Yavuz Kaya

Abdominal insufflation-deflation injury in small intestine in rabbits.

OBJECTIVE To investigate the effect of increased intra-abdominal pressure followed by abdominal deflation on small intestine with or without previous intestinal ischaemia. DESIGN Randomised experimental study. SETTING University hospital, Turkey. ANIMALS 78 male New Zealand white rabbits. INTERVENTIONS Experiment 1: 30 rabbits (10 in each group) were subjected to intra-abdominal pressure of 0 mmHg (controls), 15 mmHg or 25 mmHg for 60 minutes. Experiment 2: 48 rabbits were divided into four groups (n = 12 in each). The first comprised sham-operated controls. In the other 3, the superior mesenteric artery was occluded for 60 minutes. Reperfusion was started and maintained under intra-abdominal pressure of 0 mmHg, 15 mmHg, or 25 mmHg for one hour. Intestinal specimens were obtained five and 60 minutes after abdominal deflation in the pressure groups and at identical times in the other groups in both experiments. MAIN OUTCOME MEASURES Intestinal malondialdehyde concentration, wet:dry intestinal weight ratio, and mucosal injury score under light microscopy. RESULTS In experiment I the malondialdehyde concentration, wet:dry weight ratio, and mucosal injury scores were higher in the 25 mmHg group than in the other groups in both specimens. There was a significant increase in malondialdehyde concentration in the 15 mmHg group in only the 5-minute specimen. In experiment 2, except for the wet:dry weight ratio in the 5-minute specimen in the 15 mmHg group, there were significant increases in malondialdehyde concentration, wet:dry weight ratio, and mucosal injury score in all groups except controls in both specimens. Malondialdehyde concentration and wet:dry weight ratio were higher in the 25 mmHg group than in the 0 mmHg group in the 60-minute specimen, and higher than the 15 mmHg group in both specimens. Wet:dry weight ratio was less in the 15 mmHg group than the 0 mmHg group in both specimens. Mucosal injury score was higher in the 25 mmHg group than the other groups in both specimens. CONCLUSION Increased intra-abdominal pressure for 60 minutes followed by abdominal deflation led to an ischaemia-reperfusion-like injury in normal small intestine in rabbits, and added to reperfusion injury in the ischaemic small intestine at an intra-abdominal pressure of 25 mmHg.

Effects of silymarin and pentoxifylline on matrix metalloproteinase-1 and -2 expression and apoptosis in experimental hepatic fibrosis

BACKGROUND Many therapeutic strategies have been proposed to treat liver fibrosis, but no drugs have been proved effective. Matrix metalloproteinases (MMPs) have been reported to play a role in some cellular cascades of hepatic inflammation and fibrosis. OBJECTIVE The purpose of this study was to investigate whether silymarin and pentoxifylline (PTX) have hepatoprotective and antifibrotic effects in experimental hepatic fibrosis. METHODS Sprague-Dawley rats were divided into 4 groups: silymarin group (silymarin 4 mg/kg · d(-1) orally, common bile duct ligation [CBDL]); PTX group (PTX 2 mg/kg · d(-1) intraperitoneally, CBDL); sham group (common bile duct [CBD] exploration only); and control group (saline 1 mL/d orally, CBDL). The CBD was explored and dissected sufficiently to allow passage of a 3/0 silk suture via midline laparotomy. On day 10, all animals were euthanized via cervical dislocation. Then, 5-cm(3) liver samples from the right lobe were removed for histomorphologic evaluation and 3-mL blood samples were taken via cardiac puncture for biochemical analyses. Apoptosis was determined using the terminal deoxynucleotidyltransferase-biotin nick end-label (TUNEL) staining method. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase; total and indirect bilirubin concentration; hepatic MMP-1 and -2 and tissue inhibitor of MMP (TIMP)-l and -2 activity; and transforming-growth factor (TGF)-β1 concentration were measured. Collagen content was determined by measuring hydroxyproline in liver samples. Malondialdehyde (MDA) was used to estimate lipid peroxidation. RESULTS Thirty-two adult male Sprague-Dawley rats were divided into 4 groups: silymarin group (n = 7), PTX group (n = 7), sham group (n = 9), and control group (n = 9). Compared with the control group (14.6 [2.44]), mean (SD) hepatocyte apoptosis (as measured by the ratio of TUNEL-positive cells) was significantly suppressed in the silymarin group (1.2 [0.13]; P = 0.001) and the PTX group (3.8 [0.34]; P = 0.001). Mean (SD) MMP-2 activity in the silymarin group (57.35 [9.89] μg/mL; P = 0.04) and the PTX group (46.88 [9.56] μg/mL; P = 0.04) was significantly lower than that observed in the control group (232.32 [79.76] μg/mL). Compared with the control group (1.37 [0.38] μg/mL), TIMP-2 activity was significantly lower in the silymarin group (0.55 [0.13] μg/mL; P = 0.04) and the PTX group (0.42 [0.09] μg/mL; P = 0.01). Compared with the control group (909.17 [117.35] μg/mL), TGF-β1 was significantly lower in the silymarin group (518.24 [30.34] μg/mL; P = 0.01) and the PTX group (519.57 [47.27] μg/mL; P = 0.01). Histomorphologic changes were significantly greater in the sham group than in the silymarin and PTX groups: hemorrhage (2.44 [0.29] vs 1.29 [0.18] and 1.57 [0.20], respectively; both, P = 0.04); sinusoidal dilatation (2.22 [0.22] vs 1.57 [0.20] and 1.71 [0.18]; both, P = 0.04); presinusoidal polymorphonuclear cell infiltration (3-44 [0.24] vs 2.57 [0.20] and 2.14 [0.26]; P = 0.03 and P = 0.008, respectively); and inflammation (3.44 [0.24] vs 2.57 [0.20] and 2.14 [0.26]; P = 0.03 and P = 0.008, respectively). In the control group, all biochemical markers were elevated, supporting the presence of liver injury. Compared with the control group (630.00 [46.80] U/L), plasma AST activity was significantly lower in the silymarin group (443.11 [78.73]; P = 0.04) and the PTX group (349.42 [34.00]; P = 0.03). Compared with the control group (191.12 [32.93] U/L), plasma ALT activity was significantly lower in the silymarin group (86.14 [4.97]; P = 0.04) and the PTX group (84.14 [11.21]; P = 0.04). MDA concentration was significantly lower in the silymarin group compared with the control group (0.08 [0.01] vs 0.22 [0.03] nmol/mL; P = 0.004); MDA was also significantly lower in the silymarin group than in the PTX group (0.11 [0.02]; P = 0.03). CONCLUSIONS Silymarin and PTX were associated with lower histopathologic liver damage, hepatocyte apoptosis, and regulation of extracellular matrix proteins. Lipid peroxidation in hepatocytes was significantly lower in the silymarin group compared with the PTX group. Silymarin and PTX appeared to have hepatoprotective effects in this experimental liver fibrosis model, but further clinical and experimental studies are needed.

Inguinal keratotic Basal cell carcinoma mimicking giant solitary trichoepithelioma.

Keratotic basal cell carcinoma may not only clinically but also histologically share more or less the same features with giant solitary trichoepithelioma. It can be difficult to distinguish these two entities from each other, even for an experienced dermatopathologist. We present an unusual case of inguinal keratotic basal cell carcinoma mimicking giant solitary trichoepithelioma in a 56‐year‐old woman with a finger‐like tumor of 20 years duration. The patient presented with an asymptomatic, skin colored, firm, nonulcerative, nodular lesion. Scanty mitotic activity and apoptotic cells were the histopathologic findings against basal cell carcinoma, whereas absence of papillary mesenchymal bodies, presence of peritumoral lacunae detected only around the solid areas, and accumulation of amyloid‐like hyalinized material were the findings in favor of basal cell carcinoma. This case illustrates that keratotic basal cell carcinoma must be taken into account in the differential diagnosis of inguinally located solitary, polypoid masses, especially giant solitary trichoepithelioma.

The Effect of Tadalafil on Anastomotic Healing in Ischemic Small Intestine in Rats

PurposeTo investigate the effect of tadalafil on anastomotic healing in an ischemic small intestine.MethodsStandardized transection and anastomosis in the small intestine were performed in 48 male Sprague-Dawley rats divided into four equal groups (n = 12): group 1, normal anastomosis; group 2, ischemic anastomosis; group 3, normal anastomosis+tadalafil treatment; group 4, ischemic anastomosis+tadalafil treatment. Ischemia was established by ligating 2 cm of mesentery on either side of the anastomosis. Tadalafil was given to the rats once a day at dose of 5 mg/kg. The anastomotic bursting pressures and hydroxyproline concentrations were measured on postoperative day 4. A histopathological evaluation of the anastomoses was also performed.ResultsThe bursting pressure and hydroxyproline concentration in group 2 were significantly lower than those in the other groups. There was no difference in the hydroxyproline concentration among groups 1, 3, and 4. While there was no difference between groups 3 and 4, the bursting pressures were significantly higher in groups 3 and 4 than in group 1. The histopathological evaluation revealed no significant differences in inflammatory cell infiltration, vascularization, or anastomotic collagen deposition among the groups.ConclusionTadalafil treatment improved the anastomotic bursting pressure and the hydroxyproline concentration in both normal and ischemic small intestine anastomosis.

Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

PURPOSE It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. MATERIALS AND METHODS Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Students t test was used for statistical analyses. RESULTS In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p<0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. CONCLUSION The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

Effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial dysfunction, lipid peroxidation, and hepatocyte morphology in rats with sepsis-induced liver damage

BACKGROUND Sepsis remains a difficult problem for clinicians, with its systemic effects and high morbidity and mortality rates. The roles of oxidative stress, endothelial dysfunction, and lipid peroxidation in sepsis-induced organ damage are being investigated. OBJECTIVE The aim of this study was to investigate the effects of selective cyclooxygenase (COX)-2 inhibition on tissue lipid peroxidation, endothelial dysfunction, and hepatic cell morphology in a rat model of sepsis. METHODS Thirty rats with sepsis induced by cecal ligation and puncture were divided equally into 3 groups: treatment group (rofecoxib 1 mg/kg PO), control group (saline 1 mL PO), and sham group (sham surgery only). All the rats were sacrificed 1 day after sepsis induction. The livers were removed using a median laparotomy for histopathologic and biochemical analysis. RESULTS Histomorphologic hepatic damage and lipid peroxidation were significantly reduced in the rofecoxib treatment group compared with the control group (P < 0.05 and P = 0.001, respectively). Endothelial nitric oxide synthase and inducible nitric oxide synthase staining of liver samples was statistically significantly reduced in the treatment group compared with the control group (both, P < 0.001). The hepatic nitric oxide level and malonyldialdehyde activity decreased significantly (P < 0.001 and P = 0.001, respectively) in the rofecoxib group compared with the control group. Hepatic myeloperoxidase activity was similar between the treatment and control groups. CONCLUSION Further investigation of selective COX-2 inhibition as an alternate therapeutic choice for sepsis-induced hepatic damage should be considered.

AKUT KOLESİSTİTİN TANISINDA POWER DOPPLER USLTRASONOGRAFİK-PATOLOJİK KORELASYON

Power Doppler ultrasonography is a new Doppler examination technique which is relatively independent from flow and angle, and it is superior to color Doppler ultrasonography to display small vessels and slow lows. The aim of this study was to investigate the role of Power Doppler ultrasonography in diagnosing acute cholecystitis and differentiating acute from chronic cholecystitis. In one hundred twenty patients with acute right upper quadrant pain or clinically suspected cholecystitis, gallbladder wall vascularity underwent color Doppler ultrasonography and Power Doppler ultrasonography as an adjunct to gray-scale ultrasonography. Imaging findings were compared with pathologic findings in the 48 patients who underwent cholecystectomy. In histopathologic examinations of the operated 48 patients, 23 patients had acute cholecystitis, 25 patients had chronic cholecystitis. With power Doppler ultrasonography, 22 (95%) of 23 patients with acute cholecystitis had hypervascularity in gallbladder wall. Sensitivity and specificity of Power Doppler ultrasonography for revealing acute cholecystitis were 95% and 100%, respectively. As a result, Power Doppler ultrasonography is a very sensitive method for diagnosing acute cholecystitis and differentiating it from chronic cholecystitis. It should be routinely performed in patients with suspected cholecystitis to improve the diagnostic capabilities of gray-scale ultrasonography.