Mycophenolic acid therapy after cyclophosphamide pulses in progressive IgA nephropathy

BACKGROUND: In progressive IgA nephropathy (IgAN), cyclophosphamide or steroids have been used to reduce the loss of renal function, but disease progression may occur after the end of treatment. The value of mycophenolic acid (MPA) maintenance therapy following initial immunosuppression in progressive IgAN is largely unknown. METHODS: In a prospective single-center trial, 20 patients with advanced IgAN (median glomerular filtration rate [GFR], 22 ml/min) and disease progression after cyclophosphamide pulse (CyP; n=18) or steroid pulse therapy (n=2) were treated with MPA for a median of 27 months. MPA dosages (initially mycophenolate mofetil 500 mg twice daily) were adjusted according to predose plasma concentrations (target concentrations 1.5 to 4 microg/mL). The course of renal function was assessed by linear regression of glomerular filtration rates. RESULTS: Median loss of renal function per month was significantly reduced from -0.8 ml/min to -0.03 ml/min per month after 6 months, to -0.05 ml/min per month after 12 months, and to -0.12 ml/min per month at the end of the study after median 27 months (p<0.05). An improved or stable GFR was observed in 16 of 20 patients during the first 12 months, and sustained in 10 patients during 24 months of follow-up. Proteinuria decreased significantly from 1.1 g/L to 0.4 g/L during MPA treatment (p=0.018). CONCLUSION: Our results indicate that MPA may be beneficial to slow down the loss of renal function in patients with progressive IgAN after previous immunosuppressive treatment.     

Fermenteigenschaften roter Blutzellen bei Lebererkrankungen

Zusammenfassung Es wurden die Aktivitäten der Enzyme Diphosphofructosealdolase, Trioseisomerase, Phosphoglyceraldehyddehydrogenase, Milchsäuredehydrogenase, Pyruvatkinase, 3-Phosphoglycerat-1-Kinase, Glucose-6-Phosphatdehydrogenase, Enolase und der beiden Hämiglobin-reduzierenden Fermentsysteme in gewaschenen Erythrocyten von 7 Patienten mit akuter Hepatitis, 7 Patienten mit Verschlußikterus, 25 Patienten mit Lebercirrhose und 10 Patienten im Coma hepaticum gemessen. Zusätzlich wurden das Erythrocyteneinzelvolumen, der Hämoglobingehalt je Erythrocyt und der Erythrocytendurchmesser bestimmt.Bei unseren Fällen von akuter Hepatitis und Verschlußikterus sind das EEV und der Erythrocytendurchmesser im Mittel vergrößert, während von den untersuchten Enzymen lediglich der Hämiglobinreduktasesystem-und der Milchsäuredehydrogenasegehalt erhöht sind.Bei Lebercirrhose sind der Gehalt und die Konzentration aller untersuchten Enzyme signifikant erhöht, während das EEV normal bleibt. In 44% der untersuchten Fälle war der Erythrocytendurchmesser vergrößert.Im Coma hepaticum kommt es zu einer weiteren Erhöhung des untersuchten Enzymgehaltes ohne Zunahme der Konzentration der Fermente (zusätzliche Quellung der Erythrocyten).Auf Grund dieser Befunde wird dargelegt, daß die Fermentveränderungen in den Erythrocyten Lebercirrhosekranker durch einen Angriff an der Erythrocytopoese im Knochenmark zustande kommen und nicht durch periphere Einflüsse erklärt werden können.     

Clinical and molecular genetics of the human GnRH receptor

A functional GnRH receptor (GnRH-R) in the anterior pituitary is critical for normal LH/FSH secretion, pubertal development and reproduction. Inactivating mutations of the GnRH-R have been identified in patients with idiopathic hypogonadotrophic hypogonadism. In this article we summarize phenotypic characteristics of these patients and focus on specific functional alterations of the human GnRH-R. In-vitro studies using recombinant receptor constructs demonstrate that GnRH-R missense mutations result in impaired ligand binding and reduced signal transduction, causing gonadotrophin deficiency. A detailed molecular understanding of receptor inactivation may help to design new GnRH agonists to therapeutically modulate GnRH-R function.     

Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function

Mutations in the V2 vasopressin receptor (AVPR2) are the most frequent genetic cause of the inherited nephrogenic diabetes insipidus (NDI). About 50% of all missense mutations found in extracellular loops of AVPR2 introduce additional cysteine residues, e.g. R181C, G185C, and Y205C. To explain the loss of receptor function two mechanistic models were suggested: First, the introduction of an additional extracellular Cys residue disrupts the conserved disulfide bond connecting the first and the second extracellular loop. And second, the mutationally introduced Cys residue forms a second disulfide bond with a free Cys residue within the second exoloop. Herein, we took advantage of a new NDI-causing mutation Y205H which affects a codon frequently found to be mutated to Cys in NDI patients. In contrast to Y205C the two mechanisms described above cannot account for the loss of receptor function of Y205H. In-depth functional characterization of mutant AVPR2 showed that also for Y205C the lack of a Tyr residue at position 205 is responsible for the abolished receptor function rather than the formation of a disastrous second disulfide bond. The concerted experimental and phylogenetic analysis emphasizes that Y205 is a key residue in maintaining the structure of AVPR2 and other members of the vasopressin receptor family.     

Zur Biochemie der Alterung menschlicher Erythrocyten

Ohne Zusammenfassung     

Effect of administered human interferon on experimental rabies in monkeys.

Cynomolgus monkeys infected with rabies virus were protected by repeated intramuscular administration of human leukocyte interferon beginning 24 h after infection.