Cross-sectional association between non-soy legume consumption, serum uric acid and hyperuricemia: the PREDIMED-Plus study.

PURPOSE: To assess the association between the consumption of non-soy legumes and different subtypes of non-soy legumes and serum uric acid (SUA) or hyperuricemia in elderly individuals with overweight or obesity and metabolic syndrome. METHODS: A cross-sectional analysis was conducted in the framework of the PREDIMED-Plus study. We included 6329 participants with information on non-soy legume consumption and SUA levels. Non-soy legume consumption was estimated using a semi-quantitative food frequency questionnaire. Linear regression models and Cox regression models were used to assess the associations between tertiles of non-soy legume consumption, different subtypes of non-soy legume consumption and SUA levels or hyperuricemia prevalence, respectively. RESULTS: Individuals in the highest tertile (T3) of total non-soy legume, lentil and pea consumption, had 0.14 mg/dL, 0.19 mg/dL and 0.12 mg/dL lower SUA levels, respectively, compared to those in the lowest tertile (T1), which was considered the reference one. Chickpea and dry bean consumption showed no association. In multivariable models, participants located in the top tertile of total non-soy legumes [prevalence ratio (PR): 0.89; 95% CI 0.82-0.97; p trend = 0.01, lentils (PR: 0.89; 95% CI 0.82-0.97; p trend = 0.01), dry beans (PR: 0.91; 95% C: 0.84-0.99; p trend = 0.03) and peas (PR: 0.89; 95% CI 0.82-0.97; p trend = 0.01)] presented a lower prevalence of hyperuricemia (vs. the bottom tertile). Chickpea consumption was not associated with hyperuricemia prevalence. CONCLUSIONS: In this study of elderly subjects with metabolic syndrome, we observed that despite being a purine-rich food, non-soy legumes were inversely associated with SUA levels and hyperuricemia prevalence. TRIAL REGISTRATION: ISRCTN89898870. Registration date: 24 July 2014.

Relationship between Urinary Level of Phytate and Valvular Calcification in an Elderly Population: A Cross-Sectional Study.

Pathological calcification generally consists of the formation of solid deposits of hydroxyapatite (calcium phosphate) in soft tissues. Supersaturation is the thermodynamic driving force for crystallization, so it is believed that higher blood levels of calcium and phosphate increase the risk of cardiovascular calcification. However several factors can promote or inhibit the natural process of pathological calcification. This cross-sectional study evaluated the relationship between physiological levels of urinary phytate and heart valve calcification in a population of elderly out subjects. A population of 188 elderly subjects (mean age: 68 years) was studied. Valve calcification was measured by echocardiography. Phytate determination was performed from a urine sample and data on blood chemistry, end-systolic volume, concomitant diseases, cardiovascular risk factors, medication usage and food were obtained. The study population was classified in three tertiles according to level of urinary phytate: low (<0.610 µM), intermediate (0.61-1.21 µM), and high (>1.21 µM). Subjects with higher levels of urinary phytate had less mitral annulus calcification and were less likely to have diabetes and hypercholesterolemia. In the multivariate analysis, age, serum phosphorous, leukocytes total count and urinary phytate excretion appeared as independent factors predictive of presence of mitral annulus calcification. There was an inverse correlation between urinary phytate content and mitral annulus calcification in our population of elderly out subjects. These results suggest that consumption of phytate-rich foods may help to prevent cardiovascular calcification evolution.

Effect of consuming a grape seed supplement with abundant phenolic compounds on the oxidative status of healthy human volunteers.

BACKGROUND: Diverse enzymatic and non-enzymatic antioxidants provide protection against reactive oxygen species in humans and other organisms. The nonenzymatic antioxidants include low molecular mass molecules such as plant-derived phenols. AIM OF STUDY: This study identified the major phenolic compounds of a grape seed extract by HPLC and analyzed the effect of consumption of biscuits enriched with this extract on the urinary oxidative status of healthy subjects by measurement of urine redox potential. METHODS: The major phenolic compounds were characterized in a red grape seed extract separated by HPLC with detection by a photodiode array (PDA), fluorescence (FL) and quadrupole mass spectrometer (MS). A nutritional study in a healthy volunteers group was done. Each volunteer ate eight traditional biscuits with no red grape seed extract supplementation. The second day each volunteer ate eight traditional biscuits supplemented with 0.6% (wt/wt) of grape seed extract. An overnight urine sample was obtained for each treatment. The redox potential was measured at 25 °C using a potentiometer in each urine sample. RESULTS: Epicatechin, catechin, procyanidin dimers B1 to B4, and the procyanidin trimer C2 were the major phenolic components in the extract. Epicatechin gallate and procyanidin dimers B1-3-G and B2-3'-G were the major galloylated flavan-3-ols. The forty-six healthy volunteers each shown a reduction of the urine redox potential after the treatment by traditional biscuits supplemented with the grape seed extract. CONCLUSIONS: This simple dietary intervention significantly reduced (33%) the urine redox potential, reflecting an overall increase in antioxidant status. Incorporation of plant-derived phenols in the diet may increase anti-oxidative status.

Effects of polyphenols from grape seeds on renal lithiasis.

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity.

Internalization of Calcium Oxalate Calculi Developed in Narrow Cavities.

We describe the case of a patient with calcium oxalate monohydrate and calcium oxalate dihydrate calculi occluded in cavities. All those calculi were located inside narrow cavities covered with a thin epithelium that permits their visualization. Urinary biochemical analysis showed high calciuria, not hypercalciuria, hypocitraturia, and a ratio [calcium]/[citrate] >0.33. The existence of cavities of very low urodynamic efficacy was decisive in the formation of such calculi. It is important to emphasize that we observed a thin epithelium covering such cavities, demonstrating that this epithelium may be formed after the development of the calculi through a re-epithelialization process.

Renal papillary calcification and the development of calcium oxalate monohydrate papillary renal calculi: a case series study.

BACKGROUND: The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi. METHODS: From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis. RESULTS: The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency. CONCLUSIONS: Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi.

Effects of short and long-term indapamide treatments on urinary calcium excretion in patients with calcium oxalate dihydrate urinary stone disease: a pilot study.

OBJECTIVE: The aim of this study was to determine the relative calcium-reducing effects of indapamide at 6 and 18 months using a dose of 1.5 mg/day. MATERIAL AND METHODS: Twenty-two patients with idiopathic hypercalciuria and calcium oxalate dihydrate urinary stone disease (minimum one stone episode) were selected. Each patient began a therapy regime of 1.5 mg indapamide sustained release taken once a day in the evening. Under basal conditions and after 6 and 18 months of treatment, subjects submitted urine and blood samples for analysis. The primary aim of this study was to assess the effects on excretion and concentration of calcium in urine. RESULTS: For 2 h urine, there was a mean decrease in urinary calcium concentration of 47%, whereas urinary calcium concentrations decreased by 53% in 24 h urine (p < 0.05) at 6 months of treatment. Blood urate levels rose by 19% (p < 0.05). Treatment for 18 months resulted in significant reduction in urinary calcium levels, by approximately 48% (p < 0.05) in both 2 h and 24 h urine. A 21% increase in urate levels in the blood was observed (p < 0.05). The remaining parameters remained unaltered. CONCLUSIONS: Owing to the low effective dosage of indapamide (1.5 mg/day) and the lack of any severe side-effects, this drug would appear to be a good candidate for use in the control of hypercalciuria. As such, it could prove efficacious in the prevention of recurrent kidney stones that are often associated with this condition.

Urinary lithogenesis risk tests: comparison of a commercial kit and a laboratory prototype test.

OBJECTIVE: Renal stone formation is a multifactorial process depending in part on urine composition. Other parameters relate to structural or pathological features of the kidney. To date, routine laboratory estimation of urolithiasis risk has been based on determination of urinary composition. This process requires collection of at least two 24 h urine samples, which is tedious for patients. The most important feature of urinary lithogenic risk is the balance between various urinary parameters, although unknown factors may be involved. The objective of this study was to compare data obtained using a commercial kit with those of a laboratory prototype, using a multicentre approach, to validate the utility of these methods in routine clinical practice. MATERIAL AND METHODS: A simple new commercial test (NefroPlus®; Sarstedt AG & Co., Nümbrecht, Germany) evaluating the capacity of urine to crystallize calcium salts, and thus permitting detection of patients at risk for stone development, was compared with a prototype test previously described by this group. Urine of 64 volunteers produced during the night was used in these comparisons. The commercial test was also used to evaluate urine samples of 83 subjects in one of three hospitals. RESULTS: Both methods were essentially in complete agreement (98%) with respect to test results. The multicentre data were: sensitivity 94.7%; specificity 76.9%; positive predictive value (lithogenic urine) 90.0%; negative predictive value (non-lithogenic urine) 87.0%; test efficacy 89.2%. CONCLUSION: The new commercial NefroPlus test offers fast and cheap evaluation of the overall risk of development of urinary calcium-containing calculi.

Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.

The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.

Phytate reduces age-related cardiovascular calcification.

The aim of this research was to evaluate the effect of dietary phytate on cardiovascular calcification in rats during aging. Male Wistar rats (10 weeks old) were randomly assigned to four diet groups. The control group was fed with a balanced diet (UAR-A04) containing phytate. The AIN group was fed a purified diet (AIN-76A) with an undetectable level of phytate. The PHY group was fed with a purified diet (AIN-76A) enriched with phytate (phytin, as the calcium magnesium salt). The MOD group was fed with the AIN-76A diet (phytate undetectable) enriched with MgO, inositol and CaHPO4. At 76 weeks of age all rats were sacrificed, and the aortas, hearts, kidneys, livers and femurs were removed for chemical analysis. The most significant differences were found in the aorta calcium content. Phytate-treated rats (the control and PHY groups) had significantly lower levels of calcium in the aorta compared to nonphytate-treated rats (AIN and MOD groups). The present study demonstrated that dietary phytate treatment significantly reduced age-related aorta calcification.

Effect of crystallization inhibitors on vascular calcifications induced by vitamin D: a pilot study in Sprague-Dawley rats.

BACKGROUND: Pathological calcification in soft tissues (ie, ectopic calcification) can have severe consequences. Hydroxyapatite is the common mineral phase present in all tissue calcifications. In general, the development of tissue calcifications requires a pre-existing injury as an inducer (heterogeneous nucleant), whereas further progression requires the presence of other promoter factors (such as hypercalcemia and/or hyperphosphatemia) and/or a deficiency in calcification repressor factors (crystallization inhibitors and cellular defense mechanisms). The present study investigated the capacity of etidronate (a bisphosphonate used in osteoporosis treatment) and phytate (a natural product) to inhibit vascular calcification in rats. METHODS AND RESULTS: Six male Sprague-Dawley rats in each of the 3 treatment groups were subcutaneously injected with either a placebo (physiological serum solution), etidronate (0.825 micromol x kg(-1) x day (-1)) or phytate (0.825 micromol x kg (-1) x day(-1)) for 8 days. Four days into this regimen, calcinosis was induced by subcutaneous injections of 500,000 IU/kg vitamin D at 0 h, 24 h and 48 h. Ninety-six hours after the final vitamin D injection, the rats were killed and aortas and their hearts were removed for histological and calcium analyses. The data showed that phytate-treated rats had lower levels of aortic calcium than placebo-treated rats. All groups had similar heart calcium levels. CONCLUSIONS: The present study found that phytate acted as a vascular calcification inhibitor. Thus, the action of polyphosphates could be important in protecting against vascular calcification.

Renal lithiasis and nutrition.

Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified through diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins) and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine) is discussed.

Study of the absorption of myo-inositol hexakisphosphate (InsP6) through the skin.

Recently, some properties of myo-inositol hexakisphosphate (InsP(6)) are related to its dermatological use as discolouring agent, on preventing calcinosis cutis or due to its important role on premature aging. Some studies also seem to demonstrate a capacity of InsP(6) to inhibit skin cancer. In this paper, a first study of the absorption of InsP(6) through the skin is developed. Due to the correlation between InsP(6) absorption and its urinary excretion, these last values were used to evaluate this process. It was found that using a moisturizing cream as vehicle, the InsP(6) sodium salt was absorbed at significantly higher amounts than the InsP(6) calcium-magnesium salt. Maximum InsP(6) urinary concentrations were observed approximately at 14 d of 2% InsP(6) topical cream application, and gave 66.35+/-5.49 mg/l urinary InsP(6) when the sodium salt was used and 16.02+/-2.61 mg/l urinary InsP(6) when the calcium-magnesium salt was applied. When the InsP(6) topical cream administration ceased, the InsP(6) urinary excretion fell dramatically approximately during a period of 10 d. From these results, it can be deduced that by topical administration InsP(6) can achieve important concentrations in tissues and biological fluids, this demonstrating that it is possible to propose the topic use as a new InsP(6) administration route.

Absorption of myo-inositol hexakisphosphate (InsP6) through the skin: study of the matrix effects. mechanism of phytate topical absorption.

Myo-inositol hexakisphosphate (InsP6, phytate) is a molecule to which diverse beneficial properties have been attributed. Some of these properties are related to its dermatological use as discolouring agent, on preventing calcinosis cutis or due to its important role on premature aging. Other studies also seem to demonstrate a capacity of InsP6 to inhibit skin cancer. In this paper, the effect of the vehicle of topical administration of phytate is studied, using four groups of male Wistar rats (n = 6) fed with an InsP6 defficient diet and treated with a hydrophyl gel or an O/W moisturizing cream with two different concentrations of InsP6. Due to the correlation between InsP6 absorption and its urinary excretion, these last values were used to evaluate this process. It was found that phytate was absorbed through the skin using both a gel or a cream, demonstrating that its absorption is independent on the matrix used for topical treatment. However, urinary InsP6 values were slightly higher when using the gel, but in all cases values were much higher than those found with oral InsP6 treatment, due to the formation of insoluble species in the gastrointestinal tract when InsP6 is administered orally.

Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas.

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.

Deoxycoformycin in the treatment of patients with hairy cell leukemia: results of a Spanish collaborative study of 80 patients.

BACKGROUND: Deoxycoformycin (DCF) has been reported to produce high response rates in patients with hairy cell leukemia (HCL), but to the authors' knowledge data regarding experience with such therapy in a large HCL series are scarce. METHODS: Between 1988-1997, DCF (4 mg/m(2)/day, every 2 weeks) was administered to 80 HCL patients in 32 Spanish institutions. In 35 of 78 evaluable patients DCF was the first-line therapy; the remaining 43 patients had received other therapies. Pretreatment variables influencing the achievement of complete remission (CR) and event free survival were identified by multivariate analyses. RESULTS: The median number of cycles administered was 7 (range, 1-22 cycles). A CR was obtained in 56 patients (72%) and a partial remission was obtained in 13 patients, for an overall response rate of 88%. In the multivariate analysis previous splenectomy and an Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 were the parameters adversely influencing CR achievement. With a median follow-up of 31.2 months (range, 0.4-126.5 months), disease recurrence was observed in 11 of the CR patients, 5 of whom showed a further response to DCF. An ECOG performance status > or = 2 was the only pretreatment variable associated with a shorter event free survival. Seven patients died, four during the treatment period. The actuarial median event free survival was 46 months (95% confidence interval, 22.5-69.5 months), and 48.7% of the 56 patients who achieved a CR were expected to be alive and disease free at 5 years. Hematologic toxicity (marked neutropenia [22 cases], anemia [6 cases], and thrombocytopenia [1 case]) was the main side effect, followed by nausea and emesis (5 cases); 14 patients required hospitalization. CONCLUSIONS: The results of the current study confirm the effectiveness and acceptable toxicity of DCF in the treatment of patients with HCL.

[Philadelphia chromosome-positive chronic myeloid leukemia in the elderly: presenting features, natural history and survival]. / Leucemia mieloide crónica cromosoma Filadelfia positivo en sujetos de edad avanzada: características iniciales, historia natural y supervivencia.

BACKGROUND: Among patients with chronic myeloid leukaemia (CML) old people represent a minority whose disease characteristics are not well known. The aim of the study was to analyze the presenting features, the evolutive course, and the survival of older persons with Ph-positive CML. PATIENTS AND METHODS: Forty-four individuals > 65 years diagnosed with Ph-positive CML in a single centre were compared with 292 younger patients. RESULTS: Comparison of the presenting features of chronic phase Ph-positive CML patients yielded the following significant differences: predominance of female sex (15 males/29 females versus 155/137; p = 0.02), higher proportion of patients with anaemic syndrome (12% versus 2%; p = 0.001), lower frequency of splenomegaly (41% versus 68%; p = 0.001), and higher serum levels of uric acid (p = 0.0006) in the older group. Although the latter patients survived significantly less (median survival 36.6 months, 95% CI: 27-46.2, versus 57.6 months, 95%: 51.2-64.1; p = 0.004), 9 of the 33 deaths registered in this group (27%) occurred in the chronic phase of CML, versus 15 (9%) of the 166 deaths in the younger group (p = 0.003). When chronic phase deaths were excluded and leukaemia-related deaths only considered (i.e., those occurring in the BC or the accelerated phase of CML), old patients still had a shorter survival but the difference was no longer significant. CONCLUSIONS: Ph-positive CML features are essentially the same in older and young individuals, since most of the differences observed are attributable rather to the patients' advanced age than to the leukaemia itself.

[Primary MALT-type lymphoma of the breast]. / Linfoma primario de mama tipo MALT.

A 47 year old woman with a MALT lymphoma affecting the breast exclusively is reported. Complete response was achieved after CHOP chemotherapy but three years later a relapse was observed. Second-line chemotherapy (CNOP) and local radiotherapy were administered, and a second remission was obtained lasting for 1 year at last follow-up. A bibliographic search of MALT lymphomas of the breast showed that most such cases correspond to localized forms (stage I-II) and that from the radiologic point of view nodular lesions are almost the rule, although in the present case diffuse involvement was observed. MALT lymphomas of the breast tend to remain localized, and to relapse locally, and these facts appear as independent of the treatment applied (surgery, radiotherapy, chemotherapy or any combination).

Transient pancytopenia after non-A non-B non-C acute hepatitis preceding acute lymphoblastic leukemia.

Transient pancytopenia preceding childhood acute lymphoblastic leukemia (ALL) is an unfrequent but well-known event. The association of this preleukemic syndrome with hepatitis is extremely rare, with only two such cases having been published in the literature. We report the case of a 16-year-old boy who was diagnosed with B-cell type ALL that was preceded by transient pancytopenia with absent hemopoietic cells in the bone marrow following a seronegative hepatitis episode. The clinical, morphologic and immunophenotypic features of this patient are described and the literature on this preleukemic syndrome reviewed, with special emphasis being made on its differential diagnosis with hepatitis-associated aplastic anemia.

Cutaneous involvement as the first manifestation in a case of T-cell prolymphocytic leukaemia.

Mature T-cell malignancies of extracutaneous origin are rare disorders. T-cell prolymphocytic leukaemia (T-PLL) is the most common form of all mature T-cell leukaemias in adults. Secondary skill involvement by T-PLL has been reported in 25% of patients. A case of T-PLL which presented with cutaneous infiltration mimicking a cellulitis-like lesion resistant to antibiotic therapy is described. The diagnosis of T-PLL was subsequently fully supported by the clinical, laboratory and cytological findings, as well as by the immunophenotypic study of the skin biopsy. The present case stresses the importance of accurate evaluation of skin lesions in the diagnosis of some haematological conditions and gives additional information about T-PLL such as a previously non-reported cytogenetic abnormality [t(6;6)] and lack of cutaneous lymphocytic-associated antigen expression.