Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis

OBJECTIVES: Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. METHODS: Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. RESULTS: HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION: Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.     

Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men

Two binding proteins, SHBG and IGF-binding protein-1 (IGFBP-1), are both down-regulated by insulin and therefore could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk. We compared serum SHBG and IGFBP-1 as potential markers of abnormal glucose tolerance, the metabolic syndrome, diabetes mellitus, cardiovascular risk factors, and total, cardiovascular, and coronary heart disease mortality in elderly men. Of the original cohort of 1711 men, 524 were alive on January 1, 1989, and 413 participated in the 30-yr examination, of whom 335 men, aged 70-89 yr, formed the study group for the present analysis. Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus. SHBG was less influenced by body mass index than IGFBP-1. Low SHBG indicated increased cardiovascular and coronary disease mortality; the association remained after adjustment for abnormal glucose tolerance, but not after adjustment for prevalent cardiovascular disease. IGFBP-1 had no association with mortality. It is concluded that low SHBG is a better indicator of increased cardiovascular mortality than low or high IGFBP-1.     

Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins

Interactive genetic and environmental factors may influence the differentiation of surfactant and the risk of respiratory distress syndrome (RDS). DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population. Distributions of the SP-A and SP-B gene variants between RDS and no-RDS infants were determined alone and in combination. SP-A1 allele 6A2 (p = 0.009) and the homozygous genotype 6A2/6A2 (p = 0.003) were overrepresented in RDS of singletons when the SP-B exon 4 genotype was Thr/Thr, and underrepresented in RDS of multiples when the SP-B genotype was Ile/Thr (p = 0.012 for 6A2 and p = 0.03 for 6A2/6A2) or Thr/Thr (p = 0.12 for 6A2 and p = 0.018 for 6A2/6A2, respectively). The SP-A 6A2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS. There was a continuous association between fetal mass and risk of RDS, defined by the SP-A and SP-B variants. Labeled lung explants with the Thr/Thr genotype showed proSP-B amino-terminal glycosylation, which was absent in Ile/Ile samples. Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS.     

Trends in the prevalence, awareness, treatment and control of hypertension: the WHO MONICA Project.

OBJECTIVE: To describe the secular changes in the prevalence, awareness, treatment and control of hypertension. DESIGN: Two independent cross-sectional population surveys using standardized methods conducted between the early 1980s and mid-1990s. SETTING: Twenty-four geographically defined populations of the WHO MONICA Project. PARTICIPANTS: Randomly selected men and women aged 35-64 years. The total number of participants was 69 907. MAIN OUTCOME MEASURES: Two definitions of hypertension were used: 160/95 mmHg or above and 140/90 mmHg or above for systolic or diastolic blood pressure. Subjects on antihypertensive drug treatment were considered to be hypertensive regardless of their blood pressure. Treated subjects whose measured blood pressure level was less than 160/95 or 140/90 mmHg according to the two definitions, respectively, were considered to be adequately treated. RESULTS: The age-adjusted prevalence of hypertension decreased in most and increased in only a few populations. For both definitions of hypertension, the proportion of hypertensive subjects who were aware of their condition increased in three-quarters of the male populations and in two-thirds of the female populations. Furthermore, the proportion of hypertensive individuals on antihypertensive drug treatment increased in three-quarters of the populations. In the final survey, hypertension tended to be better treated and controlled in women than in men. Nevertheless, a large proportion of patients receiving antihypertensive drug therapy still had inadequately controlled blood pressure levels. CONCLUSION: Although awareness and treatment of hypertension according to the data obtained during the late 1980s to the mid-1990s increased in several populations, the effectiveness of antihypertensive treatment showed the continuing need for improvements.     

Effects of chitosan and bioactive glass modifications of knitted and rolled polylactide‐based 96/4 L/D scaffolds on chondrogenic differentiation of adipose stem cells

The performance of biodegradable knitted and rolled 3‐dimensional (3D) polylactide‐based 96/4 scaffolds modified with bioactive glass (BaG) 13‐93, chitosan and both was compared with regard to the viability, proliferation and chondrogenic differentiation of rabbit adipose stem cells (ASCs). Scaffold porosities were determined by micro‐computed tomography (μCT). Water absorption and degradation of scaffolds were studied during 28‐day hydrolysis in Tris‐buffer. Viability, number and differentiation of ASCs in PLA96/4 scaffolds were examined in vitro. The dimensions of the scaffolds were maintained during hydrolysis and mass loss was detected only in the BaG13‐93 containing scaffolds. ASCs adhered and proliferated on each scaffold type. Cell aggregation and expression of chondral matrix components improved in all scaffold types in chondrogenic medium. Signs of hypertrophy were detected in the modified scaffolds but not in the plain PLA96/4 scaffold. Chondrogenic differentiation was most enhanced in the presence of chitosan. These findings indicate that the plain P scaffold provided a good 3D‐matrix for ASC proliferation whereas the addition of chitosan to the PLA96/4 scaffold induced chondrogenic differentiation independent of the medium. Accordingly, a PLA96/4 scaffold modified by chitosan could provide a functional and bioactive basis for tissue‐engineered chondral implants. Copyright © 2012 John Wiley & Sons, Ltd.     

Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia

BACKGROUND: Familial combined hyperlipidemia (FCHL) is the most common hereditary lipid disorder that predisposes the patients to premature coronary heart disease. Members of FCHL families are categorised as affected or unaffected according to serum lipid levels. This study is aimed to evaluate whether there is a difference in carotid artery wall thickness between asymptomatic FCHL family members who are affected and those who are unaffected according to the currently used lipid criteria. METHODS AND RESULTS: Carotid artery ultrasonography with intima-media thickness (IMT) measurements was performed for 148 members of 39 Finnish FCHL families. Study subjects who had no history of coronary heart disease or stroke were divided into two groups according to their serum total cholesterol and/or triglyceride levels. The average carotid IMT of the affected subjects (0.75+/-0.15 mm) was not significantly different from that of their unaffected relatives (0.73+/-0.13 mm), P=0.90. In multivariate analysis, age, gender, and pulse pressure, but no lipid variables, contributed significantly to the variation of carotid IMT. CONCLUSIONS: The IMT findings in FCHL family members indicate that the current lipid criteria alone are of limited value in predicting long-term risk of cardiovascular disease in asymptomatic members of FCHL families.     

Comparison of Chondroitin Sulfate and Hyaluronic Acid Doped Conductive Polypyrrole Films for Adipose Stem Cells

Polypyrrole (PPy) is a conductive polymer that has aroused interest due to its biocompatibility with several cell types and high tailorability as an electroconductive scaffold coating. This study compares the effect of hyaluronic acid (HA) and chondroitin sulfate (CS) doped PPy films on human adipose stem cells (hASCs) under electrical stimulation. The PPy films were synthetized electrochemically. The surface morphology of PPy–HA and PPy–CS was characterized by an atomic force microscope. A pulsed biphasic electric current (BEC) was applied via PPy films non-stimulated samples acting as controls. Viability, attachment, proliferation and osteogenic differentiation of hASCs were evaluated by live/dead staining, DNA content, Alkaline phosphatase activity and mineralization assays. Human ASCs grew as a homogenous cell sheet on PPy–CS surfaces, whereas on PPy–HA cells clustered into small spherical structures. PPy–CS supported hASC proliferation significantly better than PPy–HA at the 7 day time point. Both substrates equally triggered early osteogenic differentiation of hASCs, although mineralization was significantly induced on PPy–CS compared to PPy–HA under BEC. These differences may be due to different surface morphologies originating from the CS and HA dopants. Our results suggest that PPy–CS in particular is a potential osteogenic scaffold coating for bone tissue engineering.