Risk factors associated with renal lithiasis during uricosuric treatment of hyperuricemia in patients with Gout

Objective

To find factors associated with the development of renal colic during uricosuric therapy.

Methods

We performed a prospective cohort followup study of patients with gout and no previous history of kidney stones who had been treated with uricosurics. Clearance of creatinine and urate, 24‐hour urinary uric acid (UA), undissociated urinary UA concentration, 24‐hour undissociated urinary UA, and pH and urine sediment were obtained. Cox proportional hazards regression analysis was used to identify variables associated with renal colic as the outcome. The rate of renal colic was compared with that of control patients receiving allopurinol who had no previous history of renal stones.

Results

We analyzed a 784 patient‐year exposure from 216 patients: 206 with renal underexcretion of UA and 10 with normal excretion. There were 21 clinical events. Two variables showed increased risk hazard for developing lithiasis: clearance of UA at baseline and undissociated urinary UA concentration during followup. When only patients with underexcretion of UA were included in the analysis, undissociated urinary UA during followup remained the only statistically significant variable. Patients who showed an undissociated UA concentration <20 mg/dl did not show an increase in the rate of lithiasis or events compared with patients receiving allopurinol.

Conclusion

Clearance of UA at baseline may be useful for selecting patients suitable for uricosuric treatment. The estimation of the concentration of undissociated urinary UA is useful for evaluating the risk of lithiasis during followup.     

Thigh and buttock exertional pain for the diagnosis of peripheral arterial disease

ObjectivesTo evaluate the prevalence of both non-calf intermittent claudication (IC) and classic IC in patients with no known atherosclerotic disease, and their accuracy to detect peripheral arterial disease (PAD).DesignCross sectional, observational study conducted at 96 internal medicine services.Materials and methods1487 outpatients with no known atherosclerotic disease, and either diabetes or a SCORE risk estimation of at least 3% were enrolled. IC was assessed using the Edinburgh Claudication Questionnaire and PAD was confirmed by an ankle-brachial index (ABI) < 0.9.ResultsOverall, 7.2% met criteria of classic and 5.8% of non-calf IC. PAD was diagnosed in 393 cases (26.4%). In these PAD patients, 17.8% exhibited classic and 13.2% non-calf IC. Both calf and non-calf IC had similar overall accuracy for detecting PAD. Considering both categories as a whole, the sensitivity of IC to predict a low ABI was 31% and the specificity 93%.ConclusionsNon-calf IC is comparable to classic IC for the diagnosis of PAD in patients with no known arterial disease. The systematic implementation of Edinburgh Claudication Questionnaire could be a valuable call-to-action to improve clinical evaluation of PAD, bearing in mind that PAD detected by either non-calf or classic IC must be confirmed by ABI testing.     

Extreme diversity in noncalcifying haptophytes explains a major pigment paradox in open oceans

The current paradigm holds that cyanobacteria, which evolved oxygenic photosynthesis more than 2 billion years ago, are still the major light harvesters driving primary productivity in open oceans. Here we show that tiny unicellular eukaryotes belonging to the photosynthetic lineage of the Haptophyta are dramatically diverse and ecologically dominant in the planktonic photic realm. The use of Haptophyta-specific primers and PCR conditions adapted for GC-rich genomes circumvented biases inherent in classical genetic approaches to exploring environmental eukaryotic biodiversity and led to the discovery of hundreds of unique haptophyte taxa in 5 clone libraries from subpolar and subtropical oceanic waters. Phylogenetic analyses suggest that this diversity emerged in Paleozoic oceans, thrived and diversified in the permanently oxygenated Mesozoic Panthalassa, and currently comprises thousands of ribotypic species, belonging primarily to low-abundance and ancient lineages of the “rare biosphere.” This extreme biodiversity coincides with the pervasive presence in the photic zone of the world ocean of 19′-hexanoyloxyfucoxanthin (19-Hex), an accessory photosynthetic pigment found exclusively in chloroplasts of haptophyte origin. Our new estimates of depth-integrated relative abundance of 19-Hex indicate that haptophytes dominate the chlorophyll a-normalized phytoplankton standing stock in modern oceans. Their ecologic and evolutionary success, arguably based on mixotrophy, may have significantly impacted the oceanic carbon pump. These results add to the growing evidence that the evolution of complex microbial eukaryotic cells is a critical force in the functioning of the biosphere.     

Gene expression profiling of B lymphocytes and plasma cells from Waldenstr?m's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals.

The tumoral clone of Waldenstr?m's macroglobulinemia (WM) shows a wide morphological heterogeneity, which ranges from B lymphocytes (BL) to plasma cells (PC). By means of genome-wide expression profiling we have been able to identify genes exclusively deregulated in BL and PC from WM, but with a similar expression pattern in their corresponding cell counterparts from chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), as well as normal individuals. The differentially expressed genes have important functions in B-cell differentiation and oncogenesis. Thus, two of the genes downregulated in WM-BL were IL4R, which plays a relevant role in CLL B-cell survival, and BACH2, which participates in the development of class-switched PC. Interestingly, one of the upregulated genes in WM-BL was IL6. A set of four genes was able to discriminate clonal BL from WM and CLL: LEF1 (WNT/beta-catenin pathway), MARCKS, ATXN1 and FMOD. We also found deregulation of genes involved in plasma cell differentiation such as PAX5, which was overexpressed in WM-PC, and IRF4 and BLIMP1, which were underexpressed. In addition, three of the target genes activated by PAX5 - CD79, BLNK and SYK - were upregulated in WM-PC. In summary, these results indicate that both PC and BL from WM are genetically different from the MM and CLL cell counterpart.     

Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence.

Marijuana consumption during adolescence has been proposed to be a stepping-stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self-administration (1 mg/kg), food-reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food-restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [(18)F]-fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP-treated rats showed a higher rate of cocaine self-administration as compared to vehicle-treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food-reinforced operant task, pointing to the cocaine-specific nature of the effect seen in self-administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP-treated females when compared to their vehicle-treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo-entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self-administration, in a sex-specific fashion. This increased susceptibility could be related to the changes in brain metabolic activity induced by cannabinoids during adolescence.     

Triclosan-loaded poloxamine micelles for enhanced topical antibacterial activity against biofilm

Our research group is interested in the study of different technological approaches to treat hospital biofilm as a means to constrain nosocomial-acquired infections. The present work investigated the effect of the incorporation of the antibacterial agent triclosan (TS) into polymeric micelles of poloxamine T1107 (MW=15 kDa, 70 wt% PEO). The aggregation phenomenon was primarily investigated by means of Critical Micellar Concentration in a broad range of pH. Then, the effect of the polymer concentration on the micellar size was evaluated by Dynamic Light Scattering. Solubility levels increased up to 4 orders of magnitude. The drug inclusion affected the micellization, resulting in size increase and micellar fusion. This phenomenon was only apparent in TS-saturated systems. TS-loaded aggregates proved to be active in vitro against a broad spectrum of bacteria but more importantly, also against two representative clinical pathogens: methicilin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF). While the former was sensitive to even very low TS levels attainable in poloxamine-free aqueous media, the later was inhibited only when exposed to higher drug levels affordable exclusively using an inclusion system. These findings indicated the release of the drug from the reservoir. Finally, the activity of a TS-containing 5% poloxamine combination of pH 7.4 was assessed on biofilms of Staphylococcus epidermidis. Results showed a significant decrease (p<0.001) in the number of Colony-Formation Units when the biofilm was exposed to the TS/poloxamine as compared to the limited activity of the polymer-free TS control.     

Divergences in antihypertensive therapy in special situations in nephrology.

CONTEXT AND OBJECTIVE: The choice of an antihypertensive drug is based on several criteria and specific situations give rise to doubt and controversy. The aim here was to evaluate physicians approaches towards treatment with antihypertensive agents in specific situations. DESIGN AND SETTING: Cross-sectional study, at Universidade Federal de S?o Paulo, S?o Paulo. METHODS: A questionnaire was applied during a nephrology meeting to evaluate individual approaches towards each hypothetical clinical situation. The questionnaire consisted of five multiple-choice questions (clinical cases) concerning controversial aspects of antihypertensive therapy. RESULTS: A total of 165 questionnaires were analyzed. Most participants were nephrologists (93.2%). There was a preference for angiotensin-converting enzyme (ACE) inhibitors in at least two of the cases. Only 57.2% of the physicians were correct in choosing beta-blockers as the first-line drugs for patients with ischemic coronary disease. Moreover, 66.2% chose ACE inhibitors as the first-line drugs for patients with chronic kidney disease and proteinuria. About 5% of the physicians did not follow the current recommendations for the use of ACE inhibitors in diabetic patients with microalbuminuria. The most controversial question concerned the first-line drug for advanced chronic kidney disease. Most physicians were correct in choosing calcium channel blockers and avoiding ACE inhibitors in renovascular hypertension in the case of a patient with a single functioning kidney. CONCLUSIONS: Most physicians adopted the correct approach, but some had an alternative strategy for the same situations that was not based on evidence.     

Oxidative stress in tumor microenvironment——Its role in angiogenesis

The tumor angiogenesis process is believed to be dependent on an "angiogenic switch" formed by a cascade of biologic events as a consequence of the "cross-talk" between tumor cells and several components of local microenvironment including endothelial cells, macrophages, mast cells and stromal components. Oxidative stress represents an important stimulus that widely contributes to this angiogenic switch, which is particularly relevant in lungs, where oxidative stress is originated from different sources including the incomplete reduction of oxygen during respiration, exposure to hypoxia/reoxygenation, stimulated resident or chemoattracted immune cells to lung tissues, as well as by a variety of chemicals compounds. In the present review we highlight the role of oxidative stress in tumor angiogenesis as a key signal linked to other relevant actors in this complex process.