Wear mechanisms description in nanoscale by SEM/TEM of multilayer Zr/ZrN coatings in dependence on phases ratio.

As a result of loading with an external force during the wear process, coating deforms uniformly. After a certain limit load is exceeded, coating deformation is localised through the formation of the so-called shear bands. It has been showed experimentally the process of shear bands formation. The microstructural characterisation before and after the mechanical tests was performed using scanning and transmission electron microscopy (SEM and TEM) on cross-sections of the samples. The analysis indicated that in the case of multilayer coatings where the ratio of the metallic to the ceramic phase is 1:1, the shear bands are formed at an angle of 45°. With a greater proportion of the ceramic phase to metallic (ratio 1:2), the shear band changed the shear angle from ∼45° to ∼90°. Mechanical in situ tests were carried out in the chambers of SEM and TEM. The scratch tests in the SEM were done with the simultaneous observation of the phenomena occurring on the surface of the tested materials showed that at a scratch force of 0.04 N, the additional outer a-C:H layer was damaged, which was shown in the form of a fault in the force-displacement diagram, and in the form of splits visible in the SEM image. However, the application of this additional layer had a positive effect on the wear mechanism of the entire coating structure. The test also indicated that in the case of coatings with phases ratio 1:2 and 1:4 (metallic to ceramic), the characteristics of the brittle material were demonstrated, unlike the coating with a 1:1 phase ratio, where plastic properties predominated. However, for the 1:2 phase ratio coating, the chip was more ductile than for the chip formed when testing a 1:4 phase ratio coating. For in situ mechanical testing in the TEM, a straining holder was used. The test showed that the shear band angle for a 1:1 ratio coating has changed from 45° to 90° due to the different direction of force interaction.

Small-molecule inhibitor - tyrphostin AG1296 regulates proliferation, survival and migration of rhabdomyosarcoma cells.

Rhabdomyosarcoma (RMS) is the most commonly occurring malignant soft tissue tumor in children. Despite improving its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. RMS cells are characterized by abnormal cellular signaling due to the changes in the activity of the tyrosine kinases. Thus, substances blocking the mitogenic signal transmitted by receptors with tyrosine kinase activity raise hopes for inhibition of the uncontrolled cell growth. In this study, we examined the anticancer activity of tyrphostin AG1296, a tyrosine kinase inhibitor that binds to the intracellular domain of the PDGF (platelet-derived growth factor) receptor in human RMS alveolar and embryonal cell lines. We have discovered that tyrphostin AG1296 completely inhibited cell proliferation and effectively inhibited cell viability. Tyrphostin AG1296 induced apoptosis of the RMS cells and significantly inhibited their migration. Additionally, investigated inhibitor slightly inhibited expression of AKT and phosphorylation of ERK in alveolar RMS cells. Importantly, the inhibitor exerted also potent effects on the nanomechanical properties and cytoskeleton organization of RMS cells. To conclude, tyrphostin AG1296 is a promising compound in the treatment of alveolar RMS. Undoubtedly, a better knowledge of receptor pathomechanism of tyrosine kinases may contribute to developing new, more effective ways of RMS treatment.

Effect of the mechanical properties of carbon-based coatings on the mechanics of cell-material interactions.

The paper presents an influence of the surface mechanical properties of thin-film materials on blood cell adhesion under shear stress conditions. Physical vapour deposited (PVD) coatings i.e. hydrogenated amorphous carbon (a-C:H) doped with nitrogen or silicon have been investigated. The mechanical properties of materials, namely their microhardness and Young's modulus were measured using indentation test with Rockwell indenter. The adhesion efficiency of blood cells in dynamic conditions were analysed using a radial flow chamber. Red blood cells (RBC) were used as representative cells to analyse cell-material interactions. The biomaterial examinations were performed under physiological flow conditions at the single-cell level. The 3D FVM (finite volume method) model of multi-phase radial flow test was developed to reproduce the physical test and to predict distributions of shear stresses and velocity during blood washout with PBS. Cell-material interactions were found to be strongly associated with the mechanical properties of the thin-film material. The decrease in the hardness of the coatings translated into a weaker cell - material interactions.

In situ Near-Ambient Pressure X-ray Photoelectron Spectroscopy Reveals the Influence of Photon Flux and Water on the Stability of Halide Perovskite.

For several years, scientists have been trying to understand the mechanisms that reduce the long-term stability of perovskite solar cells. In this work, we examined the effect of water and photon flux on the stability of CH3 NH3 PbI3 perovskite films and solar cells using in situ near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS), field emission scanning electron microscopy (FESEM), and current density-voltage (J-V) characterization. The used amount of water vapor (up to 1 mbar) had a negligible impact on the perovskite film. The higher the photon flux, the more prominent were the changes in the NAP-XPS and FESEM data; also, a faster decline in power conversion efficiency (PCE) and a more substantial hysteresis in the J-V characteristics were observed. Based on our results, it can be concluded that the PCE decrease originates from the creation of Frenkel pair defects in the perovskite film under illumination. The stronger the illumination, the higher the number of Frenkel defects, leading to a faster PCE decline and more substantial hysteresis in the J-V sweeps.

Microwave-assisted synthesis and characterization of novel chitosan-based biomaterials for pelvic organ prolapse treatment.

Pelvic organ disorders affect up to one in four women in the United States. The prevalence of pelvic organ prolapse (POP) is increasing with each year, particularly in the setting of prolonged life expectancy and an aging population. Current treatment approaches, including polypropylene monofilaments are associated with numerous painful and worrisome side-effects. Therefore, scientists are looking for new solutions. A promising alternative to the current treatment is tissue engineering, which can be utilized to re-create support to the vagina and pelvic organs. Tissue engineering requires the use of three-dimensional scaffolds, derived from biocompatible materials. Chitosan is a natural polymer, obtained from shellfish exoskeletons. It is known for its biodegradability, lack of cytotoxicity and non-pyrogenicity. Due to the presence of free hydroxyl and amino groups, it may undergo various modifications. In this paper, we describe a new type of chitosan-based biomaterials, which can be used as a new alternative scaffold that may provide support to prolapse organs. The chitosan scaffold was obtained under microwave radiation using multifunctional amino and organic acids. We discuss the scaffold's characteristics, with an emphasis on its chemical structure and morphology. Fourier transform infrared spectroscopy (FT-IR) analysis confirmed cross-linking processes with preservation of free amino groups. Moreover, mechanical durability, the stability and swelling ability of the scaffolds in a simulated body fluid were investigated. All of the prepared scaffolds demonstrated very good antioxidant activity and biodegradability. Importantly, the biocompatibility of chitosan scaffolds was examined on human vaginal VK2/E6E7 cell line. No evidence of toxicity was documented, and the cells maintained their presence on the studied materials. These results allude to the lack of toxicity of the scaffolds, and indicate that chitosan-based scaffold should be further investigated in in vivo studies as they may be a promising alternative treatment to pelvic organ prolapse.

Wear mechanisms of the biotribological nanocomposite a-C : H coatings implanted by metallic nanoparticles.

Recently, to reduce the residual stress and increase the mechanical properties of a-C:H coatings, metallic nanoparticles have been implanted into their structure. In the present work, to improve the properties of the coating, metallic nanoparticles, including Cu, Nb, Ta, Zr, AgPt and Ag, were inserted into the a-C:H structure. The applied biological and mechanical analysis allowed the optimal biotribological parameters to be indicated for the potential application as protective coatings for metallic medical tools. Wear mechanisms operating at the small length of the designed biotribological coating, such as a-C:H implanted by Zr nanoparticles, were studied by means of transmission electron microscopy (TEM). The TEM analysis confirmed very good coating adhesion to the metallic substrate.

Numerical technique of blood flow through catheterized arteries with overlapping stenosis.

This study is concerned with the surgical technique for the injection of a catheter through arteries with overlapping stenosis in the presence of externally applied magnetic field and Hall currents influences. The nature of blood is analyzed mathematically by considering it as a micropolar fluid. The analysis is carried out for an artery with a mild stenosis. The governing equations with the corresponding boundary conditions solved numerically using Crank-Nicolson implicit finite difference scheme. The numerical technique give excellent agreement for axial velocity of the fluid, the circumferential microrotation, the wall shear stress distribution and the contour plots of stream lines. The obtained results show that the value of axial velocity is higher for a Newtonian fluid than that for a micropolar fluid model, the effect of suitable moving magnetic field (Hall currents influences) accelerates the speed of blood, the size of trapped bolus for the stream lines decrease if the spinning movement of the fluid molecules have considerable value regardless of small or large size of the fluid molecules and the flow of fluid is better with increasing the Hall current effect and the size of trapping bolus increase clearly by increasing the maximum height of stenosis where the fluid moves as a bulk.

Understanding the growth mechanism of graphene on Ge/Si(001) surfaces.

The practical difficulties to use graphene in microelectronics and optoelectronics is that the available methods to grow graphene are not easily integrated in the mainstream technologies. A growth method that could overcome at least some of these problems is chemical vapour deposition (CVD) of graphene directly on semiconducting (Si or Ge) substrates. Here we report on the comparison of the CVD and molecular beam epitaxy (MBE) growth of graphene on the technologically relevant Ge(001)/Si(001) substrate from ethene (C2H4) precursor and describe the physical properties of the films as well as we discuss the surface reaction and diffusion processes that may be responsible for the observed behavior. Using nano angle resolved photoemission (nanoARPES) complemented by transport studies and Raman spectroscopy as well as density functional theory (DFT) calculations, we report the direct observation of massless Dirac particles in monolayer graphene, providing a comprehensive mapping of their low-hole doped Dirac electron bands. The micrometric graphene flakes are oriented along two predominant directions rotated by 30° with respect to each other. The growth mode is attributed to the mechanism when small graphene "molecules" nucleate on the Ge(001) surface and it is found that hydrogen plays a significant role in this process.

Melatonin metabolite, N(1)-acetyl-N(1)-formyl-5-methoxykynuramine (AFMK), attenuates acute pancreatitis in the rat: in vivo and in vitro studies.

Melatonin protects the pancreas from inflammation and free radical damage but the effect of the melatonin metabolite: N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) on acute pancreatitis is unknown. This study assessed the effects of AFMK on acute pancreatitis (AP) in the rats in vivo and on pancreatic cell line AR42J in vitro. AFMK (5, 10 or 20 mg/kg) was given intraperitoneally to the rats 30 min prior to the induction of AP by subcutaneous caerulein infusion (25 µg/kg). Lipid peroxidation products (MDA + 4-HNE) and the activity of an antioxidant enzyme glutathione peroxidase (GPx) were measured in pancreatic tissue. Blood samples were taken for evaluation of amylase activity and TNF-α concentration. GPx, TNF-α, proapoptotic Bax protein, antiapoptotic Bcl-2 protein and the executor of apoptosis, caspase-3, were determined by Western blot in AR42J cells subjected to AFMK or to melatonin (both used at 10(-12), 10(-10), or 10(-8)M), without or with addition of caerulein (10(-8)M). AP was confirmed by histological examination and by serum increases of amylase and TNF-α (by 800% and 300%, respectively). In AP rats, pancreatic MDA + 4-HNE levels were increased by 300%, whereas GPx was reduced by 50%. AFMK significantly diminished histological manifestations of AP, decreased serum amylase activity and TNF-α concentrations, reduced MDA + 4-HNE levels and augmented GPx in the pancreas of AP rats. In AR42J cells, AFMK combined with caerulein markedly increased protein signals for GPx, Bax, caspase-3 and reduced these for TNF-α and Bcl-2. In conclusion, AFMK significantly attenuated acute pancreatitis in the rat. This may relate to the antioxidative and anti-inflammatory effects of this molecule and possibly to the stimulation of proapoptotic signal transduction pathway.

Inflammation increases oxidative DNA damage repair and stimulates preneoplastic changes in colons of newborn rats.

Oxidative DNA damage may be a risk factor for development of various pathologies, including malignancy. We studied inflammation triggered modulation of repair activity in the intestines of three weeks old rats injected i.p. with E.coli or S. typhimurium lipopolysaccharides (LPS) at doses of 1, 5 or 10 mg/kg. Subsequent formation in these animals of colonic preneoplastic lesions, aberrant crypt foci (ACF) was also investigated. Five days after LPS administration no differences were observed in repair rate of 1,N(6)-ethenoadenine (εA), 3,N(4)-ethenocytosine (εC) and 8-oxoguanine (8-oxoG) in intestines of these rats, as measured by the nicking assay. However a significant increase in all three repair activities was found within one and two months after S. typhimurium LPS treatment. E. coli LPS significantly increased only the 8-oxoG repair. S. typhimurium LPS stimulated mRNA transcription of pro-inflammatory proteins, lipooxygenase-12 and cyclooxygenase-2, as well as some DNA repair enzymes like AP-endonuclease (Ape1) and εC-glycosylase (Tdg). mRNA level of DNA glycosylases excising εA (MPG) and 8-oxoG (OGG1) was also increased by LPS treatment, but only at the highest dose. Transcription of all enzymes increased for up to 30 days after LPS, and subsequently decreased to the level observed before treatment, with the exception of APE1, which remained elevated even two months after LPS administration. Thus, the repair efficiency of εA, εC and 8-oxoG depends on the availability of APE1, which increases OGG1 and TDG turnover on damaged DNA, and presumably stimulates MPG. One and two months after administration of E. coli or S. typhimurium LPS, the number of aberrant crypt foci in rat colons increased in a dose and time dependent manner. Thus, inflammation stimulates the repair capacity for εA, εC and 8-oxoG, but simultaneously triggers the appearance of preneoplastic changes in the colons. This may be due to increased oxidative stress and imbalance in DNA repair.

Microstructure characterization of advanced protective Cr/CrN+a-C:H/a-C:H:Cr multilayer coatings on carbon fibre composite (CFC).

Studies of advanced protective chromium-based coatings on the carbon fibre composite (CFC) were performed. Multidisciplinary examinations were carried out comprising: microstructure transmission electron microscopy (TEM, HREM) studies, micromechanical analysis and wear resistance. Coatings were prepared using a magnetron sputtering technique with application of high-purity chromium and carbon (graphite) targets deposited on the CFC substrate. Selection of the CFC for surface modification in respect to irregularities on the surface making the CFC surface more smooth was performed. Deposited coatings consisted of two parts. The inner part was responsible for the residual stress compensation and cracking initiation as well as resistance at elevated temperatures occurring namely during surgical tools sterilization process. The outer part was responsible for wear resistance properties and biocompatibility. Experimental studies revealed that irregularities on the substrate surface had a negative influence on the crystallites growth direction. Chromium implanted into the a-C:H structure reacted with carbon forming the cubic nanocrystal chromium carbides of the Cr23 C6 type. The cracking was initiated at the coating/substrate interface and the energy of brittle cracking was reduced because of the plastic deformation at each Cr interlayer interface. The wear mechanism and cracking process was described in micro- and nanoscale by means of transmission electron microscope studies. Examined materials of coated CFC type would find applications in advanced surgical tools.

Models for the spread of white pine blister rust.

White pine blister rust (WPBR, Cronartium ribicola) is a fungal pathogen and a threat to whitebark pines (Pinus albicaulis). It has a complex life cycle that requires two hosts, a white pine and an alternate host, typically a currant or gooseberry (Ribes spp.). WPBR is transmitted between hosts by means of two types of airborne spores whose average dispersal distances differ by several orders of magnitude. In this paper, we introduce a discrete-time model based on the life cycle of WPBR. We then extend this model to include a continuous spatial domain, disease-induced mortality in the pines, and a latency period. After each extension, we find the pathogen's asymptotic speed of invasion analytically using exponential transforms and the method of steepest descent. Our results show that invasion speeds are strongly reduced by the latency period in the pine host. In addition, these speeds are highly dependent on the carrying capacity and infectiousness of each host type. If these parameters are sufficiently small, high mortality in pines may stop the spread of WPBR completely.

Comparison of cardiac output measurements in critically ill patients: FloTrac/Vigileo vs transthoracic Doppler echocardiography.

Measurement of cardiac output is an integral part of patient management in the intensive care unit. FloTrac/Vigileo is a continuous cardiac output monitoring device that does not need re-calibration. However its reliability has been questioned in some studies, especially involving surgical patients. In this study, we evaluated the comparability of FloTrac/Vigileo and transthoracic Doppler echocardiography in 53 critically ill patients requiring continuous cardiac output monitoring. Most of these patients had septic or cardiogenic shock. Cardiac output was measured by both FloTrac/Vigileo and transthoracic Doppler echocardiography. The bias and precision (mean and SD) between the two devices was 0.35 +/- 1.35 l/minute. The limits of agreement were -2.3 to 3.0 l/minute (%error = 49.3%). When patients with irregular heart rhythms and aortic stenosis were excluded, the bias and precision was 0.02 +/- 0.80 l/minute (n = 42). The limits of agreement were -1.55 to 1.59 l/minute (%error = 29.5%). Patient demographics (body surface area, gender and age) did not affect the bias, but there was a mild tendency for FloTrac/ Vigileo to register a higher cardiac output at high heart rates. Changes in cardiac output for two consecutive days correlated well between the two methods (r = 0.86; P < 0.001). In summary, with the exceptions of patients with irregular heart rhythms and significant aortic stenosis, FloTrac/Vigileo is clinically comparable to transthoracic Doppler echocardiography in cardiac output measurements in critically ill patients.

Implication of umbilical cord in preeclampsia.

OBJECTIVES: To investigate the role of biochemical changes in the umbilical cord and placenta in developing preeclampsia (PE). SUBJECTS AND METHODS: Thirty women with PE and 15 healthy pregnant women as controls were enrolled in this study. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), platelet-derived endothelial cell growth factor (PD-ECGF), neutrophil elastase and nitric oxide (NO) were measured. RESULTS: Both serum (maternal and fetal) and tissue (placenta and umbilical cord) levels of VEGF, sVEGFR-1, PD-ECGF and neutrophil elastase were significantly increased, whereas NO was significantly decreased (except placental tissue showed no changes) in preeclamptic patients. The cord serum level of PD-ECGF was significantly higher in severe PE compared to mild PE and normal pregnant women. The placental and cord tissue levels of PD-ECGF and neutrophil elastase were significantly higher in severe PE, while the cord tissue level of NO was significantly lower in severe PE. CONCLUSION: Our data showed that umbilical cord vessels and stroma can serve as an additional source of vasoactive and angiogenic substances that contribute to the biochemical changes occurring in PE.

Effect of neonatal endotoxemia on the pancreas of adult rats.

UNLABELLED: Bacterial endotoxin (lipopolysaccharide, LPS), is the component of the cellular wall of Gram negative bacteria. Endotoxemia (sepsis) could produce multiorgan failure and could be particularly danger in the early period of life. The effects of endotoxemia induced in the neonatal period of life on the pancreatic secretory function and on pancreatic defense of adult organism have not been investigated yet. To induce endotoxemia suckling rats (30 g) have been injected intraperitoneally with LPS from E. coli (5, 10 or 15 mg/kg-day) during 5 consecutive days. Three months later in these animals (300 g) the studies on pancreatic secretion and acute pancreatitis were carried out. In the adult rats, which have been subjected in infancy to endotoxemia, basal pancreatic secretion was unaffected, whereas amylase secretions stimulated by caerulein or by diversion of pancreatic-biliary juice to the exterior were significantly, and dose-dependently reduced as compared to the untreated control. In the rats pretreated with LPS in the suckling period of life caerulein-induced amylase release from isolated pancreatic acini was significantly decreased, and dose-dependent reduction of mRNA signal for CCK1 receptor on pancreatic acini have been observed. Caerulein infusion (25 microg/kg) produced caerulein induced pancreatitis (AP) in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS (10 or 15 mg/kg-day x 5 days) all manifestations of AP have been reduced. In these animals acute inflammatory changes of pancreatic tissue have been significantly diminished. Pancreatic weight and plasma lipase activity, have been markedly decreased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in an antioxidative enzyme; SOD concentration was reversed and accompanied by significant reduction of lipid peroxidation products; MDA+ 4 HNE in the pancreatic tissue. CONCLUSIONS: 1/ neonatal endotoxemia reduces gene expression for CCK1 receptor and could produce impairment of the exocrine pancreatic function at adult age; 2/ Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age and this effect could be related to the increased concentration of antioxidative enzyme SOD in the pancreatic tissue.

Endotoxemia in the infant rats modulates HSP60 protein level in the pancreatic acinar cells.

Lipopolysaccharide (endotoxin, LPS) is responsible for septic shock and multiorgan failure, but pretreatment of the rats with low doses of LPS reduced pancreatic damage produced by caerulein-induced pancreatitis (CIP). In spite of this observations the effects of LPS and caerulein on pro-apoptotic HSP60 and Bax protein expression in the pancreatic acinar cells has not been examined yet. The aim of this study was to assess the effects of endotoxemia induced in the early period of life on the pro-apoptotic nuclear HSP60 and mitochondrial Bax protein expressions detected in the pancreas of adult animals. Newborn rats (25 g) were injected with endotoxin (Escherichia coli) for 5 consecutive days, at the total doses of 25, 50 or 75 mg/kg. Control animals received injections of physiological saline. Two months later the pancreatic acinar cells were isolated from all above groups of rats and subjected to caerulein over stimulation (10(-8)M). Total nuclear HSP60 and mitochondrial Bax protein expression were isolated for Western blot and co-immunoprecipitation studies. High levels of pro-apoptotic nuclear HSP60 and mitochondrial Bax protein has been observed in the pancreatic acinar cells under basal conditions. Pretreatment of newborn rats with LPS failed to affect significantly the HSP60 and Bax protein levels in the pancreatic acini isolated from the same animals 2 months later, as compared to the control group. Caerulein stimulation significantly reduced the level of these proteins. Pretreatment of suckling rats with LPS (at the total doses of 25, 50 or 75 mg/kg) reversed above caerulein-induced suppression of pro-apoptotic nuclear HSP60 and mitochondrial Bax protein levels in the pancreatic acini obtained from adult rats. We conclude that pretreatment of suckling rats with LPS reversed the suppression of pro-apoptotic HSP60 and Bax protein levels produced by caerulein overstimulation in the pancreatic acini. This mechanism could take a part in the LPS-induced protection of the pancreatic tissue against acute damage.

Endotoxemia in newborn rats attenuates acute pancreatitis at adult age.

Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar. Pretreatment of suckling rats with LPS at dose of 10 mg/kg-day x 5 days resulted in the most prominent attenuation of acute pancreatitis at adult age, whereas LPS at dose of 5 mg/kg-day x 5 days given to the neonatal rats failed to affect significantly acute pancreatitis induced in these animals 2 months later. We conclude that: 1/ Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age. 2/ This effect could be related to the increased concentration of antioxidative enzyme SO in the pancreatic tissue and to the modulation of cytokines production in these animals.

Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector.

Melatonin, the main product of the pineal gland, is also released from the gastrointestinal endocrine-neurocrine (EE) cells. The concentrations of melatonin produced in the gut exceeds that originating from central nervous system. In spite of the presence of melatonin receptors in the pancreatic tissue little is known about the role of this indole in the pancreas. Our experimental studies have shown that exogenous melatonin, as well as this produced endogenously from its precursor; L-tryptophan, strongly stimulates pancreatic amylase secretion when given intraperitoneally, or into the gut lumen. This was accompanied by significant increases of CCK plasma level. Above pancreatostimulatory effects of luminal administration of melatonin, were completely reversed by bilateral vagotomy, capsaicin deactivation of sensory nerves or pretreatment of the rats with CCK1 receptor antagonist; tarazepide as well as serotonin antagonist; ketanserin. Melatonin, as well as its precursor; L-tryptophan, effectively protects the pancreas against the damage induced by caerulein overstimulation or ischemia/reperfusion. The beneficial effects of melatonin or L-tryptophan on acute pancreatitis could be related to the ability of melatonin to scavenge the free radicals, to activate antioxidative enzymes and to modulate the cytokine production.

Involvement of vagal nerves in the pancreatostimulatory effects of luminal melatonin, or its precursor L-tryptophan. Study in the rats.

UNLABELLED: Melatonin, known as a product of pineal gland is also produced in the digestive system. Melatonin receptors have been detected on pancreatic beta cells and this indoloamine influences the endocrine pancreatic function but the role of melatonin on pancreatic exocrine secretion is not known. AIM: To evaluate the effects of intraduodenal administration of melatonin or its precursor L-tryptophan on pancreatic protein output under basal conditions or following the stimulation of exocrine pancreas with diversion of pancreato-bliliary juice (DBPJ) and to assess the involvement of vagal nerves, and CCK in this process. METHODS: Under pentobarbiturate anesthesia the Wistar rats weighting 300g were surgically equipped with silicone catheters, one of them was inserted into pancreato-biliary duct, the other one--into duodenum. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) were administered to the rats as intraduodenal (i.d.) bolus injection. Bilateral vagotomy was performed in the group of animals 7 days before the experiment. To assess the role of CCK in the melatonin or L-tryptophan-induced pancreatic secretory functions, lorglumide, the CCK(1) receptor antagonist was administered at dose of 1 mg/kg i.d. 15 minutes before the application of examine substances. During the study samples of pancreato-biliary juice were collected in 15 minutes aliquots to measure the protein outputs. RESULTS: Melatonin (1, 5, or 25 mg/kg ) or L-tryptophan (10, 50 or 250 mg/kg) produced significant and dose-dependent increases in pancreatic protein secretion under basal conditions or following the stimulation of this secretion by DBPJ. This was accompanied by a dose-dependent rise in CCK plasma level. Stimulation of pancreatic protein outputs caused by melatonin or L-tryptophan was completely abolished by vagotomy, or pretreatment with lorglumide. We conclude that melatonin as well as its precursor L-tryptophan, stimulates pancreatic exocrine function via mechanisms involving enteropancreatic reflexes and CCK.