Process analytical technology (PAT) approach to the formulation of thermosensitive protein-loaded pellets: Multi-point monitoring of temperature in a high-shear pelletization.

In the literature there are some publications about the effect of impeller and chopper speeds on product parameters. However, there is no information about the effect of temperature. Therefore our main aim was the investigation of elevated temperature and temperature distribution during pelletization in a high shear granulator according to process analytical technology. During our experimental work, pellets containing pepsin were formulated with a high-shear granulator. A specially designed chamber (Opulus Ltd.) was used for pelletization. This chamber contained four PyroButton-TH® sensors built in the wall and three PyroDiff® sensors 1, 2 and 3cm from the wall. The sensors were located in three different heights. The impeller and chopper speeds were set on the basis of 32factorial design. The temperature was measured continuously in 7 different points during pelletization and the results were compared with the temperature values measured by the thermal sensor of the high-shear granulator. The optimization parameters were enzyme activity, average size, breaking hardness, surface free energy and aspect ratio. One of the novelties was the application of the specially designed chamber (Opulus Ltd.) for monitoring the temperature continuously in 7 different points during high-shear granulation. The other novelty of this study was the evaluation of the effect of temperature on the properties of pellets containing protein during high-shear pelletization.

Videolaringoscopia e atividade de pepsina na saliva em voluntários com sintomas sugestivos de refluxo laringofaríngeo / Videolaringoscopy and pepsin activity in salive of volunteers with laryngopharyngeal reflux symptoms

O refluxo laringofaríngeo (RLF) é uma variação clínica da doença do refluxo gastroesofágico (DRGE), manifestando-se com queixas otorrinolaringológicas como rouquidão, pigarro, tosse, globus faríngeo, odinofagia, estridor lagingeo, e disfagia...

The laryngopharyngeal reflux is a clinical variation of the gastroesophageal disease, presenting with otolaryngologic complaints as: hoarseness, throat clearing, couhg, , globus pharingeus, odinopharia, laryngeal stridor and dysphagia...

[Exogenous allergic alveolitis in workers engaged in the manufacture of pepsin]. / Ekzogennyi allergicheskii al'veolit u rabochikh proizvodstva pepsina.

A case is reported of an affliction in a worker engaged in the production of enzyme powder-like drugs who in the course of his work over 30 years had been exposed to aerosols containing pepsin and hydrochloric acid. The lung X-ray disclosed pneumothorax, with the cardiovascular shadow and trachea displaced to the right. There were signs of myocardial hypoxia and pulmonary hypertension on the electrocardiogram. The described case suggests to us its occupational causation and permits classifying the form of affection of the bronchopulmonary system as an occupational health problem.

Engineering of porcine pepsin. Alteration of S1 substrate specificity of pepsin to those of fungal aspartic proteinases by site-directed mutagenesis.

The S1 substrate specificity of porcine pepsin has been altered to resemble that of fungal aspartic proteinase with preference for a basic amino acid residue in P1 by site directed mutagenesis. On the basis of primary and tertiary structures of aspartic proteinases, the active site-flap mutants of porcine pepsin were constructed, which involved the replacement of Thr-77 by Asp (T77D), the insertion of Ser between Gly-78 and Ser-79 (G78(S)S79), and the double mutation (T77D/G78(S)S79). The specificities of the mutants were determined using p-nitrophenylalanine-based substrates containing a Phe or Lys residue at the P1 position. The double mutant cleaved the Lys-Phe(4-NO2) bonds, while wild-type enzyme digested other bonds. In addition, the pH dependence of hydrolysis of Lys-containing substrates by the double mutant indicates that the interactions between Asp-77 of the mutant and P1 Lys contribute to the transition state stabilization. The double mutant was also able to activate bovine trypsinogen to trypsin by the selective cleavage of the Lys6-Ile7 bond of trypsinogen. Results of this study suggest that the structure of the active site flap contributes to the S1 substrate specificity for basic amino acid residues in aspartic proteinases.