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The effect of exhaustive exercise on the concentration of purine nucleotides and their metabolites in erythrocytes  [PDF]
E Skotnicka,I Baranowska-Bosiacka,W Dudzińska,M Suska
Biology of Sport , 2008,
Abstract: In this study we tried to obtain a complete overview of purine nucleotide metabolism in erythrocytes before and during an incremental, intermittent exhaustive exercise bout protocol for sportsmen (high-performance rowers) and untrained, healthy, active volunteers. Erythrocyte levels of the main nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP, NAD and NADP ), nucleosides (Ado, Guo, Ino) and the base Hyp were measured using the HPLC method. The parameters that can be deducted from their concentrations: TAN, TGN and AEC, GEC expressed by the ratio of high/low energy nucleoside phosphates were calculated. The effects of graded rowing exercise on the concentration and metabolism of erythrocyte purine and pyridine nucleotides and the activity Na , K -ATPase in both trained and untrained individuals. In the group of sportsmen, ATP, ADP and AMP concentrations were decreasing during the effort (for ATP rs=-0.65). However, ADP and AMP concentrations were significantly lower only during recovery (p<0.0001). We observed a negative correlation (rs=-0.72) between the ATP concentration and the Ado concentration during maximal effort. In the sportsmen group, NAD concentration was decreasing during the effort (rs=-0.68). Lower activity of Na , K -ATPase in erythrocytes was significantly correlated with the decrease in ATP concentration after maximal effort in sportsmen. This study confirms that erythrocyte energy metabolism depends on the body’s adaptation to effort and the physical efficiency of the participants.
Measurement of Tryptophan Metabolites in Healthy Old Men and Patients of Type 2 Diabetes Mellitus (T2DM)  [PDF]
Akikazu Takada, Fumiko Shimizu, Tetsuya Takao, Junichi Masuda
Food and Nutrition Sciences (FNS) , 2018, DOI: 10.4236/fns.2018.910087
Abstract: Background: Plasma levels of tryptophan (TRP) metabolites have not been measured extensively in patients of type 2 diabetes mellitus (T2DM). Methods: Metabolites analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 quadrupole mass spectrometer combined with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan). Body mass index (BMI) and TRP metabolites have been measured in healthy old men (n = 20) and patients of T2DM (n = 20). TRP metabolites were measured by using the ultrahigh speed liquid chromatography-mass spectros-copy (Shimadzu Corporation). Results: The plasma levels of 5-hydroxytryptophan (5-HTRP), 5-hydroxyindoleacetic acid (5-HIAA), kynurenic acid (KNA), 3-hydroxykynurenine (3-HKN), and 3-hydroxyanthranilic acid (3-HAA) were higher in patients of T2DM than healthy old men. Since 5HTRP and 5-HIAA belong to the serotonin pathway, and KNA, 3-HKN, and 3-HAA belong to the KN pathway of TRP metabolism, these pathways were activated more in the patients of T2DM. Since plasma levels of Indole-3-acetic acid were not elevated in T2DM, that pathway was not activated more in T2DM. Serotonin levels were not increased but 5-HIAA levels were increased in the plasma of T2DM patients, which may mean that serotonin was quickly metabolized to 5-HIAA in the patients of T2DM. Conclusion: Plasma levels of tryptophan metabolites in serotonin and kynurenine pathways increased in T2DM patients. Obesity expressed by BMI may not influence tryptophan metabolism in healthy old men and T2DM patients. These results indicate that our new method of the simultaneous measurements of all the tryptophan metabolites is the powerful measure to identify factor related to endogenous stresses seen in DM.
Bile Acid Metabolites in Serum: Intraindividual Variation and Associations with Coronary Heart Disease, Metabolic Syndrome and Diabetes Mellitus  [PDF]
Carine Steiner, Alaa Othman, Christoph H. Saely, Philipp Rein, Heinz Drexel, Arnold von Eckardstein, Katharina M. Rentsch
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025006
Abstract: Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4,are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.
Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia  [PDF]
Jeffrey K. Yao, Ruth Condray, George G. Dougherty, Matcheri S. Keshavan, Debra M. Montrose, Wayne R. Matson, Joseph McEvoy, Rima Kaddurah-Daouk, Ravinder D. Reddy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042165
Abstract: Background The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. Methodology/Principal Findings Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-na?ve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. Conclusions/Significance Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology.
Evaluation of Tumour Necrosis Factor Alpha, Interleukin-2 Soluble Receptor, Nitric Oxide Metabolites, and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus  [PDF]
Flávia Ozorio Pereira,Tania Silvia Frode,Yara Santos Medeiros
Mediators of Inflammation , 2006, DOI: 10.1155/mi/2006/39062
Abstract: This study compared the results of tumour necrosis factor alpha (TNF-α), interleukin-2 soluble receptor (sIL-2R), nitric oxide metabolites (NOx), C-reactive protein (CRP), and lipids (total cholesterol, high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), and triglycerides) between control group (nondiabetic subjects) and overweight type 2 DM subjects. To restrict the influence of variables that could interfere in the interpretation of data, subjects with obesity and/or acute or chronic inflammatory disease, haemoglobinopathies, recent use of antibiotics, antiinflammatory drugs, and trauma were excluded. Type 2 DM patients (n=39; age 53.3±9.0 years; median glycated haemoglobin A1c<8%) presented higher levels of TNF-α, triglycerides (P<.01), NOx and sIL-2R (P<.05) than control group (n=28; age 39.7±14.1 years). CRP, LDL-cholesterol, total cholesterol, and HDL-cholesterol did not differ among groups. Diabetic women (n=21) had higher levels of TNF-α, total cholesterol, LDL-cholesterol, and HDL-cholesterol than diabetic men (n=18) (P<.05), but there were no differences among sexes in the control group. This study indicates that increased level of proinflammatory markers occurs in type 2 DM even in the absence of obesity and marked hyperglycaemia, confirming that the inflammation course of the atherosclerotic process is more severe in diabetic patients than in nondiabetic subjects.
Evaluation of Tumour Necrosis Factor Alpha, Interleukin-2 Soluble Receptor, Nitric Oxide Metabolites, and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus
Flávia Ozorio Pereira,Tania Silvia Frode,Yara Santos Medeiros
Mediators of Inflammation , 2006,
Abstract: This study compared the results of tumour necrosis factor alpha (TNF- α ), interleukin-2 soluble receptor (sIL-2R), nitric oxide metabolites (NO x ), C-reactive protein (CRP), and lipids (total cholesterol, high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), and triglycerides) between control group (nondiabetic subjects) and overweight type 2 DM subjects. To restrict the influence of variables that could interfere in the interpretation of data, subjects with obesity and/or acute or chronic inflammatory disease, haemoglobinopathies, recent use of antibiotics, antiinflammatory drugs, and trauma were excluded. Type 2 DM patients ( n = 39 ; age 53.3 ± 9.0 years; median glycated haemoglobin A 1c < 8 % ) presented higher levels of TNF- α , triglycerides ( P < .01 ), NO x and sIL-2R ( P < .05 ) than control group ( n = 28 ; age 39.7 ± 14.1 years). CRP, LDL-cholesterol, total cholesterol, and HDL-cholesterol did not differ among groups. Diabetic women ( n = 21 ) had higher levels of TNF- α , total cholesterol, LDL-cholesterol, and HDL-cholesterol than diabetic men ( n = 18 ) ( P < .05 ), but there were no differences among sexes in the control group. This study indicates that increased level of proinflammatory markers occurs in type 2 DM even in the absence of obesity and marked hyperglycaemia, confirming that the inflammation course of the atherosclerotic process is more severe in diabetic patients than in nondiabetic subjects.
DIABETES MELLITUS
HAFIZ MUHAMMAD YAR
The Professional Medical Journal , 2008,
Abstract: Objective: To determine the frequency of diabetes mellitus and to assess the level of awarenessabout diabetes amongst persons attending a free health camp in cultural festival of Rahim Yar Khan. Study Design:Cross sectional observational study. Place and duration of study: Three days free health camp arranged in a culturalfestival in Rahim Yar Khan. Results: Over all frequency of type II diabetes was 19.38% and the frequency of diabetesincreased both in men and women with increasing age (p<0.001). Newly diagnosed subjects were 6.77% and thesedo not know that they were suffering from diabetes. 18.92% subjects were having glucose intolerance and 61.70%subjects were having random blood glucose level within normal limits. Diabetes was correctly defined by 57% subjectsand this was significantly associated with educational level, suffering from the disease and presence of diseaseamongst family members. 14.62% gave history of presence of disease in their families. As compared to females, maleswere more suffering from disease and these were consuming more foods and snacks than females (p<.0.01).Conclusion: High frequency of diabetes mellitus was observed amongst the study population. This may be due tohealth consciousness and higher level of educational status in the subjects who participated. Emphasis on healtheducation and preventive strategies are needed to increase public awareness and early detection of high risk groupsand risk factors of this common disease in our country. The lifestyle behaviors and environmental factors are strongmodifiers of diabetes The life style changes and interventions in early age may prove to be more effective thaninterventions done at a later stage.
DIABETES MELLITUS
NOREEN RAHAT HASHMI
The Professional Medical Journal , 2008,
Abstract: Objective: To assess the awareness of diabetes in individuals attending Out Patient Department ofGhurki Trust Teaching Hospital. Design: Descriptive study design. Place of Study: Out Patients Department, GhurkiTeaching Hospital, Lahore. Methodology: The study was conducted among a sample of 50 individuals, recruited byconvenience sampling technique. Data was collected, by administering a structured questionnaire, during a two weekperiod in December 2006. Data was presented in the form of tables and graphs. Results: General Awareness ofDiabetes Mellitus in the participants of our study was poor. Only 16% recognized it as a disease of the pancreas while50% considered it to be a disease of other systems. Majority of the respondents (78%) had no idea about the types ofthe disease. When asked about the communicability of diabetes, 76% considered it to be non-communicable, 10%thought it to be communicable. Among the respondents, 78% thought diabetes is inheritable. When asked about itsprevention, 54% considered avoiding sugar as the best way to prevent diabetes, while only 9% believed weightreduction to be important. Regarding the management of diabetes, 40% of respondents considered medication, 27%thought of diet modification as a better way, 18% considered exercise, while only 6% named weight reduction.Conclusion: The participants of the present study lacked awareness of types of diabetes, its mode of inheritance, itsprevention and management.
Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency  [PDF]
Aisha Vanessa Sauer,Immacolata Brigida,Alessandro Aiuti
Frontiers in Immunology , 2012, DOI: 10.3389/fimmu.2012.00265
Abstract: Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties.
DIABETES MELLITUS
Riwan Hashmi
The Professional Medical Journal , 1998,
Abstract: Diabetic nephropathy is a common microvascular complication of diabetes mellitus and reflects serious renaldisease specific to diabetes. It is one of the common causes of end stage renal disease. A cross sectionalstudy was carried out to find the incidence of proteinuria, microalbuminuria and transferrinuria in knowdiabetics of Rawalpindi. One hundred and forty six consecutive diabetics were included in the study (68 menand 78 women) for detection of diabetic nephropathy. Thirty age and sec matched, healthy controls were alsoincluded in the study. Urine protein, microalbumin and transferrin concentration were analysed in the 24hours urine samples submitted by all diabetics and healthy controls. The screening of protein in urine wasdone by dipstick method using Uristix Ames (UK). Quantitative urine total protein was estimated by Biuretmethod; the dipstick negative samples were analysed for microalbuminuria by using Pyrogallol-molybdatetest technique and urinary transferrin was estimated by immunoturbidimetry method. The transferrinexcretion in diabetic subjects significantly (P<0.01) exceeded that in healthy subject. The 65% of diabeticshad an abnormally high urinary transferrin excretion and 40% had high urinary protein excretion(proteinuria: 14%: microalbuminuria: 26%). It is concluded that microalbuminuria proteinuria andtransferrinuria is common in our diabetics reflecting poor metabolic control.
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