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Biomedical subjects

S Mantero

Publications and source records attributed to S Mantero.

At least 19 recordsLinked to original sources
PubMed2003

Possible role of decorin glycosaminoglycans in fibril to fibril force transfer in relative mature tendons--a computational study from molecular to microstructural level.

Experimental studies on immature tendons have shown that the collagen fibril net is discontinuous. Manifold evidences, despite not being conclusive, indicate that mature tissue is discontinuous as well. According to composite theory, there is no requirement that the fibrils should extend from one end of the tissue to the other; indeed, an interfibrillar matrix with a low elastic modulus would be sufficient to guarantee the mechanical properties of the tendon. Possible mechanisms for the stress-transfer involve the interfibrillar proteoglycans and can be related to the matrix shear stress and to electrostatic non-covalent forces. Recent studies have shown that the glycosaminoglycans (GAGs) bound to decorin act like bridges between contiguous fibrils connecting adjacent fibril every 64-68 nm; this architecture would suggest their possible role in providing the mechanical integrity of the tendon structure. The present paper investigates the ability of decorin GAGs to transfer forces between adjacent fibrils. In order to test this hypothesis the stiffness of chondroitin-6-sulphate, a typical GAG associated to decorin, has been evaluated through the molecular mechanics approach. The obtained GAG stiffness is piecewise linear with an initial plateau at low strains (<800%) and a high stiffness region (3.1 x 10(-11)N/nm) afterwards. By introducing the calculated GAG stiffness in a multi-fibril model, miming the relative mature tendon architecture, the stress-strain behaviour of the collagen fibre was determined. The fibre incremental elastic modulus obtained ranges between 100 and 475 MPa for strains between 2% and 6%. The elastic modulus value depends directly on the fibril length, diameter and inversely on the interfibrillar distance. In particular, according to the obtained results, the length of the fibril is likely to play the major role in determining stiffness in mature tendons.

Animals↗
PubMed2002

An approach to computer automation of the extracorporeal circulation.

In order to move towards extracorporeal circulation (ECC) automation, a virtual simulation of the process was designed. The ECC model is composed of a virtual patient linked to a virtual ECC circuit. A user interface panel allows to set control parameters for the simulation and to visualize results. It is possible to switch between manual and automatic control. Meaningful hemodynamic and hematochemical variables are continuously shown along with a score (from 0 to 10). The virtual model can play a crucial role in educating and training the personnel devoted to the managing of the heart-lung machine.

Computer Simulation↗
PubMed2000

Hyperplasia and impaired involution in the mammary gland of transgenic mice expressing human FGF4.

Fgf4, a member of the fibroblast growth factor family, is frequently amplified in a variety of human cancers, however, its expression in neoplastic tissues is rarely detectable. This makes uncertain its involvement in tumour aetiology, although several in-vitro studies link Fgf4 overexpression to malignant transformation and metastatization of culture cells. We generated a transgenic mouse model in which the whey acidic protein (WAP) promoter directs expression of human Fgf4 to mammary tissues during late pregnancy and throughout lactation, with the purpose of studying the involvement of this growth factor in mammary tumorigenesis. Expression of the transgene was specifically detected in lobular-alveolar cells of lactating mammary glands that, by histological analysis, displayed hyperplastic areas and a disorganized structure. This was accompanied by an increased number of red blood cells and expression, in alveolar epithelial cells, of the vascular endothelial growth factor, which is absent in wild type controls. The most striking effect caused by FGF4 overexpression was on the remodelling of mammary tissue at the end of lactation. Indeed, transgenic animals showed a delayed involution of the gland due to a dramatic reduction in the overall number of apoptotic cells, which are normally present in the organ after weaning. Nevertheless, none of the animals examined developed neoplastic lesions of the mammary gland even after several pregnancies and at old age. Our work represents the first in-vivo demonstration of the anti-apoptotic and angiogenic properties of FGF4.

Aging↗
PubMed2000

Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes.

Intravenous administration could become a delivery route of choice for prophylactic and curative gene therapies on condition that genes cross the capillary barrier and reach target tissues without being degraded. We investigated the kinetics and process of transgene delivery through mouse lung capillaries following DNA complexation with linear polyethylenimine (L-PEI) and intravenous injection. Using digoxin-labeled DNA we followed the cellular localization of DNA at different times after injection and correlated these findings with cell markers and transgene expression. At 2 h after injection some DNA was still localized on the interior of the capillary lumen, but other complexes had already crossed the barrier and resulted in gene expression. At 24 h after injection most labeled DNA was localised in pulmonary cells, as was transgene expression. Only rarely was transgene expression found in endothelial cells, suggesting that the complexes cross the capillary barrier rapidly. Levels of caspase-1-like activity did not increase following transfection implying that L-PEI/DNA complexes are transported across cellular barriers by a non-damaging, physiological process, without causing inflammation. The high levels of expression of different transgenes in pneumocytes indicates that transport of L-PEI/DNA complexes through the endothelial barrier does not affect their transfection capacity. These findings open up new possibilities for gene delivery and its application to the lung.

Animals↗
PubMed2000

Multiple functions of Dlx genes.

Dlx genes comprise a highly conserved family of homeobox genes homologous to the distal-less (Dll) gene of Drosophila. They are thought to act as transcription factors. All Dlx genes are expressed in spatially and temporally restricted patterns in craniofacial primordia, basal telencephalon and diencephalon, and in distal regions of extending appendages, including the limb and the genital bud. Most of them are expressed during morphogenesis of sensory organs and during migration of neural crest cells and interneurons. In addition, Dlx5 and Dlx6 are expressed in differentiating osteoblasts. Gene targeting of Dlx1, Dlx2, Dlx3 and Dlx5 in the mouse germ-line has revealed functions in craniofacial patterning, sensory organ morphogenesis, osteogenesis and placental formation. However, no effect on limb development has yet been revealed from gene inactivation studies. A role for these genes in limb development is however suggested by the linkage of the Split Foot/Hand Malformation human syndrome to a region containing DLX5 and DLX6. As for most transcription factors, these genes seem to have multiple functions at different stages of development or in different tissues and cell types.

Amino Acid Sequence↗
PubMed1999

Effects of cooling micrografts in hair transplantation surgery.

BACKGROUND: When isolating hair grafts in hair transplantation procedures, it is generally recommended to preserve the grafts at a low temperature (1 degrees C- 4 degrees C) in order to enhance the survival rate of the grafted hairs. This study was carried out to test the real benefits provided by cold-storing hair grafts. OBJECTIVE: The aim of this study was to evaluate, in an in vitro model, the effects of cooling micrografts during hair transplantation procedures to experimentally assess the soundness of this approach to enhance the survival and growth rates of hair micrografts. METHODS: A total of 240 anagen hair follicles were obtained from 10 healthy male patients. Follicles were thus randomly assigned to one of the following groups: group A (control; n = 120 follicles), or group B (experimental; n = 120 follicles). Follicles from group A were preserved for 5 hours at room temperature (26 degrees C), and follicles from group B were preserved for 5 hours at 1 degrees C. Immediately after that 5-hour period, follicles from both groups were then cultured for 10 days. The length of each follicle was measured immediately following the 5-hour test period and at the end of the 10-day culture period. RESULTS: No statistically significant differences were found between the survival and growth rates of follicles from the control (survival rate = 87%, mean 10-day growth rate = 2.68 mm) and experimental (survival rate = 88%, mean 10-day growth rate = 2.54 mm) groups. CONCLUSION: Although, at present, it is generally assumed that lowering the metabolism of grafts by reducing their temperature may be of some utility for enhancing their survival rate, our data indicate of that there are no effects when performing hair transplantation surgery.

Adult↗
PubMed1999

Lumbar dura mater biomechanics: experimental characterization and scanning electron microscopy observations.

UNLABELLED: There is no consensus about the anatomical structure of human dura mater. In particular, the orientation of collagen fibers, which are responsible for biomechanical behavior, is still controversial. The aim of this work was to evaluate the mechanical properties and the microstructure of the lumbar dura mater. We performed experimental mechanical characterization in longitudinal and circumferential directions and a scanning electron microscopy observation of the tissue. Specimens of human dura mater were removed from the dorsal-lumbar region (T12-L4/L5) of six subjects at autopsy; specimens of bovine dorsal-lumbar dura mater were obtained from two animals at slaughter. Human and bovine tissues both exhibited stronger tensile strength and stiffness in the longitudinal than in the circumferential direction. Scanning electron microscopy observations of dura mater showed that the collagen fibers are mainly oriented in a longitudinal direction, which accounts for its stronger tensile strength in this direction. We conclude that dura mater has a different mechanical response in the two directions investigated because the fiber orientation is predominantly longitudinal. IMPLICATIONS: In this experimental work, we studied the structural and functional relationship of human lumbar dura mater. We performed mechanical tests and microscopic observations on dura mater samples. The results show that the dura mater is mainly composed of longitudinally oriented collagen fibers, which account for higher tissue resistance in this direction.

Adult↗
PubMed1999

Evaluation of temperature distribution during hyperthermic treatment in biliary tumors: a computational approach.

A computational approach is adopted to predict the temperature distribution in the biliary tissue during hyperthermic treatments in biliary tumors. Two different models are developed: an axisymmetric model and a three-dimensional model. In the first model the Pennes bioheat transfer equation is applied. It is aimed at simulating the thermoregulatory effect of the capillary bed and it can also give a pressure criterion to determine whether the blood perfusion term should be included in the mathematical model. The second model is aimed at simulating the convective effect of the large hepatic vessels: A constant Nusselt number is assumed on the sides of the vessels. The simulations of the three-dimensional model have been carried out with and without capillary perfusion in the tissue, i.e., respectively in the worst case and in the best case that may occur during heating. The results show that it is possible to obtain therapeutic temperature values in the tissue for time intervals considered acceptable by physicians. Moreover, the model is able to give more precise information about the volumes of tumoral tissue heated above therapeutic temperatures with the hyperthermic technique considered.

Bile Duct Neoplasms↗
PubMed1999

Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5.

The Dlx5 gene encodes a Distal-less-related DNA-binding homeobox protein first expressed during early embryonic development in anterior regions of the mouse embryo. In later developmental stages, it appears in the branchial arches, the otic and olfactory placodes and their derivatives, in restricted brain regions, in all extending appendages and in all developing bones. We have created a null allele of the mouse Dlx5 gene by replacing exons I and II with the E. coli lacZ gene. Heterozygous mice appear normal. Beta-galactosidase activity in Dlx5+/- embryos and newborn animals reproduces the known pattern of expression of the gene. Homozygous mutants die shortly after birth with a swollen abdomen. They present a complex phenotype characterised by craniofacial abnormalities affecting derivatives of the first four branchial arches, severe malformations of the vestibular organ, a delayed ossification of the roof of the skull and abnormal osteogenesis. No obvious defect was observed in the patterning of limbs and other appendages. The defects observed in Dlx5-/- mutant animals suggest multiple and independent roles of this gene in the patterning of the branchial arches, in the morphogenesis of the vestibular organ and in osteoblast differentiation.

Animals↗
PubMed1998

Fresh and cryopreserved arterial homografts in the treatment of prosthetic graft infections: experience of the Italian Collaborative Vascular Homograft Group.

Following the experience of cardiac surgeons with homografts in the treatment of infective aortic valve endocarditis, cardiovascular surgeons have investigated in situ revascularization by means of homografts in the management of vascular prosthetic graft infections. Preliminary results are encouraging, but their late fate in long-term follow-up and the influence of preservation techniques are still under investigation. This article reports the experience of the Italian Collaborative Vascular Homograft Group, with the use of fresh and cryopreserved arterial homografts for the treatment of prosthetic graft infections. Between March 1994 and December 1996, 44 patients with prosthetic graft infection were treated with homografts (13 preserved at 4 degrees C, 31 cryopreserved). The mean age of the patients was 65 years. Emergency surgical procedures were performed in eight patients (18%). Sepsis was diagnosed in 11 patients, aortoenteric fistula in 13, and false aneurysms in 10. Staphylococcus was the main cause of infection. The types of vascular reconstruction with homograft were: 32 aortobifemoral, 3 aortoaortic, 2 iliofemoral, 4 peripheral, and 3 axillobifemoral. Human lymphocyte antigen (HLA) and antibody (ABO) blood group system compatibility between donors and recipients was not respected. The mean duration of follow-up was 15 months (range 1-33). Clinical and duplex scanning evaluations were routinely performed. Computed tomography (CT) or magnetic resonance (MR) scanning or arteriography were performed on the basis of duplex scanning results. There were six deaths during the early postoperative period (30 days) with a mortality rate of 13.6%. During the follow-up there were five late deaths with a mortality rate of 11.4%. Eight patients had graft occlusion. Three cases were successfully treated with thrombectomy. Two cases were successfully treated with femoropopliteal bypass with autologous vein. In three cases leg amputation was necessary. The results of fresh and cryopreserved homograft were compared. No significative differences of early postoperative mortality, late mortality, homograft related mortality, and graft occlusion were observed. We have evaluated the actuarial survival of the patients and the actuarial patency of the homografts on the aortoiliac reconstructions. Twelve months after the surgery the actuarial survival of the patients was 73% and the actuarial patency of the homografts was 56%. In our preliminary experience, we have not observed any significant difference in terms of clinical outcome by using fresh rather than cryopreserved homografts. In the near future it will be our policy to employ only cryopreserved homografts. Moreover, we will extend vessel harvesting to nonheart-beating donors, thus maximizing retrieval. The aforementioned solutions will supply the best graft availability to obtain dimensional and ABO compatibility between donors and recipients.

Adult↗
PubMed1998

Biomechanics of abdominal aortic aneurysm in the presence of endoluminal thrombus: experimental characterisation and structural static computational analysis.

OBJECTIVES: To evaluate the role played by biomechanical and geometrical parameters of endoluminal thrombus and of aortic wall on abdominal aortic aneurysm (AAA) behaviour. MATERIALS AND METHODS: Tensile tests on 21 AAA thrombus specimens from six patients undergoing AAA repair and numerical evaluation of aneurysmal aortic wall stress and strain distribution. Parameters of the analysis were lumen eccentricity, thrombus Young's Modulus and the aortic wall constitutive equation. RESULTS: There was a linear stress/strain for all the thrombus specimens. The numerical analyses show the mechanical behaviour of AAA as a function of lumen eccentricity and biomechanical parameters. CONCLUSIONS: Well organised thrombus reduces the effect of the pressure load on the aneurysmal aortic wall.

Aged↗
PubMed1998

Polyethylenimine-based intravenous delivery of transgenes to mouse lung.

Generally, cationic vector-based intravenous delivery of DNA is hindered by interactions of positively charged complexes with serum proteins. However, if optimally formulated, cationic vectors can provide reasonable levels of transfection in the lung either by intravenous or intrapulmonary routes. We investigated the in vivo transfection capacity of a cationic polymer: linear, 22 kDa polyethylenimine. PEI/DNA complexes were formulated in 5% glucose and delivered into adult mice through the tail vein. Two marker genes were used, beta-galactosidase and luciferase. High levels of luciferase expression (10(7) RLU/mg protein) were found in the lung when DNA was complexed with PEI at a ratio of 4 nitrogen equivalents per DNA phosphate. Lower levels of transfection were found in the heart, spleen, liver and kidney. Expression was dose- and time-dependent in all tissues examined. In the lung, beta-galactosidase staining showed transgene expression in clusters of 10 or more pulmonary cells including the alveolar endothelium, squamous and great alveolar epithelial cells (type I and II pneumocytes) and septal cells. These findings indicate that the complexes pass the capillary barrier in the lung. Although the delivery mechanism requires elucidation, linear PEI has promise as a vector for intravenous transfer of therapeutic genes.

Animals↗
PubMed1998

Optimisation of a stentless valve prosthesis based on an analytic parametric model of the aortic valve.

An analytical mathematical model of a stentless aortic valve has been implemented. The valve is characterised by a trileaflet geometry, cylindrical leaflets; the aortic root is schematised by a conical surface which includes the leaflet attachments. The model is defined through six geometric parameters: the base radius, the valve height, the commissure radius, the leaflet radial, circumferential and attachment line lengths. Five performance indexes have been used to optimise the valve geometry, namely: the systolic area, the leaflet circumferential stress in diastole, the leaflet bending strain in systole and two bending angles related to the rotation of the leaflets from the diastolic to the systolic configuration. The sensitivity analysis is carried out which can identify the influence of each geometric parameter on the performance indexes adopted for the optimum valve design. The analysis of the results provides the geometric configuration which optimises the overall function of the valve throughout the cardiac cycle.

Aortic Valve↗
PubMed1997

Differential regulation of the zinc finger genes Krox-20 and Krox-24 (Egr-1) suggests antagonistic roles in Schwann cells.

Krox-20 and Krox-24 (Egr-1) encode closely related zinc finger transcription factors, which interact with the same DNA target sequences. Krox-20 is required for myelination in the peripheral nervous system. Using lacZ knock-in mutant mouse lines as well as immunohistochemical analyses, we have studied the expression of Krox-20 and Krox-24 in the Schwann cell lineage during normal development and following nerve lesion in the mouse and in human neuropathies. During embryogenesis, the two genes are expressed in a successive and mutually exclusive manner, Krox-24 being restricted to Schwann cell precursors and Krox-20 to mature Schwann cells. At birth, Krox-24 is reactivated and the two genes are coexpressed. In the adult, Krox-20 is expressed in myelinating cells, while Krox-24 is restricted to nonmyelinating cells. Following nerve lesion, Krox-24 is strongly induced in Schwann cells, reinforcing the link between its expression and the nonmyelinating and/or proliferative state, whereas Krox-20 is downregulated. These data are consistent with Krox-20 and Krox-24 playing antagonistic roles during the development of the Schwann cell lineage. In particular, their balance of expression might participate in the choice between myelinating and nonmyelinating pathways.

Animals↗
PubMed1996

A lumped parameter model to evaluate the fluid dynamics of different coronary bypasses.

Coronary bypass grafting is a surgical procedure frequently performed to obtain myocardial reperfusion downstream from severe coronary stenoses. Different surgical techniques may be adopted which include the use of graft made of internal mammary artery or saphenous vein, and the adoption of multiple or sequential bypasses for more than one stenosis. The haemodynamics of the surgically reconstructed coronary bed is strongly dependent on the bypass configuration and may induce atherogenic processes affecting the long-term potency of the bypass. We have improved a closed-loop mathematical model of the cardiovascular system including a more detailed description of the coronary tree which allows the calculation of the flow rate and pressure curves in all the vessels considered. Pathological situations, such as stenoses, have been simulated and investigated. Models of the internal mammary artery and of the saphenous vein have also been developed in order to simulate coronary artery bypasses. The four simulated bypass configurations have been the single saphenous vein, the sequential saphenous vein, the single internal mammary artery and the sequential internal mammary artery. Results of the simulations of the different bypass grafting configurations indicate that between single saphenous vein and single internal mammary artery the latter shows better haemodynamics both for the flow rate pattern and for the calculated wall shear stress. The sequential bypasses show better haemodynamics in comparison with the single bypass in the proximal segments and worse performance in the distal ones. The models may be applied as an investigative tool to evaluate actual cases of surgically treatable coronary stenoses. They can predict the modification in blood flow waveforms, mean velocities, shear stress and distribution of blood flow in the coronary branches as a function of the adopted bypass configuration.

Biophysical Phenomena↗
PubMed1996

Defective bone formation in Krox-20 mutant mice.

Endochondral ossification is the prevalent mode of vertebrate skeleton formation; it starts during embryogenesis when cartilage models of long bones develop central regions of hypertrophy which are replaced by bony trabeculae and bone marrow. Although several transcription factors have been implicated in pattern formation in the limbs and axial skeleton, little is known about the transcriptional regulations involved in bone formation. We have created a null allele in the mouse Krox-20 gene, which encodes a zinc finger transcription factor, by in frame insertion of the E. coli lacZ gene and shown that hindbrain segmentation and peripheral nerve myelination are affected in Krox-20-/- embryos. We report here that Krox-20 is also activated in a subpopulation of growth plate hypertrophic chondrocytes and in differentiating osteoblasts and that its disruption severely affects endochondral ossification. Krox-20-/- mice develop skeletal abnormalities including a reduced length and thickness of newly formed bones, a drastic reduction of calcified trabeculae and severe porosity. The periosteal component to bone formation and calcification does not appear to be affected in the homozygous mutant suggesting that the major role for Krox-20 is to be found in the control of the hypertrophic chondrocyte-osteoblast interactions leading to endosteal bone formation.

Animals↗
PubMed1996

A new pericardium vascular prosthesis: mechanical behavior, SEM analyses and clinical indications.

This study deals with the mechanical characterization of a new vascular prosthesis. The prosthesis, made from a single portion of pericardial tissue, is bifurcated, crimped and not porous. The clinical use of this graft could increase hemocompatibility of the device compared to polymeric grafts and reduce the compliance mismatch between the natural vessel and the graft. Several mechanical analyses were performed to evaluate the load-displacement and the cyclic loading characteristics of the graft. Scanning electron microscopy was used to evaluate the tissue and suture line morphology before and after mechanical failure. The preliminary results of some clinical cases are also reported. The results point out that the prostheses, developed using correct technological procedures, show a mechanical behavior similar to that of natural arteries and could be successfully used in selected patients.

Aged↗