[Stem cell-based cardiac regeneration after myocardial infarction]. / Stammzellbasierte kardiale Regeneration nach Infarkt.

Myocardial infarction leads to an irreversible loss of vital myocardial cells. The transplantation of new cardiomyocytes into the heart was first described over 20 years ago and represents a straightforward approach to remuscularize a damaged heart. Due to the lack of human cells a clinical application seemed ambitious; however, dramatic progress in stem cell biology over the last two decades has paved the way towards a clinical application. This is especially important as the prognosis for patients with terminal heart failure is still poor. The transplantation of either cardiomyocytes or engineered heart tissue derived from pluripotent stem cells (either embryonic stem cells or induced pluripotent stem cells) might represent a new regenerative approach. Transplantation of either cells or tissue constructs has now been evaluated in several preclinical models, which have demonstrated that an injured heart can be (partially) remuscularized; however, major hurdles towards a clinical application are the transplantation-related occurrence of arrhythmia, the potential tumorigenicity of pluripotent cells and the required immunosuppression. Several groups are working hard to solve these problems and we are optimistic that the first clinical studies will take place within the next few years.

Temporal and spatial heterogeneity in milk and immune-related gene expression during mammary gland involution in dairy cows.

The aim of this study was to investigate heterogeneity in tissue morphology, milk protein and immune-related gene expression, and apoptosis of epithelial cells in the lactating and involuting mammary glands of the dairy cow. Mammary tissue from different regions of the gland (alveolar, cisternal, and peripheral) was collected postmortem from nonpregnant, pasture-fed, Holstein-Friesian primiparous cows in mid-lactation that were killed at different time points postmilking: 0, 6, 12, 18, 24, 36, and 72 h (n = 6 per time point). The CSN1NS1 and LALBA mRNA was decreased in alveolar, cisternal, and peripheral tissue by 12 to 36 h postmilking. In contrast, lactoferrin (LF) and mammary serum amyloid A3 (M-SAA3) mRNA was increased in these regions by 36 to 72 h. During lactation, more variability was present in gene expression in alveolar tissue between cows and between quarters within a cow, than within quarters. Histological analysis indicated the alveolar tissue from lactating cows was mostly uniform in structure; however, in situ hybridization indicated that although most of the alveolar tissue expressed milk proteins, the level of expression varied within and between alveoli. This heterogeneity became more pronounced with involution and with increasing regions of alveoli expressing lactoferrin, indicating that alveoli enter involution asynchronously. The peripheral and cisternal tissue had more variability in gene expression between cows compared with the alveolar tissue. The M-SAA3 signal was more intense in the cisternal tissue and less intense than the peripheral compartment compared with LF particularly in the earlier time points. In addition, between cows within the later time points, differences were observed in tissue morphology, the levels of milk protein and immune-related gene expression, and phosphorylated signal transducer and activator of transcription (STAT) 5-P and STAT3-P proteins, and degree of apoptosis, indicating that involution of the mammary gland occurs at different rates between cows. Understanding the mechanisms initiating the process of involution of the mammary gland provides an opportunity for enhancing milk production of the dairy cow.

Prophylactic intravenous nimodipine treatment in skull base surgery: pharmacokinetic aspects.

BACKGROUND: Nimodipine is primarily used in subarachnoid hemorrhage (SAH). Clinical trials revealed also a beneficial effect of prophylactic nimodipine treatment on cranial nerve functions following vestibular schwannoma surgery. OBJECTIVE: The unknown pharmacokinetics of prophylactically administered nimodipine were investigated. METHODS: Samples were taken from 27 patients with skull base lesions. Prophylactic intravenous nimodipine infusion was started 5.8-25.8 h (mean 17.9 h) before surgery. Nimodipine concentrations were determined in serum (intra- and postoperatively), cerebrospinal fluid (CSF) (intraoperatively), and tissue samples. RESULTS: Wide interindividual differences were observed. Mean concentrations for nimodipine were 46.9 ng/ml (SD: 6.4; min. 4.1 and max. 92.7 ng/ml) in intraoperative serum, 73.2 ng/ml (SD: 16.7; min. 6.6 and max. 253 ng/ml) in postoperative serum and 8.3 ng/ml (SD: 1.5; min. 1.0 und max. 29.7 ng/ml) in intraoperative CSF. The correlation between intra- and postoperative serum (p=0.004, r=0.560) and between intra-operative serum and CSF concentration (p=0.003, r=0.567) were statistically significant. Furthermore the correlation between intraoperative serum concentration and concentrations collected from vestibular nerves was high (r=0.711), but not statistically significant (p=0.178). CONCLUSIONS: Interindividually, continously administered intravenous nimodipine produces considerably variable serum levels. Controls of nimodipine serum concentrations may be useful to optimize nimodipine medication in skull base surgery and in the management of SAH. The serum nimodipine level is a useful marker for CSF and intracranial nerve tissue concentrations of nimodipine.

Determination of ochratoxin A in wine by liquid chromatography tandem mass spectrometry after combined anion-exchange/reversed-phase clean-up.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus and Penicillium verrucosum. It has been found and analysed in several foods and feeds. Owing to its toxicity and occurrence in food and feed, the European Community has issued directives and some countries have their own regulations for OTA contents in food, feed and beverages. This work describes a method for the determination of OTA in mulled and red wine. It is based on combined anion exchange/reversed-phase clean-up and was analysed by liquid chromatography coupled with tandem mass spectrometry (multiple reaction monitoring). The method was validated with natural contaminated and spiked wine samples with OTA contents from 1.34 to 3.48 microg kg(-1). Owing to its accuracy, good reproducibility and repeatability, this easy method is a good alternative to liquid chromatography-fluorescence detection methods.