Diamond encapsulated photovoltaics for transdermal power delivery.

A safe, compact and robust means of wireless energy transfer across the skin barrier is a key requirement for implantable electronic devices. One possible approach is photovoltaic (PV) energy delivery using optical illumination at near infrared (NIR) wavelengths, to which the skin is highly transparent. In the work presented here, a subcutaneously implantable silicon PV cell, operated in conjunction with an external NIR laser diode, is developed as a power delivery system. The biocompatibility and long-term biostability of the implantable PV is ensured through the use of an hermetic container, comprising a transparent diamond capsule and platinum wire feedthroughs. A wavelength of 980 nm is identified as the optimum operating point based on the PV cell's external quantum efficiency, the skin's transmission spectrum, and the wavelength dependent safe exposure limit of the skin. In bench-top experiments using an external illumination intensity of 0.7 W/cm(2), a peak output power of 2.7 mW is delivered to the implant with an active PV cell dimension of 1.5 × 1.5 × 0.06 mm(3). This corresponds to a volumetric power output density of ~20 mW/mm(3), significantly higher than power densities achievable using inductively coupled coil-based approaches used in other medical implant systems. This approach paves the way for further ministration of bionic implants.

Ultrananocrystalline diamond-CMOS device integration route for high acuity retinal prostheses.

High density electrodes are a new frontier for biomedical implants. Increasing the density and the number of electrodes used for the stimulation of retinal ganglion cells is one possible strategy for enhancing the quality of vision experienced by patients using retinal prostheses. The present work presents an integration strategy for a diamond based, high density, stimulating electrode array with a purpose built application specific integrated circuit (ASIC). The strategy is centered on flip-chip bonding of indium bumps to create high count and density vertical interconnects between the stimulator ASIC and an array of diamond neural stimulating electrodes. The use of polydimethylsiloxane (PDMS) housing prevents cross-contamination of the biocompatible diamond electrode with non-biocompatible materials, such as indium, used in the microfabrication process. Micro-imprint lithography allowed edge-to-edge micro-scale pattering of the indium bumps on non-coplanar substrates that have a form factor that can conform to body organs and thus are ideally suited for biomedical applications. Furthermore, micro-imprint lithography ensures the compatibility of lithography with the silicon ASIC and aluminum contact pads. Although this work focuses on 256 stimulating diamond electrode arrays with a pitch of 150 µm, the use of indium bump bonding technology and vertical interconnects facilitates implants with tens of thousands electrodes with a pitch as low as 10 µm, thus ensuring validity of the strategy for future high acuity retinal prostheses, and bionic implants in general.

Quantitative relationships of the interaction between sound and kanamycin.

It is well known that the ototoxicity resulting from the use of aminoglycoside antibiotics in experimental animals can be augmented by intense sound. However, the dose-effect relationship of this interaction is not known. This study was designed to determine the shape of this dose-effect relationship in guinea pigs at sound intensities approaching those that would be experienced by patients receiving aminoglycoside antibiotics. We found a linear relationship between the probit of the percent of missing cochlear outer hair cells and decibel-A scale sound intensity when the animals were treated with kanamycin plus white noise ranging from 115 to 45 dBA.

Augmented gentamicin ototoxicity induced by vancomycin in guinea pigs.

Vancomycin has been reported to be an ototoxic drug in the clinical literature. At best, this literature is confusing. There are no reports of ototoxicity of vancomycin in experimental animals, even when it is administered concurrently with ethacrynic acid, a drug known to augment the ototoxic effect of most other ototoxic drugs. In most of the cases of permanent ototoxicity that have been reported, the patient was treated with an aminoglycoside antibiotic as well as vancomycin. This study found no evidence of vancomycin ototoxicity in guinea pigs, but found that vancomycin greatly enhanced the ototoxicity of gentamicin.

Total extraction of aminoglycosides from guinea pig and bullfrog tissues with sodium hydroxide or trichloroacetic acid.

In most experiments when aminoglycoside antibiotic (AG) tissue levels are measured, the AG is extracted into buffered media. The data from this study reveal that buffer extraction results in only partial recovery of AG from tissues and that total recovery can be obtained after NaOH or trichloroacetic acid treatment. Tissues studied here included the whole bullfrog and guinea pig kidney and cochlear tissues after in vivo drug treatment. The AGs used were kanamycin, tobramycin, and gentamicin. Drug concentrations were determined by enzymatic assay and, in the case of tobramycin, also 3H-labeled radioactivity. Only a fraction of total concentration of AG in tissue was released into the supernatants of tissue homogenates. However, the remainder was recovered after NaOH solubilization of the residual pellet. Also, it was found that the G released from the pellet by NaOH was associated with protein. By contrast, trichloroacetic acid precipitation of tissue protein immediately released the drug into the supernatant.

Absence of ototoxicity of teichomycin A2 in guinea pigs.

Teichomycin A2 is a new antibiotic that is similar to vancomycin. Because vancomycin is reported to be ototoxic, teichomycin A2 was tested for ototoxicity. No evidence of ototoxicity was found. Furthermore, ethacrynic acid, a diuretic that augments the ototoxicity of many drugs, did not enhance ototoxicity with teichomycin A2.

Pharmacokinetics of kanamycin in the bullfrog, Rana catesbeiana.

1. Kanamycin disposition was studied in bullfrogs (Rana catesbeiana) following single doses IP. Both plasma t1/2 and Vd of the drug increased with increasing time after drug indicating redistribution and tight binding of kanamycin to deep tissue compartments. 2. Kanamycin was eliminated unchanged with a t1/2 plasma = 27 hr; perilymph = 89 hr; endolymph = 183 hr; aqueous humor = 54 hr; and CSF = 58 hr. 3. Kanamycin was absorbed by frogs from environmental water. 4. Environmental conditions must be carefully specified and monitored, as well as the physiological state of the animals when studying the effects of drugs on Amphibia.

Combined effects of noise and kanamycin. Cochlear pathology and pharmacology.

Concurrent administration of aminoglycoside antibiotics and acoustic exposure is reported to result in a cochlear damage level exceeding that predicted from the effects of either agent given alone. To investigate this interaction, guinea pigs were given daily subcutaneous injections of kanamycin sulfate at 200, 300, or 400 mg/kg followed by a ten-hour noise exposure (115 or 45 dB) for seven consecutive days. Drug levels in plasma and perilymph were measured during the 24 hours after injection and during the seven-day period of drug and noise exposures. Electrophysiological and morphological evaluation of cochlear function confirmed a dramatic interaction at the 300-mg/kg dosage. Augmentation of damage was minimal at 200 mg/kg and masked by ceiling effects at 400 mg/kg. No alteration in accumulation or elimination of kanamycin occurred as a result of high-intensity acoustic exposure.

A comparative study of the ototoxicity of gentamicin and gentamicin C1.

Dose-response experiments comparing the ototoxic liability of the aminoglycoside antibiotics gentamicin sulfate and gentamicin C1 sulfate were conducted on guinea pigs. Measures of cochlear electrophysiology, histology, and the pharmacokinetic disposition of the drugs in the plasma and perilymph were made. Electrophysiological and histological measures indicated that gentamicin is more ototoxic than is gentamicin C1.

Laser detection of latent fingerprints: preparation of fluorescent dusting powders and the feasibility of a portable system.

A simple procedure for the preparation of dusting powders with a variety of fluorescent colors is described. Such powders permit detection of latent prints by laser even when the surfaces holding the latent prints luminesce strongly. A possible portable laser detection system is also suggested.

Ototoxic effects of the interaction between kanamycin and ethacrynic acid. Cochlear ultrastructure correlated with cochlear potentials and kanamycin levels.

The effects of the interaction between kanamycin (KAN) and ethacrynic acid (EA) on the ultrastructure of the guinea pig cochlea were studied 3, 4, 6, and 24 hours following administration of EA (40 mg/kg) to animals pretreated 2 h earlier with KAN (400 mg/kg). Appropriate saline (SAL) controls were included giving 4 treatments: KAN/EA, KAN/SAL, SAL/EA and SAL/SAL. The outer hair cells of the organ of Corti showed nuclear and plasma membrane changes at 3 h and were completely destroyed at 24 h. The inner hair cells were unaffected. Severe swelling was seen in the stria vascularis of both KAN/EA and SAL/EA animals at 3 h and was gone by 24 h. KAN/EA had a greater effect on the stria than had SAL/EA. These results were consistent with the time course of the effect of the drugs on the a.c. and d.c. endocochlear potentials. KAN concentrations in perilymph were unaffected by treatment with EA.

The relationship between the cytotoxicity of kanamycin and ethacrynic acid for mammalian cells in vitro and their ototoxicity in vivo.

Dose-effect curves for inhibition of growth of P388/P mouse lymphoma cells by ethacrynic acid and kanamycin used alone and in combination were determined in vitro. Ethacrynic acid was 600 times more potent than kanamycin and combinations of the drugs resulted in overall additive effects. These results were compared with known dose-effect data on the ototoxicity of these drugs in vivo. Kanamycin was highly selective in its toxicity for cochlear hair cells compared to cultured cells. The dose-effect data for ethacrynic acid was coincident with that reported for functional and biochemical effects on the cochlea following perilymphatic perfusion with the drug. The potentiation observed following the ototoxic interaction the two drugs in vivo was not observed following combinations of the drugs in vitro.

Comparative ototoxic liability of netilmicin and gentamicin.

Netilmicin sulfate is a new aminoglycoside antibiotic currently undergoing clinical investigation. All of the aminoglycoside antibiotics now in clinical use are ototoxic. This study was done to determine the ototoxic liability of netilmicin when it is compared directly with gentamicin sulfate. Groups of ten guinea pigs each were given doses of 0, 50, 100, or 150 mg/kg of either gentamicin or netilmicin daily for four weeks. After a two-week stabilization period, the Preyer pinna reflex, the cochlea's ability to generate the ac cochlear potential, and the missing hair cells from the cochleas were determined. Additionally, the pharmacokinetics of both drugs in the plasma and perilymph were determined. Little or no cochlear damage was detected with netilmicin, even at the highest dose, while even the smallest dose of gentamicin produced measurable changes in cochlear function.