A microstructural model of cross-link interaction between collagen fibrils in the human cornea.

We propose a simplified micromechanical model of the fibrous reinforcement of the corneal tissue. We restrict our consideration to the structural function of the collagen fibrils located in the stroma and disregard the other all-important components of the cornea. The reinforcing structure is modelled with two sets of parallel fibrils, connected by transversal bonds within the single fibril family (inter-cross-link) and across the two families (intra-cross-link). The particular design chosen for this ideal structure relies on the fact that its ability to sustain loads is dependent on the degree of the cross-link and, therefore, on the density and stiffness of the bonds. We analyse the mechanical response of the system according to the type of interlacing and on the stiffness of fibres and bonds. Results show that the weakening of transversal bonds is associated with a marked increase of the deformability of the system. In particular, the deterioration of transversal bonds due to mechanical, chemical or enzymatic reasons can justify the loss of stiffness of the stromal tissue resulting in localized thinning and bulging typically observed in keratoconus corneas. This article is part of the theme issue 'Rivlin's legacy in continuum mechanics and applied mathematics'.

Computational modeling and stress analysis of columellar biomechanics.

The open approach for rhinoplasty offers excellent exposure of the various components of the nose in situ. The biggest advantage of the external approach is the complete anatomic exposure, which allows the surgeon to inspect the osteo-cartilagineous framework, while the biggest disadvantage is represented by the transcolumellar scar. The goal of this study is to numerically quantify the stress induced on the scar of a human columella by a constant load, through a fine tuned finite elasticity continuum model. Specifically we want to determine the best shape of incision which would minimize this stress. The columellar portion of the nose, together with the various constituting tissues, has been modeled in a first approximation as a hyperelastic body and seven types of scars have been studied. The determination of the best incision must be a compromise among different factors: shape and size primarily, but also position with respect to the internal structures and external loads. From this point of view, the best class of scar appears to be, both at simulated and real levels, the V-shaped one, inducing a maximum logarithmic von Mises stress in tissue of 4.67 Pa, and an absolute minimum stress distribution on the scar of 4.17 Pa. Numerical simulations appear to be in agreement with the evidence-based results coming from surgical practice, thus confirming the necessity to minimize local stresses on the tissue. A parameters' sensitivity analysis further highlighted our optimal choice. The proposed mathematical model can be applied both to theoretically designed and numerically verified new non-conventional scar geometries.

Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases?

BACKGROUND: In Caucasians, a small number of Type 1 diabetic patients do not show evidence of humoral islet autoimmunity at disease onset, at least with common screening procedures. In African- and Hispanic-American diabetic children at time of diagnosis, many show no evidence of autoimmunity but have an atypical clinical form of the disease. According to the recent American Diabetes Association classification, this subgroup of autoantibody negative patients is referred to as Type 1b diabetic subjects. In the present study, a homogeneous Caucasian Type 1 diabetic clinic-based cohort has been evaluated at diagnosis using a large panel of diabetes-related antibodies and then characterized for various genetic features in order to identify newly diagnosed Type 1 diabetics who are potentially autoantibody negative, i.e. possibly referrable to as idiopathic Type 1b diabetes. METHODS: Newly diagnosed Type 1 diabetic patients of Italian origin (n=141, mean age 12.0+/-7.6 years) were tested for anti-islet cell, anti-insulin, anti-65 kDa isoform of glutamic acid decarboxylase and anti-amino acid residues 256-979 of the tyrosine-phosphatase IA-2 molecule autoantibodies (Step 1). Only those patients found to be autoantibody negative were tested for anti-disialo-ganglioside GD3, anti-thyroid peroxidase, anti-thyroglobulin, anti-21-OH hydroxylase, anti-gastric parietal cell and anti-transglutaminase antibodies (Step 2). Sera negative for the presence of these six autoantibodies as well were characterized in terms of HLA DRB1, DQB1 and CTLA-4. RESULTS: Six out of 141 subjects (3.5%) were autoantibody negative in the first step of the study and five out of six in the second. These five autoantibody negative patients underwent genetic analysis. Three of them had at least one Type 1 diabetes-related high risk HLA haplotype (3/141, 2.1%) while the remaining two cases showed neutral (DR5-DQB1*0301/DR5-DQB1*0301) or strongly protective (DR2-DQB1*0602/DR2-DQB1*0602) HLA genotypes, respectively (2/141, 1. 4%). CONCLUSIONS: Clinically defined Type 1 diabetic patients with no sign of autoimmunity do exist in a Caucasian population. These patients (2 out of 141) that cannot be classified as Type 1a diabetic patients lack clinical characteristics of Type 1b diabetes and have to be reconsidered for a more appropriate ADA classification. These data suggest the need of further large population-based studies to understand if Type 1b diabetes really occurs in a Caucasian population. The patient with a strongly protective HLA genotype is particularly interesting considering that among Caucasians only a few sporadic cases with Type 1 diabetes and DQB1*0602, have been reported, none of whom was homozygous at DQB1 locus.

Alterations in Na+/K(+)-ATPase activity and fluidity of erythrocyte membranes from relatives of insulin dependent diabetic patients.

Several plasma membrane alterations have been described in diabetes mellitus. Data reported in gestational diabetes mellitus (GDM) suggested that these alterations might be present before the onset of overt metabolic derangement. On the basis of these data it is tempting to hypothesize that the reduction in the sodium pump activity might be due to a genetic factor acting at the membrane level before the onset of diabetes. In order to verify this hypothesis 11 insulin-dependent diabetic patients, 15 first degree relatives of the patients and 10 healthy subjects with a negative family history for diabetes mellitus were studied. Fluidity, Na+/K(+)-ATPase activity and membrane cholesterol content (C) were evaluated on plasma membranes obtained from red blood cells (RBCs). Na+/K(+)-ATPase activity was reduced with a contemporary increase in membrane fluidity in RBCs from IDDM patients in comparison to either relatives and controls. The same alterations were observed also in RBCs from the relatives in comparison to controls. We did not find any significant difference in the C content among the three groups. Data herein reported provide evidence that a reduction in the Na+/K(+)-ATPase activity is present in the plasma membrane of relatives of diabetic subjects. Furthermore, the present work suggests that the change in enzymatic activity might be related to modifications in membrane fluidity.

Influence of environmental iodine deficiency on neonatal thyroid screening results.

During a multicentric pilot screening program for congenital hypothyroidism a comparison between the results obtained from Urbino, an area characterized by low iodine supply and endemic goiter, and Rome, a non-endemic area, has been made. The evaluation of neonatal urinary iodine excretion in the two areas showed significantly lower iodine urinary excretion levels in Urbino than in Rome. A shift of TSH at screening toward higher values as well as a higher percentage of recall in Urbino area than in Rome was observed. This finding, which well correlates with a low environmental iodine supply, emphasizes the importance of screening for congenital hypothyroidism as a suitable index of the presence and action of goitrogenic factors in the environment.

Isolation and characterization of "Methanosphaera cuniculi" sp. nov.

A nonmotile, gram-positive, spherical organism was isolated from the intestinal tracts of rabbits. Both hydrogen and methanol were required for growth. No methane was produced from hydrogen-carbon dioxide, formate, acetate, methylamines, ethanol, or isopropanol. The optimum pH was 6.8, and the optimum temperature was 35 to 40 degrees C. The DNA G+C content is 23 mol%. The pseudomurein cell wall contained serine. These characteristics and the immunological fingerprinting results are consistent with its placement in the genus Methanosphaera as a new species.

[Relation between hypoxia and thyroid function]. / Rapporti tra ipossia e funzione tiroidea.

In view of the preponderant role of thyroid hormone in the regulation of oxygen consumption it is easy to understand the interest that has always been aroused by the study of the relationships between thyroid function and hypoxia. Thus far the results obtained have often been contrasting, demonstrating now an increase, now a reduction in thyroid function as evidenced by variations in the thyroid function parameters investigated (T3, T4, TSH, PBI), Thyroscintigraphy, captation curves, histological studies on thyroid tissue). Results obtained by various workers on the basis of physiopathology studies of altitude sickness (Bert, 1879; Mosso, 1909 and Barcroft, 1925) up to the more recent studies of Cramarossa, Donati and Bramati (1965), Moncloa (1966) and Galton (1972) are examined. The apparent discrepancy in results obtained is explained by the heterogeneity of experimental conditions ruling in the different investigations (difference of atmospheric pressure and PAO2, temperatures, diet, stress, duration of the experiment) and the diversity of the objects involved in the experiment (various animals, humans). It is concluded that research methods should be standardised more so as to achieve a more certain, definitive evaluation of the problem.

Polyamine levels in human semen of unfertile patients: effect of S-adenosylmethionine.

Polyamine content has been determined in the seminal plasma of unfertile men before and after S-adenosylmethionine treatment. Spermine and spermidine levels in azoospermic patients were found very low (80 and 24 microgram/ml) with respect to normospermic (1500 and 60 microgram/ml): S-adenosylmethionine treatment enhanced polyamine content (50-300%) in oligospermic patients. Furthermore, an increase of sperm count and motility has been observed in these patients.