Localized Sustained Release of Copper Enhances Antitumor Effects of Disulfiram in Head and Neck Cancer.

Drug repurposing uses approved drugs as candidate anticancer therapeutics, harnesses previous research and development efforts, and benefits from available clinically suitable formulations and evidence of patient tolerability. In this work, the drug used clinically to treat chronic alcoholism, disulfiram (DSF), was studied for its antitumor efficacy in a copper-dependent manner. The combination of DSF and copper could achieve a tumor cell growth inhibition effect comparable to those of 5-fluorouracil and taxol on head and neck cancer cells. Both bulk dendrimer hydrogel and microsized dendrimer hydrogel particles were utilized for the localized sustained release of copper in the tumor site. The localized sustained release of copper facilitated the tumor inhibition effect following intratumoral injection in a mouse's head and neck cancer model.

Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis.

[Figure: see text].

Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye.

Low bioavailability of topically applied drugs remains a significant challenge for long-term glaucoma therapy. To enhance drug delivery efficiency, we developed dendrimer gel particles that collectively exhibit structural benefits of dendrimer, hydrogel, and particles, using the inverse emulsion method coupled with the highly efficient aza-Michael addition reaction (IEaMA). This hierarchical approach would maximize the utility of the structural features of existing ocular drug delivery systems. We have tested the delivery efficiency and efficacy of two first-line antiglaucoma drugs, brimonidine tartrate (BT) and timolol maleate (TM), which were loaded into dendrimer gel particles of various sizes, i.e., nDHP (nano-in-nano dendrimer hydrogel particles, ~200 nm), µDHP3 (3 µm), and µDHP10 (9 µm). We found that nDHP was superior to µDHP3 and µDHP10 in terms of cytocompatibility, degradability, drug release kinetics, and corneal permeability. The nDHPs increased drug corneal permeability by 17-fold compared to plain drug solution and enabled zero-order prolonged drug release kinetics. The nDHP-based formulation demonstrated pronounced IOP-lowering effects in both single-dose test and 7-day chronic daily dosing test in both Brown Norway rats and glaucoma mice. Taken together, we have developed nano-in-nano dendrimer gel particles for precise dosing and enabling sustained and synergistic efficacy of antiglaucoma drugs, which could be clinically impactful for improving glaucoma treatment.

Polyamidoamine Dendrimer Grafted with an Acid-Responsive Charge-Reversal Layer for Improved Gene Delivery.

We report on a heterogeneous dendrimer (G3-acetal-NH2) derivative possessing an acid-responsive charge-reversal layer. The synthesis of G3-acetal-NH2 starts with a polyamidoamine (PAMAM) dendrimer G3 core and follows the aza-Michael addition with N-(2-(1-(allyloxy)ethoxy)ethyl)acrylamide synthesized by us and the thiol-ene click chemistry with cysteamine hydrochloride in sequence. In a weakly acidic environment, the surface of this newly formed dendrimer can turn from amine-terminated to hydroxyl-terminated due to the cleavage of the acetal groups. This charge conversion from 34.3 ± 2.7 to 18.0 ± 0.3 mV in 24 h at pH 5.3 enables its capacity as a gene delivery vehicle. G3-acetal-NH2 with a positively charged surface can condense pMAX GFP plasmid at similar weight ratios as native G4-NH2 (above 2:1), allowing for its protected uptake into cells and endosomal escape. Meanwhile, in the endosome, the drop in vesicle pH cleaves the acetal bond, releasing the genetic payload and limiting its recondensation by the reduction in the dendrimer surface charge. When the vector/plasmid weight ratio was 2:1, G3-acetal-NH2 improved transfection of pMAX GFP plasmid by 5-fold over native G4-NH2 in NIH3T3 cells in terms of GFP protein expression. Taken together, we show that this surface charge conversion performance makes the synthesized heterogeneous dendrimer an improved vehicle for gene transfection.

Drug-Conjugated Dendrimer Hydrogel Enables Sustained Drug Release via a Self-Cleaving Mechanism.

In this study, the anticancer drug, camptothecin (CPT), was covalently grafted onto polyamidoamine (PAMAM) dendrimer surface and then reacted with polyethylene glycol diacrylate (PEG-DA) to form dendrimer hydrogel (DH-G3-CPT) with low cross-linking density. In this novel drug delivery system, CPT was cleaved from dendrimer via the ammonolysis of ester bonds and then diffused out of the hydrogel network, thus leading to significantly prolonged drug release. The self-cleaving release kinetics of camptothecin can be further tuned by pH. This DH-G3-CPT drug delivery system has both injectability and sustained drug release. It showed an excellent tumor inhibition effect following intratumoral injection in a head and neck cancer model of mouse.

Biomechanics and energetics of walking in powered ankle exoskeletons using myoelectric control versus mechanically intrinsic control.

BACKGROUND: Controllers for assistive robotic devices can be divided into two main categories: controllers using neural signals and controllers using mechanically intrinsic signals. Both approaches are prevalent in research devices, but a direct comparison between the two could provide insight into their relative advantages and disadvantages. We studied subjects walking with robotic ankle exoskeletons using two different control modes: dynamic gain proportional myoelectric control based on soleus muscle activity (neural signal), and timing-based mechanically intrinsic control based on gait events (mechanically intrinsic signal). We hypothesized that subjects would have different measures of metabolic work rate between the two controllers as we predicted subjects would use each controller in a unique manner due to one being dependent on muscle recruitment and the other not. METHODS: The two controllers had the same average actuation signal as we used the control signals from walking with the myoelectric controller to shape the mechanically intrinsic control signal. The difference being the myoelectric controller allowed step-to-step variation in the actuation signals controlled by the user's soleus muscle recruitment while the timing-based controller had the same actuation signal with each step regardless of muscle recruitment. RESULTS: We observed no statistically significant difference in metabolic work rate between the two controllers. Subjects walked with 11% less soleus activity during mid and late stance and significantly less peak soleus recruitment when using the timing-based controller than when using the myoelectric controller. While walking with the myoelectric controller, subjects walked with significantly higher average positive and negative total ankle power compared to walking with the timing-based controller. CONCLUSIONS: We interpret the reduced ankle power and muscle activity with the timing-based controller relative to the myoelectric controller to result from greater slacking effects. Subjects were able to be less engaged on a muscle level when using a controller driven by mechanically intrinsic signals than when using a controller driven by neural signals, but this had no affect on their metabolic work rate. These results suggest that the type of controller (neural vs. mechanical) is likely to affect how individuals use robotic exoskeletons for therapeutic rehabilitation or human performance augmentation.

Toward Controllable Hydraulic Coupling of Joints in a Wearable Robot.

In this paper, we develop theoretical foundations for a new class of rehabilitation robot: body powered devices that route power between a user's joints. By harvesting power from a healthy joint to assist an impaired joint, novel bimanual and self-assist therapies are enabled. This approach complements existing robotic therapies aimed at promoting recovery of motor function after neurological injury. We employ hydraulic transmissions for routing power, or equivalently for coupling the motions of a user's joints. Fluid power routed through flexible tubing imposes constraints within a limb or between homologous joints across the body. Variable transmissions allow constraints to be steered on the fly, and simple valve switching realizes free space and locked motion. We examine two methods for realizing variable hydraulic transmissions: using valves to switch among redundant cylinders (digital hydraulics) or using an intervening electromechanical link. For both methods, we present a rigorous mathematical framework for describing and controlling the resulting constraints. Theoretical developments are supported by experiments using a prototype fluid-power exoskeleton.

Synthesis and photophysical properties of extended π conjugated naphthalimides.

A series of π conjugated naphthalimide derivatives having an imide group as an acceptor conjugated with a methoxy arylethynyl or a methoxyphenyl triazole as a donor were prepared by Sonogashira coupling or "click" chemistry. Their photophysical properties were investigated by steady state and time resolved fluorescence spectroscopy and modelled by TD-DFT calculations. Compound Naphth-AlkyneOMe has a high fluorescence quantum yield and displays efficient photoinduced charge transfer in solution as well as in the powder state. Compound Naphth-TriazoleOMe exhibits a very high Stokes shift and its fluorescence quantum yield is low, which can be rationalized by theoretical calculations.

Cost assessment of different routes for phosphorus recovery from wastewater using data from pilot and production plants.

Phosphorus (P) recovery from wastewater has considerable potential to supplement limited fossil P reserves. Reliable cost data are essential for investor and policymaker decisions. In this study, investment and operational costs for nine P recovery processes were calculated from the investor's perspective, taking into account all relevant side effects on the sludge treatment or the wastewater treatment plant. The assessment was based on pilot and full-scale data which were thoroughly consolidated and standardized with technical and cost data from the German wastewater-sludge treatment train to enable direct comparison. The cost influence of precipitation processes on the current wastewater-sludge treatment train ranges from -0.14 (generating profit) to 0.23 EUR per population equivalent (PE) and year, while the cost influence of sludge leaching processes is around 2.50 EUR/(PE y). The cost influence of processes using dry sludge and mono-incineration ash varies between 0.33 and 3.13 EUR/(PE y), depending on existing disposal pathways, mono-incineration, co-incineration or agricultural use of sludge. The specific costs per kg P recovered (-4 to 10 EUR/kg P) are in general higher than conventional fertilizer production (1.6 EUR/kg P). However, annual costs per PE represent less than 3% of the total costs for wastewater disposal.

[Paradoxal decrease and metabolic effects of BNP in obese patient]. / Baisse paradoxale et effet métabolique du BNP chez les obèses.

Natriuretic peptides (NP), ANP and BNP, are produced by cardiomyocytes when there is stretching of the ventricular and auricular walls in heart failure (HF). Their vasodilatator and natriuretic effect oppose to volume and pressure overload occurring in HF. Several studies have observed decreased levels of NP in obese and diabetic people and in patients with insulin resistance. This decrease could contribute to hypertension, frequently observed in obesity. NP have also a lipolytic action. Low levels of NP could promote obesity. Therefore in obese patients normal BNP levels cannot a priori exclude HF. Normal values must be adjusted according to obesity degree and heart failure stage.

Les peptides natriurétiques (PN) ANP (atrial natriuretic peptide) et BNP (brain natriuretic peptide) sont synthétisés par les cardiomyocytes lors de mise sous tension des parois musculaires des ventricules et des oreillettes en cas d'insuffisance cardiaque (IC). Leur effet vasodilatateur et natriurétique s'oppose à la surcharge de volume et de pression qui survient lors d'IC. Plusieurs études ont montré que les taux de BNP sont diminués chez les patients obèses, diabétiques ou présentant une résistance à l'insuline. La baisse de BNP pourrait contribuer à l'hypertension observée chez les obèses. De plus les PN ont une action lipolytique. Des taux abaissés de PN pourraient favoriser l'obésité. En pratique, chez les obèses, des valeurs normales de BNP ne permettent pas d'exclure une IC. Les valeurs de BNP doivent être corrigées en fonction des degrés d'obésité et d'IC.

Contraction Sensing with Smart Braid McKibben Muscles.

The inherent compliance of soft fluidic actuators makes them attractive for use in wearable devices and soft robotics. Their flexible nature permits them to be used without traditional rotational or prismatic joints. Without these joints, however, measuring the motion of the actuators is challenging. Actuator-level sensors could improve the performance of continuum robots and robots with compliant or multi-degree-of-freedom joints. We make the reinforcing braid of a pneumatic artificial muscle (PAM or McKibben muscle) "smart" by weaving it from conductive, insulated wires. These wires form a solenoid-like circuit with an inductance that more than doubles over the PAM contraction. The reinforcing and sensing fibers can be used to measure the contraction of a PAM actuator with a simple, linear function of the measured inductance. Whereas other proposed self-sensing techniques rely on the addition of special elastomers or transducers, the technique presented in this work can be implemented without modifications of this kind. We present and experimentally validate two models for Smart Braid sensors based on the long solenoid approximation and the Neumann formula, respectively. We test a McKibben muscle made from a Smart Braid in quasistatic conditions with various end-loads and in dynamic conditions. We also test the performance of the Smart Braid sensor alongside steel.

Evaluating new processes and concepts for energy and resource recovery from municipal wastewater with life cycle assessment.

Energy and resource recovery from municipal wastewater is a pre-requisite for an efficient and sustainable water management in cities of the future. However, a sound evaluation of available processes and pathways is required to identify opportunities and short-comings of the different options and reveal synergies and potentials for optimization. For evaluating environmental impacts in a holistic view, the tool of life cycle assessment (LCA, ISO 14040/44) is suitable to characterize and quantify the direct and indirect effects of new processes and concepts. This paper gives an overview of four new processes and concepts for upgrading existing wastewater treatment plants towards energy positive and resource efficient wastewater treatment, based upon an evaluation of their environmental impacts with LCA using data from pilot and full-scale assessments of the considered processes.

Learning to walk with an adaptive gain proportional myoelectric controller for a robotic ankle exoskeleton.

BACKGROUND: Robotic ankle exoskeletons can provide assistance to users and reduce metabolic power during walking. Our research group has investigated the use of proportional myoelectric control for controlling robotic ankle exoskeletons. Previously, these controllers have relied on a constant gain to map user's muscle activity to actuation control signals. A constant gain may act as a constraint on the user, so we designed a controller that dynamically adapts the gain to the user's myoelectric amplitude. We hypothesized that an adaptive gain proportional myoelectric controller would reduce metabolic energy expenditure compared to walking with the ankle exoskeleton unpowered because users could choose their preferred control gain. METHODS: We tested eight healthy subjects walking with the adaptive gain proportional myoelectric controller with bilateral ankle exoskeletons. The adaptive gain was updated each stride such that on average the user's peak muscle activity was mapped to maximal power output of the exoskeleton. All subjects participated in three identical training sessions where they walked on a treadmill for 50 minutes (30 minutes of which the exoskeleton was powered) at 1.2 ms(-1). We calculated and analyzed metabolic energy consumption, muscle recruitment, inverse kinematics, inverse dynamics, and exoskeleton mechanics. RESULTS: Using our controller, subjects achieved a metabolic reduction similar to that seen in previous work in about a third of the training time. The resulting controller gain was lower than that seen in previous work (ß=1.50±0.14 versus a constant ß=2). The adapted gain allowed users more total ankle joint power than that of unassisted walking, increasing ankle power in exchange for a decrease in hip power. CONCLUSIONS: Our findings indicate that humans prefer to walk with greater ankle mechanical power output than their unassisted gait when provided with an ankle exoskeleton using an adaptive controller. This suggests that robotic assistance from an exoskeleton can allow humans to adopt gait patterns different from their normal choices for locomotion. In our specific experiment, subjects increased ankle power and decreased hip power to walk with a reduction in metabolic cost. Future exoskeleton devices that rely on proportional myolectric control are likely to demonstrate improved performance by including an adaptive gain.

Biotherapies in stroke.

Stroke is the second leading cause of death worldwide and the most common cause of severe disability. Neuroprotection and repair mechanisms supporting endogenous brain plasticity are often insufficient to allow complete recovery. While numerous neuroprotective drugs trials have failed to demonstrate benefits for patients, they have provided interesting translational research lessons related to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to neurons but involve all brain cell type including the extracellular matrix in a "glio-neurovascular niche". Targeting a range of host brain cells, biotherapies such as growth factors and therapeutic cells, currently hold great promise as a regenerative medical strategy for stroke. These techniques can promote both neuroprotection and delayed neural repair through neuro-synaptogenesis, angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory effects. Their complex mechanisms of action are interdependent and vary according to the particular growth factor or grafted cell type. For example, while "peripheral" stem or stromal cells can provide paracrine trophic support, neural stem/progenitor cells (NSC) or mature neurons can act as more direct neural replacements. With a wide therapeutic time window after stroke, biotherapies could be used to treat many patients. However, guidelines for selecting the optimal time window, and the best delivery routes and doses are still debated and the answers may depend on the chosen product and its expected mechanism including early neuroprotection, delayed neural repair, trophic systemic transient effects or graft survival and integration. Currently, the great variety of growth factors, cell sources and cell therapy products form a therapeutic arsenal that is available for stroke treatment. Their effective clinical use will require prior careful considerations regarding safety (e.g. tumorgenicity, immunogenicity), potential efficacy, cell characterization, delivery route and in vivo biodistribution. Bone marrow-derived cell populations such as mesenchymal stromal/stem cells (MSC) or mononuclear cells (MNC), umbilical cord stem cells and NSC are most investigated notably in clinical trials. Finally, we discuss perspectives concerning potential novel biotherapies such as combinatorial approaches (growth factor combined with cell therapy, in vitro optimization of cell products, or co-transplantation) and the development of biomaterials, which could be used as injectable hydrogel scaffold matrices that could protect a cell graft or selectively deliver drugs and growth factors into the post-stroke cavity at chronic stages. Considering the remaining questions about the best procedure and the safety cautions, we can hope that future translational research about biotherapies will bring more efficient treatments that will decrease post-stroke disability for many patients.

Proof of concept for a new energy-positive wastewater treatment scheme.

For improved exploitation of the energy content present in the organic matter of raw sewage, an innovative concept for treatment of municipal wastewater is tested in pilot trials and assessed in energy balance and operational costs. The concept is based on a maximum extraction of organic matter into the sludge via coagulation, flocculation and microsieving (100 µm mesh size) to increase the energy recovery in anaerobic sludge digestion and decrease aeration demand for carbon mineralisation. Pilot trials with real wastewater yield an extraction of 70-80% of total chemical oxygen demand into the sludge while dosing 15-20 mg/L Al and 5-7 mg/L polymer with stable operation of the microsieve and effluent limits below 2-3 mg/L total phosphorus. Anaerobic digestion of the microsieve sludge results in high biogas yields of 600 NL/kg organic dry matter input (oDMin) compared to 430 NL/kg oDMin for mixed sludge from a conventional activated sludge process. The overall energy balance for a 100,000 population equivalent (PE) treatment plant (including biofilter for post-treatment with full nitrification and denitrification with external carbon source) shows that the new concept is an energy-positive treatment process with comparable effluent quality than conventional processes, even when including energy demand for chemicals production. Estimated operating costs for electricity and chemicals are in the same range for conventional activated sludge processes and the new concept.

Comparing environmental impacts of tertiary wastewater treatment technologies for advanced phosphorus removal and disinfection with life cycle assessment.

Different technologies for tertiary wastewater treatment are compared in their environmental impacts with life cycle assessment (LCA). Targeting very low phosphorus concentration (50-120 µg/L) and seasonal disinfection of wastewater treatment plant (WWTP) secondary effluent, this LCA compares high-rate sedimentation, microsieve, dual media filtration (all with UV disinfection), and polymer ultrafiltration or ceramic microfiltration membranes for upgrading the large WWTP Berlin-Ruhleben. Results of the LCA show that mean effluent quality of membranes is highest, but at the cost of high electricity and chemical demand and associated emissions of greenhouse gases or other air pollutants. In contrast, gravity-driven treatment processes require less electricity and chemicals, but can reach significant removal of phosphorus. In fact, dual media filter or microsieve cause substantially lower specific CO2 emissions per kg P removed from the secondary effluent (180 kg CO2-eq/kg P, including UV) than the membrane schemes (275 kg CO2-eq/kg P).

ABVD alone and a PET scan complete remission negates the need for radiologic surveillance in early-stage, nonbulky Hodgkin lymphoma.

BACKGROUND: Patients with early-stage, nonbulky classic Hodgkin lymphoma (cHL) undergo intensive posttreatment radiologic surveillance despite having a low risk of disease recurrence. The current study attempted to evaluate the risk of disease recurrence and the value of radiologic surveillance in patients treated with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment positron emission tomography (PET). METHODS: Forty-seven patients who underwent therapy with interim and/or posttreatment PET scans were evaluated for disease recurrence during ≥ 24 months of follow-up. Their presenting characteristics and imaging results were assessed and interpreted in relation to clinical outcome. RESULTS: All 47 patients were eligible for analysis. The majority of patients were female (35 patients) with a median age of 28 years (range, 17 years-65 years.). The nodular sclerosing subtype was the predominant histology (41 patients). A total of 34 patients were staged with IIA disease, 6 with IA disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to Cotswolds modification of the Ann Arbor staging system). All patients completed 6 cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1 interim scan and 1 posttreatment scan); both were biopsy-proven sarcoidosis. Two patients developed disease recurrence at 7 months and 24 months, respectively, after negative interim and posttreatment imaging. One case of recurrence was identified through surveillance imaging and the other was identified simultaneously by the patient and surveillance scan. A total of 45 patients experienced a durable CR; 21 had additional unscheduled imaging/workup during surveillance to investigate symptoms or imaging signs of concern. CONCLUSIONS: Because of a low risk of disease recurrence, posttreatment radiologic surveillance appears to be unnecessary in patients with early-stage, nonbulky (CD20 negative) cHL who achieve a PET-detected CR with the ABVD combination alone. This will reduce cumulative radiation exposure and health care costs in a predominantly young patient population.

Faecal carriage of oxyiminocephalosporin-resistant Enterobacteriaceae among paediatric units in different hospitals in the south of France.

The aim of this study was to determine the presence of oxyiminocephalosporin-resistant (OCR) Gram-negative bacilli and extended-spectrum ß-lactamase (ESBL)-producing isolates in stool specimens obtained from paediatric patients hospitalised for acute diarrhoea. We conducted a prospective, multicentre study over a period of 6 months in seven hospitals in the south of France. Samplings were carried out from infants admitted for acute diarrhoea with no previous antibiotic treatment in the last week. Bacteria in stool specimens were screened for the presence of OCR Gram-negative bacilli on Drigalski agar supplemented with ceftazidime and ESBL CHROMagar® media, and confirmed by the Rosco tablets test. Genetic detection was performed by the Check MDR® microarray and by polymerase chain reaction (PCR) and sequencing with bacterial DNA extracted from isolates. The presence of OCR enterobacteria was markedly high (177/1,118 patients, 15.2 %), with an important community origin (66.1 %). The majority of multidrug-resistant (MDR) bacteria were Enterobacter cloacae (106, 59.9 %) and Escherichia coli (61, 34.5 %). The prevalence of ESBL and CTX-M producers represented 5.2 and 4.3 % of the isolates, respectively. The main proportion of these ESBL carriers was found in children less than 1 year of age (53.4 %). One carbapenemase (IMP-1) was detected. The study revealed the wide dissemination of MDR bacteria in infants attending hospitals in the south of France during a non-outbreak situation, in particular, the spread of cefotaximase and the detection of a carbapenemase. This worrisome situation must reinforce the use of hygiene procedures and appropriate antibiotics to control the emergence and spread of OCR organisms.

Identifying energy and carbon footprint optimization potentials of a sludge treatment line with Life Cycle Assessment.

This study exemplifies the use of Life Cycle Assessment (LCA) as a tool to quantify the environmental impacts of processes for wastewater treatment. In a case study, the sludge treatment line of a large wastewater treatment plant (WWTP) is analysed in terms of cumulative energy demand and the emission of greenhouse gases (carbon footprint). Sludge treatment consists of anaerobic digestion, dewatering, drying, and disposal of stabilized sludge in mono- or co-incineration in power plants or cement kilns. All relevant forms of energy demand (electricity, heat, chemicals, fossil fuels, transport) and greenhouse gas emissions (fossil CO(2), CH(4), N(2)O) are accounted in the assessment, including the treatment of return liquor from dewatering in the WWTP. Results show that the existing process is positive in energy balance (-162 MJ/PE(COD) * a) and carbon footprint (-11.6 kg CO(2)-eq/PE(COD) * a) by supplying secondary products such as electricity from biogas production or mono-incineration and substituting fossil fuels in co-incineration. However, disposal routes for stabilized sludge differ considerably in their energy and greenhouse gas profiles. In total, LCA proves to be a suitable tool to support future investment decisions with information of environmental relevance on the impact of wastewater treatment, but also urban water systems in general.

[Clinical case of the month. Renovascular arterial hypertension complicated by diabetes insipidus: report of a case and review of the literature]. / Hypertension artérielle rénovasculaire compliquée de diabète insipide: cas clinique et revue de la littérature.

Mrs. A, a 62 year old patient with a history of hypertension, polyuria and polydipsia is hospitalized after a malaise. A severe hypokalemia, which is the cause of the polyuria and polydipsia, is discovered. The presence of hypertension and hypokalemia arises suspicion of a primary hyperaldosteronism and the plasma levels of renin and aldosterone are measured. Elevated aldosterone levels are combined with high plasma renin concentrations which permits to rule out primary hyperaldosteronism. Further explorations reveal a subocclusive ostial stenosis of the right renal artery. A treatment by sartan is instaured, which allows arterial pressure control and kalemia normalization. Chronic hypokalemia can be the cause of tubular nephropathy manifested by nephrogenic diabetes insipidus.