Changing pattern of primary hyperoxaluria in Switzerland

Background The clinical course of primary hyperoxaluria (PH) is greatly variable and diagnosis is often delayed. Little is known about the overall occurrence and current prognosis. Methods We evaluated all known patients with PH residing and observed in Switzerland during the last 15 years with the help of a survey among Swiss nephrologists. Results Of the 25 patients observed between 7/79 and 6/94 in Switzerland, 18 were alive in 1994—14 on conservative therapy and four on renal replacement therapy (RRT). Twenty-two patients had PH type 1; the exact type was not determined in three. The estimated prevalence of PH (type 1) is 2 per million population; the minimal incidence is 1 per 100000 live births. Diagnosis was delayed by 8 years (median) except in infants. Five patients were pyridoxine sensitive. According to life table analysis, 20% of patients were in end-stage renal failure (ESRF) and 10% had died by the age of 15 years, and 50% were in ESRF and 20% dead at 25 years. Prognosis has improved: Five of 13 patients died during the first half of the observation period as opposed to two of 20 in the second part. Conclusions Overall prognosis appears better than hitherto believed considering the large clinical spectrum of PH. Greater awareness of PH is needed to improve further long-term prognosi

Synthesis of bicyclo-DNA nucleosides with additional functionalization in the carbocyclic ring

Two novel bicyclo nucleoside isomers carrying the base thymine in the furanose ring and an ester substituent in the carbocyclic ring were synthesized from a common bicyclic sugar precursor via a cyclopropanation/fragmentation pathway in nine steps. The relative configuration of the ester substituent in both isomers as well as the anomeric configuration in one nucleoside was determined by 1H-NMR difference NOE spectroscopy

The chemical stability of abasic RNA compared to abasic DNA

We describe the synthesis of an abasic RNA phosphoramidite carrying a photocleavable 1-(2-nitrophenyl)ethyl (NPE) group at the anomeric center and a triisopropylsilyloxymethyl (TOM) group as 2′-O-protecting group together with the analogous DNA and the 2′-OMe RNA abasic building blocks. These units were incorporated into RNA-, 2′-OMe-RNA- and DNA for the purpose of studying their chemical stabilities towards backbone cleavage in a comparative way. Stability measurements were performed under basic conditions (0.1 M NaOH) and in the presence of aniline (pH 4.6) at 37°C. The kinetics and mechanisms of strand cleavage were followed by High pressure liquid chromotography and ESI-MS. Under basic conditions, strand cleavage at abasic RNA sites can occur via β,δ-elimination and 2′,3′-cyclophosphate formation. We found that β,δ-elimination was 154-fold slower compared to the same mechanism in abasic DNA. Overall strand cleavage of abasic RNA (including cyclophosphate formation) was still 16.8 times slower compared to abasic DNA. In the presence of aniline at pH 4.6, where only β,δ-elimination contributes to strand cleavage, a 15-fold reduced cleavage rate at the RNA abasic site was observed. Thus abasic RNA is significantly more stable than abasic DNA. The higher stability of abasic RNA is discussed in the context of its potential biological rol

Strong, specific, monodentate G-C base pair recognition by N7-inosine derivatives in the pyrimidine•purine-pyrimidine triple-helical binding motif

The nucleoside analogs 7-(2′-deoxy-α-D-ribofuranosyl)hypoxanthine (β7H, 1), 7-(2′-deoxy-β-D-ribofuranosyl)hypoxanthine (β7H, 2) and 7-(2′-O-methyl-β-Dribofuranosyl)hypoxanthine (β7HOMe, 3) were prepared and incorporated into triplex forming oligodeoxynucleotides, designed to bind to DNA in the parallel (pyrimidine•purine-pyrimidine) motif. By DNase I footprinting techniques and UV-melting curve analysis it was found that, at pH 7.0, the 15mer oligonucleotides d(TTTTTMeCTXTMeCTMeCTMeCT) (MeC = 5-methyldeoxycytidine, X = β7H, β7HOMe) bind to a DNA target duplex forming a H•G-C base triple with equal to slightly increased (10-fold) stability compared to a control oligodeoxynucleotide in which the hypoxanthine residue is replaced by MeC. Remarkably, triplehelix formation is specific to G-C base pairs and up to 40 µM third strand concentration, no stable triplex exhibiting H•A-T, H•T-A or H•C-G base arrangements could be found (target duplex concentration ∼0.1 nM). Multiply substituted sequences containing β7H residues either in an isolated [d(TTTTTβ7HTβ7HTβ7HTβ7HTβ7HT)] or in a contiguous [d(TTTβ7Hβ7Hβ7Hβ7HTTTTβ7HTTT)] manner still form triplexes with their targets of comparable stability as the control (MeC-containing) sequences at pH 7.0 and high salt or spermine containing buffers. General considerations lead to a structural model in which the recognition of the G-C base pair by hypoxanthine takes place via only one H-bond of the N-H of hypoxanthine to N7 of guanine. This model is supported by a molecular dynamics simulation. A general comparison of the triplex forming properties of oligonucleotides containing β7H with those containing MeC or N7-2′-deoxyguanosine (N7G) reveals that monodentate recognition in the former case can energetically compete with bidentate recognition in the latter two case

Knöchelosteotomie - Die Osteotomie als Zugang

Zusammenfassung: Bei der Behandlung osteochondraler Läsionen am oberen Sprunggelenk stehen sowohl arthroskopische als auch offene Therapieverfahren zur Verfügung. Die Osteotomien rund um das obere Sprunggelenk haben sich als Zugangserweiterung bei der Behandlung weiter posterior gelegener osteochondraler Läsionen fest etabliert. Bei den relativ häufig anzutreffenden osteochondralen Läsionen im Bereich der medialen Talusschulter wird die mediale, schräge, monoplanare Knöchelosteotomie durchgeführt. Bei den weniger häufigen posterolateralen osteochondralen Läsionen kann die distale Fibulaosteotomie erfolgen. In der vorliegenden Arbeit werden die Indikationen für einzelne Osteotomieverfahren diskutiert und deren chirurgische Techniken beschriebe

Position-dependent effects on stability in tricyclo-DNA modified oligonucleotide duplexes

A series of oligodeoxyribonucleotides and oligoribonucleotides containing single and multiple tricyclo(tc)-nucleosides in various arrangements were prepared and the thermal and thermodynamic transition profiles of duplexes with complementary DNA and RNA evaluated. Tc-residues aligned in a non-continuous fashion in an RNA strand significantly decrease affinity to complementary RNA and DNA, mostly as a consequence of a loss of pairing enthalpy ΔH. Arranging the tc-residues in a continuous fashion rescues Tm and leads to higher DNA and RNA affinity. Substitution of oligodeoxyribonucleotides in the same way causes much less differences in Tm when paired to complementary DNA and leads to substantial increases in Tm when paired to complementary RNA. CD-spectroscopic investigations in combination with molecular dynamics simulations of duplexes with single modifications show that tc-residues in the RNA backbone distinctly influence the conformation of the neighboring nucleotides forcing them into higher energy conformations, while tc-residues in the DNA backbone seem to have negligible influence on the nearest neighbor conformations. These results rationalize the observed affinity differences and are of relevance for the design of tc-DNA containing oligonucleotides for applications in antisense or RNAi therap

Synthesis, base pairing properties and trans-lesion synthesis by reverse transcriptases of oligoribonucleotides containing the oxidatively damaged base 5-hydroxycytidine

The synthesis of a caged RNA phosphoramidite building block containing the oxidatively damaged base 5-hydroxycytidine (5-HOrC) has been accomplished. To determine the effect of this highly mutagenic lesion on complementary base recognition and coding properties, this building block was incorporated into a 12-mer oligoribonucleotide for Tm and CD measurements and a 31-mer template strand for primer extension experiments with HIV-, AMV- and MMLV-reverse transcriptase (RT). In UV-melting experiments, we find an unusual biphasic transition with two distinct Tm's when 5-HOrC is paired against a DNA or RNA complement with the base guanine in opposing position. The higher Tm closely matches that of a C-G base pair while the lower is close to that of a C-A mismatch. In single nucleotide extension reactions, we find substantial misincorporation of dAMP and to a lesser extent dTMP, with dAMP almost equaling that of the parent dGMP in the case of HIV-RT. A working hypothesis for the biphasic melting transition does not invoke tautomeric variability of 5-HOrC but rather local structural perturbations of the base pair at low temperature induced by interactions of the 5-HO group with the phosphate backbone. The properties of this RNA damage is discussed in the context of its putative biological functio

Bedeutung und Entwicklung des Biologischen Landbaus in der Schweiz

Organic farming has rapidly grown in Switzerland in the past years. It is now well established in agriculture and accepted by consumers. However, recent developments show declining growth rates. This raises the question of the future that can be expected for organic farming in Switzerland. Future trends and potentials of organic farming in Switzerland made subject of two diploma theses in which prospects of the dairy and livestock sector and the fruit and vegetable sector were analysed. With a linear optimization model (farm level), taking into account probable future conditions, the development of supply was estimated. The future evolution of consumer demand was assessed by the means of a qualitative analysis. The analysis of supply and demand showed that there will be structural changes and that a future growth of the organic market is questionable. The problem does not mainly lie in the expected trend of consumer demand but rather in the development of the supply of organic products in Switzerland. In contrast to alternative production systems, organic farming is more labour-intensive, which results in higher per unit production costs. Due to the increasing abolishing of protective measures in the agricultural sector, product prices will continue to decrease. Therefore it is questionable if domestic demand for organic products can be fully met by local production.Agribusiness,

Produktionskosten-Faktoren im Deutschschweizer Weinbau

Die Produktionskosten im Weinbau werden jährlich von der AGRIDEA in einer Broschüre veröffentlicht (s. SZOW 6/07). Sie werden getrennt nach Mechanisierung und Erziehungssystem berechnet, wobei zum Teil grosse Unterschiede auch innerhalb der Kategorien feststellbar sind. Im Rahmen einer Diplomarbeit an der Hochschule Wädenswil (HSW) wurde in Zusammenarbeit mit AGRIDEA untersucht, welche Faktoren diese Streuungen bewirken. Dazu wurden 17 Betriebe der Kategorie «Mittlerer Drahtbau mit Traktoreinsatz» in der Deutschschweiz durchleuchtet