Unnatural Amino Acid-Based Ionic Liquid Enables Oral Treatment of Nonsense Mutation Disease in Mice.

This investigation addresses the challenge of suboptimal unnatural amino acid (UAA) utilization in the site-specific suppression of nonsense mutations through genetic code expansion, which is crucial for protein restoration and precise property tailoring. A facile and economical oral liquid formulation is developed by converting UAAs into ionic liquids, significantly enhancing their bioavailability and tissue accumulation. Empirical data reveal a 10-fold increase in bioavailability and up to a 13-fold rise in focal tissue accumulation, alongside marked improvements in UAA incorporation efficiency. A 4-week oral administration in mdx mice, a model for Duchenne muscular dystrophy (DMD), demonstrates the formulation's unprecedented therapeutic potential, with up to 40% dystrophin expression restoration and 75% recovery of normal fiber functions, surpassing existing treatments and exhibiting substantial long-term safety. This study presents a potent oral dosage form that dramatically improves UAA incorporation into target proteins in vivo, offering a significant advance in the treatment of nonsense mutation-mediated disorders and holding considerable promise for clinical translation.

An Ionic Liquid Ablation Agent for Local Ablation and Immune Activation in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma rapidly acquires resistance to chemotherapy, remaining a fatal disease. Immunotherapy is one of the breakthroughs in cancer treatment, which includes immune checkpoint inhibitors, chimeric antigen receptor T-cell immunotherapy, and neoantigen vaccines. However, immunotherapy has not achieved satisfactory results in the treatment of pancreatic cancer. Immunogenic death comprises proinflammatory cell death, which provides a way to enhance tumor immunogenicity and promote an immune response in solid tumors. Herein, an ionic liquid ablation agent (LAA), synthesized from choline and geranic acid, which triggers necrosis-induced immunotherapy by remodeling an immunosuppressive "cold" tumor to an immune activated "hot" tumor is described. The results indicate that LAA-treated tumor cells can enhance immunogenicity, inducing dendritic cell maturation, macrophage M1 polarization, and cytotoxic T lymphocyte infiltration. The results of the present study provide a novel strategy for solid tumor immunotherapy.

Thermofluor-Based Optimization Strategy for the Stabilization of Recombinant Human Soluble Catechol-O-Methyltransferase.

Catechol-O-methyltransferase (COMT) has been involved in a number of medical conditions including catechol-estrogen-induced cancers and a great range of cardiovascular and neurodegenerative diseases such as Parkinson's disease. Currently, Parkinson's disease treatment relies on a triple prophylaxis, involving dopamine replacement by levodopa, the use of aromatic L-amino acid decarboxylase inhibitors, and the use of COMT inhibitors. Typically, COMT is highly thermolabile, and its soluble isoform (SCOMT) loses biological activity within a short time span preventing further structural and functional trials. Herein, we characterized the thermal stability profile of lysate cells from Komagataella pastoris containing human recombinant SCOMT (hSCOMT) and enzyme-purified fractions (by Immobilized Metal Affinity Chromatography-IMAC) upon interaction with several buffers and additives by Thermal Shift Assay (TSA) and a biological activity assessment. Based on the obtained results, potential conditions able to increase the thermal stability of hSCOMT have been found through the analysis of melting temperature (Tm) variations. Moreover, the use of the ionic liquid 1-butyl-3-methylimidazolium chloride [C4mim]Cl (along with cysteine, trehalose, and glycerol) ensures complete protein solubilization as well as an increment in the protein Tm of approximately 10 °C. Thus, the developed formulation enhances hSCOMT stability with an increment in the percentage of activity recovery of 200% and 70% when the protein was stored at 4 °C and -80 °C, respectively, for 12 h. The formation of metanephrine over time confirmed that the enzyme showed twice the productivity in the presence of the additive. These outstanding achievements might pave the way for the development of future hSCOMT structural and biophysical studies, which are fundamental for the design of novel therapeutic molecules.

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years.

Topical and transdermal delivery systems are of undeniable significance and ubiquity in healthcare, to facilitate the delivery of active pharmaceutical ingredients, respectively, onto or across the skin to enter systemic circulation. From ancient ointments and potions to modern micro/nanotechnological devices, a variety of approaches has been explored over the ages to improve the skin permeation of diverse medicines and cosmetics. Amongst the latest investigational dermal permeation enhancers, ionic liquids have been gaining momentum, and recent years have been prolific in this regard. As such, this review offers an outline of current methods for enhancing percutaneous permeation, highlighting selected reports where ionic liquid-based approaches have been investigated for this purpose. Future perspectives on use of ionic liquids for topical delivery of bioactive peptides are also presented.

Recent Advances in Ionic Liquids in Biomedicine.

The use of ionic liquids and deep eutectic solvents in biomedical applications has grown dramatically in recent years due to their unique properties and their inherent tunability. This review will introduce ionic liquids and deep eutectics and discuss their biomedical applications, namely solubilization of drugs, creation of active pharmaceutical ingredients, delivery of pharmaceuticals through biological barriers, stabilization of proteins and other nucleic acids, antibacterial agents, and development of new biosensors. Current challenges and future outlooks are discussed, including biocompatibility, the potential impact of the presence of impurities, and the importance of understanding the microscopic interactions in ionic liquids in order to design task-specific solvents.

Imidazolium-Based Ionic Liquid-Assisted Preparation of Nano-Spheres Loaded with Bio-Active Peptides to Decrease Inflammation in an Osteoarthritis Model: Ex Vivo Evaluations.

Osteoarthritis is one of the most prevalent chronic diseases. Cartilage inflammation in osteoarthritis results from pain in articular joints. Anti-inflammatory drugs provide relief by hindering the production of pro-inflammatory cytokines and interleukin-6. Targeted delivery of anti-inflammatory drugs is very effective in the treatment of osteoarthritis. This approach reduces the usage of therapeutic drug dosages and unwanted side effects. Here, we fabricated a non-invasive and efficient targeted drug delivery system to reduce persistent inflammation in an osteoarthritis model. Temperature-sensitive hollow dextran/poly(N-isopropyl acrylamide) nanoparticles were synthesized by the destruction of N,N'-bis(acryloyl)cystamine crosslinked cores in imidazolium-based ionic liquids. The copolymerized 2-acrylamido-2-methylpropane sulfonic acid created sulfur functionalities that increase the loading of therapeutic KAFAK peptides. The chemical structure of the polymer nanoparticles was analyzed with UV-Visible, Fourier transform infrared, and X-ray photoelectron spectroscopy. The thermal responsive characteristics of the nanoparticles were determined with dynamic light scattering, scanning electron microscopy, and transmission electron microscopy analyses. Moreover, the synthesized nanoparticles were used as drug carriers to reduce inflammation in an Ex Vivo osteoarthritis model. The KAFAK-loaded hollow dextran/PNIPAM nanoparticles effectively delivered therapeutic peptides in cartilage explants to suppress inflammation. These thermoresponsive nanoparticles could be an effective drug delivery system to deliver anti-inflammatory therapeutic peptides in a highly osteoarthritic environment.

Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations.

Systemic antibodies targeting tumor necrosis factor-α (TNF-α) and interleukin-17A (IL-17A) are effective in plaque psoriasis. Despite their popularity, safety concerns pose a challenge for systemic biologics. While anti-TNF-α and anti-IL-17A antibodies effectively inhibit respective proteins, we hypothesize that an approach based on local silencing of an upstream target such as NFKBIZ can be advantageous for treating psoriasis. However, effective delivery of small interfering RNA (siRNA) into the skin is a substantial hurdle due to skin's barrier function and poor stability of siRNA. Using ionic liquids as an enabling technology, we report on the effective delivery of NFKBIZ siRNA into the skin and its therapeutic efficacy in a psoriasis model. Treatment with IL-siRNA suppressed aberrant gene expression and resulted in down-regulation of psoriasis-related signals including TNF-α and IL-17A. These results provide a framework for a topical delivery platform for siRNA.

Investigating the potential use of an ionic liquid (1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide) as an anti-fungal treatment against the amphibian chytrid fungus, Batrachochytrium dendrobatidis.

The disease chytridiomycosis, caused by the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd), has contributed to global amphibian declines. Bd infects the keratinized epidermal tissue in amphibians and causes hyperkeratosis and excessive skin shedding. In individuals of susceptible species, the regulatory function of the amphibian's skin is disrupted resulting in an electrolyte depletion, osmotic imbalance, and eventually death. Safe and effective treatments for chytridiomycosis are urgently needed to control chytrid fungal infections and stabilize populations of endangered amphibian species in captivity and in the wild. Currently, the most widely used anti-Bd treatment is itraconazole. Preparations of itraconazole formulated for amphibian use has proved effective, but treatment involves short baths over seven to ten days, a process which is logistically challenging, stressful, and causes long-term health effects. Here, we explore a novel anti-fungal therapeutic using a single application of the ionic liquid, 1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP-NTf2), for the treatment of chytridiomycosis. BMP-NTf2 was found be effective at killing Bd in vitro at low concentrations (1:1000 dilution). We tested BMP-NTf2 in vivo on two amphibian species, one that is relatively tolerant of chytridiomycosis (Pseudacris regilla) and one that is highly susceptible (Dendrobates tinctorius). A toxicity trial revealed a surprising interaction between Bd infection status and the impact of BMP-NTf2 on D. tinctorius survival. Uninfected D. tinctorius tolerated BMP-NTf2 (mean ± SE; 96.01 ± 9.00 µl/g), such that only 1 out of 30 frogs died following treatment (at a dose of 156.95 µL/g), whereas, a lower dose (mean ± SE; 97.45 ± 3.52 µL/g) was not tolerated by Bd-infected D. tinctorius, where 15 of 23 frogs died shortly upon BMP-NTf2 application. Those that tolerated the BMP-NTf2 application did not exhibit Bd clearance. Thus, BMP-NTf2 application, under the conditions tested here, is not a suitable option for clearing Bd infection in D. tinctorius. However, different results were obtained for P. regilla. Two topical applications of BMP-NTf2 on Bd-infected P. regilla (using a lower BMP-NTf2 dose than on D. tinctorius, mean ± SE; 9.42 ± 1.43 µL/g) reduced Bd growth, although the effect was lower than that obtained by daily doses of itracanozole (50% frogs exhibited complete clearance on day 16 vs. 100% for itracanozole). Our findings suggest that BMP-NTf2 has the potential to treat Bd infection, however the effect depends on several parameters. Further optimization of dose and schedule are needed before BMP-NTf2 can be considered as a safe and effective alternative to more conventional antifungal agents, such as itraconazole.

Unveil the Anticancer Potential of Limomene Based Therapeutic Deep Eutectic Solvents.

Deep eutectic solvents have been recently reported as an interesting alternative to improve the therapeutic efficacy of conventional drugs, hence called therapeutic deep eutectic solvents (THEDES). The main objective of this work was to evaluate the potential of limonene (LIM) based THEDES as new possible systems for cancer treatment. LIM is known to have antitumor activity, however it is highly toxic and cell viability is often compromised, thus this compound is not selective towards cancer cells. Different THEDES based on LIM were developed to unravel the anticancer potential of such systems. THEDES were prepared by gently mixing saturated fatty acids menthol or ibuprofen (IBU) with LIM. Successful THEDES were obtained for Menthol:LIM (1:1), CA:LIM (1:1), IBU:LIM (1:4) and IBU:LIM(1:8). The results indicate that all the THEDES present antiproliferative properties, but IBU:LIM (1:4) was the only formulation able to inhibit HT29 proliferation without comprising cell viability. Therefore, IBU:LIM (1:4) was the formulation selected for further assessment of anticancer properties. The results suggest that the mechanism of action of LIM:IBU (1:4) is different from isolated IBU and LIM, which suggest the synergetic effect of DES. In this work, we unravel a methodology to tune the selectivity of LIM towards HT29 cell line without compromising cell viability of healthy cells. We demonstrate furthermore that coupling LIM with IBU leads also to an enhancement of the anti-inflammatory activity of IBU, which may be important in anti-cancer therapies.

Dual-Functional Supernanoparticles with Microwave Dynamic Therapy and Microwave Thermal Therapy.

The cytotoxic reactive oxygen species (ROS) generated by photoactivated sensitizers have been well explored in tumor therapy for nearly half a century, which is known as photodynamic therapy (PDT). The poor light penetration depth severely hinders PDT as a primary or adjuvant therapy for clinical indication. Whereas microwaves (MWs) are advantageous for deep penetration depth, the MW energy is considerably lower than that required for the activation of any species to induce ROS generation. Herein we find that liquid metal (LM) supernanoparticles activated by MW irradiation can generate ROS, such as ·OH and ·O2. On this basis, we design dual-functional supernanoparticles by loading LMs and an MW heating sensitizer ionic liquid (IL) into mesoporous ZrO2 nanoparticles, which can be activated by MW as the sole energy source for dynamic and thermal therapy concomitantly. The microwave sensitizer opens the door to an entirely novel dynamic treatment for tumors.

Ultrasonication-ionic liquid synergy for the synthesis of new potent anti-tuberculosis 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines.

The aim of the study is to design and synthesis of a new series of potent anti-TB 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines with their safety profile. A synergetic effect of ultrasonication and ionic liquid was shown successfully as a green methodology for the synthesis of title compounds 6a-t. These derivatives were obtained in shorter reaction time with good yields and well characterized by various spectroscopic methods, single-crystal X-ray diffraction (6f). The in vitro anti-tuberculosis activity for newly-synthesized derivatives has been screened against Mycobacterium tuberculosis. Among all, six compounds 6e, 6k, 6l, 6n, 6q and 6r exhibited equal potent activity compared to standard drug ethambutol (MIC: 1.56 µg/mL) and another compound 6h exhibited outstanding activity (MIC: 0.78 µg/mL) than the standard drug ethambutol. Cytotoxic nature of the anti-TB active compounds was evaluated against RAW 264.7 cells. The 6h, 6e, 6k, 6l, 6n, 6q and 6r exhibited lower toxicity which could be promising hits for anti-tuberculosis.

Inorganic Nanoshell-Stabilized Liquid Metal for Targeted Photonanomedicine in NIR-II Biowindow.

Gallium and gallium-based alloys, typical types of liquid metals with unique physiochemical properties, are emerging as a next generation of functional materials in versatile biomedical applications. However, the exploration of their biomedical performance is currently insufficient, and their intrinsic low oxidative resistance is a key factor blocking their further clinical translation. Herein, we report on the surface engineering of liquid metal-based nanoplatforms by an inorganic silica nanoshell based on a novel but facile sonochemical synthesis for highly efficient, targeted, and near-infrared (NIR)-triggered photothermal tumor hyperthermia in the NIR-II biowindow. The inorganic silica-shell engineering of liquid metal significantly enhances the photothermal performance of the liquid metal core as reflected by enhanced NIR absorption, improved photothermal stability by oxidation protection, and abundant surface chemistry for surface-targeted engineering to achieve enhanced tumor accumulation. Systematic in vitro cell-level evaluation and in vivo tumor xenograft assessment demonstrate that (Arg-Gly-Asp) RGD-targeted and silica-coated nanoscale liquid metal substantially induces phototriggered cancer-cell death and photothermal tumor eradication, accompanied by high in vivo biocompatibility and easy excretion out of the body. This work provides the first paradigm for surface-inorganic engineering of liquid metal-based nanoplatforms for achieving multiple desirable therapeutic performances, especially for combating cancer.

The Use of Liquids Ionic Fluids as Pharmaceutically Active Substances Helpful in Combating Nosocomial Infections Induced by Klebsiella Pneumoniae New Delhi Strain, Acinetobacter Baumannii and Enterococcus Species.

This review deals with various microbiological activities of ionic liquids, which constitute the first anti-infective defense against multi-drug-resistant bacteria-with a particular emphasis placed on medicine and pharmacology. The quoted data on the biological activity of ionic liquids including their antimicrobial properties (depending on the type of a cation or an anion) and are discussed in view of possible applications in nosocomial infections. Dedicated attention is given to finding infections with the Klebsiella pneumoniae New Delhi strain, Acinetobacter baumannii, and Enterococcus species, which are responsible for the induction of antibiotic resistance in intensive care units. Diagnosis and treatment using current antibiotics is a significant problem in hospital care, and the relevant burden on the health systems of the European Union member states induces the search for new, effective methods of treatment. Ionic liquids, due to their antibacterial effect, can be considered topical and general medications and may provide the basis for treatment to eliminate the antibiotic resistance phenomenon in the future. At present, the number of infections with resistant pathogens in hospitals and outpatient clinics in the European Union is growing. In 2015⁻2017, a significant incidence of respiratory and bloodstream infections with bacteria resistant to antibiotics from the 3rd generation group of cephalosporins, glycopeptides, and carbapenems were observed. The paper presents examples of synthesized bifunctional salts with at least one pharmaceutically active ion in obtaining a controlled release, controlled delivery, and biological impact on the pathogenic bacteria, viruses and fungi. The ionic liquids obtained in the presented way may find applications in the treatment of wounds and infections.

Bases para la terapia con líquidos y electrólitos. Modelos fisiológicos del equilibrio ácido-base (II): Los nuevos modelos. Parte 2 / Basis for fluid and electrolyte therapy. Physiological mod­els of acid-base balance (II): the new models. Part 2

En las últimas dos décadas hemos asistido a una revolución en el conocimiento científico de la fisiología y las alteraciones del equilibrio ácido-base. En la primera parte de esta serie de artículos revisamos el modelo «tradicional», la aproximación centrada en el bicarbonato y basada en el trabajo pionero de Henderson y Halsselbalch, que es aún la más utilizada en la práctica clínica diaria. En la segunda y la tercera parte revisamos la teoría de otros modelos más modernos, particularmente el de Stewart, derivado al final de los años setenta desde las leyes de la química física. Con este modelo, tal como fue desarrollado por Peter Stewart y Peter Constable, utilizando la presión parcial de dióxido de carbono (pCO2), la diferencia de iones fuertes (SID) y la concentración total de ácidos débiles ([Atot]), somos capaces de predecir con exactitud la acidez del plasma y deducir el saldo neto de iones no medidos (NUI). La interpretación del equilibrio ácido-base no será nunca más un arte intuitivo y arcano. Se ha convertido en un cálculo exacto que puede realizarse automáticamente con ayuda del software moderno. En las últimas tres partes, utilizando a pie de cama el strong ion calculator y la historia clínica, mostraremos cómo el modelo fisicoquímico cuantitativo tiene ventajas sobre los tradicionales, principalmente en las situaciones fisiológicas extremas que se viven con los pacientes de la unidad de cuidados intensivos pediátrica o en las alteraciones congénitas del metabolismo (AU)

A revolution has recently undergone in the last two decades in the scientific understanding of acid-base physiology and dysfunction. In the first part of this series we review the "traditional" model, the current bicarbonate-centered approach based on the pioneering work of Henderson and Halsselbalch, still the most widely used in clinical practice. In the second and third part we review theoretically other modern approaches, particularly Stewart's one, derived in the late 1970s from the laws of physical chemistry. Whit this approach, as developed by Peter Stewart and Peter Constable, using the partial pressure of carbon dioxide (pCO2), the strong ion difference (SID) and the concentration of weak acids ([Atot]) we can now predict accurately the acidity of plasma and deduce the net concentration of unmeasured ions (NUI). Acid-base interpretation has ceased to be an intuitive an arcane art and became an exact computation that can be automated with modern software. In the last three parts, using at the bedside the quantitative Strong Ion Calculator together with the medical history, we show how quantitative acid-base analysis has advantages over traditional approaches, mainly in the extreme physiological situations of clinical scenarios like the paediatric intensive care unit or the congenital metabolic diseases (AU)

Ionic liquids as active pharmaceutical ingredients.

Ionic liquids (ILs) are ionic compounds that possess a melting temperature below 100 °C. Their physical and chemical properties are attractive for various applications. Several organic materials that are now classified as ionic liquids were described as far back as the mid-19th century. The search for new and different ILs has led to the progressive development and application of three generations of ILs: 1) The focus of the first generation was mainly on their unique intrinsic physical and chemical properties, such as density, viscosity, conductivity, solubility, and high thermal and chemical stability. 2) The second generation of ILs offered the potential to tune some of these physical and chemical properties, allowing the formation of "task-specific ionic liquids" which can have application as lubricants, energetic materials (in the case of selective separation and extraction processes), and as more environmentally friendly (greener) reaction solvents, among others. 3) The third and most recent generation of ILs involve active pharmaceutical ingredients (API), which are being used to produce ILs with biological activity. Herein we summarize recent developments in the area of third-generation ionic liquids that are being used as APIs, with a particular focus on efforts to overcome current hurdles encountered by APIs. We also offer some innovative solutions in new medical treatment and delivery options.

Kt como control y seguimiento de la dosis en una unidad de hemodiálisis / Kt as control and follow-up of the dose at a hemodialysis unit

Asegurar que el paciente recibe la dosis adecuada en cada sesión de diálisis debe ser un objetivo a conseguir a corto o medio plazo. La incorporación de la dialisancia iónica (DI) en los monitores durante los últimos años ha permitido monitorizar la dosis de hemodiálisis en tiempo real y en cada sesión. Lowrie y cols., recomiendan el seguimiento de la dosis con el Kt, recomendando un mínimo de 40 L en mujeres y 45 en hombres o individualizar la dosis por área de superficie corporal. El objetivo del presente estudio era hacer un seguimiento de la dosis con el Kt en cada sesión durante 3 meses, y comparar con la analítica mensual habitual. 51 pacientes (58% de la Unidad de hemodiálisis), 32 varones y 19 mujeres, de 60,7 ± 14 años de edad, en programa de hemodiálisis durante 37,7 ± 52 meses, se dializaron con monitor con DI de forma rutinaria. La etiología de su IRC era de 3 NTI, 9 GNC, 12 nefroangiosclerosis, 7 poliquistosis renal, 7 diabetes mellitus y 13 no filiada. Se analizaron 1.606 sesiones durante 3 meses. Cada paciente recibió la pauta habitual de HD, con dializadores de diacetato de celulosa de 2,1 m2 (33,3%), polisulfona de 1,9 m2 (33,3%) y helixona de 1,8 m2, con duración de 263 ± 32 minutos, con un flujo sanguíneo de 405 ± 66, con flujo baño a 712 ± 138 ml/min, peso seco de 66,7 ± 14 kg. Se valoró la DI inicial, la DI final y el Kt en cada sesión y el PRU y el Kt/V mediante la analítica mensual. La DI inicial fue de 232 ± 41 ml/min, la DI final de 197 ± 44 ml/min, la dosis media de Kt fue de 56,6 ± 14 L, el Kt/V medio de 1,98 ± 0,5 y el PRU de 79,2 ± 7%. Todos los pacientes recibieron una dosis mínima de Kt/V y PRU de 1,3 y 70%, respectivamente. No obstante, si utilizamos el Kt según el sexo, observamos que el 31% de los pacientes no alcanzaban la dosis mínima prescrita (48,1 ± 2,4 L), 34,4% de los hombres y el 26,3% de las mujeres. Si utilizamos el Kt individualizado por su superficie corporal, (49,1 ± 4 L), observamos que el 43.1% de los pacientes no alcanzaban la dosis mínima prescrita, con 4,6 ± 3,4 L menos de dosis. Concluimos que el seguimiento de la dosis de diálisis con el Kt, permite una mejor discriminación de la adecuación de diálisis, identificando entre el 30 y el 40% de pacientes que quizá no alcanzasen una dosis adecuada para su género o para su superficie corporal (AU)

To ensure our patients are receiving an adequate dose in every dialysis session there must be a target to achieve this in the short or medium term. The incorporation during the last years of the ionic dialysance (ID) in the monitors, has provided monitoring of the dialysis dose in real time and in every dialysis session. Lowrie y cols., recommend monitoring the dose with Kt, recommending at least 40 L in women and 45 L in men or individualizing the dose according to the body surface area. The target of this study was to monitor the dose with Kt in every dialysis session for 3 months,and to compare it with the monthly blood test. 51 patients (58%of our hemodialysis unit), 32 men and 19 women, 60.7 ± 14 years old, in the hemodialysis program me for 37.7 ± 52 months, were dialysed with a monitor with IC. The etiology of their chronic renalfailure was: 3 tubulo-interstitial nephropathy, 9 glomerulonephritis,12 vascular disease, 7 polycystic kidney disease, 7 diabetic nephropathy and 13 unknown. 1,606 sessions were analysed during a 3 month period. Every patient was treated with the usual parameters of dialysis with 2.1 m2 cellulose diacetate (33.3%), 1.9m2 polisulfone (33.3%) or 1.8 m2 helixone, dialysis time of 263 ±32 minutes, blood flow of 405 ± 66, with dialysate flow of 712 ±138 and body weight of 66.7 ± 14 kg. ITo ensure our patients are receiving an adequate dose in every dialysis session there must be a target to achieve this in the short or medium term. The incorporation during the last years of the ionic dialysance (ID) in the monitors, has provided monitoring of the dialysis dose in real time and in every dialysis session. Lowrie y cols., recommend monitoring the dose with Kt, recommending at least 40 L in women and 45 L in men or individualizing the dose according to the body surface area. The target of this study was to monitor the dose with Kt in every dialysis session for 3 months, and to compare it with the monthly blood test. 51 patients (58% of our hemodialysis unit), 32 men and 19 women, 60.7 ± 14 years old, in the hemodialysis programme for 37.7 ± 52 months, were dialysed with a monitor with IC. The etiology of their chronic renal failure was: 3 tubulo-interstitial nephropathy, 9 glomerulonephritis, 12 vascular disease, 7 polycystic kidney disease, 7 diabetic nephropathy and 13 unknown. 1,606 sessions were analysed during a 3 month period. Every patient was treated with the usual parameters of dialysis with 2.1 m2 cellulose diacetate (33.3%), 1.9 m2 polisulfone (33.3%) or 1.8 m2 helixone, dialysis time of 263 ± 32 minutes, blood flow of 405 ± 66, with dialysate flow of 712 ± 138 and body weight of 66.7 ± 14 kg. Initial ID, final ID and Kt were measured in each session. URR and Kt/V were obtained by means of a monthly blood test. The initial ID was 232 ± 41 ml/min, the final ID was 197 ± 44 ml/min, the mean of Kt determinations was 56.6 ± 14 L, the mean of Kt/V was 1.98 ± 0.5 and the mean of URR was 79.2 ± 7%. Although all patients were treated with a minimum recommended dose of Kt/V and URR when we used the Kt according to gender, we observed that 31% of patients do not get the minimum dose prescribed (48.1 ± 2.4 L), 34.4% of the men and 26.3% of the women. If we use the Kt individualized for the body surface area, we observe that 43.1% of the patients do not get the minimum dose prescribed with 4.6 ± 3.4 L less than the dose prescribed. We conclude that the monitoring of dialysis dose with the Kt provides a better discrimination detecting that between 30 and 40% of the patients perhaps do not get an adequate dose for their gender or body surface areanitial ID, final ID and Kt (..) (AU)