The imbalance between matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in acute pancreatitis.

BACKGROUND: The balanced activity of matrix metalloproteinases and their tissue inhibitors is an important, albeit still not completely understood, determinant of extracellular matrix homeostasis, a factor involved in the pathogenesis of acute pancreatitis (AP). AIMS: The aim of this study was to compare serum concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) in patients with AP of various severity and to investigate their relationship with prognostic indicators of AP severity, e.g., polymorphonuclear leukocyte elastase (PMN-E). PATIENTS AND METHODS: The study included 37 patients with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on days 2, 3, 5 and 10. RESULTS: Throughout the study period, the serum MMP-9 concentration in patients with severe AP was significantly higher than those in individuals with mild AP and in healthy controls. In turn, the serum MMP-9 concentrations in persons with mild AP did not differ significantly from those of the controls. The serum TIMP-1 concentrations in both groups were significantly higher than in the controls. Beginning from the 2(nd) day of hospital stay, the serum TIMP-1 concentration in patients with severe AP was significantly higher than in individuals with mild AP. There were significant correlations between: MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1. CONCLUSION: A disturbed balance between MMP-9 and TIMP-1 observed during the early stages of severe AP suggests that endogenous TIMP-1 is unable to prevent excessive activation and release of MMP-9. MMP-9 may represent a new marker of AP severity.

Creatinine or cystatin C - which is a better index of renal function in morbid obesity?

PURPOSE: The most important index of renal function is estimated glomerular filtration rate (eGFR) which can be calculated from creatinine or cystatin C concentration in serum. There is uncertainty, which formula is best suited to assess renal function in morbidly obese patients. The aim of this study was to evaluate eGFR in patients with morbid obesity using formulas: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Grubb, Le Bricon, Hoek, Larsson, and to compare the obtained results. MATERIAL AND METHODS: In 40 morbidly obese patients, serum concentration of cystatin C and creatinine were assayed. Values of eGFR were calculated using the above-mentioned formulas. RESULTS: The mean value of eGFR ranged from 85.9 to 111.1 ml/min/1.73 m², depending on the formula. The biggest difference between the obtained values was 29% (Grubb vs. Hoek p<0.01). After calculation of eGFR from creatinine concentration (MDRD), 7 patients were qualified to the 2nd and 3rd stage of chronic renal disease, while application of Hoek's formula, based on cystatin C concentration, allotted 27 patients to 2nd and 3rd stage of chronic renal disease. Le Bricon formula gave eGFR values, that correlated best with albuminuria. CONCLUSION: eGFR calculated using Le Bricon formula based on the cystatin C concentration was significantly lower than eGFR calculated from creatinine concentration and was more closely associated with albuminuria. Relying only on creatinine concentration to estimate glomerular filtration rate can lead to underestimation of renal malfunction in obese patients.

Serum profiles of E-selectin, interleukin-10, and interleukin-6 and oxidative stress parameters in patients with acute pancreatitis and nonpancreatic acute abdominal pain.

INTRODUCTION: Excessive inflammatory response is one of the major causes of early mortality in acute pancreatitis (AP). AIM: To evaluate the serum profiles of E-selectin, interleukin (IL)-6, and IL-10 along with their correlation to the markers of oxidative stress and neutrophil activation in patients with AP and patients with nonpancreatic acute abdominal pain (NPAAP). METHODOLOGY: This prospective clinical study included 56 patients with AP (28 with mild AP and 28 with severe AP) as well as 15 patients with NPAAP. RESULTS: Serum concentrations of E-selectin, IL-10, and IL-6 and plasma concentrations of polymorphonuclear leukocyte elastase (determined on days 1-3, 5, and 10 after admission) were the highest in severe AP during the first 3 days and then declined. At day 10, the E-selectin level in severe AP was still higher than that in mild AP, and the IL-10 concentration increased again. There was no elevation in the E-selectin concentration in NPAAP patients, and IL-10 levels remained unchanged in mild AP. Oxidative stress, measured by serum malondialdehyde and 4-hydroxyalkenals levels, was the most pronounced in severe AP. CONCLUSIONS: The serum E-selectin concentration is markedly elevated in severe AP and is less in mild AP but not in NPAAP. It may result from stimulation with different inflammatory mediators or indicate vascular endothelium injury mediated by oxidative stress, especially in the severe form of AP.

Serum profiles of interleukin-18 in different severity forms of human acute pancreatitis.

BACKGROUND: Interleukin 18 (IL-18) is a new mediator and modulator of the immune response; its role in acute pancreatitis (AP), however, has not yet been fully explained. The aim of our study was to evaluate the profile IL-18 serum concentrations in the course of acute pancreatitis. METHODS: The prospective study involves 30 patients with AP (n = 15 with mild AP and n = 15 with severe AP) as well as 10 healthy subjects. AP severity was defined according to Ranson's and Balthazar's criteria, supplemented by serum CRP concentration measurements. In the course of hospitalization, 2 patients with severe AP died. Serum IL-18 and plasma polymorphonuclear leukocyte elastase (PMN-E) concentrations were measured at admission (day 1) and on days 2, 3, 5 and 10. RESULTS: In both the mild and the severe forms of AP, serum IL-18 concentration was significantly higher than in the healthy controls. In severe AP, serum IL-18 reached the highest levels in all observed periods compared to that in patients with mild AP. Significant correlations, calculated for day 1, were found between serum IL-18 and plasma PMN-E (Rs = 0.514. P < 0.001) and between IL-18 and CRP (Rs = 0.463, P < 0.001) levels. CONCLUSIONS: Serum profile IL-18 during AP indicates that this cytokine was released early after AP onset and may play the key role in inflammatory and immune response. Positive correlation between serum IL-18 and commonly known early prognostic markers of AP severity suggest that serum IL-18 concentrations may represent another early marker indicating severe course of AP.

Soluble selectin profiles associated with severe trauma.

Severe trauma acts as a trigger for the complex cascade of postinjury events leading to the release of different mediators and the development of generalized inflammation. Selectins are a family of adhesion proteins that are responsible for the adherence of polymorphonuclear neutrophils to the endothelium. This interaction plays an important role in the development of severe complications after multiple trauma. The aim of the present study is to follow the sequential alterations in circulating selectin levels after severe injury and to evaluate the clinical significance of these mediators in monitoring prognosis and outcome. Thirty four severely traumatized patients were entered into the study. Serum sE-selectin, plasma sP-selectin and sL-selectin concentrations were measured and an APACHE II score was calculated on admission to the intensive care unit and during the subsequent 5 days. The patients were divided into survivors and nonsurvivors. Initial soluble P- and E-selectin concentrations were significantly elevated in all trauma patients. The highest values of these adhesion molecules were measured in all the observed days in patients with poor prognosis and outcome. In survivors we found a systematic decrease in the sP-selectin concentrations. On admission, the sL-selectin concentrations in all trauma patients were decreased. There were stable, very low values in nonsurvivors and a slow increase in circulating L-selectin in patients who survived. The pattern of soluble selectins in patients with severe trauma is characterized by increased levels of P- and E-selectin and a decreased concentration of L-selectin. These findings suggest a widespread microvascular endothelial activation on injury in the early posttraumatic period, which may be associated with increased neutrophil-endothelial adhesion, neutrophil extravasation and migration. We suppose that these parameters of endothelial cell activation/injury may be useful as another early prognostic factor in severe trauma.

[Adhesion molecules and their role in organ response after trauma]. / Czasteczki adhezyjne i ich rola w odpowiedzi ustroju na uraz.

In this paper, we presented general characterization of adhesion molecules and their role in organ response after injury. Severe trauma is frequently complicated by multiple organ dysfunction (MODS) or failure (MOF). The pathogenesis of these syndromes involves a complex interaction of humoral and cellular events. The recruitment of circulatory leukocytes into tissues is regulated in part by specific leukocyte-endothelial cell interactions with several families of cell adhesion molecules. In the adhesion cascade, the initial phase of inflammation, a transient slowing of neutrophils in postcapillary venules is mediated by selectins. Firm adhesion of neutrophils to the endothelium occurs by interaction of beta 2 integrins to ICAM-1. Diapedesis between endothelial cells requires the engagement of PECAM-1. Significance of the adhesion molecule in organ response after severe trauma permitted their diagnostic and prognostic use as well as new methods of treatment.

[Effect of severe multiple trauma complicated by acute lung injury on endothelial cell activity]. / Wplyw ciezkiego urazu wielonarzadowego powiklanego ostrym uszkodzeniem pluc na aktywnosc komórek sródblonkowych.

The pulmonary endothelium synthesizes many bioactive compounds and their activation or injury may cause release these substances into the blood. We determined the influence of trauma severity for endothelium activation/injury by measurement of specific endothelial cell markers--soluble E-selectin (sES) and von Willebrand factor antigen (vWF:Ag). Thirty six severely traumatized patients were stratified according to an Injury Severity Score (ISS). Group I--patients with ISS > or = 35, Group II--patients with ISS < 35. Eleven healthy volunteers served as controls. Serum sES and plasma vWF:Ag concentrations were measured and PaO2/FiO2 ratio, Lung Injury Score (LIS) and APACHE II ratio were calculated at the admission to IC, after 24 h and on 2, 3, 5, 7, 10th day. In all investigated time periods, we observed significant increase in serum sES concentration among patients from group I, in comparison to initial value and control. On day 3, serum sES concentration was significantly increased in group I, in comparison to group II. In the first seven days, plasma vWF:Ag concentration in patients with severe multiple trauma (ISS > or = 35) was significantly elevated, in comparison to group II and control. At the admission, significant correlation between plasma vWF:Ag and ISS was found (Rs = 0.568, p < 0.001). Significant correlation between plasma vWF:Ag and serum sES concentration was also observed (Rs = 0.501, p < 0.001). In conclusion, severe trauma patients manifest endothelial cell activation/injury. Plasma vWF:Ag concentration seems to be an important, early marker of trauma severity, while serum sE-selectin level may serve as prognostic factor in immediate postinjury period course.

The diagnosis and surgical management of diseases of the adrenal glands.

The authors present their own experience in the diagnosis and management of adrenal tumours and cysts. During the years 1980-2000, 74 patients were underwent surgical treatment. Of this group, 23 had Cushing's syndrome, 19 phaeochromocytomas, 4 Conn's syndrome, 2 virilising tumours, 2 adenocarcinomas, 2 ganglioneuromas, 7 adrenal cysts, 8 adenomas, 3 adenocortical carcinomas, 2 nodular hypertrophies, 1 myelolipoma and 1 liposarcoma. Treatment was effective in 73 (98.6%) of patients. We recommend the transperitoneal approach which allows the visual evaluation of both adrenals and extra adrenal tissue. We regard surgical intervention as being the only effective method of treating adrenal tumours.

Lysosomal activity of pulmonary alveolar macrophages in acute experimental pancreatitis in rats with reference to positive PAF-antagonist (BN 52021) effect.

The activation of pulmonary alveolar macrophages (PAM's), might play an important role in severe complications of acute pancreatitis. The aim of our study was to assess the labilization of macrophage lysosomal membranes and release of lysosomal cathepsin B (CB) and N-acetyl-beta-D-hexosaminidase (NAH) into bronchoalveolar lavage fluid (BALF) during taurocholate acute pancreatitis (AP) in rats treated with PAF-antagonist--BN 52021. Total activity of CB increased by 374% after 6 h and by 237% after 12 h of AP in lysosomal enriched fraction of PAM's. Fractional free activity of CB increased to 40% after 6 h and to 38% after 12 h of AP. Free activity of CB was increased 5 fold in the supernatant of macrophage homogenate, and 10 fold in the supernatant of BALF after 6 h of AP. The values of NAH activity roughly paralleled that of CB. Treatment with BN 52021 (5 mg x kg(-1) every 6 h i.v.) partially normalized the measured parameters. Our results indicate that the PAF-antagonist BN 52021 reduced the increase of total and free activity of lysosomal hydrolases of PAM's and partly prevented the labilization of their lysosomal membranes. Therefore, an important mechanism of BN 52021 beneficial effect in pulmonary complications of acute pancreatitis could be dependent on the stabilization of PAM's lysosomes.

von Willebrand factor antigen as a prognostic marker in posttraumatic acute lung injury.

The specific endothelial cell product von Willebrand factor antigen (vWf:Ag) was measured in plasma and lung function tests were carried out and the following lung injury parameters measured: P(a)O2/F(i)O2 ratio, static respiratory compliance and Murray's lung injury score (LIS) in a follow-up study of 36 severely traumatized patients. Injury severity score (ISS) and APACHE II scores were calculated. Patients were classified according to the presence or absence of acute respiratory distress syndrome (ARDS) complications and survival versus death. Data collection was performed on admission to hospital and after 1-3, 5, 7, 10 days of ICU stay. On all of the occasions investigated, plasma vWf:Ag levels in ARDS patients and nonsurvivors were significantly greater than those in patients without ARDS and survivors, respectively. Significant correlations were observed between initial vWf:Ag concentration and ISS, APACHE II, LIS. Our study suggests that increased concentrations of vWf:Ag in plasma are predictive of the development of ARDS and signal poor prognosis in patients following severe trauma.