Progression of burn wound depth by systemical application of a vasoconstrictor: an experimental study with a new rabbit model

The final depth of a necrosis resulting from burn trauma is determined within 3 days. The zone of stasis has the potential for complete regeneration or there may be ischemic influences that lead to necrosis. In our model, we examined the dermal influence of vasoconstrictors with reference to the development of burn necrosis. On the backs of New Zealand white rabbits (4.0–4.5 kg) standardized lesions were made with a heated aluminum stamp at 80°C, 14 s in duration.

The lesions were intradermal, whereby the border zone of the coagulated tissue was found in the middle two quarters of the dermis in 100% of untreated animals after 72 h. For dermal vasoconstriction epinephrine in a dose of 0.5 μg/kg/min was used.

There were two groups of seven animals each. One group received epinephrine and the dosage was dependent on the clinical state of the animal. Several cycles were administered within a 3-day period. The reduction of skin perfusion was documented by Laser–Doppler-flowmetry. After 3 days, the skin with the lesions was excised and using a hematoxylin dye, a histological examination followed. The parameter used to determine the efficacy was the thickness of the uncoagulated part of the excised dermis.

Over a period of 48 h, an average of 2.3 epinephrine cycles of average of 88 min per animal in duration resulted in an average reduction of skin diffusion of 41%. The uncoagulated part of the dermis in the epinephrine group was 28.6% average; in the control group, this was 43.5%. The statistical analysis revealed significant differences with a p-value of 0.0312 (significant, when value is less than 0.05). The test results indicate that temporary reduction of skin perfusion through external administration of vasocontrictors may lead to progression of burn necrosis in our animal model.

Clinically, this result indicates that for patients with burn injuries and systemic inflammatory response syndrome who have insufficient volume therapy, the administration of vasocontrictors may produce similar results in the injured area.     

Development of a rubella virus DNA vaccine

Two rubella virus DNA vaccines were constructed from a cDNA clone of the rubella virus genomic RNA, one which contained the coding sequences for all three virion proteins (C, E2 and E1) and one which contained the two envelope glycoproteins (E2 and E1). When used to immunize mice via gene gun delivery, both constructs induced an antibody response of equivalent titer to that induced by rubella virus that persisted for at least seven months. A booster injection given four weeks after the initial injection increased antibody titers by over thirty-fold. The antibody response in DNA vaccine-injected mice was directed primarily against the E1 glycoprotein, as was the case in rubella virus-injected mice, and neutralizing activity was detected. These DNA vaccines are thus prototypes for a nonreplicating rubella virus vaccine that could be used in specialized circumstances.     

Zaleplon and triazolam in humans: acute behavioral effects and abuse potential

Zaleplon, a pyrazolopyrimidine that is under development as a hypnotic, produces its pharmacological effects at the benzodiazepine-recognition site on the GABA_A benzodiazepine-receptor complex. Unlike most benzodiazepines, zaleplon binds selectively to the BZ₁ (ω₁) subtype of the benzodiazepine receptor. The present study compared the acute subject-rated effects, performance-impairing effects, and abuse potential of zaleplon and triazolam, a triazolobenzodiazepine hypnotic, in 14 healthy volunteers with histories of drug abuse. Zaleplon (25, 50, and 75 mg), triazolam (0.25, 0.5, and 0.75 mg) and placebo were administered orally in this double-blind, crossover study. Zaleplon and triazolam produced comparable dose-related effects on several subject-rated drug-effect questionnaires. Zaleplon and triazolam also produced comparable dose-dependent decrements on several performance tasks including balance, circular lights, digit-enter and recall, DSST, picture recall/recognition and repeated acquisition. Same-day and next-day subject-rated measures reflecting abuse potential (e.g., drug liking, good effects, and monetary street value) also suggest that zaleplon and triazolam were comparable. The only notable between-drug difference observed in the present study was that the time-action function of zaleplon differed from that of triazolam. The onset time, time to maximum drug effect, and duration of action were shorter with zaleplon than triazolam. Thus, despite its non-benzodiazepine structure and unique benzodiazepine-receptor binding profile, the behavioral pharmacological profile of zaleplon is similar to that of triazolam. Received: 14 April 1998/Final version: 13 January 1999     

Communication practices in the social construction of health in an AIDS kesidence

Physical illness and well-being, while grounded in bodily and psychological experiences, are also constructed socially through communication practices. Significant symbols, rituals and myths, among other forms, converge to create shared meanings that help define the health/illness experience. This article first provides a conceptual framework for understanding how communication intertwines physical, psychological and collective worlds. This perspective is then contextualized by illustrating some communication practices within a residential facility for people with AIDS that help residents cope with the 'depression bind' created by the need to 'grieve efficiently' over the loss of fellow residents. In- depth interviews with residents uncover metaphors that describe this bind, the military and journey myths embedded in the language of 'fighting AIDS' and 'passing', and the remembering and 're membering' rituals of bereavement. These communication practices help residents grasp elusive meanings, discharge deep and contradictory feelings and manage the tensions of everyday life.     

Allergen tachyphylaxis of guinea pigs in vivo: A prostaglandin E mediated phenomenon?

Ovalbumin (OA) sensitized guinea pigs were repeatedly challenged with 1% OA in saline nebulized ultrasonically at the 0, 10, 20, 60 and 70th min. The intensity of bronchial obstruction was measured by body plethysmography. The first three challenges (0, 10, 20 min) caused strong asthmatic reactions in all animals, the last two (60, 70 min) only mild ones in 10 out of 15 animals. The development of this tachyphylaxis was markedly reduced by pretreatment of the animals with cyclooxygenase inhibitors (indomethacin 10 mg/kg intraperitoneally resp. acetylsalicylic acid 10 mg/kg orally 2h before test). The effect of both inhibitors (i.e. inhibition of tachyphylaxis) was abolished by supplementing prostaglandin E₂ as aerosol simultaneously to the allergen (100–200 ng per inhalation). The results suggest that allergen tachyphylaxis we have observed in vivo might be due to synthesis of cyclooxygenase products, e.g. prostaglandin E.Supported by Deutsche Forschungsgemeinschaft (grant Do 240) in part presented at the 17th workshop on pediatric research [Göttingen 1981, Eur. J. Pediatr. 135: 336 (1981)]     

Radon daughter plateout--II. Prediction model

By a linear programming procedure, we have optimized the Jacobi room model to fit our data on the partitioning of radon daughters between air and wall surfaces (plateout), obtained at high radon concentrations in a small chamber. Subsequently, the optimized model yielded estimates that compared well with plateout data obtained at lower concentrations in a room-sized chamber. (The experimental work is described separately.) The major change made in the Jacobi model was to reduce the deposition velocity of free airborne radon daughters from 1 to 0.05 cm/sec. This value was obtained by using a fast algorithm to solve the linear programming to arrive at the "best fit". Lesser changes were made in other parameters.     

Parametric in vivo imaging of benzodiazepine receptor distribution in human brain.

Emission computed tomographic methods for the in vivo quantification of radioligand-binding sites in human brain have previously been limited either by a lack of correction for possible effects of altered ligand transport or by highly complicated physiological models that preclude display of binding data in a detailed anatomical format. We investigated the application of a simplified compartmental model to the kinetic analysis of in vivo ligand binding to central benzodiazepine receptors. The human brain distribution of [11C]flumazenil, as determined by dynamic positron emission tomography, combined with metabolite-corrected arterial blood samples, permitted estimations of local cerebral ligand transport and of receptor binding. This approach allows calculation of transport and binding "maps" on a pixel-by-pixel basis, resulting in the display of binding data in a familiar tomographic format while maintaining much of the physiological accuracy inherent in more complex methods. The results obtained in a study of 6 normal volunteers revealed good interindividual precision, with coefficients of variation between 10 and 15% of mean regional values, suggesting the utility of this approach in future clinical studies of benzodiazepine receptor binding.     

Mechanism of the cardioprotective effect of triamterene in the rat heart. Myocardial protection via elevation of extracellular K+ and Mg++ concentrations

1. 2,4,7-Triamino-6-phenyl-pteridine (triamterene) protects the rat heart against isoproterenol-induced myocardial lesions: Whilst cardiotoxic doses of isoproterenol produce deleterious myocardial Ca overload, simultaneous admistration of triamterene diminishes myocardial Ca incorporation considerably. 2. As to the mechanism of action, triamterene increases the plasma contents of K and Mg by inhibiting renal excretion. Accordingly, oral administration of K and Mg salts, leading to a similar rise in the K and Mg concentrations of the plasma, also prevents abundant myocardial Ca incorporation. 3. Cardioprotection by triamterene can, in fact, be simply explained by its action on the plasma K and (particularly) Mg levels. This conclusion is drawn from a quantitative comparison of the inhibitory effects of triamterene (40 mg/kg s.c.) with those of KCl or MgCl2 (10 mMol/kg p.o.) on the isoproterenol-induced increase in myocardial 45Ca uptake and absolute Ca concentration. 4. Isoproterenol induced cardiomyopathy of the rat, an experimental model of non-coronarogenic myocardial lesions, has hitherto been successfully prevented with the use of Ca-antagonists (verapamil, D 600, prenylamine, fendiline). These compounds reduce Ca influx by restricting the Ca conductivity of the myocardial sarcolemma membrane ("slow channel"). The action of triamterene, on the other hand, is based on a totally different cardioprotective principle, namely competitive inhibition of intracellular myocardial Ca accumulation via an increase in K and Mg supply. In the future treatment of cardiomyopathy it seems rather promising to try a combination of both a Ca-antagonist and triamterene, thus applying two different therapeutic principles simultaneously.     

Mineralization and alkaline phosphatase activity in collagen lattices populated by human osteoblasts

Adult human osteoblastic cells were grown in a native type I collagen gel. Proliferation and viability analyses showed that cells rapidly stopped dividing and became blocked in the G0G1 phase (91% on day 13). Carboxyfluorescein diacetate cell staining and flow cytometry showed that osteoblasts were viable for the first 16 days and then viability decreased (58% viable cells on day 22). Osteoblasts were able to retract the matrix. Betaglycerophosphate (βGP) stimulated the deposition of mineral particles in the collagen network, and electron probe microanalysis showed that they were principally calcium and phosphorus, with a Ca/P ratio of about 1.7. Various times of βGP supply were tested. We compared 10 mM βGP added only once at day 0, or continuously from day 0, day 8, or day 21. Mineralization was observed in conditions where βGP was added at day 0. Furthermore, 10 mM βGP added once during gel preparation was sufficient to induce mineralization with mineral accumulation up to day 15 whereas the speed of the gel contraction decreased. In every condition, cultures expressed high alkaline phosphatase (ALP) levels as early as day 3, which decreased afterwards. These kinetics might explain why the other conditions did not prove favorable to the mineralization process. The model was used to study the influence of blocking gel retraction. Blocking retraction delayed the ALP activity decrease, but had no effect on mineralization. In conclusion, human adult osteoblasts cultured in native collagen gel stopped proliferation and underwent mineralization very early. This model should be used to investigate the influence of effectors on the early stages of culture. Received: 15 October 1997 / Accepted: 1 July 1999