Trans-rectal ultrasound-coupled spectral optical tomography of total hemoglobin concentration enhances assessment of the laterality and progression of a transmissible venereal tumor in canine prostate.

OBJECTIVES: To evaluate whether trans-rectal spectral optical tomography of total hemoglobin concentration (HbT) can image longitudinal and lateral developments of a canine transmissible venereal tumor (TVT) in a canine prostate. METHODS: A near-infrared (NIR) applicator was integrated with a trans-rectal ultrasound (TRUS) transducer to perform ultrasound (US)-coupled optical tomography of the canine prostate. Spectral detection at 785 and 830 nm enabled quantitation of HbT. Canine TVT cells were injected into the right lobe of a dog's prostate gland. Longitudinal imaging assessment of the post-injection prostate was performed by coupled US/NIR imaging over a 45-day duration. RESULTS: By day 7, NIR indicated TVT infiltration in the noninjected left prostatic lobe with the gray-scale US indistinct. By day 31, both NIR and gray-scale US revealed more widespread TVT involvement in the left than in the right lobe, as well as an extensive TVT mass in the caudal aspect of the gland, of which the peak HbT increased 3-fold and the mass volume grew exponentially over the 45-day duration. Increased blood supply to the mass was also observed on Doppler US. CONCLUSIONS: TRUS-coupled spectral optical tomography enhances assessment of the laterality and progression of prostate tumor compared with using gray-scale and Doppler TRUS.

Piezo-driven deformable mirror for femtosecond pulse shaping.

We have developed a deformable, gold-coated mirror based on piezoelectric actuators with 15-micros response time. With 20 independent channels we were able to compress 72-fs pulses from a Ti:sapphire oscillator down to 45 fs in a 4f zero-dispersion compressor arrangement. Spectral interference was used to measure the mirror performance, while the spectral phase interferometry for direct electric field reconstruction (SPIDER) technique was used for the laser pulse characterization.

S17834, a new inhibitor of cell adhesion and atherosclerosis that targets nadph oxidase.

microdant stress is involved in the events that accompany endothelial cell expression of adhesion molecules and leukocyte adherence in many disease states, including atherosclerosis. A recently discovered benzo(b)pyran-4-one derivative, S17834 (10 to 50 micromol/L), reduced tumor necrosis factor-stimulated vascular cell adhesion molecule-1 (VCAM) mRNA accumulation and protein expression in human umbilical vein endothelial cells. Intercellular cell adhesion molecule-1 and E-selectin were also inhibited by S17834, but platelet endothelial cell adhesion molecule-1 was not. Adherence of U937 monocytic cells to the endothelial cells as well as to plastic plates coated with soluble VCAM, intercellular cell adhesion molecule-1, P-selectin, and E-selectin was also decreased. Consistent with an antioxidant mechanism of action, S17834 (10 to 50 micromol/L) inhibited tumor necrosis factor-stimulated release of superoxide from endothelial cells measured by cytochrome c reduction. S17834 had no effect on superoxide produced by xanthine oxidase, indicating that rather than by acting as a scavenger of superoxide anion, the drug acts by inhibiting the production of free radicals. Indeed, S17834 inhibited NADPH oxidase activity of endothelial cell membranes. The ability to inhibit superoxide anion production appears to be key in the effect of S17834 on superoxide anion production and VCAM expression, because these actions were mimicked by adenovirus-mediated overexpression of superoxide dismutase. Furthermore, these actions may be relevant in vivo, because S17834 reduced aortic superoxide anion levels by 40% and aortic atherosclerotic lesions by 60% in apolipoprotein E-deficient mice. These results indicate that S17834 inhibits adhesion molecule expression and adherence of leukocytes to endothelial cells as well as aortic atherogenesis and that perhaps these effects can be explained by its ability to inhibit endogenous superoxide anion production.

Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes.

Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in vitro. We investigated whether oxidative stress mediates hypertrophy and apoptosis in cyclically stretched ventricular myocytes. Neonatal rat ventricular myocytes cultured on laminin-coated silastic membranes were stretched cyclically (1 Hz) at low (nominal 5%) and high (nominal 25%) amplitudes for 24 hours. Stretch caused a graded increase in superoxide anion production as assessed by superoxide dismutase (SOD)-inhibitable cytochrome c reduction or electron paramagnetic resonance spectroscopy. The role of reactive oxygen species (ROS) was assessed using the cell-permeable SOD/catalase mimetics Mn(II/III)tetrakis(1-methyl-4-peridyl) (MnTMPyP) and EUK-8. Stretch-induced increases in protein synthesis ((3)H-leucine incorporation) and cellular protein content were completely inhibited by MnTMPyP (0.05 mmol/L) at both low and high amplitudes of stretch. In contrast, while MnTMPyP inhibited basal atrial natriuretic factor (ANF) mRNA expression, the stretch-induced increase in ANF mRNA expression was not inhibited by MnTMPyP. In contrast to hypertrophy, only high-amplitude stretch increased myocyte apoptosis, as reflected by increased DNA fragmentation on gel electrophoresis and an approximately 3-fold increase in the number of TUNEL-positive myocytes. Similarly, only high-amplitude stretch increased the expression of bax mRNA. Myocyte apoptosis and bax expression stimulated by high-amplitude stretch were inhibited by MnTMPyP. Both low- and high-amplitude stretch caused rapid phosphorylation of ERK1/2, while high-, but not low-, amplitude stretch caused phosphorylation of JNKs. Activation of both ERK1/2 and JNKs was ROS-dependent. Thus, cyclic strain causes an amplitude-related increase in ROS, associated with differential activation of kinases and induction of hypertrophic and apoptotic phenotypes.

Decreased sensitivity to nitric oxide in the aorta of severely hypercholesterolemic apolipoprotein E-deficient mice.

A normal response to nitric oxide donors has been cited as evidence that impaired endothelium-dependent vasodilation during hypercholesterolemia is due to decreased synthesis of nitric oxide. This tenet was examined by determining responses to nitric oxide gas as well as to acetylcholine and sodium nitroprusside in the isolated aorta of apolipoprotein E-deficient mice fed normal or Western-type cholesterol-rich diet until 21 or 35 weeks of age. In mice fed normal chow, relaxation to all agents remained comparable to that obtained in wild-type mice. In mice fed Western diet, the relaxation to acetylcholine as well as to nitric oxide was decreased at 35 weeks of age. At 21 weeks of age, decreased sensitivity to nitric oxide was observed despite a normal response to acetylcholine. The response to sodium nitroprusside was normal in all groups. A decrease in aortic superoxide dismutase activity as well as an increase in aortic superoxide anion generated in the presence of NADH as measured by lucigenin chemiluminescence was observed in the group fed Western diet at 35 weeks. This provides evidence that altered superoxide anion could contribute to the deterioration in nitric oxide sensitivity that underlies the impaired endothelium-dependent relaxation. These data indicate that decreased sensitivity to nitric oxide may contribute to the development of impaired endothelium-dependent relaxation in hypercholesterolemia. The response to sodium nitroprusside appears not to reflect the decreased sensitivity of vascular smooth muscle to authentic nitric oxide.

The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis.

Atherosclerosis involves a complex array of factors, including leukocyte adhesion and platelet vasoactive factors. Aspirin, which is used to prevent secondary complications of atherosclerosis, inhibits platelet production of thromboxane (Tx) A(2). The actions of TxA(2) as well as of other arachidonic acid products, such as prostaglandin (PG) H(2), PGF(2alpha), hydroxyeicosatetraenoic acids, and isoprostanes, can be effectively antagonized by blocking thromboxane (TP) receptors. The purpose of this study was to determine the role of platelet-derived TxA(2) in atherosclerotic lesion development by comparing the effects of aspirin and the TP receptor antagonist S18886. The effect of 11 weeks of treatment with aspirin (30 mg. kg(-1). d(-1)) or S18886 (5 mg. kg(-1). d(-1)) on aortic root atherosclerotic lesions, serum levels of intercellular adhesion molecule-1 (ICAM-1), and the TxA(2) metabolite TxB(2) was determined in apolipoprotein E-deficient mice at 21 weeks of age. Both treatments did not affect body or heart weight or serum cholesterol levels. Aspirin, to a greater extent than S18886, significantly decreased serum TxB(2) levels, indicating the greater efficacy of aspirin in preventing platelet synthesis of TxA(2). S18886, but not aspirin, significantly decreased aortic root lesions as well as serum ICAM-1 levels. S18886 also prevented the increased expression of ICAM-1 in cultured human endothelial cells stimulated by the TP receptor agonist U46619. These results indicate that inhibition of platelet TxA(2) synthesis with aspirin has no significant effect on atherogenesis or adhesion molecule levels. The effects of S18886 suggest that blockade of TP receptors inhibits atherosclerosis by a mechanism independent of platelet-derived TxA(2), perhaps by preventing the expression of adhesion molecules whose expression is stimulated by eicosanoids other than TxA(2).

Photography of shock waves during excimer laser ablation of the cornea. Effect of helium gas on propagation velocity.

Shadow photography of shock waves excited by means of a xenon chloride excimer laser was performed to determine the shock wave propagation velocity in air, nitrogen and helium. Energy densities between 500 and 2,000 mJ/cm2 were used to ablate a rotating rubber cylindrical target and porcine corneas. In ablating the rubber cylinder, a shock wave velocity of 3.3 km/s was generated in air and nitrogen at 40 ns; this decreased to 1.4 km/s at 320 ns. When helium was blown on the target, the velocity increased by a factor of approximately two, to 5.9 km/s at 40 ns and 2.7 km/s at 320 ns. We suggest that blowing helium on the surface of the cornea during excimer laser ablation may speed the dissipation of high-energy acoustic waves and gaseous particles, and thus reduce the exposure and transfer of heat energy to the surrounding tissue.

Increased efficiency for sum-frequency generation for broadband input fields.

A new method of efficient sum-frequency generation for broadband input fields is theoretically analyzed and experimentally demonstrated. The method involves using an arrangement with two or more nonlinear mixing crystals, with a time-delay line situated between the crystals, for one of the fundamental fields relative to the other. The delay line temporally shifts the fundamental fields, one relative to another, by a time longer than their coherence time. The improvement in efficiency for sum-frequency generation using this method is much higher than for difference-frequency generation.

Theory of mode-locked intracavity second-harmonic generation in a ring laser.

We model the dynamics of a Q-switched mode-locked intracavity second-harmonic-generation (SHG) ring laser. Numerical studies show that a long train of constant-pulse-duration short pulses at the second-harmonic and fundamental frequencies result. The efficiency of the mode-locked intracavity SHG laser is comparable with that of the mode-locked fundamental-frequency laser not containing SHG.

Birefringence of solid-state laser media: broadband tuning discontinuities and application to laser line narrowing.

Spectral consequences that result from using birefringent media with broadband gain inside of laser cavities containing polarizing elements are described. We show that the laser intensity is modulated as a function of the output frequency unless the cavity elements are carefully aligned so that their polarization axis coincides with a principal optical axis of the gain medium. Analysis of the tuning characteristics of a birefringent polarizationdependent gain medium is exploited to provide a simple method for line narrowing the laser output. By introduction of an intracavity birefringent compensator the narrow-band output can be continuously tuned. Experimental results for alexandrite lasers are presented.

The two-photon laser-induced fluorescence of the tumor-localizing photosensitizer hematoporphyrin derivative. Resonance-enhanced 750 nm two-photon excitation into the near-UV Soret band.

The tumor-localizing photosensitizer hematoporphyrin derivative (HPD) is shown to undergo a simultaneous two-photon excitation into the near-ultraviolet Soret band system upon intense laser irradiation at 750 nm, a spectral region where there is no significant HPD one-photon absorbance in aqueous solution. Subsequent to this excitation, internal conversion and vibrational relaxation occur, resulting in the population of the vibrationless level of the first electronically excited singlet state. This state relaxes by two channels, the emission of fluorescence in the spectral region 600-700 nm and intersystem crossing into the triplet manifold, followed by near-resonant electronic energy transfer with surrounding oxygen to result in the generation of highly reactive singlet molecular oxygen (1 delta g). Evidence for the two-photon excitation consists in the observation both of the HPD fluorescence spectrum in the region of 615 nm as a result of 750 nm excitation and the quadratic dependence of this fluorescence emission intensity upon the excitation laser intensity. Since, in general, the penetration depth of ultraviolet and visible light into tissue varies directly with wavelength (red penetrating more deeply than blue), these studies suggest the possibility that two-photon-induced localization of tumor-bound HPD might facilitate the detection of deeper lying tumors than allowed by the current one-photon photolocalization method.

Observation of resonantly enhanced sum-frequency generation involving sodium Rydberg states.

A large, dc-electric-field-induced nonlinear optical susceptibility is exploited to produce ultraviolet radiation in the range 2453-2476 A by the process of sum-frequency generation in sodium. The interaction is resonantly enhanced at the first intermediate level by the 3 (2)P(3/2) state and at the second intermediate level by a Rydberg state. Conversion efficiencies of 10(-5) have been obtained; improvement of this value by a factor of 10(3) should be possible.