Cerebral open flow microperfusion (cOFM)-HILIC-HRMS platform for in vivo and in situ monitoring of tumor microenvironment in glioblastoma.

Background: Glioblastoma exhibits a very poor prognosis and profound metabolic alterations associated to its aggressiveness. Examining tumor metabolic states is crucial for identifying potential therapeutic targets, enabling personalized medicine applications. However, direct access to the functional glioblastoma tumor microenvironment (TME) in vivo is highly challenging, particularly due to the tumor location and risk of blood-brain-barrier disruption.

Lipid Ratios for Diagnosis and Prognosis of Pulmonary Hypertension.

Pulmonary hypertension (PH) poses a significant health threat. Current biomarkers for PH lack specificity and have poor prognostic capabilities. To develop better biomarkers for PH that are useful for patient identification and management.

Open flow microperfusion to assess local drug concentrations in the buccal mucosa.

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Ex Vivo Human Skin Model to Study Immediate and Early Local Responses to External Stimuli.

Local responses of skin tissue to external stimuli are complex, thus exceeding the capability of in vitro methods but do not need the complexity of a whole organism to be simulated. Therefore, we established a human ex vivo skin model in our lab to study the local effects of various stimuli, such as burns and local topic treatments. In this chapter, we describe the experimental setup of the ex vivo model and additional technology of collecting dermal interstitial fluid.

Opportunities of topical drug products in a changing dermatological landscape.

Despite the prevalence and the impact on quality of life of dermatological indications, drug products to treat such conditions have rarely been blockbusters. The prevailing perception of a limited commercial potential of dermatological drug products has restricted innovation and encouraged a more conservative development approach. For example, the focus was on repurposing/reformulation of existing active pharmaceutical ingredients (APIs) specifically for the topical delivery route.

Psychotherapists' views on open notes: An online survey from Germany.

Background: In an increasing number of countries, patients are given online record access (ORA) to their clinical notes ("open notes"). In many places, psychotherapy notes are exempt, even if patients explicitly wish to read them. Previous research suggests that psychotherapists (PTs) have reservations that are not yet fully understood.

Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis.

Dupilumab is a monoclonal antibody approved for the treatment of atopic dermatitis (AD); however, its effects on molecular, cellular, and immunological levels remain to be elucidated. In this study, blood and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional (L) skin were collected from eight patients with moderate to severe AD, before (visit 2-v2) and at the end of a 16-week treatment with dupilumab (visit 10-v10). Clinical treatment effect was demonstrated by significantly decreased AD severity scores at the end of treatment.

Comparative Study of Dermal Pharmacokinetics Between Topical Drugs Using Open Flow Microperfusion in a Pig Model.

Purpose: Accurate methods to determine dermal pharmacokinetics are important to increase the rate of clinical success in topical drug development. We investigated in an in vivo pig model whether the unbound drug concentration in the interstitial fluid as determined by dermal open flow microperfusion (dOFM) is a more reliable measure of dermal exposure compared to dermal biopsies for seven prescription or investigational drugs. In addition, we verified standard dOFM measurement using a recirculation approach and compared dosing frequencies (QD versus BID) and dose strengths (high versus low drug concentrations).

Topical Delivery Systems Effectively Transport Analgesics to Areas of Localized Pain via Direct Diffusion.

Topical delivery systems (TDSs) enable the direct transport of analgesics into areas of localized pain and thus minimize the side effects of administration routes that rely on systemic drug distribution. For musculoskeletal pain, clinicians frequently prescribe topical products containing lidocaine or diclofenac. This study assessed whether drug delivery from a TDS into muscle tissue occurs mainly via direct diffusion or systemic transport.

Implementation and validation of a UHPLC-MS/MS method for quantification of the endocannabinoids AEA and 2-AG in cerebral interstitial fluid and plasma.

Endogenous endocannabinoids such as N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are involved in the patho-biochemistry of several neurological diseases and have been associated with mood-enhancing phenomena. Although they have been intensively studied in recent years, accurate and reliable quantification of these analytes in cerebral interstitial fluid (cISF) to elucidate their neuro-modulatory role is still challenging. Moreover, there is a need for an analytical method that can analyze plasma in addition to cISF and is thus able to address research questions in both preclinical and clinical studies.

Small volume rapid equilibrium dialysis (RED) measures effects of interstitial parameters on the protein-bound fraction of topical drugs.

The importance of plasma protein binding in the early stages of drug development is well recognized. Free and bound drug fractions in plasma are routinely determined with well-established methods. However, for physiological fluids with a small accessible volume and low protein concentrations, such as dermal interstitial fluid (dISF) validated methods are currently missing.

Detailed pharmacokinetic characterization of advanced topical acyclovir formulations with IVPT and in vivo Open Flow Microperfusion.

Successful treatment of herpes simplex viruses is currently limited by a lack of effective topical drugs. Commonly used topical acyclovir products only reduce the duration of lesions by a few days. Optimizing topical formulations to achieve an enhanced acyclovir solubility and penetration could increase the efficacy of topically applied acyclovir, but new formulations need to show reliable acyclovir delivery into at least the epidermis/dermis and need to provide sustained acyclovir release for extended time periods.

Optical glucose sensor for microfluidic cell culture systems.

Glucose is the primary energy source of human cells. Therefore, monitoring glucose inside microphysiological systems (MPS) provides valuable information on the viability and metabolic state of the cultured cells. However, continuous glucose monitoring inside MPS is challenging due to a lack of suitable miniaturized sensors.