Plasma catecholamines in hepatic coma and liver cirrhosis: Role of octopamine

Summary Plasma levels of adrenaline, noradrenaline and octopamine were estimated by a radioenzymatic method in nine cirrhotic outpatients with encephalopathy and in ten patients with hepatic coma (coma grade III–IV). In the cirrhotic outpatients normal as well as elevated plasma levels of noradrenaline were found. Octopamine could not be detected in the plasma of these patients as well as of ten healthy volunteers. Elevated noradrenaline levels were present in all patients with hepatic coma. Plasma noradrenaline remained elevated or even further increased during the course of hepatic coma, whereas adrenaline was elevated less frequently. In eight of the ten patients with hepatic coma octopamine was again not detectable in plasma. Only in two patients high levels of octopamine up to 59.5 ng/ml could be found in addition to increased noradrenaline concentrations. The infusion of the branched chain amino acid L-valine had no influence on the plasma level of either noradrenaline or octopamine.The data indicate that the sympathetic nervous system is activated during the course of hepatic coma. An accumulation of octopamine is not a common finding in chronic liver disease and hepatic coma. Since in the two patients with elevated octopamine levels the rise in octopamine occured concomitantly with a rise in noradrenaline, a displacement of noradrenaline by the false neurotransmitter octopamine in the noradrenergic neuron of the peripheral sympathetic nervous system seems unlikely. The results indicate that the development of hypotension in the course of liver cirrhosis and hepatic coma cannot be related to a deficiency of noradrenaline.Deeply moved we have to inform the readers about the sudden death of our colleague and teacher Professor Dr. F. Wewalka     

Genetic determinants: is there an "atherosclerosis gene"?

It is now clear that atherosclerotic disease is a chronic inflammatory disease triggered by a sequence of events initiated at sites with turbulent flow under normal conditions such as in the coronary arteries or at bifurcations or where normal laminar flow is replaced by turbulent flow because of vessel pathologies. Normally, laminar flow is protected by generation of NO by endothelial NO synthase (eNOS), which becomes activated via stretch activated channels. When the flow turns turbulent, such protective NO generation ceases, leading to endothelial cell activation and lipid deposition into the extra-cellular space. There, lipoproteins and specifically phospholipids become oxidized by cells of the monocytic-macrophage lineage. Only when the LDL-cholesterol level is high enough lipid peroxidation products are generated in sufficient amounts to perpetuate the disease by generating a feed forward loop of endothelial cell activation leading to an inflammatory response. That inflammatory response might also be added by bacterial or viral infections such as Chlamydia pneumoniae or viruses. The disease then progresses to a chronic inflammatory state, whereby the immune system seems to contribute significantly and markers of chronic inflammation such as fibrinogen, leukocytes, PAI-1 and CRP are found increased.     

Identification of high risk patients with severe, but asymptomatic aortic stenosis

Whether asymptomatic patients with severe aortic stenosis benefit from surgery remains unclear. We report our data recently published in the New England Journal of Medicine on the natural history of this disease and predictors of outcome.     

An evaluation of the effects of culture medium osmolality and pH on metabolic cooperation between Chinese hamster V79 cells

The Chinese hamster V79 cell metabolic cooperation assay indirectlymeasures an inhibition of intercellular communication throughgap junctions and can detect many tumor promoters. The experimentsdescribed here were designed to determine whether culture mediumosmolality and pH affect the endpoint of this assay, since hypertonicsolutions and cytoplasmic acidification can uncouple gap junctionsin other systems. Hypertonic concentrations of sucrose and mannitolin medium did inhibit metabolic cooperation, but these soluteswere active over different ranges of osmolalities. In similarexperiments, sodium chloride, choline chloride and sodium glucuronatehad no effect on metabolic cooperation. Furthermore, data wereobtained indicating that osmotic effects are not likely to contributeto the inhibition of metabolic cooperation by sodium saccharin.It is concluded that hypertonic culture conditions do not necessarilycause an inhibition of metabolic cooperation, and the propertiesof an added solute are important in determining the effectsobserved. Additionally, it was found that buffering the culturemedium pH between 6.6 and 7.7, during the period when test substancesare normally present, had no effect on metabolic cooperation.     

Perceptions,professional responsibility and management experiences of patients with alcohol,tobacco and opioid use disorder by residents in general practice and teaching general practitioners

BackgroundSubstance use disorders (SUDs) are based on pathophysiological mechanisms common to all psychoactive substances. However, general practitioners (GPs) hold different views depending on the substance in question.ObjectivesTo determine whether the perceptions that teaching GPs and final-year residents in general practice have of patients with a SUD vary according to the substance involved and explore their professional responsibility and management experiences.MethodsA cross-sectional observational study was carried out by asking residents and teaching GPs from eight faculties of medicine about their perceptions, professional responsibility and management experience of patients with tobacco, alcohol and opioid use disorders, using an online questionnaire between June and September 2017.ResultsThe responses of 238 teaching GPs (mean age 50 years SD 3.5; 58% men) and 327 residents (mean age 28 years SD 9.9; 67% women) were analysed (response rates: 9 and 15% respectively). Tobacco smokers were considered to be more responsible for their acts than the other users. Teaching GPs and residents considered that it was their responsibility to discuss substance use. They did not feel able to manage alcohol and opioid use disorders. Tobacco cessation was mainly managed alone (78%). The results were quite similar among teaching GPs and residents.ConclusionThe majority of practitioners had no difficulty managing smoking cessation. During the management of alcohol and particularly opioid use disorders, practitioners did not feel competent. The gap between their perceived responsibility and competencies should be addressed by training and promoting collaborative care.     

Characterization of butyrate-dependent electroneutral Na-Cl absorption in the rat distal colon

Recent studies have established that mucosal butyrate stimulates electroneutral sodium-chloride (NaCl) absorption in the distal colon of the rat and a model in which Na-hydrogen (H) and Cl-butyrate exchanges are coupled has been proposed as the mechanism of butyrate-dependent electroneutral Na-Cl absorption. These studies were designed to examine butyrate-dependent electroneutral Na-Cl absorption in experimental conditions in which HCO₃-dependent electroneutral Na-Cl absorption is inhibited: in Na-depleted (aldosterone-treated) animals and in the presence of increased mucosal cyclic adenosine monophosphate (AMP). Butyrate-dependent electroneutral Na-Cl absorption was markedly reduced in Na-depleted rats. In contrast, the inhibition of both net Na and net Cl absorption by 5 mM serosal theophylline was significantly less in butyrate-containing, HCO₃-free Ringer solution than in butyrate-free-HCO₃-containing Ringer solution. These studies indicate that cyclic AMP does not inhibit butyrate-dependent electroneutral Na-Cl absorption and we propose that the mechanism of cyclic AMP inhibition of HCO₃-dependent electroneutral Na-Cl absorption may be a result of its inhibition of Cl-HCO₃, not Na-H exchange.