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Biomedical subjects

G Abatangelo

Publications and source records attributed to G Abatangelo.

At least 37 records · Page 2Linked to original sources

Guiding spontaneous tissue regeneration for urethral reconstruction: long-term studies in the rabbit.

We designed long-term in vivo experiments to study rabbit urethral regeneration and remodelling over a hyaluronan biodegradable prosthesis. Seven months after the resection of a 1.5-cm-long tract of the urethra and its substitution with the prosthesis, radiological analysis showed the disappearance of the implant and the re-establishment of urethral continuity along the transmural defect. The regenerated tissue remodelled around the implant and exhibited good distensibility under pressure. Histological evaluation showed that the neo-urethra was lined with transitional epithelium and the stroma contained abundant elastic fibres. An examination of the pattern of the major cytoskeletal and cytocontractile proteins of smooth muscle cells and fibroblasts was able to distinguish fibroblasts from smooth muscle cells and myofibroblasts in the neo-urethra. These experiments provide evidence for the potential, successful use of biocompatible/bioresorbable devices for reconstructive surgery of the urethra.

Actins↗

Semisynthetic resorbable materials from hyaluronan esterification.

In recent years, research on new, biocompatible, degradable materials has seen the development of a series of modified natural polymers. Among these, a new class of materials consisting of different hyaluronan derivatives promises to be useful in a whole range of clinical applications thanks to their varied biological properties. These new materials are obtained by chemical modification of purified hyaluronan consisting of the partial or total esterification of the carboxyl groups of this natural polymer. This review on the properties of the new materials reports some of their biocompatibility and characterization aspects based on findings from studies conducted on the ethyl and benzyl hyaluronan esters, two representative members of this new class of compounds, and is intended to arouse interest in the potential of other, as yet unexplored derivatives. From the results of a number of investigations, the various derivatives appear to possess different physico-chemical properties, especially as far as the degree of hydration and polymer stability are concerned. In addition, the type of esterification and extent of chemical esterification of hyaluronan considerably affects the biological properties of these materials, offering a range of polymers either favouring or, conversely, inhibiting the adhesion of certain types of cell.

Absorbable Implants↗

Reconstructive surgery of the urethra: a pilot study in the rabbit on the use of hyaluronan benzyl ester (Hyaff-11) biodegradable grafts.

We investigated the outcome of reconstructive surgery of the urethra through guides composed of a novel biodegradable and highly biocompatible polymer, Hyaff-11. A tract of about 1.5 cm of the rabbit pendulous urethra was totally resected and replaced by a Hyaff-11 tubular graft. Eleven animals were analysed at each of the time points ranging from 7 days to 4 weeks following surgery. Histological and radiological evaluation showed a satisfactory remodelling of the neo-urethra around the implant. The regenerated connective tissue connected both urethral stumps within the first 7 days. On postoperative week 3, the Hyaff-11 guide had disappeared. At the 4-week time point the retrograde urethrogram showed a good distensibility of the neourethra. The regenerated stroma consisted of fibroblastic cells, and collagenous and elastic fibres. The neo-epithelium was pluristratified and exhibited cells of the cuboidal type.

Animals↗

Biocompatibility and enzymatic degradation studies on sulphated hyaluronic acid derivatives.

The biocompatibility and susceptibility to enzymatic degradation of new heparin-like polysaccharides obtained by hyaluronic acid sulphation (HyalSx) were evaluated. In particular, HyalSx cytotoxicity and cytocompatibility were assessed by the direct contact method using fibroblasts L929 and human endothelial cells. The results showed that hyaluronic acid derivatives are devoid of any cytotoxic effects on mouse fibroblasts and they are cytocompatible. The haemolysis test showed that the sulphated polysaccharides are not haemolytic. HyalSx susceptibility to enzymatic degradation was tested in the presence of both hyaluronidase and chondroitinase ABC. It was demonstrated that the introduction of sulphate groups along the hyaluronic acid chain makes the macromolecules resistant to enzymatic digestion.

Animals↗

Antioxidant effects of hyaluronan and its alpha-methyl-prednisolone derivative in chondrocyte and cartilage cultures.

OBJECTIVE: To compare hyaluronan and its alpha-methyl prednisolone derivative (HYC-141) with respect to their potential to directly cause tissue damage and to protect tissues from attack by reactive oxygen species. METHODS: Cartilage samples and chondrocytes were isolated from 15-day chick embryos and were exposed to enzyme-based and activated inflammatory cell-free radical generating systems in the presence of varying concentrations of alpha-methyl prednisolone, hyaluronan, and HYC-141. Tissue and cell vitality was measured by determining the incorporation of radioactive sulphate into newly synthesized glycosaminoglycans. RESULTS: Only alpha-methyl prednisolone caused a significant decrease in biosynthetic activity. All the tested substances were capable, to some extent, of protecting tissues and cells from damage by reactive oxygen species; HYC-141 demonstrated the greatest protective effect. CONCLUSION: These data suggest that HYC-141 may possess certain advantages over the individual component molecules in the local treatment of arthropathies.

Animals↗

Is stage pT4a (D1) reliable in assessing transitional cell carcinoma involvement of the prostate in patients with a concurrent bladder cancer? A necessary distinction for contiguous or noncontiguous involvement.

PURPOSE: A series of patients with concurrent transitional cell carcinoma involvement of the prostate and bladder is reviewed to define the impact of prostate involvement pathways and the degree of prostate invasion on survival rate. MATERIALS AND METHODS: A total of 72 patients who underwent radical cystectomy for pathological stage pT4a (D1) cancer was divided into contiguous--stage pT4a, transitional cell carcinoma of the bladder extended into the prostate through the bladder wall and noncontiguous--stage pT4a simultaneous transitional cell carcinoma of the prostate and bladder carcinoma that did not directly infiltrate into the prostate through the bladder wall. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement, stromal invasion and extracapsular extension. The survival rate was estimated by the Kaplan-Meier and Cox proportional hazards methods. Comparisons between curves were performed by univariate log rank and multivariate L-ratio tests. RESULTS: The overall 5-year survival rate for stage pT4a was 21.5% (median followup 64 months). Furthermore, 46% and 7% of patients in noncontiguous and contiguous pT4a groups, respectively, were estimated to be alive (p < 0.000). Those with positive nodes experienced a poor outcome in both groups. Of patients with noncontiguous pT4a stage 100% with urethral mucosal involvement, 50% with ductal/acinar involvement and 40% with stromal invasion were estimated to be alive. The major prognostic factors were bladder tumor stage, nodal involvement and degree of prostate invasion. CONCLUSIONS: The invasion pathways of the prostate in patients with transitional cell bladder carcinoma have a statistically significant prognostic role. Contiguous and noncontiguous involvements are 2 distinct clinicopathological features and they should not be included in the same stage. In the noncontiguous stage pT4a group bladder and prostate transitional cell carcinoma should be separately staged, and prostate involvement also should be staged according to invasion degree.

Carcinoma, Transitional Cell↗

Physiological aging and penile erectile function: a study in the rat.

Erectile function of adult (8-month-old) and aged (27-month-old) rats was investigated by in vivo and in vitro assays. Reflexogenic tonic erections were evoked in vivo by electrostimulation of the dorsal nerve of the penis. Aged rats developed tendentially low intracavernosal pressures, and the kinetics of erection and detumescence were significantly lower than in adult animals. The erectile tissue isolated from aged rats exhibited poor response to papaverine. When precontracted with norepinephrine, aged tissues required a 3-fold increase of papaverine concentration to full relaxation. Functional measurements were coupled with morphological analysis of elastic fibres of the tunica albuginea. Light microscopy showed degenerative signs of elastic fibres of aged rat specimens. Taken together, the present findings show that physiological aging is associated with penile tissue stiffness and abnormal corporal compliance.

Aging↗

Collagen types I and III in giant papillae of vernal keratoconjunctivitis.

AIMS: The objective of this study was to investigate alterations in conjunctival collagen and proteoglycans in the conjunctival giant papillae of patients with vernal keratoconjunctivitis (VKC). METHODS: Tissue samples from tarsal giant papillae of seven eyes from five patients with VKC, and five tarsal conjunctival samples from five normal patients were obtained. Tissues were processed and stained with haematoxylin and eosin, Van Gieson, trichromic Mallory, toluidine blue, Alcian blue, and alkaline Giemsa. Collagen extraction was performed in acetic acid and pepsin, total collagen was quantified using hydroxy-proline levels, and collagen types I and III were analysed by gel electrophoresis (SDS-PAGE). Proteoglycans were quantified using uronic acid levels. RESULTS: Histological evaluation showed a significant increase of mast cells in the epithelium (0/mm2 v 147/mm2, p < 0.01) and in the stroma (5.1/mm2 v 80/mm2, p < 0.01) of VKC patients. Collagen fibres were thicker and arranged irregularly, with the total amount significantly increased. Owing to an increased percentage of type III collagen, the ratio of collagen types I to III was decreased. Proteoglycans were also reduced in VKC samples. CONCLUSION: The well known morphological abnormalities observed in VKC correspond to alterations in the ratio between collagens and proteoglycans, and between different types of collagen. The greatly increased number of mast cells found in these tissues suggests an active role for these cells in the abnormal connective tissue metabolism observed in VKC.

Adolescent↗

Improving the efficacy of BCG immunotherapy by dose reduction.

Several clinical trials have shown intravesical bacillus Calmette-Guérin (BCG) to be effective in the prophylaxis of papillary tumour recurrences and in the therapy of bladder carcinoma in situ (CIS), as well as in delaying progression to muscle invasion. Nevertheless, the optimal regimen of BCG therapy for superficial bladder cancer has still to be defined. In a previous phase II trial, a low-dose regimen (BCG Pasteur strain, 75 mg) was able to achieve clinically significant response rates with a decrease in side-effects compared with other reported studies using standard-dose BCG. However, a phase III randomized trial--low dose versus standard dose (BCG Pasteur strain, 75 vs. 150 mg)--was considered necessary to clarify definitively the relationships between dose, efficacy and toxicity. The results of the interim analysis of 183 patients (performed in 1993) have shown response rates to be better in patients submitted to a low-dose BCG regimen (p = 0.0009) and a significant decrease in most of the common side-effects (cystitis, fever, haematuria; p < 0.05). Breaking down the results by stage, no differences in response rates were found in patients with stage TaM (70 vs. 62% in low-dose and standard-dose regimens, respectively, p = 0.5). In T1M and CIS stages, 82 and 0 (p = 0.07), and 64 and 0% (p = 0.0003) of patients were free of tumour following low-dose and standard-dose therapy, respectively. An additional 6-week course in patients who failed the induction course retrieved additional responses in both groups. No differences in progression rates were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats.

Hyaluronan (HL), a naturally occurring glycosaminoglycan, has been chemically modified through the esterification of its carboxylic groups with different types of alcohol. The physico-chemical properties of these new biopolymers allow the preparation of many biomaterials which may be used in several medical applications. In the present study both the biocompatibility and biodegradation of some water-insoluble HL esters have been evaluated, either as raw material or as manufactured devices after subcutaneous and intraperitoneal implantation in male rats. The inflammatory response and the degree of resorption for each tested material are reported. The relationships between the degree of esterification and the type of alcohol used with the above parameters are also investigated.

Animals↗

In vitro studies on biocompatibility of hyaluronic acid esters.

The biocompatibility of semisynthetic polymers formed from hyaluronic acid esters has been studied using fibroblast cultures. The polymers, added to the culture medium, used either in powdered form or as thin membranes, behave as inert materials. The cells used in the experiments grow normally in the culture dishes. With regard to adhesiveness the cells were not able to spread on the biomembranes and tended to form isolated clusters of round cells. Human fibronectin, placental collagen (type I-IV) and fibrin could be stratified on biomembranes. When these molecules reacted with the biomaterial the film became suitable for fibroblasts spreading and growth.

Animals↗

Hyaluronic acid promotes chick embryo fibroblast and chondroblast expression.

15-day-chick-embryo fibroblasts and chondroblasts were cultured in the presence of high and low molecular weight exogenous hyaluronic acid (HA). Growth range and incorporation of radiolabelled sulphate and proline were determined. HA reduced cell proliferation to about 75% of controls, while incorporation of radiolabelled sulphate and proline was higher in HA-treated cultures of both chondroblasts and fibroblasts. The effect was not due to the polyanionic or polymeric nature of the molecule and appeared to be highly specific for HA.

Animals↗

Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. II. Morphological findings.

The effect of the intraarticular sodium hyaluronate (HA) injection on the osteoarthritic knee joint has been evaluated in dogs using an experimental model of osteoarthritis induced by sectioning the anterior cruciate ligament. Seven weeks after surgery, the damage, graded according to Mankin's scale, was significantly reduced in knee joints treated with HA from the second week postsurgery compared to untreated joints. When intraarticular HA therapy was initiated after the seventh week, osteoarthritis progression was still reduced compared to controls. Both morphology and morphometry showed a beneficial effect of HA on the cartilage response to the damage, as well as a clearcut inhibitory effect on the development of the fibroblastlike cell layer on the articular cartilage in untreated joints. The beneficial effects on the cartilage integrity and response to osteoarthritic damage might be related to a primary effect of HA on the cartilage surface. However, these effects do not exclude the possibility that, in addition, HA might act on the synovial membrane by limiting the synovial reaction.

Animals↗

Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. I. Biochemical results.

An established anterior cruciate ligament deficiency-induced articular cartilage degeneration was used to evaluate the effects of intrasynovial injection of hyaluronic acid upon cartilage destruction. In this study, proteoglycan solubility under associative and dissociative conditions was compared in two treatment protocols at intervals of seven, 13, and 17 weeks after surgical breakage of the anterior cruciate ligament in 2.5-year-old Beagle dogs. Untreated joints showed a marked increase in both total soluble glycosaminoglycan (GAG measured as uronic acid) and in the associative fraction. In both treated groups, there was a reduced amount of soluble GAG. Cessation of treatment after seven weeks caused gradual regression, with an increasing amount of CaCl2-soluble material in the associative fraction, while inception at seven weeks gave biochemical evidence of reversal, with increasing GAG present in the guanidine-soluble (dissociative) fraction on the insoluble residue. The protective effects of hyaluronic acid suggest the potential clinical application of this therapy in retarding the advance of osteoarthritis.

Animals↗

Healing of hyaluronic acid-enriched wounds: histological observations.

The influence of an exogenous supply of Na hyaluronate (HA) on the healing of superficial skin wounds in healthy and alloxan-induced diabetic rats was histologically assessed. Rats were treated by topical application on the wound site of a 2% Na hyaluronate solution. A facilitating effect of the HA-enrichment on wound repair processes (particularly epithelial migration and differentiation) was markedly evident in wounded diabetic rats. This result is discussed in terms of a possible favorable influence of an HA-enriched wound environment on cell migratory processes occurring during wound healing.

Animals↗

Chemical characterization of the hen eggshell matrix: isolation of an alkali-resistant peptide.

The eggshell matrix was obtained from hen eggshells using EDTA solutions. The water-soluble organic material was separated on a DEAE-cellulose column equilibrated with 8 M urea using Tris-hydrochloric acid buffer as eluent with a linear gradient of sodium chloride. Five main fractions were obtained which differ in amino acid composition and sugar contents. As is shown from the uronic acid content, the first two fractions eluted from the column are glycoproteins, while the other three contain proteins and glycosaminoglycans From the alkaline hydrolysate of the eggshell matrix, a peptide was isolated which is composed of aspartic acid, threonine, serine, glutamic acid, proline, glycine and alanine in a molar ratio of 2:1:3:7:1:3:1 with a minimum molecular weight of 2158 daltons. The calcium ion binding to this peptide was studied, at different pH values, with both free and blocked carboxyl groups, using murexide as an indicator of free Ca2+. The importance of this acidic peptide in the calcification process of the eggshell matrix is discussed.

Amino Acids↗