NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+-K+-ATPase

NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+-K+-ATPase.BackgroundIn K+ deprivation (KD), gastric (g) H+-K+-ATPase (HKA) is suppressed, whereas colonic (c) HKA is induced in the terminal inner medullary collecting duct (IMCD). We hypothesized that in KD, cHKA is induced and can mediate the secretion of NH4+.MethodsRats were sacrificed after 2, 3, 6, or 14 days on regular (NML) or K+-free (KD) diet. mRNA expression of HKA isoforms in terminal inner medulla was examined and correlated with NH4+ secretion in perfused IMCD in vitro.ResultsUrinary NH4+ excretion increased after K+-free diet for six days. In terminal inner medulla, cHKA expression was strongly induced, whereas gHKA expression was decreased. NH4+ secretion increased by 62% in KD (JtNH4+ 0.57 vs. 0.92 pmol/min/mm tubule length, P < 0.001). Ouabain (1 mM) in perfusate inhibited NH4+ secretion in KD by 45% (P < 0.002) but not in NML. At luminal pH 7.7, which inhibits NH3 diffusion, NH4+ secretion in IMCD was 140% higher in KD (0.36 vs. 0.15, P < 0.03) and was sensitive to ouabain. ROMK-1 mRNA expression was induced in parallel with cHKA in inner medulla.ConclusionsThese data suggest that in KD, cHKA replaces gHKA and mediates enhanced secretion of NH4+ (and H+) into the lumen facilitated by K+ recycling through ROMK-1

Éléments d’aide au contrôle de gestion et au management de l’agrumiculture au Maroc

L’étude est dédiée aux grandes entreprises agrumicoles structurées et décentralisées. Elle fournit les éléments agronomiques et financiers pour un modèle de contrôle de gestion de type bottom-up concevable à partir de l’expérience sur la nouvelle agrumiculture née du plan Maroc Vert. Le modèle suppose la transparence, un travail en partenariat fermes-contrôle de gestion, un système d’information fiable et une fluidité de circulation de l’information. En agriculture, il n’y a pas d’analogie parfaite avec l’industrie concernant l’évaluation des écarts de performance par rapport aux objectifs de gestion affichés par le budget. Dans l’industrie, les mêmes inputs et le même process produisent en général le même résultat, ce qui facilite amplement l’analyse des écarts constatés et aide beaucoup à proposer des mesures correctives. En agriculture, avec une même quantité d’inputs (eau, engrais, pesticides), et un même process de production (porte greffe, variété, densité, taille), le résultat peut être très différent selon l’année climatique, la région ou le type de sol. Par conséquent, le plus important dans cette activité, n’est pas l’écart de performance lui-même, mais de pouvoir expliquer la part de cet écart qui revient à la gestion et celle due aux facteurs externes non maitrisables du milieu. Une contre-performance sur la productivité ou la qualité peut être la conséquence d’effets pervers d’un Chergui (chute des fruits, marbrures, coup de soleil) alors qu’aucune modification n’a été apportée au process usuel de production. De même qu’une excellente performance est parfois en partie le fait d’une année climatique favorable et d’un bon prix sur le marché et non d’un effort particulier de gestion. Cette énorme difficulté à prévoir avec une certaine confiance, ce que sera le comportement du verger d’une année à l’autre, rend donc malaisé l’usage de «&nbsp;normes&nbsp;» figées pour le contrôle de gestion. C’est pourquoi dans la présente étude, l’effort a plus porté sur l’exploration des causes des écarts autour des chiffres moyens que sur les chiffres eux-mêmes. Au Maroc, on est en présence d’un système économique libéral certes, mais la surproduction avec l’idée d’ensuite vendre les agrumes «&nbsp;a dime a dozen&nbsp;» ou de laisser la main invisible d’Adam Smith réguler le marché n’a jamais été un objectif du plan Maroc Vert. Le but recherché, est plutôt de produire pour ensuite exporter davantage afin d’améliorer la balance commerciale du pays. Aujourd’hui, on est en situation d’offre excessive en petits fruits aggravée par un Export qui peine à monter en charge, il est donc légitime que chacun cherche à tirer son épingle du jeu. Faute de pouvoir agir sur les prix, la mission basique du contrôle de gestion est donc de maîtriser au moins les charges. Même si la vraie solution pour le Maroc, aurait été plutôt d’instaurer un super-contrôle de gestion innovant de type filière avec notamment des prérogatives de gel provisoire des plantations, le temps de conquérir de nouveaux marchés. Ce que nous craignions est maintenant arrivé en 2018, c'est-à-dire finir après autant d’investissements par vendre la clémentine de qualité sur le marché local à 10cts/kg. L’étude suggère entre autres, comment sortir de cette période trouble et surmonter la crise avec un minimum de dégâts pour le producteur. Mots clés&nbsp;: Contrôle de gestion, agrumes, MarocThe study concerns the large structured and decentralized citrus fruit companies. It provides the agronomic and financial tools for management control. The present management model is based on a bottom-up design. It is inspired from the new citrus cropping experience born from the Green Morocco plan. The model assumes transparency, farm and management control partnership, reliable information system and fluidity of information. In agriculture, there is no perfect analogy with the industry sector concerning the assessment of performance gaps compared to the management objectives reported by the budget. In industry, the same inputs combined to the same process generally produce the same result. Thus, the analysis of the observed performance gaps become easier and corrective measures can be suggested. In agriculture, the result can’t be similar even the same amount of inputs (water, fertilizer, pesticides), and the same production process (rootstock, cultivar, density, pruning) have been used. This situation is related to climatic year, location and soil type. Therefore, the most important in agricultural activity, is to explain the causes of the performance gap. Then, to classify these causes into manageable factors and not manageable factors of the environment. A low performance on productivity or quality can be related to the negative effect of “Chergui” wind (fall, physical damage, sunburn, ...) even we keep the same usual production process. Also, an excellent performance is sometimes related to a very good climate year and not to a specific management effort. The enormous difficulty of predicting confidently the orchard behavior, for each year, constrains the establishment of fixed "standards" useful for management control. Thus, in the present study, we try to explore causes of deviations around average numbers. In Morocco, a liberal economy is established. However, the overproduction with the idea of selling the citrus fruit as dime a dozen or leaving the Adam Smith invisible hand regulates the market has never been the goal of the Green Morocco Plan. Such plan aims to produce and to export more in order to improve the country's trade balance. Today, we are in a situation of excessive clementine supply aggravated by the difficulty to increase export quantity. This situation pushes each producer to perform well. Regarding the difficulty to regulate prices, the basic mission of the management control is to master at least the production costs. The true solution would to introduce an innovative super-control management of citrus sector. This management would include a provisional plantation freezing waiting for finding new markets. In fact, the feared problem is occurred in 2018. Indeed, high quality clementine has been sold at 10 cts kg-1. on the local market after many investments of the producer. The study aims to give suggestions to producers on how to manage this troubled period and overcome the crisis with minimal damage. Key words: Management control, citrus fruits, Morocc

Éléments d’aide au contrôle de gestion et au management de l’agrumiculture au Maroc

L’étude est dédiée aux grandes entreprises agrumicoles structurées et décentralisées. Elle fournit les éléments agronomiques et financiers pour un modèle de contrôle de gestion de type bottom-up concevable à partir de l’expérience sur la nouvelle agrumiculture née du plan Maroc Vert. Le modèle suppose la transparence, un travail en partenariat fermes-contrôle de gestion, un système d’information fiable et une fluidité de circulation de l’information. En agriculture, il n’y a pas d’analogie parfaite avec l’industrie concernant l’évaluation des écarts de performance par rapport aux objectifs de gestion affichés par le budget. Dans l’industrie, les mêmes inputs et le même process produisent en général le même résultat, ce qui facilite amplement l’analyse des écarts constatés et aide beaucoup à proposer des mesures correctives. En agriculture, avec une même quantité d’inputs (eau, engrais, pesticides), et un même process de production (porte greffe, variété, densité, taille), le résultat peut être très différent selon l’année climatique, la région ou le type de sol. Par conséquent, le plus important dans cette activité, n’est pas l’écart de performance lui-même, mais de pouvoir expliquer la part de cet écart qui revient à la gestion et celle due aux facteurs externes non maitrisables du milieu. Une contre-performance sur la productivité ou la qualité peut être la conséquence d’effets pervers d’un Chergui (chute des fruits, marbrures, coup de soleil) alors qu’aucune modification n’a été apportée au process usuel de production. De même qu’une excellente performance est parfois en partie le fait d’une année climatique favorable et d’un bon prix sur le marché et non d’un effort particulier de gestion. Cette énorme difficulté à prévoir avec une certaine confiance, ce que sera le comportement du verger d’une année à l’autre, rend donc malaisé l’usage de «&nbsp;normes&nbsp;» figées pour le contrôle de gestion. C’est pourquoi dans la présente étude, l’effort a plus porté sur l’exploration des causes des écarts autour des chiffres moyens que sur les chiffres eux-mêmes. Au Maroc, on est en présence d’un système économique libéral certes, mais la surproduction avec l’idée d’ensuite vendre les agrumes «&nbsp;a dime a dozen&nbsp;» ou de laisser la main invisible d’Adam Smith réguler le marché n’a jamais été un objectif du plan Maroc Vert. Le but recherché, est plutôt de produire pour ensuite exporter davantage afin d’améliorer la balance commerciale du pays. Aujourd’hui, on est en situation d’offre excessive en petits fruits aggravée par un Export qui peine à monter en charge, il est donc légitime que chacun cherche à tirer son épingle du jeu. Faute de pouvoir agir sur les prix, la mission basique du contrôle de gestion est donc de maîtriser au moins les charges. Même si la vraie solution pour le Maroc, aurait été plutôt d’instaurer un super-contrôle de gestion innovant de type filière avec notamment des prérogatives de gel provisoire des plantations, le temps de conquérir de nouveaux marchés. Ce que nous craignions est maintenant arrivé en 2018, c'est-à-dire finir après autant d’investissements par vendre la clémentine de qualité sur le marché local à 10cts/kg. L’étude suggère entre autres, comment sortir de cette période trouble et surmonter la crise avec un minimum de dégâts pour le producteur. Mots clés&nbsp;: Contrôle de gestion, agrumes, MarocThe study concerns the large structured and decentralized citrus fruit companies. It provides the agronomic and financial tools for management control. The present management model is based on a bottom-up design. It is inspired from the new citrus cropping experience born from the Green Morocco plan. The model assumes transparency, farm and management control partnership, reliable information system and fluidity of information. In agriculture, there is no perfect analogy with the industry sector concerning the assessment of performance gaps compared to the management objectives reported by the budget. In industry, the same inputs combined to the same process generally produce the same result. Thus, the analysis of the observed performance gaps become easier and corrective measures can be suggested. In agriculture, the result can’t be similar even the same amount of inputs (water, fertilizer, pesticides), and the same production process (rootstock, cultivar, density, pruning) have been used. This situation is related to climatic year, location and soil type. Therefore, the most important in agricultural activity, is to explain the causes of the performance gap. Then, to classify these causes into manageable factors and not manageable factors of the environment. A low performance on productivity or quality can be related to the negative effect of “Chergui” wind (fall, physical damage, sunburn, ...) even we keep the same usual production process. Also, an excellent performance is sometimes related to a very good climate year and not to a specific management effort. The enormous difficulty of predicting confidently the orchard behavior, for each year, constrains the establishment of fixed "standards" useful for management control. Thus, in the present study, we try to explore causes of deviations around average numbers. In Morocco, a liberal economy is established. However, the overproduction with the idea of selling the citrus fruit as dime a dozen or leaving the Adam Smith invisible hand regulates the market has never been the goal of the Green Morocco Plan. Such plan aims to produce and to export more in order to improve the country's trade balance. Today, we are in a situation of excessive clementine supply aggravated by the difficulty to increase export quantity. This situation pushes each producer to perform well. Regarding the difficulty to regulate prices, the basic mission of the management control is to master at least the production costs. The true solution would to introduce an innovative super-control management of citrus sector. This management would include a provisional plantation freezing waiting for finding new markets. In fact, the feared problem is occurred in 2018. Indeed, high quality clementine has been sold at 10 cts kg-1. on the local market after many investments of the producer. The study aims to give suggestions to producers on how to manage this troubled period and overcome the crisis with minimal damage. Key words: Management control, citrus fruits, Morocc

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment

Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodiumdependent phosphate cotransporter, has been proposed as a cause of PAM.Weshow that epithelial deletion ofNpt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers.Microliths introduced by adoptive transfer into the lungs of wild-typemice produce markedmacrophagerich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic wholelung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAMmouse model as a preclinical platform for the development of biomarkers and therapeutic strategies

Spatial and temporal intracerebral hemorrhage patterns in Dutch-type hereditary cerebral amyloid angiopathy

Aim To investigate whether there is a topographical and temporal pattern of index and recurrent intracerebral hemorrhages (ICH) in Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) to increase our understanding on CAA-related ICH development. Methods We included patients with DNA confirmed D-CAA or a history with >= 1 lobar ICH and >= 1 first-degree relative with D-CAA. Topographical pattern was studied by location (proportion frontal/parietal/temporal/occipital; infra/supratentorial and occurrence ratios relative to lobe volume) and volume of index and recurrent ICHs were determined on CT. Temporal pattern was examined by time between recurrent ICHs was retrieved from medical records. Results We included 72 patients with D-CAA (mean age at index ICH 55 years) with in total 214 ICH. The median follow-up time was 7 years (range 0.8 to 28 years). All ICH were lobar and supratentorial. The index ICH was most frequently located in the occipital lobe (34% vs. 22% in the other three lobes; with index ICH occurrence ratios relative to lobe volume of 1.9 for occipital, 1.0 for temporal, 1.2 for parietal, and 0.5 for frontal, p = 0.001). In 16/47 (34%) patients with multiple ICH, the second ICH was located in the same lobe as the index ICH. The median time-interval between subsequent ICH was #1-2 ICH 27 months, #2-3 ICH 14 months, and #3-4 ICH 7 months (p = 0.6) There was no difference in volume between index and recurrent ICHs. Conclusions We found that index and recurrent ICHs in D-CAA have a preference for the occipital lobe and are least frequent in the frontal lobe, which adds to the existing knowledge of histopathological studies on amyloid load in CAA. Surprisingly, there was no acceleration in time nor gradual increase of hematoma volume between subsequent ICHs.Neuro Imaging Researc

Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

<p>Abstract</p> <p>Background</p> <p>Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels.</p> <p>Methods</p> <p>The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide.</p> <p>Results</p> <p>Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher.</p> <p>Conclusion</p> <p>During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system</p> <p>Trial Registration</p> <p>Clinical Trials Identifier: NCT00281762</p

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces