β-Substituierte Enamine, 12. Mitt. N-Aryl-2-nitro- und N-Aryl-2-chlor-2-nitro-enamine

β-Substituted Enamines, XII. N-Aryl-2-nitro- and N-Aryl-2-chloro-2-nitroenamines 1-Chloro-1-nitroacetone ( 4 ), obtained from sulfuryl chloride and nitroacetone ( 2 ), is a stable compound. In the presence of alkali it forms 1-chloro-1-isonitrosoacetone ( 9 ). With diazomethane it reacts to give 1 -chloro-1-methoxyiminoacetone ( 8 ). By aniline 4 is cleaved with the formation of acetanilide and chloronitromethane. In the presence of titanium tetrachloride, however, condensation to 1-chloro-1-nitro-2-phenylaminopropene ( 3a ) is achieved. The condensation of nitroacetone ( 2 ) with primary aromatic amines via β-nitroenamines 1 and subsequent chlorination with N-chlorosuccinimide also leads to N-aryl-2-chloro-2-nitroenamines 3 .     

Effect of sodium acetate on expression of K99 pili by Escherichia coli

Sodium acetate suppressed K99 production in Escherichia coli strains cultured on a minimal medium, as determined by seroagglutination and enzyme-linked immunosorbent assay. The greatest suppression occurred when the medium contained both sodium acetate and glucose. Glucose alone did not suppress K99 production.     

Effects of tamoxifen on serotonin transporter and 5-hydroxytryptamine(2A) receptor binding sites and mRNA levels in the brain of ovariectomized rats with or without acute estradiol replacement

The microtubule-associated protein tau regulates the dynamic stability of the neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system. These isoforms differ in their ability to promote the assembly of microtubules as well as in their capacity to stabilize existing microtubule structures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau might critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The present study addresses the differential expression of the six isoforms of tau in the central nervous system of 12 mammalian species including Homo sapiens. The occurrence of each of the six tau isoforms was highly variable. However, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing paradigms, which can be matched with known phylogenetic concepts based on morphological and molecular genetical studies. Especially, the unique expression pattern of tau isoforms in the human central nervous system implicates a possible link to the particular vulnerability of humans to neurodegenerative disorders with tauopathy, namely Alzheimer's disease, frontotemporal dementia and Pick's disease.     

Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist

Herein we describe the chemical synthesis and pharmacological characterization of a novel, highly potent progesterone receptor (PR) antagonist, ZK 230211. The introduction of a 17alpha-pentafluorethyl side chain in the D-ring of the steroid skeleton allowed the combination of high antiprogestagenic activity with little or no other endocrinological effects. In contrast to many other antiprogestins, ZK 230211 did not convert to an agonist in the presence of protein kinase A (PKA) activators and showed high antiprogestagenic activity on both PR isoforms PR-A and PR-B. This high antiprogestagenic activity could also be demonstrated in several in vivo models. Furthermore, this compound displayed only marginal antiglucocorticoid effects. In tumor models ZK 230211 exhibited strong antiproliferative action. The pharmacological properties of ZK 230211 may prove useful in the treatment of endometriosis, leiomyomas, breast cancer, and in hormone replacement therapy.     

Randomized multicenter comparison of 2 IMZ and 4 TPS screw implants supporting bar-retained overdentures in 425 edentulous mandibles

PURPOSE: Two treatment concepts for implant-supported bar retention of mandibular overdentures-2 intramobile cylinder (IMZ) implants and a Dolder bar and 4 titanium plasma-sprayed (TPS) screw implants and an angulated bar-were compared in a randomized controlled clinical trial with respect to postprosthetic efficacy and safety. MATERIALS AND METHODS: Four hundred twenty-five patients with edentulous mandibles were enrolled; 212 were randomized to TPS implants (control group) and 213 to IMZ implants (test group). Endpoints were occurrences of postprosthetic integration deficiency (ID), functional deficiency (FD), and complications. The trial was sized to detect a 10% difference in 5-year ID-free postprosthetic system lifetime with a power of 80%. RESULTS: With 340 protocol-completed cases, the trial achieved its predetermined power. The 2 systems did not show statistically significant differences in occurrences of postprosthetic ID and FD; 5-year occurrence-free postprosthetic system lifetime probabilities were estimated as 42.5% with IMZ and 42.8% with TPS, for ID; and as 82.6% with IMZ and 87.2% with TPS, for FD. However, at 3 to 6 months after surgery, mean Periotest values were significantly higher (P = .0001 without adjustment) with IMZ implants (5.6, SD 4.2) than with TPS implants (0.8, SD 4.3). TPS implants showed a higher incidence of inflammation and recession, while IMZ implants had a higher incidence of implant fracture after functional loading. DISCUSSION: The system-wise approach overcomes potential bias with implant-wise analyses. A combination of radiographic and clinical criteria distinguishes between desirable integration and functional anchorage. The in situ survival rates at 5 years in this study (95% for IMZ, 92% for TPS) match rates reported in the literature. CONCLUSION: This study demonstrated equivalent efficacy of 2 IMZ cylinders and 4 TPS screws in implant-supported, bar-retained mandibular overdentures and indicated a higher rate of complications with the TPS screw implants.     

Effect of human platelet concentrate, serum and PDGF on RPE cell proliferation and wound healing in vitro

PURPOSE: Biological agents like human serum or autologous platelets have recently been employed as adjuvants for macular hole surgery. However, the role of these agents on the retinal cellular level remains unclear. In the present study, we investigated the effect of human platelets, serum and PDGF on RPE migration and proliferation in cell culture. METHODS: Human RPE were cultured in DMEM + 2% FCS and experiments performed at passages 2-4. Human platelet concentrate (PC) and serum (HS) were isolated from blood of patients previewed for macular hole surgery; human PDGF-BB was from Pepro Tech. PC and HS at protein concentrations ranging from 50-1000 micrograms/ml and PDGF at 1 and 10 ng/ml were added to 5000 cells/well in the proliferation assay and to a confluent RPE monolayer on which a central mechanical "wound" (5 mm diameter) was made. Incubation times ranged from 1 h to 5 days. Cell numbers at D 5 were indirectly determined by protein measurements. In the wound model, the cells inside the wound area were counted and results compared to the control cultures that received no supplements. RESULTS: Cell proliferation was significantly stimulated over controls by all concentrations of PC, HS and PDGF with any incubation time. Compared to PC and PDGF, HS revealed less proliferation after 1-6 h of incubation; there was no significant difference from PC with other incubation times. In the wound model, both PC and PDGF significantly increased the number of cells migrating into the denuded area after 1 h incubation with the culture medium; longer incubation times had no further effect compared to controls. CONCLUSION: The present study is the first to demonstrate that human platelet concentrate induces proliferation and migration of RPE cells in vitro. However, PDGF, a growth factor which is abundantly present in platelets, was found to be at least equally effective. We assume that the majority of the mitogenic effect of platelet concentrate is due to PDGF.     

Neurotrophic estrogens: essential profile and endpoints for drug discovery

Criteria for the early recognition of selective neurotrophic action are crucial for the discovery of estrogens for supplementation therapy. The comparative characterization of 'tool' compounds in different paradigms demonstrates that estrogen-mediated CNS effects are discernible before the manifestation of changes in primary target organs. Agonist activity at, and recruitment of the coactivator SRC-1 by, the estrogen receptor alpha accurately reflect peripheral, but not neurotrophic, efficacy. Interaction with, and SRC-1 recruitment at, the estrogen receptor beta appears to be an essential prerequisite for pronounced CNS effects. Monitoring of the hypothalamo-pituitary-adrenal axis activity and the differential organ-specific induction of estrogen-responsive proteins are helpful for early delineation of CNS efficacy. Behavioral and antioxidant efficacy are useful confirmatory readouts, with limited roles in lead selection. Finally, an algorithm for the identification of estrogens with a neurotrophic profile can be generated by assigning 'performance grades' in a multifarious test array.