Intra-pancreatic release of bradykinin during the course experimental pancreatitis in rat

Kallikrein/Kininogn activation is an important pathophysiological event in acute pancreatitis, leading to microcirculatory changes within the gland. Hitherto, only indirect measurements of pancreatic bradykinin formation have been performed, monitoring the peptide in the circulation and in the peritoneal exudate. In the present study, intra-pancreatic bradykinin release was assessed using microdialysis during experimental acute pancreatitis in rat. In mild, oedematous pancreatitis, induced by caerulein hyperstimulation, the levels of bradykinin within the gland were not elevated compared with those of control rats. However, in necrotic pancreatitis, induced by retrograde injection of taurocholate into the pancreatic duct, significantly elevated levels of intraglandular bradykinin were seen. Several rats in this group died whilst in a state of circulatory shock

The interleukin-1 receptor antagonist influences interleukin-1 effects in rat and mouse

In this work we have focused on the ability of interleukin-1 to induce an acute phase protein response and a degranulation of polymorphonuclear leukocytes in vivo. The capacity of the interleukin-1 receptor antagonist to influence these events was also investigated. It was shown that interleukin-1 induced an acute phase protein response in rats and mice. In rats α2-macroglubolin levels were increased in plasma after an interleukin-1 injection whereas α1-inhibitor-3 decreased in plasma. In the mice plasma amyloid P was increased. The interleukin-1 receptor antagonist blocked the increase of α2-macroglobulin and plasma amyloid P in a dose dependent way while the effect on the α1-inhibitor-3 decrease was less pronounced. Interleukin-1 led to polymorphonuclear leukocyte degranulation in vivo as measured by increased cathepsin G plasma levels. The interleukin-1 receptor antagonist could influence the early phase of this degranulation

Matter Enhanced Neutrino Oscillations with a Realistic Earth Density Profile

We have investigated matter enhanced neutrino oscillations with a mantle-core-mantle step function and a realistic Earth matter density profile in both a two and a three neutrino scenario. We found that the realistic Earth matter density profile can be well approximated with the mantle-core-mantle step function and that there could be an influence on the oscillation channel $\nu_\mu \to \nu_\tau$ due to resonant enhancement of one of the mixing angles.Comment: 8 pages, 5 figures (PostScript), MPLA LaTe

α2-macroglobulin and α1-inhibitor-3 mRNA expression in the rat liver after slow interleukin-1 stimulation

In this study we have investigated total fiver RNA and the expression of mRNA in the rat fiver in vivo after a slow stimulation of interleukin-1. A total dose of 4 μg interleukin-1β was administered via a subcutaneously implanted osmotic minipump over a period of 7 days. Plasma concentrations of α2-macroglobulin manifested a rapid increase, reaching a peak on day 2, while α1-inhibitor-3 manifested a marked initial decrease to 50% of the baseline level, followed by a tendency to increase again. For measurement of total RNA and specific mRNAs from the fiver, rats were sacrificed at different times during the experimental period. Total RNA peaked at 6 h, the level being approximately 60% higher than baseline value. Specific mRNA from the liver for α2-macroglobulin and α1-inhibitor-3 were quantified using laser densitometry on slot blots. The amounts measured during the experimental period agreed with the pattern of corresponding plasma protein levels. From barely detectable amounts at baseline, α2-macroglobulin mRNA peaked on day 1, and then declined. Levels of α1-inhibitor-3 mRNA manifested an initial increase at 3 h, but then declined and remained low until day 5 when there was a tendency towards an increase. It was concluded that the levels of plasma concentrations of α2-macroglobulin and α1-inhibitor-3 are mainly regulated at the protein synthesis level, and that long-term interleukin-1β release could not override the initial acute phase protein counteracting mechanism triggered

IgE-mediated histamine release from nasal mucosa is inhibited by SLPI (secretory leukocyte protease inhibitor) to the level of spontaneous release.

The secretory leukocyte protease inhibitor (SLPI) is a low-molecular-weight inhibitor of proteases, such as elastase and cathepsin G which are released from leukocytes during phagocytosis. The purpose of this study was to determine whether or not SLPI is able to inhibit IgE-mediated histamine release. Nasal mucosa from 11 test subjects without atopic disposition was used for this in vitro study. We found that SLPI inhibited histamine release in a dose-dependent way but was without influence on the spontaneous release

Extracorporeal circulation causes release of neutrophil gelatinase-associated lipocalin (NGAL).

Extracorporeal circulation (ECC) used during cardiac surgery causes activation of several inflammatory systems. These events are not fully understood but are responsible for complications during the immediate postoperative period. Neutrophil gelatinase-associated lipocalin (NGAL), a member of the expanding lipocalin family, has recently been described as an inflammatory protein. In this study, the release of NGAL into the circulation in 41 patients undergoing heart surgery with ECC was evaluated. A 4- to 5-fold elevation of the concentration of NGAL in plasma was observed during the immediate postoperative course with a rapid elimination during the first postoperative day. Four patients undergoing lung surgery (without ECC) were also studied. The plasma concentration of NGAL only increased with a factor of 1.1-2.2 over the operation. We conclude that NGAL is released into the circulation during heart surgery, probably as a result of the inflammatory activation of leukocytes initiated by the extracorporeal circulation

Secretory leukocyte protease inhibitor in punch biopsies from human colonic mucosa.

Secretory leukocyte protease inhibitor (SLPI) is a well-known protease inhibitor. Its function is thought to be protease/protease-inhibitor balance. Free proteolytic activity, mainly pancreatic elastase, anionic trypsin and granulocytic elastase, has been demonstrated in faecal extracts from patients with ulcerative colitis. We wanted to verify that SLPI is actually secreted from normal human colonic mucosa. Also, we wanted to ascertain whether studies of SLPI secretion based on punch biopsies were dependent on biopsy area or on biopsy circumference. Normal colonic mucosa was sampled during surgery for colonic cancer. A total of 36 samples from four patients were used. Mucosa preparation was carried out using a punch biopsy technique, and samples of 3, 4 and 6 mm diameter were used. All media contained SLPI at varying concentrations. When expressed in terms of the sample area, the secretion per millimetre-squared seemed to decrease with increasing area. When calculated as secretion per circumference, secretion seemed to be constant. In conclusion, SLPI was secreted from normal human colonic mucosa. The SLPI secretion seemed dependent on the circumference of the biopsy rather than on the area of the biopsy