Subacute Degeneration of Fibers After Vertical Parasagittal Hemispherotomy.

Purpose: After vertical parasagittal hemispherotomy a restricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective cohort study analyses the anatomic site and the time course of the diffusion restriction after vertical parasagittal hemispherotomy.

Methods: Fifty-nine patients were included into this study, all of them having had one pre-operative and at least one post-operative MRI, including diffusion imaging at b‑values of 0 and 1000 s/mm with a calculated ADC.

Selenium-containing compounds: a new hope for innovative treatments in Alzheimer's disease and Parkinson's disease.

Neurodegenerative diseases are challenging to cure. To date, no cure has been found for Alzheimer's disease or Parkinson's disease, and current treatments are able only to slow the progression of the diseases and manage their symptoms. After an introduction to the complex biology of these diseases, we discuss the beneficial effect of selenium-containing agents, which show neuroprotective effects in vitro or in vivo.

Biorelevant subcutaneous in vitro test predicts the release of human and fast acting insulin formulations.

The administration of insulins by subcutaneous injection is nowadays widely prevalent. The injection site is located below the dermis and composed of cells and the extracellular matrix formed of a network of macromolecules such as hyaluronic acid and collagen. Following an injection, the insulins from the formulated products are timely released as drug molecules from the injection site into systemic circulation.

First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT Agents with a Beneficial Neuroprotective Profile against Alzheimer's Disease.

Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT emerged as a promising target for AD treatment; thus, here a new series of 5-HTR ligands with a 1,3,5-triazine core and selenoether linkers was explored. Among them, the 2-naphthyl derivatives exhibited strong 5-HTR affinity and selectivity over 5-HTR (-), 5-HTR ( and ), and 5-HTR ().

The Potential of Epigallocatechin-3-gallate (EGCG) as Complementary Medicine for the Treatment of Inflammatory Bowel Disease.

Complementary and alternative medicine has the potential to enrich conventional therapy to improve the treatment of various diseases. Patients that suffer from inflammatory bowel disease, which requires a constant need for medication, have to deal with the adverse effects of repeated application. Natural products such as Epigallocatechin-3-gallate (EGCG) possess the potential to improve symptoms of inflammatory diseases.

Clofazimine Inhalation Suspension Demonstrates Promising Toxicokinetics in Canines for Treating Pulmonary Nontuberculous Mycobacteria Infection.

Pulmonary nontuberculous mycobacteria (NTM) infection is recognized as a major global health concern due to its rising prevalence worldwide. As an opportunistic pathogen with increasing antibiotics resistance, prolonged systemic dosing with multiple antibiotics remains the primary treatment paradigm. These prolonged treatments, administered predominantly by oral or parenteral routes, often lead to systemic toxicity.

Method for measuring mucoadhesion of ophthalmica considering regulatory aspects.

In this technical note we present an easy to use method for determining mucoadhesion for ophthalmica, easily applicable in a regulated setting. The determined value of mucoadhesion is a combination value of adhesion and cohesion force, as both are relevant to the retention of a formulation and thus its bioavailability. The method is specifically designed to test two formulations against each other to gain information on bioequivalence.

Models using native tracheobronchial mucus in the context of pulmonary drug delivery research: Composition, structure and barrier properties.

Mucus covers all wet epithelia and acts as a protective barrier. In the airways of the lungs, the viscoelastic mucus meshwork entraps and clears inhaled materials and efficiently removes them by mucociliary escalation. In addition to physical and chemical interaction mechanisms, the role of macromolecular glycoproteins (mucins) and antimicrobial constituents in innate immune defense are receiving increasing attention.

In vitro tools for orally inhaled drug products-state of the art for their application in pharmaceutical research and industry and regulatory challenges.

The drug development process is a lengthy and expensive challenge for all involved players. Experience with the COVID-19 pandemic underlines the need for a rapid and effective approval for treatment options. As essential prerequisites for successful drug approval, a combination of high-quality studies and reliable research must be included.

Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages: an opportunity for an in vitro drug screening assay.

Unlabelled: Inflammatory bowel disease (IBD) is a widespread disease, affecting a growing demographic. The treatment of chronic inflammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput.

Pulmonary in vitro instruments for the replacement of animal experiments.

Advanced in vitro systems often combine a mechanical-physical instrument with a biological component e.g. cell culture models.

Towards More Predictive, Physiological and Animal-free Models: Advances in Cell and Tissue Culture 2020 Conference Proceedings.

Experimental systems that faithfully replicate human physiology at cellular, tissue and organ level are crucial to the development of efficacious and safe therapies with high success rates and low cost. The development of such systems is challenging and requires skills, expertise and inputs from a diverse range of experts, such as biologists, physicists, engineers, clinicians and regulatory bodies. Kirkstall Limited, a biotechnology company based in York, UK, organised the annual conference, (ACTC), which brought together people having a variety of expertise and interests, to present and discuss the latest developments in the field of cell and tissue culture and modelling.

Modulating the Barrier Function of Human Alveolar Epithelial (hAELVi) Cell Monolayers as a Model of Inflammation.

The incidence of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) remains an important problem, particularly in the present time with the Covid-19 pandemic. However, an adequate test system to monitor the barrier function of the alveolar epithelium during inflammation and for assessing anti-inflammatory drugs is urgently needed. Therefore, we treated human Alveolar Epithelial Lentivirus-immortalised cells (hAELVi cells) with the pro-inflammatory cytokines TNF-α (25 ng/ml) and IFN-γ (30 ng/ml), in the presence or absence of hydrocortisone (HC).

Development and evaluation of a quality control system based on transdermal electrical resistance for skin barrier function in vitro.

Background: In vitro skin permeation experiments are highly relevant for pharmaceutical, cosmetic, agricultural developments, and regulatory evaluation. A key requirement is the skin barrier integrity, that is accompanied by an intact stratum corneum (SC) which implements high skin quality. A variety of integrity tests are currently available, for example, measurement of transepidermal water loss, monitoring the permeation of tritiated water and the measurement of transdermal electrical resistance (TER).

Dose reduction in mammography by using imaging plate technology: A retrospective analysis.

Purpose: Conventional mammography is a decisive tool in detecting breast cancer. Continuous efforts are undertaken in order to further improve the image quality as well as to reduce the applied doses. The purpose of our study was to compare diagnostic image quality of dose reduced computed mammography with a new needle-based detector system to full dose powder imaging plates.

Safety assessment of excipients (SAFE) for orally inhaled drug products.

The development of new orally inhaled drug products requires their demonstration of safety, which must be proven in animal experiments. New in vitro methods may replace, or at least reduce, these animal experiments, provided they are able to correctly predict safety or possible toxicity in humans. However, the challenge is to link in vitro data obtained in human cells to human in vivo data.

Preparation of maltodextrin nanoparticles and encapsulation of bovine serum albumin - Influence of formulation parameters.

Maltodextrin, which is obtained by partial hydrolysis of starch, is water soluble and could serve as hydrophilic carrier for the encapsulation of protein-based active pharmaceutical ingredients. We investigated three different commercial maltodextrins (Dextrose Equivalents (DE) 4.0-7.

Vibrational spectroscopic imaging and live cell video microscopy for studying differentiation of primary human alveolar epithelial cells.

Alveolar type II (ATII) cells in the peripheral human lung spontaneously differentiate toward ATI cells, thus enabling air-blood barrier formation. Here, linear Raman and coherent anti-Stokes Raman scattering (CARS) microscopy are applied to study cell differentiation of freshly isolated ATII cells. The Raman spectra can successfully be correlated with gradual morphological and molecular changes during cell differentiation.

Human airway mucus alters susceptibility of Pseudomonas aeruginosa biofilms to tobramycin, but not colistin.

Objectives: In the context of cystic fibrosis, Pseudomonas aeruginosa biofilms often develop in the vicinity of airway mucus, which acts as a protective physical barrier to inhaled matter. However, mucus can also adsorb small drug molecules administered as aerosols, including antibiotics, thereby reducing their bioavailability. The efficacy of antibiotics is typically assessed by determining the MIC using in vitro assays.

Murine alveolar epithelial cells and their lentivirus-mediated immortalisation.

In this study, we describe the isolation and immortalisation of primary murine alveolar epithelial cells (mAEpC), as well as their epithelial differentiation and barrier properties when grown on Transwell® inserts. Like human alveolar epithelial cells (hAEpC), mAEpC transdifferentiate in vitro from an alveolar type II (ATII) phenotype to an ATI-like phenotype and exhibit features of the air-blood barrier, such as the establishment of a thin monolayer with functional tight junctions (TJs). This is demonstrated by the expression of TJ proteins (ZO-1 and occludin) and the development of high transepithelial electrical resistance (TEER), peaking at 1800Ω ·cm².

Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.

Hay fever is notoriously triggered when nasal mucosa is exposed to allergenic pollen. One possibility to overcome this pollen exposure may be the application of an ointment with physical protective effects. In this context, we have investigated Bepanthen Eye and Nose Ointment and the ointment basis petrolatum as reference while using contemporary in vitro techniques.

The role of mucus on drug transport and its potential to affect therapeutic outcomes.

A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation.

Cell and tissue-based in vitro models for improving the development of oral inhalation drug products.

The interplay of costs and ethics has increased the need for adequate models mimicking the human in vivo situation drastically. An adequate model has the ability to generate data which are predictive for a certain aspect of the human response, for example for the bioavailability. This review highlights how in vitro models can enrich pulmonary drug delivery research with more detailed insights in cellular and non-cellular barriers, allowing for faster improvements and significant innovations of inhalation drug products.

Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part II: evaluation of IL-10-loaded microparticles for the treatment of lung inflammation.

Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine.

Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation.

The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro.