OBJECTIVETo explore the significance of mitochondrial D-loop alterations in hyperplastic pancreatic ductal cells in vicinity of pancreatic cancer coexisting with chronic pancreatitis.

METHODSMalignant lesions and foci of pancreatic ductal intraepithelial neoplasia of the pancreas and paired normal gastric mucosal epithelial cells from the same patients, respectively, were assessed by polymerase chain reaction. Somatic point mutations and sequence variants of D-loop were searched by direct sequencing of the mitochondrial genome. D-loops were sequenced by BLAST to identify their mutations.

RESULTSEleven of 12 pancreatic cancers displayed at least one D-loop variants and one tumor presented heteroplasmy. There was an apparent increase in incidence of D-loop mutational rate from PanIN1 (33.3%) to PanIN3 (75%, P < 0.01).

CONCLUSIONMitochondrial D-loop alterations in the pancreas occur in the earliest premalignant lesions and exhibite an increasing occurence that parallels histological severity. These alterations may serve as a valuable marker to follow the histopathological progression of the lesions. Large number of further studies are required to clarify clinical implications of the mitochondrial DNA alterations.

Adenoma ; complications ; genetics ; Adult ; Aged ; Base Sequence ; DNA, Mitochondrial ; genetics ; Epithelial Cells ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pancreatic Ducts ; metabolism ; pathology ; Pancreatic Neoplasms ; complications ; genetics ; Pancreatitis, Chronic ; complications ; genetics ; Precancerous Conditions ; complications ; genetics ; Sequence Analysis, DNA

Hereditary pancreatitis is a rare autosomal dominant inherited disease with 80% penetration rate. The disease is characterized by recurrent episodes of pancreatitis often beginning in childhood, positive family history with at least two other affected members and no known precipitating factors. Most forms of hereditary pancreatitis are caused by one of two commoner mutations, R122H in exon 3 and N29I in exon 2 of the cationic trypsinogen (CT) (PRSS1) gene, located on chromosome 7. These genetic defects are speculated to cause excessive trypsin activity or to prevent inactivation of prematurely activated trypsin, resulting in pancreatitis. We performed mutation analysis of a Korean family with two members having clinically suspicious hereditary pancreatitis. We analyzed the CT gene in DNA samples extracted from peripheral blood of five family members. First of all, polymerase chain reaction and restriction enzyme digestion were performed in exon 3 of the CT gene. And then DNA products were purified and sequenced. We found out that three members of the family, the mother and two daughters, had a R122H mutation of the CT gene. We report the first family of hereditary pancreatitis associated with the CT gene mutation, an arginine to histidine amino acid substitution at residue 122, in Korea.
Amino Acid Substitution ; Child ; DNA Mutational Analysis ; Female ; Gastrointestinal Hemorrhage/*etiology ; Humans ; Mutation ; Pancreatic Pseudocyst/*complications ; Pancreatitis/complications/*genetics ; Trypsinogen/*genetics

OBJECTIVETo explore the relationship of apolipoprotein E (ApoE) genotype with hypertriglyceridemia-associated recurrent acute pancreatitis.

METHODSTaking the fasting serum triglyceride (TG) level > or = 2.3 mmol/L as hypertriglyceridemia, ApoE genotypes in 115 patients with hypertriglyceridemia-associated recurrent acute pancreatitis were assessed by polymerase chain reaction. According to the fasting serum TG level, all patients were divided into 3 groups: TG mild elevation group (2.3 mmol/L < or = TG < 5.5 mmol/L, Group A), TG moderate elevation group (5.5 mmol/L < or = TG < 11.3 mmol/L, Group B), and TG severe elevation group (TG > or = 11.3 mmol/L, Group C).

RESULTSGroup C had significantly fewer patients with biliary tract disease, improper diet and heavy alcohol consumption, and significantly more patients with passed history of moderate-severe hypertriglyceridemia than Group A and B (P < 0.05). The proportion of patients with E3/4, E3/2, E2/4 and E2/2 genotypes and gene frequency for epsilon 2 and epsilon 4 alleles are significantly higher in Group C than in Group A and B(P < 0.05). Group B had significantly more patients with E3/2 genotype and higher gene frequency for epsilon 2 allele than Group A (P < 0.05).

CONCLUSIONSApo epsilon 2 and epsilon 4 alleles are closely related to moderate-severe hypertriglyceridemia-associated recurrent acute pancreatitis.

Acute Disease ; Adolescent ; Adult ; Alleles ; Apolipoproteins E ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; complications ; Male ; Middle Aged ; Pancreatitis ; complications ; genetics ; Recurrence

OBJECTIVETo observe effect of acupuncture on serum macrophage inflammatory protein-2 (MIP-2) and MIP-2 mRNA expressions in isolated Fei and Dachang of severe acute pancreatitis (SAP) induced acute lung injury (ALI) rats in the acute phase.

METHODSForty male Wistar rats were randomly divided into four groups, i.e., the sham-operation group, the SAP group, the acupuncture treatment group, and the acupuncture control group, 10 in each group. The SAP model was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatobiliary duct. Under the guidance of "Fei and Dachang exterior-inferiorly related", points were acupunctured along Fei, Dachang, and Pi channels, as well as those points on the back of rats in the acupuncture treatment group 0.5 h after modeling. Besides, points were acupunctured along Fei and Pi channels, as well as those points on the back of rats in the acupuncture control group 0.5 h after modeling. Serum levels of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO), and MIP-2 expressions were examined 6 h after modeling. Expressions of MIP-2 mRNA in isolated lung and large intestine tissues were detected by reverse transcription PCR.

RESULTSCompared with the sham-operation group, serum levels of TNF-alpha and NO, and expressions of MIP-2 and MIP-2 mRNA in isolated lung and large intestine tissues were significantly higher in the SAP group (P < 0.05). Each index was lower in the acupuncture treatment group than in the SAP group and the acupuncture control group (P < 0.05). Besides, the serum level of MIP-2 and the MIP-2 mRNA expression in isolated lung and large intestine tissues were positively correlated in all groups except the sham-operation group (P < 0.05).

CONCLUSIONSUnder the guidance of "Fei and Dachang exterior-inferiorly related", acupuncture could remarkably reduce the severity of SAP induced ALI rats in the acute phase. Its mechanism might be related to suppressing over-expressions of MIP-2 mRNA in isolated lung and large intestine tissues, and lowering the serum MIP-2 expression level.

Acupuncture Therapy ; Acute Lung Injury ; blood ; complications ; metabolism ; Animals ; Chemokine CXCL2 ; blood ; genetics ; metabolism ; Disease Models, Animal ; Intestine, Large ; metabolism ; Lung ; metabolism ; Male ; Pancreatitis ; blood ; complications ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Systemic lupus erythematosus-related acute pancreatitis (SLEAP) has a poor prognosis with a high mortality. We described the clinical features of SLEAP, and discussed the feasibility of plasma exchange (PE) combined with glucocorticosteroids (GC) in short-term prognosis and possible mechanism in reducing serum inflammatory cytokine IL-6 and removing serum lipids. A retrospective study was performed by an independent rheumatologist. Medical records of SLEAP from March 2010 to December 2014 were retrieved from Tongji Hospital information system, and patients were divided into two groups according to whether PE therapy was adopted. Sixteen patients treated with PE in combination with GC were classified as group A, and the other 10 patients who were treated with merely GC were classified as group B. Patients' clinical remission rate and average daily GC dosage after two-week therapy were compared between the two groups. Patients' serum inflammatory cytokines and lipid concentration were compared between baseline and after two-week treatment in both groups. Pearson correlation test was performed to determine association between serum cytokines and Ranson score. SLEDAI score in group A patients at baseline (14.8±3.1) showed no statistical difference from that in group B (14.1±3.3). At baseline serum IL-6 levels had no significant difference between group A [13.14 (11.12, 16.57) mg/L] and group B [14.63 (11.37, 16.37) mg/L]; after two-week therapy IL-6 decreased significantly in group A [9.16 (7.93, 10.75)mg/L] while it did not show decreasing trend in group B [13.62 (9.29,17.63) mg/L]. Serum lipid concentration after two-week therapy in group A [(TC=5.02±0.53, TG=1.46±0.44) mmol/L] decreased significantly compared to baseline [(TC=6.11±0.50, TG=2.14±1.03) mmol/L], while similar tendency was not observed in group B. The remission rate after two-week therapy was higher in group A (70.0%) than in group B (25.0%). Acute pancreatitis (AP) was one of the clinical manifestations of active SLE. PE combined with GC could reduce serum IL-6 level, and remove serum lipid to improve short-term prognosis. Therefore, it might be a safe and effective way in treating SLEAP and was worth continuing to explore its feasibility.
China ; Female ; Glucocorticoids ; administration & dosage ; Humans ; Interleukin-6 ; blood ; Lipids ; blood ; Lupus Erythematosus, Systemic ; complications ; genetics ; pathology ; therapy ; Male ; Middle Aged ; Pancreatitis ; blood ; etiology ; pathology ; therapy ; Plasma Exchange ; methods ; Prognosis

OBJECTIVE: To investigate the effect of hemin on lung injury following severe acute pancreatitis (SAP) in rats and to explore its rudimentary mechanism. METHODS: Thirty-six rats were randomly divided into 3 groups: a control group, a SAP model group, and a hemin-pretreated group. Rats were sacrificed 12 hours after inducing SAP model. The pathological changes of the pancreas and lungs were observed under light microscope. Expression of heme oxygenase (HO-1) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), NF-kappaB activity in the lung tissues was detected by enzyme linked immunosorbent assay (ELISA), and the serum levels of TNF-alpha and IL-6 were measured by ELISA. RESULTS: HO-1 was induced during experimental SAP, NF-kappaB activity in the lung tissues was elevated after the induction of SAP and the serum levels of TNF-alpha and IL-6 were significantly elevated. Hemin further upregulated the expression of HO-1 mRNA, decreased NF-kappaB activity drastically, and inhibited the serum levels of TNF-alpha and IL-6 significantly (P < 0.05). Hemin could treat SAP by alleviating the pancreatic and lung injury. CONCLUSION Hemin moderates the inflammatory reaction and decreases the lung injury following SAP, the mechanism of which may be closely related to the upregulation of expression of HO-1 mRNA, the inhibitory effect on NF-kappaB, and adjustment of cytokines.
Acute Lung Injury ; drug therapy ; etiology ; Animals ; Cytokines ; genetics ; metabolism ; Female ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; Hemin ; therapeutic use ; Male ; NF-kappa B ; genetics ; metabolism ; Pancreatitis, Acute Necrotizing ; complications ; drug therapy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.
Acute Disease ; Adult ; Apolipoprotein E2/*genetics ; Apolipoprotein E3/*genetics ; Biological Markers/blood ; Combined Modality Therapy ; Diet, Fat-Restricted ; Fatty Acids, Omega-3/therapeutic use ; Female ; Fluid Therapy ; Genetic Predisposition to Disease ; Humans ; Hyperlipoproteinemia Type I/blood/diagnosis/enzymology/*genetics/therapy ; Lipids/blood ; Lipoprotein Lipase/genetics ; Pancreatitis/diagnosis/*etiology/therapy ; Parenteral Nutrition, Total ; Phenotype ; Pregnancy ; Pregnancy Complications/blood/diagnosis/enzymology/*genetics/therapy ; Recurrence ; Tomography, X-Ray Computed ; Treatment Outcome

OBJECTIVETo discuss the role of alveolar macrophage activation in rats with acute necrotizing pancreatitis (ANP) associated with lung injury.

METHODS30 adult Sprague-Dawley rats were randomly divided into five groups (n = 6): normal control group, one-hour group, three-hour group, six-hour group and twelve-hour group after ANP induction. ANP was induced by intraductal administration of 3% sodium taurocholate, while the normal control received an infusion of physiological saline. Alveolar macrophages were harvested by bronchoalveolar lavage. The protein content of lavage fluids, the myeloperoxidase of lung tissue (MPO), and tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) secreted by alveolar macrophages were examined. The expression of TNFalpha mRNA and inducible nitric oxide synthase (iNOS) mRNA was measured with reverse transcription-polymerase chain reaction technique. Histology of the lung and pancreas was scored in a blinded fashion.

RESULTSLung injury was gradually aggravated with disease progression. The level of myeloperoxidase of lung tissue and protein content of bronchoalveolar lavage fluids increased progressively and reached the peak at 12 hour [(10.78 +/- 0.58) U/g for MPO and (2 011.0 +/- 105.5) micro g/ml for protein respectively]. TNFalpha and NO secreted by alveolar macrophages were gradually elevated and peaked on the sixth hour, the maximums were (1 624.2 +/- 149.2) pg/ml and (88.8 +/- 6.5) micro mol/L respectively, but decreased on the twelfth hour. The expression of TNFalpha mRNA and iNOS mRNA was similar with the changes of TNFalpha and NO, upregulated after induction of acute necrotizing pancreatitis and reached their peaks on the sixth hour, then downregulated on the twelfth hour. All the parameters of ANP groups compared to control group were statistical significant (P < 0.05). The histology scores demonstrated an increasing damage of the lung. The expression of TNFalpha mRNA and iNOS mRNA is closely related to lung injury (r = 0.67 for TNFalpha mRNA and r = 0.64 for iNOS mRNA respectively, P < 0.01).

CONCLUSIONThe activation of alveolar macrophage may play an important role in lung injury associated with acute necrotizing pancreatitis.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Female ; Lung ; pathology ; Macrophage Activation ; Macrophages, Alveolar ; physiology ; Male ; Nitric Oxide ; Nitric Oxide Synthase ; genetics ; Nitric Oxide Synthase Type II ; Pancreatitis, Acute Necrotizing ; complications ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; etiology ; Tumor Necrosis Factor-alpha ; genetics

OBJECTIVETo discuss the role of nitric oxide (NO) in lung injury associated with acute necrotizing pancreatitis (ANP).

METHODSOne hundred and twenty SD rats were randomized into five groups: control group, ANP group, L-arginine (L-arg) pretreatment group, L-NAME pretreatment group, and mixed pretreatment group (n = 24 for each group). Rat ANP model was induced by intraductal administration of 3% sodium taurocholate. Alveolar macrophages (AMs) were obtained by bronchoalveolar lavage. The protein content of bronchoalveolar lavage fluids (BALF), the myeloperoxidase (MPO) of lung tissue and generation of tumor necrosis factor alpha (TNFalpha)and NO by alveolar macrophages were evaluated. The expression of TNFalpha mRNA and iNOS mRNA was also measured.

RESULTSLung injury was aggravated gradually with progression of the disease. The level of MPO of lung tissue and the protein content of BALF showed a steady increase with time and peaked at the 12(th) hour (10.8 +/- 0.6 U/g for MPO and 2,011.0 +/- 105.5 micro g/ml for protein, respectively). TNFalpha and NO secreted by AMs were elevated gradually and peaked at the 6(th) hour (1,624.2 +/- 149.2 pg/ml and 88.8 +/- 6.5 micro mol/L respectively) but decreased at the 12(th) hour. The expression of TNFalpha mRNA and iNOS mRNA was similar with the change of TNFalpha and NO. The parameters of the groups of L-arg, L-NAME and the mixed pretreatment were similar to those of ANP group. The parameters compared with those of the control group showed a significant difference (P < 0.05). The parameters of groups of L-Arg and L-NAME pretreatment in comparison with those of the ANP group showed significant difference (P < 0.05).

CONCLUSIONSOver production of NO mediated by iNOS aggravates lung injury caused by acute necrotizing pancreatitis. Administration of exogenous NOS substrate would worsen lung injury, whereas administration NOS inhibitor would alleviate lung injury.

Animals ; Arginine ; pharmacology ; Disease Models, Animal ; Enzyme Inhibitors ; pharmacology ; Female ; Histocytochemistry ; Lung ; drug effects ; metabolism ; pathology ; Lung Injury ; etiology ; physiopathology ; Macrophages, Alveolar ; drug effects ; metabolism ; pathology ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; physiology ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; genetics ; metabolism ; Pancreatitis, Acute Necrotizing ; complications ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; metabolism