Alveolar Retention and Clearance of Insoluble Particles in Rats Simulated by a New Physiology-Oriented Compartmental Kinetics Model

Alveolar Retention and Clearance of Insoluble Particles in RatsSimulated by a New Physiology-Oriented Compartmental KineticsModel. STOBER, W., MORROW, P. E., AND MORAWIETZ, G. (1990).Fundam Appl. Toxtcol. 15,329–349. A physiology-orientedcompartmental kinetics model of alveolar retention of inhaledinsoluble paniculate matter in rat lungs was proposed in a recentpaper, (W. Stober, P. E. Morrow, and M. D. Hoover, 1989, Fundam.Appl. Toxicol. 13, 823–843), and the retention patternsobtained with the model for a hypothetical set of input dataappeared to simulate phenomena which were observed in inhalationstudies with Fischer 344 rats. The present paper representsthe results of applying the new model for simulations of theactual experimental retention data of five different inhalationstudies with Fischer 344 rats exposed to three different materials.The experimental data showed that model adjustments had to bemade in order to account for clearance effects that appearedto be influenced by the age of the animals. After these adjustmentswere made and an appropriate set of values for the model parametersdescribing the respective exposure conditions was used, themodel was constrained to represent the empirical data of allof the studies by one unique set of parameter values. Changesin particular values of this set were considered to be acceptableonly if they reflected changes of relevant properties of theinhaled paniculate matter. The final simulations did not completelycomply with this self-imposed criterion. However, the degreeof compliance and the simulation quality achieved with a minimumof parameter variations seem to be unprecedented in retentionmodeling. The results of the study encourage attempts for furtherrefining the present model     

The Bland-White-Garland syndrome. Clinical picture and anaesthesiological management

We report a five-month-old infant with an impaired left ventricular ejection fraction as a result of Bland-White-Garland-syndrome (BWGS). Total intravenous anaesthesia with fentanyl and midazolam was used as the anaesthetic technique. After aortic reimplantation of the left coronary artery weaning from cardiopulmonary bypass (CPB) was prolonged and was only successfully managed with high dose noradrenaline, dopamine and dobutamine. Persistent myocardial dysfunction led to prolonged intensive care treatment. Seven months after surgery, left ventricular function and clinical condition have improved significantly.     

The linear model: a statistical tool applied to psychophysical research in dental prosthetics

The construction of a linear model is described, and its function in analysing variations in the perception of comfortable mandibular occlusal positions is explained. In principle, the model combines analyses of variance and regression in a number of simple computer operations. Data from a clinical study were used to demonstrate the analytical capacity of a specific model, designed to estimate the effect of factors, which were supposed to influence the perception of comfortable mandibular positions.     

Prevention of erosive oesophagitis relapse with pantoprazole

AIM: To compare the safety and efficacy of pantoprazole and ranitidine in maintaining erosive oesophagitis healing. METHODS: Gastro-oesophageal reflux disease patients (349) with endoscopically documented healed erosive oesophagitis (grade 0 or 1) were randomly assigned to receive pantoprazole (10, 20 or 40 mg/q.d.s.) or ranitidine (150 mg/b.d.). Erosive oesophagitis status was assessed endoscopically at months 1, 3, 6 and 12 or when relapse symptoms appeared (relapse = reappearance of erosive oesophagitis grade 2 within 12 months). Symptom-free days were also assessed. RESULTS: Pantoprazole 20- and 40-mg were significantly more effective than ranitidine in maintaining healing regardless of initial erosive oesophagitis grade. Response was dose-related. After 12 months 78, 55, 46 and 21% of patients remained healed (40-, 20-, 10-mg pantoprazole and ranitidine). Pantoprazole 40-mg produced significantly more symptom-free days (83%) than ranitidine (58%). Heartburn-free days/nights were significantly higher with pantoprazole 40-mg (92 and 93%) than ranitidine (73 and 77%). The most frequent reason for discontinuation, unsatisfactory efficacy, occurred most often with ranitidine (P < 0.001). CONCLUSION: Once-daily pantoprazole therapy prevented relapse of healed erosive oesophagitis more effectively than ranitidine and with fewer heartburn days. Response to pantoprazole was dose-related. Pantoprazole 40-mg was the most effective regimen and consistent in maintaining erosive oesophagitis healing with a good safety and tolerability profile.     

Neuropeptide Y: identification of the binding site

Based on the hypothetical 3D structure of neuropeptide Y (NPY), NPY 1-4-Aca-25-36, a 17 amino acid analogue, has been synthesized replacing the sequence NPY 5-24 by ε-aminocaproic acid (Aca). This low-molecular weight deletion analogue showed nearly comparable receptor affinity to NPY. In order to elucidate the structural requirements for receptor recognition each amino acid of 1-4-Aca-25-36 was exchanged by its D-enantiomer, glycine and L-alanine. In addition distinct amino acids were replaced by closely related residues. Multiple peptide synthesis was applied using Fmoc-strategy and BOP activation. Binding assay was performed on rabbit kidney membrane preparations. The results of structure affinity studies suggest that the C-terminal tetrapeptide NPY 33-36 is essential for receptor recognition.     

Noise Reversion of a Dual Chamber Pacemaker without Noise

Three patients are reported whose DDD pacemakers reverted to the asynchronous mode in the absence of skeletal muscle or electromagnetic (EMI) interference. In all three cases, the basic cardiac rhythm was atrial fibrillation with fast ventricular response due to intrinsic AV conduction. Noise reversion was triggered by the patients' own ventricular activity at cycle lengths shorter than the ventricular refractory period of the pulse generator. In one patient, asynchronous AV sequential pacing during atrial fibrillation was noted shortly after resuscitation from ventricular fibrillation; however, the initiation of the malignant ventricular arrhythmia by the pacemaker remains unproven. The mechanism of noise reversion by rapid cardiac activity and possible solutions to the problem by adequate pacemaker design are discussed.     

α-Amylases from Thermoactinomyces vulgaris: characteristics,primary structure and structure prediction

Two amylolytic active protein fractions (named α-amylase 1 and α-amylase 2) were isolated from the bacterium Thermoactinomyces vulgaris strain 94-2A. α-Amylase 1 had a molecular mass of 51.6 kDa, whereas α-amylase 2 consists of two fragments which have molecular masses of 17.0 and 34.6 kDa, respectively. These two fragments are products from a proteolytic cleavage of a-amylase 1 at amino acid position 303 (tryptophan) by a serine protease (thermitase) which is also produced by T. vulgaris. The purified α-amylase 1 and 2 follow the Michaelis-Menten kinetics in the presence of starch as substrate with K_m values of 1.37 ± 0.07 and 1.29 ± 0.18 mg/mL, respectively. In effect they differ in their stability characteristics. The amino acid sequence of α-amylase from T. vulgaris derived from DNA sequence (1) was compared with those of other α-amylases. It reveals high homologies to α-amylases from other microorganisms (e.g. B. polymyxa, A. oryzae, S. occidentalis and S.fibuligera). A three-dimensional structure model for α-amylase 1 on the basis of the 3 Å X-ray structure of Taka-amylase was constructed.