Role of the poly(ADP-ribose)polymerase activity in vancomycin-induced renal injury.

The aim of the present study was to investigate the role of poly(ADP-ribose)polymerase (PARP) activity in vancomycin (VCM)-induced renal injury and to determine whether 1,5-isoquinelinediol (ISO), a PARP inhibitor agent, could be offered as an alternative therapy in VCM-induced renal impairment. Rats were divided into four groups as follows: (i) control (Group 1); (ii) VCM-treated (Group 2); (iii) VCM plus ISO-treated (Group 3); and (iv) ISO-treated (Group 4). VCM (200mg/kg, i.p., twice daily) was administered to Groups 2 and 3 for 7 days. ISO (3mg/kg/day, i.p.) treatment was started 24h before the first administration of VCM and continued for 8 days. After the 14th VCM injection, the animals were placed in metabolic cages to collect urine samples. All the rats were sacrificed by decapitation, blood samples were taken in tubes and kidneys were excised immediately. Blood urea nitrogen (BUN) and plasma creatinine, and urinary N-acetyl-beta-d-glucosaminidase (NAG, a marker of renal tubular injury) were used as markers of VCM-induced renal injury in rats. Light microscopy was used to evaluate semi-quantitative analysis of the kidney sections. Poly(ADP-ribose) (PAR, the product of activated PARP) and PARP-1 expressions in renal tissues were demonstrated by immunohistochemistry and Western blot. VCM administration increased BUN levels from 8.07+/-0.75 mg/dL to 53.87+/-10.11 mg/dL. The plasma creatinine levels were 0.8+/-0.04 mg/dL and 3.38+/-0.51 mg/dL for the control and VCM-treated groups, respectively. Also, urinary excretion of NAG was increased after VCM injection. Besides, there was a significant dilatation of the renal tubules, eosinophilic casts within some tubules, desquamation and vacuolization of renal tubule epithelium, and interstitial tissue inflammation in VCM-treated rats. In VCM-treated rats, both PAR and PARP-1 expressions were increased in renal tubular cells. ISO treatment attenuated VCM-induced renal injury, as indicated by BUN and plasma creatinine levels, urinary NAG excretion, and renal histology. PARP inhibitor treatment also decreased PAR and PARP-1 protein expressions similar to that of controls. Herewith, the overactivation of the PARP pathway may have a role in VCM-induced renal impairment and pharmacological inhibition of this pathway might be an effective intervention to prevent VCM-induced acute renal injury.

Poly (ADP-ribose) polymerase as a potential target for the treatment of acute renal injury caused by lipopolysaccharide.

Recent studies have clearly reported that there is a relationship between endotoxemia and acute renal injury. The aim of this study was to investigate whether treatment with the new potent PARP inhibitor PJ34 could prevent the acute renal injury induced by lipopolysaccharide (LPS). Endotoxemia was induced by LPS injection (10 mg/kg, i.v.). LPS increased blood urea nitrogen (BUN) levels from 22 +/- 0.54 mg/dL to 45.7 +/- 5.79 mg/dL (p < 0.05). The plasma creatinine levels were 0.38 +/- 0.02 mg/dL and 0.47 +/- 0.03 mg/dL for the control and LPS groups, respectively. In addition, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular damage) was increased after LPS injection. By light microscopy, structural renal damage was observed in the LPS-treated group. However, PJ34 treatment (10 mg/kg, i.p.) attenuated LPS-induced renal injury, as indicated by plasma BUN and creatinine levels, urinary NAG excretion, and renal histology. These results indicated that the overactivation of the PARP pathway may have a role in LPS-induced renal impairment. Hence, pharmacological inhibition of this pathway might be an effective intervention to prevent endotoxin-induced acute renal injury.

Liver biopsy in the diagnosis of visceral leishmaniasis.

AIM: To determine whether liver biopsy might be useful in the diagnosis of visceral leishmaniasis when bone marrow examination and serologic tests are inconclusive. METHODS: Over a 10-year period, liver biopsy was performed in five children with suspected visceral leishmaniasis when indirect hemagglutination tests and bone marrow aspirations were not diagnostic. RESULTS: Leishmania amastigotes were seen in Kupffer cells in all patients. The accompanying liver histopathological findings were ischemic necrosis in two children, macrovesicular steatosis in two children, portal inflammatory inflammation in two children, and piecemeal necrosis in one child. During the study period, 32 additional pediatric visceral leishmaniasis cases were diagnosed by bone marrow examination. CONCLUSION: Liver biopsy can be recommended for diagnosing suspected visceral leishmaniasis in children when serology and bone marrow aspiration are inconclusive.

[A descending colon tumour prolapsing from anus: case report]. / Anüsten prolabe olan inen kolon tümörü: Olgu Sunumu.

Most colonic polyps are asymptomatic and the incidence rises during sixth and seventh decades. Symptoms and signs may vary with histological types and location. Clinical features include fresh rectal bleeding, mucoid diarrhea and prolapsus of stalked rectal polyps located near distal segment. Here we discuss a case with a rare clinical presentation, who had sessile malign villous adenoma located in the descending colon, which caused colocolic intussusception and prolapsed through the anus.

Abdominal tuberculosis in adolescents. Difficulties in diagnosis.

Since the nature of abdominal tuberculosis is mimicking a number of diseases, this may cause delayed diagnosis resulting in evident increased morbidity and mortality. Most of the time, serologic and bacteriologic tools are not enough. We report 3 adolescents with distinct presentations, one mimicking Crohn's disease, one with hepatitis, and the last one with ascites. Terminal ileitis and mesenteric lymphadenitis were found in laparotomy of the first case mimicking Crohn disease. Granulomatous hepatitis was found in the liver biopsy of the second patient, and peritonitis was found by laparoscopy of the third patient. Tuberculosis could be diagnosed merely by histopathologic investigation. All were treated successfully without complication.

A functional and histopathological comparison of proximal and distal saphenous vein contractility and morphology.

Variations in vascular reactivity and morphology of proximal and distal saphenous vein might affect its performance as a bypass conduit. Because peri- or postoperative graft spasm or intimal hyperplasia reduces patency, we compared the reactivity and morphology of human proximal and distal saphenous vein conduits. Isometric tension studies were performed in response to potassium chloride (80 mM), phenylephrine (10(-8) - 10(-5) M), norepinephrine (10(-8) - 10(-5) M), and angiotensin II (10(-11) - 10(-7) M). Relaxant responses were tested with acetylcholine (10(-9) - 10(-5) M), sodium nitroprusside (10(-10) - 10(-6) M), and diltiazem (10(-10) - 10(-4) M). Also, vein segments from proximal and distal leg saphenous vein grafts were collected for histopathologic investigation. In proximal and distal saphenous vein segments, we also examined the structure of intima, media, and adventitia, and we evaluated the smooth muscle cell/extracellular matrix ratio in the media. There was no significant difference (P > 0.05) between proximal and distal venous segments in response to vasoconstrictors or vasodilators. Similarly, investigation by light microscopy was unable to show any significant difference between proximal and distal conduits in vascular structure. The smooth muscle cell/extracellular matrix ratio was also similar in these graft materials. Our failure to find functional or morphologic differences between proximal and distal saphenous vein segments suggests that there is no advantage in using one of these preparations over the other as a conduit in coronary artery bypass operations.

Two rare cases of the Pentalogy of Cantrell or its variants.

The Pentalogy of Cantrell (PC) is a rare association of defects involving the lower sternum, abdominal wall, diaphragm, pericardium and heart. We report two rare cases of the PC (variant form), showing fatal progression. Case 1 only survived two hours because of severe cardio-respiratory failure. Physical examination showed midline abdominal and thoracic defects, ectopic heart, pericardial defect, diaphragmatic defect, bilateral undescended testis, scoliosis, and adherence between left upper limb and trunk. In addition, the autopsy revealed diaphragmatic agenesia, intraabdominal testis, bilateral lung hypoplasia and lymphocytic meningitis. Case 2 only survived 15 minutes. In addition to the physical findings, including lower sternal defect, ectopic heart, epigastric omphalocele and scoliosis, the autopsy showed left diaphragmatic agenesia, pericardial agenesia, bilateral lung hypoplasia, deformed rib cage, anterior thoracic myeloschisis, adreno-hepatic fusion, left renal agenesia, meckel diverticulum and multiple accessory spleens. When comparing with other cases of PC, the concurrence of bilateral intraabdominal testis and lymphocytic meningitis in case 1, and adreno-hepatic fusion, anterior myeloschisis, meckel diverticulum, multiple accessory spleens, and renal agenesia in case 2 have not been described previously.

p27 Labeling index and proliferation in gastrointestinal stromal tumors: correlations with clinicopathologic factors and recurrence.

BACKGROUND: Low expression of p27, a cyclin-dependent kinase inhibitor, has recently been reported to be associated with poor prognosis of many tumors. Moreover, an inverse relationship between p27 expression and proliferation was also noted. Although accumulating data indicate a correlation between high proliferation rate and aggressive behavior of gastrointestinal stromal tumors, no conclusive correlation between p27 expression and either tumor recurrence or proliferation has been established yet in this disease. The aim of this study was to immunohistochemically investigate the association of p27 expression (as measured by the p27 labeling index: p27LI) with recurrence and proliferation (as measured by the Ki-67 labeling index: KLI) in gastrointestinal stromal tumors. METHODS: p27LI and KLI were investigated in tumor specimens from 50 patients diagnosed with gastrointestinal stromal tumors. Quantitative evaluations of p27LI and KLI were performed on tissue sections stained immunohistochemically with anti-p27 and anti-Ki-67 monoclonal antibodies. RESULTS: Both p27LI and KLI were associated with the presence of recurrence and high mitotic index. A significant inverse correlation was noted between p27LI and KLI (r = -0.82). The recurrence-free survival time was significantly shorter in patients with high KLI (> or = 10%), low p27LI (<18%), mitosis (> or = 4), and larger tumor size (> or = 5.2 cm). Multivariate analysis indicated that p27LI, KLI, and mitosis were independent predictors of recurrence-free survival. CONCLUSIONS: These findings support the view that p27LI is a reliable marker in predicting recurrence and recurrence-free survival in gastrointestinal stromal tumors. Moreover, the concordance of high KLI together with low p27LI, and vice versa, might allow us to measure the aggressiveness of these tumors.

Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries.

Recently, considerable attention has been focused on the role of the small heat-shock protein group hsp27, hsp70 and hsp90 in the clinical outcome of several malignancies. However, conflicting data exist regarding the prognostic role of hsp27 expression in ovarian carcinoma, and the prognostic significance of hsp70 and hsp90 expression still remains unknown in these tumours. The purpose of this study was to investigate immunohistochemically whether hsp27, hsp70 and hsp90 expression was associated with clinicopathological parameters and survival in 52 epithelial ovarian carcinomas. Chi-square test, Kaplan-Meier and Cox regression analysis were used for statistical analysis. Among clinicopathological parameters, hsp27, hsp70 and hsp90 expression was only correlated with FIGO stage; hsp70 and hsp90 positivity failed to detect survival. However, the overall survival rate of patients with hsp27 expression was 13%, which was significantly worse than that of patients without hsp27 expression (47%) (p<0.01). The prognosis was also adversely affected by FIGO stage (p<0.01) and presence of ascites (p<0.01). In multivariate analysis, hsp27 expression and FIGO stage were independent prognostic variables. Our results indicate that hsp70 and hsp90 expression had no prognostic relevance in epithelial ovarian carcinomas. However, hsp27 expression and FIGO stage in these tumours could be reliable indicators of prognosis.

Clinicopathologic evaluation of CDw75 antigen expression in colorectal adenocarcinomas.

CDw75, a B lymphocyte surface antigen, is a sialylated carbohydrate epitope, which is generated by the enzyme beta galactosyl alpha 2,6 sialyltransferase (Sia-T1). In colon carcinomas, although higher levels of Sia-T1 has been described and found to be correlated with metastatic potential of tumor cells, the expression of CDw75 antigen still remains unknown. To address this issue, we investigated immunohistochemically CDw75 antigen expression in 195 colorectal adenocarcinomas and their nodal metastases. The correlation between CDw75 antigen expression with selected clinicopathologic variables was analyzed by using Chi-square and Fisher s exact tests. Positive staining was observed in 101 cases. Non-neoplastic mucosa was negative consistently. The frequency of positivity was decreased according to the degree of differentiation (p<0.001). Antigen expression was found to be associated with deeper penetration (p<0.006), positive lymph nodes (p<0.001), distant metastases (p<0.006) and advanced stage (p<0.001). Same relationships were detected in well and moderately differentiated tumors when CDw75 immunoreactivity was evaluated in each histologic grade separately. Our findings indicate that CDw75 antigen expression may be a good indicator of the biological aggressiveness of colorectal adenocarcinomas especially in tumors with well and moderately differentiated morphology.