Synthesis of cyclic tryptathionine peptides

The helicity of the tryptathionine moiety of the phallotoxins has been recognized by comparison with cyclic tryptathionine tripeptides. In order to investigate the influence of the configuration of the component amino acids on the conformation of the cyclic peptides, six analogue thioether tripeptides containing L- and D-alanine and L- and D-cysteine, respectively, have been synthesized. The CD spectra of the peptides are very similar to each other, showing mirror images of the CD of phalloidin and, therefore, negative helicity. The spectra of the D-cysteine containing compounds differ from the L-cysteine containing compounds by their weakly positive ellipticity values around 270 nm. The cyclization reaction of Boc-Hpi-D-Ala-D-Cys(STrt)OCH₃, along with the cyclic tripeptide, afforded a cyclic hexapeptide by dimerization. The CD spectrum of the dimer is very similar to that of phalloidin, thus pointing to a positive helicity of its two tryptathionine moieties. The dimeric thioether peptide forms a rather strong complex with Cu²⁺ ions.     

The ESPAD Study: implications for prevention

The European Schools Project on Alcohol and other Drugs (ESPAD) was concerned with the substance use, beliefs, attitudes and risk factors among over 50,000 16-year-olds in 26 European countries. Based on this data, the present paper focuses on critical issues in prevention and uses a country-level analysis with focus on the extent that contextual and cultural factors interact with factors influencing the use of alcohol and other drugs. The results indicate that: (i) an emphasis on risks and dangers may be a poor prevention strategy since many young people do not believe the widely accepted dangers of certain forms of substance use (e.g. cigarette smoking); (ii) misperception of norms in relation to substance use, that is, the belief that use of alcohol and other drugs is more common than it actually is, emerged in most countries with the exception of Nordic countries; (iii) the correlation between perceived access to substances and actual use depended on the substance involved; correlations were strongest for cannabis but low for alcohol; (iv) the measure of problem behaviour was used in the ESPAD study (truancy from school), is correlated with substance use in a way that is opposite to that predicted in problem behaviour theory; and (v) there were no indications that the potential restraining factors that were examined in this study (involvement in athletics and leisure) acted in a way that prevented people from experimenting with drugs. The results of this analysis suggests that far from our having identified a core set of universal influences that act to determine substance use, the importance of cultural and contextual factors have been underestimated as has the importance of the specific substance involved.     

Interindividual variability in biliary excretion of ceftriaxone: effects on biliary lipid metabolism and on intestinal microflora

Ceftriaxone is a broad spectrum parenteral cephalosporin that is eliminated through renal as well as biliary excretion. In order to characterize factors influencing the biliary excretion of ceftriaxone, and possible effects of this organic anion on biliary lipid transport, we studied six healthy volunteers before and during ceftriaxone infusion. The biliary secretion rates of cholesterol, bile acids, phospholipids and ceftriaxone were determined using a duodenal perfusion technique, and the biliary lipid composition and cholesterol saturation of stimulated hepatic bile were determined. Changes in the intestinal microflora induced by ceftriaxone treatment were also analysed. There was a three-fold interindividual variation in biliary excretion of ceftriaxone, and this was correlated with the secretion rate of bile acids (rs = 0.83, P = 0.05). During ceftriaxone infusion, the secretion rate of cholesterol was reduced by 32% (P less than 0.05), which resulted in a reduction of cholesterol saturation of bile, from 107 +/- 11 to 75 +/- 12% (SEM, P less than 0.05). The suppression of intestinal Escherichia coli and Bacteroides, and the proliferation of enterococci and lactobacilli were related to the biliary excretion of ceftriaxone. We conclude (i) that biliary excretion of ceftriaxone is of major importance for its effects on intestinal microflora, (ii) that secretion of this organic anion into bile is largely dependent on bile acid secretion, and (iii) that ceftriaxone inhibits the biliary secretion of cholesterol.     

Plasma levels of somatostatin following a test meal in dogs Initial atropine resistant vagally mediated decrease of somatostain levels and increase of gastrin and insulin levels

Plasma levels of somatostatin like immunoreactivity (SLI), below referred to as somatostatin levels, were measured in peripheral plasma of conscious dogs. Basal somatostatin levels averaged 49±10 pM. Somatostatin as well as gastrin and insulin plasma levels were measured before and after feeding with and without prior atropinization. During the first 10 min after feeding somatostatin levels fell from 49±10 to 23±9 pM, whereas gastrin and insulin levels rose from 9±2 and 140±14 pM to 48±11 and 370±91 pM respectively. Atropine 0.01 or 0.1 mg/kg did not inhibit these responses. After the initial decrease, somatostatin levels rose again and peaked at around 60 min after feeding (110±24 pM). This secondary rise was completely abolished by atropine in both doses tried. Gastrin and insulin levels remained elevated throughout the experiments with and without atropine. It is suggested that gastrin release and HCI secretion are inhibited by a tonic outflow of gastric somatostatin during basal conditions. The process of feeding induces an atropine resistant, vagally mediated decrease in somatostatin release from the gastrointestinal tract and this decreased output of somatostatin facilitates initiation of meal-related endocrine and exocrine gastric secretions.     

Dilatation of pial arterial vessels in hypercapnia and in acute hypertension

Pial arterial vessels were inspected in hypercapnia (PaCO₂ 97±9 (S.E.) mmHg) and in acute hypertension induced by 5 μg kg^-1 noradrenaline i.v. (mean arterial pressure 210±5 mmHg) by means of a cranial window. The diameter of arterial vessels with a resting diameter of 10 to 150 μm was measured either from photographs or by aid of an image splitting eyepiece. Arterioles with a resting diameter ?30 μm exhibited the highest degree of dilatation both in hypercapnia and acute hypertension. The mean dilatation was higher in hypertension than in hypercapnia in vessels of all sizes, the difference being statistically significant in arterioles up to 50 μm resting diameter.     

Neurogenic modification of the vulnerability of the blood-brain barrier during acute hypertension in conscious rats

To study the possible influence of sympathetic adrenergic tone on the blood-brain barrier function during acute hypertension in conscious unrestrained rats with indwelling catheters in the aorta and a jugular vein the blood pressure was increased by noradrenaline, 6-hydroxydopamine (6-OHDA) or baclofen. One or 60 min later the rats were sacrificed and the extravasation of ¹²⁵I labelled albumin determined in the brain. After i. v. injection of noradrenaline the baroreceptor reflex will decrease the sympathetic tone whereas the blood pressure increase induced by the other two drugs is accompanied by an increased sympathetic activity. One minute after a corresponding rise in blood pressure the albumin content in the brain was considerably lower in rats given 6-OHDA than in those given noradrenaline. 60 min after the injection of 6-OHDA or baclofen the extravasation in the brain did not differ despite a considerably more rapid increase in pressure after 6-OHDA. Pretreatment with clonidine increased the blood-brain barrier dysfunction in rats given 6-OHDA but not in those given baclofen, probably because the slower rise in pressure facilitates myogenic autoregulation. It is concluded that neurogenic influences on vessel tone can modify the response of the blood-brain barrier during acute hypertension in conscious rats.     

Caregivers' job satisfaction and empowerment before and after an intervention focused on caregiver empowerment

engström m., wadensten b. & häggström e. (2010) Journal of Nursing Management   18, 14–23
Caregivers' job satisfaction and empowerment before and after an intervention focused on caregiver empowerment
Aims  To evaluate a training programme aimed at strengthening caregivers' self-esteem and empowering them, and also to study correlations between psychological empowerment and job satisfaction.
Background  Structural and psychological empowerment have received increased attention in nursing management, yet few intervention studies on this topic, based on theoretical assumptions, have been conducted in elderly care.
Method  Data on self-assessed psychological empowerment and job satisfaction were collected in an intervention ( n  = 14) and a comparison group ( n  = 32), before and after the intervention.
Results  When compared over time in the respective groups, there were significant improvements in the intervention group regarding the factor criticism (job satisfaction scale). There were no statistically significant differences in the comparison group. Total empowerment and all factors of empowerment correlated positively with total job satisfaction. Six out of eight factors of job satisfaction correlated positively with total empowerment.
Conclusions  Caregivers' perception of criticism can improve through an intervention aimed at strengthening their self-esteem and empowering them.
Implications for nursing management  Intervention focused on psychological empowerment and especially caregivers' communication skills seems to be beneficial for caregivers. Recommendations are to increase the programme's length and scope and to include all staff at the unit. However, these recommendations need to be studied further.     

Increase in local cerebral blood flow induced by circulating adrenaline: involvement of blood-brain barrier dysfunction

The influence of intravenous infusion of adrenaline (8 μg · kg^-1· min^-1) upon local cerebral blood flow (CBF) in paralyzed and artificially ventilated rats was measured autoradio-graphically with ¹⁴C-iodoantipyrine as the diffusible tracer. At this dose, adrenaline invariably increased local CBF even though blood pressure was close to normal at the time of the CBF measurement. In average, local CBF increased to 400% of control. In 6 of 9 animals the increase in flow was inhomogenous with randomingly distributed areas of very high flow rates. Experiments with i.v. administration of Evans blue prior to infusion of adrenaline showed that areas of Evans blue extravasation appeared in 3 of 4 animals. Although areas of extravasation often corresponded to areas of high flow rates the former were much more circumscribed. Furthermore, very high flow rates were found in areas showing no sign of blood-brain barrier dysfunction. It is concluded that the increase in CBF was at least partly due to a pressure-mediated passage of adrenaline across the blood-brain barrier but that such a passage can occur in the absence of macroscopically visible extravasation of protein.     

Alveolar bone development after decoronation of ankylosed teeth

Decoronation of ankylosed teeth in infraposition was introduced in 1984 by Malmgren and co‐workers ( 1 ). This method is used all over the world today. It has been clinically shown that the procedure preserves the alveolar width and rebuilds lost vertical bone of the alveolar ridge in growing individuals. The biological explanation is that the decoronated root serves as a matrix for new bone development during resorption of the root and that the lost vertical alveolar bone is rebuilt during eruption of adjacent teeth. First a new periosteum is formed over the decoronated root, allowing vertical alveolar growth. Then the interdental fibers that have been severed by the decoronation procedure are reorganized between adjacent teeth. The continued eruption of these teeth mediates marginal bone apposition via the dental‐periosteal fiber complex. The erupting teeth are linked with the periosteum covering the top of the alveolar socket and indirectly via the alveolar gingival fibers, which are inserted in the alveolar crest and in the lamina propria of the interdental papilla. Both structures can generate a traction force resulting in bone apposition on top of the alveolar crest. This theoretical biological explanation is based on known anatomical features, known eruption processes and clinical observations.