Effects of GYKI 52466 on early vasospasm in rats.

OBJECTIVE: The pathogenesis and treatment of cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) remains a matter of discussion. The authors investigated the efficacy of GYKI 52466, a 2,3-benzodiazepine that is a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist, in a rat femoral artery vasospasm model. METHODS: Twenty-seven Wistar albino rats were used in this study. The animals were divided into 3 groups of 9 animals each: sham-operated control (group 1), vasospasm group (group 2), and vasospasm-plus-treatment group (group 3). In groups 2 and 3, autologous blood (0.1 mL) was applied to a 1-cm segment of the femoral artery, which was then wrapped with a silicone cuff. One minute after blood application, the rats in group 3 received an intraperitoneal injection of 15 mg/kg GYKI 52466 every 12 h for 24 h. Responses to blood application and treatment were evaluated with light and electron microscopy examinations of femoral artery specimens at 72 h. RESULTS: On light microscope examination, the mean diameters of the arterial lumens in groups 1, 2, and 3 were 514.47+/-15.3, 317.63+/-12.1, and 503.91+/-9.6 microm, respectively. At 24 h, the mean arterial wall thickness in group 1 was 77.69+/-4.2 microm. This mean thickness in group 2 increased to 164.82+/-9.1 microm. After GYKI treatment in group 3, the mean arterial wall thickness measured 95.37+/-5.3 microm. In group 2 rats, electron microscopy demonstrated various changes including marked luminal narrowing and increased wall thickness in the femoral arterial wall. The most striking finding were the degenerative changes in the endothelium, which presented as a corrugated appearance of the internal elastic lamina. Rats in group 3 had endothelia that were slightly constricted and smooth muscle cells that were relaxed; changes in the vessel wall and internal elastic lamina were less prominent in these rats than in the rats of group 2. CONCLUSIONS: The results of the present study suggest that GYKI 52466 inhibited AMPA receptors and induced relaxation of smooth muscle cells in the wall of the femoral artery in a rat model. This substance may be a protective and therapeutic agent in the treatment of cerebral vasospasm.

CT in differential diagnosis of benign and malignant pleural disease.

BACKGROUND: CT plays a valuable role in assessment of patients with a wide variety of diseases of the pleura, and pulmonologists should be aware of the significance of different CT findings for the differential diagnosis of benign and malignant pleural diseases. METHODS: 155 patients with pleural disease who had undergone CT scans of the lungs and thorax before treatment were enrolled. We retrospectively reviewed CT findings in 146 patients with proven pleural disease. RESULTS: Fifty-nine of the cases were malignant, 87 of them had benign pleural diseases. CT findings that were helpful in distinguishing malignant from benign pleural disease were: 1) pleural nodularity; 2) rind; 3) mediastinal pleural involvement; and 4) pleural thickening greater than 1 cm. The sensitivities and specificities were 37%/97%, 22%/97%, 31%/85%, 35%/87%, respectively. CT findings differentiating malignant pleural mesothelioma from metastatic pleural disease were identified. Findings for malignant mesothelioma were as follows: 1) involvement of interlobar fissure (sensitivity 30%, specificity 92%), 2) pleural thickening greater than 1 cm (sensitivity 60%, specificity 77%). Whereas, findings for metastatic pleural disease were mediastinal/hilar lymph node enlargement and lung parenchymal involvement (P < .05). CONCLUSION: CT is helpful in the differential diagnosis of pleural diseases, particularly in differentiating malignant from benign conditions and metastatic pleural disease from malignant mesothelioma.

Time-level relationship for nitric oxide and the protective effects of aminoguanidine in experimental spinal cord injury.

BACKGROUND: The secondary injury process following spinal cord trauma has been shown to involve different mechanisms such as excessive release of excitatory amino-acids, and induction of free radical induced lipid peroxidation. In this experimental study, the time-level relationship of the nitric oxide and the neuroprotective effects of aminoguanidine were investigated in a rat spinal cord trauma model. METHODS: The experiments were performed on 63 Wistar albino rats divided into three groups; sham-operated control (Group 1), trauma created control (Group 2) and aminoguanidine group (Group 3). In groups 2 and 3, spinal cord trauma was produced at thoracic level by using weight the drop technique (at a severity of 50 gr-cm). After the trauma, the rats in Group 3, received an intraperitoneal injection of 100 mg/kg aminoquanidine twice a day for 3 days. The effects of the injury and the efficacy of aminoguanidine were determined based on biochemical parameters (lipid peroxidation and nitric oxide levels in tissue), and on light microscopy findings in cord tissue collected at different times post-injury. Biochemical parameters were performed one hour, three and five days after injury. Functional recovery was assessed at 3, and 5 days after cord trauma with the inclined-plane technique and Tarlov's motor grading scale. FINDINGS: Although there was no statistically significant difference at the 1(st) hour, the values of the tissue nitric oxide in trauma created controls were 42% higher on the 3(rd) day and 40% higher on the 5(th) day when compared with those in sham controls. The levels of the tissue lipid peroxidation in trauma created controls were 88% higher at the 1(st) hour and 52.8% higher on the 5(th) day when compared with shame controls, but there was no meaningful difference on the 3(rd) day. In the trauma created control group, the mean motor function scores decreased to 1.16 +/- 0.40 and to 1 +/- 0 on the 3(rd) and 5(th) day, respectively. In this group the mean values of the inclined plane were 39.16 +/- 2.04 on the 3(rd) day and 37.91 +/- 1.02 on the 5(th) day. No statistically significant difference was observed in both tissue lipid peroxidation and nitric oxide levels for all time points between the aminoguanidine group and the sham-operated controls (p>0.01). The motor function scores were observed as 2.16 +/- 0.40 on the 3(rd) day and as 3 +/- 0 on the 5(th) day in aminoguanidine group. These values were significantly higher than the trauma created controls (p<0.01). Aminoguanidin treatment also improved the inclined plane performance of the rats; In this group, the mean values of the inclined plane scores were 44.58 +/- 2.92 and 52.91 +/- 1.88 on the 3(rd) and 5(th) days, respectively. These values were significantly higher than the trauma created controls (p<0.01). INTERPRETATION: This study shows that the nitric oxide level does not increase in the spinal cord tissue during the first hour after the spinal cord trauma. It increases significantly in the spinal cord tissue not only three days but also five days following the trauma. Aminoguanidine treatment, which is started just after the trauma, can prevent both the nitric oxide production and lipid peroxidation in spinal cord tissue and it can improve the functional status of the animals. In this respect, aminoguanidine may have a potential role in the treatment of acute spinal cord injury.