The synthesis of the sodium salt of β-oxybutyric acid from the acetoacetic ester

Summary A method is described for preparing the sodium salt of -oxybutyric acid from acetoacetic ester. The acetoacetic ester is reduced by aluminium amalgam in moist sulphuric acid, and the -oxybutyric acid thus obtained is then saponified to form the sodium salt of -oxybutyric acid. The yield is approximately 30%.(Presented by Active Member AMN SSSR S. E. Severin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 51, No. 6, pp. 104–105, June, 1961     

Influence of water-soluble flavonoids,quercetin-5′-sulfonic acid sodium salt and morin-5′-sulfonic acid sodium salt,on antioxidant parameters in the subacute cadmium intoxication mouse model

Water-soluble quercetin-5′-sulfonic acid sodium salt (NaQSA) and morin-5′-sulfonic acid sodium salt (NaMSA) could exert an antagonistic effect on cadmium intoxication. The aim of the study was to examine the influence of these substances on superoxide dismutase (SOD) and glutathione (GSH) levels in the mouse liver in the subacute cadmium intoxication model. NaQSA and NaMSA significantly counteracted cadmium-induced decreases in SOD and GSH levels. No significant differences in SOD and GSH levels between groups exposed to cadmium receiving NaQSA or/and NaMSA were observed.     

Sustained upregulation of sodium taurocholate cotransporting polypeptide and bile salt export pump and downregulation of cholesterol 7α-hydroxylase in the liver of patients with end-stage primary biliary cirrhosis

To examine the mRNA expression of hepatobiliary transporters in primary biliary cirrhosis (PBC) patients and to compare bile acid absorption, synthesis, and efflux in patients with non-end-stage and end-stage PBC, we obtained liver samples from PBC patients by percutaneous needle biopsy. End-stage PBC was defined as follows: histological stage IV; cirrhosis; serum total bilirubin, ≥4.0 mg/dl; and Child-Pugh Class C. The mRNA expression levels of sodium taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and hepatic cholesterol 7α-hydroxylase (CYP7A1) were significantly higher in the PBC patients than in the controls (P < 0.01). The mRNA levels of NTCP and BSEP were significantly higher in the end-stage PBC patients than in the controls (P < 0.01). However, hepatic CYP7A1 mRNA expression decreased significantly (by 70%) in the patients with end-stage PBC as compared to the controls and the patients with non-end-stage PBC (P < 0.01). The hepatic expression of transporters mediating bile acid influx and efflux showed sustained elevation, whereas that of the rate-limiting enzyme for bile acid biosynthesis was attenuated in the end-stage PBC patients. Thus, mechanisms may be present preventing the accumulation of toxic bile acids in the hepatocytes of end-stage PBC patients.     

Inhibition of the fibrinolytic and fibrinogenolytic activity of plasminogen activators in vitro by the antidotes ϵ-aminocaproic acid,tranexamic acid and aprotinin

The effects of the potential antifibrinolytic antidotes EACA, AMCA and aprotinin on the pharmacological activity of SK, u-PAs, APSAC and t-PA (alteplase) were compared in vitro. Both the initiation of human plasma clot lysis and ongoing clot lysis in the presence of SK and APSAC were effectively inhibited by concentrations of EACA (1 mM) and aprotinin (50 KIU/ml) equivalent to those found at steady state conditions during the standard therapeutic regimens. The actions of tcu-PA and scu-PA were also inhibited, at least initially, although some fibrinolytic activity appeared on extended incubation with tcu-PA. EACA (1 mM) was only moderately inhibitory to t-PA, and aprotinin (50 KIU/ml) was not an effective antidote. Ongoing fibrinogenolysis was generally less readily inhibited than fibrinolysis. A higher concentration of EACA (12 mM, equivalent to the initial peak level achieved therapeutically) effectively inhibited fibrinolytic activity for all thrombolytic agents but the higher concentration of aprotinin (500 KIU/ml) failed to inhibit t-PA completely. Inhibition by AMCA, at concentrations equivalent to those used therapeutically, was similar to the maximum effect achieved by EACA.In conclusion, aprotinin and EACA/AMCA represent useful antidotes for those rare occasions when it is necessary to terminate the action of SK, APSAC and u-PA—even when plasma levels of thrombolytic agent are high, as after the standard administration of APSAC as a short injection. Concentrations of aprotinin and EACA/AMCA achievable by current dosage regimens are relatively less able to inhibit t-PA.     

Polymerization of Lactides and Lactones, 9. Synthesis and Characterization of Novel Random Copolyesters Containing 5-Phenyl-ε-caprolactone Units

3-Ph-CL and 5-Ph-CL can copolymerize with LA or CL initiated by Sn(Oct)₂ in bulk at 150°C. The copolymerization of 3-Ph-CL with LA and CL only produced oligomer. High molecular weight P(5-Ph-CL)-PLA and P(5-Ph-CL)-PCL were obtained by copolymerizing 5-Ph-CL with LA or CL. The copolymerization of 5-Ph-CL with CL, the content of P(5-Ph-CL) is in agreement with the feed ratio. However, in the case of 5-Ph-CL with LA, irrespectively of the monomer feed ratio, the content of P(5-Ph-CL) in the copolymer is less than that in the monomer feed. The 5-Ph-CL feed ratio has little influence on the molecular weight and the molecular weight distribution of P(5-Ph-CL)-PCL and P(5-Ph-CL)-PLA, but with the increase of 5-Ph-CL feed ratio, the yield of copolymer decreases. The DSC study of P(5-Ph-CL)-PLA and P(5-Ph-CL)-PCL indicated that the content of P(5-Ph-CL) affects the properties of the copolymer. When the content of P(5-Ph-CL) reaches 50%, both copolymers became rubber-like and non-crystalline.     

Direct-acting mutagenic activity in white, rosé, and red wines with the Ara test of Salmonella typhimurium.

Thirty-two commercially produced white, rosé, and red wines from Spain were assayed for genotoxicity. The Ara forward mutagenicity assay with Salmonella typhimurium served as the test system. All the wines were mutagenic in the absence of mammalian microsomal activation (S9 mix) and/or glycosidase activities with the exception of one rosé wine which gave a clear dose-response relationship, although its mutagenic potency was considered statistically nonsignificant. The mutagenic activity covered nearly a 30-fold range. Compared to white and rosé wines, red wines showed the highest levels of mutagenicity; this wine type included four "very potent" (greater than 3,000 AraR mutants/ml) mutagenic wines. The level of wine mutagenicity did not correlate with either the region or the year of production (vintage). Individual winery methods are suggested as primarily responsible for variations in mutagenic activity. The present study with the Ara test supports the possibility that wine components other than the flavonols quercetin and rutin are the major putative mutagens: (1) white wines, as well as rosé or red wines, were detected as being mutagenic; (2) in no case was activation required for the detection of mutagenicity; (3) mutagen(s) were detected mainly (red wine) when not exclusively (white and rosé wine) in the polar fraction from XAD-2 chromatography. The high sensitivity of the Ara test has allowed the screening of the mutagenicity of a variety of wines with no previous process of extraction or concentration. The comparison of the mutagenic activity of the entire complex mixture to that of its lyophilized residue has revealed a positive synergistic role for ethanol in the mutagenicity of certain wines. Finally, this work suggests that the Ara test is a useful tool for mutagenicity screening in wines. Thus, this test might play an important role in elucidating the genotoxic mechanism of action of alcoholic beverages, and for studying optional production methods to decrease the mutagenicity of commercial wines.     

Detection of melanoma metastases with the sentinel node biopsy: the legacy of Donald L. Morton,MD (1934–2014)

Dr. Donald L. Morton was clearly the pioneer of the sentinel node biopsy, which was a major advance in oncology that has improved the management of cancer patients worldwide. He conducted a series of practice-changing clinical trials to validate the important staging role of the sentinel lymph node biopsy for melanoma, and also spawned other studies that demonstrated its staging value in multiple other cancer types, most notably in breast cancer, gastric cancer, and colorectal cancer. His many contributions in this field have provided a unique opportunity to study host/tumor relationships, since the sentinel lymph node is the first location were the host immune defenses are confronted with metastasis arising from the primary cancer.     

Anionic phospholipids differentially regulate the epithelial sodium channel (ENaC) by interacting with α, β, and γ ENaC subunits

Anionic phospholipids (APs) present a variety of lipids in the cytoplasmic leaflet of the plasma membrane, including phosphatidylinositol (PI), PI-4-phosphate (PI(4)P), phosphatidylserine (PS), PI-4,5-bisphosphate (PI(4,5)P₂), PI-3,4,5-trisphosphate (PI(3,4,5)P₃), and phosphatidic acid (PA). We previously showed that PI(4,5)P₂ and PI(3,4,5)P₃ upregulate the renal epithelial sodium channel (ENaC). Further studies from others suggested that PI(4,5)P₂ and PI(3,4,5)P₃ respectively target β- and γ-ENaC subunit. To determine whether PI(4,5)P₂ and PI(3,4,5)P₃ selectively bind to β and γ subunit, we performed lipid-protein overlay experiments. Surprisingly, the results reveal that most APs, including PI(4)P, PS, PI(4,5)P₂, PI(3,4,5)P₃, and PA, but not PI, non-selectively bind to not only β and γ but also α subunit. To determine how these APs regulate ENaC, we performed inside-out patch-clamp experiments and found that PS, but not PI or PI(4)P, maintained ENaC activity, that PI(4,5)P₂ and PI(3,4,5)P₃ stimulated ENaC, and that PA, however, inhibited ENaC. These data together suggest that APs differentially regulate ENaC by physically interacting with α-, β-, and γ-ENaC. Further, the data from cell-attached patch-clamp and confocal microscopy experiments indicate that PA, a product of phospholipase D, may provide one of the pathways for inhibition of ENaC by endothelin receptors.