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Major Causative Factor (major + causative_factor)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Intralesional bovine papillomavirus DNA loads reflect severity of equine sarcoid disease

EQUINE VETERINARY JOURNAL, Issue 4 2010
R. HARALAMBUS
Summary Reasons for performing study: Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Hypothesis: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tumour growth kinetics, lesion number and tumour type for 37 sarcoid-bearing horses and one donkey. Viral load was estimated via quantitative real-time PCR (qPCR) of the E2, E5, L1 and L2 genes from the BPV-1/-2 genome for one randomly selected lesion per horse and correlated with disease severity. Results: Quantitative PCR against E2 identified viral DNA concentrations ranging from 0,556 copies/tumour cell. Of 16 horses affected by quiescent, slowly growing single tumours or multiple mild-type lesions, 15 showed a viral load up to 1.4 copies per cell. In stark contrast, all equids (22/22) bearing rapidly growing and/or multiple aggressive sarcoids had a viral load between 3 and 569 copies per cell. Consistent results were obtained with qPCR against E5, L1 and L2. Conclusions: While tumours of the same clinical type carried variable virus load, confirming that viral titre does not determine clinical appearance, we identified a highly significant correlation between intralesional viral load and disease severity. Potential relevance: The rapid determination of BPV viral load will give a reliable marker for disease severity and may also be considered when establishing a therapeutic strategy. [source]

Protection of estrogens against the progression of chronic liver disease

HEPATOLOGY RESEARCH, Issue 4 2007
Ichiro Shimizu
Hepatitis C virus infections are recognized as a major causative factor of chronic liver disease. A characteristic feature of chronic hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory and oxidative stimuli, and to produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. Estradiol is a potent endogenous antioxidant. Hepatic steatosis was reported to become evident in an aromatase-deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures. Variant estrogen receptors were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. A better understanding of the basic mechanisms underlying the gender-associated differences observed in the progression of chronic liver disease would provide valuable information relative to the search for effective antifibrogenic therapies. [source]

Preserved Na+/H+ exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis,

INFLAMMATORY BOWEL DISEASES, Issue 7 2010
Sunil Yeruva PhD
Abstract Background: A major causative factor of diarrhea in ulcerative colitis (UC) patients is the loss of Na+ absorptive capacity of the inflamed colonic mucosa. Potential contributing mechanisms include reduced driving force for active transport, and impaired expression, mislocalization, or defective transport function of Na+ absorptive proteins. We therefore studied the expression, brush border membrane (BBM) localization, and transport capacity of the major intestinal Na+ absorptive protein, the Na+/H+ exchanger isoform 3 (NHE3) in biopsies from UC patients. Methods: In UC and control biopsies, inflammation was graded histologically, NHE3, tumor necrosis factor alpha (TNF-,), villin, as well as other housekeeping genes were analyzed by quantitative real-time polymerase chain reaction (PCR), BBM localization of NHE3 determined by immunohistochemistry, and confocal microscopy. Na+ absorptive capacity was assessed by 22Na+ isotope fluxes and NHE3 transport activity measured microfluorometrically in BCECF-loaded surface colonocytes within isolated crypts. Results: In mildly, moderately, and severely inflamed sigmoid colon of UC patients, neither NHE3 mRNA expression nor the abundance of NHE3 in the BBM was significantly altered compared to other structural components of the BBM. However, Na+ absorption was strongly reduced by ,80% and acid-activated NHE3 transport activity was significantly decreased in the surface cells of sigmoid colonic crypts even in moderately inflamed mucosa. Conclusions: In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients. (Inflamm Bowel Dis 2010) [source]

Protective effect of glucosamine against ibuprofen-induced peptic ulcer in rats

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007
Sethumadhavan Santhosh
Abstract Background:,Helicobacter pylori is the major causative factor of ulcer but the use of ibuprofen and other non-steroidal anti-inflammatory drugs have also been implicated in development of ulcer. The purpose of the present study was to determine the anti-ulcer effect of glucosamine. Methods:, The protective effect of glucosamine on ibuprofen-induced peptic ulcer in male albino rats was studied with respect to changes in the volume of gastric juice, acid output, pepsin activity, activities of membrane bound ATPases, protein content, glycoprotein components and histopathology. Results:, Oral administration of ibuprofen caused significant increase in the number of lesions in the gastric mucosa, increases in the volume of gastric juice and acidity, and decreased activity of pepsin. The levels of protein content and glycoprotein components (hexose, hexosamine and sialic acid) and ATPase activities were also observed. Oral pretreatment with glucosamine resulted in significant reduction in the number of lesions in the gastric mucosa and decreases in the volume of gastric juice and acidity. The pepsin activity was also maintained at near normalcy. Prior oral administration of glucosamine significantly prevented the ibuprofen-induced depletion of protein and glycoprotein components and maintained the activities of membrane bound ATPases as compared to untreated ulcer induced group of rats. Conclusion:, The anti-ulcerogenic activity of glucosamine might be ascribable to its ability to neutralize the hydrochloric acid secreted into the stomach and to its capability to strengthen the mucosal barrier by increasing mucosal glycoprotein synthesis and to its free radical scavenging property. Histopathological investigations of the mucosal tissue also support the anti-ulcerogenic effect of glucosamine. [source]

Hypercholesterolemia and inflammation in atherogenesis: Two sides of the same coin

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 11 2005
Daniel SteinbergArticle first published online: 3 NOV 200
Abstract An abundance of experimental, clinical, and epidemiologic data capped by stunning interventional results with the statins has established hypercholesterolemia as a major causative factor in atherogenesis. In familial hypercholesterolemia and in animal models it is a sufficient cause. Some degree of hypercholesterolemia, perhaps 30,50 mg/dL, may even be a necessary cause. It is equally clear that from the very beginning atherogenesis has a strong inflammatory component, i. e., it is characterized by penetration of monocytes and of T-cells into the developing lesion. These cells, through the secretion of cytokines and growth factors, through immune responses, and through complex cross-talk with elements of the artery wall modulate the growth of the lesion and affect its stability. But inflammation has to occur in response to something. What is that something? What is the "injury" in "response-to-injury"? The case will be made that oxidized lipids in oxidized LDL or generated in response to prooxidative changes in the cells of the artery wall should be considered a plausible candidate. There is no need to consider hypercholesterolemia and inflammation as alternative hypotheses. Both are very much involved. Optimal intervention and prevention will probably require attention to both. [source]