Dimitrios Giakoustidis

Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study

The CIAO Study (“C omplicated Intra-A bdominal infection O bservational” Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012).Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.2,152 patients with a mean age of 53.8 years (range: 4–98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified.The overall mortality rate was 7.5% (163/2.152).According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission.Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Intramuscular Administration of Very High Dose of a-Tocopherol Protects Liver from Severe Ischemia/Reperfusion Injury

The effect of intramuscular administration of high (30 mg/kg body weight for 3 days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was investigated. After a 60-minute period of total hepatic ischemia and 120 minutes of reperfusion, animals were killed, and liver samples were taken for determination of malondialdehyde (MDA) and histological examinations. Blood samples were also taken for assay of serum a-tocopherol, alanine transaminase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional animals were followed for a 7-day survival rate determination. Results showed that ischemia and reperfusion decreased the survival rate to 10%, whereas the levels of AST, ALT, and LDH in serum were increased compared with levels in animals that were sham operated. The MDA concentrations in liver were also increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol increased the viability to 50% and 70%, for the high and very high doses, respectively, and decreased the levels of AST, ALT, and LDH in serum. It also decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the high and very high doses of a-tocopherol, respectively, whereas it increased the level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very high doses, respectively. Histological examinations showed protection of the liver parenchyma in the animals treated with a-tocopherol.

Attenuation of intestinal ischemia/reperfusion induced liver and lung injury by intraperitoneal administration of (−)-Epigallocatechin-3-gallate

The aim of this study was to evaluate the effect of ( − )-epigallocatechin-3-gallate (EGCG), a natural antioxidant, on liver and lungs after warm intestinal ischemia/reperfusion (I/R). Thirty male Wistar rats were equally divided into a sham-operation group, an intestinal I/R group and an intestinal I/R group pretreated with EGCG intraperitoneally. Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 120 min. Immediately after reperfusion, liver, lung and blood samples were collected and analyzed. Results showed that intestinal I/R increased the levels of aspartate (AST) and alanine (ALT) transaminase in serum to 987 and 752 IU/l, respectively. Malondialdehyde (MDA) increased in liver to 1.524 nmol/g in the group subjected to intestinal I/R compared to 0.995 nmol/g in the sham operation group. MDA was also increased in lungs to 1.581 nmol/g compared to 0.896 nmol/g in the sham operation group. Myeloperoxidase (MPO) increased in liver, after intestinal I/R, to 5.16 U/g compared to 1.59 U/g in the sham operation group. MPO was also increased in lungs to 3.89 U/g compared to 1.65 U/g in the sham operation group. Pretreatment with EGCG decreased serum levels of AST and ALT to 236 and 178 IU/l, respectively. It also decreased mean MDA levels in liver and lungs to 1.061 and 1.008 nmol/g, respectively, and mean MPO levels in liver and lungs to 1.88 and 1.71 U/g, respectively. Light microscopy and transmission electron microscopy examinations showed significant alteration in liver and lungs and protection of liver and lung parenchyma in the animals treated with EGCG.

Attenuation of Liver Ischemia/Reperfusion Induced Apoptosis by Epigallocatechin-3-Gallate Via Down-Regulation of NF-κB and c-Jun Expression

INTRODUCTION Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and initiates severe oxidative stress with enhanced production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). ROS and TNF-alpha mediate the expression of nuclear factors and kinases, activating the signal transduction pathway, and triggering apoptosis. The aim of our study was to evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R. MATERIALS AND METHODS Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min by Pringles maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry for NF-kappaB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120min after reperfusion. RESULTS Apoptosis as indicated by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in the EGCG treated group. Liver was stained positive for NF-kappaB and c-Jun in the I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO, AST, and ALT showed marked increase in the I/R group and significant decrease in EGCG treated group. Significant alterations of liver specimens were observed by light histology and transmission electron microscopy whilst pretreatment with EGCG resulted in parenchymal preservation. CONCLUSIONS Administration of EGCG is likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF-kappaB and c-Jun signal transduction pathways.

The Protective Effect of α-Tocopherol and GdCl3 Against Hepatic Ischemia/Reperfusion Injury

PurposeTo evaluate the combined effect of α-tocopherol and gadolinium chloride (GdCl3) in reducing lipid peroxidation after severe hepatic ischemia/reperfusion (IR) injury.MethodsSixty male Wistar rats, 200–250 g, were randomly divided into six equal groups. There were two sham operation (SHAM) groups, two untreated IR groups, and two IR groups treated with GdCl3 and α-tocopherol (IRGT). After 60 min of total hepatic ischemia and 120 min reperfusion, one of each group was killed, liver samples were taken for malondialdehyde (MDA) and myeloperoxidase (MPO) analysis and light microscopy examination, and blood samples were analyzed for aspartate (AST) and alanine (ALT) transaminase, lactate dehydrogenase (LDH), and α-tocopherol content. The remaining groups were monitored for survival rate determination.ResultsThe mean MDA and MPO values in the SHAM, IR, and IRGT groups, respectively, were 1.117, 1.476, and 0.978 nmol/g wet tissue and 1.49, 6.26, and 1.78 (U/g). The mean α-tocopherol values in the SHAM, IR, and IRGT groups, respectively, were 10.4, 1.9, and 12 µmol/l. The mean serum AST, ALT, and LDH values were significantly higher in the IR group than in the SHAM group (P < 0.001), and significantly lower in the IRGT group than in the IR group (P < 0.001). Light microscopy examination revealed more severe congestion and vacuolization in the IR group than in the SHAM group, and minimal congestion and vacuolization in the IRGT group. Survival was significantly higher in the IRGT group than in the IR group.ConclusionThe administration of GdCl3 and α-tocopherol is likely to protect the liver against lipid peroxidation by suppressing Kupffer cell and polymorphonuclear leukocyte activation and enhancing endogenous antioxidant activity.

Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration

Intestinal ischemia/reperfusion (I/R) produces reactive oxygen species (ROS) activating signal transduction and apoptosis. The aim of this study was to evaluate the effect of (−)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kB, c-Jun and caspace-3 in intestinal I/R. Thirty male wistar rats were used. Group A sham operation, B I/R, C I/R-EGCG 50 mg/kg ip. Intestinal ischemia was induced for 60 min by clamping the superior mesenteric artery. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, Fragment End Labelling of DNA (TUNEL), immunocytochemistry for NF-kB, c-Jun and caspace-3 analysis in intestinal specimens were performed 120 min after reperfusion. Apoptosis as indicated by TUNEL and Caspace-3, NF-kB and c-Jun was widely expressed in I/R group but only slightly expressed in EGCG treated groups. MDA and MPO showed a marked increase in the I/R group and a significant decrease in the EGCG treated group. Light histology showed preservation of architecture in the EGCG treated group. In conclusion, EGCG pre-treatment is likely to inhibit intestinal I/R-induced apoptosis by down-regulating the expression of NF-kB, c-Jun and caspase-3.

Molecular signalling in hepatocellular carcinoma: Role of and crosstalk among WNT/ß-catenin, Sonic Hedgehog, Notch and Dickkopf-1.

Hepatocellular carcinoma is the sixth most common cancer worldwide. In the majority of cases, there is evidence of existing chronic liver disease from a variety of causes including viral hepatitis B and C, alcoholic liver disease and nonalcoholic steatohepatitis. Identification of the signalling pathways used by hepatocellular carcinoma cells to proliferate, invade or metastasize is of paramount importance in the discovery and implementation of successfully targeted therapies. Activation of Wnt/β-catenin, Notch and Hedgehog pathways play a critical role in regulating liver cell proliferation during development and in controlling crucial functions of the adult liver in the initiation and progression of human cancers. β-catenin was identified as a protein interacting with the cell adhesion molecule E-cadherin at the cell-cell junction, and has been shown to be one of the most important mediators of the Wnt signalling pathway in tumourigenesis. Investigations into the role of Dikkopf-1 in hepatocellular carcinoma have demonstrated controversial results, with a decreased expression of Dickkopf-1 and soluble frizzled-related protein in various cancers on one hand, and as a possible negative prognostic indicator of hepatocellular carcinoma on the other. In the present review, the authors focus on the Wnt⁄β-catenin, Notch and Sonic Hedgehog pathways, and their interaction with Dikkopf-1 in hepatocellular carcinoma.

Postoperative adhesion prevention using a statin-containing cellulose film in an experimental model.

Intraperitoneal adhesions are a common problem in abdominal surgery. The aim of this study was to compare the effectiveness of Statofilm, a novel antiadhesive film based on cross‐linked carboxymethylcellulose and atorvastatin, with that of sodium hyaluronate–carboxymethylcellulose (Seprafilm®) in the prevention of postoperative intraperitoneal adhesions in rats.

Impact of double-j ureteric stent in kidney transplantation: single-center experience.

We retrospectively evaluated the use of double-j stent and the incidence of urological complications in 2 groups of patients who received a kidney transplant. From January 2005 to September 2007 we studied 172 patients receiving kidney transplants, 65 and 107 from living and cadaver donors, respectively. From the 172 patients, a total of 34 were excluded due to ureterostomy or Politano-Leadbetter ureterovesical anastomosis. Another 21 patients were excluded from the study due to graft loss due to acute or hyperacute rejection, cytomegalovirus (CMV) infection, or vascular complication. The remaining patients were divided into 2 groups: group A (44 patients) and B (73 patients) with versus without the use of a double-j-stent, respectively. The 2 groups were comparable in terms of donor and recipient gender, ischemia time, and delayed graft function. We failed to observes significant differences between the 2 groups in mean hospital stay (23 +/- 9 and 19 +/- 9), urinary leak (2.3% and 4.1%), and urinary tract infection (20.4% and 19.2%), among groups A and B, respectively. The only difference observed concerned the gravity of the urinary leak; no surgical intervention was needed among the double-j stent group versus 2 patients demanding ureterovesical reconstruction in the nonstent group. In conclusion, our data suggested that the routine use of a double-j stent for ureterovesical anastomosis neither significantly increased urinary tract infection rates, nor decreased the incidence of urinary leaks, but may decrease the gravity of the latter as evidenced by the need for surgical intervention.

Severe total hepatic ischemia and reperfusion: Relationship between very high α-tocopherol uptake and lipid peroxidation

Reperfusion injury of the liver occurs in liver transplantation and in major hepatectomies. It triggers a severe oxidative stress that leads to increased lipid peroxidation. In our study we examined the effect of parenteral supranutritional administration of α-tocopherol, a vitamin that plays a key role in the endogenous antioxidant system, to rats subjected to severe ischemia/reperfusion (I/R) injury of the liver. α-Tocopherol was administered to the animals at doses of 30 and 300mg/kg bw, whereas total hepatic ischemia was induced for 60 min followed by 120 min reperfusion. Tissue and blood samples were collected for malonyldialdehyde (MDA) and serum α-tocopherol assay, respectively. In the sham operation group, mean MDA level in liver was 1.14nmole/g wet tissue in the control subgroup, and 1.01 or 0.74nmole/g wet tissue in the subgroups given 30 or 300mg/kg α-tocopherol. In the I/R group, mean MDA level was 1.57nmole/g wet tissue in the control subgroup, and 0.97 and 0.77nmole/g wet tissue in the subgroups given 30 or 300mg/kg α-tocopherol. Mean levels of α-tocopherol in serum (μmole/l) were 10.20 and 1.80 in the control subgroups, 25.28 and 11.25 in the subgroups treated with 30 and 300mg/kg bw of α-tocopherol, and 31.00 and 13.02 in the subgroups treated with 30 and 300mg/kg bw of α-tocopherol, within the sham-operation and I/R groups, respectively. A significant decrease of MDA accompanied by a significant increase of serum α-tocopherol was documented in the α-tocopherol-treated rats within both groups. Ischemia/reperfusion triggered a significant increase of the MDA level in the liver of the rats not treated with α-tocopherol as compares with the treated animals.