Detection of Raman spectra in ocular drugs for potential in vivo application of Raman spectroscopy.

Abstract Purpose: Raman spectroscopy holds potential for the assessment of intraocular pharmacokinetics. Raman spectra of ocular drugs were acquired, to determine the drug-specific Raman signature. The ability of the Raman technique to quantify drug concentrations was also investigated. Methods: The experimental setup was based on a High Performance Raman Module 2500 Raman module, designed for 180 degrees "backscatter" signal detection in the wavenumber range of 400-1,800 cm(-1). Excitation source was a diode laser emitting a beam with a wavelength of 785 nm and a power of 10 mW. Laser light was focused in the sample with a long-working-distance microscope objective (25x/0.50). Samples were measured in quartz cuvettes in 10 sequential measurements, with exposure time 30 s. The total number of measured drugs was 49. To determine whether signal intensity and drug concentration correlate, 2 drugs were diluted in water and measured with 120 s exposure time at different concentrations. Results: An active ingredient-specific Raman signature was detected in 4 glaucoma drugs, 6 mydriatics, 5 antibiotics, 4 anesthetics, 3 anti-inflammatory drugs, 2 types of artificial tears, and 5 other drugs. In 20 drugs, no specific Raman signature was detected. Linear correlation of drug concentration with signal intensity was high (R(2)>/=0.94). Conclusions: Using low laser powers, Raman signatures for 29 commonly used ocular drugs were detected. Correlation of drug concentration with signal intensity is high, which is essential for monitoring drug concentration in ocular media. The presented results encourage the use of Raman spectroscopy to acquire detailed information on the pharmacokinetics of these ocular drugs

Biological Rhythmicity in Subterranean Animals: A Function Risking Extinction?

In this chapter, we discuss evidence of regression of circadian locomotor activity in exclusively subterranean species (troglobites), having fishes as models, by comparing such findings with observations on related epigean (surface) species, that may also form self-sustained subterranean (troglophilic) populations. These results favor the hypothesis of regression of a function which may have lost its adaptive value for species permanently isolated in hypogean habitats for many generations—regression similar to the reduction of eyes and dark pigmentation, typical of troglobites in general. Recent data on feeding behavior of blind catfish compared to epigean congeners suggest a process of partial regression, affecting locomotion but not feeding, due perhaps to the persistence of regular food availability in the otherwise continuously dark cave environment. Among non-troglobitic subterranean animals, trogloxenes present regular, cyclical movements between hypogean and epigean habitats, whereas troglophiles may move between these habitats, promoting genetic connectivity between surface and subterranean populations, but without following well-defined rhythmic patterns

Circadian rhythms in Mexican blind cavefish Astyanax mexicanus in the lab and in the field

Biological clocks have evolved as an adaptation to life on a rhythmic planet, synchronising physiological processes to the environmental light–dark cycle. Here we examine circadian clock function in Mexican blind cavefish Astyanax mexicanus and its surface counterpart. In the lab, adult surface fish show robust circadian rhythms in per1, which are retained in cave populations, but with substantial alterations. These changes may be due to increased levels of light-inducible genes in cavefish, including clock repressor per2. From a molecular standpoint, cavefish appear as if they experience ‘constant light’ rather than perpetual darkness. Micos River samples show similar per1 oscillations to those in the lab. However, data from Chica Cave shows complete repression of clock function, while expression of several light-responsive genes is raised, including DNA repair genes. We propose that altered expression of light-inducible genes provides a selective advantage to cavefish at the expense of a damped circadian oscillator

Reproducibility of electrocardiographic findings in patients with suspected reflex neurally-mediated syncope

The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected neurally-mediated syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had > or =2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented syncope (index syncope) was compared with other recorded events. Twenty-two patients had > or =2 syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first syncope and sinus rhythm at recurrent syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first syncope are highly reproducible in subsequent syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of syncope, and eventually to anticipate treatment, without waiting for syncope