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Acid Therapy (acid + therapy)
Selected AbstractsBiliary physiology and disease: Reflections of a physician-scientist,HEPATOLOGY, Issue 4 2010Gustav Paumgartner A review is presented of Gustav Paumgartner's five decades of research and practice in hepatology focusing on biliary physiology and disease. It begins with studies of the excretory function of the liver including hepatic uptake of indocyanine green, bilirubin, and bile acids. The implications of these studies for diagnosis and understanding of liver diseases are pointed out. From there, the path of scientific research leads to investigations of hepatobiliary bile acid transport and the major mechanisms of bile formation. The therapeutic effects of the hydrophilic bile acid, ursodeoxycholic acid, have greatly stimulated these studies. Although ursodeoxycholic acid therapy for dissolution of cholesterol gallstones and some other nonsurgical treatments of gallstones were largely superseded by surgical techniques, ursodeoxycholic acid is currently considered the mainstay of therapy of some chronic cholestatic liver diseases, such as primary biliary cirrhosis. The major mechanisms of action of ursodeoxycholic acid therapy in cholestatic liver diseases are discussed. An attempt is made to illustrate how scientific research can lead to advances in medical practice that help patients. (HEPATOLOGY 2010:51:1095,1106.) [source] Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice,HEPATOLOGY, Issue 4 2007Megan H. Keane The marked deficiency of peroxisomal organelle assembly in the PEX2,/, mouse model for Zellweger syndrome provides a unique opportunity to developmentally and biochemically characterize hepatic disease progression and bile acid products. The postnatal survival of homozygous mutants enabled us to evaluate the response to bile acid replenishment in this disease state. PEX2 mutant liver has severe but transient intrahepatic cholestasis that abates in the early postnatal period and progresses to steatohepatitis by postnatal day 36. We confirmed the expected reduction of mature C24 bile acids, accumulation of C27,bile acid intermediates, and low total bile acid level in liver and bile from these mutant mice. Treating the PEX2,/, mice with bile acids prolonged postnatal survival, alleviated intrahepatic cholestasis and intestinal malabsorption, reduced C27,bile acid intermediate production, and prevented older mutants from developing severe steatohepatitis. However, this therapy exacerbated the degree of hepatic steatosis and worsened the already severe mitochondrial and cellular damage in peroxisome-deficient liver. Both untreated and bile acid,fed PEX2,/, mice accumulated high levels of predominantly unconjugated bile acids in plasma because of altered expression of hepatocyte bile acid transporters. Significant amounts of unconjugated bile acids were also found in the liver and bile of PEX2 mutants, indicating a generalized defect in bile acid conjugation. Conclusion: Peroxisome deficiency widely disturbs bile acid homeostasis and hepatic functioning in mice, and the high sensitivity of the peroxisome-deficient liver to bile acid toxicity limits the effectiveness of bile acid therapy for preventing hepatic disease. (HEPATOLOGY 2007;45:982,997.) [source] Oxidative stress parameters after combined fluoxetine and acetylsalicylic acid therapy in depressive patientsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2009Piotr Ga, ecki Abstract Objective There are numerous reports indicating disturbed equilibrium between oxidative processes and antioxidative defense in patients with depression. Moreover, depressive patients are characterized by the presence of elements of an inflammatory process, which is one of the sources of reactive oxygen species (ROS). In view of the above, it was decided to study both the effect of fluoxetine monotherapy and that of fluoxetine co-administered with acetylsalicylic acid on lipid peroxidation and antioxidative defense in patients with the first depressive episode in their life. Method Seventy seven patients with major depressive disorder (MDD), divided into two groups were included in the study. The first group, consisting of 52 patients, received fluoxetine 20 mg, and the second one, in addition to fluoxetine 20 mg, received 150 mg of acetylsalicylic acid. The activity of antioxidative enzymes, copper-zinc superoxide dismutase (CuZnSOD, SOD1), catalase (CAT), glutathione peroxidase (GPSH-x) and the concentration of malonyldialdehyde (MDA) was determined in erythrocytes, whereas the total antioxidant status (TAS) was determined in the plasma. All parameters were measured before and after three month therapy. Results The obtained results indicate a significant decrease in the activity of SOD1, CAT and GSHP-x, as well as in MDA concentration after the combined therapy. Also a significant TAS increase was observed after the combined therapy. The study demonstrated that combined therapy with fluoxetine and ASA is characterized by the same efficacy and clinical safety as fluoxetine monotherapy, resulting additionally in improvement of oxidative stress parameters in the patients treated for depression. Copyright © 2009 John Wiley & Sons, Ltd. [source] Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapyJOURNAL OF INTERNAL MEDICINE, Issue 5 2002T. Apeland Abstract. Apeland T, Mansoor MA, Seljeflot I, Brønstad I, Gøransson L, Strandjord RE (Rogaland Central Hospital, Stavanger; and Ullevål University Hospital, Oslo; Norway). Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy. J Intern Med 2002; 252: 456,464. Objectives. Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. Design. Longitudinal and open intervention study. Setting. Two dialysis units in the County of Rogaland. Subjects. All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. Interventions. After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. Main outcome measures. Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins , markers of endothelial activation and (iii) serum malondialdehyde (S-MDA) , a marker of oxidative stress and lipid peroxidation. Results. The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). Conclusions. Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance. [source] No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonatesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2008Barbro Malmgren Background:, Recent reports of osteonecrosis of the jaw (ONJ) after dental surgery in patients treated with second- and third-generation nitrogen-containing bisphosphonates instigated this retrospective study. As treatment with bisphosphonates in patients with osteogenesis imperfecta (OI) has become an important symptomatic therapy, especially for severe forms of the disease, we found it important to investigate whether healing after surgical exposure of jaw bone was influenced by the bisphosponate treatment in our group of children, adolescents and young adults with OI. Subjects and methods:, Disodiumpamidronate was given as monthly intravenous infusion to 64 patients with OI aged 3 months to 20.9 years at the start of treatment (mean 8.1, median 7.7). During 0.5,12.5 years of treatment (mean 4.5, median 4.0), a total individual dose of 140,4020 mg/m2 disodiumpamidronate was given (mean 1623 and median 1460). Ten patients continued with oral alendronate and two with zoledronic acid therapy. In 22 of these patients, 38 dental surgery procedures were performed at the age of 3.4,31.9 years (mean 12.2, median 12.3) after 0.03,7.9 years of treatment (mean 3.6, median 3.4). Results:, Despite long-term intravenous monthly disodiumpamidronate treatment, none of the 64 patients had any clinical signs of ONJ. Conclusions:, The risk of ONJ in these patients must be considered so low that the patients with indications for treatment should be treated and get the chance to experience the well-documented beneficial effect for children with severe OI. [source] An investigation of medication adherence to 5-aminosalicylic acid therapy in patients with ulcerative colitis, using self-report and urinary drug excretion measurementsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2009T. MOSHKOVSKA Summary Background, Non-adherence to 5-aminosalicylic acid (5-ASA) medication can limit the established benefits of this therapy in ulcerative colitis (UC). Aim, To determine rates and predictors of non-adherence to 5-ASA therapy in UC patients. Methods, Medication adherence was assessed using self-report data and urinary drug excretion measurements. Participants completed a study-specific questionnaire and two validated questionnaires: Beliefs about Medicine Questionnaire (BMQ)-Specific and Satisfaction with Information about Medicines Scale. Results, A total of 169 participants provided self-report adherence data; 151 also provided urine samples. Adherence rates were 111/151 (68%) according to self-report and 90/151 (60%) according to urine analysis, but the two measures were not correlated (,2 = 0.12, P = 0.725). Logistic regression identified a significant association between self-reported non-adherence and younger age [odds ratio (OR) for increased age 0.954, 95% confidence interval (CI) 0.932,0.976] and also doubts about personal need for medication (OR for BMQ , Specific Necessity scores 0.578, 95% CI 0.366,0.913). For non-adherence based on urine analysis, only South Asian ethnicity was independently associated with non-adherence (OR 2.940, 95% CI 1.303,6.638). Conclusions, Our observations confirm the difficulty of accurately assessing medication adherence. Nonmodifiable (younger age, South Asian ethnicity) and potentially modifiable (medication beliefs) predictors of non-adherence were identified. [source] Predictors of persistence with 5-aminosalicylic acid therapy for ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009S. V. KANE Summary Background, Individuals with ulcerative colitis (UC) are at risk for poor persistence with therapy. Aim, To identify factors predicting persistence with 5-aminosalicylic acid (5-ASA) therapy after 3 and 12 months in subjects with UC. Methods, In this retrospective cohort study, persistence with 5-ASA therapy was determined from prescription refill data from a commercial health insurance claims database. The analysis included subjects with UC who filled a prescription for any oral 5-ASA between October 2002 and September 2004. Persistence was defined as prescription refill at 3 and/or 12 months. Multivariate logistic regression modelling identified variables independently associated with persistence at 3 and 12 months. Results, In all, 3574 subjects were identified. Fifty-seven per cent (2044) were persistent at 3 months. Glucocorticoid use before the index prescription predicted improved persistence at 3 months. Psychiatric diagnosis, mail order of the index prescription, female gender and co-pay predicted decreased persistence. At 12 months, 1124 (55%) remained persistent. Rectal 5-ASA use, older age and switching to a different 5-ASA predicted improved persistence at 12 months. Hospitalization for a gastrointestinal condition, mail order of the 3-month prescription and number of co-morbid illnesses predicted lower persistence. Conclusion, Persistence with 5-ASA treatment in UC is complex and multifactorial, and differs by time period. [source] Genetic cholestasis, causes and consequences for hepatobiliary transportLIVER INTERNATIONAL, Issue 5 2003Peter L. M. Jansen Abstract: Bile salts take part in an efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum. In the liver, the sodium-dependent taurocholate transporter at the basolateral (sinusoidal) membrane and the bile salt export pump at the canalicular membrane mediate hepatic uptake and hepatobiliary secretion of bile salts. Canalicular secretion is the driving force for the enterohepatic cycling of bile salts and most genetic diseases are caused by defects of canalicular secretion. Impairment of bile flow leads to adaptive changes in the expression of transporter proteins and enzymes of the cytochrome P-450 system involved in the metabolism of cholesterol and bile acids. Bile salts act as ligands for transcription factors. As such, they stimulate or inhibit the transcription of genes encoding transporters and enzymes involved in their own metabolism. Together these changes appear to serve mainly a hepatoprotective function. Progressive familial intrahepatic cholestasis (PFIC) results from mutations in various genes encoding hepatobiliary transport proteins. Mutations in the FIC1 gene cause relapsing or permanent cholestasis. The relapsing type of cholestasis is called benign recurrent intrahepatic cholestasis, the permanent type of cholestasis PFIC type 1. PFIC type 2 results from mutations in the bile salt export pump (BSEP) gene. This is associated with permanent cholestasis since birth. Serum gamma-glutamyltransferase (gamma-GT) activity is low to normal in PFIC types 1 and 2. Bile diversion procedures, causing a decreased bile salt pool, have a beneficial effect in a number of patients with these diseases. However, liver transplantation is often necessary. PFIC type 3 is caused by mutations in the MDR3 gene. MDR3 is a phospholipid translocator in the canalicular membrane. Because of the inability to secrete phospholipids, patients with PFIC type 3 produce bile acid-rich toxic bile that damages the intrahepatic bile ducts. Serum gamma-GT activity is elevated in these patients. Ursodeoxycholic acid therapy is useful for patients with a partial defect. Liver transplantation is a more definitive therapy for these patients. [source] Fournier's gangrene and scrotal ulcerations during all-trans-retinoic acid therapy for acute promyelocytic leukemiaPEDIATRIC BLOOD & CANCER, Issue 2 2008Rahul Naithani MD Abstract Scrotal ulcers are a rare manifestation in patients with acute promyelocytic leukemia. Fournier's gangrene (FG) is even rarer. We describe three adolescents and young adults who developed scrotal ulcerations during induction with all-trans-retinoic acid. One patient developed FG. These lesions are predominantly seen in Asian population. A good outcome with supportive management occurred in all the cases. Pediatr Blood Cancer 2008;51:303,304. © 2008 Wiley-Liss, Inc. [source] Plasma vitamin values and antiepileptic therapy: Case reports of pregnancy outcomes affected by a neural tube defectBIRTH DEFECTS RESEARCH, Issue 1 2007Mirande Candito Abstract BACKGROUND: Folic acid supplementation reduces the occurrence of neural tube defects (NTDs); however, it is not clear whether it protects against teratogenic effects of antiepileptic drugs. METHODS: We report the cases of four pregnant women receiving valproic acid therapy, who all had NTD-affected offspring, despite periconceptional 5 mg/day of folic acid supplementation (cases), and investigated homocysteine metabolism, linked with folate metabolism. Their plasma homocysteine, folates, and vitamin B6 and B12 results were compared with values of two other women, who were also receiving valproic acid and folic acid complement, but who had normal pregnancies (valproic acid controls), and values of 40 pregnant women who had normal pregnancies and were not receiving any therapy (controls without therapy). Because of the possible existence of a genetic susceptibility, polymorphisms in homocysteine metabolism were sought. RESULTS: Two cases showed a decreased phosphopyridoxal level, compared with levels in the controls not receiving therapy. The genotype TT (C677T) is an NTD genetic susceptibility, but it was observed in only one valproic acid control. Various polymorphisms were observed in the cases, but were also common in the controls. Several studies have reported that valproic acid therapy lowers vitamin B6 levels. Our case with the greatest decrease in plasma phosphopyridoxal, who was taking periconceptional folic acid plus pyridoxine therapy, had a normal second pregnancy outcome. CONCLUSIONS: In addition to folates, other vitamins, such as vitamin B6, may have played a role in NTDs in our patients taking an antiepileptic drug. Birth Defects Research (Part A) 2007. © 2006 Wiley-Liss, Inc. [source] The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid,CANCER, Issue 6 2007William K. Oh MD Abstract BACKGROUND Bisphosphonates have been used to treat bone metastases in hormone-refractory prostate cancer (HRPC), but certain agents have been associated with renal toxicity. For this observational study, the authors assessed the risk of renal impairment in patients with HRPC who received zoledronic acid from December 1999 to April 2005. METHODS A comprehensive medical records review was performed in a major tertiary oncology center (n = 122 patients). The primary outcome of renal impairment was defined as an increase ,0.5 mg/dL or ,1.0 mg/dL over baseline creatinine value if the baseline value was <1.4 mg/dL or ,1.4 mg/dL, respectively. A risk factor analysis was conducted using the Andersen-Gill extension to the Cox proportional hazards model. RESULTS Renal impairment was observed in 23.8% of patients. The risk of renal impairment increased with an extended duration of zoledronic acid therapy (<6 months, 11.1%; ,24 months, 26.3%) and previous pamidronate treatment (45.5% vs 19.0% for patients with no prior pamidronate). A significantly greater risk of renal impairment was associated with increasing age at zoledronic acid initiation, prior pamidronate use, and a history of renal disease, hypertension, or smoking (P , 0.05). CONCLUSIONS In an outpatient clinic setting, the risk of renal impairment among patients with HRPC who received zoledronic acid was greater than the risk reported previously in clinical trials. Cancer 2007 © 2007 American Cancer Society. [source] The keloid phenomenon: Progress toward a solutionCLINICAL ANATOMY, Issue 1 2007Louise Louw Abstract For centuries, keloids have been an enigma and despite considerable research to unravel this phenomenon no universally accepted treatment protocol currently exists. Historically, the etiology of keloids has been hypothesized by multiple different theories; however, a more contemporary view postulates a multifactoral basis for this disorder involving nutritional, biochemical, immunological, and genetic factors that play a role in this abnormal wound healing. Critical to the process of preventing or managing keloids is the need to locally control fibroblasts and their activities at the wound site. In recent years, considerable evidence has accumulated demonstrating the importance of fatty acids and bioactive lipids in health and disease, especially those involving inflammatory disorders or immune dysfunction. If hypertrophic scarring and keloid formation can be argued to have significant inflammatory histories, then it is possible to postulate a role for lipids in their etiology and potentially in their treatment. This report briefly visits past views and theories on keloid formation and treatment, and offers a theoretical rationale for considering adjuvant fatty acid therapy for keloid management. Sufficient scientific evidence in support of fatty acid strategies for the prevention and treatment of keloids currently exists, which offer opportunities to bridge the gap between the laboratory and the clinic. The intent of this paper is to serve as a basic guideline for researchers, nutritionists, and clinicians interested in keloids and to propose new directions for keloid management. Clin. Anat. 20:3,14, 2007. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||