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Background It is critical to monitor the optic disc’s vessel density using Optical coherence tomography angiography (OCTA) and evaluate its determinants. In the current study, we investigate the superficial vessel density (VD) of the papillary microvasculature and its determinants in healthy subjects of Southern China. Methods This was a prospective, cross-sectional study. Superficial VD in healthy individuals’ optic disc region was measured by OCTA. The factors associated with ocular and systemic parameters were analyzed using a generalized estimation equation (GEE) model. Results A total of 510 eyes of 260 healthy subjects were analyzed in the study. The total VD in the optic disc area was 17.21 ± 2.15 mm− 1 (95% CI, 17.02–17.40 mm− 1). The VD in the inner ring and the outer ring of the optic disc were significantly higher compared with the central ring, while the VD of the superior quadrant and inferior quadrant was significantly higher compared with the temporal and nasal quadrant. After adjusting for the ocular factors and systemic factors, AL (β = − 0.4917, P = 0.0003), disc area (β = − 0.3748, P = 0.0143), CMT (β = − 0.0183, P = 0.0003) and SSI (β = 1.0588, P Conclusion The mean total VD in the optic disc area was 17.21 ± 2.15 mm− 1 in healthy subjects, and the superior and inferior VD was significantly higher than the temporal and nasal VD. AL, disc area, CMT, and SSI may affect the total VD in the optic disc area and should be considered in clinical practice.

Purpose The purpose of the paper is to analyze the bearing capacity of hydrostatic bearing during the change of film thickness under different working conditions and to improve the processing efficiency and precision of equipment. Design/methodology/approach In this study, Q1-205 double rectangular cavity hydrostatic thrust bearing is selected as the research object. The dynamic mesh method and ANSYS/FLUENT software are used to simulate the curves of oil film thickness and oil pressure under different operating conditions. Finally, the change of pressure in the oil cavity at different operating speeds under a certain inlet flow rate was tested through design experiments. Findings When the film thickness was thick, the maximum pressure in the oil cavity at different inlet velocities showed little difference. With a larger inlet flow, the maximum pressure in the oil cavity was higher. The pressure at the edge of the oil seal was linearly distributed. The oil pressure in the downstream side was greater than that in the counter flow side. When the working pressure was low, the pressure in the oil cavity slightly decreased with the increase of working speed. Moreover, the pressure loss at high speed was considerable. Originality/value Based on the lubrication theory, the mathematical model of the bearing oil film was set up. The bearing capacity equation of the hydrostatic cavity was derived. The double-rectangular-annular hydrostatic guides studied in this paper have not been reported in previous research literature and the method of dynamic mesh dynamic simulation of variable viscosity is seldom studied before. The bearing characteristics and the change of oil film thickness under different working conditions have been studied systematically and comprehensively. The theoretical analysis results are basically consistent with the experimental results.

In order to improve the lubrication performance of the double-rectangular cavity hydrostatic thrust bearing, this paper selects the temperature rise characteristics of hydrostatic bearing as the research object under the conditions of changing oil film thickness and different working conditions. Using the dynamic mesh method with variable viscosity dynamic simulation, the changing temperature rise curves under different inlet flow velocities and rotating speeds are obtained. This paper obtains the changing laws of oil film thickness and temperature under the hydrostatic bearing running in no-load, load 2.5 t, load 10 t and the rotating speeds of 40 r/min, 60 r/min and 80 r/min. Under the low rotating speed, the high temperature region in the oil cavity mainly concentrates on the counter flow side. With the increase of working speed, the high temperature region on the counter flow side expands to the oil seal side obviously. When the oil film thickness was in the range of 0.04 mm to 0.07 mm, the temperature of oil seal edge increased with the increase of the inlet flow velocity. Using the FLUENT software, the variable viscosity simulation of hydrostatic bearing is carried out under different oil film thickness, and the temperature distribution of oil cavity is obtained. Finally, the correctness of theoretical analysis and simulation are verified by conducting experiment.

SnO2 semiconductor is a new-typed promising photocatalyst, but wide application of SnO2-based photocatalytic technology has been restricted by low visible light utilization efficiency and rapid recombination of photogenerated electrons–holes. To overcome these drawbacks, we prepared B/Fe codoped SnO2–ZnO thin films on glass substrates through a simple sol–gel method. The photocatalytic activities of the films were evaluated by degradation of organic pollutants including acid naphthol red (ANR) and formaldehyde. UV–Vis absorption spectroscopy and photoluminescence (PL) spectra results revealed that the B/Fe codoped SnO2–ZnO film not only enhanced optical absorption properties but also improved lifetime of the charge carriers. X-ray diffraction (XRD) results indicated that the nanocrystalline SnO2 was a single crystal type of rutile. Field emission scanning electron microscopy (FE-SEM) results showed that the B/Fe codoped SnO2–ZnO film without cracks was composed of smaller nanoparticles or aggregates compared to pure SnO2 film. Brunauer–Emmett–Teller (BET) surface area results showed that the specific surface area of the B/Fe codoped SnO2–ZnO was 85.2 m2 g−1, while that of the pure SnO2 was 20.7 m2 g−1. Experimental results exhibited that the B/Fe codoped SnO2–ZnO film had the best photocatalytic activity compared to a pure SnO2 or singly-modified SnO2 film.

Objectives To evaluate the foveal avascular zone (FAZ) area in healthy volunteers using optical coherence tomography angiography (OCTA) and identify factors that influence the FAZ. Methods This single-center cross-sectional study included 526 eyes of 263 healthy volunteers who underwent macular scanning by Zeiss OCTA. A linear mixed model was used to investigate the effects of systemic factors (age, sex, blood pressure, height, and weight) and ocular factors (intraocular pressure, biometric parameters, and central macular thickness) on FAZ. Results In total, 520 eyes of 262 healthy volunteers were included in the analysis. The mean volunteer age was 38.59 ± 22.03 years (range, 5–84 years); 124 volunteers were male (47.33%) and 138 volunteers were female (52.67%). The mean FAZ area was 0.30 ± 0.03 mm2 (95% confidence interval [CI], 0.29–0.31 mm2). Univariate analysis showed that FAZ area was associated with age (β = 0.0011), anterior chamber depth (β = −0.0513), and axial length (β = −0.0202). Multivariate analysis showed that FAZ area was negatively correlated with axial length (β = −0.0181). Conclusions The mean FAZ area in healthy volunteers, measured using Zeiss OCTA, was 0.30 ± 0.03 mm2. Furthermore, FAZ area was negatively associated with axial length; this relationship should be considered in clinical practice.

A new solid substrate-room temperature phosphorescence (SS-RTP) quenching method for the determination of trace As(V) has been developed, based on the facts that 9-hydroxy-2,3,4,9-tetrahydro-1,10-anthraquinone (R) can emit intense and stable SS-RTP on solid substrate, and α,α′-dipyridyl can activate As(V) catalysis of the reaction of H2O2 oxidizing R to non-phosphorescence compound R′, which can cause the sharp quenching of SS-RTP. Under the optimum condition, the relationship between the ΔIp of the emitting intensity and 1.60–160 fg·spot−1 As(V) (corresponding concentration:0.0040–0.40 ng·mL−1, sample volume:0.4 µL·spot−1) conformed to Beer′ law. The regression equation of working curve can be expressed as ΔIp20.46+0.5492cAs(V) (fg·spot−1) (r=0.9995, n=6). The limit detection (LD) is 0.27 fg·spot−1 [As(V) corresponding concentration:6.8×10−13 g·mL−1, n=11]. The samples containing 0.0040 and 0.40 ng·mL−1 As(V) were repeatedly determined for 11 times. RSD are 3.0% and 2.7% respectively. The SS-RTP mechanism was also discussed. R was synthesized in this paper. Meanwhile, the structure was determined by NMR, IR , mass spectra and elemental analysis.

Hypospadias is one of the most common congenital malformations, and its main clinical manifestation is the abnormal opening of the urethra. Etiologically, it can be attributed to many factors, mainly including genetic, hormonal, and environmental factors. Recently studies about its genetic etiologies have found a variety of hypospadias-associated genes from the aspects of epidemiology and polymorphism, mainly those involving the formation of the penis, the development of the testis, the anabolism of androgens, and so on. This review focuses on the progress in the studies on the genetic etiology of hypospadias.

In order to enhance the photodegradation of organic pollutants, Boron-doped tin dioxide (B-doped SnO2) composite films with narrowed band gap were successfully prepared by the sol–gel method. The samples are characterized by UV–Vis absorption spectroscopy, photoluminescence (PL), X-ray diffraction (XRD), high-resolution field emission scanning electron microscope (FE-SEM), X-ray energy dispersive spectroscopy (EDS), and Brunauer–Emmett–Teller (BET). UV–Vis absorption spectroscopy results revealed that the absorption of the B-doped SnO2 film was clearly broadened to the visible light area. PL results showed that the recombination rate of the photo-generated species was effectively prohibited by B doping. The photocatalytic properties of the films were evaluated by degradation of organic pollutants including acid naphthol red (ANR) dye and formaldehyde solutions. Experimental results indicated that the B-doped SnO2 film exhibited an excellent photocatalytic activity under visible light irradiation due to its strong visible light response and diminished electron–hole recombination.

3'-Fluoro-3'-deoxythymidine (FLT), a candidate anti-AIDS compound in clinical trials, showed anti-human immunodeficiency virus type 1 (HIV-1) potency (50% effective concentration, 0.0052 microM) slightly better than or equal to that of 3'-azido-3'-deoxythymidine (AZT) in MT4 cells and was threefold more potent in H9 cells. There was no FLT resistance demonstrable in the AZT-resistant HIV-1 strains. Both FLT and AZT showed low cytotoxicity for MT4 cells, with selectivity indices (efficacy/toxicity ratio) of greater than 47,000 and greater than 33,000, respectively. Cellular permeation of FLT and thymidine (dThd) was greater than that of AZT, and FLT and dThd permeated the cell membranes by a carrier-mediated mechanism as well as by simple diffusion, as indicated by the existence of nitrobenzylthioinosine-5'-monophosphate-sensitive and -insensitive components. By contrast, transport of AZT into cells was by simple diffusion. The intracellular level of the triphosphate of FLT (FLTTP) in MT4 cells was two- to threefold higher than that of AZT (AZTTP) after exposure to 1.8 microM each compound for 12 h. The elimination kinetics of FLTTP and AZTTP in HIV-1-infected MT4 cells in fresh medium showed biphasic patterns, with initial half-lives of 1.03 and 1.09 h, respectively. In phytohemagglutinin-stimulated human peripheral blood lymphocytes, the FLTTP level was increased 59-fold compared with that in unstimulated cells at 12 h, was four- to sixfold higher than the level of AZTTP in stimulated cells at 12 h, and remained four- to fivefold higher during a 4-h elimination period in fresh medium and twofold higher at the end of a 12-h elimination period. Two- to eightfold more [3H]AZT than [3H]FLT was incorporated into the host cell DNA, and both [3H]AZT and [3H]FLT remained persistently incorporated for over 24 h. The incorporated [3H]AZT and [3H]FLT were alkali labile, whereas incorporated [3H]dThd was alkali stable. Pharmacokinetics of FLT in plasma of monkeys after intravenous (i.v.) administration showed that the FLT concentration in plasma declined, with a half-life of 1.19 +/- 0.1 h; the steady-state volume of distribution was 0.93 +/- 0.2 liter/kg of body weight, and total clearance was 0.56 +/- 0.15 liter/kg. Oral bioavailability of FLT was excellent and comparable to i.v. bioavailability in terms of areas under the concentration-time curves for three monkeys. Of the total dose, 41 to 61% was excreted in urine as unchanged FLT, and only 3.2 to 7.4% of the total dose was identified as glucuronide-conjugated FLT in urine 48 h after i.v. administration to monkeys. We conclude that FLT exhibits an anti-HIV-1 potency similar to that of AZT but with slightly better selectivity of effects and with higher intracellular active metabolite levels.

The effects of 3'-azido-3'-deoxythymidine (AZT), phosphonoformate (PFA), and 2',3'-dideoxythymidine (ddT) and their combination on human immunodeficiency type 1 (HIV-1) replication were studied by measuring the HIV-1 p24 antigen expression and reverse transcriptase (RT) release in HIV-1-infected MT4 cells in vitro. RT activity was also measured in a cell-free system by using poly(rA)-oligo(dT) as the primer-template, and cell growth inhibition was measured in noninfected MT4 cells. The interactions of these two- and three-drug combinations were evaluated by the combination index (CI) method and isobologram techniques. The 50% effective concentrations (EC50s) of AZT, PFA, and ddT were 0.014 to 0.005, 9.4 to 8.8, and 8.4 to 2.5 microM, respectively, for p24 enzyme-linked immunosorbent assays (ELISAs) and 0.005 to 0.0034, 1.43 to 1.37, and 2.87 to 2.83 microM, respectively, for RT activity in vitro; for RT activity in the cell-free system, the EC50s were 0.00019 to 0.00024, 0.012 to 0.02, and 0.00074 to 0.0005 microM, for AZT-5'-triphosphate, PFA, and ddT-5'-triphosphate, respectively. AZT in combination with PFA (1:200) or ddT (1:5) as well as the combination of these three drugs (1:200:5) synergistically inhibited HIV-1 replication and RT activity in the cell-free system over a wide range of drug concentrations, with the CIs ranging from 0.5 to 0.09, in which CIs of less than 1, 1, and greater than 1 indicate synergism, additive effect, and antagonism, respectively. Three- and two-drug combinations of AZT, PFA, and ddT showed similar degrees of synergism against HIV-1 replication in p24 assays and RT release assays, whereas the combination of AZT and ddT was found to be the most selective in terms of its anti-HIV-1 effect versus cytotoxicity. Dose reduction indices calculated from both HIV-1 replication inhibition, as measured by p24 ELISA and by RT activity in the cell-free system, indicated that two- and three-drug combinations at high effect levels and the selected combination ratios allow 2- to 240-fold dose reduction over the single drug alone in terms of their anti-HIV-1 effects. The three-drug combination showed the highest dose reduction index. These finding suggest that increased efficacy and reduced toxicity may be achieved in AIDS therapy by using AZT, PFA, and ddT in two- or three-drug combinations.

Because of the decrease in pasture and woodland proportion, soil loss is severe along the Yellow River basin. The Yellow River delta has been one of the deltas that form land most quickly. Research on the pollution of new land is important for its use and appraising the environment and food pollution along Yellow River basin. The contents of heavy metals (Mn, Cu, Zn, As, Cd, Pb, Hg and Cr) in new soils (2006) and old soils (1996) from Yellow River delta, were analyzed by the method of ICP-MS/ICP-AES, in order to determine the level of pollution along Yellow River basin. The results showed that the heavy metals pollution along Yellow River basin is increasingly severe, especially the concentrations of Mn, Cu, Zn, Cr and Cd in soil forming in 2006 are significantly higher than those in 1996, which should be noticed by our government.

To establish and optimize a real time RT-PCR system for determining the transcript levels of CatSper1 in human and mouse mature spermatozoa containing microamount of RNA.Total RNA of human and mouse mature spermatozoa was isolated by using TRIzol reagent and reversely transcribed to complementary DNA respectively. Primers for real time RT-PCR were designed in the homologous area of the human and mouse CatSper1 mRNAs. Human sperm complementary DNA was used as the template to the optimize the conditions for SYBR Green I real time RT-PCR, including annealing temperature, Mg2+ concentration, fluorescence measurement temperature and the ratio between forward and reverse primers. The standard curve was constructed with serial dilutions of complementary DNA from human sperm to ascertain the amplification efficiency of SYBR Green I real time PCR and to quantitate the CatSper1 mRNA levels in the human and mouse mature spermatozoa.The optimal conditions for real time RT-PCR, that is, annealing temperature, Mg2+ concentration and the ratio between forward and reverse primers were 63 degrees C, 3.0 mmol/L and 1:1 respectively. The fluorescence measurement temperature was 88 degrees C. The standard curves were Y = -3.402 log (X) + 25.99 and Y = -3.409 log(X) + 24.09 in the human sperm cDNA and mouse sperm cDNA as the template, with amplification efficiency of 96.8% and 96.5% respectively. The R2 value (an indicator of the quality of the fit of the standard curve to the standard data points plotted) of both standard curves was 0.998. The CatSper1 mRNA levels in the human and mouse mature spermatozoa could be determined according to the standard curve.The general RT-PCR system, by adding SYBR Green I and optimizing its conditions, could be used to quantitate the mRNA levels in both human and mouse mature spermatozoa.

With the rapid development of the society, more and more attention has been paid to the influence of human activity on environment and food pollution. Soils of different cropping systems, sampled from Daxing district of Beijing, were analyzed in terms of the contents of heavy metals (Ti, Cr, Mn, Ni, Cu, Zn, As, Cd and Pb) by the method of ICP-MS to determine the influence of cropping system on environment. The results showed that the contents of nine heavy metals in soils from the cropping systems (fruits and maize/wheat) were several times higher than those from vegetable system. Contents of Cr, Mn, Ni, Cu, Zn, As and Cd were the highest in soils from fruit system, while Ti and Pb the highest in soils from maize/wheat system. The causes of the above differences could be the different harvest organs for different crops.

The preclinical pharmacology and pharmacokinetics of 2'-fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (FEAU), a selective inhibitor of herpesvirus and hepatitis virus replication, were investigated in the mouse and rat. Following intravenous (i.v.) or oral (p.o.) administration, FEAU was cleared from the plasma primarily unchanged, with a terminal half-life of 58 to 80 min in the mouse and 63 to 78 min in the rat. The steady-state volumes of distribution times bioavailabilities of FEAU were approximately 2.1 and 3.4 times the total body water volumes after p.o. administration of 10 mg of drug per kg of body weight in mice and rats, respectively. A comparison of the area under the concentration-time curve after i.v. and p.o. FEAU administration indicated that the p.o. dose was completely absorbed in both species. When tritiated FEAU was used in mice, 35.0% of the i.v. dose and 33.5% of the p.o. dose were excreted in urine as unchanged FEAU, 8.1% (i.v. dose) and 9.2% (p.o. dose) were excreted as tritiated water, and 15.6% (i.v. dose) and 18.1% (p.o. dose) were excreted as unknown metabolite(s) in urine within 24 h of dosing. Only 1.24% (i.v. dose) and 2.6% (p.o. dose) of the total doses were found in urine as 3H2O when the FEAU dose was increased to 50 mg/kg. However, a higher percentage of the total dose (59.6% for the i.v. dose and 61.3% for the p.o. dose) was recovered within 24 h as intact FEAU in rat urine, less than 1.4% (i.v. dose) and 2.7% (p.o. dose) of the total dose were found to be 3H2O, and 5.6% (i.v. dose) and 6.7% (p.o. dose) of the total dose were excreted as known metabolite(s). The distribution ratios for total radioactivity in tissue relative to those in plasma were 0.5 to 1.3 in spleen, testes, muscle, and liver during the first hour after a 10-mg/kg dose in rats. Of the total FEAU radioactivity administered, only 1.38% was excreted in bile as unchanged FEAU. No FEAU glucuronide metabolite was detected. Tissue concentrations of 0.15 to 0.6 microM at 6 h after dosing are in the range of the effective antiviral concentration for FEAU. In conclusion, FEAU administered p.o. to mice and rats was well absorbed; FEAU was rapidly distributed into tissues and remained above in vitro antiviral concentrations for more than 6 h; in mice, [3H]FEAU showed metabolism-mediated tritium exchange with water; and in rats, FEAU was less extensively metabolized than in mice and clearance was primarily via renal processes, mainly in the form of unchanged FEAU.

The incorporation and metabolism of 2′-fluoro-5-substituted arabinosyl pyrimidine analogs, and their selective inhibition of viral DNA synthesis in herpes simplex virus type 1 (HSV-1)-infected and mock-infected Vero cells were studied by HPLC and CsCl isopycnic density gradient analysis of isolated DNAs. The amounts of radiolabeled analogs incorporated as parent compound following 10 μM exposure for 4 h were 10-fold higher in HSV-1-infected vs mock-infected cells for 2′-fluoro-5-difluoromethyl-Ara-U (F 2 FMAU); 4.3-fold higher for 5-ethyl deoxyuridine (EdU); 2.6-fold higher for 2′-fluoro-5-methyl-Ara-U (FMAU) and 1.7-fold higher for dThd. For 2′-fluoro-5-ethyl-Ara-U (FEAU), 3.0 pmole of unchanged moiety was incorporated per 10 6 HSV-1-infected cells but no incorporation was detected in mock-infected cells. HPLC profiles showed that the percentages of radiolabeled analogs incorporated as parent compound in the DNA extracted from HSV-1-infected cells were 31.0% for F 2 FMAU, 99.6% for EdU, 83.5% for FEAU and 98.3% for FMAU; from mock-infected cells, they were 63.6% for F 2 FMAU, 96.7% for EdU, 97.3% for FMAU and no incorporation into DNA for FEAU was detected. CsCl density gradient analyses of isolated DNA showed that viral DNA synthesis was inhibited 98% by 10 μM FEAU, 92% by 10 μM F 2 FMAU, 90% by 2 μM FMAU and 80% by 50 μM EdU, whereas cellular DNA synthesis was inhibited by 53, 44, 61, 66 and 54%, respectively. We conclude that: (a) FEAU incorporation into host-cell DNA was not detectable but FEAU was selectively incorporated into HSV-infected cells; (b) FMAU and FEAU were metabolically stable; however, F 2 FMAU was extensively metabolized; (c) FEAU and F 2 FMAU were among the most selective inhibitors of HSV-1 DNA synthesis while allowing cellular DNA synthesis to continue.

Selective killing of cancer cells by cytotoxic agents and the conversion of cancerous cells to normal state by differentiation agents represent two basically different approaches in chemotherapy. In this study, we examined the combination of the cell differentiation inducer, hexamethylene bisacetamide (HMBA), and the cytotoxic agents, 1-beta-D-arabinofuranosylcytosine (Ara-C), adriamycin (Adr) and harringtonine (HT), for cytotoxicity and induction of cell differentiation in HL-60 cells by measuring cell growth inhibition, morphological maturation and nitroblue tetrazolium (NBT) reduction. To determine quantitatively whether the effects produced by these combinations were additive, synergistic or antagonistic, we used a computer program based on the median-effect principle and isobologram equations (Adv. Enz. Reg. 22, 27-55, 1984), After 5-day exposure to each drug alone we found that the ED50s for cell growth inhibition were 0.01 microM for Ara-C, 0.012 microM for Adr, 0.017 microM for HT and 2.53 mM for HMBA. ED50s for differentiation were 0.089 microM (morphology), 0.06 microM (NBT) for Ara-C; 0.12 microM (morphology), 0.09 microM (NBT) for Adr; 0.04 microM (morphology) 0.06 microM (NBT) for HT; and 2.55 mM (morphology), 2.43 mM (NBT) for HMBA, respectively. At dose levels from ED50 to ED95, the combinations of Adr/HMBA and HT/HMBA produced antagonistic cytotoxic and cell differentiation effects. The combination of Ara-C/HMBA produced antagonistic cytotoxic and cell differentiation effects. The combination of Ara-C/HMBA produced antagonistic cytotoxic effects but slight synergistic cell differentiation effects. On the basis of this study, we conclude that the equipotency combinations of the above three pairs of drugs do not synergistically enhance cytotoxicity or cell differentiation effects in vitro at effect levels high enough for the successful treatment of acute leukemia. Other combinations of cell differentiation agents with cytotoxic agents or biological response modifiers remain to be explored.

A group of 2′-fluoro and 5-substituted arabinosyl pyrimidines and a group of base-substituted pseudoisocytidine analogs were evaluated for their capacity to induce differentiation in the human promyelocytic leukemia cell line, HL-60. These compounds were compared to 1-β- d -arabinofuranosylcytosine (Ara-C) by monitoring: (1) inhibition of cell growth; (2) morphological maturation; (3) nitroblue tetrazolium (NBT) reduction; (4) expression of a myeloid differentiation antigen, Mol; and (5) inhibition of colony formation. Exposure of logarithmically growing cells for 5 days to Ara-C, 2′-fluoro-Ara-C (FAC), 2′-fluoro-5-methyl-Ara-C (FMAC) and 2′-fluoro-5-ethyl-Ara-C (FEAC) resulted in cell growth inhibition at ED 50 concentrations of 0.007, 0.11, 1.7 and 18 μM, and at cytostatic concentrations of 0.1, 0.5, 5.0 and 50 μM, respectively. These compounds induced granulocytic and monocytic maturation, reduction of NBT, increased expression of Mol antigen and a decrease or loss of both cell proliferation and colony formation in semisolid medium. There were few, if any, cell differentiation effects for the uracil nucleosides and pseudoisonucleosides tested. We found that Ara-C was the most cytotoxic of the compounds, and that when comparing absolute numbers of differentiated cells, i.e. percent of positive cells multiplied by the number of viable cells, FAC, FMAC and FEAC were superior to Ara-C in inducing differentiation of HL-60 cells.

2'-Fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (FEAU) was synthesized, and its biological activities were compared with those of 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU). Earlier studies indicated that both compounds showed potent anti-herpes simplex virus activity, with a 50% effective dose (ED50) of less than 0.25 microM. In the present study the cell growth inhibitory activity of FEAU (ED50, 200 to 2,060 microM) was found to be about 100-fold less than that of FMAU. With an ED50 ranging from 630 to 3,700 microM, FEAU only weakly inhibited thymidine incorporation into DNA, as compared with FMAU with an ED50 of 9 to 28 microM. Following exposure to [2-14C]FEAU (100 microM), 0.48 pmol/10(6) cells per h was incorporated into the DNA of herpes simplex virus type 1-infected Vero cells, whereas no detectable incorporation was found in uninfected Vero cells or L1210 cells. The Ki of FEAU for thymidine kinase purified from human leukemic cells was greater than 150 microM. For herpes simplex virus type 1- and 2-encoded thymidine kinases, the Kis were 0.6 and 0.74 microM, respectively. Both FEAU and FMAU were relatively nontoxic for mice, with a 50% lethal dose of greater than 800 mg/kg per day (four intraperitoneal doses). However, the lethal dose of FEAU for dogs was 100 mg/kg per day (10 intravenous doses), a dose which is 40- to 80-fold greater than the toxic dose of FMAU. These results suggest that FEAU is a worthy candidate for further development as an antiherpetic agent.