The metabolic syndrome predicts cardiovascular mortality: a 13-year follow-up study in elderly non-diabetic Finns.

AIMS: The metabolic syndrome (MetS) is defined as a clustering of cardiovascular risk factors characterized by insulin resistance. We investigated the relationship of the MetS and its single components, defined by all six different criteria, with coronary heart disease (CHD), cardiovascular disease (CVD), and all-cause mortality in a prospective population-based study. METHODS AND RESULTS: The MetS was defined according to the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), the National Cholesterol Education Program (NCEP), the American College of Endocrinology (ACE), the International Diabetes Federation (IDF), and the American Heart Association (updated NCEP) criteria. We investgated the relationship of the MetS defined by aforementioned six criteria with CHD, CVD, and all-cause mortality with Cox regression analyses in a non-diabetic Finnish population of 1025 subjects, aged 65-74 years, during the 13-year follow-up. The MetS defined by all aforementioned criteria was associated with a statistically significant risk for CVD mortality when adjusted for all confounding variables (Hazards Ratios, HRs from 1.31 to 1.51). The MetS defined by the WHO, ACE, and IDF criteria was associated with an increased risk of CHD mortality (HRs from 1.42 to 1.58). There was no association between the MetS by any criteria and all-cause mortality. Of the single components of the MetS, the following predicted CVD mortality in multivariable models: impaired fasting glucose by the WHO, NCEP, and ACE criteria (HR 1.34) and by the IDF and updated NCEP criteria (HR 1.29); impaired glucose tolerance by the WHO and ACE criteria (HR 1.55); low HDL cholesterol by the EGIR criteria (HR 1.50) and by the NCEP, IDF, and updated NCEP criteria (HR 1.29); and microalbuminuria according to the WHO definition (HR 1.86). CONCLUSION: The MetS defined by all six current criteria predicts CVD mortality in elderly subjects. However, of the single components of the MetS, IFG, IGT, low HDL cholesterol, and microalbuminuria predicted CVD mortality with equal or higher HRs when compared with the different definitions of the MetS. Therefore, our study suggests that the MetS is a marker of CVD risk, but not above and beyond the risk associated with its individual components.     

In vitro electroretinogram for the study of the functionality of differentiated retinal pigment epithelium cells

The purpose of this study is to develop and test a method to reveal if the retinal pigment epithelium (RPE) cells differentiated from human embryonic stem cells (hESC) support the functions of photoreceptors. hESC-derived RPE (hESC–RPE) cells offer a potent cell source for cell replacement therapy that may be used to prevent certain eye diseases. Methods to assure the functionality of the RPE cells are well warranted. Electroretinograms (ERG) measure the electrophysiological response of the retina to light stimuli. A setup was developed that enables the measurement of ERG in vitro from mice retinas cultured together with hESC–RPE cells. The co-culture of RPE and retinas seems to be a viable tool to assess the functionality of RPE in vitro. However, owing to limited sample size results were somewhat mixed, and thus it was not possible to prove that hESC–RPE cells enhance the ERG response of a mouse retina in vitro. The long-term culturing of the retinas needs to be refined to acquire more conclusive evidence of the supporting role of the RPE and to explore the full potential of the co-culture and ERG methods in assessing RPE functionality.     

Connective Tissue Growth Factor and Its Correlation to Other Growth Factors in Experimental Granulation Tissue

Connective tissue growth factor (CTGF) is upregulated in a variety of fibrotic disorders, probably secondary to the activation and production of transforming growth factor-beta (TGF- &#103 ). We have studied the expression of CTGF in a rat wound-healing model using Northern blot, in situ hybridization, and immunohistochemistry. The expression of CTGF mRNA in Northern blot and immunohistochemistry were correlated to the expression of TGF- &#103 1 and platelet-derived growth factor (PDGF). Northern hybridization showed the maximum expression of CTGF mRNA on day 14, whereas TGF- &#103 1 expression was maximal on days 7 and 14 and the time-related changes were smaller than for CTGF. PDGF A and PDGF B mRNA expressions were at maximum on day 14 and on day 21, respectively. In situ hybridization showed that fibroblast-like cells expressed CTGF most intensively, expression declining rapidly after day 14. CTGF mRNA and protein were found in blood vessel cells during the first week. In immunohistochemistry, all growth factors were expressed by fibroblast-like cells, macrophage-like cells, and blood vessels but CTGF-positive cells were fewer and were more restricted on days 5 and 7. These results demonstrate that CTGF expression together with TGF- &#103 and PDGF are upregulated in wound healing, and CTGF expression in blood vessels suggests that CTGF is involved in angiogenesis.     

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

Objective:

Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features.

Methods:

A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined.

Results:

Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC).

Conclusion:

The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making.

Advances in knowledge:

The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.