Does Chronic Pancreatitis in Growing Pigs Lead to Articular Cartilage Degradation and Alterations in Subchondral Bone?

Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP's impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-ß1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP's systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management.

Adipokines in Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets.

Rheumatoid arthritis (RA) is a chronic inflammatory disease manifested by joint involvement, extra-articular manifestations, and general symptoms. Adipose tissue, previously perceived as an inert energy storage organ, has been recognised as a significant contributor to RA pathophysiology. Adipokines modulate immune responses, inflammation, and metabolic pathways in RA. Although most adipokines have a pro-inflammatory and aggravating effect on RA, some could counteract this pathological process. The coexistence of RA and sarcopenic obesity (SO) has gained attention due to its impact on disease severity and outcomes. Sarcopenic obesity further contributes to the inflammatory milieu and metabolic disturbances. Recent research has highlighted the intricate crosstalk between adipose tissue and skeletal muscle, suggesting potential interactions between these tissues in RA. This review summarizes the roles of adipokines in RA, particularly in inflammation, immune modulation, and joint destruction. In addition, it explores the emerging role of adipomyokines, specifically irisin and myostatin, in the pathogenesis of RA and their potential as therapeutic targets. We discuss the therapeutic implications of targeting adipokines and adipomyokines in RA management and highlight the challenges and future directions for research in this field.

Kidney morphology and renal expression of aquaporins 2, 3 and 4 during cerulein - Induced chronic pancreatitis in pigs.

PURPOSE: Chronic pancreatitis (CP) is associated with serious complications and reduced quality of life. Kidney failure is a frequent complication of acute pancreatitis (AP), however limited information is available regarding the impact of CP on this condition. In the kidney, 9 aquaporins (AQPs) are expressed to maintain body water homeostasis and concentrate urine. The purpose of this study was to morphologically assess and analyze the location and expression of AQP2, AQP3 and AQP4 and determine whether CP affects renal structure and expression of AQPs in collecting duct (CD) principal cells. MATERIALS/METHODS: CP was induced in domestic pigs through intramuscular injections of cerulein (1 â€‹µg/kg â€‹bw/day for 6 days; n â€‹= â€‹5); pigs without CP (n â€‹= â€‹5) were used as a control group. Kidney samples were collected 6 weeks after the last injection and subjected to histological examination. Expression of AQPs was determined by immunohistochemistry and Western blot. RESULTS: The kidneys of animals with CP exhibited moderate changes, including glomerular enlargement, increased collagen percentage, numerous stromal erythrorrhages and inflammatory infiltrations compared to control group. Although the total abundance of AQP2 in the CD decreased in pigs after cerulein administration, the difference was not statistically significant. Expression of AQP3 and AQP4 was limited to the basolateral membrane of the CD cells. AQP4 abundance remained relatively stable in both groups, while AQP3 expression increased nearly three-fold in pigs with CP. CONCLUSION: This study identified morphological alterations and a statistically significant increase in the expression of renal AQP3 when pigs developed CP.

Administration of Warfarin Inhibits the Development of Cerulein-Induced Edematous Acute Pancreatitis in Rats.

Acute pancreatitis (AP) is a severe disease with high morbidity and mortality in which inflammation and coagulation play crucial roles. The development of inflammation leads to vascular injury, endothelium and leukocytes stimulation, and an increased level of tissue factor, which results in the activation of the coagulation process. For this reason, anticoagulants may be considered as a therapeutic option in AP. Previous studies have shown that pretreatment with heparin, low-molecular-weight heparin (LMWH), or acenocoumarol inhibits the development of AP. The aim of the present study was to check if pretreatment with warfarin affects the development of edematous pancreatitis evoked by cerulein. Warfarin (90, 180, or 270 µg/kg/dose) or saline were administered intragastrically once a day for 7 days consecutively before the induction of AP. AP was evoked by the intraperitoneal administration of cerulein. The pre-administration of warfarin at doses of 90 or 180 µg/kg/dose reduced the histological signs of pancreatic damage in animals with the induction of AP. Additionally, other parameters of AP, such as an increase in the serum activity of lipase and amylase, the plasma concentration of D-dimer, and interleukin-1ß, were decreased. In addition, pretreatment with warfarin administered at doses of 90 or 180 µg/kg/dose reversed the limitation of pancreatic blood flow evoked by AP development. Warfarin administered at a dose of 270 µg/kg/dose did not exhibit a preventive effect in cerulein-induced AP. Conclusion: Pretreatment with low doses of warfarin inhibits the development of AP evoked by the intraperitoneal administration of cerulein.

Repetitive Cerulein-Induced Chronic Pancreatitis in Growing Pigs-A Pilot Study.

Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase-SOD, and reduced glutathione-GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs' pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.

Chronic Vulvar Pain and Health-Related Quality of Life in Women with Vulvodynia.

The aim of this study was to investigate the severity of chronic vulvar pain in women with vulvodynia and its impact on their health-related quality of life (QL). The study group consisted of 76 women aged 19 to 58. The study was carried out using the diagnostic survey method, i.e., (1) the questionnaire technique, comprising (A) the author's questionnaire (76 questions) and (B) the WHOQOL-BREF questionnaire, and (2) the VAS. When analyzing the severity of vulvar pain on the VAS, the highest proportion of women rated it at level 6 (23.68%). This was significantly determined by certain personal characteristics (age < 25 years old) and sociodemographic characteristics (marital status: unmarried women, divorcees, widows; high school education), each at p < 0.05. Vulvodynia causes a significant deterioration (64.47%) in QL, which is mainly caused by a reduction in the ability to perform activities of daily living (27.63%) and a decrease in sexual satisfaction (27.63%). The level of stress significantly exacerbates pain (p < 0.05). The severity correlates significantly (p < 0.05) and negatively (r < 0) with QL perception, which was rated worst in the physical domain. The use of treatment resulted in a significant improvement in the physical and psychological domains (p < 0.05), and the latter was particularly influenced by physiotherapy (p < 0.05).

Mental Health of Cystic Fibrosis Patients and the COVID-19 Pandemic in Poland: A Single-Center Comparative Study.

Research shows that people with cystic fibrosis are more prone to suffer from psychological problems than healthy people; thus, the outbreak of the COVID-19 pandemic in Poland could have had an impact on their mental health. To assess this impact, we examined the mental health of patients before and during the pandemic. Survey participants were asked to fill in questionnaires that consisted of Beck Depression Inventory (BDI), 12-Item General Health Questionnaire (GHQ-12) and Cystic Fibrosis Questionnaire-Revised (CFQ-R; for the purpose of the study, an emotional functioning domain was used) during their hospital visits. A total of 81 patients took part in the study: 39 before the COVID-19 pandemic (BP) and 42 during the COVID-19 pandemic (DP). Patients' medians were lower for the BDI, GHQ-12 and higher for the emotional domain of CFQ-R during the pandemic (3, 6, 75 vs. 4, 10, 73.33). Fewer patients felt that their mental health had deteriorated during the pandemic (Δχ2 = 7.723; p = 0.005), and GHQ-12 scores were lower in the DP group (Z = -3.044; p = 0.002). No significant differences were found between groups in terms of experiencing depressive symptoms (Δχ2 = 1.036; p = 0.309). It was found that patients with cystic fibrosis from our study group not only maintained but also improved their mental health state during the COVID-19 pandemic.

Factors Affecting Migration Intentions of Polish Physiotherapists and Students of Physiotherapy-A Cross-Sectional Study.

The phenomenon of professional migrations in the healthcare sector may exacerbate the problem of health workforce shortages. The scale of migration of medical personnel in Poland is estimated mainly on the certificates issued by the regional chambers confirming qualifications that grant the legal right to practice in other EU countries. Migrations concern also physiotherapists, who are the third largest group of health professionals. However, the problem of this phenomenon has not been assessed, and there is a lack of research in this area. The aim of the study was to compare the intention of migration among practicing physiotherapists and students in the last two years of master's studies in physiotherapy, as well as to identify the factors affecting their intentions to migrate. The study covered practicing physiotherapists and students in the last two years of master's studies in the field of physiotherapy in Poland. A total of 236 respondents took part in the study, including 119 physiotherapists and 117 students of physiotherapy. The tool used for the study was an online questionnaire. The scale of the intention to migrate was estimated at 45.3% among students and 47.1% in the group of practicing physiotherapists. The most frequently indicated destination countries for the migration of physiotherapy students and practicing physiotherapists were Germany, Norway, Switzerland, France and the United Kingdom. In both studied groups, the pull factors with the greatest impact on the intention to migrate were the possibility of obtaining higher earnings and working in better infrastructural conditions. In turn, the most important push factors turned out to be the low prestige of the profession in Poland, limited prospects for professional advancement and the stressful work environment. The respondents most often indicated separation from loved ones and poor command of foreign languages as significant barriers to professional migration. Both students of physiotherapy and practicing physiotherapists show great interest in the intention of professional migration, and the decisive determinant is economic factors.

Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines.

Obesity and ageing place a tremendous strain on the global healthcare system. Age-related sarcopenia is characterized by decreased muscular strength, decreased muscle quantity, quality, and decreased functional performance. Sarcopenic obesity (SO) is a condition that combines sarcopenia and obesity and has a substantial influence on the older adults' health. Because of the complicated pathophysiology, there are disagreements and challenges in identifying and diagnosing SO. Recently, it has become clear that dysbiosis may play a role in the onset and progression of sarcopenia and SO. Skeletal muscle secretes myokines during contraction, which play an important role in controlling muscle growth, function, and metabolic balance. Myokine dysfunction can cause and aggravate obesity, sarcopenia, and SO. The only ways to prevent and slow the progression of sarcopenia, particularly sarcopenic obesity, are physical activity and correct nutritional support. While exercise cannot completely prevent sarcopenia and age-related loss in muscular function, it can certainly delay development and slow down the rate of sarcopenia. The purpose of this review was to discuss potential pathways to muscle deterioration in obese individuals. We also want to present the current understanding of the role of various factors, including microbiota and myokines, in the process of sarcopenia and SO.

Quality of life in patients after laparoscopic cholecystectomy due to gallstone disease - evaluation of long-term postoperative results.

<b>Introduction:</b> Currently, the standard treatment of gallstone disease is laparoscopic cholecystectomy. Considering its availability, reduction of postoperative pain and shortened stay in the hospital, a constant upward trend in the number of such procedures is observed. However, about one third of patients undergoing such treatment report pain and dyspeptic disorders following the surgery. The assessment of the quality of life of patients undergoing laparoscopic cholecystectomy, based on standardized questionnaires, should be one of the elements allowing for the assessment of the impact of the applied treatment on patients' lives. </br></br> <b>Aim:</b> The aim of this retrospective study is to evaluate the impact of laparoscopic cholecystectomy on the quality of life of patients operated in one center. </br></br> <b>Materials and methods:</b> The study has been carried out retrospectively with the use of a GIQLI questionnaire completed online by the patients 6 months after undergoing laparoscopic cholecystectomy. The study included patients over 18 years of age who have not experienced any complications within the perioperative period and did not require open surgery. The study group has been divided into two subgroups depending on the presence of symptoms of acute gallstone disease in the pre-operative period. </br></br> <b>Results: </b>The study group consisted of 205 patients (53 men, 152 women, aged 19 to 87, with an average of 54.3). The subgroup with an asymptomatic gallstone disease (dyspeptic disorders, without biliary colic) consisted of 47 patients (18 men, 29 women, aged 19-87). Symptomatic gallstone disease occurred in 158 people (35 men, 123 women aged 22 to 81). There have been certain statistically significant differences in the post-operative health condition between the group of patients with symptoms of gallstone disease and the asymptomatic patients. 94.3% of symptomatic patients concluded that their condition has improved and 5.7% that it remained unchanged. Among asymptomatic patients, only 53.2% of patients stated that they felt better post-surgery, 44.7% reported no changes (p < 0.001). There have been no significant differences in the overall QIQLI scores between these subgroups, although symptomatic patients assessed their social functioning better (8.9 ±1.5 vs 8.11 ±2.08, p = 0.004). There have been certain differences between men and women in the assessment of the quality of life in the context of the presence of key symptoms (M: 28.87 ±4.23, F: 26.77 ±5.0, p = 0.007). </br></br> <b> Conclusion:</b> The patients with a symptomatic gallstone disease report they feel better after laparoscopic cholecystectomy as compared to the group of asymptomatic patients. The overall QOL score measured by the GIQLI form does not depend on the presence of symptoms in the preoperative period. Men benefited more from surgery as regards key symptoms.

Stress and Coping Strategies of Nurses Working with Patients Infected with and Not Infected with SARS-CoV-2 Virus.

INTRODUCTION: Working during the COVID-19 pandemic is a particular challenge for nurses because, while performing their daily routines, they are exposed to physical and social consequences of the SARS-CoV-2 virus, which is accompanied by intensified stress. The aim of this study was to assess the intensity of stress and coping strategies applied by nurses working with both infected and non-infected patients with SARS-CoV-2 virus during the COVID-19 pandemic. MATERIALS AND METHODS: The study was conducted between January and March 2021. Due to the epidemiological situation, the questionnaire was posted on Facebook in nurses' groups and sent out via the "Messenger" and "WhatsApp" applications. Stress intensity was assessed by means of the Perceived Stress Scale (PSS-10), whereas coping strategies were assessed using the Mini-COPE stress coping inventory. RESULTS: Among 151 surveyed nurses, more than half (52.3%) worked with infected patients and the remaining ones (47.7%) worked with non-infected patients. The level of stress perceived by nurses working with infected patients was higher than among nurses working with patients without SARS-CoV-2 infection (22.22 ± 5.94 vs. 20.21 ± 5.68, p = 0.03). The nurses working with infected patients were most likely to choose coping strategies focused on the problem (2.00 ± 0.62) and emotions (2.01 ± 0.69), whereas those working with non-infected patients usually chose strategies focused only on the problem (2.11 ± 0.58). CONCLUSIONS: During the COVID-19 pandemic, nurses working with SARS-CoV-2 patients experienced more intense stress than those working with non-infected patients. Nurses working with SARS-CoV-2 patients tended to cope with stress using strategies focused on the problem and on emotions, while those working with non-infected patients were more likely to choose strategies focused only on the problem.

A switch of N-glycosylation of proteome and secretome during differentiation of intestinal epithelial cells.

The maintenance of homeostasis of the intestinal epithelium depends on the complex process of epithelial cells differentiation, which repeatedly continues throughout the entire life. Many studies suggest, that cellular differentiation is regulated by glycosylation, or at least that changes of the latter are the hallmark of the process. The detailed description and understanding of this relationship are important in the context of gastrointestinal tract disease, including cancer. Here we employ a broadly used in vitro model of intestinal cell differentiation to track the glycosylation changes in details. We analyzed the glycoproteome- and glycosecretome-derived N-glycomes of undifferentiated Caco-2 adenocarcinoma cells and Caco-2-derived enterocyte-like cells. We used HILIC-HPLC and MALDI-ToF-MS approach together with exoglycosidases digestions to describe qualitative and quantitative N-glycosylation changes upon differentiation. Derived glycan traits analysis revealed, that differentiation results in substantial upregulation of sialylation of glycoproteome and increment of fucosylation within glycosecretome. This was also clearly visible when we analyzed the abundances of individual glycan species. Moreover, we observed the characteristic shift within oligomannose N-glycans, suggesting the augmentation of mannose trimming, resulting in downregulation of H8N2 and upregulation of H5N2 glycan. This was supported by elevated expression of Golgi alpha-mannosidases (especially MAN1C1). We hypothesize, that intensified mannose trimming at the initial steps of N-glycosylation pathway during differentiation, together with the remodeling of the expression of key glycosyltransferases leads to increased diversity of N-glycans and enhanced fucosylation and sialylation of complex structures. Finally, we propose H4N5F1 glycan as a potential biomarker of intestinal epithelial cell differentiation.

Correction: Bonior, J., et al. Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats. Int. J. Mol. Sci. 2017, 18, 1402.

We would like to submit the correction to our published paper [...].

Correction: Warzecha, Z., et al. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats. Int. J. Mol. Sci. 2017, 18, 882.

We would like to submit this correction to our published paper [...].

The Opposite Effect of L-kynurenine and Ahr Inhibitor Ch223191 on Apoptotic Protein Expression in Pancreatic Carcinoma Cells (Panc-1).

BACKGROUND: L-kynurenine, derivate of L-tryptophan, is synthetized by indoleamine 2,3-dioxygenase (IDO). The effects of L-kynurenine depend on its binding to an aryl hydrocarbon receptor (AhR). OBJECTIVE: The aim of this study was to investigate the changes within the apoptotic pathway in PANC-1 cells subjected to L-kynurenine or L-tryptophan considering the production of anti-apoptotic proteins from the IAPs and Bcl-2 family, as well as the regulation of NF-κB signaling. METHODS: The investigated substances were added alone or in combination with the AhR inhibitor (CH223191) to cultures of PANC-1 cells. Cytoplasmic and nuclear proteins were analyzed by immunoblotting and cells were incubated with the investigated substances to determine cytotoxicity and proliferative effects. RESULTS: Incubation of PANC-1 cells with L-kynurenine or L-tryptophan resulted in the increase in antiapoptotic cIAP-1, cIAP-2, XIAP and Bcl-2 expression and a decrease in pro-apoptotic Bax. These changes were accompanied by the reduction of active caspases -9, -3 and PARP-1. The treatment leads to translocation and enhanced production of nuclear NF-κB p50 and Bcl-3. Incubation of the cells with AhR blocker either alone or together with L-kynurenine or L-tryptophan resulted in the opposite effect, leading to the downregulation of IAPs and Bcl-2, upregulation of Bax and caspases expression. CONCLUSION: 1) L-kynurenine and its precursor promote anti-apoptotic effects through the modulation of IDOdependent pathway and regulation of IAPs, Bcl-2 and NF-κB family members in pancreatic carcinoma cells 2) inhibition of AhR by CH223191 exerts an apoptosis-promoting effect, and this observation might suggest the potential use of this compound in pancreatic cancer therapy.

Chemerin alleviates acute pancreatitis in the rat thorough modulation of NF-κB signal.

OBJECTIVE: Chemerin, an adipokine, works as the chemoattractant for the immune cells. The role of chemerin in the inflammatory reaction is controversial. Chemerin has been shown to aggravate the inflammatory response, but other studies demonstrated its anti-inflammatory influence. This study assessed the effects of chemerin on acute pancreatitis (AP) in vivo and in vitro. METHODS: For in vivo experiments male Wistar rats were used. For in vitro study rat pancreatic AR42J cells were employed. Chemerin (1, 5 or 10 µg/kg) was given to the rats prior to the induction of AP by subcutaneous caerulein infusion (25 µg/kg). For in vitro studies cells were subjected to caerulein (10 nM) with or without chemerin (100 nM). Serum amylase activity was measured by enzymatic method, serum TNFα concentration - by ELISA kit. Western-blot was used to examine cellular proteins. RESULTS: AP was confirmed by histological examination. Chemerin given to AP rats decreased histological manifestations of AP, reduced serum amylase activity and TNFα concentration. In AR42J cells subjected to caerulein with addition of chemerin signal for TNFα was reduced comparing to the cultures treated with caerulein alone. Analysis of the dynamics of nuclear translocation for p50, p65 and Bcl-3 points out to NF-κB attenuation as a mechanism of observed anti-inflammatory action of chemerin. CONCLUSION: Chemerin significantly alleviated severity of AP in the rat, this is possibly due to the inhibition of pro-inflammatory signaling in the pancreatic cells.

Comparison of left side or right side vagotomy in the rat subjected to acute pancreatitis.

PURPOSE: We aimed to evaluate the effects of unilateral vagotomy (right-VR or left-VL) on the severity of caerulein-induced acute pancreatitis (AP). MATERIAL AND METHODS: VR or VL was done in Wistar rats 4 days before AP, except in control, sham operated group. Following 5 h administration of subcutaneous injections of caerulein, the pancreatic blood flow (PBF), serum lipase and IL-10 in caval blood samples were measured. The pancreatic specimens were taken from sacrificed rats for the assessment of MDA-4-HNE and morphology. RESULTS: PBF decreased from 310 ± 20 ml/min/100 g of tissue in control rats to 130 ± 12 units in AP (p < 0.01). VR and VL alleviated this effect to 234 ± 22 and 229 ± 26 units, respectively, (p < 0.01). There was an immense increase of serum lipase in AP, from 100 ± 7 U/L up to 5220 ± 210 U/L (p < 0.01). Only VL limited this increase to 3469 ± 300 U/L (p < 0.01). Serum IL-10 increased uniformly in AP, without any effect of preceding VR or VL. VL performed in rats subjected subsequently to AP resulted in stronger reduction of histological changes, such as pancreatic edema and leukocyte infiltration, than the above parameters in AP rats with VR. MDA+4-HNE increased from 7.5 ± 0.1 pmol/g of tissue in control group to 30.6 ± 3 units in AP group (p < 0.01). Concentration of MDA+4-HNE in pancreatic tissue achieved 16.48 ± 3 pmol/g after VR and 13.84 ± 4 pmol/g following VL. CONCLUSION: Our observation might suggest that protective effect of VL could be stronger than VR in the protection on AP. However changes of PBF seem to be similar in both groups of rats.

Melatonin and its metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (afmk) enhance chemosensitivity to gemcitabine in pancreatic carcinoma cells (PANC-1).

BACKGROUND: Gemcitabine is a standard chemotherapeutic agent for patients suffering from pancreatic cancer. However, the applied therapy is not effective due to the resistance of tumor cells to cytostatics, caused by inefficiency of the apoptotic mechanisms. Herein, we present the hypothesis that melatonin and its metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) modify the effect of gemcitabine on PANC-1 cells and that this phenomenon is dependent on the modulation of apoptosis. METHODS: PANC-1 cells have been incubated with melatonin, AFMK or gemcitabine alone or in combination to determine the cytotoxity and proliferative effects. In subsequent part of the study, cells were harvested, the proteins were isolated and analyzed employing immunoprecipitation/immunoblotting. RESULTS: Incubation of PANC-1 cells with gemcitabine resulted in upregulation of pro-apoptotic bax and caspases proteins expression, downregulation of anti-apoptotic Bcl-2, heat shock proteins (HSPs) and modulation of cellular inhibitors of apoptosis (IAPs). Both melatonin and AFMK administered to PANC-1 in combination with gemcitabine inhibited the production of HSP70 and cIAP-2 as compared to the results obtained with gemcitabine alone. These changes were accompanied by upregulation of Bax/Bcl-2 ratio and reduction of procaspases-9 and -3 abundance, followed by an increase in the formation of active caspase of PANC-1 cells with combination of gemcitabine plus low doses of melatonin or AFMK led to enhanced cytotoxicity and resulted in the inhibition of PANC-1 cells growth as compared to effects of gemcitabine alone. CONCLUSION: Melatonin and AFMK could improve the anti-tumor effect of gemcitabine in PANC-1 cells presumably through the modulation of apoptotic pathway.

Pretreatment with obestatin inhibits the development of acetic acid-induced colitis in rats.

INTRODUCTION: Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies have shown that obestatin exhibits some protective and therapeutic effects in the pancreas and stomach. The aim of this study was to examine the effect of pretreatment with obestatin on the development of acetic acid-induced colitis. MATERIAL AND METHODS: Studies were performed on Wistar rats. Before induction of colitis, rats were treated intraperitoneally with saline or obestatin, administered twice at a dose of 4, 8 or 16 nmol/kg/dose. The first dose of saline or obestatin was administered 8 h before the induction of colitis, the second one 7 h after the first dose. Colitis was induced by enema with 1 ml of 4% acetic acid solution. The severity of colitis was assessed 1 or 24 h after administration of enema. RESULTS: Pretreatment with obestatin administered at a dose of 8 or 16 nmol/kg/dose significantly reduced the area of mucosal damage evoked by enema with acetic acid (p < 0.05). This effect was accompanied by an improvement of mucosal blood flow and DNA synthesis in the colon. Moreover, obestatin administered at a dose of 8 or 16 nmol/kg/dose significantly reduced mucosal concentration of IL-1ß and activity of myeloperoxidase (p < 0.05). CONCLUSIONS: Pretreatment with obestatin exhibited a protective effect in the colon, leading to a reduction of colonic damage in acetic acid-induced colitis. This effect was associated with an improvement of mucosal blood flow, an increase in mucosal cell proliferation, and a decrease in local inflammation.

Effect of Endotoxemia in Suckling Rats on Pancreatic Integrity and Exocrine Function in Adults: A Review Report.

Background. Endotoxin (LPS), the component of Gram-negative bacteria, is responsible for sepsis and neonatal mortality, but low concentrations of LPS produced tissue protection in experimental studies. The effects of LPS applied to the suckling rats on the pancreas of adult animals have not been previously explored. We present the impact of neonatal endotoxemia on the pancreatic exocrine function and on the acute pancreatitis which has been investigated in the adult animals. Endotoxemia was induced in suckling rats by intraperitoneal application of LPS from Escherichia coli or Salmonella typhi. In the adult rats, pretreated in the early period of life with LPS, histological manifestations of acute pancreatitis have been reduced. Pancreatic weight and plasma lipase activity were decreased, and SOD concentration was reversed and accompanied by a significant reduction of lipid peroxidation products (MDA + 4 HNE) in the pancreatic tissue. In the pancreatic acini, the significant increases in protein signals for toll-like receptor 4 and for heat shock protein 60 were found. Signal for the CCK1 receptor was reduced and pancreatic secretory responses to caerulein were diminished, whereas basal enzyme secretion was unaffected. These pioneer studies have shown that exposition of suckling rats to endotoxin has an impact on the pancreas in the adult organism.