The synthesis and characterization of magnesium and calcium complexes of sterically demanding aminopyridinato ligands is reported. The reaction of the 2-Me3SiNH-6-MeC5H3N (L 1 H), ...2-MePh2SiNH-6-MeC5H3N (L2 H), and 2-Me3SiNH-6-PhC5H3N (L 3 H) with KH in tetrahydrofuran (THF) yielded potassium salts L 1 K(thf)0.5 (1), L 2 K (2), and L 3 K(thf)0.5 (3), which, through subsequent reaction with MgI2 and CaI2, afforded the homoleptic complexes (L)2Ae(thf) n L = L 1 , Ae = Mg, n = 1 (4); L = L 2 , Ae = Mg, n = 0 (5); L = L 3 , Ae = Mg, n = 0 (6); L = L 2 , Ae = Ca, n = 2 (7) and heterobimetallic calciates {(L)3CaK}∞ L = L 1 (8); L = L 2 (9). The solid state structure of 8 reveals a polymeric arrangement in which the calciate units are interlocked by bridging potassium ions. Metalation reactions between L 1 H or L 2 H and ( n Bu)2Mg lead to the solvent-free compounds (L)2Mg L = L 1 (10); L = L 2 (5). The bridged butyl mixed-metal complex (L 1 )Li(μ2- n Bu)Mg(L 1 )∞ (11) was also obtained via a cocomplexation reaction with n BuLi and ( n Bu)2Mg. 11, which adopts a monodimensional polymeric array in the solid state, is a rare example of an alkyl-bridged Li/Mg complex and the first complex to feature an unsupported bridging butyl interaction between two metals. Changing the cocomplexation reaction conditions, the order of reagents added to the reactions mixture, and with the use of a coordinating solvent (tetrahydrofuran) formed the magnesiate complex (L 1 )3MgLi(thf) (12).
Abstract
Nationwide, wastewater-based monitoring was newly established in Scotland to track the levels of SARS-CoV-2 viral RNA shed into the sewage network, during the COVID-19 pandemic. We present a ...curated, reference dataset produced by this national programme, from May 2020 to February 2022. Viral levels were analysed by RT-qPCR assays of the N1 gene, on RNA extracted from wastewater sampled at 162 locations. Locations were sampled up to four times per week, typically once or twice per week, and in response to local needs. We report sampling site locations with geographical coordinates, the total population in the catchment for each site, and the information necessary for data normalisation, such as the incoming wastewater flow values and ammonia concentration, when these were available. The methodology for viral quantification and data analysis is briefly described, with links to detailed protocols online. These wastewater data are contributing to estimates of disease prevalence and the viral reproduction number (R) in Scotland and in the UK.
Alpha-1 antitrypsin deficiency (AATD) is an important, inherited cause of chronic liver disease. Marked variation in fibrosis stages in patients with homozygous deficiency and those factors that ...determine whether heterozygous carriers develop liver fibrosis, remain unexplained. Murine studies implicate polymerized alpha-1 antitrypsin (AAT) within hepatocytes as pathogenic.
The relationship between the quantity of polymerized AAT within hepatocytes (polymer load), stage of hepatic fibrosis and liver-related clinical outcomes (death, evolution to hepatocellular carcinoma, or need for liver transplantation) were investigated using liver tissue from 92 patients at first presentation with either homozygous or heterozygous AATD. Further tissue-based studies were undertaken to determine if polymerized AAT was associated with failure of cell cycle progression, accelerated aging or hepatocyte senescence by immunohistochemical analysis.
The AAT polymer load correlated closely with hepatic fibrosis stage and long-term clinical outcome, independent of homozygous or heterozygous status. AAT polymers within hepatocytes correlated closely with failure of cell cycle progression assessed using cell cycle phase markers, accelerated aging manifest as shortened telomeres and other markers consistent with hepatocyte senescence manifest as the presence of nuclear p21 expression and enlarged nuclei. The proportion of p21 positive hepatocytes or hepatocytes with enlarged nuclei correlated with hepatic fibrosis stage and the long-term clinical outcome.
These data suggest that accumulation of AAT polymers within hepatocytes drives senescence. Quantitation of both the AAT polymer load or hepatocyte senescence markers correlated with hepatic fibrosis stage and the long-term clinical outcome. Either or both could be considered markers of disease severity and treatment response in clinical trials.
It is unclear whether hepatitis C virus (HCV) has been eradicated or persists at a low level in HCV antibody–positive HCV RNA–negative individuals. The natural history and liver histology are not ...well characterized. One hundred seventy‐two HCV antibody–positive, serum HCV RNA–negative patients underwent diagnostic liver biopsy between 1992 and 2000 and were followed a median 7 years (range, 5–12). Patients with any possible cause of liver injury other than HCV were excluded. A single histopathologist scored sections using Ishak criteria. Characterization of the inflammatory infiltrate in selected cases used a novel semiquantitative technique and compared with HCV RNA–positive patients and healthy controls. One hundred two patients were excluded because of a risk factor for liver injury other than HCV. Seventy patients met the study criteria; four (5.7%) became HCV RNA–positive during follow‐up. Sixty‐six cases remained HCV RNA–negative; five (7.5%) had a normal liver biopsy; 54 (82%) had fibrosis (stage 2 or 3 in 16 (24%)). Nonviremic cases revealed expanded portal tracts (P < 0.05), with fewer CD4+ (P < 0.05) and more CD8+ cells (P < 0.05) than healthy controls, but were indistinguishable from HCV RNA–positive cases for these parameters. Lobular CD4 staining, absent in healthy controls, was noted in both HCV RNA–negative and –positive cases and was more marked in the latter (P < 0.05) with a sinusoidal lining cell distribution. Conclusion: Nonviremic HCV antibody–positive patients have a liver biopsy that is usually abnormal. Fibrosis was present in most with similar inflammatory infiltrate to viremic cases. The presence of a CD8+ rich inflammatory infiltrate suggests an ongoing immune response in the liver, supporting the view that HCV may persist in the liver in the majority of HCV RNA–negative cases. (HEPATOLOGY 2008;48;1737‐1745.)
Hypertension and hypercholesterolemia are recognized complications of liver transplantation, but whether they contribute to the development of cardiovascular disease is uncertain. We aimed first to ...determine the prevalence of risk factors for coronary heart disease (CHD) after liver transplantation and second to study the effect of liver transplantation on the predicted 10-year risk of developing CHD and the incidence of cardiovascular events in comparison with a matched local population.
Data on blood pressure, serum lipids, weight, diabetes mellitus, smoking, and incidence of myocardial infarction (MI) and stroke were obtained retrospectively from the case notes of 181 consecutive adult liver transplant recipients (median follow-up 54 months). The Framingham coronary risk equations were used to calculate the 10-year probability of developing CHD.
The prevalences of hypertension and hypercholesterolemia after transplantation were 77% and 62%, respectively. The predicted 10-year risk of CHD increased from 6.9% before transplantation to 11.5% at 1 year after transplantation, whereas that of a matched local population was 7%. Compared with a matched nontransplant population, the incidence ratios for MI and stroke were 0.55 (95% confidence interval, 0.01-3.06 ) and 1.45 (95% confidence interval, 0.18-5.22), respectively. No patients died from MI or stroke.
Liver transplant recipients have a high prevalence of risk factors for cardiovascular disease, exceeding that of the general population, and have a higher predicted risk of developing CHD. Despite this, there were no deaths from CHD or stroke during the study period.
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