Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0024523 (malabsorption)
7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied changes in serum cholestanol and plant sterols (indexes of cholesterol absorption) and cholesterol precursors (indexes of cholesterol synthesis) in response to cholesterol reduction by way of 1 year's treatment with atorvastatin (n = 102) and simvastatin (n = 105) treatments in patients with coronary heart disease. Serum cholesterol levels and ratios of the precursor sterols to cholesterol after 1 year of treatment were reduced in proportion to the pretreatment values (33% +/- 1% by simvastatin and 36% +/- 1% by atorvastatin; P <.01 for difference between groups) for cholesterol; the respective reductions in the precursor sterol:cholesterol ratios were also higher with atorvastatin (50% +/- 2% for lathosterol) than with simvastatin (42% +/- 1%; P <.01 between groups), but the ratio of squalene to cholesterol was increased (17% +/- 5%, P <.001) by atorvastatin. Plant sterol concentrations were gradually increased by atorvastatin but decreased initially by simvastatin. However, their ratios with respect to cholesterol were increased by as much as 82% with atorvastatin and by as much as 39% with simvastatin. In conclusion, effective inhibition of cholesterol synthesis and subsequent reduction in serum cholesterol levels by statins lead to increases in serum plant-sterol levels, probably as a result of reduced biliary secretion and enhanced absorption of these sterols. Because serum plant sterols have been claimed to be involved in the early development of atherosclerosis, the question arises whether continuously increasing serum plant sterols during long-term statin treatment should be prevented by cholesterol malabsorption (eg, by plant stanol ester consumption), especially in subjects with high baseline plant sterol values and effective sterol absorption.
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PMID:Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. 1257 49

The aim of this study was to investigate the sterol regulatory element-binding protein 1c (SREBP1c) mRNA muscle expression in morbid obese subjects before and after massive lipid malabsorption due to bariatric surgery (bilio-pancreatic diversion, BPD). We studied 11 obese subjects (BMI 49+/-2 kg/m2) before and 24 months after BPD. Skeletal muscle SREBP1c mRNA expression was determined using RT-competitive PCR. Intramyocytic triglycerides were quantified by HPLC. Insulin sensitivity (M/I) was assessed by euglycemic-hyperinsulinemic clamp. Energy expenditure and respiratory quotient (RQ) were measured over 24 h in a calorimetric chamber. Total cardiovascular risk dropped from 2 before to -2.5 after BPD (P<0.0001). The M/I value was normalized after surgery (0.036+/-0.0148 to 0.095+/-0.0147 micromol kgFFM(-1) min(-1) pmoles(-1) P<0.001). SREBP-1c mRNA levels were decreased (from 4.12+/-2.43 to 2.69+/-1.83% of cyclophilin mRNA, P=0.02) after BPD. In a multiple regression analysis, M/I values (P<0.0001) as well as the intramyocytic triglyceride levels (P=0.039) were the most powerful independent variables for predicting cardiovascular risk. Our results show that the reduction of cardiovascular risk after bariatric massive weight loss is strongly related to the reversion of insulin resistance and to the lowering of intramyocytic triglyceride depots. These two parameters are associated with a significant reduction in SREBP-1c mRNA expression in skeletal muscle, suggesting that this transcription factor might be involved in the accumulation of triglycerides in muscle cells of morbidly obese subjects.
Atherosclerosis 2003 Sep
PMID:Intramyocitic lipid accumulation and SREBP-1c expression are related to insulin resistance and cardiovascular risk in morbid obesity. 1295 94

Proctocolectomy modifies the enterohepatic circulation and activity of bacterial enzymes depending on the structure of the stoma and function of the terminal ileum. We evaluated in our comparative study effects of different colectomy constructions on cholesterol metabolism. Levels of lipoprotein cholesterol and triglycerides, noncholesterol sterols, and squalene in serum, fecal fat, and bile acids, cholesterol absorption efficiency, and cholesterol metabolism by sterol balance technique were analyzed in human subjects with ileal pouch-anal anastomosis (n = 34), conventional ileostomy (n = 8), ileorectostomy (n = 6), and controls (n = 29). Malabsorption of bile acids, but not of fat, and low serum levels of total and low-density lipoprotein cholesterol, but high levels of high-density lipoprotein cholesterol and increased cholesterol synthesis were evident in the colectomy groups. In contrast to the ileorectostomy group, expressing high absorption and biliary secretion of cholesterol, a low cholesterol absorption percentage accompanied by elevated serum proportions of cholesterol precursor sterols and phytosterols characterized the ileal pouch-anal anastomosis and conventional ileostomy groups. After colectomy, fecal excretion of secondary bile acids was low, whereas relative proportions of identifiable bile acids remained the same in each study group. Low serum levels of total and low-density lipoprotein cholesterol of colectomized subjects may decrease the risk of premature atherosclerosis. The favorable serum lipid profile was due to enhanced fecal loss of cholesterol as bile acids despite abnormally high cholesterol synthesis. Ileal dysfunction probably diminished cholesterol absorption in subjects with ileal pouch-anal anastomosis and conventional ileostomy, with no explanation for those with ileorectostomy with no clinical gastrointestinal dysfunction. Relative synthesis of identifiable primary bile acids remained unchanged postoperatively, but formation of secondary bile acids was weak due to scarce bacterial flora.
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PMID:Ileal pouch-anal anastomosis, conventional ileostomy and ileorectal anastomosis modify cholesterol metabolism. 1548 17

Since 1967, fructose has become the primary commercial sweetener in the food industry. Large amounts of fructose can be toxic and have been correlated with atherosclerosis, malabsorption, hyperuricemia, lactic acidosis, and cataracts. To understand the deleterious and critical role(s) fructose plays in normal metabolism, it is essential to know how and where fructose is metabolized. The fructose transporter, GLUT5, and the specialized enzymes ketohexokinase, aldolase, and triokinase comprise the well-defined fructose-specific metabolic pathway found in liver, kidney, and small intestine. It is estimated that 50-70% of ingested fructose is metabolized in these tissues; where and how the remaining 30-50% is metabolized is not well defined. Prediction of tissues capable of metabolizing fructose via this pathway was done using expressed sequence tags (ESTs) in Unigene and a gene-specific virtual northern blot (VNB) algorithm. Unigene and VNB combined correctly predicted the expression of the genes required for fructose metabolism in liver, kidney, and small intestine. Both methods indicated brain, breast, lymphocytes, muscle, placenta, and stomach additionally express this set of genes. Expression of the genes for GLUT5 (glut5) and ketohexokinase (khk) in neurons was validated by immunohistochemistry and RNA in situ hybridization, respectively. Using stringent controls, clear expression of glut5 and khk was localized to Purkinje cells in the cerebellum. Cerebellum was used to oxidize fructose to carbon dioxide. Together, these data suggest that these neurons in the brain are able to utilize fructose as a carbon source.
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PMID:Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum. 1626 70

Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-30 are not detectable in plasma; they are more frequent in patients with the most severe phenotype. Only a single amino acid substitution (R463W) has been reported as the cause of FHBL. Approximately 50% of FHBL subjects are carriers of pathogenic mutations in APOB gene; therefore, a large proportion of FHBL subjects have no apoB gene mutations or are carriers of rare amino acid substitutions in apoB with unknown effect. In some kindred FHBL is linked to a locus on chromosome 3 (3p21) but the candidate gene is unknown. Recently a FHBL plasma lipid phenotype was observed in carriers of mutations of the PCSK9 gene causing loss of function of the encoded protein, a proprotein convertase which regulates LDL-receptor number in the liver. Inactivation of this enzyme is associated with an increased LDL uptake and hypobetalipoproteinemia. HBL carriers of PCSK9 mutations do not develop fatty liver disease.
Atherosclerosis 2007 Dec
PMID:Molecular diagnosis of hypobetalipoproteinemia: an ENID review. 2718 Jun 45

The importance of Zn for optimal functioning of the immune system and antioxidant stress response is well documented. Zn homeostasis influences development and function of immune cells, activity of stress-related and antioxidant proteins [metallothioneins (MT), chaperones, ApoJ, Poly(ADP-Ribose) polymerase-1 (PARP-1) and Methionione Sulfoxide Reductase (Msr), Superoxide Dismutase (SOD)], and helps to maintain genomic integrity and stability. During ageing, the intake of Zn decreases due to inadequate diet and/or intestinal malabsorption, contributing to frailty, general disability and increased incidence of age-related degenerative diseases (cancer, infections and atherosclerosis). Although many factors contributing to Zn deficiency have been identified, the biochemical markers of Zn deficiency as well as the possibility to achieve relevant health benefits through Zn supplementation in the elderly are still a matter for evaluation. Taking into account that Zn homeostasis is regulated by proteins and enzymes for which polymorphisms have been previously found to be associated with successful/unsuccessful ageing, genetic screening might be of added value in evaluating the individual response to Zn supplementation. Biochemical, immunological, dietary and genetic studies aimed at understanding the impact of Zn in healthy ageing, the effect of Zn supplementation in the elderly and finally formulating a rationale for the promotion of correct Zn supplementation were discussed at the international Zincage conference held in Ancona in January 2007.
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PMID:Zinc and ageing: third Zincage conference. 1788 56

Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon -2, Q[-2]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small alpha-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow alpha migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.
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PMID:Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency. 1799 56

Inflammation and genetics are prominent mechanisms in the pathogenesis of atherosclerosis (AT) and its complications. In this review we discuss the possible impact on AT development of several genetic determinants involved in inflammation, oxidative stress and cytoprotection (IL-6, TNF-alpha, IL-10, CD14, TLR4, MT, HSP70). Genetic polymorphisms of these genes may affect a differential inflammatory response predisposing to AT. However, allelic polymorphisms of genes which increase the risk of AT frequently occur in the general population but, only adequate gene-environment-polymorphism interactions promote the onset of the disease. Zinc deficiency has been suggested as an environmental risk factor for AT. With advancing age, the incidence of zinc deficiency increases for several reasons. Among them, dietary intake, malabsorption and genetic background of inflammatory markers may be involved. A crucial contribution may also be played by increased oxidative stress which may lead to the appearance of dysfunctional proteins, including metallothioneins (MT) that are in turn involved in zinc homeostasis. The detection of candidate genes related to inflammation and promoting AT and their reciprocal influence/interaction with zinc status might allow earlier appropriate dietary interventions in genetically susceptible subjects.
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PMID:Pro-inflammatory genetic background and zinc status in old atherosclerotic subjects. 1861 49

Cholesterol 7alpha-hydroxylase (CYP7A1) plays a crucial role in cholesterol metabolism and has been implicated in genetic susceptibility to atherosclerosis. Thus, an understanding of its transcriptional regulation is of considerable importance. We evaluated the effect of a common -203A>C polymorphism in the CYP7A1 promoter region on the activity of CYP7A1, estimated as the ratios of serum 7alpha-hydroxycholest-4-en-3-one (C4) to either total or non-HDL-cholesterol. The study was performed on patients after resection of the distal ileum, leading to upregulation of CYP7A1 activity (n = 65). Healthy volunteers served as the control group (n = 66). Whereas higher CYP7A1 activity was associated with the -203A allele in the patient group (C4/cholesterol ratio, 29.0 vs. 14.8 microg/mmol, P = 0.032; C4/non-HDL-cholesterol ratio, 53.3 vs. 21.3 microg/mmol in -203AA and -203CC, P = 0.017, respectively), no differences were observed in the healthy controls. We conclude that under physiological conditions, the -203A>C polymorphism in the CYP7A1 gene promoter region does not seem to have any clinically relevant effect. However, in patients with severe bile salt malabsorption, this polymorphism markedly affects CYP7A1 activity.
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PMID:CYP7A1 promoter polymorphism -203A>C affects bile salt synthesis rate in patients after ileal resection. 1872 90

Evidence exists that well-planned vegetarian diets provide numerous health benefits and are appropriate for all stages of the life cycle. It is also known that animal foods provide micronutrients that are nonexistent or available only in limited amounts in plant foods. Restriction or exclusion of all animal foods may therefore result in low intake of certain micronutrients such as vitamin B-12, thereby affecting vitamin B-12 status and elevating plasma homocysteine concentrations. Overall, the studies we reviewed showed reduced mean vitamin B-12 status and elevated mean homocysteine concentrations in vegetarians, particularly among vegans. Low vitamin B-12 intake may lead to decreased bioavailability and functional deficiency of cobalamin. Although early noticeable symptoms of vitamin B-12 deficiency are nonspecific (unusual fatigue, digestion problems, frequent upper respiratory infections), the best-known clinical manifestations of cobalamin malabsorption are hematologic (pernicious anemia) and neurologic symptoms. Hyperhomocysteinemia is associated with an increased risk of atherosclerosis and cardiovascular disease. Given these health concerns, vegetarians, particularly vegans, must be advised to carefully plan their diets, to monitor their plasma vitamin B-12 on a regular basis to facilitate early detection of low cobalamin status, and to use vitamin B-12-fortified foods or take vitamin B-12 supplements if necessary.
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PMID:Vitamin B-12 and homocysteine status among vegetarians: a global perspective. 1935 23


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