Aptamer-based Field-Effect Biosensor for Tenofovir Detection.

During medical treatment it is critical to maintain the circulatory concentration of drugs within their therapeutic range. A novel biosensor is presented in this work to address the lack of a reliable point-of-care drug monitoring system in the market. The biosensor incorporates high selectivity and sensitivity by integrating aptamers as the recognition element and field-effect transistors as the signal transducer. The drug tenofovir was used as a model small molecule. The biointerface of the sensor is a binary self-assembled monolayer of specific thiolated aptamer and 6-mercapto-1-hexanol (MCH), whose ratio was optimized by electrochemical impedance spectroscopy measurements to enhance the sensitivity towards the specific target. Surface plasmon resonance, performed under different buffer conditions, shows optimum specific and little non-specific binding in phosphate buffered saline. The dose-response behavior of the field-effect biosensor presents a linear range between 1 nM and 100 nM of tenofovir and a limit of detection of 1.2 nM. Two non-specific drugs and one non-specific aptamer, tested as stringent control candidates, caused negligible responses. The applications were successfully extended to the detection of the drug in human serum. As demonstrated by impedance measurements, the aptamer-based sensors can be used for real-time drug monitoring.

Nano-fabricated memristive biosensors for biomedical applications with liquid and dried samples.

Nanowire based platforms are widely reported for sensing applications and for their potential in the bio-detection field. In the present work, memristive nanowire devices are implemented for label-free sensing in liquid samples as well as in dried samples via leveraging the modification of the hysteresis in the devices electrical response as a consequence of the surface modification. First, pH sensing in liquid conditions is demonstrated. In addition, the memristive devices are bio-functionalized using antibodies for Prostate Specific Antigen (PSA) as case of study. In this way, the nanowires are converted to memristive biosensors paving the way for future molecular diagnostics applications in general, and for detection of prostate cancer disease in particular.

Study on the bio-functionalization of memristive nanowires for optimum memristive biosensors.

Semiconductor nanowires are emerging as promising building blocks for biosensors enabling direct electrical detection of various biomolecules. In this framework, two-terminal Schottky-barrier silicon (Si) nanowire arrays that exhibit memristive electrical response, so-called memristive devices, are bio-functionalized and converted to memristive biosensors for bio-detection purposes. A comparative analysis of three bio-functionalization strategies is proposed here in order to design and develop optimum memristive biosensors to be implemented in label-free sensing applications. The surface of the device is modified with an anti-free-Prostate Specific Antigen (PSA) antibody as the case of study via: (a) direct adsorption on the device surface, (b) a bio-affinity approach using biotin-streptavidin combination and (c) covalent attachment using (3-glycidyloxypropyl)trimethoxysilane (GPTES). The optimum memristive biosensor is defined via the calibration and comparative study of the biosensors' electrical response under controlled environmental conditions (humidity and temperature) in order to maximize the performance of the biosensor. In addition, it is demonstrated that the direct passive adsorption strategy presents double the performance of the other two methods. The uptake of biological molecules on the nanostructure surface is verified by atomic force microscopy and confocal microscopy. Scanning electron microscopy reveals the details of the surface morphology of the nanofabricated structures before and after bio-functionalization for the three methods applied. The system shows potential for general application in molecular diagnostics, and, in particular, for the early detection of prostate cancer.

Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor.

This paper reports the characterization of an electrochemical biosensor for the continuous monitoring of Naproxen based on cytochrome P450. The electrochemical biosensor is based on the drop-casting of multi-walled carbon-nanotubes (MWCNTs) and microsomal cytochrome P4501A2 (msCYP1A2) on a graphite screen-printed electrode (SPE). The proposed biosensor was employed to monitor Naproxen (NAP), a well-known anti-inflammatory compound, through cyclic voltammetry. The dynamic linear range for the amperometric detection of NAP had an upper limit of 300 µM with a corresponding limit of detection (LOD) of 16 ± 1 µM (S/N=3), which is included in NAP physiological range (9-300 µM). The MWCNT/msCYP1A2-SPE sensor was also calibrated for NAP detection in mouse serum that was previously extracted from mice, showing a slightly higher LOD (33 ± 18 µM). The stability of the msCYP1A2-based biosensor was assessed by longtime continuous cyclic voltammetric measurements. The ability of the sensor to monitor drug delivery was investigated by using a commercial micro-osmotic pump. Results show that the MWCNT/msCYP1A2-SPE sensor is capable of precisely monitoring the real-time delivery of NAP for 16 h. This work proves that the proposed electrochemical sensor might represent an innovative point-of-care solution for the personalization of drug therapies, as well as for pharmacokinetic studies in both animals and humans.

Mental stress as a provocative test in patients with various clinical syndromes of coronary heart disease.

To assess the prevalence of mental stress-induced myocardial ischemia and investigate the pathogenetic mechanisms by which emotional stress may induce myocardial ischemia, we studied 372 patients with angina pectoris who underwent mental arithmetic and exercise stress testings. Hyperventilation tests were also performed in 176 patients, and 340 patients underwent coronary arteriography. Sixty-one patients showed significant ST segment abnormalities during mental arithmetic and exercise stress testings (group 1). Two hundred eleven patients had negative responses to mental stress but positive exercise tests (group 2), whereas both tests were negative in 100 patients (group 3). Mental stress induced significant increases in heart rate and systolic blood pressure in the three groups of patients; however, group 1 patients had higher increases in rate-pressure product (mm Hg x beats/min) than group 2 and group 3 patients (14,909 +/- 3,894 versus 12,985 +/- 2,900 versus 12,724 +/- 4,400 mm Hg x beats/min, p less than 0.01). Group 1 patients had shorter exercise durations than group 2 or group 3 (4.06 +/- 1.55 versus 7.65 +/- 3.07 versus 13.9 +/- 5.31 minutes, p less than 0.01), although rate-pressure products at peak exercise were similar in groups 1 and 2 (20,277 +/- 6,058 versus 20,768 +/- 3,864, p = NS) and significantly higher in group 3 (26,221 +/- 7,100/mm Hg x beats/min, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Use of urokinase in the occlusion of the vascular access routes in chronic hemodialysis. 7 years' experience]. / Uso dell'urochinasi nell'occlusione di accessi vascolari per emodialisi cronica. Sette anni di esperienza.

Pharmacological treatment with urokinase in obstructions of vascular accesses due to chronic dialysis is a tried and tested technique. Retrospective investigation of a group of 111 cases treated with urokinase makes it possible to calculate the actuarial survival curve of vascular access in the period subsequent to fibrinolytic treatment. Mathematical analysis provides a precise indication to the use of the drug in thromboses of a-v fistulas and anatomically unimpaired vascular prothesies. In the presence of stenosis of a-v anastomosis, pharmacological thrombolysis permits restoration of a blood flow suitable to the conduction of haemodialytic treatment for a period useful to surgical correction. Infusion of urokinase is useless in cases of vascular prosthesis thrombosis complicated by the presence of stenosis of the lumen.

[Management of electron accelerators for radiotherapy. Data as of 31 December 1984]. / La gestione di acceleratori di elettroni per radioterapia. Dati aggiornati al 31 dicembre 1984.

Several italian radiotherapeutic centers have supplied the data analysed, regarding problems connected with the management of electron accelerators in the years 1982-1983-1984. The data concern 27 out of the 35 accelerators settled in Italy. The average cost of purchase has proved to be of 940 M pounds with an expense of annual allowance of 94 M pounds. We have then analysed the incidences of the allowance of the purchase expenditure of the machine (23%), the allowance of the expenses for the construction of the bunker (22%), the expenses of maintenance of the machine (5%), the cost of the staff (48%) and the cost of the power supply (2%) on the management costs (about pounds 820.000 per each handled patient). The duration of the various phases of the machinery installment, from the purchase to the beginning of the treatment, the charge of work supported in the three considered years, the daily use of the machinery and the problems deriving from days of time out of services due to failures or to periodical maintenance have then been studied. The analysis of the average values of the parameters studied and of the range of their variability allows us to find out the sector in which it is possible, also at present, to intervene in order to ameliorate the employment of a linear accelerator, regarding the costs and the performance.

Surgical treatment of cerebrospinal fluid otorrhea. Translabyrinthine approach in posterior petrous bone fractures.

The authors intend to define the treatment of cerebrospinal fluid otorrhea according to the type of fracture involving the petrous bone. Fractures of the petrous bone causing cerebrospinal fluid otorrhea can be classified in two types: (1) fractures extending anteriorly toward the anterior foramen lacerus; (2) fractures extending posteriorly through the labyrinth to the internal auditory meatus. The former usually resolve spontaneously; the latter, because of different anatomy and embryogenesis, require a surgical procedure using a translabyrinthine approach.