Noninvasive Method and Metric for Monitoring Lung Condition.

For hospitalized patients with pulmonary conditions, the onset of respiratory decline can occur unnoticed, due to the absence of a way to continuously and noninvasively monitor lung condition. Based on the relationship between lung volume and pleural pressure, we hypothesized that the time delay (∆t) between the start of a respiratory cycle and the occurrence of lung sounds associated with inspiration would correlate with lung volume. Additionally, we developed a re-search tool, consisting of a respiration belt, digital stethoscope, data collection system and MATLAB algorithm, to measure this delay. We conducted a feasibility study with three healthy individuals that involved safely manipulating lung volume, through subject position and activity, and plotting ∆t against volume measurements obtained via spirometry. The results indicated that ∆t was measurable and changed with lung volume and, therefore, has the potential to serve as a lung condition monitoring tool.

A reduced zinc diet or zinc transporter 3 knockout attenuate light induced zinc accumulation and retinal degeneration.

Our previous study on retinal light exposure suggests the involvement of zinc (Zn(2+)) toxicity in the death of RPE and photoreceptors (LD) which could be attenuated by pyruvate and nicotinamide, perhaps through restoration of NAD(+) levels. In the present study, we examined Zn(2+) toxicity, and the effects of NAD(+) restoration in primary retinal cultures. We then reduced Zn(2+) levels in rodents by reducing Zn(2+) levels in the diet, or by genetics and measured LD. Sprague Dawley albino rats were fed 2, or 61 mg Zn(2+)/kg of diet for 3 weeks, and exposed to 18 kLux of white light for 4 h. We light exposed (70 kLux of white light for 50 h) Zn(2+) transporter 3 knockout (ZnT3-KO, no synaptic Zn(2+)), or RPE65 knockout mice (RPE65-KO, lack rhodopsin cycling), or C57/BI6/J controls and determined light damage and Zn(2+) staining. Retinal Zn(2+) staining was examined at 1 h and 4 h after light exposure. Retinas were examined after 7 d by optical coherence tomography and histology. After LD, rats fed the reduced Zn(2+) diet showed less photoreceptor Zn(2+) staining and degeneration compared to a normal Zn(2+) diet. Similarly, ZnT3-KO and RPE65-KO mice showed less Zn(2+) staining, NAD(+) loss, and RPE or photoreceptor death than C57/BI6/J control mice. Dietary or ZnT3-dependent Zn(2+) stores, and intracellular Zn(2+) release from rhodopsin recycling are suggested to be involved in light-induced retinal degeneration. These results implicate novel rhodopsin-mediated mechanisms and therapeutic targets for LD. Our companion manuscript demonstrates that pharmacologic, circadian, or genetic manipulations which maintain NAD(+) levels reduce LD.