Scanning force microscopy in the applied biological sciences.

Fifteen years after its invention, the scanning force microscope (SFM) is rooted deep in the biological sciences. Here we discuss the use of SFM in biotechnology and biomedical research. The spectrum of applications reviewed includes imaging, force spectroscopy and mapping, as well as sensor applications. It is our hope that this review will be useful for researchers considering the use of SFM in their studies but are uncertain about its scope of capabilities. For the benefit of readers unfamiliar with SFM technology, the fundamentals of SFM imaging and force measurement are also briefly introduced.

Laser irradiation of biological tissue through water as a means of reducing thermal damage.

BACKGROUND AND OBJECTIVE: Reduction of thermal damage inbred with laser surgery is an ongoing challenge. The cavitation effect has been shown to facilitate the transmission of a laser beam through the otherwise opaque water layer. We suggest that by immersing the target tissue in water during laser surgery, thermal damage will be diminished. STUDY DESIGN/MATERIALS AND METHODS: A method of irradiating tissue by CO2 laser through a layer of a few millimeters of water is described. A series of experiments was conducted on fresh bovine cornea immersed in water or in air, histology of thermal damage was compared. RESULTS: We were able to show that irradiation of tissue immersed in water reduces the thermal damage caused to the area surrounding the incision as compared to the damage caused during irradiation of tissue in air (P < 0.001). CONCLUSION: Laser surgery of tissue immersed in water can reduce the inbred thermal damage. Application of this method to clinical use may result in precise, clean cutting, and enable the use of CO2 laser through water.

Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations.

The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control.

Modulation of the dose-dependent effects of atropine by low-dose pyridostigmine: quantification by spectral analysis of heart rate fluctuations in healthy human beings.

The interaction between a low-dose cholinesterase inhibitor, pyridostigmine (PYR), and atropine was investigated by spectral analysis of heart rate fluctuations in eight healthy humans. Each subject was given increasing boluses of IV atropine during treatment with PYR (30 mg.3/day) or placebo. PYR attenuated the bimodal dose-dependent changes in the respiratory peak (which respresents the parasympathetic control) in response to atropine. We suggest that spectral analysis can be used for quantifying the complex dose-dependent cholinergic agonist-antagonist interactions, and may help to disclose an asymptomatic low-dose intoxication with acetylcholinesterase inhibitors.

Pharmacological modulation of vagal cardiac control measured by heart rate power spectrum: a possible bioequivalent probe.

The autonomic cardiac control was studied as a sensitive parameter of anticholinergic treatment in humans, using heart-rate (HR) power spectrum. A cross-over placebo controlled study was performed in 8 young volunteers who received increasing bolusdoses of IV atropine (from 1.3 micrograms/kg to 29.9 micrograms/kg) or placebo. Computing the HR power spectrum and integrating over specific frequency bands, we focused in particular on the respiratory frequency band (usually between 0.2-0.4 Hz) which is purely of vagal mediation. At small atropine doses (less than 5.2 micrograms/kg), the respiratory peak increased, relative to baseline, with maximal response at 2.6 micrograms/kg (from 1.0 to 1.9 +/- 0.9). Larger doses of atropine (greater than or equal to 6.5 micrograms/kg) reduced the power of the respiratory peak, by a few orders of magnitude, in a dose-dependent way. Corresponding changes were observed in mean HR but in the opposite direction i.e., a maximal bradycardia at 2.6 micrograms/kg and a nearly two fold increase in mean HR at 29.9 micrograms/kg. We conclude that atropine has a bimodal dose-dependent effect on parasympathetic cardiac control. Since the use of HR spectral analysis has been demonstrated in various animal species, we suggest that it can be used as a sensitive noninvasive probe for animal to man transformation studies.