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SYNOPSIS Out of 245 patients admitted to a two‐month single‐blind phase in a study with propranolol vs. placebo, 148 (72%) were propranolol responders. These responders were randomly assigned to propranolol or placebo for the following double‐blind phase. After four weeks, they opted to either (1) remain on the assigned drug for 6 to 12 months or (2) to switch to the other drug for 6 to 12 months. In either case, they then switched drugs for a final one or two months of the study. No tolerance was found in 80 patients who remained on propranolol for at least six months. Resurgence of migraine was analyzed in 75 patients who took propranolol for at least six months and crossed over to placebo. Thirty‐five patients (46%) continued to show the improvement achieved during propranolol therapy when it was discontinued and only 8 patients (11%) had rebound headaches. No serious complications were noted.

Addition of 50 micrograms/ml sodium ascorbate to confluent cultures of isolated rat calvarium bone cells resulted in a 21% increase in DNA production, a 50-60% increase in incorporation of [14C]proline into collagenous and noncollagenous proteins, and a 200% increase in alkaline phosphatase activity; under identical conditions, [35S]sulfate incorporation into proteoglycans (glycosaminoglycans) was not affected. These results suggest that ascorbate may be important in maintaining or stimulating the osteogenic phenotype of normal bone cells.

Twenty young male coffee-drinkers consumed 150 mg of caffeine in decaffeinated coffee three times a day for 8 days. On days 3, 4, 7, and 8, caffeine or a placebo was administered in the laboratory at 11 A.M., 8 A.M., 11 A.M., and 8 A.M., respectively, in a randomized double-blind crossover design. There was a blood pressure increase relative to the placebo 45 min after taking caffeine at 8 A.M. (5.8/6.5 mm Hg). An increase of 2.4/5.2 mm Hg was seen with the second cup of coffee at 11 A.M. The lower the subject's pre-coffee serum caffeine level, the higher the systolic response, both at 8 A.M. (r = -0.60) and at 11 A.M. (r = -0.62). Because of the pressor effect resulting from habitual caffeine intake, the adverse implications of caffeine use should be considered.

Perinatal rat calvarial bone cells were isolated by sequential collagenase digestion and grown in oxygen tensions ranging from 1 to 60% O2. Cell proliferation as determined by automated cell counting and DNA content was greatest in the lower oxygen tensions (less than or equal to 9% O2), whereas alkaline phosphatase activity and [35S]sulfate and [14C]proline incorporation were greatest in the higher oxygen tensions (greater than or equal to 13% O2). It is concluded that lower oxygen concentrations favor bone cell proliferation, whereas higher oxygen concentrations favor macromolecular synthesis. These findings, when related to the known pO2 of the fracture callus, suggest the following sequence of events: first, at the time of fracture an ingrowth of osteoprogenitor cells, capillary buds, and primitive mesenchymal cells occurs in the fracture site, a region of low pO2; second, a great increase in cellular proliferation accompanied by an initiation of macromolecular synthesis follows; finally, as the pO2 levels begin to increase, cellular proliferation decelerates, accompanied by an increase in macromolecular synthesis.

Alcohol overconsumption disrupts the gut microbiota and intestinal barrier, which decreases the production of beneficial microbial metabolic byproducts and allows for translocation of pathogenic bacterial-derived byproducts into the portal-hepatic circulation. As ethanol is known to damage liver sinusoidal endothelial cells (LSEC), here we evaluated dietary supplementation with a previously studied synbiotic on gut microbial composition, and hepatocyte and LSEC integrity in mice exposed to ethanol. We tested a chronic-binge ethanol feeding mouse model in which C57BL/6 female mice were fed ethanol (5% vol/vol) for 10 days and provided a single ethanol gavage (5 g/kg body weight) on day 11, 6 h before euthanasia. An ethanol-treatment group also received oral supplementation daily with a synbiotic; and an ethanol-control group received saline. Control mice were pair-fed and isocalorically substituted maltose dextran for ethanol over the entire exposure period; they received a saline gavage daily. Ethanol exposure decreased gut microbial abundance and diversity. This was linked with diminished expression of adherens junction proteins in hepatocytes and dysregulated expression of receptors for advanced glycation end-products; and this coincided with reduced expression of endothelial barrier proteins. Synbiotic supplementation mitigated these effects. These results demonstrate synbiotic supplementation, as a means to modulate ethanol-induced gut dysbiosis, is effective in attenuating injury to hepatocyte and liver endothelial barrier integrity, highlighting a link between the gut microbiome and early stages of acute liver injury in ethanol-exposed mice.

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