Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pathogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1996

Collagenous colitis: pathogenesis and management.

INTRODUCTION: Collagenous colitis is a rare disease of unknown etiology that primarily affects middle-aged women. It presents with chronic watery diarrhea and thickening of the subepithelial collagen layer of the colonic mucosa in the absence of endoscopic abnormalities. PURPOSE: This study was undertaken to review the current literature on clinical course, pathology, diagnosis, and current management of collagenous colitis. RESULTS: Collagenous colitis is an inflammatory disease of the colon, clinically characterized by a waxing and waning course of watery diarrhea, an inflammatory infiltration of the colonic mucosa, and a thickening of the subepithelial collagen layer. Its pathogenesis remains unclear, but there is evidence for an inflammatory process triggered possibly by an uncommon luminal agent. Diagnosis is established by colonic biopsies; in the setting of normal colonic mucosa, the disorder is primarily managed medically with virtually no role for surgery. CONCLUSIONS: Pathogenesis of collagenous colitis remains unclear. Current data favor an inflammatory etiology, possibly involving an initiating luminal insult. Guidelines for diagnosis are being established, and medical treatment options are variably effective in the majority of cases. Very unusual refractory cases may benefit from surgical management.

Biopsy↗
PubMed1995

Nonhereditary colonic angiodysplasias: histomorphometric approach to their pathogenesis.

The pathogenesis of colonic angiodysplasias, more accurately termed vascular ectasias (VE) has not been definitely established. The aim of this study was to assess that the VE of noncirrhotic patients are not associated with diffuse abnormalities of the colonic mucosal microvasculature unlike the VE of cirrhotic patients. Three groups of nine consecutive patients were studied: group I, control patients with an irritable bowel syndrome; group II, noncirrhotic patients with VE; and group III, alcoholic cirrhotics with VE. A histomorphometric analysis of normal-appearing colonic mucosa was achieved from biopsies taken at six predetermined sites. Noncirrhotics with VE had a significantly lower mean number of mucosal capillaries and a significantly lower mean cross-sectional area of mucosal capillaries than alcoholic cirrhotics with VE. Alcoholic cirrhotics with VE had a significant increase of all the vascular parameters compared to the control group. There was no difference between the control patients and the noncirrhotic patients with VE. These results suggest that the VE of noncirrhotic and cirrhotic patients are entities of distinct pathogenesis.

Angiodysplasia↗
PubMed1994

Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha.

To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P = 0.0026), beta 2-microglobulin (P = 0.046), soluble interleukin-2 receptor (P = 0.021), and soluble CD8 (P < 0.039), than healthy controls; conversely, interferon-gamma levels were significantly lower (P = 0.023). Significant correlations were observed between beta 2-microglobulin concentration and Knodell's index (r = 0.638, P = 0.00045), the score of piecemeal necrosis (r = 0.572, P = 0.0023), and the degree of fibrosis (r = 0.527, P = 0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r = 0.412, P = 0.037), and the degree of lobular cytolysis (r = 0.389, P = 0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P = 0.042) in patients with a sustained biochemical response. On interferon-alpha treatment, the levels of beta 2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P < 0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-gamma.

Adult↗
PubMed1996

Role of salivary and seric epidermal growth factor in pathogenesis of reflux esophagitis in chronic alcoholics and nondrinkers.

Our objective was to investigate the putative role of epidermal growth factor (EGF) in esophagitis pathogenesis in both nondrinkers and chronic alcoholics. We studied the EGF serum level, the EGF salivary concentration, and the esophageal EGF receptor expression in different groups of patients with esophagitis: nondrinkers with typical symptoms of gastroesophageal reflux (N = 12) and chronic alcoholics (N = 12), and in controls: chronic alcoholics without esophagitis (N = 16) and healthy nondrinkers (N = 12). All patients had an endoscopy with esophageal biopsies, 24-hr esophageal pH-metry, and esophageal manometry. EGF serum levels and EGF salivary concentrations were determined by radioimmunoassay. EGF receptor expression was determined by immunohistochemistry. Both the EGF serum level and the EGF salivary concentration remained constant, 328 +/- 21 pg/ml and 305 +/- 48 pg/ml, respectively, regardless of alcohol intake and the presence or absence of esophagitis. In addition, the presence of esophagitis did not affect the EGF receptor expression. These results suggest that seric and salivary EGF is not involved in the pathogenesis of reflux esophagitis in nondrinkers and in chronic alcoholics.

Adult↗
PubMed1996

Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerative colitis.

It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.

Biopsy↗
PubMed1989

Interleukin-1 in the pathogenesis of and protection from inflammatory bowel disease.

Inflammatory bowel disease affects millions of people, some with fatal consequences. Little is known about the factors which contribute to its pathogenesis particularly regarding cytokine production and action. In this paper we summarize our recent findings using the rabbit model for immune complex-generated experimental colitis, a model which is similar to ulcerative colitis in humans. Recombinant human IL-1 was perfused through rabbit colons and we observed elevated levels of PGE2, TxB2 and 6-keto-PGF1 alpha, the stable metabolite of PGI2. Using radioimmunoassays specific for rabbit IL-1 alpha and IL-1 beta, we induced immune complex colitis and measured the generation of these IL-1's in various tissues. Markedly elevated levels of IL-1 were detected only in inflamed tissues. The levels of IL-1 correlated with the degree of inflammation as judged by a blinded assessment of pathological changes. Similar to other disease models in which small doses of the agonist can afford protection or result in a state of "desensitization" when administered prior to the onset of the disease, we accordingly injected rabbits with a single, small (300 ng/kg) dose of IL-1 and observed a significant reduction in the inflammatory index and necrosis of immune complex colitis. However, unlike other models of IL-1-induced protection, in this model cyclooxygenase products were required since we prevented the IL-1-induced protection with a single dose of ibuprofen given at the same time as the IL-1. This correlated with the reduction in IL-1-induced PGE2. These results demonstrate that IL-1 plays a key role in the pathogenesis of inflammatory bowel disease in the rabbit and that the protection afforded by a low dose of IL-1 24 hours before the onset of the colitis requires IL-1-induced cyclooxygenase products.

Animals↗
PubMed1995

Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.

In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of ITP.

Antibody Formation↗
PubMed1990

Antibodies to DNA in patients with systemic lupus erythematosus. Their role in the diagnosis, the follow-up and the pathogenesis of the disease.

In this paper an overview of the present knowledge on antibodies against DNA will be presented. Diagnostic, prognostic and pathogenic aspects of anti-DNA will be highlighted. Detection of antibodies to DNA in the circulation of a patient by an assay selective for high avidity anti-DNA is highly diagnostic for SLE. Anti-DNA of low avidity occurs in rheumatic diseases other than SLE as well, making detection of such antibodies of less diagnostic value. Furthermore, data will be presented that show that the anti-DNA ELISA in its present form is not suited as a diagnostic tool. Not only disease features of SLE vary from patient to patient, anti-DNA avidity does so too. A relationship between anti-DNA avidity and clinical features can be found: high avidity anti-DNA is more abundant in patients with nephritis, low avidity anti-DNA in patients with CNS involvement. Prognostically, a steady increase of the level of high avidity anti-DNA generally heralds an upcoming exacerbation in a patient. Furthermore, 85% of the patients who do not have SLE at the time (high avidity) anti-DNA is detected in their serum, will develop the disease within the next few years. It is noteworthy, that patients with only low avidity anti-DNA in their circulation develop a more mild form of SLE; the (low) avidity of their anti-DNA seldomly increases during the course of their disease. The relevance of anti-DNA to the pathogenesis of SLE still is a matter of debate. On the one hand, the association of parameters of anti-DNA that determine the size of the complexes formed with DNA is in favour of the classical hypothesis, which states that SLE is primarily an immune complex disease. On the other hand, recent data on crossreactions of anti-DNA with phospholipids, glycosaminoglycans and other (poly-negative) structures plead for a role of such crossreactivities in the pathogenesis of SLE.

Antibodies, Antinuclear↗
PubMed2000

Schistosomal pelvic floor myopathy contributes to the pathogenesis of rectal prolapse in young males.

PURPOSE: Rectal prolapse is common in young males in Egypt. The role of schistosomiasis in the pathogenesis of rectal prolapse is not clearly defined. The purpose of this work is to study changes in the pelvic floor muscles in patients of rectal prolapse associated with schistosomiasis. METHODS: This study included 33 male patients with rectal prolapse of whom 27 patients with schistosomiasis and 6 patients free from schistosomiasis. Biopsies were taken from the pelvic floor muscle during surgery. The prepared sections were examined for histopathologic structural changes, for ultrastructural changes (by using electron microscopy) and after immunohistochemical staining by using anti-IgG and anti-IgM antibodies. RESULTS: The muscles from the patients without schistosomiasis had no histologic or EM changes and showed negative staining for IgG and IgM. Myopathic changes were found in the group of patients with schistosomiasis, including increased variation in the fiber diameter in 66.6 percent of patients, degenerative changes in 59.26 percent of patients, fiber splitting and fragmentation in 44.4 percent of patients, and endomysial fatty changes in 55.5 percent of patients. Ultrastructural study revealed starting loss of striation and margination of the nucleus in 70.37 percent of patients, distorted myofibrillar pattern in 51.85 percent of patients, disturbed endoplasmic reticulum and increased glycogen granules in all patients, the mitochondria are irregularly arranged with electron dense matrix in 40.74 percent of patients, and prominent nuclear sap in 13.72 percent of patients. The muscles of all the schistosomal patients showed a positive cytoplasmic staining for immunoglobulin G, of them only 12 patients showed positive staining for IgM. CONCLUSION: Patients with schistosomiasis suffer from pelvic floor myopathic changes that may contribute to the pathogenesis of rectal prolapse in young males. The immunohistochemical findings suggest immunologic mechanism for this myopathy.

Adolescent↗
PubMed1996

Monocytes and lymphocytes as active participants in the pathogenesis of experimental shock.

We investigated the role played by monocytes and lymphocytes in the pathogenesis of experimental shock. Splanchnic artery occlusion (SAO) shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min followed by reperfusion. Sham operated animals were used as controls. SAO shocked rats had a decreased survival time (80 +/- 11 min, while sham shocked rats survived more than 4 h), increased serum (248 +/- 21 U/ml) and macrophage (145 +/- 15 U/ml) levels of TNF-alpha, enhanced myeloperoxidase (MPO) activity in the ileum (3.38 +/- 0.2 U x 10(-3)/g tissue), decreased number of monocytes, lymphocytes and neutrophils and a profound hypotension. In addition we found an increased expression of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium and a reduced percentage of VLA-4 positive monocytes and lymphocytes. Inhibition of TNF-alpha synthesis, reversed the increased endothelial expression of VCAM-1, increased the percentage of integrin VLA-4 positive leukocytes and improved monocyte, lymphocyte and neutrophil count. Furthermore a passive immunization with specific antibodies raised against VCAM-1 (2 mg/kg, i.v. 3 h before SAO) increased survival, reduced MPO activity in the ileum (0.034 +/- 0.04 U x 10(-3)/g tissue) and improved mean arterial blood pressure. Our data suggest that monocytes and lymphocytes participate in the pathogenesis of splanchnic ischaemia-reperfusion injury and may amplify the adhesion of neutrophils to peripheral tissues.

Animals↗
PubMedDate not supplied

The nonstructural NS5A protein of hepatitis C virus: an expanding, multifunctional role in enhancing hepatitis C virus pathogenesis.

The hepatitis C virus (HCV) NS5A gene product is a phosphorylated 56- to 58-kD nonstructural protein that displays a multitude of activities related to enhancement of viral pathogenesis. Although associated with other viral encoded proteins as part of the viral replicase complex positioned on the cytoplasmic side of the endoplasmic reticulum, a role for NS5A in viral replication has not been defined. Post-translational modifications of NS5A include phosphorylation and potential proteolytic processing to smaller molecular weight forms able to translocate to the nucleus. Both the identification of a putative interferon (IFN) sensitivity-determining region within NS5A, as well as the direct interaction with and inhibition of the IFN-induced double-stranded RNA-dependent protein kinase (PKR) by NS5A remain controversial. Truncated versions of NS5A can act as transcriptional activators, while other recently characterized interactions of NS5A with cellular proteins indicate its pleiotropic role in HCV-host interactions. NS5A itself has no direct effect on IFN-alpha signaling or activation, but other abundant interactions with members of the cellular signaling apparatus, transcription activation machinery and cell cycle-regulatory kinases have been described (e.g. growth factor receptor-bound protein 2, p53, p21/waf and cyclins). Many of these interactions block the apoptotic cellular response to persistent HCV infection. More recently, another altogether different mechanism attenuating the IFN-alpha response was reported based on induction of interleukin (IL)-8. IL-8, in model systems, potentiates viral replication and mutes the nonspecific intracellular IFN antiviral response. Evidence supporting a complex multimechanistic role of NS5A in promoting viral persistence, pathogenesis and, indirectly, viral-related hepatocarcinogenesis indicates its key role in HCV pathobiology.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: the differences and implications in pathogenesis.

Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have implications in the pathogenesis of these diseases. We performed a comparative study to examine the possible differences in the TNF-TNF receptor (TNFR) response between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40 patients with CHC and 9 patients with dual hepatitis B and C, and compared them with the baseline levels of 12 healthy controls. The plasma levels of TNF-alpha, interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR-1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC by semiquantitative reverse transcription polymerase chain reaction. The results showed that sTNFR-1 levels correlated with liver inflammation in all patients, whereas this correlation was not found with sTNFR-2 or other cytokines. Liver inflammation indicators were higher in HCV RNA+ than in HCV RNA- CHC. Most significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB and CHC. These findings suggest that the TNFR signal transduction pathway is modulated differently in HBV and HCV infection.

Antigens, CD↗
PubMed1997

Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome.

The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.

Adult↗
PubMed1996

Vitreomacular observations. II. Data on the pathogenesis of idiopathic macular breaks.

BACKGROUND: The pathogenesis of idiopathic macular breaks is still uncertain. Their formation has been ascribed to anteriorly oriented intravitreous traction and to shrinkage of the prefoveal cortical vitreous. The validity of both hypotheses is considered in this paper. METHODS: In order to clarify the pathogenesis of idiopathic macular breaks 127 consecutive patients had their vitreous examined and photographed with the El Bayadi-Kajiura precorneal lens and a slit-lamp microscope. RESULTS: A comparison with 127 matched controls demonstrated that the vitreous was significantly more often attached in eyes with a macular break than in controls (P < 0.01). In eyes with a macular break the vitreous was significantly more often attached in early cases (Gass stage 1) than in Gass stages 3 and 4 (P < 0.01). Still photographs and observation of the movements of the operculum demonstrated that, in some cases of stage 3 and also in stage 4, it moved inside the partially liquefied posterior vitreous, anteriorly to the retinal surface and frequently without evidence of posterior vitreous detachment over the macular area. The following anatomical features characterize the vitreomacular area: extremely thin hyaloid membrane (< 100 microns) and inner limiting lamina (10 nm) that adhere strongly to each other and to the underlying Mueller cells. There is no evidence that these structures can shrink selectively to cause a macular break. The premacular vitreous gel contains collagen fibers that attach posteriorly to the macula and anteriorly to the vitreous base. CONCLUSIONS: Our working hypothesis is that when detachment of the posterior vitreous is abnormally delayed, anteroposterior traction by collagen fibers may pull a foveal operculum off the retina. Our observations make this hypothesis attractive. However, the generally accepted hypothesis of Johnson and Gass cannot be entirely dismissed. In reality, since the two hypotheses are not mutually exclusive, they may both the partially correct.

Aged↗
PubMed1983

Pathogenesis of polyps (adenomas).

The pathogenesis of adenomas in adenomatous polyposis of the gastrointestinal tract (familial polyposis coli, FPC) is not completely known. The morphologic features of the dysplastic epithelium and the morphogenesis of adenomas in FPC have been well described. Studies of the precursors to adenomatous epithelium have identified histopathologic, ultrastructural, and epithelial proliferative abnormalities in grossly normal colonic mucosa of FPC patients. The role of the intraluminal environment and the mechanisms of its interaction with the mucosa appear to be important areas for research directed at the pathogenesis of adenomas in FPC, due to the implications for therapy.

Adenoma↗
PubMed1981

The possible involvement of Kupffer cell-mediated hepatocytotoxicity in the pathogenesis of liver injuries.

The possible involvement of cell-mediated immune response to liver specific lipoprotein (LSP) in the pathogenesis of liver injury was investigated. The subjects were consisted of one patient with acute hepatitis, five cases with chronic active hepatitis and one case with chronic failure inactive hepatitis. When peripheral blood lymphocytes from these patients were cultured in the presence of LSP and lymphocyte transformation was determined by measuring the uptake of [3H]-thymidine into the acid-insoluble materials, positive blastogenesis was seen in three cases with chronic active hepatitis. Furthermore, when peripheral blood lymphocytes from halothane-induced cholestatic hepatitis were cultured with offending drug in the presence of LSP and lymphocyte transformation was determined, a positive blastogenesis was seen. The factor which activated Kupffer cells (KCAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from four patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into Kupffer cells. The macrophage activating factor (MAF) was detectable in culture medium of activated lymphocytes from three patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into macrophages. Furthermore, the KCAF-activated Kupffer cells and MAF-activated macrophages were shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. The observations suggest that Kupffer cell-mediated cytotoxicity and macrophage-mediated cytotoxicity play a role in the pathogenesis of liver disease.

Cytotoxicity, Immunologic↗
PubMed1991

Experimental study on the pathogenesis of acute acalculous cholecystitis, with special reference to the roles of microcirculatory disturbances, free radicals and membrane-bound phospholipase A2.

To elucidate the pathogenesis of acute acalculous cholecystitis, the gallbladder was subjected to ischemia-reperfusion by simultaneously occluding the middle hepatic artery and the superior mesenteric vein in dogs, and the degree of inflammation and biochemical changes in the gallbladder mucosa were studied by varying the duration of ischemia or reperfusion. Ischemia alone did not induce cholecystitis either macroscopically and histologically, although it increased phospholipase A2 (PLA2) activity, content of lipid peroxide, and superoxide dismutase (SOD) activity in the mucosa with prolongation of the ischemic time. Cholecystitis was produced in all animals by 45-min ischemia followed by 90-min reperfusion as the shortest ischemia and reperfusion times. In this model, prolongation of the ischemic time increased the area of mucosal inflammation horizontally with increases of the PLA2 activity, content of lipid peroxide, and SOD activity, whereas by prolonging the reperfusion time the inflammation area spread deeper vertically toward the serosal side with significant increase in the mucosal PLA2 activity, content of lipid peroxide, and SOD activity. These results revealed that ischemia-reperfusion plays an important role in the pathogenesis of acute acalculous cholecystitis, causing the generation of free radicals and the activation of membrane-bound PLA2.

Acute Disease↗
PubMed1996

Role of hypertriglyceridemia in the pathogenesis of experimental acute pancreatitis in rats.

CONCLUSION: The pancreatic damage initiated via different pathogenetic pathways can be increased by triglycerides. Thus, triglycerides seem to play an important role in the pathogenesis of acute pancreatitis. BACKGROUND: Lipolytic enzymes and their substrates may play a role in the pathogenesis of acute necrotizing pancreatitis. We investigated, therefore, whether triglycerides alter the course of acute pancreatitis in three experimental models of rats. METHODS: 1. Edematous acute pancreatitis induced by repeated sc injections of cerulein; 2. Necrotizing acute pancreatitis by retrograde duct injection of sodium taurocholate; and 3. Pancreatic edema by ligation of: a. The bile duct at the liver hilus; b. The common bile/pancreatic duct close to the duodenal wall; or c. A combination of a. and b. Six hours later, rats were sacrificed and the isolated perfused pancreas prepared. The pancreases were perfused with either HEPES/Ringer/HAES alone or in combination with various concentrations of triglycerides (1-5% wt/vol). The activities of lipase and amylase in the portal venous effluents were regarded as a marker of pancreatic injury. In addition, the pancreases were evaluated by light microscopy. RESULTS: In both cerulein and taurocholate acute pancreatitis, amylase/lipase activities were significantly higher compared to controls during 45 min of perfusion. In both models, addition of triglycerides caused a dose-dependent marked elevation of enzymes. Ligation (a) did not cause any rise in enzymes in the venous effluent; triglycerides had no effect. Ligation (b) or (c) caused a significant increase of pancreatic enzymes, which was further increased by triglycerides. Histology showed various degrees of severity of tissue damage depending on the model used. The additional damaging effect of a 45-min perfusion with triglycerides, however, could not be detected by histology.

Acute Disease↗