Antagonistes de l'angiotensine II et cancer: un bilan rassurant [Angiotensin II receptor blockers (ARBs) and cancer: a reassuring balance].

The effects of drugs on new cancer and cancer-related death are a major concern. Recently, a meta-analysis raised the possibility that ARBs might have an adverse impact in this respect. This point of view was highly debated until the publication of two other meta-analyses which did not demonstrate any increased risk of new cancer occurrence as well as of cancer related-death with the use of ARBs in patients with hypertension, heart failure and/or nephropathy. This illustrates that the results of meta-analyses should be interpreted cautiously and critically in order to avoid biased conclusions. Overall the bulk of evidence today indicates that ARBs are not associated with an increased cancer risk.

Energy balance, physical activity, and thermogenic effect of feeding in premature infants.

In order to assess the contribution of the thermogenic effect of feeding and muscular activity to total energy expenditure, nine premature infants were studied for 2 consecutive days during which time repeated measurements of energy expenditure by indirect calorimetry were performed throughout the day, combined with a visual activity score based on body movement. The infants were growing at 16.6 +/- 4.0 g/kg/day (mean +/- SD) and received 110 +/- 8 kcal/kg/day metabolizable energy (milk formula) and 522 +/- 40 mgN/kg/day. Their total energy expenditure was 68 +/- 4 kcal/kg/day indicating that 41 +/- 7 kcal/kg/day was retained for growth. Based on the combination of energy + N balances it was estimated that 80% of the weight gain was fat-free tissue and 20% was fat tissue. The rate of energy expenditure measured minute-by-minute was significantly and linearly correlated with the activity score in both the premeal (r = 0.75;p less than 0.001) and the postmeal periods (r = 0.74; p less than 0.001) with no difference in the regression slope, but with a significant difference in intercept. In preset feeding schedules the latter allowed an estimation of the thermogenic effect without the confounding effect of activity. This was found to be 3.1 +/- 1.8% when expressed as a percentage of metabolizable energy intake. However when the "classical" approach was used as a comparison (integration of extra energy expenditure induced by the meal), the thermogenic effect was found to be greater, i.e. 9.5 +/- 3.8% of the meal's metabolizable energy, due to the superimposed effect of physical activity in the postprandial state.(ABSTRACT TRUNCATED AT 250 WORDS)

ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.

Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.

Smart instrumentation for determination of ligament stiffness and ligament balance in total knee arthroplasty.

Ligament balance is an important and subjective task performed during total knee arthroplasty (TKA) procedure. For this reason, it is desirable to develop instruments to quantitatively assess the soft-tissue balance since excessive imbalance can accelerate prosthesis wear and lead to early surgical revision. The instrumented distractor proposed in this study can assist surgeons on performing ligament balance by measuring the distraction gap and applied load. Also the device allows the determination of the ligament stiffness which can contribute a better understanding of the intrinsic mechanical behavior of the knee joint. Instrumentation of the device involved the use of hall-sensors for measuring the distractor displacement and strain gauges to transduce the force. The sensors were calibrated and tested to demonstrate their suitability for surgical use. Results show the distraction gap can be measured reliably with 0.1mm accuracy and the distractive loads could be assessed with an accuracy in the range of 4N. These characteristics are consistent with those have been proposed, in this work, for a device that could assist on performing ligament balance while permitting surgeons evaluation based on his experience. Preliminary results from in vitro tests were in accordance with expected stiffness values for medial collateral ligament (MCL) and lateral collateral ligament (LCL).

Increased alpha activity and modulations of fronto-parietal balance during motor transitions in the elderly

A hallmark of aging is the sensorimotor deficit, characterized by an increased reaction time and a reduction of motor abilities. Some mechanisms such as motor inhibition deteriorate with aging because of neuronal density alterations and modifications of connections between brain regions. These deficits may be compensated throughout a recruitment of additional areas. Studies have shown that old adults have increased difficulty in performing bimanual coordination tasks compared with young adults. In contrast, motor switching is poorly documented and is expected to engage increasing resources in the elderly. The present study examines performances and electro-cortical correlates of motor switching in young and elderly adults.

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis.

The measurement of fat balance (fat input minus fat output) involves the accurate estimation of both metabolizable fat intake and total fat oxidation. This is possible mostly under laboratory conditions and not yet in free-living conditions. In the latter situation, net fat retention/mobilization can be estimated based on precise and accurate sequential body composition measurements. In case of positive balance, lipids stored in adipose tissue can originate from dietary (exogenous) lipids or from nonlipid precursors, mainly from carbohydrates (CHOs) but also from ethanol, through a process known as de novo lipogenesis (DNL). Basic equations are provided in this review to facilitate the interpretation of the different subcomponents of fat balance (endogenous vs exogenous) under different nutritional circumstances. One difficulty is methodological: total DNL is difficult to measure quantitatively in man; for example, indirect calorimetry only tracks net DNL, not total DNL. Although the numerous factors (mostly exogenous) influencing DNL have been studied, in particular the effect of CHO overfeeding, there is little information on the rate of DNL in habitual conditions of life, that is, large day-to-day fluctuations of CHO intakes, different types of CHO ingested with different glycemic indexes, alcohol combined with excess CHO intakes, etc. Three issues, which are still controversial today, will be addressed: (1) Is the increase of fat mass induced by CHO overfeeding explained by DNL only, or by decreased endogenous fat oxidation, or both? (2) Is DNL different in overweight and obese individuals as compared to their lean counterparts? (3) Does DNL occur both in the liver and in adipose tissue? Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro. The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes.

Transpiration stimulée afin d'améliorer l'équilibre hydro-sodé chez les patients hémodialysés : à propos d'un cas [Stimulated sweating in order to improve the water-and-salt balance in hemodialysis patients. A case report].

Obtaining the desired dry weight in dialysis patients is challenging once residual diuresis has disappeared, considering the trend of increasing dietary salt intake and shortening dialysis time over the last 40 years. We describe the case of a 55-year-old patient of Sudanese origin, who presented excessive interdialytic weight gain and hypertension on maintenance hemodialysis. After failure of conservative measures, a therapy of daily hot water baths of 30minutes each on non-dialysis days was introduced. All clinical parameters improved, including potassium profile. In this article, we review the history, pathophysiological mechanisms, efficacy and possible side effects of this interesting, somewhat forgotten technique.

Impact of restrictive intravenous fluid replacement and combined epidural analgesia on perioperative volume balance and renal function within a Fast Track program.

BACKGROUND AND OBJECTIVE: Key factors of Fast Track (FT) programs are fluid restriction and epidural analgesia (EDA). We aimed to challenge the preconception that the combination of fluid restriction and EDA might induce hypotension and renal dysfunction. METHODS: A recent randomized trial (NCT00556790) showed reduced complications after colectomy in FT patients compared with standard care (SC). Patients with an effective EDA were compared with regard to hemodynamics and renal function. RESULTS: 61/76 FT patients and 59/75 patients in the SC group had an effective EDA. Both groups were comparable regarding demographics and surgery-related characteristics. FT patients received significantly less i.v. fluids intraoperatively (1900 mL [range 1100-4100] versus 2900 mL [1600-5900], P < 0.0001) and postoperatively (700 mL [400-1500] versus 2300 mL [1800-3800], P < 0.0001). Intraoperatively, 30 FT compared with 19 SC patients needed colloids or vasopressors, but this was statistically not significant (P = 0.066). Postoperative requirements were low in both groups (3 versus 5 patients; P = 0.487). Pre- and postoperative values for creatinine, hematocrit, sodium, and potassium were similar, and no patient developed renal dysfunction in either group. Only one of 82 patients having an EDA without a bladder catheter had urinary retention. Overall, FT patients had fewer postoperative complications (6 versus 20 patients; P = 0.002) and a shorter median hospital stay (5 [2-30] versus 9 d [6-30]; P< 0.0001) compared with the SC group. CONCLUSIONS: Fluid restriction and EDA in FT programs are not associated with clinically relevant hemodynamic instability or renal dysfunction.

c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation.

The activity of adult stem cells is essential to replenish mature cells constantly lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. Here, we provide genetic evidence for an unexpected function of the c-Myc protein in the homeostasis of hematopoietic stem cells (HSCs). Conditional elimination of c-Myc activity in the bone marrow (BM) results in severe cytopenia and accumulation of HSCs in situ. Mutant HSCs self-renew and accumulate due to their failure to initiate normal stem cell differentiation. Impaired differentiation of c-Myc-deficient HSCs is linked to their localization in the differentiation preventative BM niche environment, and correlates with up-regulation of N-cadherin and a number of adhesion receptors, suggesting that release of HSCs from the stem cell niche requires c-Myc activity. Accordingly, enforced c-Myc expression in HSCs represses N-cadherin and integrins leading to loss of self-renewal activity at the expense of differentiation. Endogenous c-Myc is differentially expressed and induced upon differentiation of long-term HSCs. Collectively, our data indicate that c-Myc controls the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSCs and their niche.

Entre psychanalyse et systémique : est-ce que mon coeur balance ?

Se référant à son propre parcours psychothérapeutique qui l'a conduit de la psychanalyse à la systémique, sans qu'il n'ait dû renier les apports de sa première formation, l'auteur réfléchit sur les connivences possibles entre ces deux approches, et plus largement sur les possibilités d'une pratique psychothérapeutique non uniréférencée. Selon lui, la diversité des méthodes psychothérapeutiques ne doit pas nécessairement conduire à un éclectisme hypertolérant, souvent confusionnant. Il importe pour le psychothérapeute de se savoir ici plutôt que là, tout en maintenant une ouverture aux autres pratiques grâce à l'intégration assimilative de certaines de leurs techniques.

Sediment budget monitoring of a debris-flow torrent (French Prealps)

The Manival near Grenoble (French Prealps) is a very active debris-flow torrent equipped with a large sediment trap (25 000 m3) protecting an urbanized alluvial fan from debris-flows. We began monitoring the sediment budget of the catchment controlled by the trap in Spring 2009. Terrestrial laser scanner is used for monitoring topographic changes in a small gully, the main channel, and the sediment trap. In the main channel, 39 cross-sections are surveyed after every event. Three periods of intense geomorphic activity are documented here. The first was induced by a convective storm in August 2009 which triggered a debris-flow that deposited ~1,800 m3 of sediment in the trap. The debris-flow originated in the upper reach of the main channel and our observations showed that sediment outputs were entirely supplied by channel scouring. Hillslope debris-flows were initiated on talus slopes, as revealed by terrestrial LiDAR resurveys; however they were disconnected to the main channel. The second and third periods of geomorphic activity were induced by long duration and low intensity rainfall events in September and October 2009 which generate small flow events with intense bedload transport. These events contribute to recharge the debris-flow channel with sediments by depositing important gravel dunes propagating from headwaters. The total recharge in the torrent subsequent to bedload transport events was estimated at 34% of the sediment erosion induced by the August debris-flow.

The epithelial sodium channel and the control of sodium balance.

Studies aiming at the elucidation of the genetic basis of rare monogenic forms of hypertension have identified mutations in genes coding for the epithelial sodium channel ENaC, for the mineralocorticoid receptor, or for enzymes crucial for the synthesis of aldosterone. These genetic studies clearly demonstrate the importance of the regulation of Na(+) absorption in the aldosterone-sensitive distal nephron (ASDN), for the maintenance of the extracellular fluid volume and blood pressure. Recent studies aiming at a better understanding of the cellular and molecular basis of ENaC-mediated Na(+) absorption in the distal part of nephron, have essentially focused on the regulation ENaC activity and on the aldosterone-signaling cascade. ENaC is a constitutively open channel, and factors controlling the number of active channels at the cell surface are likely to have profound effects on Na(+) absorption in the ASDN, and in the amount of Na(+) that is excreted in the final urine. A number of membrane-bound proteases, kinases, have recently been identified that increase ENaC activity at the cell surface in heterologous expressions systems. Ubiquitylation is a general process that regulates the stability of a variety of target proteins that include ENaC. Recently, deubiquitylating enzymes have been shown to increase ENaC activity in heterologous expressions systems. These regulatory mechanisms are likely to be nephron specific, since in vivo studies indicate that the adaptation of the renal excretion of Na(+) in response to Na(+) diet occurs predominantly in the early part (the connecting tubule) of the ASDN. An important work is presently done to determine in vivo the physiological relevance of these cellular and molecular mechanisms in regulation of ENaC activity. The contribution of the protease-dependent ENaC regulation in mediating Na(+) absorption in the ASDN is still not clearly understood. The signaling pathway that involves ubiquitylation of ENaC does not seem to be absolutely required for the aldosterone-mediated control of ENaC. These in vivo physiological studies presently constitute a major challenge for our understanding of the regulation of ENaC to maintain the Na(+) balance.