deoxycholic-acid and Chronic-Disease

It has recently become apparent that obesity is associated with chronic inflammation and several common types of cancer development. Although several events were proposed to be involved in these pathologies, the precise mechanisms underlying obesity-associated inflammation and cancer largely remain unclear. Here, we show that senescence-associated secretory phenotype (SASP) plays crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of a bacterial metabolite that cause DNA damage. The enterohepatic circulation of the bacterial metabolites provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn, secretes various inflammatory and tumour promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Importantly, reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the induction of SASP by the gut bacterial metabolite in HSCs plays key roles in obesity-associated HCC development. Interestingly, moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with nonalcoholic steatohepatitis (NASH), implying that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer.

Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Cellular Senescence; Chronic Disease; Cytokines; Deoxycholic Acid; Digestive System; Hepatic Stellate Cells; Humans; Inflammation; Inflammation Mediators; Liver Neoplasms; Mice; Non-alcoholic Fatty Liver Disease; Obesity

Topics: Cholestasis, Intrahepatic; Chronic Disease; Deoxycholic Acid; Humans; Ursodeoxycholic Acid

Different bile acids have different effects on liver cells, depending on the degree of hydroxylation of the bile acid and the orientation of hydroxy groups. In decreasing order of hydrophobicity, and therefore hepatotoxicity, the bile acids may be ranked as follows: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. The rationale for the use of ursodeoxycholic acid in chronic liver disease is to increase the overall hydrophilicity of the bile acid pool, which, because of cholestasis, retains potentially hepatotoxic bile acids. Recent clinical studies have indicated that ursodeoxycholic acid improves liver function indices in patients with primary biliary cirrhosis and chronic hepatitis at doses ranging between 10 and 15 mg/kg/day. These doses would be considered in the high range in the use of ursodeoxycholic acid for gallstone dissolution. In a preliminary study we found that also lower doses were effective in primary biliary cirrhosis. Two studies to determine the optimal dose of ursodeoxycholic acid for chronic hepatitis and anicteric primary biliary cirrhosis were then carried out. Eighteen patients with primary biliary cirrhosis and 12 patients with chronic hepatitis were treated with 250, 500, and 750 mg of ursodeoxycholic acid per day for three consecutive 2-month periods. Highly significant decreases in serum enzyme levels were seen with the 250 mg/day dose, which were further improved by the higher doses. The improvement roughly paralleled the enrichment of conjugated bile acids with ursodeoxycholic acid. A separate study investigating the effect of shifting the bile acid pool composition toward less detergent moieties was also done.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Clinical Trials as Topic; Deoxycholic Acid; Hepatitis; Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid

Different bile acids have different effects on liver cells, depending on the degree of hydroxylation of the bile acid and the orientation of hydroxy groups. In decreasing order of hydrophobicity, and therefore hepatotoxicity, the bile acids may be ranked as follows: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. The rationale for the use of ursodeoxycholic acid in chronic liver disease is to increase the overall hydrophilicity of the bile acid pool, which, because of cholestasis, retains potentially hepatotoxic bile acids. Recent clinical studies have indicated that ursodeoxycholic acid improves liver function indices in patients with primary biliary cirrhosis and chronic hepatitis at doses ranging between 10 and 15 mg/kg/day. These doses would be considered in the high range in the use of ursodeoxycholic acid for gallstone dissolution. In a preliminary study we found that also lower doses were effective in primary biliary cirrhosis. Two studies to determine the optimal dose of ursodeoxycholic acid for chronic hepatitis and anicteric primary biliary cirrhosis were then carried out. Eighteen patients with primary biliary cirrhosis and 12 patients with chronic hepatitis were treated with 250, 500, and 750 mg of ursodeoxycholic acid per day for three consecutive 2-month periods. Highly significant decreases in serum enzyme levels were seen with the 250 mg/day dose, which were further improved by the higher doses. The improvement roughly paralleled the enrichment of conjugated bile acids with ursodeoxycholic acid. A separate study investigating the effect of shifting the bile acid pool composition toward less detergent moieties was also done.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Clinical Trials as Topic; Deoxycholic Acid; Hepatitis; Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid

Golgi protein 73 (GP73) is upregulated in a variety of liver diseases, yet the detailed mechanism is poorly characterized. We analyzed GP73 in a retrospective cohort including 4211 patients with chronic liver disease (CLD) or hepatocellular carcinoma (HCC). The effect of deoxycholic acid (DCA) and nuclear factor-kappa B (NF-κB) on expression and release of GP73 in Huh-7 and SMMC7721 cells were studied. A mouse study was used to confirm our findings in vivo. A positive correlation was found between serum GP73 and total bile acid (TBA) in cirrhotic patients (

Topics: Adult; Animals; Bile Acids and Salts; Carcinoma, Hepatocellular; Cell Line, Tumor; Chronic Disease; Deoxycholic Acid; Female; Fibrosis; Gene Expression Profiling; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Middle Aged; NF-kappa B p50 Subunit; Phosphoproteins; Retrospective Studies; Up-Regulation

Cryptococcal meningoencephalitis (CM) may present as an acute, subacute, or chronic infection. It manifests as a chronic process in over 75 % of cases, but, sometimes, it presents with a more acute onset, mostly in HIV-associated patients. Until now, there has been no study performed on the clinical features of HIV-negative CM patients with acute/subacute onset. We collected 106 HIV-negative patients diagnosed with CM in our hospital during a 15-year period, analyzed their epidemiological and clinical features, as well as the outcomes, and explored the independent prognosis factors and the factors related to the survival time among them. We found that impaired consciousness (23.4 % vs. 3.4 %, p = 0.017) was more common in CM patients with acute/subacute onset, while decreased cerebrospinal fluid (CSF) glucose (51.9 % vs. 75.9 %, p = 0.026) was less common. The ratio of CSF glucose/blood glucose [odds ratio (OR) 0.04, 95 % confidence interval (CI) 0.004-0.262, p = 0.02], impaired consciousness (OR 5.09, 95 % CI 1.477-17.522, p = 0.01), and hospitalization length (OR 0.98, 95 % CI 0.977-0.999, p = 0.04) were indicated to be not only independent prognosis factors in HIV-negative CM patients with acute/subacute onset, but also factors significantly related to the survival time. The results of our study demonstrated that the contact history and potential history risk factors would not affect the onset process of HIV-negative CM patients, and the mortality, hospitalization length, and survival time has not been related to the onset process. However, the ratio of CSF glucose/blood glucose, consciousness level, and hospitalization length of the HIV-negative CM patients with acute/subacute onset should be of greater focus in the clinical work.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Blood Glucose; Child; Child, Preschool; Chronic Disease; Consciousness Disorders; Cryptococcus; Deoxycholic Acid; Drug Combinations; Female; Glucose; HIV Infections; Hospitalization; Humans; Infant; Infectious Encephalitis; Male; Meningitis, Cryptococcal; Meningoencephalitis; Middle Aged; Retrospective Studies; Risk Factors; Young Adult

Chronic visceral hyperalgesia is considered an important pathophysiologic symptom in irritable bowel syndrome (IBS); previous gastrointestinal inflammation is a potent etiologic factor for developing IBS. Although there are several animal models of adult visceral hypersensitivity after neonatal perturbation or acute colonic irritation/inflammation, current models of postinflammatory chronic visceral hyperalgesia are unsatisfactory. The aim of this study was to establish a model of chronic visceral hyperalgesia after colonic inflammation in the rat.. Deoxycholic acid (DCA) was instilled into the rat colon daily for 3 days and animals were tested for up to 4 weeks.. DCA induced mild, transient colonic inflammation within 3 days that resolved within 3 weeks. An exaggerated visceromotor response, referred pain to mechanical stimulation, increased spinal Fos expression, and colonic afferent and dorsal horn neuron activity were apparent by 1 week and persisted for at least 4 weeks, indicating chronic dorsal horn hyperexcitability and visceral hyperalgesia. There was no spontaneous pain, based on open field behavior. There was a significant increase in opioid-receptor activity.. DCA induces mild, transient colitis, resulting in persistent visceral hyperalgesia and referred pain in rats, modeling some aspects of postinflammatory IBS.

Topics: Abdominal Pain; Animals; Chronic Disease; Colitis; Colon; Deoxycholic Acid; Disease Models, Animal; Electrophysiology; Follow-Up Studies; Ganglia, Sensory; Immunohistochemistry; Male; Pain Measurement; Rats; Rats, Sprague-Dawley

Meningitis is a common evolution in progressive disseminated histoplasmosis in children, and is asymptomatic in many cases. In leukemia, the impaired of the T cells function can predispose to the disseminated form. The attributed mortality rate in this case is 20%-40% and the relapse rate is as high as 50%; therefore, prolonged treatment may be emphasized. We have described a child with acute myeloid leukemia (AML), that developed skin lesions and asymptomatic chronic meningitis, with a good evolution after prolonged treatment with amphotericin B deoxycholate followed by fluconazole.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Chronic Disease; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fluconazole; Histoplasmosis; Humans; Immunocompromised Host; Leukemia, Myeloid; Male; Meningitis, Fungal; Treatment Outcome

Topics: Adolescent; Adult; Alternaria; Amphotericin B; Antifungal Agents; Chronic Disease; Deoxycholic Acid; Drug Combinations; Female; Humans; Mouth Diseases; Mycoses; Treatment Outcome; Triazoles

To establish an experimental animal model of chronic gastritis in a short term and to investigate the effects of several potential inflammation-inducing factors on rat gastric mucosa.. Twenty-four healthy, male SD rats were treated with intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of vitamins (factor B), and/or indomethacin (factor C), according to an L(8) (2(7)) orthogonal design. After 12 wk, gastric antral and body mucosae were pathologically examined.. Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk. After the treatment of animals, the gastric mucosal inflammation was significantly different from that in controls, and the number of pyloric glands at antrum and parietal cells at body were obviously reduced (P<0.01). Indomethacin induced gastritis but without atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and gastric atrophy. In addition, indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied.. Combined intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic gastritis only. The long-term roles of these factors in gastric inflammation and carcinogenesis need to be further elucidated.

Topics: Alcohols; Ammonia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Atrophy; Chronic Disease; Deoxycholic Acid; Disease Models, Animal; Gastric Mucosa; Gastritis; Indomethacin; Male; Rats; Rats, Sprague-Dawley; Vitamins

We evaluated the effect of ursodeoxycholic acid on the defective natural killer activity in primary biliary cirrhosis. Administration of ursodeoxycholic acid (600 mg daily) for one month significantly increased natural killer activity in patients with primary biliary cirrhosis (P < 0.05). Ursodeoxycholic acid also enhanced the in vitro natural killer activity of lymphocytes from healthy volunteers, while other hydrophobic bile acids depressed it. Furthermore, ursodeoxycholic acid reduced the prostaglandin E2 concentration in culture supernatants of lymphocytes from healthy volunteers to a lower level than that in culture incubated with chenodeoxycholic acid (P < 0.05) or control cultures (P < 0.01). Urosdeoxycholic acid normalized the defective natural killer activity in primary biliary cirrhosis by reducing the levels of other hydrophobic bile acids and inhibiting prostaglandin E2 production, suggesting that it may be a useful immunomodulating agent for primary biliary cirrhosis.

Topics: Adult; Aged; Cells, Cultured; Chenodeoxycholic Acid; Cholic Acid; Cholic Acids; Chronic Disease; Deoxycholic Acid; Dinoprostone; Female; Hepatitis C; Humans; Indomethacin; Killer Cells, Natural; Liver Cirrhosis, Biliary; Liver Diseases; Male; Middle Aged; Ursodeoxycholic Acid

Topics: Adult; Arteriosclerosis; Cholestasis, Intrahepatic; Chronic Disease; Deoxycholic Acid; Female; Humans; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Risk Factors; Ursodeoxycholic Acid

The prevalence of biliary and hepatic diseases is increasing in patients with cystic fibrosis as more of them reach adult life. There is no effective treatment or method of preventing cholestasis in cystic fibrosis, although beneficial effects have been ascribed to the tertiary bile acid, ursodeoxycholate, in other forms of chronic cholestasis. We evaluated prospectively the effects of a six month course of ursodeoxycholate (15-20 mg/kg per day) in eight, mostly adult, patients with cystic fibrosis and chronic cholestasis. Bile acid treatment improved inflammatory activity (average decrease in alanine aminotransferase, 60%, p less than 0.005) and cholestasis (alkaline phosphatase, 47%; p less than 0.01) in all patients. Quantitative liver function, measured by 45 minute sulphobromophthalein retention and by the 14C-aminopyrine breath test, improved in all patients while galactose elimination capacity showed a slight decrease. Patients' nutritional state improved as evidenced by a 1.8 kg weight gain and an increase in muscle mass suggested by a 26% increase in 24 hour urinary creatinine excretion. Steatorrhea was not affected by bile acid treatment. Ursodeoxycholic acid may be beneficial in the treatment of chronic cholestasis in cystic fibrosis by improving liver function and also the patient's nutritional state.

Topics: Adolescent; Adult; Child; Cholestasis; Chronic Disease; Cystic Fibrosis; Deoxycholic Acid; Female; Humans; Liver; Liver Function Tests; Male; Nutritional Status; Prospective Studies; Ursodeoxycholic Acid

Topics: Adult; Biliary Tract; Chronic Disease; Deoxycholic Acid; Female; Humans; Liver; Liver Diseases; Male; Middle Aged; Organometallic Compounds; Organotechnetium Compounds; Pyridoxal; Radionuclide Imaging; Tryptophan; Ursodeoxycholic Acid

Topics: Bile Acids and Salts; Chronic Disease; Deoxycholic Acid; Glucagon; Humans; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Predictive Value of Tests; Ursodeoxycholic Acid

Serum bile acids were studied in 27 patients with chronic noncalculous cholecystitis. It was ascertained that the total concentration of bile acids under study was appreciably increased as compared with the data derived in the control group patients. There was noticeable differences between modulations in individual fractions of serum bile acids, attesting to an unusual distress of the synthetic function of hepatocytes. Alterations in the metabolism of cholates seen in chronic cholecystitis agreed well with the pattern of the disordered motor function of the gallbladder and were more pronounced in patients with hypokinesia.

Topics: Adult; Bile Acids and Salts; Chenodeoxycholic Acid; Cholecystitis; Cholic Acid; Cholic Acids; Chromatography, Gas; Chronic Disease; Dehydrocholic Acid; Deoxycholic Acid; Female; Gallbladder; Humans; Male; Middle Aged

Topics: Animals; Chronic Disease; Deoxycholic Acid; Dogs; Lymph; Pancreas; Pancreatic Diseases

Portal-systemic spill-over of unconjugated ursodeoxycholic acid (UDCA) was assessed in ten healthy subjects, six patients with mild chronic liver disease and eight patients with cirrhosis. Following oral administration of UDCA (1.5 mg/kg body weight), serum concentrations of unconjugated UDCA were measured during 2 h using a capillary gas-liquid chromatographic method. Peak time of UDCA varied from 15 to 30 min, but was not significantly different in the three groups studied. Peak concentration was increased up to two-fold in patients with mild, and up to three-fold in patients with cirrhotic liver disease. Since, in addition, plasma disappearance rate (k) was markedly impaired in cirrhotics (1.7 +/- SD 0.5%/min, compared to 2.8 +/- 0.6 in healthy controls), the calculated area under the curve (AUC) was on the average five-fold that in controls. In two healthy and four cirrhotic subjects, the data obtained after oral administration were compared with those after i.v. loading with the same UDCA dose. The k-values after the two routes of administration were practically identical. Calculated systemic availability was 50% in normals, 78-87% in cirrhotics, 90 and 136% in two patients with surgical porta-caval shunt. It is concluded that the portal-systemic spill-over of UDCA in patients with liver disease is increased primarily due to portal-systemic shunting. Since in the normal liver hepatic extraction of conjugated, endogenous bile acids is greater than 80%, diminished first-pass elimination is expected to augment systemic concentrations even more, particularly when measured after a meal.

Topics: Adult; Bile Acids and Salts; Chronic Disease; Deoxycholic Acid; Female; Humans; Kinetics; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Ursodeoxycholic Acid

Topics: Adolescent; Adult; Aged; Chronic Disease; Deoxycholic Acid; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Neostigmine; Pancreas

To investigate the possibility that bowel-related liver disease is due to accumulation of abnormal bile acids in the enterohepatic circulation, bile acids have been measured in gall-bladder bile and portal blood of patients with chronic bowel disease, none of whom had liver disease. There was no difference in the composition and concentration of bile acids in bile and portal blood compared with control patients. In a second study, serum bile acid composition and concentrations were similar in two groups of patients with liver disease, whether they had bowel disease or not. In a further study, post-prandial serum bile acid concentrations were not elevated in a group of patients with chronic bowel disease, making it unlikely that subcliical liver disease was present. No evidence has been found to support the hypothesis that bowel-related liver disease in man results from the action of abnormal bile acids.

Topics: Adult; Aged; Bile; Bile Acids and Salts; Cholangitis; Cholic Acids; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Deoxycholic Acid; Enterohepatic Circulation; Female; Humans; Lithocholic Acid; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

Topics: Adult; Aged; Bile Acids and Salts; Cholic Acids; Chronic Disease; Crohn Disease; Deoxycholic Acid; Diarrhea; Feces; Female; Gastrointestinal Motility; Humans; Ileostomy; Male; Middle Aged; Postoperative Complications; Time Factors

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chronic Disease; Deoxycholic Acid; Hepatic Encephalopathy; Hepatitis; Humans; Lithocholic Acid; Liver Cirrhosis; Liver Diseases