deoxycholic-acid and Necrosis

Phosphatidylcholine and deoxycholate (PC-DC) injections are a popular nonsurgical method to eliminate unwanted fat. The safety and efficacy of this approach is uncertain.. The authors evaluate the effects of PC-DC treatments on body composition, adipocyte function, and mechanisms responsible for fat loss.. This randomized, open-label study enrolled 13 women with a body mass index (BMI) ≤30 kg/m(2) and lower abdominal subcutaneous fat suitable for small-volume liposuction. Patients were randomized by the final digit of their Social Security numbers and received between 2 and 4 PC-DC treatments, spaced 8 weeks apart. One side below the umbilicus was injected with PC-DC. The contralateral, control side received no treatment. Adipose tissue biopsies were performed on the treated side at baseline, 1 week after the first treatment, and 8 weeks after the final treatment. The primary outcome was change in adipose tissue thickness at baseline and 8 weeks after the final treatment.. Seven women completed the study. Treatment with PC-DC significantly reduced the thickness of the anterior subcutaneous abdominal fat (P = .004). Adipose tissue showed rapid increases in crown-like structures, macrophage infiltration, and reduced expression of leptin, hormone-sensitive lipase, adipose tissue triglyceride lipase, and CD36. Plasma C-reactive protein, lipid profile, and plasma glucose concentrations were unchanged.. PC-DC injections can effectively reduce abdominal fat volume and thickness by inducing adipocyte necrosis. These treatments do not appear to increase circulating markers of inflammation or affect glucose and lipid metabolism.

Topics: Absorptiometry, Photon; Adipocytes; Adiposity; Adult; Analysis of Variance; Biomarkers; Biopsy; Blood Glucose; Cosmetic Techniques; Deoxycholic Acid; Female; Gene Expression Regulation; Humans; Inflammation Mediators; Injections, Subcutaneous; Lipids; Lipolysis; Magnetic Resonance Imaging; Middle Aged; Missouri; Necrosis; Patient Satisfaction; Phosphatidylcholines; Subcutaneous Fat, Abdominal; Time Factors; Treatment Outcome

Subcutaneous injections of phosphatidylcholine (PC), sodium deoxycholate (NADC), and a mixture of them were found to be an effective option for treating cellulite. However, it is noteworthy that the injection of NADC may result in inflammation as well as necrosis in the injection area. The preparation of a sustained release formulation based on lipid-liquid crystal that controls the release of NADC could be a potential solution to address the issue of inflammation and necrosis at the site of injection. To present a practical and validated approach for accurately determining the concentration of NADC in LLC formulations, spectrofluorimetry was used based on the International Council for Harmonization (ICH) Q2 guidelines. Based on the validation results, the fluorometric technique has been confirmed as a reliable, efficient, and economical analytical method for quantifying NADC concentrations. The method demonstrated favorable attributes of linearity, precision, and accuracy, with an r

Topics: Delayed-Action Preparations; Deoxycholic Acid; Humans; Inflammation; Lipids; Liquid Crystals; Necrosis

Phosphatidylcholine/deoxycholate (PC/DC) combination is frequently used for injection lipolysis in body contouring and size reduction of subcutaneous lipomas. Nonetheless, studies that assess possible injurious effects of PC/DC combination on tissues at injection sites are inadequate. The current work attempts to evaluate the effects of repeated PC/DC injection on skeletal muscles and neural tissues at the injection site. For this purpose, female Wistar rats were randomly assigned into 2 groups, 10 rats each, and injected percutaneously via either normal saline (control group) or PC/DC (treated group) in the groin area for 4 consecutive days. Biopsies were harvested on the 4(th) day for histopathological studies. The results of the present work demonstrated that repeated injection of PC/DC caused neural damage and intense inflammation at the injection site leading to skeletal muscle degeneration, necrosis and fibrosis. Electron microscopic examination of the neural tissues in the injected area showed intra-neural fibroblasts, deposition of intra-neural collagen fibers and marked myelin degeneration. In addition, PC/DC injection caused thickening of intra-neural blood vessel walls and evident endo-neural mast cells. The current data highlight the attendant risk of neuromuscular injury associated with repeated PC/DC injection during the treatment of undesirable fat deposits and lipomas.

Topics: Animals; Deoxycholic Acid; Female; Fibrosis; Microscopy, Electron, Transmission; Muscle, Skeletal; Necrosis; Peripheral Nerves; Phosphatidylcholines; Rats; Rats, Wistar

The objective of this study is to investigate the effect of deoxycholic acid (DCA) on rat pancreatic acinar cell line AR42J and the functional mechanisms of DCA on AR42J cells. AR42J cells were treated with various concentrations of DCA for 24 h and also treated with 0.4 mmol/L DCA for multiple times, and then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect the AR42J cell survival rate. Flow cytometric was used to detect the cell apoptosis and necrosis in AR42J cells treated with 0.4 mmol/L and 0.8 mmol/L DCA. The cells treated with phosphate buffer saline (PBS) were served as control. In addition, the DNA-binding activity assays of transcription factors (TFs) in nuclear proteins of cells treated with DCA were determined using Panomics Procarta Transcription Factor Assay Kit. The relative survival rates were markedly decreased (P < 0.05) in a dose- and time-dependent manner. Compared with control group, the cell apoptosis and necrosis ratio were both significantly elevated in 0.4 mmol/L DCA and 0.8 mmol/L DCA groups (P < 0.01). A significant increase (P < 0.05) in the activity of transcription factor 2 (ATF2), interferon-stimulated response element (ISRE), NKX-2.5, androgen receptor (AR), p53, and hypoxia-inducible factor-1 (HIF-1) was observed, and the activity of peroxisome proliferator-activated receptor (PPAR), activator protein 1 (AP1), and E2F1 was reduced (P < 0.05). In conclusion, DCA inhibited proliferation and induced apoptosis and necrosis in AR42J cells. The expression changes of related genes regulated by TFs might be the molecular mechanism of AR42J cell injury.

Topics: Acinar Cells; Animals; Apoptosis; Cell Line; Cell Proliferation; Deoxycholic Acid; Flow Cytometry; Necrosis; Pancreas; Rats; Transcription Factors

Phosphatidylcholine (PPC) and sodium deoxycholate (DC) injections have been used cosmetically to reduce localized fat, but to date, few studies have addressed the histological effect of human fat tissue following injections of PPC and DC. We injected PPC and DC mixed with normal saline into the patient's abdominal area. Examinations of postinjection tissue revealed marked changes within the subcutaneous fat. We observed important microscopic evidence of substitution of fat by fibrosis, marked inflammatory infiltration with microabscess formation in the dermis, and septal and lobular panniculitis with thick fibrous septa. Fat necrosis with microcalcification and cyst formation were observed in the subcutaneous fat. Fibroid necrosis with extravasation was noted in the small vessels around fat necrosis. Therefore, careful use of PPC and DC is recommended when patients want to cosmetically reduce localized fat.

Topics: Adipose Tissue; Adult; Deoxycholic Acid; Female; Fibrosis; Humans; Mesotherapy; Necrosis; Obesity, Abdominal; Panniculitis; Phosphatidylcholines

Injections with phosphatidylcholine- and deoxycholate-containing substances are used to treat localized fat accumulation and lipomas. It is believed that the injected substances induce fat cell destruction with subsequent acute panniculitis followed by a repair process of the treated fat tissue.. We investigated whether necrosis or apoptosis of fat cells was induced by the injected substances.. Samples of fat tissue of lipoma were collected at various times after injection and evaluated by light and electron microscopy, by immunostaining for active caspase-3 and antideoxyribonuclease I, in situ end-labelling (TUNEL staining), and biochemical caspase-3 assays.. Light and electron microscopy showed fat cell necrosis in all areas of the treated lipomas. Low levels of active caspase-3 indicated the absence of apoptosis.. Injection of the lipolytic substances phosphatidylcholine and deoxycholate leads to fat cell necrosis rather than apoptosis. However, additional studies evaluating different dosing and further time points after treatment are necessary.

Topics: Adipose Tissue; Caspase 3; Deoxycholic Acid; Deoxyribonuclease I; Humans; In Situ Nick-End Labeling; Lipolysis; Microscopy, Electron; Necrosis; Phosphatidylcholines

The continuous exposure of the colonic epithelium to high concentrations of bile acids may exert cytotoxic effects and has been related to pathogenesis of colon cancer. A better knowledge of the mechanisms by which bile acids induce toxicity is still required and may be useful for the development of new therapeutic strategies. We have studied the effect of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) treatments in BCS-TC2 human colon adenocarcinoma cells. Both bile acids promote cell death, being this effect higher for CDCA. Apoptosis is detected after 30 min-2 h of treatment, as observed by cell detachment, loss of membrane asymmetry, internucleosomal DNA degradation, appearance of mitochondrial transition permeability (MPT), and caspase and Bax activation. At longer treatment times, apoptosis is followed in vitro by secondary necrosis due to impaired mitochondrial activity and ATP depletion. Bile acid-induced apoptosis is a result of oxidative stress with increased ROS generation mainly by activation of plasma membrane enzymes, such as NAD(P)H oxidases and, to a lower extent, PLA2. These effects lead to a loss of mitochondrial potential and release of pro-apoptotic factors to the cytosol, which is confirmed by activation of caspase-9 and -3, but not caspase-8. This initial apoptotic steps promote cleavage of Bcl-2, allowing Bax activation and formation of additional pores in the mitochondrial membrane that amplify the apoptotic signal.

Topics: Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Survival; Chenodeoxycholic Acid; Colonic Neoplasms; Deoxycholic Acid; Humans; Membrane Potential, Mitochondrial; Mitochondria; Necrosis; Oxidative Stress; Reactive Oxygen Species

Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate on Caco-2 enterocyte monolayers using transepithelial electrical resistance to assay barrier function. A bisphenol A coupled triblock polyethylene glycol (PEG), PEG 15-20, was shown to prevent sodium deoxycholate-induced barrier failure. Enzyme-linked immunosorbent assay, lactate dehydrogenase, and caspase 3-based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens 1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weight greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia.

Topics: Apoptosis; Benzhydryl Compounds; Bile Acids and Salts; Caco-2 Cells; Caspase 3; Deoxycholic Acid; Humans; Intestinal Mucosa; Membrane Proteins; Microscopy, Fluorescence; Necrosis; Phenols; Phosphoproteins; Polyethylene Glycols; Polymers; Zonula Occludens-1 Protein

A new treatment variation in the spectrum of aesthetic medicine has been investigated worldwide since 2004: so-called injection lipolysis. Advances in knowledge regarding the efficacy and mechanism of action have been achieved especially in Germany because most users are found in Germany when compared on an international level. The reason for this is that the combination of phosphatidylcholine and deoxycholic acid as active substances has been approved for i.v. treatment of fat embolisms. It is thus readily available, but the subcutaneous injection of the drug Lipostabil N® is considered as off-label use. Meanwhile injection lipolysis has become an integral component for many in the practice of aesthetic medicine. The international association of physicians performing lipolysis in the so-called NETWORK-Lipolysis (with more than 2,000 members worldwide) has in particular called for the development of internationally recognized treatment standards and protocols. When the indication for its use adheres to strict criteria and the physicians applying the method have participated in intensive training, subcutaneous injection of phosphatidylcholine/deoxycholic acid represents a meaningful addition to the scope of minimally invasive aesthetic medicine.

Topics: Adipocytes; Deoxycholic Acid; Embolism, Fat; Esthetics; Germany; Humans; Injections, Subcutaneous; Lipolysis; Lipoma; Minimally Invasive Surgical Procedures; Necrosis; Off-Label Use; Phosphatidylcholines; Plastic Surgery Procedures; Soft Tissue Neoplasms

This study was undertaken to determine whether necrosis or apoptosis was the predominant mechanism responsible for gastric mucosal cellular death using the cell line known as AGS cells. Cells were exposed to various concentrations of deoxycholate (DC; 50-500 muM) for periods ranging from 30 min to 24 h. Lactic dehydrogenase (LDH) activity was used as a marker for necrotic cell death, whereas apoptosis was characterized by 4',6-diamidino-2 phenylindole staining, DNA gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and DNA-histone-associated complex formation. When cells were bathed in Hank's balanced salt solution, DC-induced necrosis was the predominant mechanism of cell death. In contrast, when cells were bathed in Ham's F-12 solution (a more physiologically relevant medium), no evidence of cytotoxicity (by LDH assay) was discernible when cells were exposed to DC (50-300 muM) for periods as long as 8 h; instead, clear evidence of apoptosis was noted that was time and dose dependent. When cells were exposed for 24 h to these DC concentrations, cytotoxicity was also present, indicating necrosis as well. Furthermore, acidification of the ambient environment also evoked a necrotic response when exposed to DC. We demonstrated that apoptosis induced by DC shows early activation of caspase-3 that is dependent on both receptor and mitochondrial pathways. Our results indicate that physiological concentrations of DC (50-300 muM) primarily induce cellular death through an apoptotic process. Only after prolonged exposure to DC or acidification of the bathing solution does necrosis also occur.

Topics: Acids; Apoptosis; Caspases; Cell Line; Cell Survival; Deoxycholic Acid; Detergents; Dinoprostone; Gastric Mucosa; Humans; Necrosis

We previously demonstrated that the cytotoxicity associated with exposure of HCT116 cells to deoxycholic acid was due to the induction of apoptosis. Here we show that this results in activation of caspase 3 and that over expression of bcl-2 can suppress this. Surprisingly, inhibition of apoptosis by over expression of bcl-2 or incubation with calphostin C, a PKC inhibitor, did not enhance cell survival, but instead caused a switchover to death by necrosis. Hence, DCA-induced apoptosis requires caspase activity and both bcl-2 and PKC can determine the type of cell death induced by deoxycholic acid.

Topics: Apoptosis; Caspase 3; Caspases; Cell Survival; Deoxycholic Acid; Humans; Naphthalenes; Necrosis; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Anthraquinones; Bacterial Infections; Cathartics; Deoxycholic Acid; Disease Models, Animal; Endotoxemia; Endotoxins; Gastrointestinal Motility; Hemorrhage; Intestinal Mucosa; Jejunum; Lymph Nodes; Male; Necrosis; Pancreatic Diseases; Pancreatitis; Rats; Rats, Wistar; Senna Extract; Sennosides

We examined the effects of feeding deoxycholic acid (1% and 0.4% of diet), alone and in combination with ursodeoxycholic acid, on serum and biliary bile acid concentrations, hepatic morphology, and the activities and steady-state messenger RNA (mRNA) levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in the rat. Feeding 1% deoxycholic acid increased serum bile acid concentrations (cholestasis), produced portal triad inflammation, bile duct proliferation, and severe hepatocyte necrosis with nuclear pleomorphism. Hepatic damage was prevented when ursodeoxycholic acid (1%) was combined with the deoxycholic acid (1%), or when deoxycholic acid intake was reduced to 0.4%. HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities were markedly inhibited (-56% and -55%, respectively) with either 1% or 0.4% deoxycholic acid. Ursodeoxycholic acid alone produced an insignificant decline in HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities, and when combined with 1% deoxycholic acid did not lessen the inhibitory effect of the latter. Steady-state mRNA levels increased 20-fold for HMG-CoA reductase and 53-fold for cholesterol 7 alpha-hydroxylase in rats fed 1% deoxycholic acid. In contrast, 0.4% deoxycholic acid decreased HMG-CoA reductase mRNA levels 76%, and cholesterol 7 alpha-hydroxylase mRNA levels 82%. Ursodeoxycholic acid alone did not affect HMG-CoA reductase or cholesterol 7 alpha-hydroxylase steady-state mRNA levels. Steady-state mRNA levels and activities of sterol 27-hydroxylase, a key enzyme in the alternative acidic pathway of bile acid synthesis, did not change with either high or low doses of deoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bile; Bile Acids and Salts; Cell Nucleus; Chemical and Drug Induced Liver Injury; Cholagogues and Choleretics; Cholestanetriol 26-Monooxygenase; Cholesterol 7-alpha-Hydroxylase; Cytochrome P-450 Enzyme System; Deoxycholic Acid; Diet; Hydroxymethylglutaryl CoA Reductases; Liver; Liver Diseases; Male; Necrosis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Steroid Hydroxylases; Ursodeoxycholic Acid

Interleukin-1 (IL-1) is a mediator in some critical conditions such as septic shock and multiple organ failure. Acute pancreatitis is one of the noted causes of multiple organ failure but the mechanism by which local inflammation progresses to systemic disease is unknown. In this study, we used an IL-1 receptor antagonist (IL-1ra) to investigate whether multiple organ failure due to acute pancreatitis is mediated by IL-1, as in other causes such as severe infection, trauma, and major surgery.. Prospective, randomized, controlled trial.. Research laboratory of a university medical school.. Specific pathogen-free male Wistar rats weighing 200 to 250 g.. Necrotizing pancreatitis was induced by retrograde injection of deoxycholate solution into the biliopancreatic duct. IL-1ra was injected intravenously at a dose of 10 mg/kg 15 mins before induction of acute pancreatitis and then infused continuously at a rate of 5 mg/kg/hr for the following 24 hrs.. Although treatment with recombinant human IL-1ra did not affect the degree of local pancreatic insult, it significantly reduced mortality, improved urine output as an indicator of the state of shock, and ameliorated the accumulation of neutrophils into the lung in a rat experimental pancreatitis model.. We concluded that multiple organ failure in severe pancreatitis is mediated, at least in part, by IL-1 through the activation of neutrophils. Furthermore, we concluded that circulatory collapse may also be important in the mechanism of the lethal effect of pancreatitis.

Topics: Acute Disease; Animals; Deoxycholic Acid; Disease Models, Animal; Drug Evaluation, Preclinical; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Male; Multiple Organ Failure; Necrosis; Pancreas; Pancreatitis; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Receptors, Interleukin-1; Recombinant Proteins; Sialoglycoproteins; Specific Pathogen-Free Organisms

Rapid epithelial restitution is an important protective mechanism which enables the gastrointestinal mucosa to reestablish epithelial integrity following superficial injury within hours. In this study we examined the influence of an acidic luminal pH, removal of the necrotic layer, nutrient bicarbonate, calcium and sodium desoxycholate (Na-DOC) on restitution in the rabbit duodenum in vitro and the role of Na-DOC and calcium for rapid restitution of the human colon in vitro. Transmucosal potential difference (PD), short-circuit current (lsc) were measured and resistance against passive ion flux (R) was calculated. Electrophysiological changes paralleled morphological injury but did not necessarily reflect restitution in all experiments. The extent of mucosal injury was assessed by computerized real-time morphometry. 5 hrs after luminal exposure to 10 mH HCl for 10 min residual damage (RD) was 14% in the duodenum. Luminal pH of 3.0 (RD of 30%), removal of necrotic layer at acidic luminal pH (RD of 66%), absence of bicarbonate from the serosal solution (RD of 35% at neutral luminal pH; RD of 96% at acidic luminal pH) and removal of calcium from the serosal solution (RD of 58%) impaired restitution in the duodenum. Continuous postinjury luminal Na-DOC exposure did not influence restitution in the duodenum (RD of 19%). 5 hrs after luminal exposure to 0.5 mM Na-DOC for 10 min RD was 26% in the human colon. Continuous postinjury luminal Na-DOC exposure (RD of 51%) and removal of calcium from the nutrient solution (RD of 65%) impaired restitution in the human colon. Thus we conclude that restitution of the rabbit duodenum in vitro requires a necrotic layer and bicarbonate flux to withstand acidic luminal pH, while restitution is not affected by Na-DOC. In the human colon Na-DOC inhibits restitution. Both the duodenum and colon require calcium for rapid restitution.

Topics: Animals; Bicarbonates; Calcium; Colon; Deoxycholic Acid; Duodenum; Epithelial Cells; Epithelium; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Necrosis; Rabbits

The integrity of rat pancreatic acinar cells under the influence of human phospholipase A2 (PLA2) was studied. Isolated pancreatic acini showed no increased discharge of aspartylaminotransferase (ASAT) when incubated either in solutions containing human pancreatic PLA2 or the bile salt sodium deoxycholate (DEC), the latter in concentrations that augment PLA2 activity but have no destructive detergent effect. When human pancreatic PLA2 was injected into the rat pancreatic duct, uneven distribution was observed at 15 min and 3 h in immunohistochemical sections. Edema and a mild inflammatory reaction were the main changes in the pancreas. The necrotic areas seen by light and electron microscopy were quite small and located mostly at the periphery of lobules corresponding the spread of the injected material. Necrosis was of the coagulation type and showed equal extent after the injection of PLA2 with or without DEC. Internalized human pancreatic PLA2 was present already 15 min after the injection in the cytoplasm of some intact acinar cells, indicating a functioning protective mechanism. It was concluded that pancreatic acinar cells are quite resistant to PLA2-catalyzed hydrolysis of membrane phospholipids in vitro, but additional trauma, e.g., pressure caused by intraductal injection, and tissue related factors, such as the mediators of the inflammatory reaction, make acinar cells susceptible to the effect of PLA2.

Topics: Acute Disease; Animals; Aspartate Aminotransferases; Deoxycholic Acid; In Vitro Techniques; Male; Necrosis; Pancreas; Pancreatitis; Phospholipases A; Phospholipases A2; Rats; Rats, Inbred Strains

Alterations in the permeability and histology of the pancreatic ductal mucosa have been demonstrated in the cat after an intraductal infusion of deoxycholic acid. In order to define the role of prostaglandins in the pathogenesis of the mucosal lesion, an isotonic electrolyte solution was perfused through a segment of the pancreatic duct of anesthetized rats for 1 h, before and after a 10-min perfusion with 10 mM deoxycholic acid. Prostaglandin E2 or I2 was infused (intraarterially, intravenously, or intraductally) for 30 min beginning 20 min before deoxycholic acid infusion. Indomethacin (5 mg/kg intravenously) was given 30 min before deoxycholic acid. Deoxycholic acid increased ductal permeability and produced severe epithelial necrosis. Neither prostaglandin nor indomethacin affected the alterations induced by deoxycholic acid. In the experimental model tested, neither inhibition of prostaglandin synthesis nor administration of exogenous prostaglandins altered the effects of deoxycholic acid.

Topics: Animals; Deoxycholic Acid; Dinoprostone; Epithelium; Epoprostenol; Female; Indomethacin; Mucous Membrane; Necrosis; Pancreatic Ducts; Perfusion; Permeability; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains

In the last years non operative and surgical efforts could not diminish the high lethality of severe acute haemorrhagic necrotising pancreatitis. While majority of patient die in consequence of pancreatitis-shock, hyperbaric oxygen therapy (HBO) can improve all hypoxic circulation situations. Therefore the value in treatment of experimental necrotising pancreatitis in pig is examined. 5 pigs were treated with, 5 without HBO and 5 served as control. With HBO liquid sequestration was diminished and total protein loss prevented significantly, but foremost survival time was significantly prolonged. In consequence demarcation of necrosis with connective tissue was possible, but nevertheless operative treatment remain necessary. Without HBO all pigs and with HBO only 2 pigs died in consequence of necrotising pancreatitis. It is demonstrated, that HBO as additive therapy can improve the prognosis of necrotising pancreatitis.

Topics: Acute Disease; Animals; Deoxycholic Acid; Female; Hyperbaric Oxygenation; Male; Necrosis; Pancreatitis; Prognosis; Swine

Topics: Animals; Biliary Tract; Chenodeoxycholic Acid; Cholic Acids; Common Bile Duct; Deoxycholic Acid; Dose-Response Relationship, Drug; Epithelium; Female; Gallbladder; Lithocholic Acid; Liver; Mice; Necrosis; Stimulation, Chemical; Thymidine; Time Factors

Topics: Amphotericin B; Animals; Deoxycholic Acid; Electroretinography; Fundus Oculi; Injections; Necrosis; Rabbits; Retina; Retinal Detachment; Sodium; Vitreous Body