Time-of-day-dependent adaptation of the HPA axis to predictable social defeat stress.

In modern societies, the risk of developing a whole array of affective and somatic disorders is associated with the prevalence of frequent psychosocial stress. Therefore, a better understanding of adaptive stress responses and their underlying molecular mechanisms is of high clinical interest. In response to an acute stressor, each organism can either show passive freezing or active fight-or-flight behaviour, with activation of sympathetic nervous system and the hypothalamus-pituitary-adrenal (HPA) axis providing the necessary energy for the latter by releasing catecholamines and glucocorticoids (GC). Recent data suggest that stress responses are also regulated by the endogenous circadian clock. In consequence, the timing of stress may critically affect adaptive responses to and/or pathological effects of repetitive stressor exposure. In this article, we characterize the impact of predictable social defeat stress during daytime versus nighttime on bodyweight development and HPA axis activity in mice. While 19 days of social daytime stress led to a transient reduction in bodyweight without altering HPA axis activity at the predicted time of stressor exposure, more detrimental effects were seen in anticipation of nighttime stress. Repeated nighttime stressor exposure led to alterations in food metabolization and reduced HPA axis activity with lower circulating adrenocorticotropic hormone (ACTH) and GC concentrations at the time of predicted stressor exposure. Our data reveal a circadian gating of stress adaptation to predictable social defeat stress at the level of the HPA axis with impact on metabolic homeostasis underpinning the importance of timing for the body's adaptability to repetitive stress.

Rapidly progressive necrotising fasciitis following a stonefish sting: a report of two cases.

Two patients developed rapidly progressive necrotising fasciitis after being stung by a stonefish. Both were given a hot-water bath for pain relief. The hot water may have accelerated bacterial growth and the consequent development of necrotising fasciitis. Vibrio vulnificus was cultured from one patient. It is recommended that patients should receive high dose of oral and intravenous antibiotic prophylaxis for vibrio prevention. Antibiotics should be given before or during, not after, a hot-water bath, and the patient's condition should be monitored closely.

A digit-serial architecture for gray-scale morphological filtering.

We present a digit-serial architecture for gray-scale morphological operations that operate on radix-2 redundant numbers. We present new implementations for a redundant number adder and a maximum unit that are used in the morphological dilation unit. These new designs have areas comparable to 2's complement implementations but have significantly smaller latencies.

[Improvement of the absorption of the active substance 2'-hydroxy-5'-methyllaurophenoxamine (FLM 5011) with prodrugs and preparations]. / Verbesserung der Absorption des Wirkstoffes 2'-Hydroxy-5'-methyllaurophenonoxim (FLM 5011) durch Herstellung von Prodrugs und Zubereitungen.

Methods to improve the absorption of problem drugs are presented for the strongly lipophilic, poorly water-soluble, potential lipoxygenase inhibitor FLM 5011 (1). The water-solubility is improved by using prodrugs or by solubilizing. The characterization of solubility has been characterized with an suitable in vitro model system. The bioavailability of 1 in rabbits after oral administration is markedly increased using 1-prodrugs studied. The good correlation between the ABC measured in vitro and the AUC estimated in vivo demonstrates that it is possible to predict the bioavailability at the rabbit of highly lipophilic drugs such as 1 using the flow through model system.

Use of an in vitro absorption model system for predicting sustained release of verapamil.

It is shown that it is possible to characterize sustained release formulations in vitro using not only dissolution data but also an absorption model system. The mean dissolution time (MDT) has been shown to be a suitable parameter for evaluating sustained release formulations in vitro. t1/2 and mean residence time (MRT) have been shown to be convenient pharmacokinetic parameters for characterizing sustained release formulations. For comparing in vitro and in vivo results the quotients MDT normal/MDT retard and MRT normal/MRT retard do seem to be useful.

[Triperidin (Norakin): separation, stability and structure of stereoisomers]. / Triperiden (Norakin): Trennung, Stabilität und Struktur der Stereoisomeren.

The antiparkinsonian triperiden (1; as hydrochloride Norakin) is a mixture of the stereoisomers 1a and 1b. Their identification and separation by chromatographic methods or fractional crystallisation of the tartrates is described. By means of IR- und 13C-NMR spectral data structures of 1a and 1b are proposed. Under proton catalysis 1b racemizes to 1a. In acidic solution (heating in 0.1 mol.1-1 HCl or storage in gastric juice at 37 degrees C) hydrolysis of 1 takes place and four isomeric products were observed (Z1-Z4), which arise by cleavage of the cyclopropyl moiety. The main product Z2 was identified as the 2"-hydroxy derivative. The solid drug is stable at least for 5 years.