Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

UNLABELLED: Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. RESULTS: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. CONCLUSIONS: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.

Apoptotic proteins and markers of differentiation in childhood pineal parenchymal tumors: relationships and prognostic value.

Pineal parenchymal tumors (PPTs) in children and adolescents are uncommon and more data on their biological activity and behavior are still needed. The aim of our study was to estimate the expression and prognostic value of some proteins regulating apoptosis and cell cycle as well as being markers of cellular differentiation in PPTs. Tumor specimens obtained from 27 patients who underwent surgical treatment for PPTs were evaluated in immuno-histochemical analysis. The expression of Bcl-2, Bax, p53, NSE (neuron specific enolase), GFAP (glial fibrillary acidic protein), beta-III tubulin and nestin were studied. Co-localization of two chosen antibodies (e.g. Bcl-2/Bax, BCl-2/NSE, p53/NSE, etc.) was also made with a scanning confocal microscope. Histopathological examination revealed: 15 pineocytomas, 1 intermediately differentiated PPT and 11 pineoblastomas. For further analysis two groups were created: Group I: patients with pineocytoma or intermediately differentiated PPTs (16 cases) Group II: patients with pineoblastoma (11 cases). A statistically significant positive correlation between patients' survival time and tubulin and NSE expression was found. Bcl-2, p53 and nestin correlated negatively with survival time.

Surgical management of pancreaticopleural fistulas.

BACKGROUND: Pancreaticopleural fistula is defined as a communication between the pancreatic duct and the pleural cavity. Initially, it is treated conservatively and endoscopically. Surgery is performed within a small group of patients in whom other therapeutic approaches failed. PATIENTS AND METHODS: In this retrospective study, nine patients with pancreaticopleural fistulas were treated. In 8 of nine patients, conservative treatment was used experimentally. Patients were considered as having a pancreaticopleural fistula before operation if a fistulous tract was seen on radiologic examination or if a large exudative pleural effusion was present with an amylase level > 5.000 U/L and total pleural fluid protein content > 3 g/L. All patients were evaluated for computed tomography (CT), ultrasonography (USG) examination and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The mean age of patients was 47 (35-51) years. Pancreatic effusion was present in the left pleural cavity in 6 cases, in the right cavity in 2 and on both sides in 1 case. The causes of fistula formation were as follows : chronic pancreatitis due to alcohol abuse--seven patients, rupture of the pancreas and main pancreatic duct due to trauma--one patient and pancreatolithiasis--1 patient. Endoscopic stenting of the main pancreatic duct was unsuccessful in all patients except one. Five patients underwent distal (n = 4) or corporocaudal pancreatectomy (n = 1) with splenectomy, two underwent pancreatic duct anastomosis with an intestinal loop (the Partington-Rochelle procedure) and one underwent pancreaticoduodenectomy. Postoperative complications were observed in two patients. There were no cases of hospital mortality. The mean time of hospitalization was 16 days. Seven patients reported for the follow-up examination in the postoperative period of 10 to 67 months. No recurrence of pleural effusion was noted in any case. CONCLUSION: Surgical treatment is effective and safe for the management of a pancreaticopleural fistula when conservative and endoscopic therapy has failed.

The role of melatonin in the neurodegenerative diseases.

Melatonin is a product of the pineal gland. Synthesis and release of this hormone is inhibited by light. The biological activity of melatonin is associated with its receptors--ML1 and ML2. Melatonin plays a role in the biologic regulation of circadian rhythms, sleep, mood, reproduction, tumor growth and aging. It may also modulate the activity of various receptors in cancer cells. The hormone is a free radical scavenger, an antioxidant and immunomodulatory agent. Antioxidant properties of melatonin are connected with its neuroprotective activity in several degenerative disorders. The etiology of the neurodegenerative diseases which are characterized by the progressive and irreversible destruction of specific neuronal populations is complex and multifactorial. One of causes of neurodegenerative damage in the nervous system is oxidative injury, which results from an inbalance between free radical formation and antioxidative mechanisms. The efficacy of melatonin in the inhibition of the oxidative stress was estimated in various neurodegenerative disorders whose pathogenesis is associated with cytotoxic activity of free oxygen radicals, such as Alzheimer's or Parkinson's disease. Melatonin may have a clinical potential for the treatment of neurodegenerative disorders in the central as well as peripheral nervous system. (Ref. 38.)

Neuroendocrine pancreatic carcinoma causing sinistral portal hypertension.

BACKGROUND: Non-functioning neuroendocrine pancreatic tumors are usually connected with non-specific syndromes. CASE REPORT: This case history presents the diagnosis and treatment of a non-functioning neuroendocrine pancreatic tumor causing sinistral portal hypertension and gastrointestinal bleeding in a 36-year-old man. RESULTS: A peripheral resection of the pancreas with splenectomy was performed. Intraoperative examination of the specimen revealed a malignant neoplasm, probably neuroendocrinal carcinoma. CONCLUSIONS: Peripheral resection of the pancreas with splenectomy treats not only the symptoms of segmental portal hypertension caused by pathology of this organ, but also allows the etiology of the disease to be determined.

Role of histamine in cardiac muscle function--an attempt at demonstrating the presence of intracellular histaminergic H2-type receptors.

BACKGROUND: Histamine is one of the biologically active substances that activate adenyl cyclase enzymatic system through H2 receptor. The aim of the study is demonstration of the presence of membranous histamine receptors in cardiomyocytes and determination of their role in function of the cardiac muscle cell. MATERIAL AND METHODS: The experiments were carried out on 20 rabbits divided into two experimental groups. Electric and mechanical activity of cardiac muscle trabecula was registered by glass microelectrodes' method in group I and by saccharose slit method in group II. RESULTS: In group I after administration of 2.5 microM x l-1 of histamine mean rhythm rate increased to 61 +/- 2.7 stimulations x min-1, contractile tone increased by 55.7 +/- 4.9% in relation to the control values, relaxation time shortened to 139.2 +/- 1.8 ms, while time to pike decreased to 229.6 +/- 2.5 ms. The following effects were observed after administration of 5 microM x l-1 of histamine: mean rhythm rate increased to 76.4 +/- 4.5 x min-1, amplitude of the potentials was unchanged, while their duration shortened to 227.7 +/- 3.2 ms, contractile tone increased by 122.4 +/- 12.9%, average. In group II contractile tone increased by mean 110%, time to pike decreased to 103 +/- 1.5 ms, while relaxation time--to 210.2 +/- 4.2 ms. Frequency of spontaneous stimulations as well as amplitude and duration of the action potential remained unchanged in all of the experiments. CONCLUSIONS: Positive chronotropic and inotropic action of histamine added to the extracellular fluid point to the presence of histaminergic receptor in rabbit's cardiac muscle. H2 histaminergic receptors are situated not only on the external surface of cellular membrane of rabbit's right heart atrium trabeculae, but also inside the cells. Experiments with histamine administration by the "cut end" method suggest that the role of intracellular H2 histaminergic receptors is associated with controlling the contractile processes of the cardiac muscle.