Determinants of platelet responsiveness to nitric oxide in patients with chronic heart failure.

Congestive heart failure (CHF) is associated with oxidative stress. Platelet responsiveness to nitric oxide (NO) donors, are impaired in patients with angina pectoris, possibly by increasing oxidative stress. We investigated the occurrence of platelet resistance to NO in patients, with ischaemic or non-ischaemic cardiomyopathy compared with normal subjects. Anti-aggregatory effects of sodium nitroprusside (SNP), oxidative stress and whole blood superoxide anion content were determined, with correlates of responsiveness to SNP. Inhibition of platelet aggregation by SNP was 65.4+/-3.55% in controls and 59.3+/-4.1% in CHF (P=ns) despite increased oxidative stress and post-aggregation O2- in CHF patients. However, subsets of CHF patients have NO-resistant platelets: this is associated with increasing age and/or increased oxidative stress (both p<0.05).

Beneficial clinical effects of perhexiline in patients with stable angina pectoris and acute coronary syndromes are associated with potentiation of platelet responsiveness to nitric oxide.

AIMS: To examine whether the prophylactic antianginal agent perhexiline potentiates platelet responsiveness to nitric oxide (NO) in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS: unstable angina pectoris or non-Q-wave myocardial infarction). METHODS AND RESULTS: Blood samples were obtained from patients before and after initiation of treatment with perhexiline. ADP-induced platelet aggregation and its inhibition by the NO donor sodium nitroprusside (SNP) were determined via impedance aggregometry in whole blood (WB) and platelet-rich plasma (PRP). Intraplatelet cGMP content was assayed by RIA, and superoxide (O(2)(-)) level by lucigenin-derived chemiluminescence. In patients with ACS not receiving perhexiline (n=12), platelet responsiveness to SNP did not vary significantly over the first 3 days post admission to hospital. Therapy with perhexiline for 3 days was associated with increases in SNP-induced inhibition of aggregation from 29+/-2% to 43+/-4% (n=50,P <0.001) in WB and from 20+/-5% to 42+/-7% (n=12, P<0.01) in PRP. Resolution of symptomatic ischaemia (n=39) was associated with significantly greater (P<0.01) increases than non-resolution (n=11). Similar increases in SNP responsiveness (P<0.001) occurred following institution of perhexiline therapy in patients with SAP (n=30), associated with a 85% decrease in anginal frequency. Treatment with perhexiline potentiated the cGMP-elevating effects of SNP in platelets (n=9,P =0.03). Although perhexiline did not alter whole blood O(2)(-) concentration ex vivo, it inhibited (P<0.01) O(2)(-) release from neutrophils in vitro. CONCLUSION: Perhexiline potentiates platelet responsiveness to NO both in SAP and ACS patients; in the latter group this improvement was predictive of resolution of ischaemic symptoms. The predominant mechanism of perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for NO clearance by neutrophil-derived O(2)(-).

Stable angina and acute coronary syndromes are associated with nitric oxide resistance in platelets.

OBJECTIVES: The study examined possible clinical determinants of platelet resistance to nitric oxide (NO) donors in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS), relative to nonischemic patients and normal subjects. BACKGROUND: We have shown previously that platelets from patients with SAP are resistant to the antiaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP). METHODS: Extent of adenosine diphosphate (1 micromol/liter)-induced platelet aggregation (impedance aggregometry in whole blood) and inhibition of aggregation by NTG (100 micromol/liter) and SNP (10 micromol/liter) were compared in normal subjects (n = 43), nonischemic patients (those with chest pain but no fixed coronary disease, (n = 35) and patients with SAP (n = 82) or ACS (n = 153). Association of NO resistance with coronary risk factors, coronary artery disease (CAD), intensity of angina and current medication was examined by univariate and multivariate analyses. RESULTS: In patients with SAP and ACS as distinct from nonischemic patients and normal subjects, platelet aggregability was increased (both p < 0.01), and inhibition of aggregation by NTG and SNP was decreased (both p < 0.01). Multivariate analysis revealed that NO resistance occurred significantly more frequently with ACS than with SAP (odds ratio [OR] 2.3:1), and was less common among patients treated with perhexiline (OR 0.3:1) or statins (OR 0.45:1). Therapy with other antianginal drugs, extent of CAD, intensity of angina and coronary risk factors were not associated with variability in platelet responsiveness to NO donor. CONCLUSIONS: Patients with symptomatic ischemic heart disease, especially ACS, exhibit increased platelet aggregability and decreased platelet responsiveness to the antiaggregatory effects of NO donors. The extent of NO resistance in platelets is not correlated with coronary risk factors. Pharmacotherapy with perhexiline and/or statins may improve platelet responsiveness to NO.

Apodization technique for fiber grating fabrication with a halftone transmission amplitude mask.

Experimental results of fiber Bragg gratings fabricated with halftone amplitude transmission masks and 10-cm-long phase masks are presented for the first time to our knowledge. The performance of the devices is evaluated in terms of their spectral characteristics and deviation from linear group delay. Good out-of-band sidelobe suppression of -27 dB and group-delay ripple of ?9.5 ps is achieved for fully apodized grating devices.

Nitrate resistance in platelets from patients with stable angina pectoris.

BACKGROUND: Hemodynamic resistance to nitrates has been previously documented in congestive heart failure. In patients with stable angina pectoris (SAP), we have observed a similar phenomenon: decreased platelet response to disaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP). METHODS AND RESULTS: In blood samples from normal subjects (n=32) and patients with SAP (n=56), we studied effects of NO donors (NTG and SNP) on ADP-induced platelet aggregation and on intraplatelet cGMP. NTG and SNP inhibited platelet aggregation in patients to lesser extents than in normal subjects (P<0.01). The cGMP-elevating efficacy of NTG and SNP was diminished in platelets from patients in comparison with those from normals (P<0.001). Inhibition of the anti-aggregatory effects of NTG and SNP by ODQ, a selective inhibitor of NO-stimulated guanylate cyclase, was significantly less pronounced in patients than in normal subjects. Content of O2- was higher in blood samples from patients than in those from normal subjects (P<0. 01). In blood samples from patients with SAP, but not in normal subjects, the O2- scavenger superoxide dismutase (combined with catalase) suppressed platelet aggregation (P<0.01) and increased the extent of anti-aggregatory effect of SNP (P<0.01). CONCLUSIONS: In patients with SAP, platelets are less responsive to the anti-aggregating and cGMP-stimulating effects of NO donors; this may reflect both reduction in guanylate cyclase sensitivity to NO and inactivation of the released NO by O2-. The implied impairment of anti-platelet efficacy of endogenous NO (in the form of EDRF) may contribute to platelet hyperaggregability associated with angina pectoris.

Metal Ion Quenching Kinetics of DTDCI in Viscous Solution and Nafion Membranes: Model System for Near Infrared Fluorescence Sensing.

Fo¨rster type energy transfer offers opportunities as a sensitive and frequently selective method of monitoring the concentration of analytes in medical sensing applications. However, the fluorescence quenching kinetics observed in microheterogeneous media such as tissue are likely to be less than ideal. In the present article, the quenching kinetics of the carbocyanine dye DTDCI by transition metal ions in solutions and in the microheterogeneous polymer Nafion (a registered trademark of Dupont Corporation) are reported and compared with a view to understanding the complex fluorescence kinetics likely to be encountered in biological media. © 1998 Society of Photo-Optical Instrumentation Engineers.

Multiplexed time-correlated single-photon counting.

We review the technique of multiplexed time-correlated single-photon counting whereby multiple fluorescence decay curves are recorded in parallel by statistically time-sharing a single time-to-amplitude converter. Application of the multiplexing technique to measuring the fluorescence lifetime topography of a self-absorbing sample is demonstrated. Further possibilities are discussed for multiplexed optical fiber sensor networks with built-in intelligence for detecting and discriminating between different metal ions in solution.

Fluorescence quenching by metal ions in lipid bilayers.

Fluorescence quenching of perylene by Co2+ and Ni2+ ions has been investigated both below and above the phase transition temperature in small unilamellar DPPC vesicles. Classic Förster type energy transfer was observed for perylene quenched by Co2+ ions below the phase transition when the effects of donor-donor energy transfer are taken into account. In the liquid crystalline phase a simple diffusion theory incorporating energy transfer was found to model the system well. For quenching by Ni2+ ions both above and below the phase transition temperature in lipid bilayers and in glycerol the data did not follow classic Förster type energy transfer but indicated that an additional quenching mechanism was present. A mechanism other than Förster behaviour was also observed for the quenching by Cr3+ ions in glycerol.

Fabrication of buried channel waveguides on silicon substrates using spin-on glass.

A new process for the deposition of thick (≈10-µm) films of silica and titania-doped silica on silicon substrates is described. Films are built up by repetitive operation of a simple process cycle in which a layer of sol-gel material is deposited by spin coating, then densified by rapid thermal annealing. Stressfree layers are obtained through careful choice of the anneal temperature. Bilayer structures suitable for waveguide fabrication may also be constructed by performing two successive deposition runs using sol-gel precursors with different titania concentrations. These bilayers may be patterned topographically into ridges by using reactive ion etching, and the ridges may be planarized by applying additional layers of sol-gel material to form buried channel waveguides.

Quenching of perylene fluorescence by Co(2+) ions in dipalmitoylphosphatidylcholine (DPPC) vesicles.

We report the fluorescence quenching of perylene by CoCl2·6H2O in small unilamellar DPPC vesicles via energy transfer. At the probe-to-lipid ratio of 1∶200 and quencher to lipid ratios of ≥12.5∶1, donor-donor energy transfer between clustered perylene molecules was observed as well as energy transfer from the perylene molecules to cobalt ions bothabove andbelow the main phase transition temperature of the lipid. The fluorescence quenching of perylene by CoCl2·6H2O in the lipid gel state is shown to be well described by Förster long-range energy transfer when both donor-donor and donor-acceptor energy transfer are considered. In the liquid crystalline phase diffusion of the molecules is described as well as energy transfer. The interaction radiusR 0 for energy transfer from perylene to Co(2+) is found to be ∼13.4±1.1 Å in the gel phase at 303 K, in good agreement with the theoretical value forR 0 of 13.9 Å. In the liquid crystalline phase at 323 K the lower value obtained forR 0, ∼11.3±1.6 Å, is attributed to saturation of the Co(2+) ions at the interfacial region of the bilayer. A diffusion coefficient of (1.06±0.15)×10(-6) cm(2) s(-1) is obtained for perylene-cobalt diffusion in the liquid crystalline phase at 323K.

High-speed optical signal processing potential of grating-coupled waveguide filters.

The application of grating-coupled waveguides to spread spectrum fiber-optic communications systems is described. It is first shown that such a device can act as its own matched filter for impulsive excitation, which allows its use as an encoder and decoder of ultrashort pulses. This is true even in the case of strong coupling, although considerable pulse distortion occurs. A typical performance that might be expected from existing technology is then outlined, and a number of numerical examples are presented to illustrate typical signal processing operations.

Spontaneous regression of testicular seminoma: case report.

A 33-year-old man had a 1-year history of a painless testicular mass and a 2-month history of an enlarging left supraclavicular mass. Biopsy of the supraclavicular mass showed classical seminoma. Massive abdominal lymphadenopathy was demonstrated by computerized tomography. Radical orchiectomy was performed and examination of the specimen showed only fibrous scar tissue consistent with regression of a primary tumor in the testis. While complete regression of a primary testicular tumor with progressive growth of metastases is well recognized in cases of nonseminomatous germ cell tumors, this phenomenon is reported rarely with seminoma.