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1.
PeerJ ; 6: e6117, 2018.
Article in English | MEDLINE | ID: mdl-30588405

ABSTRACT

Magnetoreception, the ability to sense the Earth's magnetic field (MF), is a widespread phenomenon in the animal kingdom. In 1966, the first report on a magnetosensitive vertebrate, the European robin (Erithacus rubecula), was published. After that, numerous further species of different taxa have been identified to be magnetosensitive as well. Recently, it has been demonstrated that domestic dogs (Canis lupus familiaris) prefer to align their body axis along the North-South axis during territorial marking under calm MF conditions and that they abandon this preference when the Earth's MF is unstable. In a further study conducting a directional two-choice-test, dogs showed a spontaneous preference for the northern direction. Being designated as putatively magnetosensitive and being also known as trainable for diverse choice and search tests, dogs seem to be suitable model animals for a direct test of magnetoreception: learning to find a magnet. Using operant conditioning dogs were trained to identify the MF of a bar magnet in a three-alternative forced-choice experiment. We excluded visual cues and used control trials with food treats to test for the role of olfaction in finding the magnet. While 13 out of 16 dogs detected the magnet significantly above chance level (53-73% success rate), none of the dogs managed to do so in finding the food treat (23-40% success rate). In a replication of the experiment under strictly blinded conditions five out of six dogs detected the magnet above chance level (53-63% success rate). These experiments support the existence of a magnetic sense in domestic dogs. Whether the sense enables dogs to perceive MFs as weak as the Earth's MF, if they use it for orientation, and by which mechanism the fields are perceived remain open questions.

2.
Hepatogastroenterology ; 61(129): 111-4, 2014.
Article in English | MEDLINE | ID: mdl-24895804

ABSTRACT

BACKGROUND/AIMS: Anastomotic leakage is a feared complication after gastrectomy and esophagectomy. We report our experience in the treatment with endoscopic stent placement. METHODOLOGY: Seventeen patients with anastomotic leakage after resection of a malignant tumor of the stomach or the distal esophagus have been long-term followed-up. RESULTS: In 10 patients the implanted stent did successfully close the leakage in the first attempt. In 3 out of 7 patients with unsuccessfully sealed leakage a stent-in-stent-manoeuvre did successfully seal the leakage. We had no major complications upon implantation of the stents. We did have no recurrence of a once sealed leakage. CONCLUSIONS: Endoscopic stent placement is a safe procedure in the treatment of anastomotic leakage after gastrectomy and esophagectomy. It should be performed in any clinically relevant leakage if possible. In cases where stent placement is not successful at first, correction of position, stent replacement or a stent-in-stent manoeuvre can be performed, with promising results.


Subject(s)
Anastomotic Leak/therapy , Esophageal Neoplasms/surgery , Esophagectomy , Esophagoscopy , Gastrectomy , Gastroscopy , Postoperative Complications/therapy , Stents , Stomach Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Treatment Outcome
3.
Eur J Pediatr ; 170(2): 241-5, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20924605

ABSTRACT

A severe rare complication in patients with branched-chain organic acidurias (BCOA) is pancreatitis with a limited number of patients published so far. Here, we report on a patient with methylmalonic aciduria (MMA) who developed chronic pancreatitis after several episodes of acute pancreatitis. In addition, an overview is given about some previous published cases with BCOA who developed pancreatitis in the course of the disease. In half of the published MMA patients with pancreatitis, an acute pancreatitis was reported while the rest suffered from a chronic form of this disease. Acute pancreatitis in BCOA patients can clinically present in the context of recurrent vomiting and an impaired general physical condition even without typical signs of pancreatitis. Any form of pancreatitis should be ruled out in the assessment of acutely ill patients with BCOA.


Subject(s)
Amino Acids, Branched-Chain/urine , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/etiology , Acute Disease , Amino Acid Metabolism, Inborn Errors/complications , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Pancreatitis/diagnosis , Pancreatitis/etiology , Prognosis , Severity of Illness Index , Time Factors
4.
J Med Microbiol ; 59(Pt 2): 239-241, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19815666

ABSTRACT

Mycoplasma salivarium, preferentially an inhabitant of the human oral cavity, has rarely been found in other locations associated with disease. We describe here, for what is believed to be the first time, the detection of M. salivarium, together with Candida glabrata, in an occluded biliary stent of an icteric, cholestatic patient.


Subject(s)
Candida glabrata/isolation & purification , Candidiasis/diagnosis , Mycoplasma Infections/diagnosis , Mycoplasma salivarium/isolation & purification , Stents/microbiology , Aged , Anti-Bacterial Agents/therapeutic use , Antifungal Agents , Candidiasis/drug therapy , Candidiasis/microbiology , Fatal Outcome , Humans , Liver Cirrhosis, Biliary/surgery , Male , Mycoplasma Infections/drug therapy , Mycoplasma Infections/microbiology
5.
Hepatobiliary Pancreat Dis Int ; 8(6): 650-2, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20007086

ABSTRACT

BACKGROUND: Obstructive jaundice caused by an intraductal hepatocellular carcinoma is a rare initial symptom. We report a rare case of an extrahepatic icteric type hepatocellular carcinoma. METHODS: A 75-year-old patient was admitted to our hospital because of obstructive jaundice 3 months after resection of multilocular hepatocellular carcinoma. A postoperative bile leakage was treated by placement of a decompressing stent in the common bile duct. Endoscopic retrograde choledochoscopy showed extended blood clots filling the bile duct system and computed tomography revealed a local swelling in the common extrahepatic bile duct. The level of alpha-fetoprotein (AFP) was only slightly elevated but that of CA19-9 was dramatically increased. Cholangiography showed an intraductal filling defect typical of a cholangiocellular carcinoma. RESULTS: Bile duct brushing cytology showed no cholangiocellular carcinoma but hepatocellular carcinoma cells in the extrahepatic bile duct. An extrahepatic bile duct resection was performed. Histological examination confirmed the diagnosis of extrahepatic intraductal growth of hepatocellular carcinoma. CONCLUSION: Ectopic hepatocellular carcinoma is a rare but important differentially diagnosed of extrahepatic bile duct filling defect.


Subject(s)
Bile Duct Neoplasms/complications , Bile Ducts, Extrahepatic/pathology , Carcinoma, Hepatocellular/complications , Cholestasis, Extrahepatic/etiology , Jaundice, Obstructive/etiology , Liver Neoplasms/complications , Aged , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Bile Ducts, Extrahepatic/diagnostic imaging , Bile Ducts, Extrahepatic/surgery , Biomarkers, Tumor/blood , Biopsy , CA-19-9 Antigen/blood , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis, Extrahepatic/diagnostic imaging , Cholestasis, Extrahepatic/pathology , Cholestasis, Extrahepatic/surgery , Humans , Jaundice, Obstructive/diagnostic imaging , Jaundice, Obstructive/pathology , Jaundice, Obstructive/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Tomography, X-Ray Computed , Treatment Outcome , alpha-Fetoproteins/analysis
6.
Vaccine ; 27 Suppl 1: A30-3, 2009 May 29.
Article in English | MEDLINE | ID: mdl-19480958

ABSTRACT

Despite worldwide human papillomavirus (HPV) types distribution showed constant rates of HPV 16/18 in cervical cancers, regional variations have been consistently documented. Very little data is available on HPV genotype prevalence among Italian women with invasive cervical cancer. This study aims to determine the HPV type distribution in cervical specimens obtained from Italian women diagnosed with invasive cervical cancer and referred to the European Institute of Oncology (IEO). Two hundred-sixty eight cervical specimens were obtained from patients diagnosed with invasive cervical cancer referred to the European Institute of Oncology between 1996 and 2006. Following preparation, all cervical samples were sent to laboratories at the International Agency for Research on Cancer (IARC, Lyon, France) for DNA extraction and HPV typing by the multiplex PCR/APEX assay. The study population was divided into four groups from different macro regions: (i) Milan and surrounding area (n=57, 21.3%), (ii) northern Italy (n=81, 30.2%), (iii) central Italy (n=64, 23.9%) and (iv) southern Italy (n=66, 24.6%). The present study is the first at our knowledge that examines a fair number of Italian cervical cancers, about one tenth of all estimated cervical cancer cases occurring yearly, distributed across the whole country. Two-hundred and fifty-one patients (93.7%) resulted HPV DNA positive; of these 201 patients (80.1%) presented a single infection, whereas 50 women (19.9%) presented multiple infection. One hundred and eighty-nine specimens (75.3%) tested positive for either HPV 16 or HPV 18, whereas 62 (24.7%) resulted positive for other high-risk HPV genotypes only. The proportion of HPV 16/18 positive invasive cervical cancers was similar for all the four geographical Italian areas considered. A statistically significant association with younger age and earlier stage was observed for HPV 16/18 related invasive cervical cancers. The results demonstrate that the proportion of HPV 16/18 cervical cancers is fairly constant in all the areas and covers more than 70% of Italian cervical cancer cases. This observation strengthens the decision to start the vaccination programme in all the Italian regions. In addition, the present study provides new and original data on the genotype related differences of the disease that are worth of further investigation.


Subject(s)
Genotype , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/virology , Adult , Aged , Cervix Uteri/virology , Cohort Studies , DNA, Viral/genetics , Female , Geography , Humans , Italy/epidemiology , Middle Aged , Papillomavirus Infections/virology , Prevalence , Uterine Cervical Neoplasms/epidemiology , Young Adult , Uterine Cervical Dysplasia/epidemiology
7.
Cases J ; 1(1): 307, 2008 Nov 13.
Article in English | MEDLINE | ID: mdl-19014528

ABSTRACT

INTRODUCTION: There are numerous cases of abdominal injuries due to bullets. Abdominal injuries due to bullets are a diagnostic and therapeutic challenge. Here, an unusual case of an abdominal perforation caused by a metal projectile, lead to confusion in the interpretation of the preoperative computer tomography. CASE PRESENTATION: We present an unusual case of a 32-year-old male worker who sustained a "shot" to the left upper abdominal quadrant, as a result of a work-related accident. The projectile derived from a special wire that tore during operation. One chain element happened to accelerate towards the patients belly and perforated the abdominal wall. Computer tomography located the radiopaque projectile to the cortex of the left kidney and showed a lesion of the tail of the pancreas. The presence of intraperitoneal free air suggested a gastrointestinal perforation. Immediate open exploration of the peritoneal cavity and the retroperitoneal space revealed perforating lesions of the anterior and posterior gastric wall, as well as the pancreatic tail. The projectile was finally retrieved in the upper pole of the left kidney. The patient had a good clinical course subsequent to surgery and was discharged in good general condition. CONCLUSION: This case represents a rare form of a retained bullet injury and corroborates the need of sufficient measures of worker-protection in area of diamond-studded wire cutting devices.

8.
World J Gastroenterol ; 14(16): 2593-5, 2008 Apr 28.
Article in English | MEDLINE | ID: mdl-18442213

ABSTRACT

Gastrointestinal ulcers occur frequently and are mainly caused by H. pylori infection. In this report, we present a rare case of gastro-duodenal ulcer following selective internal radiation therapy (SIRT). SIRT is a palliative treatment for unresectable liver tumours. During SIRT, (90)Y-microspheres are infused into the hepatic artery. Pre-treatment evaluation for the presence of arterial shunts to neighbouring organs should be determined in order to avoid complications of SIRT.


Subject(s)
Adenocarcinoma/radiotherapy , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Peptic Ulcer/diagnostic imaging , Radiotherapy/adverse effects , Sigmoid Neoplasms/radiotherapy , Adenocarcinoma/drug therapy , Gastric Mucosa/pathology , Gastric Mucosa/radiation effects , Humans , Intestinal Mucosa/pathology , Intestinal Mucosa/radiation effects , Peptic Ulcer/pathology , Radionuclide Imaging , Sigmoid Neoplasms/drug therapy , Yttrium Radioisotopes/adverse effects , Yttrium Radioisotopes/therapeutic use
9.
World J Surg Oncol ; 6: 8, 2008 Jan 26.
Article in English | MEDLINE | ID: mdl-18221555

ABSTRACT

BACKGROUND: Malignant esophageal stenosis with complete obstruction and esophagorespiratory fistula (ERF) is difficult to treat with standard endoscopic techniques. CASE PRESENTATION: We report a patient in whom with local recurrence of esophageal carcinoma an esophagotracheal fistula occurred. Initially the patient had undergone esophageal resection with interposition of a gastric tube. Due to complete obstruction of the lumen by recurrent tumor conventional transoral stent placement failed. For retrograde dilatation a laparotomy was performed. Via a duodenal incision endoscopic access to the gastric tube was achieved. Using a guidewire the esophageal obstruction was traversed and dilated. Then it was possible to place an esophageal stent via an antegrade approach. CONCLUSION: Open surgery enables a safe access for retrograde endoscopic therapy in patients who had undergone esophageal resection with gastric interposition.


Subject(s)
Dilatation, Pathologic , Esophageal Diseases/surgery , Laparotomy , Respiratory Tract Infections/surgery , Stents , Tracheoesophageal Fistula/surgery , Aged , Esophageal Diseases/diagnostic imaging , Esophageal Diseases/therapy , Humans , Male , Radiography , Respiratory Tract Infections/therapy , Tracheoesophageal Fistula/therapy
10.
Hepatology ; 47(2): 592-5, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18098325

ABSTRACT

UNLABELLED: Transient elastography [FibroScan (FS)] is a rapid, noninvasive, and reproducible method for measuring liver stiffness, which correlates with the degree of liver fibrosis in patients with chronic hepatitis. Whether FS is useful in the detection of preexisting liver fibrosis/cirrhosis in patients presenting with acute liver damage is unclear. Patients with acute liver damage of different etiologies were analyzed. Liver stiffness was measured during the acute phase of the liver damage and followed up to the end of the acute phase. A total of 20 patients were included in the study. In 15 of the 20 patients, initial liver stiffness values measured by FS during the acute phase of the liver damage were suggestive of liver cirrhosis. However, none of these 15 patients showed any signs of liver cirrhosis in the physical examination, ultrasound examination, or liver histology [performed in 11 of 15 (73%) patients]. A significant difference was observed in the initial bilirubin levels (5.8 +/- 6.5 mg/dL versus 15.7 +/- 11.8 mg/dL; P = 0.042) and age (32.4 +/- 17.5 years versus 49.7 +/- 15.8 years; P = 0.042) between patients with liver stiffness below or above 12.5 kPa. Six patients with initially high liver stiffness were followed up to abatement of the acute hepatitic phase; in all of them, liver stiffness values decreased to values below the cutoff value for liver cirrhosis. CONCLUSION: Transient elastography frequently yields pathologically high values in patients with acute liver damage and is unsuitable for detecting cirrhosis/fibrosis in these patients.


Subject(s)
Elasticity Imaging Techniques/methods , Hepatitis/diagnosis , Liver Cirrhosis/diagnosis , Liver Cirrhosis/physiopathology , Liver/injuries , Acute Disease , Adolescent , Adult , Biopsy, Needle , Female , Hepatitis/etiology , Hepatitis/pathology , Hepatitis/physiopathology , Humans , Liver/pathology , Liver/physiopathology , Liver Cirrhosis/pathology , Male , Middle Aged , Reproducibility of Results
11.
Hum Psychopharmacol ; 23(1): 43-51, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17926336

ABSTRACT

OBJECTIVE: The present study investigated the effects of rapid tryptophan depletion (RTD) and the ensuing reduction of central nervous levels of serotonin (5-HT) on reactive aggression with respect to personality factors comprising aspects of trait-impulsivity and -aggression in boys with attention-deficit/hyperactivity-disorder (ADHD). METHODS: Twenty-two male adolescent patients with ADHD received the RTD test on one day, and, on another day a tryptophan balanced placebo in a double-blind within-subject crossover design. Impulsive personality factors and trait-impulsivity were assessed in advance of the study. Aggression was provoked using a competitive reaction time game 270 min after RTD/placebo intake. RESULTS: RTD had a significant effect on increased aggressive behaviour with which low-grade impulsive patients responded. High-grade impulsive patients were not affected by RTD or even responded with increased aggressive behaviour while receiving placebo treatment. CONCLUSIONS: The present study supports the hypothesis that 5-HT functioning in ADHD patients influences reactive aggression depending on aspects of trait-impulsivity. Future studies are necessary in order to detect the specific influence of ADHD as regards the relevance to 5-HT-induced changed aggressive responding.


Subject(s)
Diet, Reducing/adverse effects , Impulsive Behavior/metabolism , Serotonin/metabolism , Tryptophan/deficiency , Aggression , Attention Deficit Disorder with Hyperactivity/complications , Child , Cross-Over Studies , Double-Blind Method , Drug Administration Schedule , Humans , Impulsive Behavior/etiology , Male , Psychiatric Status Rating Scales , Reaction Time/physiology
12.
J Clin Ultrasound ; 36(3): 169-73, 2008.
Article in English | MEDLINE | ID: mdl-17685458

ABSTRACT

Sonographers increasingly face imported diseases such as subcutaneous myiasis. In myiasis, some fly species such as the American Dermatobia hominis and the African Cordylobia anthropophaga use humans as intermediate hosts for the maturation of their larvae. High-resolution gray-scale and color Doppler sonography enabled us to identify D hominis larvae in 2 travelers to Central America by visualizing their typical shape, segmentations, and the continuous fluid transport inside the larval body cavity and spiracles. The small C anthropophaga larva in an individual returning from Namibia was initially not detected. Only when using color Doppler sonography was the larva discerned by its intralarval fluid transport. Sonography enables clinicians to locate viable subcutaneous larvae in suspected cases of myiasis.


Subject(s)
Diptera , Myiasis/diagnosis , Subcutaneous Tissue/diagnostic imaging , Subcutaneous Tissue/parasitology , Adult , Animals , Female , Humans , Larva , Male , Middle Aged , Myiasis/parasitology , Myiasis/surgery , Subcutaneous Tissue/surgery , Travel , Ultrasonography, Doppler, Color
13.
World J Gastroenterol ; 13(40): 5397-9, 2007 Oct 28.
Article in English | MEDLINE | ID: mdl-17879415

ABSTRACT

Endoscopic biliary stent insertion is a well-established procedure. It is especially successful in treating postoperative biliary leaks, and may prevent surgical intervention. A routine change of endoprostheses after 3 mo is a common practice but this can be prolonged to 6 mo. We reported a colonic perforation due to biliary stent dislocation and migration to the rectosigmoid colon, and reviewed the literature.


Subject(s)
Foreign-Body Migration/complications , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Stents/adverse effects , Cholestasis/surgery , Colon/injuries , Colon/pathology , Female , Humans , Intestinal Perforation/diagnosis , Middle Aged
14.
J Clin Oncol ; 23(10): 2310-7, 2005 Apr 01.
Article in English | MEDLINE | ID: mdl-15800321

ABSTRACT

PURPOSE: Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown. PATIENTS AND METHODS: Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time. RESULTS: The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001). CONCLUSION: Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Esophageal Neoplasms/surgery , Etoposide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoadjuvant Therapy , Survival Analysis
15.
J Hepatol ; 41(2): 274-83, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15288477

ABSTRACT

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is expressed by many tumors, including hepatocellular carcinoma (HCC) and is involved in tumor angiogenesis. Little is known about its role for HCC infiltration into normal liver parenchyma. METHODS: The effects of VEGF on the integrity of tight junctions were studied in HepG2 cells and human HCC by means of confocal laser scanning microscopy. RESULTS: VEGF induced within 45 min a marked loss of pseudocanaliculi and disruption of occludin-delineated tight junctions. This effect of VEGF was mimicked by phorbol-12-myristate-13-acetate (PMA) and was sensitive to protein kinase C (PKC) inhibition by Gö6850. VEGF induced within 15 min the translocation of the PKC alpha-isoform to the plasma-membrane, but had no effect on the activity of Erks and p38(MAPK). Sections from surgically removed HCC showed expression of VEGF in the tumor and occludin disassembly in normal liver parenchyma next to the tumor. CONCLUSIONS: VEGF induces disruption of tight junctions in a PKC-alpha dependent manner. In addition to its known angioneogenic properties, VEGF may promote HCC spreading into normal liver parenchyma. The data may provide another rationale for the use of VEGF antagonists for tumor therapy.


Subject(s)
Carcinoma, Hepatocellular/ultrastructure , Liver Neoplasms/ultrastructure , Tight Junctions/drug effects , Tight Junctions/ultrastructure , Vascular Endothelial Growth Factor A/pharmacology , Carcinoma in Situ/metabolism , Carcinoma in Situ/pathology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/physiopathology , Cell Line, Tumor , Fluorescent Antibody Technique , Humans , Liver/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/physiopathology , Membrane Proteins/drug effects , Membrane Proteins/metabolism , Neoplasm Invasiveness/physiopathology , Occludin , Phosphoproteins/metabolism , Tetradecanoylphorbol Acetate/pharmacology , Tight Junctions/metabolism , Tissue Distribution , Vascular Endothelial Growth Factor A/metabolism , Zonula Occludens-1 Protein
16.
Pancreas ; 28(2): 181-90, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15028951

ABSTRACT

Caerulein-induced pancreatitis is a widely used experimental model for studies on acute pancreatitis, however, the molecular mechanisms underlying pancreatitis in response to caerulein hyperstimulation are incompletely understood. We therefore studied early effects of caerulein on tight junctional integrity. Mice were injected with the cholecystokinin analogue caerulein (50microg/kg BW/h) to induce pancreatitis. In pancreatic tissue occludin, claudin 1, zonula occludens protein 1 (ZO-1) were stained immunohistochemically and F-actin was visualized with phalloidin-TRITC. Stained sections and isolated acini were studied by confocal laser scanning microscopy. Under control conditions occludin, claudin1, ZO-1, and F-actin showed a linear staining pattern delineating the apical membranes of intralobular duct cells and of acinar cells. While in vitro caerulein hyperstimulation induced within 10 minutes disassembly of both occludin and ZO-1, in vivo caerulein hyperstimulation induced disassembly of occludin and claudin1 but not of ZO-1 from the tight junctions. Subsequent progressive disruption of ZO-1 was detected in a time dependent manner. Disruption of the transmembrane tight junction proteins occludin and claudin1 is an early event of caerulein hyperstimulation and may allow evasion of noxious luminal content into the interstitium, which may augment edema formation in acute pancreatitis.


Subject(s)
Membrane Proteins/metabolism , Pancreatitis/metabolism , Acute Disease , Amylases/blood , Amylases/metabolism , Animals , Blotting, Western , Ceruletide , Claudin-1 , Immunohistochemistry , Lipase/blood , Lipase/metabolism , Male , Mice , Occludin , Pancreas, Exocrine/cytology , Pancreas, Exocrine/metabolism , Pancreatitis/chemically induced , Phosphoproteins/metabolism , Tight Junctions/metabolism , Zonula Occludens-1 Protein
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