Intraoperative blood salvage in cancer surgery: safe and effective?

To support blood supply in the growing field of cancer surgery and to avoid transfusion induced immunomodulation caused by the allogeneic barrier and by blood storage leasions we use intraoperative blood salvage with blood irradiation. This method is safe as it provides efficient elimination of contaminating cancer cells, and as it does not compromise the quality of RBC. According to our experience with more than 700 procedures the combination of blood salvage with blood irradiation also is very effective in saving blood resources. With this autologous, fresh, washed RBC a blood product of excellent quality is available for optimal hemotherapy in cancer patients.     

Primary porcine proximal tubular cells as a model for transepithelial drug transport in human kidney.

BACKGROUND: Kidney proximal tubular cells play a major role in the transport of endogenous and exogenous compounds. A multitude of different transporters are expressed starting with multidrug ABC transporters (e.g. abcb1, abcc1-6), slc22a6-8 (organic anion transporters) and slc22a1-3 (organic cation transporters). For transport studies of renal drug transport, cell lines like MDCK and LLC-PK1 are often used to overexpress and study one or two transporters, such as abcb1 or abcc1-6. However, the use is limited since under physiological conditions xenobiotics are transported through different transporters at the same time. Therefore, a primary in vitro model expressing functionally different transporters simultaneously, as it is the case in vivo, would be of great benefit. METHODS: Primary proximal tubular cells were isolated from porcine kidney. Cells were cultured under selective culturing conditions leading to specific growth of primary proximal tubular cells. Expression of important proximal transporters was checked at mRNA level with RT-PCR, at protein level with immunocytochemistry and functionally by transport and uptake assays. RESULTS: A model of primary proximal tubular cells was established expressing the most important transporters: abcb1, abcc1, abcc2, slc22a8, slco1a2, slc15a1, slc5a2 and slc4a4. In freshly isolated cells, slc22a1 and slc22a6 were expressed, but were down-regulated in culture. Abcb1, abcc1, abcc2 and slc4a4 were detected at protein level with immunostaining. Functional activity was confirmed for abcb1, abcc1/2, slc22a8, slc15a1/2 and slc5a1/2. The tightness of the monolayers of this model was better than in previously established in vitro models. CONCLUSION: This primary cell culture model might be an interesting tool to investigate proximal tubular transport and to predict toxicity and drug interactions since it expresses functionally several transporters simultaneously.     

Effects of topography and composition of titanium surface oxides on osteoblast responses

To investigate the roles of composition and characteristics of titanium surface oxides in cellular behaviour of osteoblasts, the surface oxides of titanium were modified in composition and topography by anodic oxidation in two kinds of electrolytes, (a) 0.2 M H(3)PO(4), and (b) 0.03 M calcium glycerophosphate (Ca-GP) and 0.15 M calcium acetate (CA), respectively. Phosphorus (P: ca.10at%) or both calcium (Ca: 1-6at%) and phosphorus (P: 3-6at%) were incorporated into the anodized surfaces in the form of phosphate and calcium phosphate. Surface roughness was slightly decreased or enhanced (R(a) in the range of 0.1-0.5 microm) on the anodized surfaces. The geometry of the micro-pores in the anodized surfaces varied with diameters up to 0.5 microm in 0.2 M H(3)PO(4) and to 2 microm in 0.03 M Ca-GP and 0.15 M CA, depending on voltages and electrolyte. Contact angles of all the anodic oxides were in the range of 60-90 degrees. Cell culture experiments demonstrated absence of cytotoxicity and an increase of osteoblast adhesion and proliferation by the anodic oxides. Cells on the surfaces with micro-pores showed an irregular and polygonal growth and more lamellipodia, while osteoblasts on the titanium surface used as a control or on anodic oxides formed at low voltages showed many thick stress fibres and intense focal contacts. Alkaline phosphatase (ALP) activity of the cells did not show any correlation with surface characteristics of anodic oxides.     

Mild phenotype in two unrelated patients with a partial deletion of 21q22.2-q22.3 defined by FISH and molecular studies

We describe two unrelated patients with cytogenetically visible deletions of 21q22.2-q22.3 and mild phenotypes. Both patients presented minor dysmorphic features including thin marfanoid build, facial asymmetry, downward-slanting palpebral fissures, depressed nasal bridge, small nose with bulbous tip, and mild mental retardation (MR). FISH and molecular studies indicated common deleted areas but different breakpoints. In patient 1, the breakpoint was fine mapped to a 5.2 kb interval between exon 5 and exon 8 of the ETS2 gene. The subtelomeric FISH probe was absent on one homologue 21 indicating a terminal deletion spanning approximately 7.9 Mb in size. In patient 2, the proximal breakpoint was determined to be 300-700 kb distal to ETS2, and the distal breakpoint 2.5-0.3 Mb from the 21q telomere, indicating an interstitial deletion sized approximately 4.7-7.3 Mb. The 21q- syndrome is rare and typically associated with a severe phenotype, but different outcomes depending on the size and location of the deleted area have been reported. Our data show that monosomy 21q of the area distal to the ETS2 gene, representing the terminal 7.9 Mb of 21q, may result in mild phenotypes comprising facial anomalies, thin marfanoid build, and mild MR, with or without signs of holoprosencephaly.     

Miltefosine (Impavido): the first oral treatment against leishmaniasis

Miltefosine is a novel antileishmanial drug that has significant selectivity in both in vitro and in vivo models. Clinical efficacy was demonstrated for the treatment of visceral leishmaniasis with the advantage of oral administration over the currently recommended antileishmanial drugs that require parenteral administration. Miltefosine produces high cure rates also in patients resistant to the standard antimonial therapy.     

Infrared spectroscopy: A new diagnostic tool in Alzheimer disease

Biological markers play an evolving role in the diagnosis of Alzheimer disease (AD). We compare conventional measurements of cerebrospinal fluid (CSF) tau and β-amyloid_1–42 proteins to a novel approach – Fourier transformed infrared (FT-IR) spectroscopy – a simple technique derived from chemical and physical sciences that characterizes intramolecular bonds. For automatic diagnostic analysis, we developed an artificial neural network (ANN). We examined 71 patients with a clinical diagnosis of AD and 66 controls. β-Amyloid_1–42 was decreased (sensitivity 80% and specificity 78%); tau was elevated (sensitivity 76% and specificity 88%) in CSF of AD patients. The combined tau/β-amyloid_1–42 quotient was able to distinguish healthy from diseased subjects with 99% sensitivity and 86% specificity. The ANN could separate FT-IR spectroscopy data with 88.5% sensitivity and 80% specificity. FT-IR spectroscopy proved to be cost-effective and simple to perform. Diagnostic sensitivity and specificity is in the range of CSF tau and β-amyloid_1–42 protein analysis. Larger sample numbers for ANN training and validation could increase diagnostic accuracy and thus prove to be a useful screening tool.     

Spatio-Temporal Monitoring of Benthic Anatoxin-a-Producing Tychonema sp. in the River Lech,Germany

Incidents with toxic benthic cyanobacteria blooms have been increasing recently. In 2019, several dogs were poisoned in the river Lech (Germany) by the benthic anatoxin-a-producing genus Tychonema. To characterize spatial and temporal distribution of potentially toxic Tychonema in this river, a systematic monitoring was carried out in 2020, focusing on the occurrence of the genus, its toxin production and habitat requirements. Tychonema and cyanobacterial community composition in benthic mats and pelagic samples were identified using a combined approach of microscopy and DNA sequencing of the 16S rRNA gene. In addition, anatoxin-a concentrations of selected samples were measured using the ELISA method. The habitat was characterized to assess the ecological requirements and growth conditions of Tychonema. Tychonema mats and anatoxin-a were detected at several sampling sites throughout the entire study period. Toxin concentrations increased with the progression of the vegetation period and with flow direction, reaching values between 0 and 220.5 µg/L. Community composition differed among pelagic and benthic samples, with life zone and substrate condition being the most important factors. The results of this study highlight the importance of monitoring and understanding the factors determining occurrence and toxin production of both pelagic and benthic cyanobacteria due to their relevance for the health of humans and aquatic ecosystems.