Ketone bodies: from enemy to friend and guardian angel.

During starvation, fasting, or a diet containing little digestible carbohydrates, the circulating insulin levels are decreased. This promotes lipolysis, and the breakdown of fat becomes the major source of energy. The hepatic energy metabolism is regulated so that under these circumstances, ketone bodies are generated from ß-oxidation of fatty acids and secreted as ancillary fuel, in addition to gluconeogenesis. Increased plasma levels of ketone bodies thus indicate a dietary shortage of carbohydrates. Ketone bodies not only serve as fuel but also promote resistance to oxidative and inflammatory stress, and there is a decrease in anabolic insulin-dependent energy expenditure. It has been suggested that the beneficial non-metabolic actions of ketone bodies on organ functions are mediated by them acting as a ligand to specific cellular targets. We propose here a major role of a different pathway initiated by the induction of oxidative stress in the mitochondria during increased ketolysis. Oxidative stress induced by ketone body metabolism is beneficial in the long term because it initiates an adaptive (hormetic) response characterized by the activation of the master regulators of cell-protective mechanism, nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, and AMP-activated kinase. This results in resolving oxidative stress, by the upregulation of anti-oxidative and anti-inflammatory activities, improved mitochondrial function and growth, DNA repair, and autophagy. In the heart, the adaptive response to enhanced ketolysis improves resistance to damage after ischemic insults or to cardiotoxic actions of doxorubicin. Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors may also exert their cardioprotective action via increasing ketone body levels and ketolysis. We conclude that the increased synthesis and use of ketone bodies as ancillary fuel during periods of deficient food supply and low insulin levels causes oxidative stress in the mitochondria and that the latter initiates a protective (hormetic) response which allows cells to cope with increased oxidative stress and lower energy availability. KEYWORDS: Ketogenic diet, Ketone bodies, Beta hydroxybutyrate, Insulin, Obesity, Type 2 diabetes, Inflammation, Oxidative stress, Cardiovascular disease, SGLT2, Hormesis.

Handling of and preferences for available dry powder inhaler systems by patients with asthma and COPD.

The correct handling of dry powder inhalers (DPIs) is crucial for efficient therapy, and acceptance of the device can improve compliance. The handling of seven different dry powder inhalers was studied in 72 patients with asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to identify possible handling errors and investigate patient preferences. Patients inhaled twice with each inhaler; first after reading the device leaflet, and second after device handling was explained by the investigator. The investigator identified handling errors and critical handling errors, which might lead to insufficient or no dose delivery. Afterward, the patients selected their preferred device and judged different aspects of device handling. The lowest number of patients with critical handling errors was observed for the Diskus/Accuhaler, the highest numbers for the Jethaler and the Easyhaler (% of patients during first/second use): Diskus/Accuhaler 25%/13.9% (group A) and 38.9%/8.3% (group B); Clickhaler 50.0%/52.8%, Cyclohaler 58.3%/13.9%, Jethaler 66.7%/30.6% (group A) and Benosid N Inhaler 52.8%/22.2%, Novolizer 52.8%/25.0%, Easyhaler 72.2%/47.2% (group B). Device handling improved after instruction by the investigator. Device handling and preferences of patients closely correlated in this study. Both devices producing the lowest numbers of handling errors (Diskus/Accuhaler and Clickhaler) had the highest preference by the subjects (score from 1 = very good to 7 = very bad): Diskus/Accuhaler 2.21 (group A) and 2.02 (group B); Clickhaler 2.21, Cyclohaler 2.80, Jethaler 3.16 (group A); Novolizer 2.33, Easyhaler 2.37, Benosid N Inhaler 2.43 (group B). Critical handling errors may reduce therapy outcome due to a reduced dose delivery. In addition, reduced patients acceptance of a device, being dependent on device handling, may have a similar effect by reducing patients' compliance.

Kytococcus schroeteri sp. nov., a novel Gram-positive actinobacterium isolated from a human clinical source.

A strain of a gram-positive, coccoid, yellow-pigmented bacterium was isolated from human blood. The bacterium was aerobic, non-encapsulated and non-motile. Phenotypically, the bacterium closely resembled Kytococcus sedentarius, but could be distinguished from this species by physiological tests and chemotaxonomic investigations. The peptidoglycan type is L-Lys-Glu2, variation A4alpha. The predominant menaquinones are MK-8 and MK-7. The major cellular fatty acids are iso-C17:1, iso-C17:0, iso-C15:0 and anteiso-C17:0. The strain contains catalase and does not produce acid from carbohydrates. The ability to hydrolyse Tween 80 and the lack of alpha-glucosidase activity are the most characteristic features. The results of comparative 16S rDNA analysis revealed that the strain represents a novel species within the genus Kytococcus, for which the name Kytococcus schroeteri sp. nov. is proposed. The type strain is strain Muenster 2000T (= DSM 13884T = CCM 4918T).