Open reconstructions for symptomatic atherosclerotic lesions of the supra-aortic vessels: thirty years results from two university hospitals.

BACKGROUND: Atherosclerotic lesions at the origin of common carotid, subclavian, and innominate arteries are causes for brain and hand ischemic symptoms. Surgical reconstructions of symptomatic cases remain the golden standard treatment, although the endovascular approach has been promising as well. In this retrospective study, long-term results of open reconstructions from 2 University Hospitals are presented. METHODS: Through a 30-year period, prospective data of 107 patients, suffering from symptomatic atherosclerotic supra-aortic artery disease, were retrospectively reviewed and included in this study. Demographic data, arterial risk factors, presenting symptoms and signs, diagnostic evaluation, operative treatment and complications, resolution of symptoms, redo surgery, and overall mortality were analyzed. RESULTS: Eighty-one patients were operated on for subclavian, 14 for innominate, and 12 for common carotid severe lesions, through an extra-thoracic reconstruction (91 patients) or a transthoracic one (16 patients). Perioperative mortality was null although morbidity was 16.8%, and primary perioperative patency was 97.2% (secondary patency 100%). The cumulative primary patency was 95.3%, 90.7%, and 86.0% at 5, 10, and 15 years, respectively. The mean time of patency was 214.6 months (95% confidence interval = 198.5-230.6), with no difference between transthoracic and extrathoracic reconstructions (P = 0.278). CONCLUSIONS: Open reconstructions remain a therapeutic strategy with a considerably low perioperative morbidity/mortality offering excellent long-term results regarding patency of the reconstructions and clinical resolution of the symptoms. However, in the modern era of the endovascular techniques, we need more studies for establishing anatomic and clinical criteria regarding patient selection for endovascular angioplasty/stenting or open repair.

Melatonin attenuates high fat diet-induced fatty liver disease in rats.

AIM: To investigate melatonin's preventive action in oxidative stress in a rat model with high fat diet-induced non-alcoholic fatty liver disease (NAFLD). METHODS: NAFLD was induced by high fat diet (HFD) in adult, male, Wistar rats, weighing 180-230 g. After acclimatization for one week, they were randomly assigned to 6 experimental groups that comprised animals on regular diet plus 5 or 10 mg/kg melatonin, for 4 or 8 wk; animals on HFD, with or without 5 or 10 mg/kg melatonin, for 4 or 8 wk; and animals on HFD for 8 or 12 wk, with melatonin 10 mg/kg for the last 4 wk. Liver damage was assessed biochemically by the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histologically. Lipid peroxidation and oxidative stress were assessed by malondialdehyde and glutathione levels in liver tissue. Lipidemic indices and portal vein pressure were also measured. RESULTS: Compared to rats not receiving melatonin, rats on 5 or 10 mg/kg of melatonin had lower mean liver weight (-5.0 g and -4.9 g) (P < 0.001) and lower liver weight to body weight ratio (-1.0%) (P < 0.001), for the two doses, respectively. All rats fed HFD without melatonin developed severe, grade III, steatosis. Rats on HFD with concurrent use of melatonin showed significantly less steatosis, with grade III steatosis observed in 1 of 29 (3.4%) rats on 10 mg/kg melatonin and in 3 of 27 (11.1%) rats on 5 mg/kg melatonin. Melatonin was ineffective in reversing established steatosis. Melatonin also had no effect on any of the common lipidemic serum markers, the levels of which did not differ significantly among the rats on HFD, irrespective of the use or not of melatonin. Liver cell necrosis was significantly less in rats on HFD receiving melatonin than in those not on melatonin, with the AST levels declining by a mean of 170 U/L (P = 0.01) and 224 U/L (P = 0.001), and the ALT levels declining by a mean of 62.9 U/L (P = 0.01) and 93.4 U/L (P < 0.001), for the 5 and 10 mg/kg melatonin dose, respectively. Melatonin mitigated liver damage due to peroxidation and oxidative stress in liver tissue as indicated by a significant decline in MDA production by 12.7 (P < 0.001) and 12.2 (P < 0.001) µmol/L /mg protein /mg tissue, and a significant increase in glutathione by 20.1 (P = 0.004) and 29.2 (P < 0.001) µmol/L /mg protein /mg tissue, for the 5 and 10 mg/kg melatonin dose, respectively. CONCLUSION: Melatonin can attenuate oxidative stress, lessen liver damage, and improve liver histology in rats with high fat diet-induced NAFLD, when given concurrently with the diet.

Endoscopic ultrasound staging and guided fine needle aspiration biopsy in patients with resectable pancreatic malignancies: a single-center prospective experience.

BACKGROUND: Endoscopic ultrasound staging and guided fine needle aspiration biopsy (EUS-FNA) is a highly accurate diagnostic method, useful in characterizing pancreatic lesions, obtaining definitive tissue diagnosis in patients with suspected pancreatic lesions, and providing accurate locoregional staging that enhances diagnostic certainty and evaluation of appropriateness of surgical intervention. The aims of this study were to evaluate the preoperative contribution of EUS staging and EUS-FNA in patients with suspected resectable pancreatic malignancies. PATIENTS AND METHODS: A prospective study was conducted in a tertiary referral center. During a 54-month period, a total of 103 consecutive patients were prospectively evaluated with EUS and EUS-FNA. Enrolled in the study were patients with resectable pancreatic lesions, who underwent surgery. RESULTS: The overall operating characteristics of EUSFNA were sensitivity 96.7%, specificity 90.0%, positive predictive value 98.9%, negative predictive value 75.0%, and diagnostic accuracy 96.1%. CONCLUSION: EUS and EUS-FNA have a high accuracy and positive predictive value in the preoperative determination of resectability in pancreatic cancer.

Increased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF-κB pathway.

Unstable atherosclerotic plaques of the carotid arteries are at great risk for the development of ischemic cerebrovascular events. The degradation of the extracellular matrix by matrix metalloproteinases (MMPs) and NO-induced apoptosis of vascular smooth muscle cells (VSMCs) contribute to the vulnerability of the atherosclerotic plaques. Basic fibroblast growth factor (bFGF) through its mitogenic and angiogenic properties has already been implicated in the pathogenesis of atherosclerosis. However, its role in plaque stability remains elusive. To address this issue, a panel of human carotid atherosclerotic plaques was analyzed for bFGF, FGF-receptors-1 and -2 (FGFR-1/-2), inducible nitric oxide synthase (iNOS) and MMP-9 expression. Our data revealed increased expression of bFGF and FGFR-1 in VSMCs of unstable plaques, implying the existence of an autocrine loop, which significantly correlated with high iNOS and MMP-9 levels. These results were recapitulated in vitro by treatment of VSMCs with bFGF. bFGF administration led to up-regulation of both iNOS and MMP-9 that was specifically mediated by nuclear factor-kappaB (NF-kappaB) activation. Collectively, our data demonstrate a novel NF-kappaB-mediated pathway linking bFGF with iNOS and MMP-9 expression that is associated with carotid plaque vulnerability.

Malondialdehyde as an indicator of oxidative stress during abdominal aortic aneurysm repair.

Ischemia-reperfusion injury significantly contributes to abdominal aortic aneurysm (AAA)- related mortality and morbidity; therefore, we measured oxidative stress during open AAA repair and investigated any potential associations with intraoperative or perioperative events (aortic clamping time, blood loss, and the need to transfer to the intensive care unit). Blood samples were collected at specific time points from 53 patients undergoing open AAA repair: (1) before induction of anesthesia; (2) 15, 30, 60, and 120 minutes after aortic clamping; (3) 15 and 60 minutes after clamp removal; and (4) 24 hours postoperatively. Malondialdehyde (MDA) levels were measured by a spectrophotometric method. Baseline MDA values in patients with AAA were significantly higher than in controls (P < .0001). A positive correlation was found between preoperative MDA levels and the size of AAAs (Pearson correlation = 0.578, P < .001). No difference was observed in MDA levels between ruptured and nonruptured AAAs; however, when all symptomatic patients (ruptured and elective symptomatic AAAs, n = 18) were considered, there was a significant elevation in MDA levels (P < .001). There was also a significant increase in MDA values in patients transferred postoperatively to the intensive care unit (P < .001). Finally, a positive association was found between the duration of aortic clamping with MDA values at 15 and 60 minutes after declamping, but not after 24 hours (Pearson correlation = 0.467, P < .001). MDA levels may predict the postoperative course of elective and ruptured AAAs.

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

BACKGROUND: The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. METHODS: Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. RESULTS: Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). CONCLUSION: High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Histological and lipid peroxidation changes after administration of 2-acetylaminofluorene in a rat liver injury model following selective periportal and pericentral damage.

Administration of 2-acetylaminofluorene (2-AAF) suppresses mature hepatocyte proliferation following selective periportal or pericentral damage induced by allyl-alcohol (AA) or carbon tetrachloride (CCl(4)) administration, respectively. The aim of the present study was to investigate the histological and the lipid peroxidation changes after 2-AAF administration following CCl(4) and AA treatment. The study comprised 108 male Wistar rats that were assigned in four groups: Group A: a placebo pellet was implanted in their neck and on 7th day single dosages of AA and CCl(4) were administrated. Group B: 28-day release 2-AAF pellets (7 0mg-2.5mg per day) were implanted on the neck and on 7th day received a single dose of CCl(4). Group C: 28-day release 2-AAF pellets (70-2.5mg per day) were implanted on the neck and on 7th day a single dose of AA and CCl(4) were administrated. Group D: Sham-operated. Rats of each group were sacrificed on the 9th, 11th, 13th and 21st day. Liver tissue was obtained for histological examination and blood was collected for lipid peroxidation evaluation by measuring malondialdehyde (MDA) and for liver enzymes. On the 9th and 21st day the histological score of liver necrosis was statistically higher on Groups B and C compared to Group A. Concentration of MDA in Group A was significantly higher than in Groups B and C on 9th and 11th days. Transaminase levels, however, were significantly higher in Group A on 9th day compare to the Groups B and C. In conclusion, it appears that oxidative stress was correlated with liver necrosis and with liver regeneration. Suppression of liver regeneration after 2-AAF administration leads to lower malondialdehyde concentrations.