Increased epithelial permeability is a key feature of IBD pathogenesis and it has been proposed that agents which promote barrier function may be of therapeutic benefit. We have previously reported the secondary bile acid, ursodeoxycholic acid (UDCA), to be protective in a mouse model of colonic inflammation and that its bacterial metabolism is required for its beneficial effects. The current study aimed to compare the effects of UDCA, LCA, and a non-metabolizable analog of UDCA, 6-methyl-UDCA (6-MUDCA), on colonic barrier function and mucosal inflammation in a mouse model of colonic inflammation. Bile acids were administered daily to C57Bl6 mice by intraperitoneal injection. Colonic inflammation, induced by addition of DSS (2.5%) to the drinking water, was measured as disease activity index (DAI) and histological score. Epithelial permeability and apoptosis were assessed by measuring FITC-dextran uptake and caspase-3 cleavage, respectively. Cecal bile acids were measured by HPLC-MS/MS. UDCA and LCA, but not 6-MUDCA, were protective against DSS-induced increases in epithelial permeability and colonic inflammation. Furthermore, UDCA and LCA inhibited colonic epithelial caspase-3 cleavage both in DSS-treated mice and in an in vitro model of cytokine-induced epithelial injury. HPLC-MS/MS analysis revealed UDCA administration to increase colonic LCA levels, whereas LCA administration did not alter UDCA levels. UDCA, and its primary metabolite, LCA, protect against intestinal inflammation in vivo, at least in part, by inhibition of epithelial apoptosis and promotion of barrier function. These data suggest that clinical trials of UDCA in IBD patients are warranted.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.14814/phy2.14456

The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis.

Inflammatory bowel diseases (IBD) are chronic, inflammatory processes that affect the gastrointestinal tract and are mainly represented by ulcerative colitis (UC) and Crohn’s disease (CD). Omega 3 (ω3) fatty acids (eicosapentanoic acid and docosahexaenoic acid) show an indispensable role in the inflammatory processes and, for these reasons, we aimed to review the effects of these acids on UC and CD. Databases such as PUMED and EMBASE were searched, and the final selection included fifteen studies that fulfilled the inclusion criteria. The results showed that ω3 fatty acids reduce intestinal inflammation, induce and maintain clinical remission in UC patients, and are related with the reduction of proinflammatory cytokines, decrease disease activity and increase the quality of life of CD patients. Furthermore, the consumption of these fatty acids may be related to a reduced risk of developing IBD. Many studies have shown the beneficial effects of ω3 as adjunctive in the treatment or prevention of UC or CD. Nevertheless, most were performed with a small number of patients and there are many variations in the mode of consumption, the type of food or the type of formulation used. All these factors substantially interfere with the results and do not allow reliable comparisons.

https://www.mdpi.com/1422-0067/20/19/4851/pdf

Omega Fatty Acids and Inflammatory Bowel Diseases: An Overview.

The rapid progress of research into inflammatory bowel disease (IBD) has resulted in increasingly more treatment options. Different options have different advantages and disadvantages, and the preferences of patients may also differ. If patients can be invited to the formulation of medical decision-making, their compliance and satisfaction would be improved, thus possibly achieving better therapeutic results. The present review aims to summarize the current literature on shared decision-making (SDM) in the management of IBD, with the goal of promoting the application of SDM.

Shared decision-making in the management of patients with inflammatory bowel disease

Malassezia is the most prevalent fungus identified in the human skin microbiota; originally described at the end of the nineteenth century, this genus is composed of at least 14 species. The role of Malassezia on the skin remains controversial because this genus has been associated with both healthy skin and pathologies (dermatitis, eczema, etc.). However, with the recent development of next-generation sequencing methods, allowing the description of the fungal diversity of various microbiota, Malassezia has also been identified as a resident fungus of diverse niches such as the gut or breast milk. A potential role for Malassezia in gut inflammation and cancer has also been suggested by recent studies. The aim of this review is to describe the findings on Malassezia in these unusual niches, to investigate what is known of the adaptation of Malassezia to the gut environment and to speculate on the role of this yeast in the host physiology specifically related to the gastrointestinal tract.

/pdf/overview-of-the-potential-role-of-malassezia-in-gut-health-3orgaf5l9p.pdf

Overview of the Potential Role of Malassezia in Gut Health and Disease.

Context Intensive diet and exercise or metformin can prevent the development of diabetes in individuals with impaired fasting glucose, but the effects of these interventions on development of the metabolic syndrome are unknown. Contribution This secondary analysis of Diabetes Prevention Program data showed that lifestyle intervention and metformin each reduced the development of the metabolic syndrome among the 45% of participants who did not have it at baseline. The impact of lifestyle intervention was much more marked than that of metformin. Implications Interventions that prevent diabetes will also reduce the development of the metabolic syndrome. The Editors Considerable attention has recently been paid to the metabolic syndrome, a constellation of risk factors associated with insulin resistance and increased cardiovascular and diabetes risk. The third report of the National Cholesterol Education Program's Adult Treatment Panel now calls for the identification and treatment of this high-risk state and provides a simple set of criteria for diagnosis (1). The World Health Organization (WHO) and the American College of Endocrinology have also provided definitions (2). Although recent studies have provided estimates of the prevalence of the metabolic syndrome in the United States (3, 4), its interrelationship with impaired glucose tolerance is unclear. In particular, it is largely unknown what proportion of participants with impaired glucose tolerance have the metabolic syndrome and whether this varies by ethnicity, age, and sex. Clearly, because an elevated blood glucose level is a common criterion for all definitions, a close association is to be expected. This association may be even stronger in the subgroup of persons with both impaired glucose tolerance and impaired fasting glucose (that is, a fasting plasma glucose level 6.1 to 6.9 mmol/L [110 to 125 mg/dL]). The extent to which we may be able to reduce cardiovascular risk in patients with impaired glucose tolerance by preventing the metabolic syndrome through lifestyle or medication interventions is also unknown. The Diabetes Prevention Program (5, 6) provides a unique opportunity to begin to address these issues. It involves a large sample of more than 3000 participants with impaired glucose tolerance who were carefully followed and randomly allocated to treatment with an intensive lifestyle intervention, metformin, or placebo. In this report, we address 2 questions: the prevalence of the metabolic syndrome at baseline in the trial population (and how this varies by age and sex) and whether the 2 interventions reduced the incidence of new cases of the metabolic syndrome or increased resolution of existing cases compared with placebo. Methods Participants and Procedures Full details of the protocol have been published elsewhere (5, 6). The current report includes 3234 participants seen at baseline. This number includes participants from the 3 treatment arms investigated (that is, standard lifestyle or placebo, intensive lifestyle, and metformin), but not participants from the troglitazone arm, which was discontinued. Individuals were recruited between June 1996 and May 1999 from a variety of sources, including community screenings and household mailings, on the basis of perceived risk for diabetes. Written informed consent was obtained from all participants before screening, consistent with the Declaration of Helsinki and the guidelines of each center's institutional review board. The initial screening step consisted of a fasting glucose measurement. If the participant was eligible, this was followed by a 75-g oral glucose tolerance test. Inclusion criteria were as follows: a fasting plasma glucose level of 5.3 to 7.0 mmol/L (95 to 125 mg/dL) (7.0 mmol/L [125 mg/dL] for Native Americans); a 2-hour plasma glucose level of 7.8 to 11.1 mmol/L (140 to 199 mg/dL) following the glucose load; age of at least 25 years; and body mass index of at least 24 kg/m2 (22 kg/m2 for Asian Americans because of differences in body size in this group). Main exclusion criteria were recent myocardial infarction, symptoms of coronary heart disease, major illness, previous diagnosis of diabetes, use of medications known to impair glucose tolerance, or triglyceride level of at least 6.8 mmol/L (600 mg/dL), as previously detailed (5). Standardized interviewer-administered questionnaires were used to obtain self-reported data on personal medical history, medications, and diet. Self-reported race or ethnicity was classified according to the question used in the 1990 U.S. Census questionnaire (7). Overall, adiposity was assessed by body mass index. Waist circumference was assessed in the standing position midway between the highest point of the iliac crest and the lowest point of the costal margin in the mid-axillary line. All anthropometric measures reflected the average of 2 measurements. Blood pressure was measured twice at 30-second intervals by using a standard mercury manometer. The participant was seated in a chair for 5 minutes before the first measurement was taken, and the mean of the 2 readings was used in the analyses. The metabolic syndrome was defined according to criteria from the National Cholesterol Education Program's Adult Treatment Panel III (1), namely 3 or more of the following conditions: waist circumference greater than 102 cm in men and greater than 88 cm in women; serum triglyceride level of at least 1.7 mmol/L (150 mg/dL); high-density lipoprotein (HDL) cholesterol level less than 1.03 mmol/L (<40 mg/dL) in men and less than 1.3 mmol/L (<50 mg/dL) in women; blood pressure of 130/85 mm Hg or greater; and fasting plasma glucose level of 6.2 mmol/L (110 mg/dL). Participants who were being treated with blood pressurelowering or triglyceride-lowering medications (niacin or fibric acid derivatives) were classified as positive for the respective criterion. We chose the Adult Treatment Panel III (1) criteria because they are commonly used in the United States and are simpler to apply in clinical practice than, for example, the WHO criteria (2). Participants were randomly assigned to receive 1 of 3 interventions: standard lifestyle recommendations plus metformin, 850 mg twice per day; standard lifestyle recommendations plus placebo; or an intensive program of lifestyle intervention. The randomization was done centrally by computer; assignments to the lifestyle group were blinded until randomization, while assignments to the medication groups were blinded until the end of the study. The goals of the lifestyle program were to achieve and maintain a weight reduction of at least 7% of clinical body weight through a healthy low-calorie, low-fat diet and to engage in physical activity of moderate intensity, such as brisk walking, for at least 150 minutes per week. Participants were seen quarterly, when blood pressure was assessed. Fasting glucose levels were determined at the 6-month visits, and fasting lipid levels and waist circumference were measured annually. Further details have been published elsewhere (5, 6). Figure 1 shows the number of participants observed at each annual examination by treatment group. Figure 1. Randomly assigned participants by treatment group and annual visit. Laboratory Methods All of the analytic measurements were performed at the central biochemistry laboratory (Northwest Lipid Research Laboratories, University of Washington, Seattle, Washington). Fasting plasma glucose level was measured on a chemistry autoanalyzer by the glucokinase method. Insulin measurements were performed by using a polyethylene glycolaccelerated double antibody radioimmunoassay method developed in the Diabetes Endocrinology Research Center Immunoassay Core Laboratory (University of Washington, Seattle, Washington). This method is based on the use of an antihuman insulin guinea pig antibody and measures total immunoreactive insulin. The homeostasis model assessment for insulin resistance was calculated as follows (8): Measurements of total plasma cholesterol and triglycerides were performed enzymatically on a chemistry autoanalyzer by using methods standardized to the Centers for Disease Control and Prevention reference methods (9). We obtained HDL fractions for cholesterol analysis by treating whole plasma with dextran sulfate magnesium chloride to precipitate all of the apolipoprotein Bcontaining lipoproteins (10). We calculated low-density lipoprotein cholesterol by using the Friedewald equation (11). In participants with triglyceride levels higher than 4.5 mmol/L (>400 mg/dL), the lipoprotein fractions were separated by using preparative ultracentrifugation of plasma by beta quantification (12). Statistical Analyses Participants were followed for an average of 3.2 years (range, 0.04 to 5.0 years) from the start of the study in June 1996 through 31 July 2001, a period 4 months longer than that reported previously (5). This period was chosen to maximize the available data that were collected during the masked phase of the Diabetes Prevention Program, since unmasking occurred in early August 2001. Random treatment assignments were stratified according to clinical center and were generated by the coordinating center through computer linkup to the field center at time of randomization. Therefore, assignment was unknown until randomization. Assignments to metformin and placebo were double-blinded. The study design and analysis followed the intention-to-treat principle. Nominal (unadjusted) P values and confidence intervals are reported. Logistic regression was used to compare the prevalence of the metabolic syndrome and its components at baseline among the demographic variables. The time to the outcome was assessed by using life-table methods (13). Modified product-limit curves for the cumulative incidence of the metabolic syndrome and for its resolution were compared by using the log-rank test. The estimated cumulative incidence, or resolution, at 3 years and the ris

The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial.[summary for patients in Ann Intern Med. 2005 Apr 19;142(8):I46; PMID: 15838061]

Ulcerative colitis (UC) and Crohn's disease (CD) are classified as chronic inflammatory bowel diseases (IBD) which have similar symptoms and lead to digestive disorders and inflammation in the digestive system. The reason why they occur is still a mystery. A number of factors can be attributed to the prevalence of CD and UC, some of which include geographical location, inappropriate diet, genetics, and inappropriate immune response. Both diseases are more often diagnosed in urban areas compared to rural areas and both have their own challenges and side effects, but the patients can still have a good quality of life. Given the fact that the prevalence of this disease is higher at younger ages and that it disrupts half the life of the patient, it will, most likely, become a major health problem in the near future, even in developing countries. By reviewing valid scientific resources and evaluating new methods of addressing this disease, the present study aims to provide researchers and patients with new insights into this field and facilitate access to new treatments.

A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease.

* لوئسم هدنسيون : ،زاوها  راولب  ،ناتسلگ  نابايخ  ،دنفسا هاگشناد  مولع  يكشزپ  يدنج  روپاش  ،زاوها  زكرم  تاقيقحت  تبايد .  نفلت : 33743063 061  E-mail: Nokhostin.F@ajums.ac.ir فده و هنيمز : لوباتم مردنس ي ك  (Metabolic syndrome) هعومجم  ا ي ارب زاسرطخ لماوع زا ي ب زورب ي رام ي اه ي ـبلق ي  قورع ي د و ي تبا تسا .  ب طابترا ي ن سا حطس ي د روا ي ك لوباتم مردنس زورب و مرس ي ك هـب زوـنه ناناوجون رد لـماك روـط تسا هدشن صخشم . سررب فده اب رضاح هعلاطم ي ا ي ن حارط زاوها رهش ناناوجون رد عوضوم ي دش .  يسررب شور : ا رد ي ن عطقم هعلاطم ي ،  240 لوباتم مردنس گرزب هعلاطم رد هدننك تكرش دارفا زا رفن ي ك لاـس رـهم هك 1388  ات رهم 1389 فداصت تروص هب دوب هدش ماجنا زاوها رهش رد ي زا سپ و هدش باختنا اهنآ هـب لاتـبم هورـگ ود هب لوباتم مردنس ي ك مرس حطس ملاس و ي سا ي د روا ي ك ا ي ود ن اقم دروم هورگ ي هس تفرگ رارق . دارـفا ملاـس هورـگ رد ي هـك تح ي  ي ك ي عم زا ي اهرا ي لوباتم مردنس ي ك  ATPIII ) قاچ ي مكـش ي س نوخراشـف ، ـ ي لوتس ي  ـ ي ا د ي لوتـسا ي ،لااـب  mg/dl  40

The association between concentration of Uric Acid and metabolic syndrome among adolescents

The prevalence of metabolic syndrome (MS) increased in recent years in both adolescents and children groups. The aim of the study is evaluating the relationship between insulin and uric acid (UA) level in MS in adolescents we studied 120 adolescence aged 10 to 19 in two groups: control group without metabolic syndrome and case group with metabolic syndrome. The Criteria of ATP III was considered as a diagnosis factor for metabolic syndrome. Various studies have been conducted in various populations to evaluate the relationship between UA level and MS in adolescents. Abdominal obesity, low HDL, hypertriglyceridemia and hypertension are associated with high UA level. In their analysis, the MS OR in UA level⩽4.9, 4.9-5.8 and ⩾5.8 mg/dl was 1, 2.53 and 9.03, respectively, which were higher than our findings in current study. Hyperinsulinemia caused by insulin resistance is one of the complications associated with MS, which puts individuals at risk of diabetes and cardiovascular events. Uric acid level in the Case group was significantly higher than the control group (p = 0.0001, 43.8±1.4 vs. 4.1±1 mg/dl, respectively). Insulin level was significantly higher in the case group in compare to the control group (p = 0.008, 9.8± 5.3 vs. 12.2±6 μU/ml, respectively). The findings of this case-control study showed that adolescents with metabolic syndrome have a higher uric acid and insulin level in compare to normal subjects. We hypothesis that increase in serum insulin and uric acid level can be a risk factor in the development of metabolic syndrome.

The comparison of insulin and uric acid levels in adolescents with and without metabolic syndrome

Introduction: Ankylosing spondylitis (AS) is an autoimmune disease, which causes mild to severe clinical symptoms in patients. Several inherited and acquired factors are involved in the pathogenesis of the disease. Human leukocyte antigen B27 (HLA-B27) is one of the factors, whose expression affects patients’ susceptibility to AS. Objectives: In this study, we evaluated HLA-B27 frequency in AS patients of Khuzestan province of Iran. Patients and Methods: The study population (N=114) including patients with AS. Patients were examined and confirmed by a rheumatologist based on New York modified criteria. Clinical information was extracted from patients’ documents. Furthermore, general characteristics of the patients and several clinical variables (physio-pathological, self-report, and imaging) were taken into consideration. Results: The results showed that 62.3% of the patients were HLA-B27 positive, while 37.7% of which were HLA-B27 negative. This difference was statistically significant (P <0.05). The disease duration was shown to be almost equal in both groups (i.e., HLA-B27 positive and HLA-B27 negative). According to the results, various clinical symptoms (like ocular complications and peripheral arthritis) were observed in patients, and the complications of which were higher in HLA-B27 negative patients compared to HLA-B27 positive ones (P <0.05). Besides, it was seen that the male patients have shown a higher physio-pathological (using polymerase chain reaction [PCR] technique) report for positive HLA-B27 and a higher magnetic resonance imaging involvement compared with females, whereas the women showed higher disease activity score i.e., higher mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) value. Conclusion: For the AS patients, negative HLA-B27 cases show more progressive involvement sacroiliac joints compared with the positive HLA-B27 cases. More importantly, of hundred percent of patients who responded to anti-tumor necrosis factor (TNF) treatment, 52.6% were positive for the HLA-B27 antigen, and 47.4% were negative for the HLA-B27 antigen. Overall, it can be said that HLA-B27 lonely is not involved in the pathogenesis of AS and environmental factors should be investigated and involved in the disease development.

/pdf/evaluation-of-hla-b27-frequency-in-patients-with-ankylosing-7btyssqe.pdf

Forogh Nokhostin

Papers

A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease.

The association between concentration of Uric Acid and metabolic syndrome among adolescents

The comparison of insulin and uric acid levels in adolescents with and without metabolic syndrome

Evaluation of HLA-B27 frequency in patients with ankylosing spondylitis, and its relationship with clinical symptoms in Khuzestan province