A rare case of aggressive, hereditary paraganglioma associated with a pathogenic variant in SDHD.

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Combination of endosonography-guided fine-needle aspiration and conventional endoscopic techniques in sarcoidosis diagnosis. Optimal strategy to achieve high diagnostic yield.

INTRODUCTION: Diagnosis of sarcoidosis is based on clinical status and radiologic specific findings. Tissue confirmation of noncaseating granulomas is crucial. Pathological confirmation of pulmonary sarcoidosis is most commonly accomplished by bronchoscopy, which has a diagnostic yield of approximately 60%-70%. OBJECTIVES: In this prospective study, we analysed potential benefit of EBUS-TBNA and EBB combination, application of cell blocks and smears with puncturing more than one station of lymph nodes in order to determine optimal strategy in diagnosis of sarcoidosis. METHODS: About 133 patients with suspicion of sarcoidosis (stage I and stage II) were included in this study. Each patient underwent conventional bronchoscopy with endobronchial biopsy (EBB) followed by the EBUS and puncturing at least two different lymph node stations. RESULTS: Positive cytopathological verification of sarcoidosis in our study was obtained in 123 patients (92.5%). EBUS-TBNA was diagnostic in 116 patients (87.2%). EBB was positive in 26 patients (19.55%). Combination of EBUS-TBNA and EBB statistically increased diagnostic yield of sarcoidosis to 92.5%. Sensitivity of EBUS-TBNA with EBB was 93.9%, specificity 100%, PPV 100% and NPV 20%. CONCLUSIONS: Combining EBUS-TBNA from at least two lymph node stations and EBB increased diagnostic yield of sarcoidosis. Such diagnostic strategy had almost 93% of diagnostic yield in stage I and stage II of sarcoidosis. Taking into account the safety of the whole procedure with endobronchial ultrasonography combined with conventional endoscopy with EBB and its cost effectiveness, TBLB can be intended to diagnose stage III or IV of pulmonary sarcoidosis.

Correction: Warzecha, Z. et al. Protective Effect of Pretreatment with Acenocoumarol in Cerulein-Induced Acute Pancreatitis. Int. J. Mol. Sci. 2016, 17, 1709.

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 [...].

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.

Rationale and feasibility of mucin expression profiling by qRT-PCR as diagnostic biomarkers in cytology specimens of pancreatic cancer.

BACKGROUND: Aberrantly expressed mucin glycoproteins (MUC) play important roles in pancreatic ductal adenocarcinoma (PDAC), yet their use as a diagnostic aid in fine-needle aspiration biopsy (FNAB) is poorly documented. The aim of this study was to investigate the rationale and feasibility of mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) expression profiling by RT-PCR for diagnostic applications in cytology. METHODS: Mucin expression was examined by RT-PCR and immunohistochemistry in specimens resected from patients with pancreatic (n = 101), ampullary (n = 23), and common bile duct (n = 10) cancers and 33 with chronic pancreatitis. Furthermore, mucin profiling by RT-PCR was prospectively compared in surgical and biopsy specimens of 40 patients with pancreatic solid tumours qualified for FNAB prior to surgery. RESULTS: A logistic regression model to distinguish PDAC from chronic pancreatitis using RT-PCR profiling included MUC3, MUC5AC, and MUC6. The same set of mucins differentiated ampullary and bile duct cancers from chronic pancreatitis. AUCs for the ROC curves derived from the two models were 0.95 (95%CI 0.87-0.99) and 0.92 (95%CI 0.81-0.98), respectively. The corresponding positive likelihood ratios were 6.02 and 5.97, while the negative likelihood ratios were 0.10 and 0.12. AUCs of ROC curves obtained by RT-PCR and immunohistochemistry demonstrated that both analytical methods were comparable. Surgical and cytological samples showed significantly correlated values of ΔCt for individual mucins with the overall Pearson's correlation coefficient r = 0.841 (P = 0.001). CONCLUSIONS: Mucin expression profiling of pancreatic cancer with RT-PCR is feasible and may be a valuable help in discriminating malignant lesions from chronic pancreatitis in FNAB cytology.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. RESULTS: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1ß, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. CONCLUSION: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms in Krakow and Krakow district in 2007-2011.

INTRODUCTION: Gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) are rare and heterogeneous tumours with variable biology. The aim of this study was to evaluate the epidemiology of GEPNEN in the population of Krakow and Krakow district in 2007-2011. MATERIAL AND METHODS: The Database of the Chair and Department of Endocrinology, Jagiellonian University Medical College, comprising the data on NEN cases collected from the Endocrinology Department, University Hospital in Krakow and from independent sources: surgery, pathology, and endocrinology departments located in the Krakow area, was searched for cases of GEPNEN patients living in Krakow and Krakow district, diagnosed between 2007 and 2011. Eighty-eight such patients (39 males, 49 females, median age at diagnosis 59 ± 17 years) were identified and characterised. RESULTS: The mean follow-up time was 2.67 ± 1.6 years. The most frequent primary location of GEPNEN was small intestine (20%), followed by the appendix (18%), stomach (16%), pancreas (16%), rectum (15%), and colon (15%). NENG1 predominated (64%) in the analysed group. Most well-differentiated GEPNEN (63%) were diagnosed at stage I; however, 18% of them were diagnosed at stage IV. Metastases at diagnosis were found in 31% of patients. The GEPNEN incidence rate in 2007-2011 was 2.1/100000 inhabitants/year, without significant increase during the studied period. CONCLUSIONS: GEPNEN incidence and epidemiology in the population of Krakow and Krakow district is similar to the incidence observed in most European countries. Registers are important tools to evaluate GEPNEN epidemiology. (Endokrynol Pol 2017; 68 (1): 42-46).

Endosonography­guided fine­needle aspiration in the diagnosis of sarcoidosis: a randomized study.

INTRODUCTION    There are no widely accepted standards for the diagnosis of sarcoidosis. OBJECTIVES    The aim of this study was to assess the relative diagnostic yield of endobronchial ultrasound fine-needle aspiration (EBUS -FNA) and endoscopic ultrasound fine needle aspiration (EUS -FNA), and to compare them with standard diagnostic techniques such as endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA), and mediastinoscopy. PATIENTS AND METHODS    This was a prospective randomized study including consecutive patients with clinical diagnosis of stage I or II sarcoidosis. EBB, TBLB, and TBNA were performed at baseline in all patients. Subsequently, patients were randomized to group A (EBUS -FNA) or group B (EUS -FNA). Next, a crossover control test was performed: all patients with negative results in group A underwent EUS -FNA and all patients with negative results in group B underwent EBUS -FNA. If sarcoidosis was not confirmed, mediastinoscopy was performed. RESULTS    We enrolled 106 patients, of whom 100 were available for the final analysis. The overall sensitivity and accuracy of standard endoscopic methods were 64% each. When analyzing each of the standard endoscopic methods separately, the diagnosis was confirmed with EBB in 12 patients (12%), with TBLB in 42 patients (42%), and with TBNA in 44 patients (44%). The sensitivity and accuracy of each endosonographic technique were significantly higher than those of EBB+TBLB+TBNA (P = 0.0112 vs P = 0.0134). CONCLUSIONS    The sensitivity and accuracy of EBUS -FNA and EUS -FNA are significantly higher than those of standard endoscopic methods. Moreover, the sensitivity and accuracy of EUS -FNA tend to be higher than those of EBUS -FNA.

Validation of the intervertebral disc histological degeneration score in cervical intervertebral discs and their end plates.

BACKGROUND CONTEXT: Vertebral joints consist of intervertebral discs (IVDs) and cartilaginous end plates (EP) that lie superiorly and inferiorly to the IVDs and separate them from the adjacent vertebral bodies. With aging, both IVDs and EPs undergo degeneration. The Histologic Degeneration Score (HDS) is a grading system that microscopically evaluates the degree of degeneration in lumbar discs and predicts it with high accuracy basing on several histological markers of IVD and EP. There is currently a lack of validated histologic grading schemes for cervical spine degeneration. PURPOSE: The aim of our study was to describe the changes in cervical IVDs and EPs with degeneration and to test the validity of the HDS in the cervical spine. STUDY DESIGN: A histological study on degenerative changes in cervical IVDs and EPs was conducted. METHODS: Thirty human cadavers were dissected to obtain 60 cervical IVDs from the lower half of C4 to the level of the upper half of C6. The IVDs were carefully excised along with EPs and then sectioned to obtain midsagittal samples for macroscopic examination according to a five-grade classification system. The samples were further dissected, fixed, and stained for histological examination according to HDS. RESULTS: Thirty C4-C5 IVDs and thirty C5-C6 IVDs were macroscopically examined for degeneration. The averaged Thompson's grade was found to be 2.9±1.3. The mean HDS for IVDs was 13.1±5.8 and for EP was 10.2±5.2. The interrater reliability estimates indicated excellent reliability (κ values>0.81, percentage agreement 86.1%-96.1%). Spearman's rank correlation coefficients for IVD and EP scores showed good consistency in predicting macroscopic degeneration. No significant differences were found between the values for cervical IVDs and EPs in the present study and those for lumbar discs derived in previous studies. CONCLUSIONS: The HDS was confirmed to be as accurate in predicting the degree of degeneration in the cervical spine as in the lumbar region. To our best knowledge, this is the first reported and validated histological classification system intended for assessing histological degeneration in the cervical spine. Therefore, HDS can be recommended for academic and pathologic purposes in cervical disc degeneration.

Protective Effect of Pretreatment with Acenocoumarol in Cerulein-Induced Acute Pancreatitis.

Coagulation is recognized as a key player in inflammatory and autoimmune diseases. The aim of the current research was to examine the effect of pretreatment with acenocoumarol on the development of acute pancreatitis (AP) evoked by cerulein. METHODS: AP was induced in rats by cerulein administered intraperitoneally. Acenocoumarol (50, 100 or 150 µg/kg/dose/day) or saline were given once daily for seven days before AP induction. RESULTS: In rats with AP, pretreatment with acenocoumarol administered at the dose of 50 or 100 µg/kg/dose/day improved pancreatic histology, reducing the degree of edema and inflammatory infiltration, and vacuolization of acinar cells. Moreover, pretreatment with acenocoumarol given at the dose of 50 or 100 µg/kg/dose/day reduced the AP-evoked increase in pancreatic weight, serum activity of amylase and lipase, and serum concentration of pro-inflammatory interleukin-1ß, as well as ameliorated pancreatic DNA synthesis and pancreatic blood flow. In contrast, acenocoumarol given at the dose of 150 µg/kg/dose did not exhibit any protective effect against cerulein-induced pancreatitis. CONCLUSION: Low doses of acenocoumarol, given before induction of AP by cerulein, inhibit the development of that inflammation.

Neuroendocrine neoplasms and somatostatin receptor subtypes expression.

Neuroendocrine neoplasms (NENs) show wide spectrum of clinical course - from benign biological potential to recurrences and rapidly progressive disease. Somatostatin analogs that bind to somatostatin receptor are part of the therapy; detection and evaluation of activation of somatostatin receptor subtypes are part of the process of new therapy induction. When using RT-PCR method and immunohistochemistry, it is possible to detect more than two SSTR subtypes in majority or all neuroendo-crine neoplasms regardless tumor origin. Generally with some exceptions, from the viewpoint of tumor grade - apart the site of origin, there is a tendency to decrease the percentage of SSTRs expression; 100% (G1, 2)-85.7% (G3) for SSTR 1; 81.8% (G1, 2)-61.9% (G3) for SSTR 2; 54.5% (G1, 2)-52.4% (G3) for SSTR 3; 9% (G1, 2)-4.8% (G3) for SSTR 5. Different studies indi-cate significant differences in the expression of SSTR 1 and 2A and 2B between NEC G3 small cell type and non-small cell type. Further research on SSTRs expression in NEN could serve as base to development and improvement of somatostatin analogs' pharmacotherapy in patients with unsatisfactory course.

Semiquantitative immunohistochemistry for mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) profiling of pancreatic ductal cell adenocarcinoma improves diagnostic and prognostic performance.

AIMS: Mucin (MUC) glycoproteins are involved in various steps of the carcinogenesis and progression of human malignancies. The aim of this study was to verify whether semiquantitative evaluation of MUC staining by immunohistochemistry may help to differentiate pancreatic ductal cell adenocarcinoma (PDAC) from chronic pancreatitis and normal pancreas. METHODS AND RESULTS: Mucin expression was examined by immunohistochemistry in surgical specimens resected from 101 patients with PDAC and 33 with chronic pancreatitis, and in 40 normal pancreatic tissue specimens. A quickscore (QS, range 0-300) was calculated by multiplying staining intensity by the percentage of positive cells. A diagnostic model was developed for MUC QS (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6), based on a receiver operating characteristic (ROC) curve and logistic regression analysis. Median QS values for MUC1 and MUC5AC were significantly higher for PDAC, whereas patients with non-malignant tissues had higher values for MUC3 and MUC6. The area under the curve for the ROC curve derived from the diagnostic model including MUC3, MUC5AC and MUC6 was 0.96 [95% confidence interval (CI) 0.91-0.98], with 85% sensitivity and 94% specificity. Median QS values for MUC2 were significantly higher in patients with less advanced tumours, whereas venous invasion was associated with a lower QS for MUC6. Moreover, multivariate survival analysis revealed that low MUC6 expression was a negative prognostic factor, with a hazard ratio of 1.73 (95% CI 1.07-2.81). CONCLUSIONS: The three-MUC diagnostic model (MUC3, MUC5AC, and MUC6) showed an excellent ability to discriminate pancreatic cancer from non-malignant tissues, and yielded information that may prove useful for the development of clinical applications.

IgG4-related disease in the head and neck region: report of two cases and review of the literature.

IgG4-related disease (IgG4-RD) is a rare immune-mediated condition characterized by extensive tissue fibrosis and infiltration by immunoglobulin G4 positive plasma cells in a single organ or systemic appearance. Two cases are presented including an unusual case of a 30-year-old man with IgG4-RD appearing simultaneously in the cervical lymph nodes, ethmoid, maxillary sinuses, and upper gingiva, with spontaneous loss of teeth. According to the literature, this is the first case with loss of teeth occurring in the course of the disease. The second case is a 46-year-old man suffering from IgG4-related chronic sclerosing sialadenitis of the right submandibular gland.

Immunohistochemical predictors in squamous cell carcinoma of the tongue and floor of the mouth.

BACKGROUND: The purpose of this study was to evaluate the clinical usefulness of the immunoexpression of Ki-67, matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF)-C, and VEGF-D in predicting follow-up treatment in patients with squamous cell carcinoma (SCC) of the tongue and floor of the mouth (FOM). METHODS: Marker expression was evaluated in surgical specimens taken from 60 patients who underwent surgery because of primary SCC without prior therapy. RESULTS: Strong MMP-2 expression was positively correlated with a higher risk of nodal recurrence (p = .047). Strong VEGF-C expression was found in patients with distant metastases (p = .008). Cox's regression model showed high Ki-67, MMP-2, and VEGF-C expression, which were independent predictors of disease-specific survival (p = .001, p = .002, and p < .001, respectively). CONCLUSION: It seems that targeting MMP-2 and VEGF-C may improve local control, thereby reducing the risk of distant metastasis in patients with SCC of the tongue and FOM. © 2015 Wiley Periodicals, Inc. Head Neck 38: E747-E753, 2016.

Therapeutic Effect of Obestatin in the Course of Cerulein-Induced Acute Pancreatitis.

OBJECTIVE: The aim of this study was to determine the impact of obestatin therapy on the course of cerulein-induced pancreatitis. METHODS: Acute pancreatitis was induced by cerulein given intraperitoneally 5 times with 1 hour intervals at the dose of 50 µg/kg per dose. Obestatin was administered twice a day at the dose of 8 nmol/kg per dose, starting the first dose 24 hours after the last injection of cerulein. Severity of acute pancreatitis (AP) was examined at 0 hour or 1, 2, 3, 5, 7, and 10 days after the last injection of cerulein. RESULTS: Administration of cerulein led to development of acute edematous pancreatitis in all rats, and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with obestatin reduced morphological signs of pancreatic damage (pancreatic edema, leukocyte infiltration, vacuolization of acinar cells) and led to earlier regeneration of the pancreas. Biochemical indexes of severity of pancreatitis such as serum activity of pancreatic digestive enzymes were significantly reduced in animals treated with obestatin. These effects were accompanied by increase in pancreatic DNA synthesis and decrease in serum level of proinflammatory interleukin 1ß. In addition, administration of obestatin improved pancreatic blood flow in rats with AP. CONCLUSIONS: Treatment with exogenous obestatin reduces severity of AP and accelerates pancreatic recovery.

Age- and degeneration-related variations in cell density and glycosaminoglycan content in the human cervical intervertebral disc and its endplates.

The first aim of this study was to quantify cell density in cervical intervertebral discs (IVDs) and endplates of varying age and degeneration grade. The second aim was to analyze glycosaminoglycan (GAG) content in cervical IVDs and their endplates. Sixty cervical IVDs were excised from 30 human cadavers, not later than 24 hours post-mortem. Each sample underwent sectioning. Half of each sample underwent GAG content analysis using the dimethylmethylene blue binding assay. The other half underwent histological processing, histological degeneration grading, and cell density assessment using the Abercrombie method. The nucleus pulposus (NP) (4218 ± 417 cells/mm³) had significantly higher cell density than the anterior annulus fibrosus (AF) (3283 ± 438 cells/mm³; p < 0.0001), and similar cell density (4464 ± 551 cells/mm³; p = 0.36) to the posterior AF. Cell density was similar throughout the different regions of the endplate. The NP (619 ± 178 µg/mg dry weight) had a significantly higher GAG content than both the anterior (428 ± 199 µg/mg dry weight; p < 0.0001) and posterior AF (524 ± 218 µg/mg dry weight; p < 0.0001). In conclusion, this study introduces detailed 3D maps of cervical IVD and endplate cell density and GAG content. Furthermore, it shows that cervical IVDs and their endplates only slightly differ, in terms of cell density and GAG content, from lumbar IVDs.

Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

OBJECTIVE: Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis. AIM: The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion. METHODS: Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula. RESULTS: Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1ß level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and pancreatic exocrine secretion. Administration of obestatin at doses used was without significant effect with regard to daily food intake or pancreatic exocrine secretion in sham-operated rats, as well as in rats with acute pancreatitis. On the other hand, obestatin abolished a statistical significance of difference in food intake between animals with AP and control animals without pancreatic fistula and induction of AP. CONCLUSION: Treatment with the exogenous obestatin reduces severity of ischemia/reperfusion-induced acute pancreatitis and accelerates recovery in this disease. The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

Pretreatment with obestatin reduces the severity of ischemia/reperfusion-induced acute pancreatitis in rats.

UNLABELLED: Obestatin, as ghrelin, has been originally extracted from the stomach, which remains its major source. Previous studies have shown that administration of obestatin exhibits protective and healing-promoting effects in several organs, including the stomach and kidney. In pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis and promotes survival of pancreatic beta cells and human islets. The aim of the present study was to check the universality of protective effect of obestatin in the pancreas. For this reason we investigated the influence of obestatin administration on the development of ischemia/reperfusion-induced pancreatitis. Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the gland. Obestatin (4, 8 or 16 nmol/kg/dose) was administered intraperitoneally twice: 0.5h before exposure to ischemia, and 3h after the first injection. The effect of obestatin on the course of necrotizing pancreatitis was assessed after 6-h reperfusion, and included histological, functional, and biochemical analyses. Treatment with obestatin reduced morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland. These effects were accompanied by an improvement of pancreatic DNA synthesis and superoxide dismutase activity, and a decrease in serum level of lipase and pro-inflammatory interleukin-1ß. Moreover pretreatment with obestatin reduced myeloperoxidase activity and malondialdehyde concentration in pancreatic tissue of rats with acute pancreatitis. CONCLUSIONS: Administration of obestatin inhibits the development of ischemia/reperfusion-induced acute pancreatitis. This observation, taken together with previous findings that obestatin protects the pancreas against cerulein-induced pancreatitis, indicates that protective effect of obestatin in the pancreas is universal and independent of the primary cause of acute pancreatitis.