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In the fields of clinical diagnostics and point-of-care diagnosis as well as food and environmental monitoring there is a high demand for reliable high-throughput, rapid and highly sensitive assays for a simultaneous detection of several analytes in complex and low-volume samples. Sensor platforms based on solution-processable electrolyte-gated carbon nanotube field-effect transistors (CNT-FETs) are a simple and cost-effective alternative for conventional assays. In this work we demonstrate a selective as well as direct detection of the products of an enzyme-substrate interaction, here the for metabolic processes important urea-urease system, with sensors based on spray-coated CNT-FETs. The selective and direct detection is achieved by immobilizing the enzyme urease via certain surface functionalization techniques on the sensor surface and further modifying the active interfaces with polymeric ion-selective membranes as well as pH-sensitive layers. Thereby, we can avoid the generally applied approach for a field-effect based detection of enzyme reactions via detecting changes in the pH value due to an on-going enzymatic reaction and directly detect selectively the products of the enzymatic conversion. Thus, we can realize a buffering-capacity independent monitoring of changes in the substrate concentration.

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In this work the ion-selective response of an electrolyte-gated carbon-nanotube field-effect transistor (CNT-FET) towards K(+), Ca(2+) and Cl(-) in the biologically relevant concentration range from 10(-1) M to 10(-6) M is demonstrated. The ion-selective response is achieved by modifying the gate-electrode of an electrolyte-gated CNT-FET with ion-selective membranes, which are selective towards the respective target analyte ions. The selectivity, assured by the ion-selective poly(vinyl chloride) based membrane, allows the successful application of the herein proposed K(+)-selective CNT-FET to detect changes in the K(+) activity in the µM range even in solutions containing different ionic backgrounds. The sensing mechanism relies on a superposition of both an ion-sensitive response of the CNT-network as well as a change of the effective gate potential present at the semiconducting channel due to a selective and ion activity-dependent response of the membrane towards different types of ions. Moreover, the combination of a CNT-FET as a transducing element gated with an ion-selective coated-wire electrode offers the possibility to miniaturize the already well-established conventional ion-selective electrode setup. This approach represents a valuable strategy for the realization of portable, multi-purpose and low-cost biosensing devices.

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BACKGROUND: Nowadays, there is a tremendous need for cheap disposable sensing devices for medical applications. Materials such as Carbon Nanotubes (CNTs) and regioregular P3HT are proven to offer a huge potential as cost-effective and solution processable semiconductors for (bio)sensing applications. METHODS: CNT-based field-effect transistors (CNT-FETs) as well as regioregular P3HT-based ones (P3HT-FETs) are fabricated and operated in the so-called electrolyte-gated configuration. The active layer of the P3HT-FETs consists of a spin-coated regioregular P3HT layer, which serves on one hand as the active sensing element and on the other hand as passivation layer for the transistor's metal contacts. The active layer of the nanotube transistors consists of a randomly distributed single walled CNT-network (>90% semiconducting tubes) deposited from a CNT-ink solution by spin-coating. RESULTS: We compare both devices concerning their stability in aqueous environment and their response when exposed to buffers with different pH. We found that even if P3HT shows lower stability its pH sensitivity is reproducible even after long-term measurements. CONCLUSION: CNT-FETs and P3HT-FETs offer different advantages and drawbacks concerning their stability in solution and the ease of fabrication. A discussion of their different sensing mechanisms as well as sensitivity is given here. GENERAL SIGNIFICANCE: This work reports on fast and cost-effective production of solution processable thin-film transistors based on carbon nanotubes and regioregular P3HT and demonstrates their suitability as reliable pH sensors. This article is part of a Special Issue entitled Organic Bioelectronics - Novel Applications in Biomedicine.

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Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

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We report on back-gated carbon nanotube (CNT) thin-film transistors (CNTFETs) and their performance in electrolytic solutions to assess their suitability for future application as biosensors. Spray-deposited CNT networks were used as the sensitive active layer which offers the opportunity for integration on flexible sensing platforms at low-cost. We characterized the transistors' behavior in electrolytes by analyzing the response to different KCl solutions and buffers over a wide pH range. We observed a linear response of the drain current upon changing the pH in low molarity buffers and obtained an exponential dependence on the salt concentration of the electrolyte. These responses can be attributed to electrostatic gating effects that go along with shifts in the threshold voltage. Even though a lot of effort has been put into understanding the biosensing mechanism a detailed theory is still missing. Back-gated CNTFETs operated in electrolytic solutions can be a further tool to investigate and clarify the existing unsolved phenomena.

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BACKGROUND: Thrombangiitis obliterans or Buerger's disease is a segmental inflammatory disease affecting small and medium-sized veins and arteries, which most often affects young smokers leading to thrombophlebitis and acral ischaemic syndromes, inducing high amputation rates. Based on positive results of a former pilot study we report on our results of immunoadsorption (IA) in clinical routine care, where IA was offered as a treatment option. PATIENTS AND METHODS: The uncontrolled course of 12 consecutive TAO-patients treated by IA on a series of 5 consecutive days was observed. Follow-up period was 14.1 (ranging from 1-26) months. RESULTS: Eight patients were treated with one, four patients completed 2 IA-series. In 9 patients an early onset and lasting clinical improvement and an improvement of ischaemia was noted. The intake of pain-relievers (especially opioids) sank drastically. Eight patients returned to work. Retrospectively, in two out of three treatment failures the correct diagnosis of TAO was questionable. CONCLUSION: IA seems to be a promising treatment option for patients suffering from TAO which should be further evaluated in controlled clinical trials.

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In human oncology, novel targeted therapy focusing on monoclonal antibodies and tyrosine kinase inhibitors has become an attractive anticancer strategy. The introduction of antiangiogenetic drugs and metronomic chemotherapy has also increased the therapeutic arsenal. Chemotherapy still plays a key role in the treatment of many tumors affecting dogs and cats. However, novel anticancer strategies (including tyrosine kinase inhibitors and monoclonal antibodies, as well as antiangiogenetic treatments) are becoming relevant in veterinary medicine, too. The goal of this review is to describe new therapeutic strategies for cancer treatment in veterinary medicine, including less well-known chemotherapeutic drugs.

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OBJECTIVES: Labour and delivery represent a considerable effort for pregnant women. Lack of aerobic fitness may limit pushing efforts during childbirth and represents increased cardiovascular strain and risk. Increasing prevalence of sedentary behaviour and lack of aerobic fitness may reduce heart rate reserve during labour. STUDY DESIGN: We quantified maternal heart rate reserve (maximum heart rate minus resting heart rate) of 30 healthy pregnant women during labour and delivery and related it to habitual daily physical activity levels quantified during the third pregnancy trimester by the Pregnancy Physical Activity Questionnaire. RESULTS: Heart rates during labour reached values similar to those observed during moderate to heavy physical exercise. During active pushing one out of five women reached heart rates more than 90% of their heart rate reserve (188 ± 7 beats per min). Half of the women reached more than 70% of heart rate reserve (172 ± 14 beats per min). Physically inactive women used more of their heart rate reserve as physically more active women (87 ± 20% vs. 65 ± 12%, upper and lower tertile respectively, p<0.05). CONCLUSIONS: Use of heart rate reserve for the effort of labour is increased in physically inactive women and may potentially limit the intensity and duration of pushing efforts. Such higher cardiovascular strain in physically less active women may represent increased cardiovascular risk during labour.

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Obesity has progressively become a global epidemic that constitutes one of the biggest current health problems worldwide. Pregnancy is a risk factor for excessive weight gain. Factors that may predict development of obesity in later life mainly include gestational weight gain, pre-pregnancy nutritional status, age, parity and race. Change in lifestyle factors, such as eating habits, enrollment in physical activity, smoking and duration of lactation, in addition to the above factors, may also contribute to the development of obesity but are still not fully understood. Women who retain more body weight after pregnancy have, in general, larger pregnancy body weight gain, higher pre-pregnancy body mass index, marked weight changes in previous pregnancies, lactate slightly less and stop smoking during pregnancy to a larger extent. In addition, irregular eating habits and decreased leisure time activity after delivery influence postpartum weight retention. Taking into consideration the epidemic of obesity, with all its adverse long-term consequences, there is an increasing need to promote counseling before, during and after pregnancy on the role of diet and physical activity in reproductive health.

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BACKGROUND/OBJECTIVES: To measure resting metabolic rate (RMR), activity energy expenditure (AEE), total energy expenditure (TEE) and physical activity pattern, that is, duration and intensity (in metabolic equivalents, METs) of activities performed in late pregnancy compared with postpartum in healthy, well-nourished women living in Switzerland. SUBJECTS/METHODS: Weight, height, RMR, AEE, TEE and physical activity patterns were measured longitudinally in 27 healthy women aged 23-40 years at 38.2+/-1.5 weeks of gestation and 40.0+/-7.2 weeks postpartum. RESULTS: The RMR during late pregnancy was 7480 kJ per day, that is, 1320+/-760 kJ per day (21.4%) higher than the postpartum RMR (P<0.001). Absolute changes in RMR were positively correlated with the corresponding changes in body weight (r=0.61, P<0.001). RMR per kg body weight was similar in late pregnancy vs postpartum (P=0.28). AEE per kg during pregnancy and postpartum was 40+/-13 and 50+/-20 kJ/kg, respectively (P=0.001). There were significant differences in daily time spent at METs<1.5 (1067 vs 998 min, P=0.045), at 2.5< or =METs <3.0 (58 vs 82 min, P=0.002) and METs> or =6 (1 vs 6 min, P=0.014) during pregnancy and postpartum, respectively. CONCLUSIONS: Energy expenditure in healthy women living in Switzerland increases in pregnancy compared with the postpartum state. Additional energy expenditure is primarily attributed to an increase in RMR, which is partly compensated by a decrease in AEE. The decrease in physical activity-related energy costs is achieved by selecting less demanding activities and should be taken into account when defining extra energy requirements for late pregnancy in Switzerland.

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A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzyme-linked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.

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Bone cells form a wired network within the extracellular bone matrix. To analyse this complex 3D structure, we employed a confocal fluorescence imaging procedure to visualize live bone cells within their native surrounding. By means of newly developed image processing software, the "Image-Equalizer", we aimed to enhanced the contrast and eliminize artefacts in such a way that cell bodies as well as fine interconnecting processes were visible.

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We investigated the role of alterations of HDM2, the human homologue of murine mdm2, in the tumorigenesis and progression of cutaneous melanoma. A well-characterized cohort of 172 cases representing different points in the spectrum of melanocyte transformation (16 dysplastic nevi, 11 melanomas in situ, 107 invasive primaries, and 38 metastatic lesions), as well as 11 human melanoma cell lines were examined by immunohistochemistry and Western blotting for HDM2 protein expression, and by either Southern blotting (SB) or fluorescence in situ hybridization for HDM2 gene amplification. HDM2 overexpression, defined as >20% tumor cells showing nuclear immunoreactivity, was observed in 1 of 16 (6%) dysplastic nevi, 3 of 11 (27%) melanomas in situ, and 81 of 145 (56%) invasive primary and metastatic melanomas. Comparable frequencies of HDM2 overexpression were observed among invasive primary cases with differing tumor thicknesses as well as among the metastatic cases: 21 of 40 (53%) at < or =1.5 mm; 31 of 50 (62%) at 1.6-3.9 mm; 10 of 17 (58%) at >4 mm; and 19 of 38 (50%) metastases. HDM2 amplification was observed in 1 of 88 (1%) primary cases using fluorescence in situ hybridization, and in 0 of 12 (0%) metastatic cases that overexpressed HDM2 using SB. Melanoma cell lines expressed HDM2 protein, but there was no evidence of amplification by SB. Our data suggest that HDM2 protein overexpression is common in invasive and metastatic melanoma. Observing HDM2 overexpression in noninvasive melanoma suggests that expression of this oncogene may play an early role in melanocyte transformation. HDM2 amplification occurs infrequently, and other mechanisms that up-regulate HDM2 expression are under investigation.

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Borna disease (BD) is a rare immunopathological disorder of the central nervous system (CNS) caused by infection with Borna disease virus (BDV) and histologically characterized by mononuclear encephalomyelitis. BD primarily affects equines and sheep in well defined endemic areas of central Europe, but BDV infections have also been reported in other host species including humans, as well as in non endemic regions. In this paper recent data on the pathogenesis of BD are reviewed and the current situation in Switzerland and the Principality of Liechtenstein is summarized.

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