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Biomedical subjects

A Santini

Publications and source records attributed to A Santini.

At least 109 records · Page 6Linked to original sources

[Current status in transplantation of the endocrine pancreas in the treatment of diabetes mellitus 2. Transplantation of fetal pancreas].

The latest findings support hypotheses that diabetes complications are secondary to metabolic control which current insulin therapy is unable to render constant. Surgical attempts to transplant the pancreas and Langerhans islets in the treatment of diabetes mellitus are reviewed and special attention paid to the use of the foetal pancreas which has proved particularly suitable in preventing microangiopathic complication. Comments are based on a careful review of the literature, made in the light of personal experience.

Animals↗

Conformational characterization of the 1-aminocyclobutane-1-carboxylic acid residue in model peptides.

A series of N- and C-protected, monodispersed homo-oligopeptides (to the dodecamer level) from the small-ring alicyclic C alpha, alpha-dialkylated glycine 1-aminocyclobutane-1-carboxylic acid (Ac4c) and two Ala/Ac4c tripeptides were synthesized by solution methods and fully characterized. The conformational preferences of all the model peptides were determined in deuterochloroform solution by FT-IR absorption and 1H-NMR. The molecular structures of the amino acid derivatives Z-Ac4c-OH and Z2-Ac4c-OH, the tripeptides Z-(Ac4c)3-OtBu, Z-Ac4c-(L-Ala)2-OMe and Z-L-Ala-Ac4c-L-Ala-OMe, and the tetrapeptide Z-(Ac4c)4-OtBu were determined in the crystal state by X-ray diffraction. The average geometry of the cyclobutyl moiety of the Ac4c residue was assessed and the tau(N-C alpha-C') bond angle was found to be significantly expanded from the regular tetrahedral value. The conformational data are strongly in favour of the conclusion that the Ac4c residue is an effective beta-turn and helix former. A comparison with the structural propensities of alpha-aminoisobutyric acid, the prototype of C alpha, alpha-dialkylated glycines, and the other extensively investigated members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc, with n = 3, 5-8) is made and the implications for the use of the Ac4c residue in conformationally constrained peptide analogues are briefly examined.

Amino Acids↗

Conformational analysis of the dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide and its analogues by NMR spectroscopy, computer simulations and X-ray diffraction studies.

A dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide was found to be about 2000 times more potent than sucrose. To investigate the molecular basis of its potent sweet taste, we carried out conformational analysis of this molecular and several related analogues by NMR spectroscopy, computer simulations and X-ray crystallographic studies. The results of the studies support our earlier model that an L-shape molecular array is essential for eliciting sweet taste. In addition, we have identified an aromatic group located between the stem and the base of the L-shape, which is responsible for enhancement of sweetness potency. In this study, we also assessed the optimal size of the essential hydrophobic group (X) and the effects of the chirality of the second residue toward taste.

Aminobutyrates↗

Sweet and bitter taste: structure and conformations of two aspartame dipeptide analogues.

The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.

Aspartame↗

Inversion of 3(10)-helix screw sense in a (D-alpha Me)Leu homo-tetrapeptide induced by a guest D-(alpha Me)Val residue.

The terminally blocked tetrapeptide pBrBz-[D-(alpha Me)Leu]2-D-(alpha Me)Val-D-(alpha Me)Leu-OfBu is folded in the crystal state in a left-handed 3(10)-helical structure stabilized by two consecutive 1<--4 C = O...H-N intramolecular H-bonds, as determined by X-ray diffraction analysis. A CD study strongly supports the view that this conformation is also that largely prevailing in MeOH solution. A comparison with the published conformation of pBrBz-[D-(alpha Me)Leu]4-OfBu indicates that incorporation of a single internal beta-branched (alpha Me)Val guest residue into the host homo-tetrapeptide from the gamma-branched (alpha Me)Leu residue is responsible for a dramatic structural perturbation, i.e. an inversion of the 3(10) screw sense from right to left-handed.

Amino Acid Sequence↗

Preferred conformation of peptides rich in Ac8c, a medium-ring alicyclic C (alpha,alpha)-disubstituted glycine.

A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C (alpha,alpha)-disubstituted glycine 1-aminocyclooctane-1-carboxylic acid (Ac8c), and two Ala/Ac8c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 1H-NMR. The molecular structures of the amino acid derivative Z-Ac8c-OH, the dipeptide pBrBz-(Ac8c)2-OH and the tripeptide pBrBz-(Ac8c)3-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Ac8c residue is an effective beta-turn and helix former. A comparison is also made with the conformational preferences of alpha-aminoisobutyric acid, the prototype of C (alpha,alpha)-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc with n = 3, 5-7) investigated so far. The implications for the use of the Ac8c residue in peptide conformational design are considered.

Amino Acids↗

Response of brain metastases from lung cancer to systemic chemotherapy with carboplatin and etoposide.

30 consecutive patients suffering from cerebral metastases from lung cancer [12 small cell lung cancer (SCLC), 18 non-small cell lung cancer (NSCLC)] were given systemic chemotherapy with carboplatin (300 mg/m2/day 1 every 4 weeks) associated with etoposide (120 mg/m2 days 1-3 every 4 weeks). 21 patient were untreated; 9 patients had had previous chemotherapy, 8 with platinum derivatives. Altogether 98 cycles of chemotherapy were administered. The results were as follows: 3 complete response (3 SCLC; 10%), 7 partial response (4 SCLC, 3 NSCLC; 23.3%), 5 stable disease (1 SCLC, 4 NSCLC; 16.7%), 15 progressive disease (4 SCLC, 11 NSCLC; 50%). The overall response was 33.3%. Of the 10 patients who responded to treatment, 4 had had previous chemotherapy with platinum derivatives. Treatment was generally well tolerated; 5 patients experienced grade 4 bone marrow toxicity; in 4 treatment was suspended because of progression, and 1 patient died after the 4th cycle due to pneumonia with bone marrow aplasia. Mean survival of patients responsive to treatment was 38.6 weeks (range 15-99); overall survival was 24.8 weeks (range 2-99), in SCLC 23 weeks (range 6-52) and in NSCLC 29.8 weeks (range 2-99). The combination of carboplatin and etoposide is highly successful in the treatment of cerebral metastases from lung cancer and it could be a valid alternative to the traditional radiotherapy.

Aged↗

[Protocol for health surveillance of workers exposed to repetitive arm movements].

BACKGROUND: Repetitive movements of the upper limbs at work can cause the onset of musculo-skeletal disorders and therefore an adequate planning of health surveillance is needed. A Work Group on this problem was constituted in Brescia, Italy, following the great interest raised by recent scientific meetings on this topic. OBJECTIVES: The aim of the Group was to prepare a proposal for a health surveillance protocol for the use of Occupational Health Physicians. RESULTS: Health surveillance for the prevention of upper limb disorders must be based on the degree of risk. The risk assessment procedure should be based on the methodology currently available for ergonomic analysis and should also consider the frequency of upper limb disorders in the exposed workers. In case of moderate risk, it is necessary to identify hyper-susceptible individuals, in order to reduce exposure to repetitive movements by means of an adequate task fitness evaluation and suitable health education programmes. In situations of medium-to-high risk, a specific programme of health surveillance must be planned in order to identify early disorders and prevent the onset of more severe damage using task fitness evaluation and rehabilitation therapies. The appropriate diagnostic procedure is indicated for this purpose and a classification is proposed to divide the upper limb disorders into two stages, according to the clinical picture: a first acute-subacute stage, which is potentially reversible, and a chronic-subchronic stage, which is non-reversible. Legal reports are required according to the stage of the disease identified and must be supported by an adequate risk assessment.

Arm↗

[Determination of colonic transit time in healthy subjects in Mexico City. Prospective study].

UNLABELLED: Colonic transit time (CTT) is determined by multiple factors; currently, normal values for the Mexican population are not available. In order to get an estimate one must look at the values reported in the international literature, but cultural, ethnical, nutritional and economic differences may lead to different values. OBJECTIVE: To determine the normal values of colonic transit time in healthy people in Mexico City by the use of radiopaque markers. PATIENTS AND METHODS: Prospective, longitudinal and observational study, which included healthy patients ranging from 18 to 60 years old; excluding pregnant women. The whole group of patients was given before breakfast a gelatin capsule which had 20 radiopaque markers inside -the markers were each 2mm long, and were made by the researcher-. After that, they were taken a simple abdominal X-ray film every 24 hours until they totally eliminated the markers. Their eating and defecation habits were evaluated and also the total amount of liquid they consumed. Inferential statistics were used; data was validated with both parametric and non-parametric tests, considering a significance of p < 0.05. RESULTS: A hundred patients were included in the sample in which 48% were female and 52% male, they were divided in three groups: group A (31%)from 18 to 25 years, group B (37%)from 26 to 40 and group C (32%)from 41 to 60 years; there were no important differences in their water consumption, which was in average of 1.87 lts. in 24 hours; also, there were no considerable differences regarding to their meat, vegetables and fruits' consumption, which was in average of 4.4 times a week; the whole group eliminated the markers according to X-rays which was in 54% after 72 hrs, 45% after 48 hrs and 1% after 24 hrs. We can observe an increase of the CTT related to age: in group C 94% eliminated the markers after 72 hrs and there was no significant difference (statistically) with regards to the other groups. A tendency of an increase of CTT with regards to age was observed: in group A, 80% eliminated the markers after 48 hrs, in group B 49% eliminated them after 48 hrs and 51% after 72 hrs and, in group C, 94% eliminated them after 72 hrs without any statistically significant differences among the study groups. CONCLUSION: The CTT in healthy patients is in a 100% of the cases studied lower or equal to 72 hrs with a tendency to increase in relation to age.

Adolescent↗

[Recent findings on pathology caused by Campylobacter and Yersinia. Preliminary results of an epidemiologic study on a pediatric population in Florence].

The authors, after a review of the literature concerning Campylobacter and Yersinia infections, report the preliminary results of an epidemiologic study carried out in florentine territory based on the stool-cultures of children with acute diarrhoea in the years 1984-85-86. From the dates results that in florentine territory too, Campylobacter isolation is second only to Salmonella isolation, as we can find in other searches++ of literature. Therefore the conclusion is that these two microorganisms, from "emergent" have become as interesting as to be investigated as routine practice.

Campylobacter Infections↗

[Hypohidrotic ectodermal dysplasia].

The authors report a case of Hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome). Diagnosed at the age of 2 months.

Ectodermal Dysplasia↗