Global Transcriptional Programs in Peripheral Nerve Endoneurium and DRG Are Resistant to the Onset of Type 1 Diabetic Neuropathy in Ins2Akita/+ Mice

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2Akita/+ mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2Akita/+ and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2Akita/+ mice and sex-matched littermate controls. Our phenotypic analysis of Ins2Akita/+ mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM

Mechanical characterization of microparticles by scattered ultrasound

A technique for determining the compressibility and density of individual microparticles in suspension is described. The particles have diameters on the order of 10 pro. Ultrasonic tone bursts of 2-ps duration and 30-MHz center frequency scatter from individual particles as they traverse the confocal zone of two transducers. The resulting scattered tone bursts are detected at 90 ø and 180 ø (backscattering). The received rf signals are demodulated, peak detected, digitized, and stored in computer memory. Using Rayleigh scattering theory, the compressibility and density of a particle can be computed given knowledge of the particle size and host fluid properties. Results of experiments with latex microspheres are presented and compared with calculations based on long-wavelength (Rayleigh) and elastic scattering theory

Mechanical characterization of microparticles by scattered ultrasound

A technique for determining the compressibility and density of individual microparticles in suspension is described. The particles have diameters on the order of 10 pro. Ultrasonic tone bursts of 2-ps duration and 30-MHz center frequency scatter from individual particles as they traverse the confocal zone of two transducers. The resulting scattered tone bursts are detected at 90 ø and 180 ø (backscattering). The received rf signals are demodulated, peak detected, digitized, and stored in computer memory. Using Rayleigh scattering theory, the compressibility and density of a particle can be computed given knowledge of the particle size and host fluid properties. Results of experiments with latex microspheres are presented and compared with calculations based on long-wavelength (Rayleigh) and elastic scattering theory

Acoustic microcavitation: Its active and passive acoustic detection

In this work acoustic microcavitation in water is studied primarily at 0.75 MHz and 1% duty cycle. To detect cavitation, two kinds of acoustic detectors are used. The first one is an unfocused, untuned 1‐MHz receiver transducer that serves as a passive detector. The other one is a focused 30‐MHz transducer that is used in pulse‐echo mode and is called the active detector. Cavitation itself is brought about by a focused PZT‐8 crystal driven in pulse mode. The active detector is arranged confocally with respect to the cavitation transducer. Both the interrogating pulse and the cavitation pulse arrive simultaneously at the common focus, which is the region of cavitation. With the test chamber filled with clean water, no cavitation is observed, even when the cavitation transducer is driven to give its peak output of 22 bar peak negative. Cavitation is, however, observed when polystyrene microparticles are added to the host water. Our view of how these smooth, spherical, monodispersed microparticles give rise to cavitation is described with some estimates. An attempt has been made to understand whether the presence of ‘‘streaming’’ affects the thresholds, and it has been found that the active detector field affects the cavitation process

An acoustic backscattering technique for the detection of transient cavitation produced by microsecond pulses of ultrasound

An acoustic backscattering technique for detecting transient cavitation produced by 10‐μs‐long pulses of 757‐kHz ultrasound is described. The system employs 10‐μs‐long, 30‐MHz center frequency tone bursts that scatter from cavitation microbubbles. Experiments were performed with suspensions of hydrophobic polystyrene spheres in ultraclean water. Transient cavitation threshold pressures measured with the active cavitation detector (ACD) were always less than or equal to those measured using a passive acoustic detection scheme. The measured cavitation thresholds decreased with increasing dissolved gas content and increasing suspended particle concentration. Results also show that ultrasonic irradiation of the polystyrene sphere suspensions by the ACD lowered the threshold pressure measured with the passive detector. A possible mechanism through which suspensions of hydrophobic particles might nucleate bubbles is presented

Acoustic microcavitation: Its active and passive acoustic detection

In this work acoustic microcavitation in water is studied primarily at 0.75 MHz and 1% duty cycle. To detect cavitation, two kinds of acoustic detectors are used. The first one is an unfocused, untuned 1‐MHz receiver transducer that serves as a passive detector. The other one is a focused 30‐MHz transducer that is used in pulse‐echo mode and is called the active detector. Cavitation itself is brought about by a focused PZT‐8 crystal driven in pulse mode. The active detector is arranged confocally with respect to the cavitation transducer. Both the interrogating pulse and the cavitation pulse arrive simultaneously at the common focus, which is the region of cavitation. With the test chamber filled with clean water, no cavitation is observed, even when the cavitation transducer is driven to give its peak output of 22 bar peak negative. Cavitation is, however, observed when polystyrene microparticles are added to the host water. Our view of how these smooth, spherical, monodispersed microparticles give rise to cavitation is described with some estimates. An attempt has been made to understand whether the presence of ‘‘streaming’’ affects the thresholds, and it has been found that the active detector field affects the cavitation process

An acoustic backscattering technique for the detection of transient cavitation produced by microsecond pulses of ultrasound

An acoustic backscattering technique for detecting transient cavitation produced by 10‐μs‐long pulses of 757‐kHz ultrasound is described. The system employs 10‐μs‐long, 30‐MHz center frequency tone bursts that scatter from cavitation microbubbles. Experiments were performed with suspensions of hydrophobic polystyrene spheres in ultraclean water. Transient cavitation threshold pressures measured with the active cavitation detector (ACD) were always less than or equal to those measured using a passive acoustic detection scheme. The measured cavitation thresholds decreased with increasing dissolved gas content and increasing suspended particle concentration. Results also show that ultrasonic irradiation of the polystyrene sphere suspensions by the ACD lowered the threshold pressure measured with the passive detector. A possible mechanism through which suspensions of hydrophobic particles might nucleate bubbles is presented