41 research outputs found
Ein mathematisches Kompartimentmodell der murinen Erythro- und Granulopoese unter simultaner Gabe von Erythropoietin und G-CSF
In dieser Arbeit wird das in vivo-Verhalten der murinen Erythro- und Granulopoese, einschlieĂlich der hĂ€matopoetischer Stammzellen, unter dem EinfluĂ von exogen appliziertem G-CSF und Erythropoietin mit Hilfe eines mathematischen Kompartimentmodelles untersucht. Der Schwerpunkt liegt auf der Identifizierung von linienĂŒbergreifenden Wachstumsfaktoreffekten. Zu diesem Zweck werden experimentelle Daten mit den Modellsimulationen unter BerĂŒcksichtigung verschiedener Modellannahmen verglichen.
Die experimentellen Daten fĂŒr die Modellentwicklung stammen zum einem kleinen Teil aus der Literatur, hauptsĂ€chlich betrachtet wurden jedoch Daten einer kooperierenden niederlĂ€ndischen Arbeitsgruppe. Die beiden Wachstumsfaktoren wurden kontinuierlich und simultan mittels osmotischer Minipumpen subkutan ĂŒber einen lĂ€ngeren Zeitraum appliziert. Die experimentellen Daten werden zunĂ€chst mit Hilfe eines nichtlinearen Regressionsmodelles analysiert und quantitativ beschrieben, wobei Interaktionseffekte zwischen den Wachstumsfaktoren besondere BerĂŒcksichtigung finden. Es wird dann ein umfassendes mathematischen Differentialgleichungsmodell der murinen Erythro- und Granulopoese unter BerĂŒcksichtigung der linienĂŒbergreifenden Wachstumsfaktoreffekte und Interaktionen aufgestellt. Es wird zunĂ€chst ĂŒberprĂŒft, ob sich die beobachteten Daten unter Simultanstimulation durch die einfache Zusammenschaltung zweier bereits existierender Einzelmodelle der Erythro- und Granulopoese ohne weitere Modellannahmen erklĂ€ren lassen. Dazu werden Daten von normalen als auch splenektomierten Tieren berĂŒcksichtigt. Es zeigt sich nach PrĂŒfung verschiedener Hypothesen, dass erst unter Annahme einer durch Erythropoietin potenzierten Amplifikation der primĂ€r G-CSF-abhĂ€ngigen Zellstufe der lienalen CFU-GM die experimentell beobachteten Effekte erklĂ€rt werden können. Es wird auĂerdem gezeigt, daĂ sich mit demselben Modell und denselben Modellparametern die bei splenektomierten Tieren zu beobachtetende G-CSFabhĂ€ngige Entwicklung einer EPO-resistenten AnĂ€mie gut erklĂ€rt wird.
In einem zweiten Teil der Arbeit wird ein Modellkonzept erarbeitet, mit welchem sich die Effekte nach Langzeitgabe von G-CSF mittels rezeptorvermitteltem G-CSF-Abbau erklĂ€ren lassen. In einem dritten Teil wird geprĂŒft, ob sich die hĂ€matopoetische Zellzahldynamik nach Absetzen der G-CSF-Gabe durch eine aktive RĂŒckmigration von Progenitoren aus der Milz in das Knochenmark erklĂ€ren lĂ€Ăt.
Das in dieser Arbeit entwickelte kombinierte Modell der Erythro- und Granulopoese impliziert eine Reihe von weiteren Fragen und bedarf der ĂberprĂŒfung und Weiterentwicklung anhand weiterer experimenteller Daten. DafĂŒr werden entsprechende VorschlĂ€ge erarbeitet, die weitere Einblicke in das komplexe Systemverhalten der HĂ€matopoese liefern könnten
Analysis of the Endogenous Peptidomes of Different Infant Formula Types and Human Milk
Infant formula (IF) is a commonly used replacement whenever motherâs own milk is not available. Most IFs are based on cow milk (powders, liquids). Alternatives, based on other sources such as goat milk or plants, exist. Independent of the source, IF production and composition are strictly regulated. Besides proteins, minerals, and lipids, milk contains a variety of endogenous peptides. Whereas the human milk peptidome has been studied intensively, the peptidomes of IFs have been mostly neglected. This study investigated the peptidomes of different types of first stage IF, including cow milk-based powders and liquids, and powdered goat milk-based IF, highlighting major similarities and differences to human milk. Extracted native peptidomes were analyzed by nanoRPC-ESI-MS/MS using two different fragmentation techniques allowing the confident identification of 1587 peptides. ÎČ-Casein peptides dominated in all samples. Interestingly, powdered and liquid cow milk-based IFs differed in the numbers of ÎČ- and αS1-casein peptides, indicating processing-derived variations. However, the peptidomes of cow and goat milk-based IF appeared to be more comparable to each other than to human milk. Despite an overlap in the major source proteins, many peptide sequences were different, i.e., species-specific. Remarkably, the data indicate that the human milk peptidome might be donor-specific as well
Handling of Breast Milk by Neonatal Units: Large Differences in Current Practices and Beliefs
Background: Breast milk (BM) for premature infants is subjected to multiple steps of processing, storage and distribution. These steps may influence the quality and safety of BM. Guidelines concerning the use of mother's own milk are either not available or limited to specific aspects of BM handling and are based on evidence of variable strength. This may result in diverse BM handling routines by health care professionals.Objective: We surveyed neonatal units to increase the knowledge about the current practice of BM handling routines of mother's own milk and to identify controversial aspects that could give directions for future research.Methods: An online-based questionnaire was sent to 307 different neonatal departments providing level III to level I neonatal care within Germany, Austria and Switzerland. Practices concerning screening for cytomegalovirus and BM bacteria, pasteurization, fortification, storage, workforce and the incidence of BM administration errors were surveyed.Results: A total of 152 units, 56% of contacted level III units and 51% of level II units, participated in the survey (Germany 53%, Switzerland 71%, and Austria 56%). We found differences concerning indication and method of CMV inactivation (performed by 58%), bacterial count screening (48%) and bacterial count reduction (17%) within participating units. Thirty different thresholds for bacterial BM counts were reported by 65 units, resulting in pasteurization or discarding of BM. The use of nutrient analysis (12%) and fortification regimens in addition to standard multicomponent fortifiers (58%) using either individual (93%), targeted (3%), or adjusted (4%) fortification protocols varied profoundly. There is a high variability in staff and available facilities for BM handling. 73% of units report about BM administration errors.Conclusion: There is a wide variability in most aspects of BM handling in the participating units. Despite limited evidence labor and cost intensive procedures are applied which may have an impact on BM quality
CSF Surfactant Protein Changes in Preterm Infants After Intraventricular Hemorrhage
Introduction: Surfactant proteins (SP) have been shown to be inherent proteins of the
human CNS and are altered during acute and chronic disturbances of CSF circulation.
Aim of the study was to examine the changes of surfactant protein concentrations in CSF
of preterm babies suffering from intraventricular hemorrhage.
Patients and Methods: Consecutive CSF samples of 21 preterm infants with
intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were
collected at primary intervention, after 5â10 days and at time of shunt insertion 50
days after hemorrhage. Samples were analyzed for surfactant proteins A, B, C, and G by
ELISA assays and the results were compared to 35 hydrocephalus patients (HC) without
hemorrhage and 6 newborn control patients.
Results and Discussion: Premature patients with IVH showed a significant elevation
of surfactant proteins SP-A, C, and G compared to HC and control groups: mean
values for the respective groups were SP-A 4.19 vs. 1.08 vs. 0.38 ng/ml. Mean SP-C
3.63 vs. 1.47 vs. 0.48 ng/ml. Mean SP-G 3.86 vs. 0.17 vs. 0.2 ng/ml. SP-A and G
concentrations were slowly falling over time without reaching normal values. SP-C levels
declined faster following neurosurgical interventions and reached levels comparable to
those of hydrocephalus patients without hemorrhage.
Conclusion: Intraventricular hemorrhages of premature infants cause posthemorrhagic
CSF flow disturbance and are associated with highly significant elevations of surfactant
proteins A, C, and G independent of total CSF protein concentrations
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Mutations in topoisomerase IIÎČ result in a B cell immunodeficiency.
B cell development is a highly regulated process involving multiple differentiation steps, yet many details regarding this pathway remain unknown. Sequencing of patients with B cell-restricted immunodeficiency reveals autosomal dominant mutations in TOP2B. TOP2B encodes a type II topoisomerase, an essential gene required to alleviate topological stress during DNA replication and gene transcription, with no previously known role in B cell development. We use Saccharomyces cerevisiae, and knockin and knockout murine models, to demonstrate that patient mutations in TOP2B have a dominant negative effect on enzyme function, resulting in defective proliferation, survival of B-2 cells, causing a block in B cell development, and impair humoral function in response to immunization
A descriptive analysis of human milk dispensed by the Leipzig Donor Human Milk Bank for neonates between 2012 and 2019
BackgroundHuman milk banking has become an important aspect of Nutritional medicine. It is not just about the provision of motherâs own milk (MOM) or donor human milk (DHM) in the hospital, but also a strategy to encourage breastfeeding in the clinical setting and beyond.ObjectiveTo describe the feeding patterns of hospitalised infants including human milk dispensed by the Leipzig Donor Human Milk Bank (LMB).DesignA descriptive analysis of daily data on milk feeds dispensed by LMB for hospitalised infants distinguishing between MOM or DHM, either fresh or frozen, and raw/pasteurised milk from 2012â2019.ResultsWe included 2,562 infants with median hospitalisation of 23âdays, for whom human milk was dispensed on median 76% of those days and other nutrition on the remaining days. Raw MOM and raw DHM comprised 52% and 8% of the dispensed milk, respectively. Dispensing exclusive DHM instead of MOM for at least one full day was required for 55% of the infants, mostly at the beginning but also later during hospitalisation. Exclusive raw DHM was dispensed on at least 1âday for 37% of the infants, in different birthweight strata <1,000âg: 10%, 1,000-1500âg: 11%, 1,500-2500âg: 13% andâ>â2,500âg: 3%. At discharge, MOM was dispensed for more than 60% of the infants.ConclusionDuring an infantâs hospital stay, LMB dispenses various human milk feeds with interspersed DHM resulting in complex intra-individual and time-variant feeding patterns. LMB dispenses raw MOM and especially raw DHM with the intention to retain the properties of human milk unlike a diet containing pasteurised DHM and/or formula. Although raw DHM comprises a small percentage of all dispensed milk, raw DHM is dispensed for a substantial portion of infants. Our results document that dispensing raw DHM, is possible in routine settings
Wirkungsanalyse bestehender KlimaschutzmaĂnahmen und -programme sowie Identifizierung möglicher weiterer MaĂnahmen eines Energie- und Klimaschutzprogramms der Bundesregierung
Eine Analyse der deutschen Energie- und Klimapolitik hat ergeben:
Nur im MaĂnahmenfeld "Ausbau der Erneuerbaren Energien im Strombereich" wird voraussichtlich das Ziel ereicht. Dagegen wird in allen anderen MaĂnahmenfeldern das Ziel verfehlt oder es bestehen Wirkungsdefizite der eingesetzten Politikinstrumente. Das betrifft insbesondere die Energieeffizienz auf der Nachfrageseite, aber auch die Kraft-WĂ€rme-Kopplung und Erneuerbare Energien-WĂ€rme. FĂŒr die MaĂnahmenfelder "Fluorierte Treibhausgase", "Industrieprozesse" und "Landwirtschaft" mĂŒssen ĂŒberhaupt erst verbindliche Reduktionsziele festgelegt und Politikinstrumente eingefĂŒhrt werden
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Introduction
Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to hostâs innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects.
Patients and Methods
CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0â84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated.
Results
SP AâD are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations.
Conclusion
The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SPâs requires further thorough investigations
Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification
Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that âStandard Fortification,â which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of âIndividualized Fortificationâ to optimize nutrient intake. âAdjustable Fortificationâ and âTargeted Fortificationâ are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge
Recommendations for the Establishment and Operation of Human Milk Banks in Europe: A Consensus Statement From the European Milk Bank Association (EMBA)
Objectives: To develop recommendations from the European Milk Bank Association (EMBA) for the establishment and operation of human milk banks (HMB) in Europe.Method: A working group comprising members of the EMBA was convened in 2015 to develop Europe-wide recommendations for milk banks. Each member had experience of guideline development and/or milk banking operations. An initial survey was agreed using collated published global recommendations. A total of 108 potential recommendations were included in the survey; responders noted which were included in their national guidelines. The responses were collated, compared, and discussed and the group determined where there was consensus and where substantial or minor differences were identified. Where there was consensus or robust published evidence on which to base recommendations these were included. When there was no consensus and no clear evidence base, a statement of explanation based on collective expert opinion was agreed.Results: Published, internationally available guidelines with recommendations for human milk banks from France, Italy, and the UK, together with guidelines from Austria, Denmark, Germany, Norway, Slovakia, Spain, Sweden, and Switzerland were included as source materials. These covered: General recommendations; Donor recruitment and screening; Expression, handling, and storage of donor human milk (DHM); Pooling of DHM; Milk screening; Milk treatment (pasteurization); Delivery of DHM to recipients.Conclusions: Evidence based recommendations and consensus statements from the EMBA will now be published on the EMBA website to assist in the safe establishment and operation of HMBs throughout Europe. These have also been used to inform the chapter on human milk to be included in the 2019 edition of the Guide to the quality and safety of tissues and cells for human application, published by the European Directorate for the Quality of Medicines & HealthCare (EDQM)