Donn M. Dennis

Enzymatic glucose detection using ZnO nanorods on the gate region of AlGaN∕GaN high electron mobility transistors

ZnO nanorod-gated AlGaN∕GaN high electron mobility transistors (HEMTs) are demonstrated for the detection of glucose. A ZnO nanorod array was selectively grown on the gate area using low temperature hydrothermal decomposition to immobilize glucose oxidase (GOx). The one-dimensional ZnO nanorods provide a large effective surface area with high surface-to-volume ratio and provide a favorable environment for the immobilization of GOx. The AlGaN∕GaN HEMT drain-source current showed a rapid response of less than 5s when target glucose in a buffer with a pH value of 7.4 was added to the GOx immobilized on the ZnO nanorod surface. We could detect a wide range of concentrations from 0.5nMto125μM. The sensor exhibited a linear range from 0.5nMto14.5μM and an experiment limit of detection of 0.5nM. This demonstrates the possibility of using AlGaN∕GaN HEMTs for noninvasive exhaled breath condensate based glucose detection of diabetic application.

Fentanyl Abuse and Dependence: Further Evidence for Second Hand Exposure Hypothesis

Abstract We have proposed a novel hypothesis regarding the potential role of occupational or second-hand exposure in physician substance use, abuse, and addiction. While only 5.6% of licensed physicians in Florida are anesthesiologists, nearly 25% of physicians followed for substance abuse/dependence are anesthesiologists. When we sort by drug of choice, anesthesiologists have more opioid abuse and dependence than other physicians and appropriate controls. Abuse of one opioid, fentanyl, appears to be increasing and has been noted among the State of Floridas causes of opioid deaths. Fentanyl and sufentanyl are commonly administered highly potent opioid analgesics, as much as 80-800 times as potent as morphine. We have recent data from the State of Florida impaired physicians database, which has allowed us to categorize all fentanyl abusing and/ or dependent physicians. Just knowing that a physician abuses fentanyl gives you a good clue as to their specialty; 75% are anesthesiologists! While drug abuse researchers, oncologists and others who handle drugs of abuse everyday, have no greater incidence of opioid abuse or dependence, anesthesiologists are at the top of every list. Can this be due to just access and stress? We have proposed an alternative hypothesis of second hand exposure. To test this hypothesis, we developed a sensitive LC/MS/MS assay to measure the intravenous anesthetic and analgesic agents, propofol and fentanyl in air. Not only did we detect propofol and fentanyl in cardiovascular surgery operating room air, we also found the highest concentrations were close to the patients mouth where anesthesiologists work for hours. Like tobacco, second hand opioid exposure can sensitize and change the brain making abuse, dependence and behavioral disorders more likely. Thus environmental exposure and sensitization may be an important risk factor in physician addiction. Second hand exposure may affect treatment outcome and explain anesthesiologists inability to return to work in the operating room. We are developing an animal model for second hand exposure and additional studies of the operating room and cardiac anesthesiologists are underway.

Frequency-dependent effects of propofol on atrioventricular nodal conduction in guinea pig isolated heart : mechanisms and potential antidysrhythmic properties

Background The use of propofol has been associated with episodes of bradycardias. The mechanism(s) underlying these phenomena are not well defined. Therefore we investigated (1) the chronotropic and dromotropic effects of propofol, (2) the frequency-dependent effects of propofol on the atrioventricular (AV) node, and (3) the physiologic mechanism(s) underlying propofols effects on AV nodal conduction.

Enzyme-based lactic acid detection using AlGaN∕GaN high electron mobility transistors with ZnO nanorods grown on the gate region

The detection of lactic acid with ZnO nanorod-gated AlGaN∕GaN high electron mobility transistors (HEMTs) was demonstrated. The array of ZnO nanorods provided a large effective surface area with a high surface-to-volume ratio and a favorable environment for the immobilization of lactate oxidase. The HEMT drain-source current showed a rapid response when various concentrations of lactic acid solutions were introduced to the gate area of the HEMT sensor. The HEMT could detect lactic acid concentrations from 167nM to 139μM. Our results show that portable, fast response, and wireless-based lactic acid detectors can be realized with AlGaN∕GaN HEMT based sensors.

Demonstration of a Left Atrial Input to the Atrioventricular Node in Humans

Background—During right atrial stimulation, the anterior and posterior approaches provide inputs to the atrioventricular (AV) node. The purpose of the present study was to determine how activation proceeding from the left atrium reaches the AV node. Methods and Results—We studied AV nodal conduction during right and left atrial (coronary sinus) stimulation in 46 patients (27 women and 19 men; mean age, 46±4 years) who had structurally normal hearts. At an identical cycle length (600 ms), left atrial stimulation resulted in shorter A-H intervals than right atrial stimulation (73±3 ms versus 99±3 ms;P <0.05). In addition, atrial electrograms recorded close to the His bundle changed from near to far field potentials when stimulation was shifted to the left atrium. The A-H interval prolonged as the site of pacing was progressively moved from the distal to the proximal coronary sinus. During constant pacing from the distal coronary sinus, atrial activation close to the His bundle could be advanced by late extrastimuli delivered at the anterior and posterior approaches (up to 11±2 ms and 9±1 ms, respectively), without altering His bundle activation time. In contrast, late extrastimuli delivered at the inferoparaseptal mitral annulus advanced both the A and H electrograms in 19 of 20 patients, which is consistent with a left-sided input to the AV node. Right and left atrial stimulation resulted in similar AV nodal function. Conclusion—The mitral annulus provides a left atrial input to the human AV node.

Preparation and Anesthetic Properties of Propofol Microemulsions in Rats

Background:The lipophilicity of propofol has required dispersion in a soybean macroemulsion. The authors hypothesized that the anesthetic properties of propofol are preserved when reformulated as a transparent microemulsion rather than as a turbid macroemulsion and that the dose–response relation can be selectively modified by altering the microemulsion’s surfactant type and concentration. Methods:Microemulsions of propofol were formulated using purified poloxamer 188 (3%, 5%, 7%), and sodium salt of fatty acids (C8, C10, C12) in saline and characterized using ternary/binary diagrams, particle sizing, and stability upon dilution. Rats received propofol (10 mg · kg−1 · min−1) as either a microemulsion or a conventional macroemulsion to determine these end points: induction (dose; stunned; loss of lash reflex, righting reflex, withdrawal to toe pinch) and recovery (recovery of lash, righting, withdrawal reflexes). After a 14-day recovery period, rats were crossed over into the opposite experimental limb. Results:Forty-eight microemulsions (diameter, 11.9–47.7 nm) were formulated. Longer carbon chain length led to a marked increase in the volume of diluent necessary to break these microemulsions. All rats experienced anesthetic induction with successful recovery, although significantly greater doses of propofol were required to induce anesthesia with microemulsions irrespective of surfactant concentration or type than with macroemulsions. The sodium salt of C10 fatty acid microemulsion required the greatest dose and longest time for anesthetic induction. Conclusion:Propofol microemulsions cause induction in rats similar to that from macroemulsions. The surfactant concentration and type markedly affect the spontaneous destabilization and anesthetic properties of microemulsions, a phenomenon suggesting a mechanism whereby dose–response relation can be selectively modified.

CO2 detection using polyethylenimine/starch functionalized AlGaN∕GaN high electron mobility transistors

AlGaN∕GaN high electron mobility transistors (HEMTs) functionalized with polyethylenimine/starch were used for detecting CO2 with a wide dynamic range of 0.9%–50% balanced with nitrogen at temperatures from 46to220°C. Higher detection sensitivity to CO2 gas was achieved at higher testing temperatures. At a fixed source-drain bias voltage of 0.5V, drain-source current of the functionalized HEMTs showed a sublinear correlation upon exposure to different CO2 concentrations at low temperature. The superlinear relationship was at high temperature. The sensor exhibited a reversible behavior and a repeatable current change of 32 and 47μA with the introduction of 28.57% and 37.5% CO2 at 108°C, respectively.

c-erbB-2 sensing using AlGaN∕GaN high electron mobility transistors for breast cancer detection

Antibody-functionalized, Au-gated AlGaN∕GaN high electron mobility transistors (HEMTs) were used to detect c-erbB-2, which is a breast cancer marker. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN∕GaN HEMT drain-source current showed a rapid response of less than 5s when target c-erbB-2 antigen in a buffer at clinically relevant concentrations was added to the antibody-immobilized surface. We could detect a range of concentrations from 16.7to0.25μg∕ml. These results clearly demonstrate the promise of portable electronic biological sensors based on AlGaN∕GaN HEMTs for breast cancer screening.

Ionic basis of the differential effects of Intravenous anesthetics on erythromycin-induced prolongation of ventricular repolarization in the guinea pig heart

Background: Dysrhythmias and death occur in patients with acquired long QT syndrome (LQTS). Little information exists regarding interactions between anesthetics and drugs that prolong ventricular repolarization. Therefore the effects of three commonly used intravenous anesthetics on ventricular repolarization were investigated in the setting of drug‐induced, long QT syndrome. Methods: The effects of increasing concentrations (0, 10, 25, and 50 micro Meter) of propofol, ketamine, and thiopental on ventricular repolarization were evaluated by measuring the monophasic action potential duration at 90% repolarization (MAPD90) in guinea pig Langendorff‐perfused hearts in the absence or presence of erythromycin (100 micro Meter). If an anesthetic enhanced erythromycin‐induced prolongation of MAPD90, its effects on the delayed rectifier (IK) and inward rectifier (IKl) potassium currents were measured using the whole‐cell patch‐clamp technique. Results: At clinically relevant concentrations, only thiopental significantly modulated erythromycins effect on MAPD90. Thiopental at 10, 25, and 50 micro Meterr prolonged MAPD90 from a control of 163 +/‐ 6 ms by 18 +/‐ 4, 30 +/‐ 3, and 31 +/‐ 4 ms, respectively. In a separate group, erythromycin prolonged MAPD90 from 155 +/‐ 2 ms to 171 +/‐ 2 ms (n = 21, P < 0.001). In the presence of erythromycin, thiopental at 10, 25, and 50 micro Meter caused significantly greater prolongation from a control of 171 +/‐ 2 ms by 39 +/‐ 2, 58 +/‐ 3, and 72 +/‐ 6 ms, respectively. Whole‐cell patch‐clamp experiments indicated that thiopental inhibited IK and IKl. Conclusions: Intravenous anesthetics caused markedly different effects on ventricular repolarization. Thiopental, unlike propofol and ketamine, potentiated the effects of erythromycin on ventricular repolarization by inhibiting IK and IKl.

Anesthetic Properties of a Propofol Microemulsion in Dogs

Microemulsions of propofol with nanometer droplet diameter are alternatives to soybean macroemulsions for inducing anesthesia, and may have important advantages. We used a propofol (10 mg/mL) microemulsion (particle diameter 24.5 ± 0.5 nm) and a commercial macroemulsion to induce anesthesia in dogs (n = 10) using a randomized, crossover design separated by a 7-day rest interval. The end points were loss of leg withdrawal after a toe pinch and changes in vital signs. Venous blood samples were acquired at multiple times to measure plasma propofol concentrations and indices of erythrocytes, leukocytes, and coagulation. All dogs were rendered insensitive to pain followed by successful recovery without noticeable complications. Comparing indices between microemulsion and macroemulsion formulations, no differences were noted with respect to dose (10.3 ± 1.2 and 9.7 ± 1.6 mg/kg, respectively, P = 0.39), time to induction (1.0 ± 0.1 and 1.0 ± 0.2 min, P = 0.39), time to recovery (17.4 ± 4.6 and 18.2 ± 3.8 min, P = 0.70), heart rate (P = 0.62), arterial blood pressure (P = 0.81), respiratory rate (P = 0.60), hemogram variables, prothrombin time (P = 0.89), activated partial thromboplastin time (P = 0.76), fibrinogen concentration (P = 0.52), platelet concentration (P = 0.55), or plasma propofol concentrations (P = 0.20). Induction with a propofol microemulsion or macroemulsion did not significantly vary with respect to vital signs, the hemogram, clotting variables, and plasma propofol concentrations.