ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish.

Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities. Hence, zebrafish can bridge the gap between preclinical in vitro safety assays and rodent models in a fast and cost-effective manner. ZeGlobalTox is an innovative assay that sequentially integrates in vivo cardio-, neuro-, and hepatotoxicity assessment in the same animal, thus impacting strongly in the 3Rs principles. It Reduces, by up to a third, the number of animals required to assess toxicity in those organs. It Refines the drug toxicity evaluation through novel physiological parameters. Finally, it might allow the Replacement of classical species, such as rodents and larger mammals, thanks to its high predictivity (Specificity: 89%, Sensitivity: 68% and Accuracy: 78%).

Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.

To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[(d,l-lactide-co-glycolide)-co-PEG] (PLGA-co-PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. FROM THE CLINICAL EDITOR: Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase.

Specificity and sensitivity of objective tests to detect possible malingering in fibromyalgia: a case-control study in 211 Spanish patients.

OBJECTIVES: To characterise patients diagnosed with fibromyalgia (FM) who present a clinical profile suggestive of simulation. METHODS: Observational case-control study of 218 patients who met the classification criteria for FM. The profile supporting simulation was based on the proposed criteria for evaluating disability related to the simulation of pain. RESULTS: Compared with controls (n=105), patients with suspected simulation of FM (n=106) had a higher mean age (52.5 vs. 49.2 years, p=0.003), a higher frequency of primary education (88.7% vs. 58.1%; p<0.001), a higher percentage of separated/widowed persons (33.9% vs. 8.6%, p<0.001), a higher frequency of psychiatric disorders (100% vs. 67.6%, p<0.001), a higher mean number of positive 'control' tender points (4.5 vs. 1.3, p<0.001), a higher mean FIQ questionnaire score (89.8 vs. 68.8, p<0.001) and a lower mean LHS questionnaire score (41.0 vs. 59.9, p<0.001). Patients with suspected simulation were able to walk a shorter distance in the 6-minute walk test than controls (231.0 vs. 356.3 metres, p<0.001), while the appearance of allodynia was achieved with a significantly lower mmHg pressure (159.8 vs. 229.9 mm Hg, p<0.001). CONCLUSIONS: Some physical/functional tests, together with the administration of specific questionnaires, may identify a subgroup of patients with FM with a profile consistent with simulation or malingering; these patients have a differentiated demographic and psychiatric profile in comparison with FM patients without a profile of simulation.

The life of the cell membrane: A paradigmatic reading from Deleuze and Guattari.

While the Fluid Mosaic model (FMM) is widely accepted as an account of the cell membrane's structure-function, its inability to explain certain phenomena has led to the lipid rafts hypothesis (nanodomains) that spontaneous spatiotemporal enriched zones of sphingolipids-cholesterol-protein exist within the membrane. In this text, we propose a novel approach that conceives the cell membrane as a living entity. The questions regarding the FMM revolve around the fact that, although these molecular components are present in many cell types, the membrane does not react in the same way to every external agent; for example, a virus evokes a particular response: why is there some marked specificity of virus (or toxin) attack on one (or some) of these cell types and not to other cell types that nevertheless have a similar membrane protein constitution? The crucial question, to explain this selectivity, would be what determines the specificity of attack on some cells and not others? While FMN assumes a dynamism between macrostates at the intramolecular, intermolecular, and/or collective levels in the membrane, the approach of the lipid raft model presupposes a much greater and more complex dynamics of microstates (even nano-states) of these molecular components. In other words, it implies higher and instantaneous mobility as assemblages ("intentional") and thus, of the membrane itself (as a collective), in response to changes in the internal and external physicochemical environment over a broad spatiotemporal scale. This suggests a mechanism of membrane adaptation in the face of evolutionary constraints. In this text, we propose a paradigmatic approach, from Deleuze-Guattari's philosophy: to conceive the cell membrane as living and not as a mere molecular conglomerate with particular functions and mechanical processes between molecules. For this, we employ the functional concepts of territory and machinic assemblage, whence the vitality of the membrane would allow us to postulate instantaneous updates, within wider spatiotemporal scales in its composition in contrast with the model that dominates as a more plausible explanation nowadays, that does not include smaller spatiotemporal events. If we resort to the concept of territory and its different media components, we could offer a more plausible explanation of the vigorous dynamism in the composition of the cell membrane since it would allow more subtle and complex differentiations between media and thus make visible the constant and instant changes. We propose that the model of nanodomains, understood as a process of dynamic territorialization, offers a more complex and subtle explanation of the instantaneous changes in the cell membrane's composition. This approach expands the explanatory framework for cellular phenomena and reveals their spatiotemporal complexity in accordance with other research.

Estimated Phytate Intake Is Associated with Bone Mineral Density in Mediterranean Postmenopausal Women.

The main objective of this work was to explore the association of dietary phytate intake with bone mineral density (BMD) in a Mediterranean population of postmenopausal women. For this purpose, a cross-sectional analysis of 561 women aged 55-75 years with overweight/obesity and metabolic syndrome from a Mediterranean area and with data on dual-energy X-ray absorptiometry (DXA) scans in femur and lumbar spine was performed. Estimated phytate intake was calculated using a validated food frequency questionnaire. Our results indicated that phytate intake was associated with BMD [ß(95%CI) per each 25 mg/100 kcal] in femoral neck [0.023(0.060-0.040) g/cm2], femoral Ward's triangle [0.033(0.013-0.054) g/cm2], total femur [0.018(0.001-0.035) g/cm2], and all the analyzed lumbar spine sites [L1-L4: 0.033(0.007-0.059) g/cm2] after adjusting for potential confounders. The sensitivity analysis showed that phytate intake was directly associated with lumbar spine BMD in women younger than 66 years, with a body mass index higher than 32.6 kg/cm2 and without type 2 diabetes (all p-for interactions < 0.05). The overall results indicated that phytate, a substance present in food as cereals, legumes and nuts, was positively associated with BMD in Mediterranean postmenopausal women. Phytate may have a protective effect on bone resorption by adsorbing on the surfaces of HAP. Nevertheless, large, long-term, and randomized prospective clinical studies must be performed to assess the possible benefits of phytate consumption on BMD in postmenopausal women.

Characterization of γ-glutamyltransferase- and phytochelatin synthase-mediated catabolism of glutathione and glutathione S-conjugates in Arabidopsis thaliana.

Glutathione (GSH, γ-L-glutamyl-L-cysteinyl-glycine) has been implicated in a multitude of cellular functions, such as protection of cells against oxidative stress, detoxification of xenobiotics via degradation of GSH S-conjugates, and disease resistance. Glutathione also serves as a precursor of phytochelatins, and thereby plays an essential role in heavy metal detoxification. The Arabidopsis genome encodes three functional γ-glutamyltransferase genes (AtGGT1, AtGGT2, AtGGT4) and two phytochelatin synthase genes (AtPCS1, AtPCS2). The function of plant GGT has not yet been clearly defined, although it is thought to be involved in GSH and GSH S-conjugate catabolism. On the other hand, besides its role in heavy metal detoxification, PCS has also been involved in GSH S-conjugate catabolism. Herein we describe the HPLC characterization of GSH and GSH S-conjugate catabolism in Arabidopsis mutants deficient in GSH biosynthesis (pad2-1/gsh1), atggt and atpcs1 T-DNA insertion mutants, atggt pad2-1, atggt atpcs1 double mutants, and the atggt1 atggt4 atpcs1 triple mutant. The results of our HPLC analysis confirm that AtGGT and AtPCS play important roles in two different pathways related with GSH and GSH S-conjugate (GS-bimane) catabolism in Arabidopsis.

Implementation of Zebrafish Ontologies for Toxicology Screening.

Toxicological evaluation of chemicals using early-life stage zebrafish (Danio rerio) involves the observation and recording of altered phenotypes. Substantial variability has been observed among researchers in phenotypes reported from similar studies, as well as a lack of consistent data annotation, indicating a need for both terminological and data harmonization. When examined from a data science perspective, many of these apparent differences can be parsed into the same or similar endpoints whose measurements differ only in time, methodology, or nomenclature. Ontological knowledge structures can be leveraged to integrate diverse data sets across terminologies, scales, and modalities. Building on this premise, the National Toxicology Program's Systematic Evaluation of the Application of Zebrafish in Toxicology undertook a collaborative exercise to evaluate how the application of standardized phenotype terminology improved data consistency. To accomplish this, zebrafish researchers were asked to assess images of zebrafish larvae for morphological malformations in two surveys. In the first survey, researchers were asked to annotate observed malformations using their own terminology. In the second survey, researchers were asked to annotate the images from a list of terms and definitions from the Zebrafish Phenotype Ontology. Analysis of the results suggested that the use of ontology terms increased consistency and decreased ambiguity, but a larger study is needed to confirm. We conclude that utilizing a common data standard will not only reduce the heterogeneity of reported terms but increases agreement and repeatability between different laboratories. Thus, we advocate for the development of a zebrafish phenotype atlas to help laboratories create interoperable, computable data.

Non-infectious phosphate renal calculi: fine structure, chemical and phase composition.

BACKGROUND: Chemical composition of internally non-homogeneous phosphate stones should be related to the conditions prevailing during the formation of each individual part. OBJECTIVE: The object of this paper was to provide a detailed study of phosphate stone composition on the micro- and macro-scales. METHODS: Fine inner structure, chemical and phase composition of 10 phosphate calculi from different patients were determined by chemical (wet) analysis, observation by scanning microscope, semi-quantitative determination of Ca, Mg, P and C by energy dispersive X-ray and by X-ray diffraction. Results. Eight calculi are formed by amorphous calcium phosphate and two by hydroxyapatite. Magnesium was inversely related to Ca/P ratio. Point chemical composition of solid phase varies in wide limits, i.e. composition of calculus interior is highly inhomogeneous on the microscale. All studied calculi contained an abundance of organic matter incorporated in their volume; the content of carbon was double the calcium content in molar quantities. CONCLUSIONS: Phosphate renal calculi with the low Ca/P molar ratio predominantly consist of amorphous calcium phosphate whereas those with a high Ca/P molar ratio are composed of poorly crystalline hydroxyapatite which can be partially carbonated. Magnesium may be an inhibitor of HAP formation from urine. Abundant organic matter incorporated into the calculus volume indicates its decisive role at stone formation. Variable point composition of stones implies widely varying conditions during their development.

Rare calcium oxalate monohydrate calculus attached to the wall of the renal pelvis.

Most renal calculi can be classified using well-established criteria in a manner that reflects both composition and fine structure under specific pathophysiological conditions. However, when a large patient population is considered, rare renal calculi invariably appear, some of which have never been classified; careful study is required to establish stone etiology in such cases. The patient in the present case report formed two types of calculi. One was attached on the wall of the renal pelvis near the ureter and part of the calculus was embedded inside pelvic renal tissue. The calculus developed on an ossified calcification located in the pelvis tissue. Current knowledge on the development of calcification in soft tissues suggests a pre-existing injury as an inducer of its development. A mechanism of calculus formation is proposed. The second stone was a typical jack-stone calculus.

Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators.

Patients with immune conditions and immune-modifying therapies were excluded from the Covid-19 vaccine trials. Studies have shown conflicting response to different vaccines in persons receiving immune suppressors or biologics. The aim of this study is to evaluate humoral and cellular response to Covid-19 vaccines in patients with Inflammatory Bowel Disease (IBD) using biologic and/or immunomodulatory (IMM) therapies. Methods: Participants are adults with IBD receiving biologics or IMM planning to receive a Covid 19 vaccine. Cellular immunity (CD4+ and CD8+ T cell levels) with flow cytometry are measured at baseline and 2 weeks after each vaccine dose. Humoral immunity (antibody titers and neutralizing capacity,VNT%) is analyzed by ELISA at baseline, 2 weeks after each dose, and 6 and 12 months after vaccine. We present the early results of the first 19 subjects. The study is approved by the IRB. Results: 19 subjects (18 in biologics and 1 in IMM) who received 2 doses of the Pfizer-BioNTech vaccine are included. Total IgG antibodies increased 21.13 times after the first dose and 90 times after the second dose. VTN% increased 11.92 times after the first dose and 53.79 times after the second dose. When compared with a healthy control cohort, total IgG antibodies and VTN% were lower in the subjects after the first dose. After the second dose, IgG antibodies increased but remained lower than controls, but VTN% were similar to controls. CD4 and CD8 mean levels had an upward trend after vaccination. Conclusions: Neutralizing capacity response to the vaccine in subjects was similar to a healthy cohort in spite of lower increases in total IgG antibodies. The CD4 and CD8 results observed may support the capacity to mount an effective cellular response in patients on biologics. Larger studies are needed to determine vaccine efficacy in these patients.

Effects of Mediterranean diets with low and high proportions of phytate-rich foods on the urinary phytate excretion.

BACKGROUND: Important health benefits have been reported recently to phytate intake. This includes the prevention of pathological calcifications such as renal calculi, dental calculi and cardiovascular calcification, due its action as crystallization inhibitor of calcium salts, and as preventive of cancer. AIM OF STUDY: The aim of this study was to establish a relation between the intake of phytate, through consumption of typical components of the Mediterranean diet (including nuts), and its excretion in urine. METHODS: This study recruited participants from subjects included in a larger trial (PREDIMED) of food habits, that were assigned to one of two diet groups: (1) the Mediterranean diet with low proportion of phytate-rich food group, where participants were asked to maintain their usual diet; and (2) the Mediterranean diet with high proportion of phytate-rich food group, where participants were asked to increase phytate-rich foods in their diet. Phytate intake was assessed on the basis of a food frequency questionnaire. Urinary phytate excretion was determined in 2-h urine samples. RESULTS: The overall phytate consumption of the Mediterranean diet with high proportion of phytate-rich food group (672 +/- 50 mg) was significantly higher than the Mediterranean diet with low proportion of phytate-rich food group (422 +/- 34 mg), representing a 59% difference. Urinary phytate excretion was also significantly higher (54%) in the Mediterranean diet with high proportion of phytate-rich food group (1,016 +/- 70 microg/L) than the Mediterranean diet with low proportion of phytate-rich food group (659 +/- 45 microg/L). CONCLUSIONS: Mediterranean diets high in whole cereals, legumes and nuts compared to Mediterranean diets low in these phytate-rich foods increase the urinary phytate excretion in humans.

Phytotherapy and renal stones: the role of antioxidants. A pilot study in Wistar rats.

Since ancient times, various herbal preparations have been used in renal lithiasis therapy, but conclusive scientific data on their therapeutic effects and efficacy are not available. To address this issue, the present study evaluated the antilithiasic activity of a traditional Mallorcan herbal preparation, and compared its effects with those of the antioxidant flavonoids, catechin and epicatechin. Thirty-six male Wistar rats were assigned randomly to four groups (n = 9): a control group, a catechin (CAT) treatment group, an epicatechin (EPI) treatment group, and a group treated with a folk herbal extract (FHE). After 16 days of treatment, calcium oxalate lithiasis was induced in the rats using ethylene glycol. After 8 days (treatment + ethylene glycol), 24-h rat urine was collected, the animals were sacrificed and their kidneys were removed for histological and chemical analysis. The calcium concentration in kidney tissue was significantly lower in the CAT-treated (2.4 +/- 0.3 mg/g), EPI-treated (1.8 +/- 0.3 mg/g) and FHE-treated (2.1 +/- 0.3 mg/g) groups, than in the control group (5.4 +/- 1.4 mg/g). Examination of paraffin-embedded kidney sections showed that control group rats had the greatest amount of calcification. There were no significant differences between control and treated groups with respect to urinary calcium, magnesium, oxalate and citrate concentrations. These results demonstrate the ability of herbal preparations and antioxidants to prevent the development of papillary and intratubular calcification in the kidney.

Association of Adherence to The Mediterranean Diet with Urinary Factors Favoring Renal Lithiasis: Cross-Sectional Study of Overweight Individuals with Metabolic Syndrome.

Our purpose was to study the relationship of adherence to the Mediterranean diet (MedDiet) with urinary factors that favor the formation of renal calcium and uric acid stones in overweight and obese participants who had metabolic syndrome. This cross-sectional study examined 267 participants. A well-known MedDiet score (range 0-9) was calculated for each patient, and patients were then categorized has having low (≤3), medium (4-5), or high (≥6) adherence to the MedDiet. Baseline characteristics and urinary parameters were also analyzed. High calcium salt urinary crystallization risk (CaUCR) and high uric acid urinary crystallization risk (UrUCR) were calculated from urinary parameters using pre-defined criteria. More than half of patients with MedDiet scores ≤3 had high UrUCR (55.4%) and high CaUCR (53.8%). In contrast, fewer patients with high adherence (≥6) to the MedDiet had high UrUCR (41.2%) and high CaUCR (29.4%). Relative to those with low adherence, individuals with high adherence had a prevalence ratio (PR) of 0.77 for a high UrUCR (95% CI: 0.46-1.12; p for trend: 0.069) and a PR of 0.51 for a high CaUCR (95% CI: 0.26-0.87; p for trend: 0.012) after adjusting for age, sex, body mass index, type 2 diabetes, and total energy intake. Our findings indicate that greater adherence to the MedDiet was associated with a reduced CaUCR and a reduced UrUCR. This suggests that adequate dietary management using the MedDiet patterns may prevent or reduce the incidence and recurrence of calcium salt and uric acid renal stones.

Impaired Liver Size and Compromised Neurobehavioral Activity are Elicited by Chitosan Nanoparticles in the Zebrafish Embryo Model.

The use of chitosan nanoparticles (ChNPs) in various biological and environmental applications is attracting great interest. However, potential side effects related to ChNP toxicity remain the major limitation hampering their wide application. For the first time, we investigate the potential organ-specific (cardiac, hepatic, and neuromuscular) toxicity of ChNPs (size 100⁻150 nm) using the zebrafish embryo model. Our data highlight the absence of both acute and teratogenic toxic effects of ChNPs (~100% survival rate) even at the higher concentration employed (200 mg/L). Although no single sign of cardiotoxicity was observed upon exposure to 200 mg/L of ChNPs, as judged by heartbeat rate, the corrected QT interval (QTc, which measures the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle), maximum cardiac arrest, and ejection fraction assays, the same dosage elicited the impairment of both liver size (decreased liver size, but without steatosis and lipid yolk retention) and neurobehavioral activity (increased movement under different light conditions). Although the observed toxic effect failed to affect embryo survival, whether a prolonged ChNP treatment may induce other potentially harmful effects remains to be elucidated. By reporting new insights on their organ-specific toxicity, our results add novel and useful information into the available data concerning the in vivo effect of ChNPs.

Phytate inhibits bovine pericardium calcification in vitro.

OBJECTIVE: The present study examined the inhibitory effects of pyrophosphate, etidronate, and phytate on bovine pericardium calcification in vitro. METHODS: Bovine pericardium was glutaraldehyde fixed and then placed in a flow chamber in the presence of a synthetic physiological fluid alone (control) or the fluid plus various concentrations of pyrophosphate, etidronate, or phytate. Following a 96-h incubation, fragments were removed and assayed for calcification by measuring calcium and phosphorus levels. RESULTS: The data indicated that both pyrophosphate and etidronate at 1 mg/l (5.75 and 4.95 microM, respectively) inhibited bovine pericardium calcification, whereas neither agent had an effect at 0.5 mg/l (2.87 and 2.47 microM, respectively). Phytate was the most potent inhibitor of calcification, and the effects of this agent were apparent at levels as low as 0.25 mg/l (0.39 microM). CONCLUSIONS: While pyrophosphate, etidronate, and phytate were all able to inhibit bovine pericardium calcification in vitro, phytate was found to be the most effective.

Role of phytate and osteopontin in the mechanism of soft tissue calcification.

BACKGROUND: Understanding the mechanism of calcium deposition in soft tissues is of great importance in a variety of pathological conditions such as chronic kidney disease. The present study examined the role of phytate and osteopontin during the development of soft tissue calcification in an animal model. METHODS: Male Wistar rats (16 rats per treatment) were fed with a diet (AIN-76A) in which phytate is undetectable (non-phytate-treated group), or with a phytin-enriched AIN-76A diet (phytate-treated group). After 21 days on the respective diets, all rats were subjected to calcinosis induction by subcutaneous injection with KMnO4 at 2 sites on either side of the interscapular region. At 2, 5, 8 and 10 days after the calcinosis induction, 4 rats of each group were sacrificed, and the injured tissues were removed for histological analysis and for calcium determination. RESULTS: Calcification was notably and significantly reduced in phytate-treated rats compared with non-phytate-treated rats. Calcified deposits appeared as soon as 2 days after calcinosis induction, but inflammation with the presence of macrophages, lymphocytes and eosinophils was not typically observed until 5 days postinduction. Osteopontin was only detected 8 days postinduction, and was clearly associated with calcified areas. CONCLUSIONS: The results suggest an important role for crystallization inhibitors such as phytate in reducing hydroxyapatite crystal formation in the first steps of soft tissue calcification. Histological analysis indicated that osteopontin was not involved during initiation of soft tissue calcification. Osteopontin appears be involved in the control of calcification rather than its genesis.

[Continuous use of PDE5 inhibitors in the treatment of erectile dysfunction: New insights and opportunities]. / Uso continuado de inhibidores de la PDE5 en el tratamiento de la disfunción eréctil: nuevas perspectivas y oportunidades.

At present, there is debate regarding the continuous use of phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Cumulative evidence supports the benefit, even at low doses, thatcontinuous treatment has on erectile function -even in difficult-to-treat patients-, and on the spontaneity and naturalness of sexual relationships. Safety and tolerability have also proven to be good. Beyond phosphodiesterase 5 inhibition, the effect of continuous treatment of erectile function appears to be based on improvement of endothelial function and oxygenation of the penile vascular bed as a result of the increased number of erections, hence playing down the importance of pharmacokinetics. Although evidence is still limited, this new scenario opens new paths for the treatment of erectile dysfunction patients in whom on-demand treatments are not effective or deemed appropriate, and would benefit the spontaneity of sexual life.

Effect of Consumption of Cocoa-Derived Products on Uric Acid Crystallization in Urine of Healthy Volunteers.

The purpose of this study was to determine the effects of consumption of different cocoa-derived products on uric acid crystallization in urine of 20 healthy volunteers. Participants were requested to select the specific diet that they wished to follow during the 12 h prior to collection of urine. The only restriction was that the diet could not include any product with cocoa, coffee, or caffeine. On the first day, each volunteer followed their selected diet, and an overnight 12 h urine sample was collected as the baseline urine. After seven days on an unrestricted diet, each volunteer repeated the same diet with 20 g of milk chocolate, chocolate powder, or dark chocolate during breakfast and another 20 g during dinner. Overnight 12 h urine samples were then collected. Urine volume, pH, oxalate, creatinine, uric acid, theobromine, and a uric acid crystallization test were determined for each sample. The results for all 20 patients show that uric acid crystallization was significantly lower following the consumption of chocolate powder or dark chocolate relative to baseline or following the consumption of milk chocolate. The results indicated that increased concentrations of urinary theobromine reduced the risk of uric acid crystallization.

Relationship Between Erectile Dysfunction, Diabetes and Dyslipidemia in Hypertensive-Treated Men.

PURPOSE: PRESIDEN study is a large study to analyze the erectile dysfunction (ED) incidence in Spanish population. The present study is a pilot sub-analysis from PRESIDEN to determine if ED or plasma testosterone (TST) level in controlled hypertensive patients may be associated with comorbidities and/or plasma nitrite+nitrate and antioxidant capacity. MATERIALS AND METHODS: Forty-four hypertensive individuals were aleatory selected from PRESIDEN study, matching by age (28 showing ED and 16 without ED). RESULT: Diabetes was present in 28.57% of ED patients and in 18.75% of patients without ED. In patients with and without ED, increasing age showed tendency of higher frequency of an additional comorbidity (diabetes or dyslipemia) (P = .09). Apparently, plasma TST levels were lower in older ED patients compared to younger patients with and without ED, although it did not reach statistical significance (P = .69). Older ED patients also showed lower TST levels than older patients without ED, although it was not statistical significant (16.15 ± 2.84 vs 13.91± 2.77; P = .69). Dyslipidemia was showed by 52.17% with lower TST (? nmol/L) while 23.80% of patients with plasma TST levels > 15 nmol/L had dyslipidemia. The percentage of ED patients was similar between patients with low and high TST levels. CONCLUSION: More ED hypertensive patients seem to show two comorbidities (diabetes and dyslipidemia) than hypertensivepatients without ED. Younger patients with ED tended to show more commonly diabetes than older ED patients. Plasma TST levels were not associated with more prevalence of ED but lower plasma TST levels showed tendency to higher prevalence of dyslipidemia.

[May renal lithiasis be really prevented? New trends and therapeutic tools.] / Se puede realmente prevenir la litiasis renal? Nuevas tendencias y herramientas terapéuticas.

Renal calculi are generally formed as a result of the combination of certain factors, some related to urine composition (concentration of lithogenic substances, deficiency of crystallization inhibitors, presence of heterogeneous nucleants) and others with renal morphology and anatomy (urinary tract stasis, low urodynamic efficiency cavities, morpho-anatomic deformations, renal papillary tissue lesions). In fact, the composition, macrostructure and microstructure of the calculus will clearly depend on the factors that have induced it. For this reason, the appropriate study and classification of the renal calculi simplifies the diagnosis and allows a more effective therapeutic approach since it can be oriented to directly correct the etiological factors responsible for stone formation. In this article, we review the main etiological factors involved in the formation of each type of calculus and the prophylactic measures that can be adopted for proper correction. The most frequent kidney stones have been classified into the following types: calcium oxalate monohydrate papillary calculi, calcium oxalate monohydrate non-papillary calculi, calcium oxalate dihydrate calculi, mixed hydroxyapatite/ calcium oxalate calculi, carboxyapatite/hydroxyapatite calculi, brushite calculi, struvite/carboxyapatite calculi, uric acid calculi, uric acid/calcium oxalate monohydrate calculi, and cystine calculi. Occasionally, however, the calculus is not available for study, in which case the only way forward is to use all available information (clinical history, life habits, radiological data), together with basic biochemical information, to identify and correct all etiological factors related to renal lithiasis that have been identified.