Intravenous therapy | EPFL Graph Search

Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use. The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route of administration is also used for the consumption of som

Studying the interactions between electro-magnetic elds and biological tissue

Laurine Kolly

Drug delivery systems (DDS) were engineered to overcome the drawbacks of more common methods such as oral pills and intravenous injections. Implantable capsules that release anesthetic drugs locally for pain management after Total Knee Arthroplasty (TKA) are currently in development within the LMIS1. The capsule will be implanted at the site of the wound during the operation and will be controlled wirelessly through resonant inductive coupling, enabling a local release of analgesics. Within this framework, this project aimed to investigate the interaction of electro-magnetic elds with the tissue that separates the transmitting coil of the controller from the implanted capsule. The main aspects that were studied consisted of the penetration of the magnetic eld and the Specic Absorption Rate (SAR). As the receiving coils on the reservoirs of capsule will each resonate at specic frequency between 300 MHz and 1.1 GHz, the aforementioned aspects were assessed at the two ends of the frequency spectrum. This was performed through the means of Finite Element Analysis, using COMSOL simulation software. To do so, models with three dierent types of media were built: air as a baseline, multi-layered tissue as an anatomically representative model, that reproduced remote power transfer to a capsule implanted at the level of the knee, and water as an approximation of the multi-layered tissue model. As a result, it appeared that, at the higher frequencies, the magnetic eld is subject to considerable attenuation, such that the power input necessary to generate sucient eld intensity at the level of the capsule in a multi-layered tissue model must be increased from a baseline of 5 W, to 10 W at 300 MHz and to 50 W at 1.1 GHz. The analysis of the SAR revealed that average peak SAR values reached are higher than the safety limit (in an uncontrolled environment) at a frequency of 1.1 GHz, and that the SAR is proportional to the power input. This implies that there is a trade-o to increasing the power input to adjust the intensity of the magnetic eld that could potentially be resolved by modifying the circuit design. Furthermore, it was concluded that approximating tissue with water may cause for the magnetic eld intensity as well as the SAR to be underestimated, due to the diering dielectric properties and to the density of water being lower than that of skin or tendon. Thus, a more anatomically accurate multi-layered tissue model should be favoured.

2020

New Evidence of Neuroprotection by Lactate after Transient Focal Cerebral Ischaemia: Extended Benefit after Intracerebroventricular Injection and Efficacy of Intravenous Administration

Ximena Castillo, Pierre Magistretti

Background: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Methods: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 mu l of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 mu mol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Results: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p

Karger2012

Introducing tolerance to foreign and partly foreign proteins by erythrocyte binding and artificial glycosylations

Kym Lorenz Brünggel

Over the last few years, protein drugs have steadily gained importance in the clinic. Compared to small molecule drugs, protein drugs are taken up by antigen presenting cells, which degrade the proteins into peptides that are then presented on major histocompatability complex I and II to CD8+ respectively CD4+ T-cells. CD4+ T-cells are then able to activate B-cells, which upon activation will produce anti-drug antibodies. While anti-drug antibodies have mostly been viewed as a safety risk leading to drug injection related side effects, they have recently been proven to diminish the efficacy of the treatment. High antibody titers against Humira, a clinically approved monoclonal antibody used to treat rheumatoid arthritis, have been associated with low serum drug concentration and high disease activity score, ultimately leading to treatment failure. Two approaches to induce tolerance were developed in the Hubbell lab. One approach utilizes protein variants that are designed to bind to circulating erythrocytes. As 1 % of erythrocytes undergo apoptosis each day and are taken up by antigen presenting cells, along with the bound protein, they are presented to the immune system in a non-inflammatory tolerogenic fashion. Immunological tolerance is thereby induced against the apoptotic erythrocyte debris and the associated bound protein. The second approach uses synthetic glucose, galactose or mannose polymers conjugated to the target protein. The polymers target C-type lectins, which are known to clear apoptotic debris, leading to presentation of the protein by hepatic antigen presenting cells in a tolerogenic liver microenvironment. This thesis investigates the potential of these approaches to induce tolerance towards protein drugs. Arylsulfatase B was used as a model protein to investigate the potential of tolerance induction by targeting circulating erythrocytes, as 97% of patients receiving arylsulfatase B develop anti-drug antibodies. An erythrocyte binding variant of arylsufatase B was created by chemically conjugating the erythrocyte binding peptide ERY1 to arylsulfatse B. In mice receiving two doses of ERY1-arylsulfatase B one week apart followed by weekly doses of arylsulfatase B a significant delay of four week in the production of anti-drug Antibodies was found when compared to mice receiving weekly doses of only arylsulfatase B. To investigate the ability of synthetic glyco-polymers to induce tolerance towards protein drugs we used asparaginase as model protein. Between 37.5 % to 75% of patients treated with asparaginase develop anti-drug antibodies. Administering three intravenous injections of asparaginase-conjugated to glucose polymers before eight weeks of treatment with asparaginase significantly reduced anti-drug antibody titers by a factor of 125 when compared to animals only receiving eight weeks of treatment with asparaginase. Three pre-injections with asparaginase conjugated to the galactose or mannose polymer led to a reduction in anti-drug antibody titers by a factor of 12 respectively 400 after 5 weeks of treatment with asparaginase when compared to mice receiving only asparaginase for 5 weeks. These results indicates that synthetic glyco polymers, especially mannose and glucose based ones, are able to induce long term tolerance towards asparaginase. Synthetic glucose and mannose polymers therefore represent an excellent molecular approach to induce tolerance towards protein drugs.

EPFL2018