Protein transduction: A novel tool for tissue regeneration

Tissue regeneration in humans is limited and excludes vitals organs like heart and brain. Transformation experiments with oncogenes like T antigen have shown that retrodifferentiation of the respective cells is possible but hard to control. To bypass the risk of cancer formation a protein therapy approach has been developed. The transient delivery of proteins rather than genes could still induce terminallydifferentiated cells to reenter the cell cycle. This approach takes advantage of proteintransducing domains that mediate the transfer of cargo proteins into cells. The goal of this brief review is to outline the basics of protein transduction and to discuss potential applications for tissue regeneration

A Systematic Analysis of Eluted Fraction of Plasma Post Immunoaffinity Depletion: Implications in Biomarker Discovery

Plasma is the most easily accessible source for biomarker discovery in clinical proteomics. However, identifying potential biomarkers from plasma is a challenge given the large dynamic range of proteins. The potential biomarkers in plasma are generally present at very low abundance levels and hence identification of these low abundance proteins necessitates the depletion of highly abundant proteins. Sample pre-fractionation using immuno-depletion of high abundance proteins using multi-affinity removal system (MARS) has been a popular method to deplete multiple high abundance proteins. However, depletion of these abundant proteins can result in concomitant removal of low abundant proteins. Although there are some reports suggesting the removal of non-targeted proteins, the predominant view is that number of such proteins is small. In this study, we identified proteins that are removed along with the targeted high abundant proteins. Three plasma samples were depleted using each of the three MARS (Hu-6, Hu-14 and Proteoprep 20) cartridges. The affinity bound fractions were subjected to gelC-MS using an LTQ-Orbitrap instrument. Using four database search algorithms including MassWiz (developed in house), we selected the peptides identified at <1% FDR. Peptides identified by at least two algorithms were selected for protein identification. After this rigorous bioinformatics analysis, we identified 101 proteins with high confidence. Thus, we believe that for biomarker discovery and proper quantitation of proteins, it might be better to study both bound and depleted fractions from any MARS depleted plasma sample

Cerebral cortex expression of Gli3 is required for normal development of the lateral olfactory tract

<div><p>Formation of the lateral olfactory tract (LOT) and innervation of the piriform cortex represent fundamental steps to allow the transmission of olfactory information to the cerebral cortex. Several transcription factors, including the zinc finger transcription factor Gli3, influence LOT formation by controlling the development of mitral cells from which LOT axons emanate and/or by specifying the environment through which these axons navigate. <i>Gli3</i> null and hypomorphic mutants display severe defects throughout the territory covered by the developing lateral olfactory tract, making it difficult to identify specific roles for <i>Gli3</i> in its development. Here, we used <i>Emx1Cre</i>;<i>Gli3</i>^<i>fl/fl</i> conditional mutants to investigate LOT formation and colonization of the olfactory cortex in embryos in which loss of <i>Gli3</i> function is restricted to the dorsal telencephalon. These mutants form an olfactory bulb like structure which does not protrude from the telencephalic surface. Nevertheless, mitral cells are formed and their axons enter the piriform cortex though the LOT is shifted medially. Mitral axons also innervate a larger target area consistent with an enlargement of the piriform cortex and form aberrant projections into the deeper layers of the piriform cortex. No obvious differences were found in the expression patterns of key guidance cues. However, we found that an expansion of the piriform cortex temporally coincides with the arrival of LOT axons, suggesting that <i>Gli3</i> affects LOT positioning and target area innervation through controlling the development of the piriform cortex.</p></div

Besondere Bluthochdruckfälle: Leitlinienempfehlungen der European Society of Cardiology und European Society of Hypertension [Special cases of high blood pressure: Guideline recommendations of the European Society of Cardiology and European Society of Hypertension]

In 2013 the new European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines for the treatment of arterial hypertension were published. The focus in these new guidelines is the treatment of hypertensive patients under special conditions. Particular attention is paid, for instance to the treatment of white coat hypertension and masked hypertension. Older patients, the so-called octogenarians benefit from antihypertensive treatment but with a higher target blood pressure. Women in childbearing years should avoid blockers of the renin-angiotensin system due to the potential teratogenic effects of these substances. An antihypertensive therapy with methyldopa, labetalol or nifedipin should be initiated in pregnant women when the blood pressure is over 160/110 mmHg. A decrease of blood pressure to less than 130/80 mmHg does not bring benefits for patients with diabetes mellitus or renal failure. In cases of concomitant proteinuria, systolic target values of 130 mmHg can be considered. An antihypertensive treatment is not recommended in acute stroke but must be weighed against the clinical situation. Blood pressure in patients with coronary heart disease should not be below 120/70 mmHg due to an increase in cardiovascular morbidity and mortality. Therapeutic alternatives in patients with resistant hypertension are mineralocorticoid receptor blockers, the alpha blocker doxazosin or an intensified diuretic therapy, for example as a sequential blockade of nephrons

Hypertonie und Schwangerschaft [Hypertension and pregnancy]

Hypertensive disorders complicate pregnancy in more than 10 % worldwide. Generally several forms were differentiated from one another. Especially pre-eclampsia, namely hypertension and proteinuria after the 20th week of gestation, is the most common cause of maternal and fetal mortality and morbidity. Their aetiology is unknown. Because elective delivery remains the only effective management approach, the main complication is neonatal death due to prematurity. Now we do not have sufficient evidence to know when to begin antihypertensive treatment, how vigorously to treat, or whether to stop treatment in mild chronic hypertension and hope that the hypotensive effect of normal pregnancy will be enough to control blood pressure. In several studies treatment of hypertension in pregnancy resulted in an increased risk of growth restriction in their infants. These results and the unknown long-term effects on the infant of any treatment led to current recommendations to treat only blood pressure elevations with a potential acute risk for the mother. Only less antihypertensive drugs are available which can be used in pregnancy. The only trial for treatment of hypertension during pregnancy with adequate infant follow-up was performed over 30 years ago with alpha-methyldopa, the antihypertensive drug of choice in pregnancy as yet. Epidemiological data indicate that women with preeclampsia are more likely to develop cardiovascular disease (e. g. myocardial infarction, stroke) later in life, compared with normotensive pregnancy. Many risk factors are shared by cardiovascular diseases and preeclampsia, including endothelial dysfunction, obesity, hypertension, hyperglycemia, insulin resistance, and dyslipidemia. Therefore, it has been proposed that the metabolic syndrome may be a possible underlying mechanism. A lifelong follow-up and counselling of women with a history of preeclampsia may be an opportunity for prevention of future disease

Aldosteronantagonisten: Welchen Stellenwert haben sie in der antihypertensien Therapie? [Mineralocorticoid receptor antagonists: inhibition of the renin angiotensin system]

Aldosteronantagonisten sind heute in der Hochdrucktherapie etabliert. Unabhaengig von ihrer blutdrucksenkenden Wirkung ueben sie einen positiven Einfluss auf das kardiovaskulaere System aus und erweisen sich zudem als nephroprotektiv. In der Kombination werden sie deshalb u.a. fuer Patienten mit refraktaerer Hypertonie, bei Herzinsuffizienzund bei Diabetikern zur zum Schutz der Niere eingesetzt