Dissociative ionization and Coulomb explosion of CH4 in two-color asymmetric intense laser fields.

Directional fragment ejection from a tetrahedral molecule CH4 in linearly polarized two-color (ω and 2ω) asymmetric intense laser fields (50 fs, 1.4 × 1014 W cm-2, 800 nm and 400 nm) has been studied by three-dimensional ion coincidence momentum imaging. The H+ fragment produced from dissociative ionization, CH4 → H+ + CH3 + e-, is preferentially ejected on the larger amplitude side of the laser electric fields. Comparison with theoretical predictions by weak-field asymptotic theory shows that the observed asymmetry can be understood by the orientation selective tunneling ionization from the triply degenerated highest occupied molecular orbital (1t2) of CH4. A similar directional ejection of H+ was also observed for the low kinetic energy components of the two-body Coulomb explosion, CH4 → H+ + CH3+ + 2e-. On the other hand, the fragment ejection in the opposite direction were observed for the high energy component, as well as H2+ produced from the Coulomb explosion CH4 → H2+ + CH2+ + 2e-. Possible origins of the characteristic fragmentation are discussed.

Helicity-dependent dissociative tunneling ionization of CF4 in multicycle circularly polarized intense laser fields.

Dissociative tunneling ionization of tetrafluoromethane (CF4) in circularly polarized ultrashort intense laser fields (35 fs, 0.8 × 1014 W cm-2, 1035 nm), CF4 → CF4+ + e- → CF3+ + F + e-, has been studied by three-dimensional electron-ion coincidence momentum imaging. The photoelectron angular distribution in the recoil frame revealed that the dissociative tunneling ionization occurs efficiently when the laser electric field points from F to C. The obtained results are qualitatively consistent with the theoretical predictions by the weak-field asymptotic theory (WFAT) for tunneling ionization from the highest and next-highest occupied molecular orbitals, HOMO (1t1), and HOMO-1 (4t2), respectively. On the other hand, the angular distribution shows clear dependences on the polarization helicity, indicating that the breaking of the C-F bonds is sensitive to the helicity of the multicycle circularly polarized laser fields.

Multielectron-Ion Coincidence Spectroscopy of Xe in Extreme Ultraviolet Laser Fields: Nonlinear Multiple Ionization via Double Core-Hole States.

Ultrafast multiphoton ionization of Xe in strong extreme ultraviolet free-electron laser (FEL) fields (91 eV, 30 fs, 1.6×10^{12} W/cm^{2}) has been investigated by multielectron-ion coincidence spectroscopy. The electron spectra recorded in coincidence with Xe^{4+} show characteristic features associated with two-photon absorption to the 4d^{-2} double core-hole (DCH) states and subsequent Auger decay. It is found that the pathway via the DCH states, which has eluded clear identification in previous studies, makes a large contribution to the multiple ionization, despite the long FEL pulse duration compared with the lifetime of the 4d core-hole states.

Enhanced nonlinear double excitation of He in intense extreme ultraviolet laser fields.

Nonlinear, three-photon double excitation of He in intense extreme ultraviolet free-electron laser fields (∼24.1 eV, ∼5 TW/cm2) is presented. Resonances to the doubly excited states converging to the He+ N=3 level are revealed by the shot-by-shot photoelectron spectroscopy and identified by theoretical calculations based on the time-dependent Schrödinger equation for the two-electron atom under a laser field. It is shown that the three-photon double excitation is enhanced by intermediate Rydberg states below the first ionization threshold, giving a greater contribution to the photoionization yields than the two-photon process by more than 1 order of magnitude.

Multiphoton double ionization of Ar in intense extreme ultraviolet laser fields studied by shot-by-shot photoelectron spectroscopy.

Photoelectron spectroscopy has been performed to study the multiphoton double ionization of Ar in an intense extreme ultraviolet laser field (hν ∼ 21 eV, ∼ 5 TW/cm²), by using a free electron laser (FEL). Three distinct peaks identified in the observed photoelectron spectra clearly show that the double ionization proceeds sequentially via the formation of Ar(+): Ar+hν→Ar (+) + e⁻ and Ar²(+) + 2hν→Ar(+) + e⁻. Shot-by-shot recording of the photoelectron spectra allows simultaneous monitoring of FEL spectrum and the multiphoton process for each FEL pulse, revealing that the two-photon ionization from Ar(+) is significantly enhanced by intermediate resonances in Ar(+).

[Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (1)--A study on oral administration prior to and in the early stages of pregnancy in rats].

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to rats at doses of 100, 300 or 1000 mg potency/kg/day prior to and in the early stage of pregnancy to assess its adverse effects on parental reproductive ability and embryo-fetal development. Loose and/or reddish brown feces were observed in both males and females of all the S-1090 dosing groups, and abdominal distention was also observed in males throughout the dosing period. No drug-related deaths occurred in either males or females. In males, body weight and food consumption were increased at a dose of 1000 mg potency/kg/day throughout the dosing period. In females, body weight gain was restrained during late pregnancy, and food consumption was decreased transiently following the initiation of dosing, and then remained high on the day before parturition in all the S-1090 dosing groups. Necropsy of male and female rats revealed an increase in the cecum weight. The reproductive ability of males and females was normal in all the S-1090 dosing groups. No effects of S-1090 were observed in the implantation ratio, embryo-fetal viability, fetal body weight, and incidence of external, skeletal and visceral anomalies. Based on these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for parental general toxicity, 1000 mg potency/kg/day for reproductive toxicity, and 1000 mg potency/kg/day for developmental toxicity in embryo-fetuses under the conditions of the present study.

[Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (2)--A study on oral administration during the period of organogenesis in rats].

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to female rats at doses of 100, 300 or 1000 mg potency/kg/day from Days 7 to 17 of pregnancy to assess its effects on dams and on development of the embryo-fetuses and offspring. Loose or reddish-brown feces were observed in dams of all the S-1090 dosing groups. Body weight gain was increased from the early stage of administration to the end of pregnancy, food consumption was transiently decreased at the early stage of administration, and water consumption was increased from the middle to the end of pregnancy in all the S-1090 dosing groups. However, no effects on pregnancy, parturition and lactation were observed. Necrospy revealed an increased cecum weight in pregnant and lactating dams of all the S-1090 dosing groups. No effects of S-1090 were observed in viability, growth, incidences of external, skeletal and visceral anomalies, and degree of ossification in F1 fetuses. No effects of S-1090 were observed in such parameters as viability, incidence of external and skeletal anomalies, physical development, sensory functions/reflexes, behavior and reproductive function in F1 offspring. No adverse effects were observed in F2 offspring. On the basis of these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for maternal general toxicity, 1000 mg potency/kg/day for maternal reproductive toxicity and the developmental toxicity in the embryo-fetuses and offspring under the conditions of the present study.

[Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (4)--A study on oral administration during the perinatal and lactation periods in rats].

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to female rats at doses of 100, 300 or 1000 mg potency/kg/day from Day 17 of pregnancy to Day 20 of lactation to assess its effects on pregnant/lactating females and on development of the offspring. In dams, loose feces/reddish brown feces, increased cecum weight, decreased weights of the heart, spleen and submaxillary gland in all the S-1090 dosing groups and a decreased weight of the thymus in the 1000 mg potency/kg dosing group were observed. However, no effects on parturition and lactation were observed in any of the dosing groups. In F1 offspring, although increased cecum weight was found at weaning in all the S-1090 dosing groups, no abnormalities in viability, physical development, sensory functions/reflexes, behavior and reproductive function were observed. No adverse effects were observed in F2 fetuses and offspring. On the basis of these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for maternal general toxicity, and 1000 mg potency/kg/day for maternal reproductive toxicity and for developmental and reproductive toxicity in offspring under the conditions of the present study.

Epididymal sperm motion as a parameter of male reproductive toxicity: sperm motion, fertility, and histopathology in ethinylestradiol-treated rats.

The present study was designed to characterize the effect of ethinylestradiol (EE) on epididymal sperm motion using a computer-assisted sperm analysis system (CASA), and to elucidate the correlation between sperm motion endpoints and other measures including fertility, histopathologic, and endocrinologic endpoints. EE was orally given to adult male rats at a daily dosage of 10 mg/kg for 3 and 5 d, and at daily dosages of I and 10 mg/kg for 1, 2, 3, and 4 weeks. Changes in sperm motion were first detected after one week of treatment. Of nine sperm motion parameters, the percentage of motile sperm, velocity, and amplitude of the lateral head displacement (ALH) were decreased in the 10 mg/kg dosing group. Accompanying the decreases in those parameters, the male fertility indices in the 10 mg/kg dosing group were reduced after one week of treatment, and no males in this group could impregnate intact females after 2 weeks or more of treatment. The number of sperm heads in the cauda epididymis in the 10 mg/kg dosing group was reduced to about one-half that in the control group after one week of treatment, whereas the total number of homogenization-resistant advanced spermatids in the testis was not altered and only a slight change was detected in the number and morphology of germ cells in the testis. These results suggest that reduction in the number of epididymal sperm and in sperm motion are not secondary to testicular alteration. However, after 3 weeks of treatment, the number of sperm heads in the testis was drastically reduced with severe atrophy of the seminiferous tubules both in the 1 and 10 mg/kg dosing groups. The profiling of epididymal luminal fluid proteins indicated that two major bands that migrated with molecular weights of about 22 and 23 kDa were weakened and their density was reduced to approximately 70% of the control after 5-d and one week treatments in the 10 mg/kg dosing group. Circulating testosterone declined drastically after 3 d of treatment and remained at undetectable levels with a concomitant decline of circulating LH and FSH, suggesting that EE inhibits testosterone secretion immediately via a negative feedback system, and there follow changes in the accessory reproductive organs including the epididymis. These results indicate that EE affects epididymal spermatozoa before testicular germ cells via a testosterone deficiency, when it is administered at extremely high dosages. The reduction in the sperm motion manifested as decreases in the percentage of motile sperm, ALH, and velocity, is considered to be responsible for the onset of infertility. Sperm motion analysis could be particularly useful for detecting the toxic effects of chemicals that act through the endocrinologic system on the epididymis.