Effects of some analgesics and antidepressants on the (Na+ + K + )-adenosine triphosphatase from cortices of brain and kidney

The effects of benzomorphans, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors and chlorpromazine on the microsomal (Na+ + K+)-adenosine triphosphatase (ATPase) from beef cerebral cortex were studied. As a comparison, the interaction of these drugs with the corresponding enzyme from kidney cortex was also investigated. In addition to chlorpromazine, the benzomorphans and the tricyclic antidepressants inhibited the brain enzyme considerably, whereas the MAO inhibitors had little effect. The (Na+ + K+)-ATPase from kidney was not affected by the benzomorphans or MAO inhibitors, but its activity diminished in the presence of the tricyclic antidepressants and chlorpromazine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34064/1/0000342.pd

Hyperuricemia and hypertriglyceridemia: Metabolic basis for the association

Hypertriglyceridemia has been reported frequently in patients with hyperuricemia and gout. The current studies have evaluated this relationship. To examine whether hypertriglyceridemia leads to hyperuricemia, IV Intralipid was given to three gouty patients. Triglycerides increased from 169 to 700 mg/dl for three hours but caused no change in serum urate level or urine uric acid and oxypurine excretion. We next examined whether high carbohydrate intake increases serum urate and triglyceride levels. Four obese patients were placed on a 2000 kcal/d sucrose diet for seven days. The serum urate increased from 6.3 +/- 1.7 to 7.9 +/- 2.0 mg/dL. The percent uric acid clearance to creatinine clearance decreased from 5.9 +/- 1.3 to the lowest mean value of 3.7 +/- 1.2, while serum triglycerides increased from 106 +/- 33 to 252 +/- 57 mg/dL and blood lactate from 607 +/- 227 to 1167 +/- 381 [mu]mol/L. A 3000 kcal/d glucose diet in four other obese subjects produced no change in serum urate levels but increased lactate and triglyceride levels. During an isocaloric sucrose diet in two normal men, the serum urate level increased from 5.3 and 4.0 to peak values of 9.5 and 7.4 mg/dL. The percent uric acid to creatinine clearance decreased from 5.6 and 6.6 to 2.9 and 3.3. The uric acid turnover did not increase. In three gouty patients the mean serum urate increased from 8.5 +/- 1.5 to 10.6 +/- 1.4 mg/dL following an isocaloric sucrose diet. The urine uric acid excretion increased from 0.30 and 0.25 to 0.37 and 0.38 mg/mg creatinine in two patients. The percent uric acid clearance to creatinine clearance decreased from 3.8 to 2.5 in one patient. The serum triglycerides were substantially elevated during the sucrose diet in the normal subjects and the gouty patients. Our studies show that a pure sucrose diet increases both the serum urate and triglyceride levels. The mechanism of the hyperuricemia is decreased renal clearance of uric acid in the obese normal controls and the normal subjects. Increased urate production and decreased uric acid clearance accounted for the hyperuricemia in the gouty patients. The contribution of excessive sucrose ingestion to clinically associated hyperuricemia and hypertriglyceridemia remains to be elucidated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25613/1/0000161.pd

Elaborations, Revisions, Dissents: Alfred D. Chandler, Jr.’s., The Visible Hand after Twenty Years

Two decades have passed since the publication of 'The Visible Hand,' Alfred D. Chandler, Jr.'s, magisterial account of the rise of the modern business enterprise in the United States. Although Chandler's pathbreaking work has been widely hailed as a landmark in business history, only rarely has anyone considered systematically its influence on the large body of historical scholarship on related topics. This essay is intended to help fill this gap. It is divided into two sections. The first section reviews Chandler's argument, touches on the relationship of Chandler's oeuvre to his personal background, and locates 'The Visible Hand' in the context of American historical writing. The second considers how three groups of historians have responded to Chandler's ideas. These groups consist of champions who creatively elaborated on Chandler's intellectual agenda; critics who probed anomalies between Chandler's argument and their own research; and skeptics who rejected Chandler's analysis outright

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe