Ultrafast laser surgery probe with a calcium fluoride miniaturized objective for bone ablation

We present a miniaturized ultrafast laser surgery probe with improved miniaturized optics to deliver higher peak powers and enable higher surgical speeds than previously possible. A custom-built miniaturized CaF₂ objective showed no evidence of the strong multiphoton absorption observed in our previous ZnS-based probe, enabling higher laser power delivery to the tissue surface for ablation. A Kagome fiber delivered ultrashort pulses from a high repetition rate fiber laser to the objective, producing a focal beam radius of 1.96 μm and covering a 90×90 μm² scan area. The probe delivered the maximum available fiber laser power, providing fluences >6 J/cm² at the tissue surface at 53% transmission efficiency. We characterized the probe’s performance through a parametric ablation study on bovine cortical bone and defined optimal operating parameters for surgery using an experimental- and simulation-based approach. The entire opto-mechanical system, enclosed within a 5-mm diameter housing with a 2.6-mm diameter probe tip, achieved material removal rates >0.1 mm³/min, however removal rates were ultimately limited by the available laser power. Towards a next generation surgery probe, we simulated maximum material removal rates when using a higher power fiber laser and found that removal rates >2 mm³/min could be attained through appropriate selection of laser surgery parameters. With future development, the device presented here can serve as a precise surgical tool with clinically viable speeds for delicate applications such as spinal decompression surgeries.     

Penetration of chlorhexidine into human skin

This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 μm following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 ± 0.047 and 0.077 ± 0.015 μg/mg tissue within the top 100 μm), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 μg/mg tissue below 300 μm). After 24 h of exposure, there was more chlorhexidine within the upper 100-μm sections (7.88 ± 1.37 μg/mg tissue); however, the levels remained low (less than 1 μg/mg tissue) at depths below 300 μm. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice.     

Yttrium(iii) coordination polymer micro/nanospheres with single ligand and dual ligands

In this work, yttrium(iii) coordination polymer (Y-CP) ball-flower-shaped microparticles with diameters ranging from 5 μm to 10 μm were synthesized using vanillin and asparagine as ligands under solvothermal conditions at 150 °C for 24 h. Then, we investigated the reaction influencing factors such as the concentration of reactants (involving vanillin, asparagine, and rare earth), reaction temperature, and reaction time. Both uniform and sphere-like nanoparticles with an average size of ∼50 nm were obtained using vanillin as a ligand at 120 °C for 12 h. Furthermore, the products were characterized and the results of cytotoxicity research demonstrated that the nanoparticles had low cytotoxicity and the coordination polymer nanospheres were perfectly biocompatible.

In this work, yttrium (III) coordination polymer (Y-CP) ball-flower-shaped microparticles with diameters ranging from 5 μm to 10 μm were synthesized using vanillin and asparagine as ligands under solvothermal conditions at 150 °C for 24 h.     

Optimizing deep bone ablation by means of a microsecond Er:YAG laser and a novel water microjet irrigation system

The microsecond Er:YAG pulsed laser with a wavelength of λ = 2.94 μm has been widely used in the medical field, particularly for ablating dental tissues. Since bone and dental tissues have similar compositions, consisting of mineralized and rigid structures, the Er:YAG laser represents a promising tool for laserosteotomy applications. In this study, we explored the use of the Er:YAG laser for deep bone ablation, in an attempt to optimize its performance and identify its limitations. Tissue irrigation and the laser settings were optimized independently. We propose an automated irrigation feedback system capable of recognizing the temperature of the tissue and delivering water accordingly. The irrigation system used consists of a thin 50 μm diameter water jet. The water jet was able to penetrate deep into the crater during ablation, with a laminar flow length of 15 cm, ensuring the irrigation of deeper layers unreachable by conventional spray systems. Once the irrigation was optimized, ablation was considered independently of the irrigation water. In this way, we could better understand and adjust the laser parameters to suit our needs. We obtained line cuts as deep as 21 mm without causing any visible thermal damage to the surrounding tissue. The automated experimental setup proposed here has the potential to support deeper and faster ablation in laserosteotomy applications.     

Sheath-less high throughput inertial separation of small microparticles in spiral microchannels with trapezoidal cross-section

Various mechanisms of different designs have emerged for the purpose of microparticle separation and cell sorting. The main goals behind such designs are to create high throughput and high purity sample isolation. In this study, high efficiency, high throughput and precise separation of microparticles under inertial lift and drag forces induced by trapezoidal curvilinear channels are reported. This work is the first to focus and recover 2 from 5 μm and 2 from 10 μm particles in spiral channels in a sheath-less flow device, which reduces the overall complexity of the system and allows for higher throughput. The new microfluidic chip design is fabricated in glass using femtosecond laser ablation. In addition, mathematical force calculations were conducted during the design phase of the microfluidic channels and compared with experiments. The results show a close prediction of the equilibrium position of the tested microparticles.

This work is the first to focus and recover 2 from 5 μm and 2 from 10 μm particles in spiral channels in a sheath-less flow device, which reduces the overall complexity of the system and allows for higher throughput.     

Silver nanoribbons achieved by picosecond ablation using cylindrical focusing and SERS-based trace detection of TNT

We report the fabrication of silver nanoribbons by picosecond laser ablation of bulk silver (Ag) targets submerged in double distilled water (DDW) using a cylindrical focusing geometry. The laser ablation was performed by ∼2 picosecond laser pulses and the corresponding light sheet engendered by a cylindrical lens of focal length ∼4.5 cm. The input pulse energies employed at a wavelength ∼800 nm in the experiments were ∼1000 μJ, ∼1200 μJ, and ∼1400 μJ. In contrast to the case of ablation with spherical lenses, cylindrical lens ablation produced nanoparticles (NPs) and nanostructures (NSs) in 20% less time. The data obtained from the optical characterizations exemplify that localized surface plasmon resonance (LSPR) was observed at 406 nm, 408 nm, and 410 nm for the input energies of ∼1000 μJ, ∼1200 μJ, and ∼1400 μJ, respectively. Interestingly, it was observed that the ablation performed at an input energy of ∼1200 μJ demonstrated the fabrication of Ag nanoribbons rather than the formation of Ag NPs. Selected area electron diffraction (SAED) data of the nanoribbons recorded revealed their crystalline phase and linear morphology. Ag nanomaterials (NPs and ribbons) synthesized in these experiments were employed to detect the explosive molecules of 2,4,6-trinitrotoluene (TNT) at a concentration 25 nM using the technique of surface enhanced Raman scattering. The enhancement factor in the case of Ag nanoribbons (width of ∼20–30 nm, length of ∼0.6–2 μm), obtained using the cylindrical focussing geometry at input pulse energies of ∼1200 μJ, was estimated to be ∼10⁷ for the 1362 cm⁻¹ mode, corresponding to the symmetric NO₂ stretch of TNT.

We synthesised silver nanomaterials by laser ablation of Ag in DDW with ∼2 ps pulses using cylindrical focussing geometry. Ag nanoribbons were obtained at ∼1200 μJ input pulse and were utilized to detect TNT via surface enhanced Raman scattering studies.     

28 MHz swept source at 1.0 μm for ultrafast quantitative phase imaging

Emerging high-throughput optical imaging modalities, in particular those providing phase information, necessitate a demanding speed regime (e.g. megahertz sweep rate) for those conventional swept sources; while an effective solution is yet to be demonstrated. We demonstrate a stable breathing laser as inertia-free swept source (BLISS) operating at a wavelength sweep rate of 28 MHz, particularly for the ultrafast interferometric imaging modality at 1.0 μm. Leveraging a tunable dispersion compensation element inside the laser cavity, the wavelength sweep range of BLISS can be tuned from ~10 nm to ~63 nm. It exhibits a good intensity stability, which is quantified by the ratio of standard deviation to the mean of the pulse intensity, i.e. 1.6%. Its excellent wavelength repeatability, <0.05% per sweep, enables the single-shot imaging at an ultrafast line-scan rate without averaging. To showcase its potential applications, it is applied to the ultrafast (28-MHz line-scan rate) interferometric time-stretch (iTS) microscope to provide quantitative morphological information on a biological specimen at a lateral resolution of 1.2 μm. This fiber-based inertia-free swept source is demonstrated to be robust and broadband, and can be applied to other established imaging modalities, such as optical coherence tomography (OCT), of which an axial resolution better than 12 μm can be achieved.OCIS codes: (140.4050) Mode-locked lasers, (140.3615) Lasers, ytterbium, (110.3175) Interferometric imaging     

Optical modulation of microfibers and application to ultrafast fiber lasers

Microfibers with different waist diameters were prepared successfully by a flame-brushing technique. Their saturable absorption properties were investigated. The non-saturable loss and modulation depth both decreased with the increase of the diameter. According to the mode distribution of microfibers with a waist diameter of 25 μm, it could be supposed that the evanescent field effect may be useful for microfibers being saturable absorbers (SAs). Based on the 25 μm-diameter microfiber, an all-fiber-structure mode-locked fiber laser was achieved successfully with long term stability in the span of a week. The results indicated that microfibers with suitable diameters were excellent SAs. To the best of our knowledge, this is first report on the usage of microfibers as a SA for building ultrafast fiber lasers.

Microfibers with suitable diameters were used as saturable absorbers, realizing an all-fiber-structure mode-locked fiber laser.     

Polymeric nanoparticles based on carboxymethyl chitosan in combination with painless microneedle therapy systems for enhancing transdermal insulin delivery

Biodegradable nanoparticles (NPs) have been frequently used as insulin transdermal delivery vehicles due to their grand bioavailability, better encapsulation, controlled release and less toxic properties. However, the skin''s barrier properties prevent insulin-loaded NP permeation at useful levels. Nowadays, microneedles have been spotlighted as novel transdermal delivery systems due to their advantages such as painlessness, efficient penetration and no hazardous residues. Herein, we introduce polymeric nanocarriers based on carboxymethyl chitosan (CMCS) for insulin delivery, combining with microneedle therapy systems, which can rapidly deliver insulin (INS) into the skin. The resulting CMCS-based nanocarriers are spherical nanoparticles with a mean size around 200 nm, which could generate supramolecular micelles to effectively encapsulate insulin (EE% = 83.78 ± 3.73%). A nanocrystalline microneedle array (6 × 6, 75/150 μm) was used to penetrate the stratum corneum (SC) for enhancing transdermal insulin delivery, while minimizing the pain sensation caused by intravenous injection. Compared with the transdermal rate of passive diffusion [2.77 ± 0.64 μg (cm⁻² h⁻¹)], the transdermal rate of the insulin-loaded NP combined with microneedle penetration shows a 4.2-fold increase [10.24 ± 1.06 μg (cm⁻² h⁻¹)] from permeation experiment in vitro. In vivo hypoglycemic experiments demonstrate the potential of using nanocarrier combination with microneedle arrays for painless insulin delivery through the skin in a clinical setting. Thus, the developed combination scheme of nanoparticles and microneedle arrays offers an effective, user-friendly, and low-toxicity option for diabetes patients requiring long-term and multiple treatments.

Biodegradable nanoparticles (NPs) have been frequently used as insulin transdermal delivery vehicles due to their grand bioavailability, better encapsulation, controlled release and less toxic properties.     

High-throughput multiphoton-induced three-dimensional ablation and imaging for biotissues

In this study, a temporal focusing-based high-throughput multiphoton-induced ablation system with axially-resolved widefield multiphoton excitation has been successfully applied to rapidly disrupt biotissues. Experimental results demonstrate that this technique features high efficiency for achieving large-area laser ablation without causing serious photothermal damage in non-ablated regions. Furthermore, the rate of tissue processing can reach around 1.6 × 10⁶ μm³/s in chicken tendon. Moreover, the temporal focusing-based multiphoton system can be efficiently utilized in optical imaging through iterating high-throughput multiphoton-induced ablation machining followed by widefield optical sectioning; hence, it has the potential to obtain molecular images for a whole bio-specimen.OCIS codes: (140.3390) Laser materials processing, (170.1020) Ablation of tissue, (190.4180) Multiphoton processes     

Enhanced inertial focusing of microparticles and cells by integrating trapezoidal microchambers in spiral microfluidic channels

In this work, manipulating width and equilibrium position of fluorescent microparticles in spiral microchannel fractionation devices by embedding microchambers along the last turn of a spiral is reported. Microchambers with different shapes and sizes were tested at Reynolds numbers between 15.7 and 156.6 (100–1000 μL min⁻¹) to observe focusing of 2, 5 and 10 μm fluorescent microparticles. This paper also discusses the fabrication process of the microfluidic chips with femtosecond laser ablation on glass wafers, as well as a particle imaging velocimetry (μPIV) study of microparticle trajectories inside a microchamber. It could be demonstrated with an improved final design with inclined microchamber side walls, that the 2 μm particle equilibrium position is shifted towards the inner wall by ∼27 μm and the focusing line''s width is reduced by ∼18 μm. Finally, Saccharomyces cerevisiae yeast cells were tested in the final chip and a cell focusing efficiency of 99.1% is achieved.

In this work, manipulating width and equilibrium position of fluorescent microparticles in spiral microchannel fractionation devices by embedding microchambers along the last turn of a spiral is reported.     

Explosives sensing using Ag–Cu alloy nanoparticles synthesized by femtosecond laser ablation and irradiation

Herein we demonstrate the synthesis of Ag–Cu alloy NPs through a consecutive two-step process; laser ablation followed by laser irradiation. Initially, pure Ag and Cu NPs were produced individually using the laser ablation in liquid technique (with ∼50 femtosecond pulses at 800 nm) which was followed by laser irradiation of the mixed Ag and Cu NPs in equal volume. These Ag, Cu, and Ag–Cu NPs were characterised by UV-visible absorption, HRTEM and XRD techniques. The alloy formation was confirmed by the presence of a single surface plasmon resonance peak in absorption spectra and elemental mapping using FESEM techniques. Furthermore, the results from surface enhanced Raman scattering (SERS) studies performed for the methylene blue (MB) molecule suggested that Ag–Cu alloy NPs demonstrate a higher enhancement factor (EF) compared to pure Ag/Cu NPs. Additionally, SERS studies of Ag–Cu alloy NPs were implemented for the detection of explosive molecules such as picric acid (PA – 5 μM), ammonium nitrate (AN – 5 μM) and the dye molecule methylene blue (MB – 5 nM). These alloy NPs exhibited superiority in the detection of various analyte molecules with good reproducibility and high sensitivity with EFs in the range of 10⁴ to 10⁷.

Herein we demonstrate the synthesis of Ag–Cu alloy NPs through a consecutive two-step process; laser ablation followed by laser irradiation.     

Fabrication of paper microfluidic devices using a toner laser printer

This paper describes a method to fabricate microfluidic paper-based analytical devices (μPADs) using a toner laser printer. Multiple methods have been reported for the fabrication of μPADs for point-of-care diagnostics and environmental monitoring. Despite successful demonstrations, however, existing fabrication methods depend on particular printers, in-house instruments, and synthetic materials. In particular, recent discontinuation of the solid wax printer has made it difficult to fabricate μPADs with readily available instruments. Herein we reported the fabrication of μPADs using the most widely available type of printer: a toner laser printer. Heating of printed toner at 200 °C allowed the printed toner to reflow, and the spreading of the hydrophobic polymer through the filter paper was characterized. Using the developed μPADs, we conducted model colorimetric assays for glucose and bovine serum albumin (BSA). We found that heating of filter paper at 200 °C for 60 min caused the pyrolysis of cellulose in the paper. The pyrolysis resulted in the formation of aldehydes that could interfere with molecular assays involving redox reactions. To overcome this problem, we confirmed that the removal of the aldehyde could be readily achieved by washing the μPADs with aqueous bleach. Overall, the developed fabrication method should be compatible with most toner laser printers and will make μPADs accessible in resource-limited circumstances.

We developed a method to fabricate microfluidic paper-based analytical devices (μPADs) using a toner laser printer. We addressed a potential problem of pyrolysis that resulted from long duration of heating required for the penetration of the toner.     

Development of a high power supercontinuum source in the 1.7 μm wavelength region for highly penetrative ultrahigh-resolution optical coherence tomography

We developed a high power supercontinuum source at a center wavelength of 1.7 μm to demonstrate highly penetrative ultrahigh-resolution optical coherence tomography (UHR-OCT). A single-wall carbon nanotube dispersed in polyimide film was used as a transparent saturable absorber in the cavity configuration and a high-repetition-rate ultrashort-pulse fiber laser was realized. The developed SC source had an output power of 60 mW, a bandwidth of 242 nm full-width at half maximum, and a repetition rate of 110 MHz. The average power and repetition rate were approximately twice as large as those of our previous SC source [20]. Using the developed SC source, UHR-OCT imaging was demonstrated. A sensitivity of 105 dB and an axial resolution of 3.2 μm in biological tissue were achieved. We compared the UHR-OCT images of some biological tissue samples measured with the developed SC source, the previous one, and one operating in the 1.3 μm wavelength region. We confirmed that the developed SC source had improved sensitivity and penetration depth for low-water-absorption samples.OCIS codes: (110.4500) Optical coherence tomography, (170.3880) Medical and biological imaging     

Characterization of three-point bending properties of metal–resin interpenetrating phase composites

Metal–resin composites provide improved combinations of mechanical properties of raw materials. A novel metal–resin interpenetrating phase composite (IPCs) has been fabricated by spontaneously infiltrating unsaturated polyester resin into porous short-fiber preforms under vacuum conditions. In this study, three-point bending experiments are performed to characterize the bending properties of the IPCs. The fractographs after bending are examined to distinguish their characteristics. The flexural strength increases almost linearly from 42 ± 4 MPa to 119 ± 5 MPa in the in-plane direction and 59 ± 4 MPa to 151 ± 8 MPa in the through-thickness direction with an increasing fiber fraction ranging from 16.78 vol% to 32.11 vol%. The structures and bending properties of the IPCs exhibit significant anisotropy. Compared with the in-plane direction, higher bending strength and flexural modulus with smaller displacement at maximum bending force are observed in the through-thickness direction. The finer fibers contribute to improving the flexural strength (from 76 ± 6 MPa to 98 ± 5 MPa for the IPCs with about 23 vol% fiber fraction from 160 μm to 90 μm fiber diameters in the in-plane directions) and modulus. The fracture of the IPC after bending presents different appearances in different directions and the anisotropy becomes less severe with decreasing fiber fraction. Resin fracture, fiber necking and fracture, and debonding are the main fracture mechanisms.

Three-point bending properties of the metal–resin IPCs exhibit anisotropy. Flexural strength increases with increasing fiber fractions and finer fibers improve the properties. The fracture shows both brittle and plastic characteristics.     

Band offset and an ultra-fast response UV-VIS photodetector in γ-In2Se3/p-Si heterojunction heterostructures

High-quality γ-In₂Se₃ thin films and a γ-In₂Se₃/p-Si heterojunction were prepared using pulse laser deposition (PLD). The band offset of this heterojunction was studied by XPS and the band structure was found to be type II structure. The valence band offset (ΔE_v) and the conduction band offset (ΔE_c) of the heterojunction were determined to be 1.2 ± 0.1 eV and 0.27 ± 0.1 eV, respectively. The γ-In₂Se₃/p-Si heterojunction photodetector has high responsivity under UV to visible light illumination. The heterojunction exhibits highly stable photodetection characteristics with an ultrafast response/recovery time of 15/366 μs. The ultrafast response time was attributed to type II structure band alignment, which was good for the separation of electron–hole pairs and it can quickly reduce recombination. These excellent properties make γ-In₂Se₃/p-Si heterojunctions a promising candidate for photodetector applications.

High-quality γ-In₂Se₃ thin films and a γ-In₂Se₃/p-Si heterojunction were prepared using pulse laser deposition (PLD).     

In-vivo imaging of psoriatic lesions with polarization multispectral dermoscopy and multiphoton microscopy

Psoriasis is a skin autoimmune disease characterized by hyperkeratosis, hyperproliferation of the epidermis and dilatation of dermal papillary blood vessels. Healthy skin (5 volunteers) and psoriatic lesions (3 patients) were visualized in vivo, with high contrast and resolution, with a Polarization Multispectral Dermoscope and a Multiphoton Microscope. Psoriatic features were identified and quantified. The effective diameter of the superficial blood vessels was measured at 35.2 ± 7.2 μm and the elongated dermal papillae had an effective diameter of 64.2 ± 22.6 μm. The methodologies developed could be employed for quantitative diagnostic purposes and furthermore serve as a monitoring method of the effect of personalized treatments.OCIS codes: (180.4315) Nonlinear microscopy, (170.1870) Dermatology, (100.2980) Image enhancement, (170.6900) Three-dimensional microscopy, (170.6510) Spectroscopy, tissue diagnostics     

Spectrally-selective mid-IR laser-induced inactivation of pathogenic bacteria

Micrometer-thick layers of Pseudomonas aeruginosa bacteria were prepared on fluorite substrates and scanned by focused mid-IR femtosecond laser radiation that was spectrally tuned to achieve the selective excitation of either the stretching C–H vibrations (3 μm), or stretching C = O, C–N vibrations (6 μm) of the amide groups in the bacteria. The enhanced biocidal efficiency of the latter selective excitation, compared to the more uniform 3-μm laser excitation, was demonstrated by performing viability assays of laser-treated bacterial layers. The bacterial inactivation by the 6-μm ultrashort laser pulses is attributed to dissociative denaturation of lipids and proteins in the cell membranes and intra-cell nucleic acids.     

Preparation and investigation of a novel iodine-based visible polyvinyl alcohol embolization material

Polyvinyl alcohol (PVA) embolization particles, currently used in clinical practice, have good expansibility and are capable of permanent embolization. However, the lack of adhesion of embolization particles contributes to facilitated recanalization after embolization, while the lack of visualization facilitates misembolization. At present, embolization materials with good expansion, adhesion, and visualization potential are urgently required in clinical practice. Here, we report the development of PVA/gelatin/iohexol (I) fiber blocks as a novel embolization material for liver embolization in rats. In our work, electrospun PVA/gelatin/I nanofibrous mats were first prepared, homogenized, centrifuged in a gradient manner, and freeze-dried to obtain fiber blocks (fiber diameter ​= ​296.2 ​± ​74.23 ​nm, length 99.6 ​± ​17.0 ​μm ​× ​width 46.9 ​± ​13.3 ​μm). The fiber blocks exhibited excellent cytocompatibility and hemocompatibility. Fiber blocks with a PVA/gelatin/I mass ratio of 8:2:10 were selected due to their excellent expansibility and adhesive properties. The PVA/gelatin/I fiber blocks display excellent liver embolic effects and computed tomography (CT) imaging potential due to a combination of the following characteristics: expansibility of PVA and gelatin, adhesive property of gelatin, and CT imaging potential of I. The developed fiber block material is an embolic material that may potentially be used in interventional medicine.     

Pharmacology of a New 1-Oxa-β-lactam (LY127935) in Normal Volunteers

The pharmacokinetics of 1-oxa-β-lactam (LY127935), a new semisynthetic β-lactam antibiotic, was studied in four healthy adult volunteers (mean age of 27 years, mean body surface area ± standard error [SE] of 1.87 ± 0.08 m², and mean creatinine clearance ± SE of 116 ± 12 ml/min per 1.73 m²). Immediately after completion of a 1-g, 20-min intravenous (i.v.) infusion, the mean serum level ± SE was 70.7 ± 8.5 μg/ml. After a 1-g intramuscular (i.m.) injection, peak serum levels occurred from 30 min to 1 h, and the mean peak serum level ± SE was 52.3 ± 1.6 μg/ml. Beginning at 1 h, the serum concentrations after i.m. administration were higher than those after i.v. administration. At 8 h, the mean serum level ± SE was 3.8 ± 0.6 μg/ml after completion of the i.v. infusion and 4.8 ± 0.7 μg/ml after the i.m. injection. The mean serum half-lives for the β phase i.v. and i.m. administration were similar (2.3 ± 0.7 h and 2.4 ± 0.2 h, respectively). The mean apparent volume of distribution ± SE was 16.6 ± 1.9 liters per 1.73 m². The mean serum clearance ± SE of LY127935 was 85.4 ± 12.7 ml/min per 1.73 m², and the mean renal clearance ± SE was 54.5 ± 4.4 ml/min per 1.73 m.² Urine concentrations of LY127935 were at least 140 μg/ml in each volunteer during the first 12 h after i.m. or i.v. administration. The mean percentages of the dose recovered in the urine ± SE within 2 h after i.v. or i.m. administration were similar (30 ± 4 and 34 ± 11, respectively). Only 67 ± 3% and 75 ± 13% were recovered in the urine within 24 h after i.v. and i.m. administration, respectively.