No abstract

SummaryIn a double-blind crossover study the symptomatic and metabolic effects of propranolol, acebutolol, and atenolol were studied during insulin-induced hypoglycaemia in diabetics treated with diet or hypoglycaemic tablets. All the drugs prevented tachycardia, but did not affect the other symptoms of hypoglycaemia. Propranolol delayed the recovery of the blood glucose concentration and impaired the secondary rise in the concentrations of blood lactate and non-esterified fatty acids in diet-treated diabetics. Acebutolol potentiated the hypoglycaemic effect of insulin in tablet-treated diabetics (mean difference of blood glucose concentration 0 7 mmol/l (12 6 mg/100 ml)) and this difference was maintained during the recovery phase4 the blood lactate response was also impaired. Atenolol did not differ perceptibly from placebo in its effects on the metabolic responses to acute hypoglycaemia.The results may be explained by differences in the known pharmacological actions of these drugs. They support the hypothesis that beta-adrenoreceptor blocking drugs that are highly beta, specific and without membrane-stabilising activity should be safer than the non-selective drugs when used in diabetic patients at risk from hypoglycaemia.

1. Mean intracellular pH (pHj) and lactate have been measured simultaneously in the isolated perfused rat liver on two successive occasions separated by an interval of 20 min. In some experiments extra lactate was added to the perfusion medium immediately after the first measurement of pHj.2. There was a direct relationship between the change in pHj over this interval and the simultaneous change of lactate uptake.3. This finding is consistent with the hypothesis that lactate enters the liver cell at least partly in the ionized form and that its metabolism is accompanied by the effective production of hydroxyl ions.4. These observations are discussed in terms of a possible control mechanism for lactate uptake by the liver.

Background: Despite the widespread prescription of antibiotics for the treatment of chronic rhinosinusitis (CRS), their efficacy remains uncertain. Limited penetration of systemic antibiotics into the sinonasal mucosa has been reported previously by this group. This study aimed to investigate the short-term effects of antibiotics on the sinus and gut microbiota as well as any relationships these had with drug distribution.Methods: Thirty subjects undergoing functional endoscopic sinus surgery for CRS were randomized to one of three groups: (1) doxycycline (100 mg daily for 7 days); (2) roxithromycin (300 mg daily for 7 days); and (3) control (no antibiotics given). Sinonasal and stool samples collected before and after treatment were analyzed using 16S ribosomal RNA (rRNA) gene-targeted amplicon sequencing and Droplet Digital polymerase chain reaction (PCR) for bacterial community composition and the quantification of bacterial DNA, respectively.Results: There were no significant major bacterial community shifts or changes to bacterial diversity and load following the treatment period in all patient groups. Non-significant trend reductions were observed in gut microbial diversity with antibiotics. For the roxithromycin group, sinonasal bacterial diversity was negatively correlated with serum drug levels and reduced overall compared to controls (p < 0.05). The relative abundance of Staphylococcus ASV129 in sinonasal samples reduced with increasing mucus doxycycline levels (p = 0.01). Conclusion:Antibiotic prescription for CRS should be further investigated because of preliminary evidence of poor sinonasal drug penetration, unproven efficacy, and the potential impact of dysbiosis in the sinuses and off-target sites. Further studies should consider distinguishing the presence of DNA from viable and nonviable bacteria.