Einfluss unterschiedlicher Proteinqualität und –quantität auf die Zusammensetzung und den Energiegehalt des Urins bei der Katze

In der vorliegenden Arbeit wurde der Einfluss von drei unterschiedlichen Proteinquellen (fettarmes Muskelfleisch Rind, Lunge Rind, Sojaproteinkonzentrat) und zwei unterschiedlichen Proteingehalten (20 % bzw. 60 % der Energie aus Protein) im Futters auf die Ausscheidung von freiem Stickstoff, Protein, Harnstoff, Kreatinin, Ammoniak und freien Aminosäuren über den Harn, sowie auf den Bruttoenergiegehalt des Urins untersucht. Während sieben Tagen wurden von sechs adulten Katzen der Futterverzehr gemessen und Kot- und Urinproben gesammelt. Aus den analysierten Daten wurden Stickstoffbilanzen und umsetzbare Energie berechnet. Für die Ausscheidung von Harnstoff, Ammoniak und freiem Stickstoff mit dem Urin konnte eine Abhängigkeit zur Proteinaufnahme nachgewiesen werden. Die Kreatininausscheidung über den Urin war, im Gegensatz zu bisher veröffentlichten Angaben, nicht von der Proteinaufnahme abhängig. Die Ausscheidung einzelner freier Aminosäuren über den Urin wurde nicht durch die aufgenommene Ration beeinflusst. Die N-Bilanzen ergaben keinen klaren Zusammenhang. Die Überprüfung der Formel von Hoffmann und Klein (1980), mit deren Hilfe der Energiegehalt des Urins aus dem Stickstoff- und dem Kohlenstoffgehalt des Urins bei Rindern, Schafen, Schweinen und auch Ratten berechnet werden kann, ergab keinen direkten Zusammenhang. Es scheint daher sinnvoll zu sein, Bestimmungen für Bilanzversuche weiterhin über den analytischen Weg vorzunehmen

Asymmetric Morita-Baylis-Hillmann reaction : catalyst development and mechanistic insights based on mass spectrometric back reaction screening

The aim of the research project described in chapter 2 of this thesis was to develop an efficient bifunctional phosphine catalyst that outperforms literature-known catalysts in the Morita-Baylis-Hillman reaction of methyl acrylate with aldehydes. For the evaluation of the chiral organocatalysts a mass spectrometric back reaction screening protocol of quasi-enantiomeric substrates was applied. Based on this technique, a multi-catalyst screening was developed which allowed the simultaneous determination of the intrinsic enantioselectivities of phosphines in a crude catalyst mixture. Finally, based on the data from the back reaction screening in hand together with kinetic measurements, the rate- and enantioselectivity-determining step in the catalytic cycle were identified. In chapter 3, the synthesis of new morpholine- and piperidine-based triazolium salts and their use as NHC catalysts for the asymmetric cross-benzoin reaction is discussed. In particular, the cross-benzoin reaction between benzaldehyde and hydrocinnamaldehyde was studied. The aim of this project was to design a catalyst that could produce the desired cross-benzoin product with high enantiomeric excess and chemoselectivity. Chapter 4 deals with the development of chiral NHC-phosphine ligands for the asymmetric iridium-catalyzed hydrogenation of different model substrates. This project was inspired by the previous work of Nanchen, a former member of the Pfaltz group. He synthesized a small library of different NHC-phosphine ligands for the hydrogenation of various substrates, however only moderate results in terms of reactivity and enantioselectivity were achieved. The aim of this project was to investigate NHC-based catalysts with conformationally more rigid structures

Glucocorticosteroid-induced spinal osteoporosis: scientific update on pathophysiology and treatment

Glucocorticosteroid-induced osteoporosis (GIOP) is the most frequent of all secondary types of osteoporosis. The understanding of the pathophysiology of glucocorticoid (GC) induced bone loss is of crucial importance for appropriate treatment and prevention of debilitating fractures that occur predominantly in the spine. GIOP results from depressed bone formation due to lower activity and higher death rate of osteoblasts on the one hand, and from increased bone resorption due to prolonged lifespan of osteoclasts on the other. In addition, calcium/phosphate metabolism may be disturbed through GC effects on gut, kidney, parathyroid glands and gonads. Therefore, therapeutic agents aim at restoring balanced bone cell activity by directly decreasing apoptosis rate of osteoblasts (e.g., cyclical parathyroid hormone) or by increasing apoptosis rate of osteoclasts (e.g., bisphosphonates). Other therapeutical efforts aim at maintaining/restoring calcium/phosphate homeostasis: improving intestinal calcium absorption (using calcium supplementation, vitamin D and derivates) and avoiding increased urinary calcium loss (using thiazides) prevent or counteract a secondary hyperparathyroidism. Bisphosphonates, particularly the aminobisphosphonates risedronate and alendronate, have been shown to protect patients on GCs from (further) bone loss and to reduce vertebral fracture risk. Calcitonin may be of interest in situations where bisphosphonates are contraindicated or not applicable and in cases where acute pain due to vertebral fracture has to be managed. The intermittent administration of 1-34-parathormone may be an appealing treatment alternative, based on its documented anabolic effects on bone resulting from the reduction of osteoblastic apoptosis. Calcium and vitamin D should be a systematic adjunctive measure to any drug treatment for GIOP. Based on currently available evidence, fluoride, androgens, estrogens (opposed or unopposed) cannot be recommended for the prevention and treatment of GIOP. However, substitution of gonadal hormones may be indicated if GC-induced hypogonadism is present and leads to clinical symptoms. Data using the SERM raloxifene to treat or prevent GIOP are lacking, as are data using the promising bone anabolic agent strontium ranelate. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatmen

Cemented Thompson versus cemented bipolar prostheses for femoral neck fractures

To compare early functional outcomes, complications, and mortality in elderly patients treated with the less costly, cemented Thompson prosthesis or the cemented bipolar prosthesis in order to identify factors affecting outcomes. Records of 303 patients with femoral neck fractures treated with the cemented Thompson monoblock prosthesis (n=206) or the cemented bipolar prosthesis (n=97) were reviewed. The choice of prosthesis was solely determined by surgeon's preference. Data relating to patient demographics, clinical and residential status, mobility, mental function, mortality, and complications during hospitalisation and rehabilitation were collected. After adjusting for confounding variables, independent postoperative indoor mobility was associated with preoperative indoor mobility (p=0.002) and mental function (p=0.001), whereas postoperative outdoor mobility was associated with preoperative outdoor mobility (p=0.003), daily living activity (p=0.02), and mental function (p=0.02). Mortality within 6 months was only associated with poor mental function (p=0.009). At 6-month follow-up, there was no significant difference between the 2 types of prosthesis in terms of functional outcomes, mortality and complication rates. In elderly patients with limited mobility, treatment with the bipolar prosthesis was not associated with better short-term outcomes than those receiving the Thompson prosthesis

Reasons to withhold intra-arterial thrombolysis in clinical practice

Background: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce. Methods: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center. Results: 76 patients (33.0%) presented within 3hours, 69 (30%) between 3 and 6hours of symptom onset and 85 (37%) later than 6hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6hours did not undergo arteriography and thrombolysis, mostly because of mild (n=44) or rapidly improving neurological deficits (n=13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n=7), limiting comorbidty (n=7) and baseline international normalized ratio>1.7 (n=1). Conclusions: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6hours time window and mild or rapidly improving symptom

PRACTISE Survey-PhaRmAcist-led CogniTIve Services in Europe: first results

Poster presented at the 10th PCNE Working Conference, 1-4 February 2017, Bled, SloveniaN/

PRACTISE - PhaRmAcist-led CogniTIve Services in Europe: preliminary results

Communication presented at the 2nd International Congress of CiiEM: Translational Research and Innovation in Human and Health Sciences. 11-13 June 2017, Campus Egas Moniz, Caparica, PortugalN/

Community pharmacist-led medication review procedures across Europe: characterization, implementation and remuneration

Background: Pharmaceutical Care Network Europe (PCNE) proposed a definition and classification system (type 1, 2a, 2b, 3) for medication review in 2016. However, to date, a description of the implementation and remuneration of such procedures across Europe is lacking. Objective: The aim of this study was to describe the medication review procedures and the level of implementation and remuneration in community pharmacies across Europe. Methods: An online survey was developed to characterize medication review procedures (PCNE classification), level of implementation (considering regional or national) and remuneration by a third party. This survey was sent to a purposive sample of three individuals per country, with a working background in community pharmacy, pharmacy practice research, or health policy to ensure reliable data. Data triangulation was used and consensus sought between the responses. Results: Data were received from 34 out of 44 targeted European countries (November 2016–October 2017) [response rate = 77%]. Overall, 55.9% of the countries provided at least one type of medication review as an implemented service or project. Type 1 medication review (based on the medication history) was provided in 13 countries, type 2a (medication history + patient interview) in 14, type 2b (medication history + clinical data) in two, and type 3 medication review (medication history + patient interview + clinical data) in four countries. Ten of the mentioned services or projects were remunerated by a third-party. Conclusion: Substantial heterogeneity was observed across Europe in various aspects, including the procedures, implementation level and remuneration obtained. Type 1 and 2a medication review services seem to be more feasible to implement in the community pharmacy than type 2b and 3. A large number of medication review projects were ongoing in community pharmacies, which suggests that new medication review services could become implemented in the coming years.info:eu-repo/semantics/publishedVersio

Post-translational insertion of boron in proteins to probe and modulate function

Boron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) in proteins. Precise anchoring of boron within complex biomolecular systems allows dative bond-mediated, site-dependent protein Lewis acid–base-pairing (LABP) by Bal. Dynamic protein-LABP creates tunable inter- and intramolecular ligand–host interactions, while reactive protein-LABP reveals reactively accessible sites through migratory boron-to-oxygen Cβ–Oγ covalent bond formation. These modes of dative bonding can also generate de novo function, such as control of thermo- and proteolytic stability in a target protein, or observation of transient structural features via chemical exchange. These results indicate that controlled insertion of boron facilitates stability modulation, structure determination, de novo binding activities and redox-responsive ‘mutation’

Post-translational insertion of boron in proteins to probe and modulate function

Boron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) in proteins. Precise anchoring of boron within complex biomolecular systems allows dative bond-mediated, site-dependent protein Lewis acid–base-pairing (LABP) by Bal. Dynamic protein-LABP creates tunable inter- and intramolecular ligand–host interactions, while reactive protein-LABP reveals reactively accessible sites through migratory boron-to-oxygen Cβ–Oγ covalent bond formation. These modes of dative bonding can also generate de novo function, such as control of thermo- and proteolytic stability in a target protein, or observation of transient structural features via chemical exchange. These results indicate that controlled insertion of boron facilitates stability modulation, structure determination, de novo binding activities and redox-responsive ‘mutation’