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.     

Low total haemoglobin mass, blood volume and aerobic capacity in men with type 1 diabetes

Blood O₂ carrying capacity affects aerobic capacity (VO_2max). Patients with type 1 diabetes have a risk for anaemia along with renal impairment, and they often have low VO_2max. We investigated whether total haemoglobin mass (tHb-mass) and blood volume (BV) differ in men with type 1 diabetes (T1D, n = 12) presently without complications and in healthy men (CON, n = 23) (age-, anthropometry-, physical activity-matched), to seek an explanation for low VO_2max. We determined tHb-mass, BV, haemoglobin concentration ([Hb]), and VO_2max in T1D and CON. With similar (mean ± SD) [Hb] (144 vs. 145 g l^?1), T1D had lower tHb-mass (10.1 ± 1.4 vs. 11.0 ± 1.1 g kg^?1, P < 0.05), BV (76.8 ± 9.5 vs. 83.5 ± 8.3 ml kg^?1, P < 0.05) and VO_2max (35.4 ± 4.8 vs. 44.9 ± 7.5 ml kg^?1 min^?1, P < 0.001) than CON. VO_2max correlated with tHb-mass and BV both in T1D (r = 0.71, P < 0.01 and 0.67, P < 0.05, respectively) and CON (r = 0.54, P < 0.01 and 0.66, P < 0.001, respectively), but not with [Hb]. Linear regression slopes were shallower in T1D than CON both between VO_2max and tHb-mass (2.4 and 3.6 ml kg^?1 min^?1 vs. g kg^?1, respectively) and VO_2max and BV (0.3 and 0.6 ml kg^?1 min^?1 vs. g kg^?1, respectively), indicating that T1D were unable to reach similar VO_2max than CON at a given tHb-mass and BV. In conclusion, low tHb-mass and BV partly explained low VO_2max in T1D and may provide early and more sensitive markers of blood O₂ carrying capacity than [Hb] alone.     

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.     

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.