Local release of histamine,prostaglandin F2α and thromboxane B2 into the tracheal lumen and its influence on airways reactivity

Summary The influence of tracheal lavage with ascaris extract (AE) on airway response to acetylcholine (ACH) and histamine (Hi) was investigated in a series of 24 dogs. AE administered to a restricted area of the trachea resulted in a release of various mediators such as Hi, prostaglandin F₂ (PGF₂, measured as the metabolite 15-keto-13, 14-dihydro-PGF₂) and thromboxane B₂ (TXB₂) into the tracheal lumen. This differed from H₂O administration which resulted in no increased release of these mediators. The relatively small concentrations of these substances measured in arterial plasma argue for the role of these mediators on a local basis. On the other hand, tracheal lavage with allergen induced changes in airway response to ACH and Hi aerosols which was not observed after tracheal lavage with water. An interaction between this allergen-induced mediator release into the trachea and peripheral airways reactivity could be demonstrated.     

Der Einflu\ von Β-Sympathomimetika und sog. Ca++-antagonistischer Hemmstoffe auf den menschlichen Herzmuskel in vitro

Zusammenfassung Es wird erstmals im überlebenden fetalen Herzmuskel in der Gewebekultur über elektive Parenchymnekrosen durch überstimulation mit -Sympathomimetika berichtet. Das zur Langzeittokolyse verwendete Fenoterolhydrobromid induziert über ein von Fleckenstein beschriebenes pathogenetisches Prinzip Nekrosen einzelner Herzmuskelfasern in vitro. Fenoterolhydrobromid in Kombination mit einem Ca⁺⁺-Antagonisten verhindert über eine Verringerung des Ca⁺⁺-Einstroms in die Herzmuskelfaser sog. elektive Parenchymnekrosen. Diese Untersuchungsergebnisse zeigen, da\ elektive Herzmuskelfasernekrosen nicht nur coronarogen, sondern auch metabolisch in Szene gehen können.Für die ausgezeichnete technische Durchführung der Versuche danken wir M. Frick, E. Hufnagel (Gewebekultur), A. Tischendorf, S. Weisschedel, A. Mayer (Histologie und Foto), U.L. Kiesewetter (Elektronenmikroskopie)     

Ungewöhnliche Markläsionen bei eitriger Meningitis

Zusammenfassung Bei einer 47jährigen Patientin mit eitriger Meningitis konnte durch intensive Antibiotica-Therapie, vor allem mit Penicillin, keine Besserung erreicht werden. Sie verstarb nach 5tägigem Krankenhausaufenthalt in tiefem Koma.Die Untersuchung des Gehirns ergab außer der eitrigen Meningitis ausgedehnte Markläsionen in beiden Großhirnhemisphären. Es wird diskutiert, ob diese ungewöhnliche schwere Markschädigung außer durch den primär entzündlichen Prozeß auch durch zusätzliche Faktoren verursacht sein könnte.

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Peculiar white matter lesions associated with purulent meningitis

Summary A case of a 47-year old female patient with a staphylococcus-meningitis and extensive white matter lesions is reported. The patient did not respond to intensive antibiotic therapy, mainly penicillin, and died in coma 5 days after admission to the hospital. Autopsy disclosed purulent meningitis associated with widespread necrotic lesions of the cerebral white matter. The neuropathological findings raise the question whether factors other than the purulent meningitis might have been responsible for the development of the white matter lesions.

     

The treatment of cardiac arrhythmias with sotalol

Summary Sotalol, at a fixed dose of 20 mg was given intravenously to 34 patients with cardiac arrhythmias of varying aetiology. It was effective in the treatment of supraventricular tachycardias, acute onset atrial and ventricular ectopics and acute onset atrial fibrillation. In chronic arrhythmias sinus rhythm was not restored, but in 77% there was slowing of the cardiac rate. Side effects were seen in only one patient who developed moderate bronchospasm.     

Reduced phospholipid breakdown in Alzheimer’s brains: a 31P spectroscopy study

Background Abnormalities of membrane phospholipid metabolism have been described in Alzheimers disease (AD). We investigated, with the aid of ³¹P magnetic resonance spectroscopy, the in vivo intracerebral availability of phosphomonoesters (PME) and phosphodiesters (PDE) in patients with AD.Methods Eighteen outpatients with mild or moderate probable AD and 16 nondemented elderly volunteers were assessed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and its cognitive subscale of the CAMDEX schedule (CAMCOG). Scans were performed on a 1.5 T magnetic resonance imager addressing a 40-cm³ voxel in the left prefrontal cortex. Main outcome measures were mean relative peak areas of PME and PDE, which provide an estimate of membrane phospholipid metabolism.Results PME resonance and the PME/PDE ratio were increased in AD patients as compared to controls (p<0.05). PME was negatively correlated with global cognitive performance as shown by the Mini-Mental State Examination (r_s=–0.36, p=0.05) and CAMCOG scores (r_s=–0.49, p=0.007), as well as with discrete neuropsychological functions, namely, memory (r_s=–0.53, p=0.004), visual perception (r_s=–0.54, p=0.003), orientation (r_s=–0.36, p=0.05), and abstract thinking (r_s=–0.48, p=0.01).Conclusions We provide evidence of reduced membrane phospholipid breakdown in the prefrontal cortex of mild and moderately demented AD patients. These abnormalities correlate with neuropsychological deficits that are characteristic of AD.     

Novel human α<Subscript>1a</Subscript>-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function

We identified nine naturally-occurring human single nucleotide polymorphisms (SNPs) in the _1a-adrenoceptor (_1aAR) coding region, seven of which result in amino acid change. Utilizing rat-1 fibroblasts stably expressing wild type _1aAR or each SNP at both high and low levels, we investigated the effect of these SNPs on receptor function. Compared with wild type, two SNPs (R166K, V311I) cause a decrease in binding affinity for agonists norepinephrine, epinephrine, and phenylephrine, and also shift the dose–response curve for norepinephrine stimulation of inositol phosphate (IP) production to the right (reduced potency) without altering maximal IP activity. In addition, SNP V311I and I200S display altered antagonist binding. Interestingly, a receptor with SNP G247R (located in the third intracellular loop) displays increased maximal receptor IP activity and stimulates cell growth. The increased receptor signaling for _1aAR G247R is not mediated by altered ligand binding or a deficiency in agonist-mediated desensitization, but appears to be related to enhanced receptor–G protein coupling. In conclusion, four naturally-occurring human _1aAR SNPs induce altered receptor pharmacology and/or biological activity. This finding has potentially important implications in many areas of medicine and can be used to guide _1aAR SNP choice for future clinical studies.     

Assessment of the environmental hazard from municipal and industrial wastewater treatment sludge by employing chemical and biological methods

Chemical analyses and toxicity testing were employed in conjunction to evaluate the environmental hazard from the wasted sludge generated during the biological treatment of urban and industrial wastewaters. Chemical analyses included determination of seven polychlorinated biphenyls (PCBs), 13 polycyclic aromatic hydrocarbons (PAHs), total organic carbon (TOC), and seven heavy metals (As, Cd, Cr, Cu, Pb, Mn, and Zn) in sludge and sludge leachates deriving from two standard leaching procedures: (a) the mild leaching test EN-12457-2 proposed by EC and (b) the relatively aggressive toxicity characteristic leaching procedure (TCLP) leaching test proposed by US EPA. Acute toxicity measurements were performed in aqueous sludge elutriates and leachates by using bioluminescence bacteria. The urban sludge was found to be more enriched with PAHs than the industrial sludge, however, at levels below the EU limits for sludge application. The total PCB content (Sigma7PCBs) in both sludges, particularly in the industrial sludge, exceeded the proposed European limit for sludge use as soil amendment. With regards to their heavy metal content, both sludges met the requirements for use in agriculture. The urban sludge exhibited high ecotoxicity, while the industrial sludge with almost two times lower toxicity was classified as not toxic to slightly toxic. The EN and the TCLP leaching procedures resulted in different sludge characterizations both from chemical and from ecotoxicological points of view. The EN procedure appeared to be more sensitive to the potential environmental risk from sludge disposal. The results of the study revealed the necessity for combining chemical with ecotoxicological criteria for integrated characterization of wasted sludge and the need for harmonization of the methods employed for waste classification.     

Effect of prolonged mechanical ventilation on diaphragm muscle mitochondria in piglets

BACKGROUND: Respiratory muscle weakness is a common problem in the intensive care unit and could be involved in difficulties in weaning from the ventilator after prolonged mechanical ventilation. Animal models have shown that mechanical ventilation itself impairs diaphragm muscle function. In this study we investigated whether diaphragm contractile impairment caused by mechanical ventilation and immobilization in piglets is associated with a derangement in diaphragm mitochondria. METHODS: Seven piglets received controlled mechanical ventilation during 5 days. A control group of eight piglets were anaesthetized and surgically manipulated in the same way, but were mechanically ventilated for 4-6 h. After mechanical ventilation, diaphragm muscle biopsies were taken for measurements of mitochondria content, mitochondrial respiratory enzymes and markers of oxidative stress. RESULTS: Diaphragm mitochondrial content, as assessed by citrate synthase activities and volume density, was not different between the control and ventilated piglets. Activity of complex IV of the mitochondrial respiratory chain decreased by 21% (P=0.02) when expressed per muscle weight and by 11% (P=0.03) when expressed per citrate synthase activity. There were no changes in the markers of oxidative stress between the two groups. CONCLUSION: Five days of mechanical ventilation and immobilization decreased the activity of complex IV of the mitochondrial respiratory chain in the diaphragm muscle of the piglets.     

Motivation to change in eating disorder patients: a conceptual clarification on the basis of self-determination theory

OBJECTIVE: The current study critically reviews the different motivational frameworks that are applied in the study of eating disorders and provides a more comprehensive conceptualization of motivation to change on the basis of self-determination theory. METHOD: The most important conceptualizations of motivation to change among eating disorder patients are identified. RESULTS: Eating disorder patients' motivation to change has been defined very differently, adding confusion to the field and preventing research from being cumulative. On the basis of self-determination theory we argue (a) that the quality of motivation to change is primarily reflected in the degree of internalization of change rather than by the intrinsic motivation to change; (b) that the internalization of change suggests more than only the change being initiated from within the person (internal motivation) for it requires an acceptance of the personal importance of change; and (c) that, in addition to its quality, the quantity of motivation to change should be considered too. DISCUSSION: These three conceptual issues are applied to the study of motivational dynamics in eating-disordered patients.