Magnetic resonance imaging in the prenatal diagnosis of neural tube defects

OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) in the prenatal diagnosis of neural tube defects (NTDs). BACKGROUND: NTDs comprise a heterogeneous group of congenital anomalies that derive from the failure of the neural tube to close. Advances in ultrasonography and MRI have considerably improved the diagnosis and treatment of NTDs both before and after birth. Ultrasonography is the first technique in the morphological study of the fetus, and it often makes it possible to detect or suspect NTDs. Fetal MRI is a complementary technique that makes it possible to clear up uncertain ultrasonographic findings and to detect associated anomalies that might go undetected at ultrasonography. The progressive incorporation of intrauterine treatments makes an accurate diagnosis of NTDs essential to ensure optimal perinatal management. The ability of fetal MRI to detect complex anomalies that affect different organs has been widely reported, and it can be undertaken whenever NTDs are suspected. CONCLUSION: We describe the normal appearance of fetal neural tube on MRI, and we discuss the most common anomalies involving the structures and the role of fetal MRI in their assessment. KEY POINTS: • To learn about the normal anatomy of the neural tube on MRI • To recognise the MR appearance of neural tube defects • To understand the value of MRI in assessing NTD

Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats

<p>Abstract</p> <p>Background</p> <p>GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats.</p> <p>Methods</p> <p>Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight^-1* day^-1) for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states). ATP synthesis in isolated mitochondria was determined by an enzymatic method.</p> <p>Results</p> <p>Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations.</p> <p>Conclusions</p> <p>We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.</p

Climate-induced changes in grapevine yield and must sugar content in Franconia (Germany) between 1805 and 2010

When attempting to estimate the impacts of future climate change it is important to reflect on information gathered during the past. Understanding historical trends may also aid in the assessment of likely future agricultural and horticultural changes. The timing of agricultural activities, such as grape harvest dates, is known to be influenced by climate and weather. However, fewer studies have been carried out on grapevine yield and quality. In this paper an analysis is undertaken of long-term data from the period 1805-2010 on grapevine yield (hl/ha) and must sugar content (°Oe) and their relation to temperature. Monthly mean temperatures were obtained for the same time period. Multiple regression was used to relate the viticulture variables to temperature, and long-term trends were calculated. Overall, the observed trends over time are compatible with results from other long term studies. The findings confirm a relationship between yield, must sugar content and temperature data; increased temperatures were associated with higher yields and higher must sugar content. However, the potential increase in yield is currently limited by legislation, while must sugar content is likely to further increase with rising temperatures

Dose Dependent Effects on Cell Cycle Checkpoints and DNA Repair by Bendamustine

Bendamustine (BDM) is an active chemotherapeutic agent approved in the U. S. for treating chronic lymphocytic leukemia and non-Hodgkin lymphoma. Its chemical structure suggests it may have alkylator and anti-metabolite activities; however the precise mechanism of action is not well understood. Here we report the concentration-dependent effects of BDM on cell cycle, DNA damage, checkpoint response and cell death in HeLa cells. Low concentrations of BDM transiently arrested cells in G2, while a 4-fold higher concentration arrested cells in S phase. DNA damage at 50, but not 200 µM, was efficiently repaired after 48 h treatment, suggesting a difference in DNA repair efficiency at the two concentrations. Indeed, perturbing base-excision repair sensitized cells to lower concentrations of BDM. Timelapse studies of the checkpoint response to BDM showed that inhibiting Chk1 caused both the S- and G2-arrested cells to prematurely enter mitosis. However, whereas the cells arrested in G2 (low dose BDM) entered mitosis, segregated their chromosomes and divided normally, the S-phase arrested cells (high dose BDM) exhibited a highly aberrant mitosis, whereby EM images showed highly fragmented chromosomes. The vast majority of these cells died without ever exiting mitosis. Inhibiting the Chk1-dependent DNA damage checkpoint accelerated the time of killing by BDM. Our studies suggest that BDM may affect different biological processes depending on drug concentration. Sensitizing cells to killing by BDM can be achieved by inhibiting base-excision repair or disrupting the DNA damage checkpoint pathway

Selection of the solvent and extraction conditions for maximum recovery of antioxidant phenolic compounds from coffee silverskin

The extraction of antioxidant phenolic compounds from coffee silverskin (CS) was studied. Firstly, the effect of different solvents (methanol, ethanol, acetone, and distilled water) on the production of antioxidant extracts was evaluated. All the extracts showed antioxidant activity (FRAP and DPPH assays), but those obtained with methanol and ethanol had significantly higher (p < 0.05) DPPH inhibition than the remaining ones. Due to the lower toxicity, ethanol was selected as extraction solvent, and further experiments were performed in order to define the solvent concentration, solvent/solid ratio, and time to maximize the extraction results. The best condition to produce an extract with high content of phenolic compounds (13 mg gallic acid equivalents/g CS) and antioxidant activity [DPPH = 18.24 μmol Trolox equivalents/g CS and FRAP = 0.83 mmol Fe(II)/g CS] was achieved when using 60 % ethanol in a ratio of 35 ml/g CS, during 30 min at 60–65 °C.This work was supported by the Portuguese Foundation for Science and Technology (FCT). The authors gratefully acknowledge Teresa Conde, student of Biological Engineering, for the help and interest in this work

Genomic and functional regulation of TRIB1 contributes to prostate cancer pathogenesis

Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that TRIB1 is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that TRIB1 amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, TRIB1 transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer