Influence of clinical therapy and nutritional counseling on the recurrence of urolithiasis

PURPOSE: To evaluate the influence of combined clinical therapy and nutritional guidance on the recurrence of urolithiasis. METHODS: From our registry of patients with recurrent urolithiasis we selected 57 who had at least 5-years of follow-up. We collected 24h urine samples in order to analyze Ca, Na, uric acid, citrate, oxalate, and Mg concentrations and to assess urine volume. Patients filled out a clinical questionnaire before treatment, and abdominal radiographs and/or ultrasound were performed both before treatment and during the follow-up period. During follow-up, specific and individualized dietary advice was given based on the individual's metabolic disorders. Patients also received specific pharmacological treatment for their metabolic alterations. Outcome measures were metabolites in urine and the urolith recurrence rate. Pre- and post- intervention values were compared using tests as appropriate. RESULTS: Fifty six of the patients were male and the majority of patients were overweight. The mean BMI was 27 kg/m2. Urinary excretion of calcium, uric acid and sodium decreased significantly over the five year follow-up period. The number of uroliths that formed during the 5-year follow-up also decreased significantly compared to pre-treatment values. CONCLUSION: Individualized dietary advice combined with pharmacological treatment significantly reduces long-term urolithiasis recurrence.

Efeitos da sobrecarga calórica em ratos machos submetidos ou não a restrição protéica in útero

Pós-graduação em Biologia Geral e Aplicada - IBB

Metabolic parameters of postmenopausal women after quinoa or corn flakes intake - a prospective and double-blind study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação da função tireoidiana, iodúria e estresse oxidativo em gestantes

Pós-graduação em Alimentos e Nutrição - FCFAR

The first cardiac transplant experience in a patient with mucopolysaccharidosis

Hunter syndrome (MPSII) is a rare X-linked lysosomal storage disorder that can affect multiple systems but primarily affects the heart. We report the case of a previously asymptomatic 23-year-old patient who had an attenuated form of MPSII and presented with refractory heart failure that required a heart transplant. The diagnosis was confirmed by detection of an increase in urinary excretion of glycosaminoglycans, a deficiency in enzymatic activity, and molecular analysis. A myocardial biopsy revealed hypertrophic cardiomyocytes, mild fibrosis, and lysosomal storage in interstitial cells. Molecular analysis identified a novel mutation in the iduronate-2-sulfatase gene. Although the clinical outcome was not favorable, we believe that this approach may be valid in end-stage heart failure. (C) 2012 Elsevier Inc. All rights reserved.

Fish Oil Supplementation Reduces Cachexia and Tumor Growth While Improving Renal Function in Tumor-Bearing Rats

The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FENa+) of FO rats was similar to C. Proximal Na+ reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B-2 (TXB2) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

Treatment Adherence and Blood Pressure Control in Older Individuals with Hypertension

Background: Non-adherence to treatment has been identified as the main cause of uncontrolled blood pressure (BP), and may represent a greater risk in older individuals. Objective: The aim of this study was to evaluate and compare the rate of adherence to hypertension treatment using different methods, to estimate the BP control rate, and to observe if there is an association between BP control and adherence. Methods: Treatment adherence was evaluated in older patients with hypertension, followed by the public primary health care, through four methods, including the Morisky-Green test (reference), the Attitude regarding the Medication Intake questionnaire (AMI), an evaluation of adherence by the nurse in the office (Nurse Adherence Evaluation - NAE), and at home (Home Adherence Evaluation - HAE). Salt intake was estimated by 24-hour sodium urinary excretion. BP control was assessed by the awake ambulatory blood pressure monitoring. Results: Concordance between the Morisky-Green test and AMI (Kappa=0.27) or NAE (Kappa=0.05) was poor. There was a moderate concordance between the Morisky-Green test and HAE. Eighty percent had controlled BP, including 42% with white-coat effect. The group with lower salt excretion informed to avoid salt intake more times (p<0.001) and had better medication adherence (p<0.001) than the higher salt excretion group. Conclusion: The evaluated tests did not show a good concordance to the Morisky-Green test. Adherence to hypertension treatment was low; however, there was a high rate of BP control when subjects with the white-coat effect were included in the analysis. (Arq Bras Cardiol 2012;99(1):636-641)

UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model

Since the development and prognosis of alcohol-induced liver disease (ALD) vary significantly with genetic background, identification of a genetic background-independent noninvasive ALD biomarker would significantly improve screening and diagnosis. This study explored the effect of genetic background on the ALD-associated urinary metabolome using the Ppara-null mouse model on two different backgrounds, C57BL/6 (B6) and 129/SvJ (129S), along with their wild-type counterparts. Reversed-phase gradient UPLC-ESI-QTOF-MS analysis revealed that urinary excretion of a number of metabolites, such as ethylsulfate, 4-hydroxyphenylacetic acid, 4-hydroxyphenylacetic acid sulfate, adipic acid, pimelic acid, xanthurenic acid, and taurine, were background-dependent. Elevation of ethyl-β-d-glucuronide and N-acetylglycine was found to be a common signature of the metabolomic response to alcohol exposure in wild-type as well as in Ppara-null mice of both strains. However, increased excretion of indole-3-lactic acid and phenyllactic acid was found to be a conserved feature exclusively associated with the alcohol-treated Ppara-null mouse on both backgrounds that develop liver pathologies similar to the early stages of human ALD. These markers reflected the biochemical events associated with early stages of ALD pathogenesis. The results suggest that indole-3-lactic acid and phenyllactic acid are potential candidates for conserved and pathology-specific high-throughput noninvasive biomarkers for early stages of ALD.

A comprehensive understanding of thioTEPA metabolism in the mouse using UPLC-ESI-QTOFMS-based metabolomics

ThioTEPA, an alkylating agent with anti-tumor activity, has been used as an effective anticancer drug since the 1950s. However, a complete understanding of how its alkylating activity relates to clinical efficacy has not been achieved, the total urinary excretion of thioTEPA and its metabolites is not resolved, and the mechanism of formation of the potentially toxic metabolites S-carboxymethylcysteine (SCMC) and thiodiglycolic acid (TDGA) remains unclear. In this study, the metabolism of thioTEPA in a mouse model was comprehensively investigated using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based-metabolomics. The nine metabolites identified in mouse urine suggest that thioTEPA underwent ring-opening, N-dechloroethylation, and conjugation reactions in vivo. SCMC and TDGA, two downstream thioTEPA metabolites, were produced from thioTEPA from two novel metabolites 1,2,3-trichloroTEPA (VII) and dechloroethyltrichloroTEPA (VIII). SCMC and TDGA excretion were increased about 4-fold and 2-fold, respectively, in urine following the thioTEPA treatment. The main mouse metabolites of thioTEPA in vivo were TEPA (II), monochloroTEPA (III) and thioTEPA-mercapturate (IV). In addition, five thioTEPA metabolites were detected in serum and all shared similar disposition. Although thioTEPA has a unique chemical structure which is not maintained in the majority of its metabolites, metabolomic analysis of its biotransformation greatly contributed to the investigation of thioTEPA metabolism in vivo, and provides useful information to understand comprehensively the pharmacological activity and potential toxicity of thioTEPA in the clinic.

Capillary electrophoresis contributions to the hydromorphone metabolism in man

CE-ESI multistage IT-MS (CE-MS(n), n < or = 4) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of hydromorphone (HMOR) in human urine. Using the same CE conditions as previously developed for the analysis of urinary oxycodone and its metabolites, HMOR and its phase I metabolites produced by N-demethylation, 6-keto-reduction and N-oxidation and phase II conjugates of HMOR and its metabolites formed with glucuronic acid, glucose, and sulfuric acid could be detected in urine samples of a patient that were collected during a pharmacotherapy episode with daily ingestion of 48 mg of HMOR chloride. The CE-MS(n) data obtained with the HMOR standard, synthesized hydromorphol and hydromorphone-N-oxide, and CYP3A4 in vitro produced norhydromorphone were employed to identify the metabolites. This approach led to the identification of previously unknown HMOR metabolites, including HMOR-3O-glucide and various N-oxides, structures for which no standard compounds or mass spectra library data were available. Furthermore, the separation of alpha- and beta-hydromorphol, the stereoisomers of 6-keto-reduced HMOR, was achieved by CE in the presence of the single isomer heptakis(2,3-diacetyl-6-sulfato)-beta-CD. The obtained data indicate that the urinary excretion of alpha-hydromorphol is larger than that of beta-hydromorphol.

Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.

Eicosanoids in exhaled breath condensates in the assessment of childhood asthma

The value of measurements of eicosanoids in exhaled breath condensate (EBC) for the evaluation of childhood asthma is still inconclusive most likely because of the limited value of the methods used. In this case-control study in 48 asthmatic and 20 healthy children, we aimed to characterize the baseline profile of the inflammatory mediators cysteinyl leukotrienes (cysLTs), 9(alpha)11(beta)PGF(2), PGE(2), PGF(2alpha), 8-isoprostane (8-iso-PGF(2alpha)) within EBC in asthmatic compared with healthy children using new methods. In addition, we investigated their relation to other inflammatory markers. The assessment included collection of EBC, measurement of fractional exhaled nitric oxide (FE(NO)) and evaluation of urinary excretion of leukotriene E(4.) cysLTs were measured directly in EBC by radioimmunoassay and prostanoids were measured using gas chromatography negative-ion chemical ionization mass spectrometry. Only cysLT levels were significantly higher in asthmatic compared with healthy children (p = 0.002). No significant differences in cysLTs were found between steroid naïve and patients receiving inhaled corticosteroids. In contrast, FE(NO) was significantly higher in steroid naïve compared with steroid-treated asthmatic and healthy children (p = 0.04 and 0.024, respectively). The diagnostic accuracy of cysLTs in EBC for asthma was 73.6% for the whole group and 78.2% for steroid-naïve asthmatic children. The accuracy to classify asthmatic for FE(NO) was poor (62.9%) for the whole group, but improved to 79.9% when only steroid-naïve asthmatic children were taken into consideration. cysLTs in EBC is an inflammatory marker which distinguishes asthmatics, as a whole group, from healthy children.

(18)F-Immuno-PET: Determination of Anti-CD66 Biodistribution in a Patient with High-Risk Leukemia

The monoclonal antibody anti-CD66 labeled with (99m)Tc is widely used as Scintimun((R)) granulocyte for bone marrow immunoscintigraphy. Further, recently performed clinical radioimmunotherapy studies with [(90)Y]Y-anti-CD66 proved to be suitable for the treatment of hematologic malignancies. Before radioimmunotherapy with [(90)Y]Y-anti-CD66, dosimetric estimations are required to minimize radiotoxicity and determine individual applicable activities. Planar imaging, using gamma-emitting radionuclides, is conventionally carried out to estimate the absorbed organ doses. In contrast, immuno-PET (positron emission tomography) enables the quantification of anti-CD66 accumulation and provides better spatial and temporal resolution. Therefore, in this study, a semiautomated radiosynthesis of [(18)F] F-anti-CD66 was developed, using the (18)F-acylation agent, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). As a proof of concept, an intraindividual comparison between PET and conventional scintigraphy, using (18)F- and (99m)Tc-labeled anti-CD66 in 1 patient with high-risk leukemia, is presented. Both labeled antibodies displayed a similar distribution pattern with high preferential uptake in bone marrow. Urinary excretion of [(18)F] F-anti-CD66 was increased and bone marrow uptake reduced, in comparison to [(99m)Tc]Tc-anti-CD66. Nevertheless, PET-based dosimetry with [(18)F] F-anti-CD66 could provide additional information to support conventional scintigraphy. Moreover, [(18)F]F-anti-CD66 is ideally suited for bone marrow imaging using PET.

A gamma-glutamyl peptide isolated from onion (Allium cepa L.) by bioassay-guided fractionation inhibits resorption activity of osteoclasts

One gram of onion added to the food of rats inhibits significantly (p < 0.05) bone resorption as assessed by the urinary excretion of tritium released from bone of 9-week-old rats prelabeled with tritiated tetracycline from weeks 1 to 6. To isolate and identify the bone resorption inhibiting compound from onion, onion powder was extracted and the extract fractionated by column chromatography and medium-pressure liquid chromatography. A single active peak was finally obtained by semipreparative high-performance liquid chromatography. The biological activity of the various fractions was tested in vitro on the activity of osteoclasts to form resorption pits on a mineralized substrate. Medium, containing the various fractions or the pure compound, was added to osteoclasts of new-born rats settled on ivory slices. After 24 h of incubation, the tartrate-resistant acid phosphatase positive multinucleated cells, that is, osteoclasts, were counted. Subsequently, the number of resorption pits was determined. Activity was calculated as the ratio of resorption pits/osteoclasts and was compared to a negative control, that is, medium containing 10% fetal bovine serum only and to calcitonin (10(-12) M) as a positive control. Finally, a single peak inhibited osteoclast activity significantly (p < 0.05). The structure of this compound was elucidated with high-performance liquid chromatography-electrospray ionization-mass spectrometry, time-of-flight electrospray ionization mass spectrometry, and nuclear magnetic resonance spectroscopy. The single peak was identified as gamma-L-glutamyl-trans-S-1-propenyl-L-cysteine sulfoxide (GPCS). It has a molecular mass of 306 Da and inhibits dose-dependently the resorption activity of osteoclasts, the minimal effective dose being approximately 2 mM. As no other peak displayed inhibitory activity, it likely is responsible for the effect of onion on bone resorption.