Beurteilung der Posttransplantationsosteopathie unter oraler Ibandronattherapie nach Lebertransplantation: ein 5-Jahres-Follow-Up

Fragestellung: Die Posttransplantationsosteopathie rückt in den letzten Jahren in den Vordergrund der Langzeitbetreuung nach solider Organtransplantation. Eine Therapie mit Bisphosphonaten in Kombination mit Kalzium und Vitamin D3 hat sich bereits etabliert. In dieser Studie berichten wir von einer oralen Ibandronattherapie nach Lebertransplantation in Form eines Langzeit-Follow-up’s, mit Hauptaugenmerk auf Frakturauftreten und Knochenmineraldichtemessungen nach Beendigung der medikamentösen Therapie. Methodik: Wir schlossen 57 der 142 von Mai 2006 bis Dezember 2008 lebertransplantierten Patienten in die Studie ein. 40 Patienten wurden über einen Zeitraum von 5 Jahren nachbeobachtet. Diese Patienten erhielten eine orale Ibandronattherapie über min-destens 24 Monate. 33 Patienten wurden retrospektiv in die Kontrollgruppe aufge-nommen. Es erfolgten Laboruntersuchungen und DXA- Messungen der LWS und des Femur zum Zeitpunkt vor LTX, 3, 6, 12, 24, 36, 48, 60 Monate nach LTX. Ergebnis: Unter oraler Ibandronattherapie zeigte sich ab 6 Monate nach LTX eine signifikante höhere absolute lumbale Knochenmineraldichte im Vergleich zur Kon-trollgruppe. Die prozentualen Veränderungen erreichten statistische Signifikanz zum Zeitpunkt 12, 48 und 60 Monate nach LTX. Die Ibandronatgruppe wies eine signifi-kant niedrigere Frakturhäufigkeit als die Kontrollgruppe auf. Eine präoperative Pred-nisolontherapie hat einen signifikanten Einfluss auf die lumbale Knochenmineral-dichte 3 und 12 Monate nach Lebertransplantation. Schlussfolgerung: Eine orale Ibandronattherapie nach Lebertransplantation redu-ziert das Auftreten pathologischer Knochenfrakturen und steigert die Knochenmi-neraldichte im Posttransplantationszeitraum von 5 Jahren

The Effects of Vitamin D Deficiency on Neurodegenerative Diseases

Approximately 90% of the elderly population in the western countries has at least a mild to moderate vitamin D hypovitaminosis. Besides the well-known function of vitamin D in calcium homeostasis, it has been recently found that several enzymes and receptors involved in its homeostasis are expressed in the nervous system and brain suggesting also an important role in the brain homeostasis. Interestingly, epidemiological and clinical studies found reduced vitamin D level associated with an increased risk of several neurodegenerative disorders. In this chapter, we focus on a potential link between vitamin D and Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, prion disease, and motor neuron disease. Epidemiological studies were summarized, an overview of the known potential underlying pathomolecular mechanisms are given, and results from clinical studies dealing with vitamin D supplementation were presented. As an outlook, recent literature suggesting an impact of vitamin D on autism spectrum disease, depression, and schizophrenia are briefly discussed. In conclusion, the identification of an abundant vitamin D metabolism in the brain and the tight link between the increasing number of several neurological and mental disorders emphasize the need of further research making a clear recommendation of the intake and supplementation of vitamin D in a growing elderly population

Информационная система сравнения программных продуктов в области медицины

Целью данной работы является сравнение медицинских программных продуктов для использования в области медицины. В процессе исследования проводился теоретический анализ, обзор аналогов, проектирование и разработка информационной системы. Среда разработки: "Встроенный язык 1С". Область применения: "Поликлиника №1" г. Юрги Разрабатываемая информационная система должна обеспечивать выполнение следующих функций: 1.Учет информации об экспертах; 2.Учет информации о программном обеспечение (ПО); 3.Сравнение ПО методом комплексной оценки. Проанализированы производственные и вредные факторы. В целом, рабочее место пользователя удовлетворяет стандартам и нормам безопасности.The aim of this work is to compare medical software products for use in the field of medicine. In the course of the research, a theoretical analysis, a review of analogs, design and development of an information system were carried out. Development environment: "Built-in 1C language". Scope: "Polyclinic No. 1" in Yurga. The developed information system must ensure the performance of the following functions: 1. Accounting for information about experts; 2. Accounting for information about software (software); 3. Comparison of software by the method of integrated assessment. The production and harmful factors are analyzed. In general, the user's workplace meets safety standards and regulations

Methylxanthines and Neurodegenerative Diseases: An Update

Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases

Development of an autonomous mobile towing vehicle for logistic tasks

Frequently carrying high loads and performing repetitive tasks compromises the ergonomics of individuals, a recurrent scenario in hospital environments. In this paper, we design a logistic planner of a fleet of autonomous mobile robots for the automation of transporting trolleys around the hospital, which is independent of the space configuration, and robust to loss of network and deadlocks. Our robotic solution has an innovative gripping system capable of grasping and pulling nonmodified standard trolleys just by coupling a plate. Robots are able to navigate autonomously, to avoid obstacles assuring the safety of operators, to identify and dock a trolley, to access charging stations and elevators, and to communicate with the latter. An interface was built allowing users to command the robots through a web server. It is shown how the proposed methodology behaves in experiments conducted at the Faculty of Engineering of the University of Porta and Braga's Hospital.This work is financed by the ERDF - European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation- COMPETE 2020 Programme, and by National Funds through the Portuguese funding agency, FCT-Fundação para a Ciência e a Tecnologia, within project SAICTPAC/0034/2015 - POCI-01- 0145-FEDER-016418. Authors would like to acknowledge to Trivalor, Itau and Gertal for the support of the project RDH.info:eu-repo/semantics/publishedVersio

Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class

Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells

Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood. As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in many tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism. However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many diseases, such as Alzheimer’s disease, cancer, fatty liver disease and type-2 diabetes, treatment with gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase in intracellular triglycerides (SH-SY5Y: 170.3%; HEK: 272.1%; Calu-3: 448.1%), suggesting that the decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which could be important in diseases, such as Alzheimer’s disease

Vitamin D and Its Analogues: From Differences in Molecular Mechanisms to Potential Benefits of Adapted Use in the Treatment of Alzheimer’s Disease

Lifestyle habits and insufficient sunlight exposure lead to a high prevalence of vitamin D hypovitaminosis, especially in the elderly. Recent studies suggest that in central Europe more than 50% of people over 60 years are not sufficiently supplied with vitamin D. Since vitamin D hypovitaminosis is associated with many diseases, such as Alzheimer’s disease (AD), vitamin D supplementation seems to be particularly useful for this vulnerable age population. Importantly, in addition to vitamin D, several analogues are known and used for different medical purposes. These vitamin D analogues differ not only in their pharmacokinetics and binding affinity to the vitamin D receptor, but also in their potential side effects. Here, we discuss these aspects, especially those of the commonly used vitamin D analogues alfacalcidol, paricalcitol, doxercalciferol, tacalcitol, calcipotriol, and eldecalcitol. In addition to their pleiotropic effects on mechanisms relevant to AD, potential effects of vitamin D analogues on comorbidities common in the context of geriatric diseases are summarized. AD is defined as a complex neurodegenerative disease of the central nervous system and is commonly represented in the elderly population. It is usually caused by extracellular accumulation of amyloidogenic plaques, consisting of amyloid (Aβ) peptides. Furthermore, the formation of intracellular neurofibrillary tangles involving hyperphosphorylated tau proteins contributes to the pathology of AD. In conclusion, this review emphasizes the importance of an adequate vitamin D supply and discusses the specifics of administering various vitamin D analogues compared with vitamin D in geriatric patients, especially those suffering from AD

The impact of capsaicinoids on APP processing in Alzheimer's disease in SH-SY5Y cells

The vanilloid capsaicin is a widely consumed spice, known for its burning and "hot" sensation through activation of TRPV1 ion-channels, but also known to decrease oxidative stress, inflammation and influence tau-pathology. Beside these positive effects, little is known about its effects on amyloid-precursor-protein (APP) processing leading to amyloid-β (Aβ), the major component of senile plaques. Treatment of neuroblastoma cells with capsaicinoids (24 hours, 10 µM) resulted in enhanced Aβ-production and reduced Aβ-degradation, leading to increased Aβ-levels. In detailed analysis of the amyloidogenic-pathway, both BACE1 gene-expression as well as protein-levels were found to be elevated, leading to increased β-secretase-activity. Additionally, γ-secretase gene-expression as well as activity was enhanced, accompanied by a shift of presenilin from non-raft to raft membrane-domains where amyloidogenic processing takes place. Furthermore, impaired Aβ-degradation in presence of capsaicinoids is dependent on the insulin-degrading-enzyme, one of the major Aβ-degrading-enzymes. Regarding Aβ-homeostasis, no differences were found between the major capsaicinoids, capsaicin and dihydrocapsaicin, and a mixture of naturally derived capsaicinoids; effects on Ca2+-homeostasis were ruled out. Our results show that in respect to Alzheimer's disease, besides the known positive effects of capsaicinoids, pro-amyloidogenic properties also exist, enhancing Aβ-levels, likely restricting the potential use of capsaicinoids as therapeutic substances in Alzheimer's disease

Osteoarthritis of the knee – clinical assessments and inflammatory markers11Supported by a grant from the Robert Bosch Stiftung, Stuttgart, Germany.

AbstractObjective: The present cross sectional study was performed to test the hypothesis that in osteoarthritis (OA) of the knee severity of this disease is related to local levels of inflammatory metabolites and their corresponding enzymes.Methods: From 41 patients with OA of the knee (age range 45–79 years) undergoing arthroscopy blood, synovial fluid (SF) and synovial membrane (SM) were collected. Clinical conditions were primarily assessed by the WOMAC-index and radiographic grading (K&L-grade). Concentrations of PGE2, TxB2and NO2/3and that of IL-6, IL-1α, IL-1β, TNFα, COX-2 and iNOS were determined in SF and SM, respectively.Results: With advancing age K&L-grade and COX-2 in SM increased significantly (P=0.005 and P=0.01, respectively). TNFα and IL-1α were not detectable in SM samples. Apart from a correlation between PGE2and WOMAC-index (r=0.36, P=0.035) no significant relationships could be found between the various inflammatory parameters and any of the assessed clinical signs.Conclusions: Apparently no direct relationships exist between the measured markers of inflammation (e.g. PGE2, NO2/3) or the involved enzymes (e.g. COX-2, iNOS) and the severity of OA of the knee. The degenerative condition of this disease might be due to the more local, mainly mechanical injury with little systemic upset. However, further longitudinal studies are needed to clarify whether the assessed biochemical markers could serve as predictors for the progression of OA