Endothelial dysfunction induced by hydroxyl radicals - the hidden face of biodegradable Fe-based materials for coronary stents.

Fe-based materials are currently considered for manufacturing biodegradable coronary stents. Here we show that Fe has a strong potential to generate hydroxyl radicals (HO) during corrosion. This HO generation, but not corrosion, can be inhibited by catalase. Oxidative stress was observed (increased HO-1 expression) in aortic rings after direct exposure to Fe, but not in the presence of catalase or after indirect exposure. This oxidative stress response induced an uncoupling of eNOS in, and a consequent reduced NO production by endothelial cells exposed to Fe. In isolated rat aortic rings NO production was also reduced by HO generated during Fe corrosion, as indicated by the protective role of catalase. Finally, all these mechanisms contributed to impaired endothelium-dependent relaxation in aortic rings caused by HO generated during the direct contact with Fe. This deleterious impact of Fe corrosion on the endothelial function should be integrated when considering the use of biodegradable Fe-based alloys for vascular implants.

Hydroxyl radicals and oxidative stress: the dark side of Fe corrosion.

Fe-based materials are considered for the manufacture of temporary implants that degrade through the corrosion of Fe by oxygen. Here we document the generation of hydroxyl radicals (HO) during this corrosion process, and their deleterious impacts on human endothelial (ECs) and smooth muscle cells (SMCs) in vitro. The generation of HO was documented by two independent acellular assays, terephtalic acid hydroxylation (fluorescence) and spin trapping technique coupled with electron paramagnetic resonance spectroscopy. All Fe-based materials tested exhibited a strong potential to generate HO. The addition of catalase prevented the formation of HO. Cellular responses were assessed in two ECs and SMCs lines using different cytotoxicity assays (WST-1 and CellTiter-Glo). Cells were exposed directly to Fe powder in the presence/absence of catalase, or to extracts obtained from the corrosion of Fe. Cell viability was dose-dependently affected by the direct contact with Fe materials, but not in the presence of catalase or after indirect exposure to cell extracts. The deleterious effect of HO on ECs and SMCs was confirmed by the dose-dependent increase of the transcripts of the oxidative stress gene heme oxygenase-1 4 h or 6 h after direct exposure to the particles, but not in presence of catalase or after indirect exposure. The demonstration of HO production during corrosion and consequent oxidative stress on human ECs and SMCs newly reveals a deleterious consequence of Fe-corrosion that should be integrated in the assessment of the biocompatibility of Fe-based alloys.

Experimental study of a new open stent for vessel banding in a swine model: long-term results.

AIM: A new stent was designed, conceived for being placed externally around blood vessels to perform vessel banding in a much simple and fast way. In fact it requires the dissection of a single segment of the aortic wall, as its mechanical features allow it to slide on the tunica adventitia. After previous tests (ex vivo and in vivo test), the new stent has been evaluated in vivo long-term study. METHODS: In female pig of average weight of 60 kg, after placement of endoprosthesis in infrarenal abdominal aorta, immediately below renal arteries, aortic banding was performed with new stent at the level of each end of endoprosthesis, identified under fluoroscopic guidance. Pigs were followed up for six months, and acetylsalicylic acid was administrated: 100 mg once a day. After six months, histological evaluation of explanted abdominal aorta was performed. RESULTS: New stent made the aortic banding simple and fast. Postoperative course was uneventful. Histological results were similar to previous 10-week survival tests and not damages of aortic wall were observed. CONCLUSION: Positive outcome of three last long-term survival tests, as of all those ex vitro and in vivo tests previously performed, makes conceivable further scientific investigation and trials.

[Complications of cytoreductive surgery associated with intraperitoneal chemohyperthermia: prevention and treatment]. / Complicanze della chirurgia citoriduttiva associata a chemioipertermia intraperitoneale (CIIP) prevenzione e trattamento.

New approach to peritoneal carcinomatosis combining cytoreductive surgery and hypertermic intraperitoneal chemotherapy suggest improved survival when it is possible to achieve a complete cytoreduction. In this study we consider the major complications related to this procedure and purpose our approach for their prevention and treatment.

[Cytoreduction and intraoperative peritoneal chemohyperthermia in carcinomatosis from colonic carcinoma and in peritoneal pseudomyxoma]. / Citoriduzione e chemioipertermia intraoperatoria peritoneale (CIIP) nella carcinosi da carcinoma del colon e nello pseudomixoma peritonei.

New approach in treatment of peritoneal carcinomatosis combining cytoreductive surgery and intraperitoneal chemotherapy suggests improved survival when it is possible to achieve a complete cytoreduction. In this study we consider the carcinomatosis from colorectal and appendiceal adenocarcinoma. In all cases, patients in whom cytoreductive surgery was complete had a median survival much longer compared with patients in whom was not possible and, as perfusion works on minimal residual disease, peritonectomy is the only surgical technique that aim at total removal of parietal and visceral peritoneal lesions.

Different expressivity of two adjacent mutations of the APC gene.

AIMS AND BACKGROUND: The phenotypic expression of different APC mutations in familial adenomatous polyposis (FAP) is variable: two to three variants of the disease have been defined based on the severity of colonic manifestations. Age of onset and number of polypectomies per person-year of post-surgical follow-up were compared in two FAP families with very close mutation sites in the APC gene, in order to ascertain mutation-specific variation of expressivity. FAMILIES AND APC MUTATIONS: Family A (5 patients) carried a newly characterized mutation, a four bp deletion at codon 843. Family B (5 patients) carried a previously identified mutation at codon 835. RESULTS: Mean age of onset was 49.7 years in family A and 30.5 years in family B; number of polypectomies per person-year of follow-up was 1.05 for family A and 10.1 for family B (P < 0.001). CONCLUSIONS: There is significant variation of expressivity (allelic heterogeneity) in FAP between two mutations separated by only eight codons, located at the 5' extremity of APC gene exon 15.

Three-dimensional versus two-dimensional video system for the trained endoscopic surgeon and the beginner.

Because of the lack of depth perception in current two-dimensional endoscopic video systems, the performance of fine motor movements is impaired. Endoscopic surgeons are generally able to cope with this limitation, and the performance of complex procedures becomes easy with experience. To assess the value of three-dimensional vision, two groups of surgeons, with and without experience in endoscopic surgery, underwent dexterity tests at a simulator. Data from use of two- and three-dimensional video systems were analysed and are discussed in this paper. The three-dimensional system improved the ability to perform endoscopic procedures, particularly when the highest degree of hand-eye coordination was needed. A common sensation of ocular fatigue, related to the prolonged use of this equipment, may limit its usefulness in advanced endoscopic procedures.

[Familial neoplasms: investigation of genealogic trees of patients surgically treated for colonic adenocarcinoma]. / Familiarità dei tumori: indagine sugli alberi genealogici di pazienti operati per adenocarcinoma del grosso intestino.

In order to study the familial aggregation of colorectal cancer we investigated the pedigrees of the patients with adenocarcinoma of the large bowel who underwent a surgical operation between november 1990 and october 1992 at the Istituto di Chirurgia Generale e Sperimentale Of Pisa University. For each proband, information was obtained on his/her four grandparents and all their second generation descendants. The final sample included 99 probands and 1455 relatives. Only two cases with diagnosis of familial adenomatous polyposis were excluded. As a control group, we applied the same methodology to the spouses of probands, collecting in the end a sample of 72 families including 1163 individuals. The frequency of both colorectal and extracolonic cancer was higher in the relatives of cases than in the control group, for all the relationships. Among the first degree relatives, the empirical risk of colorectal cancer was 1/30 among the case families and 1/139 among the control families, for a 4.6 fold increase in risk. For cancers at all sites (colorectal excluded), the corresponding risk were 1/8 and 1/12. We computed the posterior probability of dying from cancer for a random individual, given the known affection status of one or more of his/her relatives of specified relationship. For an individual with one first degree relative affected by colorectal cancer the posterior risk of the same tumor was 1/15, compared to a value of 1/70 for the entire control population. Considering all cancers, colorectal excluded, we obtained the result that for a person with at least three affected relatives, one of first, one of second and one of third degree, the probability of dying from colorectal cancer was 6%. The distribution of the number of affected individuals for kindred was highly skewed, with a few families responsible of a large part of the observed familial aggregation. This was true for both the cases of colorectal cancer and for all-site cancer. However, no family fulfilled the criterion of hereditary nonpolyposis colorectal cancer (Lynch syndromes I or II).