Hypertension, left ventricular hypertrophy and chronic kidney disease.

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH

Effects of wine and grape polyphenols on blood pressure, endothelial function and sympathetic nervous system activity in treated hypertensive subjects

In a randomized double-blind crossover trial, the effect of 8 week supplementation with grape and wine polyphenols on functional and structural vascular parameters and autonomic activity was evaluated in 40 essential hypertensive patients treated with diuretic monotherapy. Ambulatory blood pressure, brachial artery flow mediated dilation (FMD) and pulse-wave velocity (PWV) were measured at baseline and after each 8-week intervention. Forearm resistance artery endothelial function and muscle sympathetic nerve activity (MSNA) response to mental stress and cold-pressor test were measured in two separate sub-groups. No statistically significant differences were found across time or between groups in either blood pressure, FMD, PWV, or resistance artery endothelial function. The MSNA response to the two stressors was non-significantly attenuated after grape-wine polyphenol supplementation. These results do not support the hypothesis that daily consumption of a high dose of grape and wine polyphenols lowers blood pressure or affects vascular function in patients already on antihypertensive medication. © 2016 Elsevier Lt

The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes

Bergantin LB, Figueiredo LB, Godinho RO. the lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes. J Appl Physiol 111: 1710-1718, 2011. First published September 15, 2011; doi:10.1152/japplphysiol.00586.2011.-The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with beta-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. in conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 São Paulo, BrazilFAPESP: 05/59006-1FAPESP: 08/55988-2CNPq: 304602/2008-6Web of Scienc

Subbarrel patterns in somatosensory cortical barrels can emerge from local dynamic instabilities

Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In the rodent somatosensory cortex, groups of neurons called "barrels" correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. Here we demonstrate that similar patterns can be simulated by means of local growth-promoting and growth-retarding interactions within the circular domains of single barrels. The model correctly predicts that larger barrels contain more spatially complex subbarrel patterns, suggesting that the development of barrels and of the patterns within them may be understood in terms of some relatively simple dynamic processes. We also simulate the full nonlinear equations to demonstrate the predictive value of our linear analysis. Finally, we show that the pattern formation is robust with respect to the geometry of the barrel by simulating patterns on a realistically shaped barrel domain. This work shows how simple pattern forming mechanisms can explain neural wiring both qualitatively and quantitatively even in complex and irregular domains. © 2009 Ermentrout et al

Kerr-CFT From Black-Hole Thermodynamics

We analyze the near-horizon limit of a general black hole with two commuting killing vector fields in the limit of zero temperature. We use black hole thermodynamics methods to relate asymptotic charges of the complete spacetime to those obtained in the near-horizon limit. We then show that some diffeomorphisms do alter asymptotic charges of the full spacetime, even though they are defined in the near horizon limit and, therefore, count black hole states. We show that these conditions are essentially the same as considered in the Kerr/CFT corresponcence. From the algebra constructed from these diffeomorphisms, one can extract its central charge and then obtain the black hole entropy by use of Cardy's formula.Comment: 19 pages, JHEP3, no figures. V2: References added, small typos fixe

Carbon in the Moon

International audienceThe Moon was once thought to be depleted in volatile elements. Analyses of the carbon contents of lunar volcanic glasses reveal that carbon monoxide degassing could have produced the fire-fountain eruptions from which these glasses were formed

TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma

To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were represented in 14, 7, and 6 patients, respectively (31% 15%, and 16%). Five LSCC patients (6%) showed a mutation in H-Ras gene. Sixty-three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-nine patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy, high SPF (> 15.1%), TP53 mutations and, in particular, the mutations that occur in exons 5 and 8 were significantly related to quicker disease relapse and short OS. At Multivariate analysis, the major significant predictors for both disease relapse and death were high SPF and any TP53 mutations. While histological grade G3 was an independent factor only for relapse. In conclusions, any TP53 mutations and high SPF are important biological indicators to predict the outcome of LSCC patients

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic

PROBIOTICI E TERAPIA CONVENZIONALE: NUOVE FRONTIERE NELLA GESTIONE DELLE MANIFESTAZIONI ARTICOLARI DELLE MALATTIE INFIAMMATORIE INTESTINALI (IBD)

Summary: This work reports a clinical trial performed at palermo University Hospital "paolo Giaccone". From January 2004 to December 2011, 79 patients were enrolled (40 men and 39 women). All patients suffered from Inflammatory Bowel Disease (IBD) and were subjected to orthopedic consultation at the institute of Orthopaedics, University Hospital of palermo, for arthropathy to IBD. The patients were divided into two groups (A and B) and dealt with different therapies for the resolution of the inflammatory picture of the colonic mucosa and the treatment of the extraintestinal articular manifestations. Group A was treated with drug therapy: Diclofenac (75 mg im/ day for 10 days9 and Mesalazine (800 mg gastro-resistant tabletes, one tablet twice a day in mild forms, and one tablet three times per day in moderate forms). In group B, in addition to the previous treatment protocol, two probiotic mixture were added in a time of two weeks: in the first week, twice a day, one capsule containing mixture of Enterococcus faecium and saccharomices boluard was administered, with the main purpose to mitigate the intestinal inflammation; in the second week, twice a day too, one capsule containing a mixture of lactobacillus salivarius and lactobacillus acidophilus was administered, with the main purpose to mitigate the intestinal inflammation, in the second week, twice a day too, one capsule containing a mixture of lactobacillus salivarius and lactobacillus acidophilus was administered, with the aim to promote the restoration of a normal intestinal microenvironment. The attenuation of intestinal inflammation, improved by the presence of probiotics, could have important effects on the articular manifestations, resulting in a significant improvement of the arthropathy. All patients were evaluated with the Harvey-Bradshaw Index. Both Crohn Disease and Ulcerative Cholitis diagnosis was made with clinical, laboratory, endoscopic and instrumental tests; the degree of disease activity was evaluated using the criteria of Truelove and witts. The WOMAC-Score (Western Ontario Mcmaster) was used in our study to investigate the degree of articular involvement of the patients. The data were statistically evaluated and these are shown that the B group of patients treated with conventional therapy + probiotic mixture had a better resolution of the clinical and of this post-treatment parameters: WOMAC score, ESR, CRP and white blood cells; and also the B group of patients have a better response to standard therapy compared with patients who did not receive the probiotic with a remarkable statistic significance (p>0,0001)