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Lipopolysaccharide (LPS), a significant virulence factor of gram-negative bacteria, adversely affects female reproduction, especially the maturation and early embryonic development of oocytes, through inducing of inflammatory and oxidative stress-associated toxic responses. Resveratrol (Res), a potent antioxidant, exhibits many beneficial effects on the maturation and developmental competence of oocytes. However, it is unclear whether Res can restore LPS-induced defects in the maturation of oocytes during meiosis. In this study, we used porcine oocytes to explore the protective effects of Res and its underlying mechanism against the toxic impacts of LPS exposure on meiotic maturation and developmental competence of oocytes during meiosis. The oocytes were randomly assigned to a control, LPS-exposed or Res-supplemented group. Nuclear and cytoplasmic maturation was assessed after 26 h (MI) or 44 h (MII) of in vitro maturation (IVM). Our results showed that 10 µM Res significantly improved the rates of oocyte maturation and blastocyst formation after exposure to 15 µg/mL LPS. In addition, Res preserved the normal spindle/chromosome structure and maintained acetylated tubulin levels, actin polymerization and cortical granules (CGs) distribution. Additionally, Res protected mitochondrial content and function, scavenges reactive oxygen species (ROS), and reduced DNA damage and apoptosis in LPS-exposed oocytes. Furthermore, inhibition of SIRT1 by its specific inhibitor EX527 suppressed the recovery of ROS levels, mitochondrial content, and spindle/chromosome structure by Res supplementation. In summary, this study shows that Res can alleviate the impacts of LPS-induced toxicity on meiosis in porcine oocytes by upregulating SIRT1, which ameliorates oxidative stress and increasing mitochondrial content.

Female pubic hair grooming (PHG) habits have changed in the last 20 years. Most studies present findings around female PHG attitudes, practices, and behaviours, lacking data on male attitudes and practices.We explored the attitudes and practices of PHG from male and female perspectives.A cross-sectional convenience survey was conducted online with 1560 male and female young adult participants aged 18 to 25 years. The study was conducted over two time periods (2014 and 2021). The survey explored attitudes, practices, and behaviours around PHG. Descriptive statistics included frequencies and proportions for categorical variables and the median for continuous variables. Males and females were compared using the χSeventy-two percent (n = 471/728) of females and 64.7% (n = 257/728) of males were likely to engage in PHG. Participants were more likely to groom their pubic hair for reasons associated with religion (adjusted odds ratio (aOR): 9.01, 95% CI: 2.87-28.2), comfort when wearing clothing (aOR: 3.85, 95% CI: 1.52-9.71), a neater and cleaner genital appearance (aOR: 3.90, 95% CI: 1.62-9.41) and before attending a healthcare consultation (aOR: 4.79, 95% CI: 2.27-10.09). Moreover, twice as many females compared with male groomers reported watching pornography (69.7% vs 30.3%).Several factors can influence PHG. Our findings demonstrate that the reasons participants engage in PHG practices are for hygiene, aesthetics, comfort, and sexual satisfaction.

Background Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions within the dentato-rubro-olivary pathway, resulting in ocular nystagmus and palatal myoclonus (oculopalatal tremor) but not usually dystonia. Dystonia is an uncommon association, and we present the first reported association of hypertrophic olivary degeneration with bilateral vocal cord dystonia. Case presentation A 33 year old male presented initially with acute hydrocephalus on the background of previous ventriculoperitoneal (VP) shunting for previously treated medulloblastoma. After revision of the VP shunt, the patient developed progressive hiccups and stridor leading to respiratory failure requiring intubation. Ocular pendular nystagmus and palatal myoclonus at 3 Hz was observed. Flexible nasendoscopy (FNE) demonstrated bilateral tonic adduction of the vocal folds with 3 Hz coarse supraglottic, pharyngeal and palatal rhythmic myoclonus. MRI imaging demonstrated T2 hyperintensity within the bilateral inferior olivary nuclei consistent with stage 3 radiological HOD. Conclusions Dystonia is a rarely reported phenomenon in HOD but is not unexpected with the inferior olivary nucleus implicated in dystonic disorders. We report the association of HOD with bilateral vocal cord adductor dystonia, a potentially life threatening condition.

With phase-sensitive optical time-domain reflectometry (Φ-OTDR), an optic fiber can be used as a distributed vibration sensor to perceive the external disturbance along the fiber through the phase variation of the Rayleigh backscatter light. However, due to the inevitable interference fading phenomenon, the signal-to-noise ratio (SNR) of Rayleigh backscatter light at certain points is insufficient, thus affecting the fidelity of vibration sensing. In this paper, we propose the spectrum extraction and the rotated-vector-sum (SERVS) method to suppress the interference fading in the pulse-intensity-coding Φ-OTDR, which applies Golay complementary sequence through acousto-optic modulator (AOM). Benefited from the easier implementation, the experimental results demonstrate that the percentage of fading points can be reduced from 2.98% to 0.33% significantly and the standard deviation of differential phase is also decreased from 0.6556 rad to 0.2901 rad. Also the minimum level of averaged power spectral density (PSD) of the differential phase at whole locations along the fiber is reduced about 6 dB/Hz effectively. For the demodulated disturbance signal, no influence on the SNR is observed thus it maintains a SNR improvement of 8.6 dB compared to the traditional single pulse Φ-OTDR system, achieving a noise floor of 2.38 pϵ/√Hz.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment., Graphical abstract Nanomedicine has demonstrated great potential in achieving specific targeting and amplifying therapeutic efficiency. This review focuses on the recent breakthroughs and targeting strategies to provide insights into nanomedicine for acute respiratory distress syndrome treatment.Image 1

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) in particulate matter that has a diameter of ≤2.5 μm (PM2.5). Studies have demonstrated that BaP exposure causes oocyte meiotic arrest in mice. However, whether BaP exposure also affects oocyte maturation in offspring remains unclear. To test this, female mice were administered BaP before pregnancy to generate BaP-exposed offspring. Our findings showed that BaP exposure reduced the in vitro maturation and increased the abnormalities of meiotic apparatus in offspring oocytes. In addition, BaP exposure reduced the mitochondrial content and intracellular ATP generation, induced early apoptosis, increased reactive oxidative species accumulation and the genomic DNA 5-methylcytosine (5mc) level in offspring oocytes. Along with the abovementioned defective parameters, maternal BaP exposure further compromised the embryo developmental competence of offspring oocytes. In summary, our study demonstrated that maternal BaP exposure compromised offspring oocyte maturation and quality.

Mogroside-rich extract (MGE), the main bioactive component of dried

Accumulating evidence has demonstrated that lipopolysaccharide (LPS) compromises female reproduction, especially oocyte maturation and competence. However, methods to protect oocyte quality from LPS-induced deterioration remain largely unexplored. We previously found that mogroside V (MV) can promote oocyte maturation and embryonic development. However, whether MV can alleviate the adverse effects of LPS exposure on oocyte maturation is unclear. Thus, in this study, we used porcine oocytes as a model to explore the effects of MV administration on LPS-induced oocyte meiotic defects. Our findings show that supplementation with MV protected oocytes from the LPS-mediated reduction in the meiotic maturation rate and the subsequent blastocyst formation rate. In addition, MV alleviated the abnormalities in spindle formation and chromosome alignment, decrease in α-tubulin acetylation levels, the disruption of actin polymerization, and the reductions in mitochondrial contents and lipid droplet contents caused by LPS exposure. Meanwhile, LPS reduced m6A levels in oocytes, but MV restored these epigenetic modifications. Furthermore, MV reduced reactive oxygen species (ROS) levels and early apoptosis in oocytes exposed to LPS. In summary, our study demonstrates that MV can protect oocytes from LPS-induced meiotic defects in part by reducing oxidative stress and maintaining m6A levels.

Artificial light at night (ALAN) exposes us to prolonged illumination, that adversely affects female reproduction. However, it remains to be clarified how prolonged light exposure affects oocyte meiotic maturation and quality. To this end, we exposed female mice to a constant light (CL) of 250 lux for different durations. Our findings showed that CL exposure for 7 weeks reduced the oocyte maturation rate. Meanwhile, CL exposure caused greater abnormalities in spindle assembly and chromosome alignment and a higher rate of oocyte aneuploidy than the regular light dark cycle. CL exposure also induced oxidative stress and caused mitochondrial dysfunction, which resulted in oocyte apoptosis and autophagy. Notably, our results showed that CL exposure reduced the levels of α-tubulin acetylation, DNA methylation at 5 mC, RNA methylation at m6A and histone methylation at H3K4me2 but increased the levels of histone methylation at H3K27me2 in oocytes. In summary, our findings demonstrate that constant bright light exposure causes oocyte meiotic defects and reduces cytoplasmic quality. These results extend the current understanding of ALAN-mediated defects in female reproduction.

The increasing demand for energy and environmental protection has stimulated intensive interest in fundamental research and practical applications. Nickel dichalcogenides (Ni

We present an active infrared monitoring system based on the power-over-fiber technique. The system realizes the following main functions: the power supply via optical fibers, the laser lighting, the image acquisition and processing. In the demonstration system, the high-power laser light (at the wavelength of 808 nm) in the base station is transmitted to the remote unit via a 200-m long multi-mode fiber, whose core diameter is 200 µm. The remote unit includes an optical beam splitter, a power manager module behind a photovoltaic power converter (PPC) to ensure a quasi-maximum power-supply, a camera, a microcontroller, and an optical transmitter. As the laser beam enters the remote unit, it is divided into three parts by an optical beam splitter. The first part is converted by the PPC to provide the required electrical power of the remote unit. Besides, to improve the power-supply ability of PPC, a maximum power point tracking technique is applied, and more than 77% of PPC’s maximum output power can be obtained. The other two parts of the laser beam pass through respective beam-shaping lenses and are used directly for the infrared laser lighting. Therefore, the active infrared monitoring is achieved without extra laser lighting sources. The collected image data are transmitted via another single-mode fiber to the base station for further data processing. Experiment result shows an active and unnoticed image monitoring in the dark environment.

MXene with low band gap and excellent metallic conductivity is a novel ultrathin two-dimensional transition metal carbide, and has been widely used as the photocatalytic carrier of semiconductor material. Herein, ZnO/MXene composites were fabricated by a facile two-step chemical reaction method and their structures and photocatalytic performances were investigated systematically. At lower growth temperatures, ZnO particles were dispersed on the Ti3C2 layers whereas ZnO microrods covered the Ti3C2 layers at higher growth temperatures. Especially, ZnO microrods/MXene composites show good photocatalytic performances. Under UV irradiation, about 97.5% Rhodamine B was degraded by the composite within 18 min and retained more than 90% of the photocatalytic efficiency after 7 cycles. Therefore, ZnO microrods/MXene composites can be regarded as a potential candidate for applications in waste water treatment and environmental protection.

Commercial production of unconventional oil and gas resources will not be easily achieved without large-scale engineering measures, let alone the additional operation cost, increasingly stricter requirement for safety and environment, fluctuating low oil and gas prices, etc., defeating the confidence of those investors. Therefore, unconventional measures are urgently needed to guide the exploration and exploitation of unconventional oil and gas resources. Thus, we put forward the concept of joint exploration and development by integrating research methodologies and operating techniques for a variety of oil and gas resources to simultaneously achieve analysis, construction, gathering and exploitation of multiple hydrocarbon sources. In this way, the annoying interference between the produced mixture of hydrocarbon flow resulting in the reduction of single-well flowrate will be possibly turned into a dynamic mutual force to enhance the well's flowrate. We also point out that the inevitability of joint exploration and development is determined by the occurrence conditions of oil and gas resources, its feasibility relies on the advancement of technologies, and its arduous and long-term nature is attributed to the current energy market and environment. In spite of various problems and difficulties, we believe that joint exploration and development will be a feasible option to achieve both cost reduction and production & benefit enhancement, boost investors' confidence, raise energy comprehensive utilization, and enhance energy supply efficiency. In conclusion, the advantages of joint exploration and development outweigh its disadvantages for both countries and enterprises.

3D Ni3S2 /Ni foam electrocatalysts were successfully synthesized through a facile one-step solvothermal method in Methanol, Ethanol and Ethylene glycol solutions, then directly applied as the electrodes for hydrogen evolution reaction and the oxygen evolution reaction. The electrochemical measurements demonstrated the excellent electrochemical activity and stability toward water splitting, Moreover, the electrocatalytic behaviors of the samples were also investigated at various temperatures (0–60 °C), systematically. Remarkably, the electrolyzer based on 3D Ni3S2 /Ni foam electrodes delivered a current density of 20 mA cm−2 at a cell of voltage of 1.89 V and shows excellent long-term stability. The porous three dimensional structure of Ni3S2/NF electrodes, electrical conductivity, and large electrochemical surface area are responsible for the excellent electrocatalytic performances The study presents a feasible and effective strategy to prepare highly efficient electrocatalysts for water splitting.

Abstract Platelet-activating factor (PAF, 1- O -alkyl-2-acetyl- sn -glycero-3-phosphocholine) is a potent phospholipid mediator of numerous inflammatory and thrombotic responses. The purpose of this study was to determine if PAF synthesis is elevated in damaged coronary arteries after a sustained period of cyclic flow variation (CFV), a phenomenon caused by alternating periods of thrombosis and reperfusion at sites of endothelial injury. Cyclic flow was established and maintained in the left anterior descending coronary arteries (LADs) of 10 dogs. After 8 hours of CFV, the section of damaged LAD containing the thrombus and control sections of the circumflex artery, carotid artery, and saphenous vein was excised, and the total lipids were extracted. The PAF was then purified by silica column chromatography and high-performance liquid chromatography and assayed by both a rabbit platelet bioassay and a PAF radioimmunoassay. With the platelet bioassay, PAF levels of 8.9±4.0 (range, 4.8 to 15.5) pg/mg wet wt were found in the damaged LADs from the 10 dogs. This PAF bioactivity was completely inhibited by a PAF receptor antagonist. When the radioimmunoassay was used, slightly higher PAF levels of 16.3±12.9 (range, 4.5 to 41.8) pg/mg wet wt were observed in the LADs. Overall, these PAF levels were 3- to 64-fold higher than in the control vessels when either assay method was used. Although increases in PAF were observed in the damaged LADs, measurements of PAF in blood samples taken from the LAD and the aorta (control) failed to demonstrate any site-specific increase of PAF in the blood. In related experiments, PAF was also measured in 23 endarterectomy samples taken from the coronary arteries of 16 patients with severe atherosclerosis. The PAF levels in these samples were highly variable (2.9±2.2 [range, 0.3 to 8.5] pg/mg wet wt) and showed no correlation with tissue mass, suggesting that PAF is affected by factors other than the simple presence of atherosclerotic tissue in the vessel. These findings provide direct evidence that PAF is synthesized locally at the site of endothelial injury during thrombosis and that PAF accumulates in the atherosclerotic plaque of some patients with advanced coronary artery disease.

The objectives of this study were to test the hypotheses that thrombin inhibitors 1) enhance tissue-type plasminogen activator (t-PA)-induced coronary thrombolysis and 2) prevent or delay coronary artery reocclusion. Seventy-one dogs developed occlusive coronary thrombi after introducing a copper coil into the left anterior descending coronary artery (LAD). Coronary blood flows were monitored by an externally positioned pulsed Doppler flow probe. t-PA was given with or without heparin at different times after LAD occlusions. In some experiments, hirugen, a synthetic hirudin-based peptide and specific thrombin inhibitor, was given as 4 mg/kg i.v. bolus and 3 mg.kg-1.h-1 i.v. infusion at 30 min after LAD occlusion with t-PA and a bolus of heparin. Thrombolysis times were significantly shorter in t-PA- and heparin-treated dogs than in dogs treated with t-PA alone. Reocclusion times were significantly longer in t-PA- and heparin-treated dogs than in dogs treated with t-PA alone. Continuous heparin infusions prolonged reocclusion times to greater than 180 min in all treated dogs. The addition of hirugen to t-PA plus one bolus heparin prolonged reocclusion times to 90 +/- 6 min in dogs with 30-min thrombi. Thus heparin enhances t-PA-induced thrombolysis and delays reocclusion. Addition of a specific thrombin inhibitor, such as hirugen, to heparin enhances its effect on delaying reocclusion.

A new acoustic temperature field reconstruction algorithm is proposed. First expand the sound slowness function over a finite set of inverse multiquadrics series, and then obtain a stable solution by using truncated singular value decomposition of matrix. Reconstructions of five temperature field models by using exact and corrupted time-of-flight data demonstrate that the new algorithm has good ability in complex temperature field reconstruction.

The key for acoustic temperature field measurement is to measure acoustic travel-time accurately. Restricted by sample interval, the acoustic travel-time estimation accuracy by fast correlating of the transmitted and the received signals is not high enough. A new method based on fast correlation combined with up-sampling is proposed. Ideal anti-imaging filters are implemented in frequency domain. Simulation research in MATLAB shows that it has much higher estimation accuracy compared with the fast correlation method. The larger the up-sampling factor, the higher the accuracy will be.

The key for acoustic temperature field measurement is to measure acoustic travel-time accurately. An acoustic travel-time measurement system based on virtual instrument for acoustic temperature field monitoring is introduced. The estimation methods of travel-time using cross-correlation and interpolation are proposed and investigated. Simulation research in MATLAB shows that: restricted by the sampling interval, the accuracy of acoustic travel-time estimation by directly cross-correlating of the transmitted and received sampling signals is not high; a higher accuracy can be achieved by cubic spline interpolating the part cross-correlogram near the cross-correlation peak when the noise is weak; if the noise is moderate or strong, a higher accuracy can be achieved by linear interpolating the transmitted and received sampling signals before calculating their cross-correlation function.

BACKGROUND Platelets play an important role in the pathophysiology of acute coronary syndromes. The interaction between the platelet glycoprotein Ib receptor and von Willebrand factor is a critical event allowing platelet adhesion and aggregation and subsequent thrombus formation in vessels with high shear rates and damaged endothelium. Therefore, we tested the hypotheses that VCL, an antagonist of von Willebrand-glycoprotein Ib binding domain, (1) attenuates/abolishes cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates and (2) reduces botrocetin-induced platelet aggregation in vitro after intravenous in vivo administration. METHODS AND RESULTS Cyclic flow variations were established in anesthetized, open-chest baboons (n = 18). The baboons were divided into three groups. One group (n = 8) received a bolus of VCL (4 mg/kg IV) followed by an infusion (6 mg.kg-1.h-1) for 90 minutes (schedule A). Another group (n = 6) received a 2-mg/kg bolus followed by an infusion of 3 mg.kg-1.h-1 for 90 minutes (schedule B). The third group received a placebo infusion of normal saline. Under dosing schedule A, cyclic flow variations were abolished in 7 of 8 baboons after 33 +/- 18 minutes and markedly attenuated in 1. The frequency of cyclic flow variations fell from 18 +/- 9.4 per hour during the control period to 1 +/- 2.5 per hour after VCL infusion, P < .002. After cessation of infusion, cyclic flow variations remained abolished in 5 of 7 animals for > 3 hours and returned in 2 of 7 after 2 to 2.5 hours. Under schedule B, cyclic flow variations were abolished in 3 of 6 baboons and markedly reduced in the remainder. The number of cyclic flow variations fell from 17 +/- 4.8 per hour during the control period to 5 +/- 4.9 per hour after the VCL infusion, P < .001. The cyclic flow variations returned spontaneously at 38 +/- 40 minutes under this dosing schedule. Placebo infusion of saline had no effect on cyclic flow frequency or severity. VCL administration was associated with slight prolongation in bleeding time and a reduction in botrocetin-induced platelet aggregation. The bleeding time increased from a control time of 88 +/- 32 to 276 +/- 204 seconds, P < .03, and from 142 +/- 28 to 176 +/- 36 seconds, P = .056, for schedules A and B, respectively. VCL decreased platelet aggregation in response to botrocetin (20 micrograms/mL), from a control value of 66 +/- 30.3 to 33 +/- 31.3 omega, P < .05, and from 64 +/- 23.5 to 46 +/- 15.8 omega, P = .006, for dosing schedules A and B, respectively. CONCLUSIONS Therefore, administration of a peptide fragment corresponding to von Willebrand-glycoprotein Ib binding domain (1) is effective in abolishing cyclic flow variations in stenosed, endothelium-injured coronary arteries and (2) reduces platelet aggregation in vivo in response to botrocetin in nonhuman primates.

BACKGROUND This study was designed to test the hypothesis that clopidogrel, a potent inhibitor of platelet aggregation, can eliminate cyclic flow variations in stenosed and endothelium-injured coronary and femoral arteries in nonhuman primates. METHODS AND RESULTS We studied five anesthetized, open-chest baboons. Blood flow velocity in the coronary and femoral arteries was monitored by pulsed Doppler flow probes placed around the arteries. Cyclic flow variations were established by mechanically injuring the endothelium of the arteries and by narrowing the arteries with external constrictors. Clopidogrel (10 to 20 mg/kg i.v. bolus plus 2.5 mg.kg-1 x h-1 continuous infusion) was administered 60 minutes after cyclic flow variations were established. Clopidogrel abolished cyclic flow variations in the coronary and femoral arteries of all five baboons (frequency of cyclic flow variations, 0/h versus 14/h at baseline, P < .001). Then epinephrine was infused (maximum average dose, 2.2 micrograms.kg-1 x min-1 i.v.). Epinephrine did not restore cyclic flow variations in the coronary or femoral arteries of any baboon. Before treatment with clopidogrel, ADP, collagen, and U46619, a thromboxane A2 mimetic, induced dose-dependent platelet aggregation in vitro. Serotonin, however, did not induce platelet aggregation in vitro. Clopidogrel given in vivo completely inhibited ADP-induced platelet aggregation and significantly diminished collagen- and U46619-induced platelet aggregation in vitro. CONCLUSIONS Clopidogrel eliminates cyclic flow variations in stenosed and endothelium-injured coronary and femoral arteries of nonhuman primates at least in part by antagonizing the platelet proaggregatory effects of ADP and thromboxane A2.

The goal of this study was to test the hypotheses that endogenous ADP plays an important role in vivo in mediating platelet aggregation and cyclic coronary artery blood flow variations (CFVs) in stenosed and endothelium-injured coronary arteries in an experimental canine model. Anesthetized animals were studied and coronary blood flow velocities monitored by a pulsed Doppler flow probe positioned around the left anterior descending coronary artery. CFVs were established by an external constrictor positioned at sites with injured endothelium. Apyrase, an ADP-removing enzyme, was infused into the left anterior descending coronary artery (0.3-1.8 units/min) 30 minutes or 2 hours after the establishment of CFVs. Complete abolition of CFVs was achieved in 81% (13/16) of dogs with 30-minute CFVs and in 83% (five of six) of dogs with 2-hour CFVs. In other dogs, a potent inhibitor of ADP-induced platelet aggregation, clopidogrel, was administered as a 10 mg/kg i.v. bolus and a 2.5 mg/kg/hr infusion 30 minutes and 3 hours after the establishment of CFVs. This treatment resulted in complete abolition of CFVs in 14 dogs (100%) with either 30-minute or 3-hour CFVs. Epinephrine was infused into some dogs after CFVs had ceased as a result of either apyrase or clopidogrel administration and into some dogs in whom SQ29548, a thromboxane A2 receptor antagonist, had been given when apyrase failed to abolish CFVs. Epinephrine restored CFVs in all dogs treated with apyrase alone, 67% (four of six) of dogs treated with the combination of apyrase and SQ29548, and 29% (two of seven) of dogs treated with clopidogrel. The plasma epinephrine levels required for CFV restoration were 20 times higher than baseline values in dogs receiving apyrase alone, 100 times higher when a combination of apyrase and SQ29548 had been given, and more than 5,000 times higher in dogs receiving clopidogrel. In vitro studies showed that apyrase only inhibited ADP-induced platelet aggregation, whereas clopidogrel not only inhibited ADP-induced platelet aggregation, but also reduced platelet aggregation induced by the thromboxane mimetic U46619 and serotonin. These data suggest that 1) ADP is an important mediator of platelet aggregation and CFVs in vivo and 2) combined inhibition of thromboxane A2 and ADP's effects provides marked protection against CFVs in experimentally stenosed and endothelium-injured canine coronary arteries. These data and our previous observations are consistent with the possibility that specific antagonists of thromboxane A2, serotonin, and ADP, alone and together, may provide substantial protection against platelet aggregation leading to CFVs at sites of endothelial injury and coronary artery stenosis.