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ABSTRACT: BACKGROUND: Apigenin (4[prime],5,7-trihydroxyflavone, AP), an active component of many medicinal Chinese herbs, exhibits anticancer properties in vitro and in vivo. This study aims to investigate the genotoxic, cytostatic, and cytotoxic effects of AP and time course changes in the levels of anti- and pro-apoptotic proteins involved in the DNA damage response in HepG2 cells. METHODS: The genotoxic potential of AP was determined by sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) analysis. The levels of cytostaticity and cytotoxicity were evaluated by the proliferation rate and mitotic indices, respectively. MTT was used to study cytotoxicity, while the induction of apoptosis and the expression of apoptosis-related proteins were determined by ELISA. RESULTS: At concentrations greater than 10 muM, AP decreased cell survival in a dose- (48 h: 10 vs. 20 muMu, P < 0.001 and 20 vs. 50 muMu, P = 0.005; 72 h: 10 vs. 20 muMu, P < 0.001 and 20 vs. 50 muMu, P = 0.001) and time-dependent manner (20 muMu: 24 vs. 48 h, P < 0.001 and 48 vs. 72 h, P = 0.003; 50 muMu: 24 vs. 48 h, P < 0.001 and 48 vs. 72 h, P < 0.001; 100 muMu: 24 vs. 48 h, P < 0.001 and 48 vs. 72 h, P < 0.001). SCEs rates, cell proliferation, and mitotic divisions were also affected in a dose-dependent manner (P < 0.001). There was no change in the frequency of aberrant cells (1 muMu AlphaP: P = 0.554; 10 muM AP: P = 0.337; 20 muMu AP: P = 0.239). Bcl-2 levels were reduced 3 h after AP administration (P = 0.003) and remained reduced throughout the 48 h observation period (6 h, P = 0.044; 12 h, P = 0.001; 24 h, P = 0.042; 48 h, P = 0.012). Bax and soluble Fas exhibited a transient upregulation 24 h after AP treatment. The Bax/Bcl-2 ratio was also increased at 12 h and remained increased throughout the 48 h observation period. CONCLUSION: AP exhibited dose-dependent genotoxic potential in HepG2 cells. The protein levels of sFas, Bcl-2, and Bax were affected by AP to promote cell survival and cell death, respectively.
Chinese Medicine 05/2013; 8(1):9. · 1.79 Impact Factor
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ABSTRACT: Laparoscopic cholecystectomy is associated with attenuated acute-phase response and hypercoagulable state compared with the open procedure. Single-incision laparoscopic cholecystectomy is a new technique aiming to minimize the invasiveness of the procedure. By comparing the degree of coagulation and fibrinolysis activation after conventional multiport (CLC) and single-incision (SILC) laparoscopic cholecystectomy, we aimed to determine whether the reduced incision size induces a lower thrombophilic tendency. Thirty-two adult patients with noncomplicated symptomatic cholelithiasis were nonrandomly assigned to CLC or SILC. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), D-dimers, fibrinogen, and von Willebrand factor levels were measured at baseline, at 1st, and 24th hour, postoperatively. Twenty-six patients were finally included in the study. Fifteen patients underwent CLC (male/female: 5/10) and 11 underwent SILC (male/female: 1/10). There were no perioperative complications. An almost similar postoperative pattern and degree of activation of coagulation and fibrinolysis pathways was noted in both groups. No statistically significant differences were found between SILC and CLC for F1 + 2, TAT, D-dimers, fibrinogen, and von Willebrand factor levels, duration of surgery, length of hospital stay, and postoperative morbidity. A similar pattern and extent of coagulation and fibrinolysis activation is present in SILC and CLC, and therefore there is no difference in tendency for thrombosis. Thromboembolic prophylaxis should be considered in SILC as recommended for CLC, pharmacologic or mechanical, considering the hemorrhagic risk and the presence of additional thromboembolism risk factors. SILC appears to be a safe, feasible technique that can be recommended for its potential advantages in cosmesis and reduced incisional pain.
Surgical Innovation 04/2013; · 2.13 Impact Factor
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ABSTRACT: Small-intestinal nonmeckelian diverticula are very uncommon and are considered to be acquired pulsion diverticula. Most of these diverticula are asymptomatic and are simply incidental findings. Complicated-acquired diverticular disease of the jejunum and ileum is a diagnostic dilemma. Small-bowel diverticulum is diagnosed with the aid of radiography techniques, such as small-bowel contrast series or enteroclysis. Laparotomy remains the gold standard for a definite diagnosis of asymptomatic and complicated diverticula, but laparoscopy is also very useful in the diagnosis and treatment of this condition. A surgical approach is the best form of treatment for complicated jejunoileal diverticula. The current report is about a patient who presented with iron deficiency anemia caused by a complicated jejunal diverticulum and managed with single-trocar transumbilical laparoscopy.
Surgical laparoscopy, endoscopy & percutaneous techniques 04/2013; 23(2):e78-80. · 1.23 Impact Factor
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ABSTRACT: AIM: The aim of the present study is to evaluate pathologic changes in the pancreatic parenchyma in an experimental model of acute pancreatitis (AP) following bilio-pancreatic duct ligation. An effort was made to clarify the role of apigenin, a substance that is well-known for its antioxidant and anti-inflammatory role and its likely beneficial activity to the pancreatic parenchyma following AP in rats. MATERIAL AND METHOD: One hundred twenty-six male Wistar rats 3-4 mo old and weighing 220-350 g were used. At time 0, the following groups were randomly assigned: group sham: rats were subjected to virtual surgery; group control: rats were subjected to surgery for induction of AP, by ligation of the bilio-pancreatic duct; group apigenin: rats were subjected to surgery for induction of AP and enteral feeding with apigenin. Pathologic changes of the pancreatic parenchymal and myeloperoxidase activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h. RESULT: From the pathologic reports, by comparing the control group with the apigenin group, an improvement of pancreatic tissue architecture following apigenin administration was observed. Inflammatory infiltration, edema, ductal dilation, and necrosis were reduced following apigenin administration over time (P = 0.049, P = 0.228, P = 0.387, P = 0.046). Treatment with apigenin significantly reduced the bilio-pancreatic duct ligation and evoked an increase in pancreatic myeloperoxidase activity (P = 0.030). CONCLUSION: Oral apigenin administration in rats, following experimentally induced pancreatitis, seems to protect the pancreatic tissue. Thus, apigenin administration to humans could potentially ameliorate the damages to the pancreas.
Journal of Surgical Research 12/2012; · 2.25 Impact Factor
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ABSTRACT: Introduction The aim of this study was to investigate the expression of vascular endothelial growth factor (VEGF) in pedicle penile skin flaps (PPSFs) used for urethral reconstruction in rabbits and the effect of exogenous VEGF on the angiogenesis process in the PPSFs.Methods We randomly divided 28 male New Zealand rabbits into two sets of animals. A ventral urethral defect was created in all animals. In the first set of animals (first experiment, n = 10), a PPSF was used for the repair and VEGF expression in the flap was estimated on days 1, 2, 3, 5, and 7 postoperatively. The second set of animals (second experiment, n = 18) included three groups: control, untreated, and VEGF groups. In control group (n = 6), the defect was repaired by simple closure. In untreated (n = 6) and VEGF (n = 6) groups, a PPSF was used for the reconstruction. In VEGF group, exogenous VEGF was injected subdermally on the postoperative day corresponding to the peak endogenous VEGF expression (first experiment results). The animals were sacrificed on the 21st postoperative day and the angiogenic activity was assessed. A p < 0.05 was considered statistically significant.Results The highest expression of endogenous VEGF in PPSFs was noted on postoperative day 3. Angiogenesis in control, untreated, and VEGF groups was 23.06 ± 4.1, 30.00 ± 6.9, and 34.7 ± 6.9 (mean values ± standard deviation) vessels per optical field, respectively. There were statistically significant differences between control-untreated groups (p = 0.04) and untreated-VEGF groups (p < 0.0001), and indicative difference between untreated and VEGF groups (p = 0.064).Conclusions VEGF is expressed in PPSFs, used for urethral reconstruction in rabbits. Flap angiogenesis is much higher than angiogenesis in simple wound closure. VEGF injection on postoperative day 3 seems to enhance angiogenesis in flaps.
European Journal of Pediatric Surgery 07/2012; · 0.81 Impact Factor
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ABSTRACT: INTRODUCTION: Smoking is associated with loss of body weight (BW) and reduced appetite, while smoking abstinence with the opposite effect. The role of peripheral signaling by appetite-controlling hormones leptin and ghrelin is not clear. In the present study, the relationship of circulating leptin and ghrelin with BW and food intake rate (FIR) changes was studied during cigarette smoke exposure (CSE) and after its cessation in the rat. METHODS: Male Wistar rats were subjected to CSE for 8 weeks by confinement to plexiglass chambers (Group S). Control animals were confined to identical chambers without smoke (Group C). During CSE and an equivalent follow-up period, BW and FIR was recorded and serum leptin and ghrelin levels were measured. RESULTS: A sharp decrease in BW was noted during the first 4 weeks of CSE, while FIR, after a substantial decrease noted at Week 1, returned to control levels. Thereafter, rats started to regain their BW until they reached control levels by the 1st week postCSE. BW regain was accompanied by a rebound increase of FIR, which plateaued during the first 4 weeks postCSE and then normalized. Serum leptin was decreased in Group S during both periods, normalizing at the 7th week postCSE. Ghrelin levels did not differ between groups.Conclusions:Circulating leptin could not explain by its own BW and FIR changes during the first few week of CSE in rats, in contrast to the rest of the CSE period as well as after its cessation. Serum ghrelin levels did not justify BW and FIR changes.
Nicotine & Tobacco Research 05/2012; · 2.58 Impact Factor
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ABSTRACT: Periampullary duodenal diverticula are not uncommon and are usually asymptomatic although complications may occasionally occur. Here, we report the case of a 72-year-old woman who presented with painless obstructive jaundice. Laboratory tests showed abnormally elevated serum concentrations of total and direct bilirubin, of alkaline phosphatase, of γ-glutamyl transpeptidase, and of aspartate and alanine aminotransferases. Serum concentrations of the tumor markers carbohydrate antigen 19-9 and carcinoembryonic antigen were normal. Abdominal ultrasonography showed dilatation of the common bile duct (CBD), but no gallstones were found either in the gallbladder or in the CBD. The gallbladder wall was normal. Computed tomography failed to detect the cause of CBD obstruction. Magnetic resonance imaging and magnetic resonance cholangiopancreatography revealed a periampullary diverticulum measuring 2 cm in diameter and compressing the CBD. The pancreatic duct was normal. Hypotonic duodenography demonstrated a periampullary diverticulum with a filling defect corresponding to the papilla. CBD compression by the diverticulum was considered as the cause of jaundice. The patient was successfully treated by surgical excision of the diverticulum. In conclusion, the presence of a periampullary diverticulum should be considered in elderly patients presenting with obstructive jaundice in the absence of CBD gallstones or of a tumor mass. Non-interventional imaging studies should be preferred for diagnosis of this condition, and surgical or endoscopic interventions should be used judiciously for the effective and safe treatment of these patients.
Case Reports in Gastroenterology 05/2012; 6(2):523-9.
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Journal of Gastrointestinal Cancer 04/2012;
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ABSTRACT: PURPOSE: We studied the late angiogenic activity of free grafts and a pedicle flap in a rabbit urethroplasty model to determine whether angiogenic activity plays a role in late outcomes of urethral reconstruction in rabbits. METHODS: Twenty-eight rabbits were randomly divided into five groups according to the method used to bridge a urethral defect as an onlay patch: Control, simple closure of urethral defect (Group O(1)); free penile skin graft (FPSG, Group A(1)); buccal mucosal graft (BuMG, Group B(1)); bladder mucosal graft (BlMG, Group C(1)); and pedicle penile skin flap (PPSF, Group D(1)). Angiogenic activity of the patch on postoperative day 84 was assessed by immunohistochemistry. RESULTS: The angiogenic activity in Groups O(1), A(1), B(1), C(1), and D(1) was 23.33 ± 4.92 (means ± SD), 42.89 ± 6.52, 55.78 ± 3.46, 53.61 ± 6.17, and 24.11 ± 9.07 vessels per optical field, respectively. There were statistically significant differences (p < .001) between Group O(1) and A(1) B(1), C(1), Group A(1) and B(1), C(1), D(1), Groups B(1) and D(1) and Groups C(1) and D(1), but not between Groups O(1) and D(1) (p = 1.000) and Groups B(1) and C(1) (p = .872). The long-term angiogenic activity of all the groups was significantly lower (p < .001) than in the corresponding early groups. CONCLUSIONS: Although the angiogenic activity of all the groups decreased in the late assessment, the buccal mucosal graft continued to exhibit elevated angiogenesis above bladder or skin (free or pedicle) graft. Therefore, buccal mucosal patch graft might be preferable because of its easier harvesting.
World Journal of Urology 04/2012; · 2.41 Impact Factor
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ABSTRACT: Adhesion to the intestine represents a critical parameter for probiotic action. In this study, the adhesion ability of Lactobacillus casei ATCC 393 to the gastrointestinal tract of Wistar rats was examined after single and daily administration of fermented milk containing either free or immobilized cells on apple pieces. The adhesion of the probiotic cells at the large intestine (cecum and colon) was recorded at levels ≥6 logCFU/g (suggested minimum levels for conferring a probiotic effect) following daily administration for 7 days by combining microbiological and strain-specific multiplex PCR analysis. Single dose administration resulted in slightly reduced counts (5 logCFU/g), while they were lower at the small intestine (duodenum, jejunum, ileum) (≤3 logCFU/g), indicating that adhesion was a targeted process. Of note, the levels of L. casei ATCC 393 were enhanced in the cecal and colon fluids both at single and daily administration of immobilized cells (6 and 7 logCFU/g, respectively). The adhesion of the GI tract was transient and thus daily consumption of probiotic products containing the specific strain is suggested as an important prerequisite for retaining its levels at an effective concentration.
Anaerobe 04/2012; 18(4):417-20. · 2.41 Impact Factor
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ABSTRACT: The extent of surgical trauma is reflected by systemic inflammatory response (SIR). The aim of this study was to assess SIR after single-incision laparoscopic surgery (SILS) versus the standard laparoscopic approach.
Twenty pigs were assigned into 4 groups: SILS (group SILS), laparoscopy using 4 trocars (group LAPSC), pneumoperitoneum (group PNE), or a sham-operation (group Sham) group. Blood samples were taken at 0, 1, 3, 6, 24, and 48 hours and 1 week postoperation to measure tumor necrosis factor-α, interleukin (IL)-6, IL-18, and C-reactive protein serum levels.
No significant changes were noted among groups for each time point studied regarding tumor necrosis factor-α, IL-6, and IL-18. C-reactive protein levels were significantly lower (P<0.05) in group PNE compared with the other groups at 24 hours, 48 hours, and 1 week.
There is no difference in SIR after SILS versus the standard laparoscopic approach.
Surgical laparoscopy, endoscopy & percutaneous techniques 02/2012; 22(1):21-4. · 1.23 Impact Factor
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ABSTRACT: We sought to develop a rat model of cigarette smoke exposure (CSE) that created cotinine serum levels comparable to those of smokers and induced conditioned place preference (CPP) suggestive of cigarette smoke abuse liability. Rats were exposed to sidestream cigarette smoke delivered semicontinuously for 2 periods of 20 (group S20), 40 (group S40), or 60 (group S60) min daily for 12 wk. Serum cotinine concentration in blood samples was determined at 1 and 20 h after CSE. A biased (black versus white chamber) CPP paradigm was used. In the high CSE group (group S60), serum cotinine at 1 h (250 to 300 ng/mL) was comparable to average cotinine levels reported for addicted smokers (around 300 ng/mL). Cotinine levels at 20 h after CSE were higher than the smoker-nonsmoker cut-off value (greater than 14 ng/mL) in all smoking groups, with the S60 group having the highest levels. All rats preferred the black chamber to the white chamber during the preexposure CPP test. The time spent in the white chamber was increased compared with 0-wk values in group S40 at 8 wk, group S60 at 4 and 8 wk, and the control group at 4 and 8 wk but not at 12 wk; however, the shift in CPP was significantly higher at 8 wk in group S60 compared with other groups. In conclusion, interrupted 2-h daily CSE for 8 wk induced serum cotinine levels in rats comparable to those of smokers and induced CPP suggestive of cigarette smoke abuse liability.
Comparative medicine 01/2012; 62(5):395-9. · 1.05 Impact Factor
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Journal of Gastrointestinal Cancer 11/2011;
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Pancreas 10/2011; 40(7):1157-9. · 2.39 Impact Factor
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Journal of Gastrointestinal Cancer 09/2011;
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ABSTRACT: The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration.
Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30 min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio-GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48 h, 1 wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens.
Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48 h.
Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma.
Journal of Surgical Research 07/2011; 169(1):44-50. · 2.25 Impact Factor
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Petros Ypsilantis,
Maria Politou,
Dimitrios Mikroulis,
Maria Lambropoulou,
Ioannis Bougioukas,
Georgios Theodoridis,
Christina Tsigalou,
Constantinos Manolas,
Nikolaos Papadopoulos,
Georgios Bougioukas, Constantinos Simopoulos
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ABSTRACT: Prolonged sedation with propofol at high doses may lead to fatal multi-organ dysfunction, know as propofol infusion syndrome. We tested the hypothesis that propofol plus remifentanil co-administration attenuates propofol tolerance to its sedative effect and assessed if such an effect has an impact on propofol toxicity in rabbits under prolonged mechanical ventilation.
Eighteen healthy male rabbits were mechanically ventilated and received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6), or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under sedation (group P) or sedation/analgesia (groups PR and RS) for up to 48 h. Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed, to maintain the desired level of sedation and analgesia, respectively (groups P and PR). In group RS, remifentanil was infused at IRs equivalent to those of group PR. Propofol IRs were recorded, propofol concentrations were measured in the arterial plasma, and blood biochemical parameters and organ histopathology were assessed.
Animals survived for 29-36 h in group P and 22-38 h in group PR (100% mortality rate). Tolerance was developed to propofol's sedative effect. The onset of tolerance was delayed and its magnitude was decreased in group PR compared with group P. Propofol was accumulated in the systemic circulation. Propofol clearance rate was gradually decreased. Arterial lactate, and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and skeletal muscles were seriously injured in groups P and PR. In group RS, mortality was 0%, while there was only mild injury of the lungs, liver, gallbladder, kidneys, and urinary bladder.
Although propofol tolerance is attenuated in propofol plus remifentanil receiving rabbits under prolonged mechanical ventilation, fatal multi-organ injury occurs resembling human propofol infusion syndrome.
Journal of Surgical Research 06/2011; 168(2):253-61. · 2.25 Impact Factor
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ABSTRACT: Breast cancer in men is relatively rare and its coexistence with other primary non-breast cancers exceptional. Here, we report the case of a 50-year-old man who presented with symptoms of rectal adenocarcinoma and in whom a synchronous, asymptomatic cancer of the left breast was found incidentally at physical examination.
Case Reports in Oncology 05/2011; 4(2):281-6.
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ABSTRACT: Carcinoma of the papilla of Vater is a relatively rare tumor and its coexistence with other primary sporadic cancers is very exceptional. Here we report the case of a 76-year-old man who presented with painless obstructive jaundice, pathologically elevated liver function tests and increased serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. Endoscopic retrograde cholangiography revealed a large polypoid mass in the ampulla of Vater. A large tumor in the ascending colon was also incidentally detected by abdominal computed tomography. Endoscopic biopsies from both lesions showed adenocarcinomas. Metastases to the liver and to the hepatoduodenal ligament and hepatic artery lymph nodes were found during surgery. Right colectomy and a biliary bypass were performed. Histological analysis showed an ampullary adenocarcinoma with metastases to regional lymph nodes and the liver and a colonic adenocarcinoma with local invasion into the pericolic fat. Treatment with gemcitabine plus cisplatin was suggested postoperatively. The association of sporadic ampullary and colonic adenocarcinomas and the mutually increased risk of developing either a synchronous or a metachronous tumor following each other should be considered in patients with primary ampullary or colorectal cancer during the preoperative evaluation and postoperative follow-up of these patients.
Case Reports in Gastroenterology 05/2011; 5(2):301-7.
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ABSTRACT: To assess the systemic inflammatory response (SIR) and the multi-organ damage after large-volume liver radiofrequency ablation (RFA) with or without concurrent Pringle maneuver.
Wistar rats were subjected to 30% liver RFA (group RFA), liver RFA under 30-min Pringle maneuver (group RFA + P), Pringle only (group P) or sham operation (group S). Serum levels of interleukin-1α (IL-1α), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), serum biochemical profile, multiple-organ pathology and the activity of nuclear factor-κB (NF-κB) in the liver were assessed post-operatively.
The levels of IL-6 and TNF-α were increased from 1h up to 1w and 6h, respectively, in both RFA groups, while IL-6 was only mildly increased at 3 h in group P. IL-6 was higher in group RFA + P compared to group RFA. Serum biochemical profile was altered more intensely in group RFA + P compared to RFA. There was tissue injury in the non-ablated liver portion as well as in adjacent and remote organs with lesions being more severe in group RFA + P. At 1 h, NF-κB was equally activated in all study groups.
Extended liver RFA causes SIR and multi-organ injury, which are exacerbated when a concurrent Pringle maneuver is applied.
Human & Experimental Toxicology 03/2011; 30(11):1855-64. · 1.31 Impact Factor
