Involvement of Oxygen-Derived Free Radicals in L-Arginine-Induced Acute Pancreatitis

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 × 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800 ± 3813 vs 6382 ± 184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00 ± 1.75 vs 0.28 ± 0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 ± 2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55 ± 0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.     

Influence of the timing of cardiac catheterization and the amount of contrast media on acute renal failure after cardiac surgery

Postoperative acute renal failure (ARF) is not uncommon after cardiac surgery and after angiography. However, limited information exists regarding the influence of the interval between cardiac catheterization and subsequent cardiac surgery and amount of contrast agent used during this procedure on the occurrence of postoperative ARF. Data for 423 consecutive adult patients who underwent elective cardiac surgery after cardiac catheterization were examined retrospectively. The influence of interval between cardiac catheterization and cardiac surgery on postoperative ARF (defined as postoperative serum creatinine > or =2 times baseline and >2 mg/dl and/or need for renal replacement therapy) was evaluated using multivariable logistic regression. ARF occurred in 24 patients (5.7%). Median time to angiography was 2 days (interquartile range 1 to 4.5), and median dose of contrast used was 1.36 ml/kg (interquartile range 1.12 to 1.69). Surgery on the day of cardiac catheterization was independently associated with increased risk of ARF (adjusted odds ratio 3.1, 95% confidence interval 1.1 to 8.8). This risk of ARF was highest in patients who underwent surgery on the same day as angiography and with a dose of contrast higher than median (14.6%) and lowest when surgery was delayed beyond 1 day of angiography and contrast dose was median or less (2.4%; adjusted odds ratio for same-day surgery and dose higher than median 4.2, 95% confidence interval 1.2 to 14.2). Cardiac surgery performed on the day of cardiac catheterization and higher dose of contrast agent used were both independently associated with increased risk of postoperative ARF. In conclusion, these findings suggest that delaying cardiac surgery beyond 24 hours of exposure to contrast agents (when feasible) and minimizing the use of these agents have significant potential to decrease the incidence of postoperative ARF in patients undergoing elective cardiac surgery.     

Early stage of adjuvant arthritis alters behavioral responses in male but not female rats

Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known about how inflammatory disease in its early stage, before any clinical manifestation, may affect general activity. The aim of this study was to compare the anxiety-like behaviour in the early stage of adjuvant arthritis (AA), and the paw edema, and corticosterone (CORT) levels in the developed stage of AA among male and female Long Evans rats. The behavioural activity was evaluated by elevated plus maze tests. These revealed significantly reduced number of entries into the open arm of the maze in arthritic males compared to controls or to females 4 days after AA induction. Arthrihtic and control females did not differ. The number of entries into the closed arm of the maze was the same across the genders and studied intervals. Time spent in the open arm was significantly lower in arthritic males against controls or arthitic females. Time spent in the closed arm showed inverse picture to the time spent in the open arm. Hind paw swelling measured on day 23 of AA was the same in males and females, as was the elevation of CORT levels in plasma. Male rats showed anxiety-like behaviour on day 4 of AA, while female rats did not show any change, indicating different brain sensitivity to early inflammation among the genders.     

Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4–6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, -buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC₅₀ of 10⁻⁴ M, after 48–72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10⁻⁴ M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.     

Genetic and clinical characterization of sporadic cystic parathyroid tumours

objective The hyperparathyroidism–jaw tumour (HPT–JT) syndrome is one of the familial disorders characterized by primary hyperparathyroidism and has been linked to the chromosomal region of 1q32–q21. The parathyroid tumours related to this syndrome have shown loss of wild‐type alleles at this locus suggesting that inactivation of a tumour suppressor gene might be responsible for the disease. In the majority of these tumours cysts are a prominent feature. By loss of heterozygosity (LOH) studies, we investigated the region of interest in an attempt to clarify its possible role in a series of cystic sporadic parathyroid adenomas. design and subjects A total of 30 patients diagnosed with sporadic hyperparathyroidism were included in the study, genotyped with 17 polymorphic microsatellite markers at chromosome 1q, and additional markers from 1p and 11q13 which are commonly involved in sporadic parathyroid tumours. The cystic parathyroid tumours were characterized clinically, and immunohistochemistry against PTH was carried out to confirm the parathyroid origin of the cysts. results LOH was found in six of 30 tumours (20%) on 1q, six of 30 tumours (20%) on 1p and five of 30 tumours (17%) on 11q13. We found a significant correlation between allelic alterations and the clinical parameters, tumour weight and PTH. Furthermore, we found a significant difference between tumour weight and PTH in cases of cystic parathyroid tumours compared with unselected sporadic cases. conclusions These results suggest that cystic parathyroid tumours might represent a new subgroup among parathyroid tumours based on the genetic and clinical findings. Loss of heterozygosity at 1q further supports the presence of a tumour suppressor gene at this locus.     

Transhepatic fibrinolysis of mesenteric and portal vein thrombosis in a patient with ulcerative colitis： A case report

AIM: To present a case of acute mesenteric and portal vein thrombosis treated with thrombolytic therapy in a patient with ulcerative colitis in acute phase and to review the literature on thrombolytic therapy of mesenteric-portal system. Treatment of acute portal vein thrombosis has ranged from conservative treatment with thrombolysis and anticoagulation therapy to surgical treatment with thrombectomy and/or intestinal resection. METHODS: We treated our patient with intraportal infusion of plasminogen activator and then heparin through a percutaneous transhepatic catheter. RESULTS: Thrombus resolved despite premature interruption of the thrombolytic treatment for neurological complications, which subsequently resolved. CONCLUSION: Conservative management with plasminogen activator, could be considered as a good treatment for patients with acute porto-mesenteric thrombosis.     

Lack of amyloid in abdominal fat aspirates from patients undergoing long-term hemodialysis

Recent reports describe the carpal tunnel syndrome (CTS) due to amyloid infiltration of the beta 2 microglobulin protein as a frequent complication of long-term hemodialysis. Carpal synovial and cystic bone lesion amyloid deposits have been reported; however, the extent of systemic amyloid deposition has not been determined. We examined 30 patients undergoing long-term hemodialysis for CTS and performed abdominal fat tissue aspiration for amyloid staining to evaluate the presence of systemic amyloid disease. In this group, CTS was frequent (37%) and its prevalence correlated with the duration of hemodialysis. In all patients, the abdominal fat tissue, stained with Congo red, was negative for amyloid deposits. These results confirm that CTS is a frequent complication of long-term hemodialysis; however, in this study, no detectable amyloid deposits were found in abdominal subcutaneous fat tissue. Thus, abdominal fat aspiration may not be a reliable screening test for hemodialysis-associated amyloidosis.     

Effects of intracoronary streptokinase in acute myocardial infarction

Intracoronary streptokinase (SK) was administered to 11 patients with evolving acute transmural myocardial infarction 5.5 ± 0.4 hours from the onset of symptoms. Ten patients (91%) had total coronary occlusion, and one had subocclusion of the vessel corresponding to the ECG site of infarction. Intracoronary nitroglycerin failed to restore patency of total occlusion in all patients. In 9 of 11 patients (82%), patency was restored or improved with intracoronary SK. Thrombolysis was successful in 8 of 11 patients (73%), and one patient with transient patency developed acute reocclusion. Average time from SK infusion to reperfusion was 24 ± 7 minutes. Patients with successful thrombolysis had patency initially restored at a dosage of 61,000 ± 15,000 IU of SK and received a total dosage of 136,000 ± 17,000 IU. Patency persisted at late study in six of eight patients, and two patients developed late reocclusion. Successful thrombolysis was associated with significant improvement in left ventricular ejection fraction (LVEF) from early to late study, in contrast to deterioration of LVEF in patients with unsuccessful recanalization (p < 0.001). Systemic fibrinolytic activity occurred in 8 of 11 patients at a mean dosage of 125,000 ± 15,000 IU of SK and was unassociated with significant bleeding. Significant decrease in hemoglobin concentration in the early hospital phase occurred in patients receiving SK but did not differ from decreases occurring in a matched control population receiving conventional therapy for infarction. Thus intracoronary thrombolysis with SK was successful in the majority of patients during the early phase of evolving transmural infarction, and successful thrombolysis was associated with significant improvement in LVEF. Systemic fibrinolysis occurs in most patients despite small total doses of SK, and the significant decrease in hemoglobin in these patients may be unrelated to SK, since similar changes occurred in a control population receiving conventional therapy.