Gelatine was crosslinked by means of an enzymatic treatment using tissue transglutaminase (tTGase) (Sigma) and microbial transglutaminase (mTGase) (Ajinomoto) which catalyses the formation of isopeptide bonds between the gamma-carbonyl group of a glutamine residue and the epsilon-amino group of a lysine residue. The reaction is an interesting alternative to the traditional glutaraldehyde crosslinking, which has several drawbacks (e.g., in medical application) due to the toxicity of the chemical reagent. To further investigate the possibility to utilize the modified protein for tissue engineering application, TGase crosslinked gelatine was incorporated in a gellan matrix, a polysaccharide, to enhance the stability in aqueous media. Films obtained by casting were characterized by thermal analysis, chemical imaging, swelling behaviour and cell adhesion.
Endemic cretinism is still present in an endemic goiter area of the central Apennines (Montefeltro) (goiter prevalence 55%; mean urinary iodine level 39 micrograms/g creatinine). Clinical and biochemical features of patients with myxedematous, neurologic, and mixed cretinism were studied. Also, in this area, as in most other, neurologic cretinism is more prevalent than myxedematous and mixed forms. The hormonal profiles of the three types of cretinism were clearly different. Nevertheless, all myxedematous cretins had some neurologic disorders (hyperreflexia, increased muscle tone, disorder of gait, Babinski sign, hypoacusia) that were similar to those present in neurologic cretins. These findings suggest that neurologic damage is very similar in all forms of endemic cretinism, reflecting a diffuse insult to the developing fetal nervous system. Furthermore, these data support the hypothesis that the primary pathophysiologic event in the different types of endemic cretinism is represented by maternal and fetal hypothyroidism, while differences may be explained by the extent and duration of postnatal hypothyroidism. All the cretins were over 35 of age, suggesting a severe iodine deficiency in the past decades, and a progressive improvement of nutritional status resulted in "silent iodine prophylaxis." However, recent studies have revealed the persistence of a moderate iodine deficiency, a high prevalence of neurologic hypoacusia, and reduction of mental performance in normal schoolchildren of this area. These findings constitute strong evidence in favor of adequate iodine prophylaxis.
The preparation of an enzymatic controlled drug release system from blends of PVA/starch/alphaA, in the form of films, is described. It was shown that alphaA hydrolyses the starch within these films, resulting in a time-dependent change of the porosity in the matrix. Films were characterized by calorimetric analysis to study the interactions between the enzyme and the polymeric constituents at the molecular level. The presence of alphaA, in fact, influenced the PVA crystallization in the blends. Release tests and permeability experiments were carried out to evaluate the transport properties of the films. An increase in porosity and permeability was observed by increasing alphaA content (16-28 wt.-%). Films loaded with theophylline and caffeine were also prepared to analyze drug release properties of the matrix. Drug release kinetics were coherent with the measured changes in porosity: at higher alphaA concentrations the amount of released drug increased under the influence of diffusion and erosion processes. The results obtained are promising for the realization of drug delivery devices for a rapid release or for the release of poorly soluble drugs which usually remain entrapped in the matrix.SEM images of a PVA/starch/alphaA film before (A) and after (B) the erosion.
A biological–synthetic hybrid material was prepared as a support for proteinic molecules. To control the conformational stability and ‘vitality’ of the entrapped compound, an enzyme, which catalyses a chemical reaction, was chosen. The physical immobilisation of α‐amylase on a novel biological–synthetic hybrid material was realised using a synthetic (poly[ethylene‐co‐(vinyl alcohol)]) and a biological (dextran) component. The supports were obtained in the form of porous sponges using the phase inversion process. The kinetic parameters of enzymatic hydrolysis of soluble starch were obtained by determining the maltose (reaction product) concentration in the test solution by a spectrophotometric method. A high amount of enzyme (10 and 15 mg per g of polymer matrix) was successfully entrapped in the polymer support and a rather good enzyme activity of entrapped α‐amylase and a constant activity for repeated use, compared with native α‐amylase, were observed. The results obtained clearly indicated that the bioartificial polymer sponges, showing an immobilisation of α‐amylase with maintenance of the catalytic function of the enzyme, can be used as suitable supports for proteins. Copyright © 2005 Society of Chemical Industry
A 72-year-old woman was referred to our hospital for diarrhea, abdominal and back pain, weight loss, low serum potassium level. Pathological findings and high circulating Vasoactive Intestinal Peptide (VIP) levels allowed us to diagnose "VIPoma syndrome". The patient underwent a treatment with SMS 201-995 with improvement of symptomatology and reduction of circulating VIP levels. After a wash-out period the patient was treated with salmon calcitonin with a net improvement of diarrhea, normalization of potassium serum level and reduction of VIP level. The symptomatology recurred after calcitonin withdrawal. These data confirm the effectiveness of SMS 201-995 in the VIPoma syndrome and suggest that calcitonin may ameliorate symptomatology and reduce circulating VIP level in patients with VIPoma tumor.
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