Aliskiren affects fatty-acid uptake and lipid-related genes in rodent and human cardiomyocytes

International audienceWe investigated whether the direct renin inhibitor aliskiren can affect metabolism in cardiomyocytes from rat, mouse and human sources. METHODS AND RESULTS: At 10-50μmol/L, aliskiren significantly increased medium-chain-fatty-acid uptake in primary-cultured neonatal-rat and HL-1 adult-mouse-derived cardiomyocytes (BODIPY-induced fluorescence intensity). The fatty-acid transporter CD-36 was correspondingly translocated to, but the glucose transporter Glut-4 away from, the sarcoplasmic reticulum/plasma membrane, in primary-cultured neonatal-rat (CD-36, Glut-4) and adult-human (CD-36) cardiomyocytes (confocal immunocytochemistry). Immunoblotting showed that aliskiren induced phosphorylation of ERK1/2 in cardiomyocytes from all three sources; responses were dose- and time-dependent, unaffected by renin treatment, and did not cause alterations in expression of (P)R or Igf2/M6P receptors. Microarray analysis of the complete genome of aliskiren-treated neonatal-rat cardiomyocytes, with RT-qPCR and immunoblot confirmation assays in rat and human primary cardiomyocytes, showed that aliskiren up-regulated mRNA and increased protein expression of several enzymes important in lipid and glucose metabolism and in cholesterol biosynthesis. Cardiomyocyte cell-cycle and viability were unaffected by aliskiren

Memorial acadêmico para Professor Titular

Os memoriais têm longa tradição acadêmica no Brasil, constituem-se em documentos que expõem trajetórias de professores universitários para fins de concursos ou de progressões ao longo das suas carreiras. No caso específico das universidades federais e da progressão para a classe de Professor Titular a ampliação do acesso a esse nível da carreira é a resultante de uma greve do movimento docente. Entre as concessões ao Estado e as conquistas da categoria, essa greve garantiu que todos os professores que alcançarem o nível de Professor Associado 4 possam pleitear essa ascensão. Nas regras anteriores de distribuição de vagas para Professor Titular, a possibilidade dessa promoção era muito reduzida, envolvia a perda de direitos trabalhistas, além de produzir uma competição intensa entre pares do mesmo departamento

Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat

Abstract Background Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics–pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. Methods A prospective, experimental, randomized study was carried out in adult male Sprague–Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP). Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans) was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC). The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90%) for 80 and 100% of Tfree > minimum inhibitory concentration (MIC) for 80 and 100% of dosing interval. Measurements and main results After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104–1 × 105 CFU in CLP rats). CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004), while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p  90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. Conclusions Sepsis causes changes in the PK of CTX and an alteration in the sialic components of the GFB, with consequent loss of protein-bound CTX. Among factors that can affect drug pharmacokinetics during the early phases of sepsis, urinary loss of both free and albumin–bound antimicrobials should be considered

A monolithic 2.5 Gb/s clock and data recovery circuit based on Silicon bipolar technology

A monolithic Clock and Data Recovery (CDR) circuit for SDH STM-16 (2.5 Gb/s) digital receivers has been designed and fabricated using Maxim GST-2 27 GHz Silicon bipolar technology. The main functions carried out by the IC are: signal amplification (40 dB) and limitation, clock recovery and decision. The design is intended to achieve a complete 2.5 Gb/s receiver by using the IC and a low noise preamplifier (transimpedance stage), mounted in a DIL package. The integrated circuit comprises about 400 active devices, used both for analog and digital blocks, and uses two supply voltages of 5 and -4.5 V. The input port is decoupled by external capacitors and matched to 50 Omega using on-chip resistors, whereas clock and data outputs are open collector type. The die size is 2 x 2 mm(2) and the chip has been packaged using a TQFP 48 pins plastic package. Measurements under 2(31)-1 PRBS data stream have shown an input sensitivity below 5 mVpp, rms output jitter below 7 ps and total power consumption of 0.8 W

High CMRR GaAs single-input to differential convertor

In this paper a new topology for Single Input to Differential convertors is presented. Among the capabilities of convertors realised with this topology, 6 dB of extra conversion gain respect to a single differential cell and suppression of the common mode can be mentioned. An exact model of the circuit and considerations about design optimisation are also presented

Wearable Systems for Personalised Health Care

Smartex Srl and the University of Pisa has jointly developed several new textile-based systems for vital signs monitoring, upper limb gesture, and posture capturing, to be mostly used in medical applications. The conductive and the basal yarn, used to realize the piezoresistive domains, behave as strain gage sensors and show piezoresistive properties in response to an external mechanical stimulus. The device uses fabric sensors, which improve the comfort and wearability of health care devices, enabling to obtain signals and performances comparable to gold standards. The Kinematic Sensor System (KSS), which integrates both signal acquisition and processing, provides a visualization of joint segment motion in a tridimensional interactive environment. The sensing glove, in its posture detection functionality, has been tested in movements involving the metacarpophalangeal (MP) joint of the forefinger. The main advantage ensured by these prototypes is the possibility of wearing them for a long period without discomfor