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ABSTRACT: Arterial hypertension is often associated with a stiff aorta as a result of collagen accumulation in the aortic wall and may produce chest pain. In the present study, possible interrelationships between aortic function, collagen turnover and exercise-induced chest pain in patients with arterial hypertension and angiographically normal coronary arteries were investigated.
Ninety-seven patients with arterial hypertension, angiographically normal coronary arteries and no evidence of myocardial ischemia on nuclear cardiac imaging during exercise test were studied. Of these, 43 developed chest pain during exercise (chest pain group) while 54 did not (no chest pain group). Carotid femoral pulse-wave velocity (PWVc-f) was used to assess the elastic properties of the aorta. Amino-terminal pro-peptides of pro-collagen type I, (PINP, reflecting collagen synthesis), serum telopeptides of collagen type I (CITP, reflecting collagen degradation), pro-metalloproteinase 1 (ProMMP-1), and tissue inhibitor of metalloproteinase 1 (TIMP-1, related to collagen turnover) were measured in plasma by immunoassay.
The chest pain group had higher PWVc-f, higher and /CITP ratio, and lower proMMP-1/ TIMP-1 ratio compared to the no chest pain group. PWVc-f (t=2.53, p=0.02) and PINP (t=2.42, p=0.02) were independently associated with the presence of chest pain in multiple regression analysis.
Patients with arterial hypertension, exercise-induced chest pain and angiographically normal coronary arteries, without evidence of exercise-induced myocardial ischemia, had a stiffer aorta compared to those without chest pain. Alterations in collagen type I turnover that favor collagen accumulation in the aortic wall may contribute to aortic stiffening and chest pain in these patients.
Hellenic journal of cardiology: HJC = Hellēnikē kardiologikē epitheōrēsē 01/2013; 54(1):25-31. · 1.23 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: 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: 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: 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
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ABSTRACT: Alterations in plasma leptin and adiponectin concentrations are associated with an adverse metabolic profile in obese children.
To simultaneously assess multiple factors with possible effects on plasma leptin and adiponectin concentrations in healthy, non-obese children.
We studied 170 healthy non-obese children (86 males, age 10+1.5 years), with available medical records from birth.
Plasma leptin and adiponectin concentrations were assessed by immunoassay. The ratio of current weight/birth weight (WBWR) was used as an index of children growth from birth. Children's intensity of physical activity and parental characteristics were also assessed.
Leptin was positively associated with WBWR (p<0.0001); parental smoking (analysis of variance, ANOVA; p-=0.03) and parental obesity (ANOVA; p<0.001) were negatively associated with breastfeeding (p<0.01) and children's access to exercise (p<0.0001). Adiponectin was negatively associated with WBWR (p<0.0001) and parental smoking (p=0.04), with an additive negative effect of parental smoking status and parental obesity on children's adiponectin levels (ANOVA; p=0.02).
Children's and parental factors are related and could possibly influence leptin and adiponectin concentrations in healthy non-obese children. Early preventive strategies that target both children and parents could improve the profile of adipocytokine in these children.
Journal of pediatric endocrinology & metabolism: JPEM 01/2011; 24(5-6):313-8. · 0.88 Impact Factor
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ABSTRACT: Large volume radiofrequency ablation (RFA) of the liver disrupts intestinal mucosa barrier with subsequent bacterial translocation.
To investigate the effect of the Pringle maneuver applied concurrently with extended liver RFA on gut barrier integrity and bacterial translocation.
Rats were subjected to 30% liver RFA following laparotomy (group RFA), RFA plus 30 min Pringle (group RFA + P), Pringle (group P) or sham operation (group S). Intestinal tissue specimens were excised for histopathological examination and assessment of mucosal morphometry, apoptotic activity, mitotic activity and oxidative state. Tissue specimens were collected from the mesenteric lymph nodes, non-ablated liver parenchyma, kidneys and lungs for bacterial culture. Blood samples were collected from the portal and systemic circulation for endotoxin level measurement.
In group RFA + P, intestinal histopathologic lesions, mucosal atrophy and crypt cell apoptosis were more prominent compared to group RFA. Mitotic activity was suppressed. Oxidative stress was equally induced in all experimental groups. The incidence of positive bacterial cultures, bacterial counts and endotoxin levels were higher in group RFA + P compared to the other groups.
The application of the Pringle maneuver concurrently with extended liver RFA aggravates gut barrier dysfunction with more aggressive translocation of endotoxins and intestinal bacteria.
Digestive Diseases and Sciences 10/2010; 56(5):1548-56. · 2.12 Impact Factor
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ABSTRACT: Studies have suggested that collagen accumulation in the aortic wall may contribute to the stiff aorta in arterial hypertension. However, data in human hypertension are limited. In this investigation, relations between markers of collagen metabolism and aortic function in patients with arterial hypertension were evaluated.
We studied 72 hypertensive patients (age 53 +/- 5 years) and 27 age- and gender-matched normotensive individuals. Elastic properties of the aorta were assessed by aortic pulse wave velocity (carotid-to-femoral pulse wave velocity (PWVc-f)). Free amino-terminal propeptides of precollagen type I (PINP, reflecting collagen I synthesis), serum telopeptides of collagen type I (CITP, an index of collagen I degradation), free amino-terminal propeptides on precollagen type III (PIIINP, reflecting collagen III metabolism), prometalloproteinase-1 (proMMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined by commercially available immunoassays.
Patients with arterial hypertension had greater PWVc-f (P = 0.01); and higher levels of PINP/CITP compared to control (P = 0.04). PWVc-f was significantly associated with PINP/CITP ratio (analysis of variance (ANOVA), P = 0.03). Hypertensive patients had significantly higher levels of proMMP-1/TIMP-1 (P = 0.04); PWVc-f was significantly associated with proMMP-1 (ANOVA, P = 0.03) and proMMP-1/TIMP-1 (ANOVA, P = 0.04). Associations between PWVc-f and proMMP-1 and between PWVc-f and PINP/CITP ratio remained significant after adjustment for PWVc-f confounders and antihypertensive treatment.
Alterations in collagen turnover that favor collagen type I synthesis; as well as proMMP-1 expression are related to increased aortic stiffness in treated hypertensive individuals without left ventricular (LV) hypertrophy.
American Journal of Hypertension 05/2010; 23(5):488-94. · 3.18 Impact Factor
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ABSTRACT: In this experimental study, we investigated the possibility of bacterial translocation, constituting a potential cause of infectious complications, after performing large volume hepatic radiofrequency ablation (RFA).
Wistar rats were subjected to RFA of the left median liver lobe (approximately 28.5% of the liver volume) after midline laparotomy. At 30 min, 24 h, 48 h, 72 h or 1 wk postoperatively, (1) blood samples were collected from the portal and systemic circulation for assessment of endotoxin concentration, (2) tissue specimens were excised from mesenteric lymph nodes, non-ablated liver, pancreas, spleen, kidneys, and lungs for bacterial culture, and (3) segments of terminal ileum were excised for histopathologic examination, morphometric analysis, and apoptotic and mitotic rate estimation. At 1 and 48 h, ileal mucosa was collected for oxidative state assessment on the basis of glutathione to glutathione disulfate (GSH/GSSG) ratio.
Endotoxin levels were increased in both the portal and systemic circulation. Intestinal bacteria were isolated from all the organs at all time points. Ileal mucosa became gradually atrophic, with a decrease in villous height and density. There was an increase of crypt apoptotic rate, a decrease of GSH/GSSG ratio, while there were only mild signs of inflammation.
Large volume liver RFA in the rat resulted to endotoxemia and translocation of intestinal bacteria to proximal and distal to the intestine organs at both the early and late post-RFA periods. The intestinal mucosa barrier was disrupted as suggested by ileal mucosal atrophy, increased crypt apoptosis, and induction of oxidative stress.
Journal of Surgical Research 03/2009; 161(2):250-8. · 2.25 Impact Factor
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ABSTRACT: We investigated the role of the prophylactic administration of the antioxidant 2-mercaptoethane sulfonate (mesna) on the hepatocyte-regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver.
Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor-kappaB (NF-kappaB) activity were assessed.
Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF-kappaB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF-kappaB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle-induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF-kappaB, while attenuating liver injury after PH under Pringle.
The excessive activation of NF-kappaB is related to the suppression of hepatocyte-regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle-induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF-kappaB activation.
Journal of Gastroenterology and Hepatology 12/2008; 24(4):623-32. · 2.87 Impact Factor
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ABSTRACT: Radiofrequency ablation (RFA) of the liver leads to reduction of liver parenchymal volume. We sought to evaluate the regenerative response of the liver following RFA.
Thirty healthy New Zealand white rabbits were subjected to a single session liver RFA using a cool-tip electrode after midline laparotomy. The regenerative process of the liver was assessed at various time-points (0 h, 48 h, 1 wk, 3 wk, 10 wk) in terms of computed tomography-based liver volume measurements, histological examination, hepatocyte mitotic activity, and serum biochemistry.
According to computed tomography-measurements, intact liver volume was gradually restored to the initial liver volume by the 10th week, while liver ablated volume was confined down to 50% of the initial ablated volume. At histology, inflammation, edema, and hepatocellular necrosis in the intact liver parenchyma, noted at 48 h, started to regress by 1 wk. Mitotic activity, initiated by 48 h, was substantially increased at 1 wk and remained high up to the 10th week. Serum transaminase levels were elevated up to 1 wk.
Liver RFA triggers a slow but sustained regenerative response of the liver with subsequent delayed restoration of parenchymal volume, while the ablated volume is gradually condensed.
Journal of Surgical Research 11/2007; 150(1):60-5. · 2.25 Impact Factor
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Petros Ypsilantis,
Maria Politou,
Dimitrios Mikroulis,
Michail Pitiakoudis,
Maria Lambropoulou, Christina Tsigalou,
Vasilios Didilis,
Georgios Bougioukas,
Nikolaos Papadopoulos,
Constantinos Manolas,
Constantinos Simopoulos
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ABSTRACT: Prolonged administration of propofol at large doses has been implicated in propofol infusion syndrome in intensive care unit patients. In this study we investigated organ toxicity and mortality of propofol sedation at large doses in prolonged mechanically ventilated rabbits and determined the role of propofol's lipid vehicle.
Eighteen healthy male rabbits were endotracheally intubated and sedated with propofol 2% (Group P), sevoflurane (Group S) or sevoflurane while receiving Intralipid 10% (Group SI). Sedation lasted 48 h or until death (Group P) or the maximum surviving period of Group P (Groups S and SI). The initial propofol infusion rate (20 mg x kg(-1) x h(-1)) or sevoflurane concentration (1.5%) was adjusted, if needed, to maintain a standard level of sedation. Blood biochemical analysis was performed in serial blood samples and histologic examination in the heart, lungs, liver, gallbladder, kidneys, urinary bladder, and quadriceps femoris muscle at autopsy.
The mortality rate was 100% (surviving period, 26-38 h) for Group P, whereas 0% for Groups S and SI. The initial propofol infusion rate had to be increased up to 65.7 +/- 4.6 mg x kg(-1) x h(-1) and sevoflurane concentration up to 4%. Serum liver function indices, lipids and creatine kinase were significantly increased (P < 0.05) in Groups P and SI and lactate was increased only in Group P, whereas amylase was increased in all groups. In Group P, histologic examination revealed myocarditis, pulmonary edema with interstitial pneumonia, hepatitis, steatosis, and focal liver necrosis, cholangitis, gallbladder necrosis, acute tubular necrosis of the kidneys, focal loss of the urinary bladder epithelium, and rhabdomyolysis of skeletal muscles; in Group S, low-grade bronchitis and incipient inflammation of the liver and the kidneys; and in Group SI, low-grade bronchitis, liver steatosis and hepatitis, and incipient inflammation of the gallbladder, kidneys, and urinary bladder.
Continuous infusion of 2% propofol at large doses for the sedation of rabbits undergoing prolonged mechanical ventilation induced fatal multiorgan dysfunction syndrome similar to the propofol infusion syndrome seen in humans. Our novel findings including lung, liver, gallbladder, and urinary bladder injury were also noted. The role of propofol's lipid vehicle in the manifestation of the syndrome was minor. Sevoflurane proved to be a safe alternative medication for prolonged sedation.
Anesthesia and analgesia 08/2007; 105(1):155-66. · 3.08 Impact Factor
