NF‐κB activation mediates LPS‐or zymosan‐induced hypotension and inflammation reversed by BAY61‐3606, a selective Syk inhibitor,in rat models of septic and non‐septic shock

We have previously demonstrated that the activation of the spleen tyrosine kinase (Syk)/inhibitory‐κB (IκB)‐α/nuclear factor‐κB (NF‐κB) p65 signalling pathway contributes to hypotension and inflammatory response in a rat models of zymosan (ZYM)‐induced non‐septic shock. The purpose of this study was to further examine the possible mechanism underlying the effect of inhibition of Syk by BAY61‐3606 via NF‐κB activity at the level of nuclear translocation regarding the production of vasodilator and proinflammatory mediators in lipopolysaccharide (LPS) (septic)‐ and ZYM (non‐septic)‐induced shock. Administration of LPS (10 mg/kg, ip) or ZYM (500 mg/kg, ip) to male Wistar rats decreased mean arterial pressure and increased heart rate that was associated with an increase in the activities of cyclooxygenase and nitric oxide synthase, tumour necrosis factor‐α, and interleukin‐8 levels, and NF‐κB activation and nuclear translocation in sera and/or cardiovascular and renal tissues. BAY61‐3606 (3 mg/kg, ip), the selective Syk inhibitor, given 1 hour after LPS‐ or ZYM injection reversed all the above‐mentioned effects. These results suggest that Syk contributes to the LPS‐ or ZYM‐induced hypotension and inflammation associated with transactivation of NF‐κB in septic and non‐septic shock.     

Utilization of membrane filtration for preconcentration and determination of Cu(II) and Pb(II) in food,water and geological samples by atomic absorption spectrometry

A method for separation–preconcentration of Cu(II) and Pb(III) ions by membrane filtration has been presented. The analyte ions were collected on acetate membrane filter as their 1-2-pyridylazo 2-naphthol (PAN) complexes. The analytes were determined by flame atomic absorption spectrometry. The analytical parameters including pH, eluent type, sample volume, amount of PAN, etc. were examined in order to gain quantitative recoveries of analyte ions. The effects of foreign ions on the recoveries of analyte ions were also investigated. The detection limits by three sigma were found to be 1.2 and 3.5 μg L⁻¹ for Cu(II) and Pb(II), respectively. The preconcentration factor was 60 for Cu(II) and 20 for Pb(II). The validation of the presented procedure was checked by the analysis of certified reference materials. The optimized method was successfully applied to food, water and geological samples with good results.     

Acromesomelic dysplasia associated with mild lumbar spine stenosis

A rare case of acromesomelic dysplasia is reported. The radiological findings were consistent with shortness of all tubular bones, especially those of the forearms. There was also evidence of mild lumbar spine stenosis. Received: 16 June 1997; Revision received: 13 January 1998; Accepted: 24 March 1998     

Treatment of renal artery bifurcation stenosis due to fibromuscular dysplasia by kissing balloon technique and intrarenal stent deployment: A case report

Renal artery stenosis due to fibromuscular dysplasia is well treated by PTA, but in some cases repeat PTA or stent placement may be necessary. In this paper, we report a case of distal renal arterial lesion affecting both branches of the renal artery and complicated with a bifurcation aneurysm which was treated by kissing PTA and intrarenal stent placement in a hypertensive patient. Satisfactory angiographic result was achieved and the patient remained normotensive on no medication for nine months follow up period. In rare ocasions, renal artery stent placement even into intrarenal branches can be used safely and effectively.     

Diagnostic usefulness of carbohydrate antigen-125 in cancerous and noncancerous peritoneal effusions

Carbohydrate antigen-125 (CA-125) is a tumor marker that has been used for differential diagnosis of peritoneal malignancies. The aim of the present study was to evaluate the diagnostic usefulness of simultaneous quantification of CA-125 in peritoneal fluid and serum for abdominal cancer cases and noncancer diseases. Noncancer disease group included cirrhotic patients (n=28) and spontaneous bacterial peritonitis (SBP) patients (n=11). Abdominal cancer group was composed of histologically diagnosed various malignancies (n=10), such as gastric cancer. CA-125 levels were quantified by chemiluminescent enzyme immuno-assay. Diagnostic usefulness tests and receiver operating characteristics (ROC) curve analysis were performed for the levels of peritoneal fluid CA-125 (pCA-125) and serum CA-125 (sCA-125), and the ratio of pCA-125 to sCA-125 (p/sCA-125). The sCA-125 levels were significantly higher in noncancer patients than those in the cancer patients, while the pCA-125 levels showed no significant difference between the two groups. Notably, the p/sCA-125 ratio was significantly lower in the noncancer patients than that in the cancer patients. Area under the ROC curve was 0.267 for sCA-125, 0.542 for pCA-125 and 0.831 for p/sCA-125. The accepted cutoff values were the combination of values that gave the greatest diagnostic sensitivity plus specificity. Either sCA-125 or pCA-125 value gave lower diagnostic accuracy, whereas p/sCA-125 value demonstrated a significantly higher diagnostic accuracy (sensitivity-specificity pairs: 0.40-0.33 for sCA-125, 0.60-0.54 for pCA-125, and 0.80-0.72 for p/sCA-125, respectively). Hence, determination of p/sCA-125 improves the biochemical discrimination of abdominal cancerous cases from noncancerous diseases.     

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

PURPOSE: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. METHODS AND MATERIALS: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. RESULTS: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. CONCLUSIONS: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.