procyanidins [50 mg/kg i.v] produced marked increases in urinary Na+excretion [4.8 folds] and urine flow [2.6 folds] accompanied by insignificant change of potassium excretion in the rats. The reduction in serum uric acid most probably is due to inhibiting enzymes, ADA and 5-nucleotidase. The antihyperuricemic and diuretic effects of procyanidins recommended it as a good drug for the treatment of gout and renal uric acid calculi

Single dose of rasburicase for treatment of hyperuricemia in acute kidney injury: a report of 3 cases

Severe hyperuricemia accompanied by the other comorbidities such as anuria, fluid overload, calcium-phosphate imbalance, and/or tumor lysis syndrome is one of the indications for dialysis in the setting of acute kidney injury. Rasburicase is used in different clinical conditions such as tumor lysis syndrome and uric acid nephropathy. Among referred patients to our center from 2008 to 2010, there were 3 patients who had an indication for dialysis because of hyperuricemia. Contributing factors to the acute kidney injury were multi-organ dysfunction, rapidly progressive glomerulonephritis, and spontaneous tumor lysis syndrome. None of the patients showed any response to treatment with bicarbonate and hydration. After rasburicase administration, serum uric acid level declined, and urine output increased. Treatment with a single low dose of rasburicase would be effective to decrease the serum uric acid level and reverse kidney injury secondary to uric acid nephropathy

Hypouricemic and antioxidant activities of Allium cepa Lilliaceae and quercetin in normal and hyperuricemic rats

To evaluate the hypouricemic and antioxidant effects of Allium cepa Lilliaceae [Allium cepa L.] and quercetin in normal and hyperuricemic rats. The following study was conducted in the Department of Nutrition and Biochemistry, Tehran University of Medical Science, Iran, between May 2007 and March 2008. A total of 48 male Wistar rats [body weights: 180-200 g] were randomly divided into 8 equal groups including normal; normal + Allium cepa L. [5g/kg]; normal + quercetin [5mg/kg]; normal + allopurinol [5mg/kg]; hyperuricemic; hyperuricemic + Allium cepa L. [5g/kg]; hyperuricemic + quercetin [5mg/kg]; hyperuricemic + allopurinol [5mg/kg] once a day for 14 days. Experimentally, hyperuricemia in rats was induced by intraperitoneal injection of potassium oxonate [250mg/kg]. Allium cepa L. and quercetin treatments for 14 days significantly reduced [p=0.000] the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited hepatic xanthine oxidase/xanthine dehydrogenase activity. Allium cepa L. and quercetin treatments led also to a significant improvement in biomarkers of oxidative stress in hyperuricemic rats [p=0.000]. Although the hypouricemic effect of allopurinol was much higher than that of Allium cepa L. and quercetin, it could not significantly change oxidative stress biomarkers. These results may be responsible partly for the beneficial effects of Allium cepa L. and its major flavonoid on hyperuricemia and oxidative stress