Cytotoxicity, in Vivo Skin Irritation and Acute Systemic Toxicity of the Mesoporous Magnesium Carbonate Upsalite ®

Abstract Upsalite ® is a mesoporous magnesium carbonate synthesized without using surfactants and therefore highly attractive from environmental and production economy points of view. The material has recently been suggested as drug delivery vehicle and as topical bacteriostatic agent. In order to continue exploring these and other bio-related applications of the material, primary biocompatibility studies are needed. Herein we present the first in vivo acute systemic toxicity and skin irritation analyses as well as in vitro cytotoxicity evaluations of Upsalite ® . The material was found to be non-toxic for human dermal fibroblasts cells up to a concentration of 1000 µg/ml and 48 h exposure in contrast to the mesoporous silica material SBA-15, used as reference, which significantly affected cell viability at particle concentration of 500 and 1000 µg/ml after the same exposure time. Topical application of Upsalite ® resulted in negligible cutaneous reactions in a rabbit skin irritation model and no evidence of significant systemic toxicity was found when saline extracts of Upsalite ® were injected in mice. Injection of sesame oil extract, however, resulted in transient weight loss, most likely due to injection of particles, and not toxic leachables. The presented results form the basis for future development of Upsalite ® and similar mesoporous materials in biomedical applications and further toxicity as well as biocompatibility studies should be directed towards specific areas of use

Immunodepletion in xenotransplantation

Xenograft transplantation is perhaps the most immunologically difficult problem in transplantation today. An overwhelming hyperacute rejection reaction (HAR) occurs within minutes of organ implantation. Preformed antibodies are thought to initiate this process. We used a pig-to-dog renal xenograft transplant model and investigated methods of decreasing the severity of hyperacute rejection. Female pigs weighing 15-20 kg were used as donors. Recipients were mongrel dogs weighing 15-25 kg. Experimental dogs were all given a number of treatments of IgG depletion using an antibody removal system (Dupont-Excorim). This machine immunoadsorbs plasma against a column containing immobilized staphylococcal protein A, which is known to bind the IgG Fc receptor. An 84% reduction in the IgG levels and a 71% reduction in IgM levels was achieved. Postoperative assessment was made of urine output, time to onset of HAR, and histopathological examination of the rejected kidneys. Although cross-matches between donor lymphocytes and recipient sera remained strongly positive in the treated dogs, there was a two- to fourfold reduction in the titers. The time to onset of HAR was prolonged in the experimental group, and the urine output was increased slightly. The histopathologic changes in the experimental group generally showed signs of HAR, but of less intensity than in the nonimmunodepleted control group. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial

ICT-based solution approach for collaborative delivery of customised products

© 2016 Taylor & Francis. Growing interest on business collaboration motivates todays industries, especially small and medium enterprises (SMEs) to establish and manage dynamic and non-hierarchical business networks to respond to market opportunities with added business benefits. This business environment requires concurrent work and real-time information sharing between key business partners in order to design and develop customised products. The use of traditional communication media such as e-mail, phone and fax is not satisfactory to get real-time information and is time-consuming and most often ineffective. In such environments, an Information and Communication Technology (ICT)/Web-based technology supports real-time information sharing among networked SMEs for the collaborative design and manufacturing of customised products. This study proposes an innovative ICT platform supporting SMEs collaboration, through Web and the Internet of Things technologies, which follows the Net-Challenge conceptual approach and methodological guidelines for SMEs to form and operate virtual organisations for the collaborative development and delivery of customised products. The ICT Platform was assessed in three different industry domains, namely the textile and apparel, the footwear and the machine tools, respectively. This ICT solution promotes collaboration, with substantial advantages for SMEs including the reduction of costs and delivery time and improvement of the innovation potential

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction Are Altered in Parkinson's Disease and Related Disorders

Background: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects. Objective: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders. Methods: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort. Results: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021). Conclusions: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Honeybee Colony Vibrational Measurements to Highlight the Brood Cycle

Insect pollination is of great importance to crop production worldwide and honey bees are amongst its chief facilitators. Because of the decline of managed colonies, the use of sensor technology is growing in popularity and it is of interest to develop new methods which can more accurately and less invasively assess honey bee colony status. Our approach is to use accelerometers to measure vibrations in order to provide information on colony activity and development. The accelerometers provide amplitude and frequency information which is recorded every three minutes and analysed for night time only. Vibrational data were validated by comparison to visual inspection data, particularly the brood development. We show a strong correlation between vibrational amplitude data and the brood cycle in the vicinity of the sensor. We have further explored the minimum data that is required, when frequency information is also included, to accurately predict the current point in the brood cycle. Such a technique should enable beekeepers to reduce the frequency with which visual inspections are required, reducing the stress this places on the colony and saving the beekeeper time

Deep Mining of Oxysterols and Cholestenoic Acids in Human Plasma and Cerebrospinal Fluid: Quantification using Isotope Dilution Mass Spectrometry

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient