Sodium colistin methanesulfonate (CLM), a polypeptide antibiotic, was administered intravenously to ICR-JCL mice at dosage levels of 60, 125 and 250mg/kg/day to determine its effects on the ...reproductive process and fetal development. Male mice were continuously treated from day 63 prior to mating through copulation, and female mice from day 14 before mating through day 7 of gestation. Results were obtained as follows; 1. CLM did not affect general behavior, body weight, food consumption, mating performance and fertility in all the treated groups of both sexes. 2. CLM did not affect general behavior and food consumption in pregnant mice, but body weight gain of dams was increased in 125 and 250mg/kg groups. 3. There were no significant differences between the control group and the treated groups in number of implantations, live fetuses, resorptions in the uterus and sex ratio. However, body weight of live fetuses and weight of placentas were increased in 125 and 250mg/kg groups. 4. No significant increase of the prevalence of external, Visceral and skeletal anomalies of the fetuses was observed in any treated group. The progress of ossification was not affected, either. It can be concluded that CLM, at lower dosage than 60mg/kg, has no unfavorable influence on fertility and fetal development in mice.
Teratogenicity study of sodium colistin methanesulfonate (CLM) was performed with ICR-JCL mice. CLM was administered intravenously at dosage levels of 125, 250 and 500mg/kg/day from day 6 to day 15 ...of gestation. About two-thirds of pregnant mice in each group were sacrificed on day 18 of gestation and their fetuses were examined. The remaining mothers were allowed to deliver naturally. Results were obtained as follows; 1. CLM did not affect general behavior, body weight and food consumption in pregnant mice. 2. There were no significant differences between the control group and the treated groups in number of implantations, live fetuses, resorptions in the uterus, body weight of live fetuses, sex ratio and weight of placentas. 3. No significant increase of the prevalence of external, visceral and skeletal anomalies of the fetuses was observed in any treated group. 4. The ossifications of cervical and sacral vertebrae were delayed by treatment with CLM at dosage levels of 250 and 500mg/kg. 5. The were no significant differences between the control and the treated groups of delivery in duration of pregnancy, number and body weight of liveborn, sex ratio, number of implantation sites, delivery rate and nuring rate. Moreover, no stillborn and external anomaly of liveborn were observed in any treated group of delivery. 6. CLM did not affect postnatal growth, development and differentiation in newborn mice. 7. CLM did not affect sensory function of reflex, motor coordination, emotionality and learning ability in newborn mice. But, spontaneous activity of both sexes was reduced by treatment with CLM at dosage levels of 250 and 500mg/kg. It can be concluded that CLM, in this study, has little unfavorable influence on fetuses and newborn mice, and that the maximum non-toxic level of CLM is 125mg/kg in mice.
A perinatal and postnatal study on sodium colistin methanesulfonate (CLM) was carried out in ICRJCL mice. CLM was administered intravenously at dosage levels of 125, 250 and 500mg/kg/day from day 15 ...of gestation to day 21 after birth. Results were obtained as follows; 1. CLM did not affect general behavior, body weight and food consumption in pregnant mice. 2. There were no significant differences between the control group and the treated groups during delivery and lactation in duration of pregnancy, number of liveborns, sex ratio, number of implantation sites, delivery rate and nursing rate. Moreover, no stillborn and external anomaly of liveborn were observed in any treated group of delivery. 3. CLM did not affect postnatal growth, development and differentiation in newborn mice. 4. CLM did not affect sensory function of reflex, spontaneous act ivity, motor coordination, emotionality, learning ability and reproductive ability in newborn mice. It can ire concluded that CLM, in this study, does not have any influence on the dams and postnatal development of their offspring, and that maximum non-toxic level of CLM is 500mg/kg in mice.
Teratogenicity study on sodium colistin methanesulfonate (CLM) were carried out in New Zealand white Sat. rabbits. Pregnant rabbits were given CLM intravenously, once daily, at doses of 50 mg, 63 mg ...and 80 mg/kg for 13 days from day 6 to day 18 of gestation. Results were given as follows: 1. CLM did not affect general condition, body weight and food consumption in pregnant rabbits. 2. There was no significant difference between the CLM treated groups and the control group in number of implantation, number of live fetuses, weight of live fetuses, sex ratio, number of resorptions, number of dead fetuses and weight of placentas. 3. No internal and external malformation as well as anomalous ossification of fetuses were observed in CLM treated groups. 4. The ossifications were not delayed by treatment with CLM. It can be concluded that CLM does not influence the health of pregnant rabbits or the development of their fetuses. In this study the maximum non-effect dose of CLM was 80 mg/kg in rabbits.
Sodium colistin methanesulfonate (CLM) was intravenously injected to male and female Wistar strain rats, once daily, at doses of 6.25mg, 12.5mg and 25mg/kg to examine the influences on their ...fertility and development of fetuses. Male rats were treated with CLM for more than 60 days before mating until copulation. Female rats were treated with CLM for 14 days before mating, furthermore the treatment was continued until day 7 of gestation. Results were given as follows; 1. CLM did not affect general condition, body weight, food consumption, copulation and pregnancy. 2. CLM did not affect general condition, body weight and food consumption in preganant rats. 3. There was no significant difference between the CLM treated groups and the control group in number of implantations, number of live fetuses, weight of live fetuses, sex ratio, number of resorptions, number of dead fetuses and weight of placentas. 4. No internal and external malformation as well as anomalous ossifications of fetuses were observed in any treated group. 5. The ossifications of cervical vertebral centra, epiphysis of the caudal vertebral and proximal diaphysis of the hind paw were delayed by treatment with CLM at dose of 25mg/kg. It can be concluded that CLM has no unfavourable influence on fertility and fetal development in rats. In this study, the maximum non-effect dose of CLM was 12.5mg/kg in rats.
Perinatal and postnatal study of sodium colistin methanesulfonate (CLM) was performed with Wistar strain rats. The dams were given CLM intravenously at doses of 6.25mg, 12.5mg and 25mg/kg from dary ...17 of gestation to the 21st day post partum. Results were given as follows; 1. CLM did not affect general condition, maternal body weight and food consumption in the dams. 2. There was no significant difference between the CLM treated groups and the control group in duration of pregnancy, number of newborns, number of liveborns, number of stillborns, sex ratio and weight of liveborns at delivery. Moreover, no external malformations of liveborns were observed in any treated group. 3. CLM did not affect delivery rate or nursing rate. 4. CLM did not affect postnatal growth, development and differentiation in newborn rats. 5. CLM did not affect postnatal behavior, sensational reflex, spontaneous activity, nerve-muscle ability, learning ability, emotional pattern and reproductive ability in newborn rats. It can be concluded that CLM does not influence the health of dams and postnatal development of their offspring. In this study, the maximum non-effect dose of CLM was 25 mg/kg in rats.
Teratogenicity study on sodium colistin methanesulfonate (CLM) was carried out in Wistar strain rats. Pregnant rats were given CLM intravenously, once daily, at doses of 6.25 mg, 12.5 mg and 25 mg/kg ...for 11 days from day 7 to day 17 of gestation. Results were given as follows; 1. CLM did not affect general condition, body weight and food consumption in pregnant rats. 2. There was no significant difference between the CLM treated groups and the control group: in number. of implantation, number of live fetuses, weight of live fetuses, sex ratio, number of resorptions, number of dead fetuses and weight of placentas. 3. No interanl and external malformation as well as anomalous ossifications of fetuses were observed in CLM treated groups. 4. The-ossifications of odontoid process and proximal diaphysis of the hind liaw-were delayed by treatment with CLM at dose of 25 mg/kg. 5. There was no significant difference between the CLM treated groups and the control group in duration of pregnancy, number of newborns, number of liveborns, number of stillborns, number of implantation sites, sex ratio and weight of liveborns at delivery. Moreover, no external malformations of liveborns were observed in any treated group. 6. Delivery rate and nursing rate were reduced by treatment with CLM at dose of 25ing/kg. 7. CLM did not affect postnatal growth, development and differentiation in newborn rats. 8. CLM did not affect postnatal behavior, sensational reflex, spontaneous activity, learning ability, emotional pattern and reproductive ability in newborn rats. It can be concluded that CLM has no unfavourable influence on fetuses or newborn rats. In this study, the maximum no-effect dose of CLM was 12.5 mg/kg in rats.
Ocularl toxicity of;spdium coliatin methanesulfonate (CLM) on visual organs was studied histopathologicalr, funduscopically and electroretinographically (ERG) in Wistar strain rats, rabbits and ...beagle dogs. CLM (25 mg, 40 mg/kg in rat; 80 mg/kg in rat, rabbit and beagle dog) dissolved in pyrogen free physiological saline was administered intravenously daily for 35 days except every Sunday. In the control group, the same volume of physiological saline was administered. Results were given as follows: 1. Throughout the experiment, no toxic symptoms and abnormal behaviors by CLM administration were observed. There was no significant changes of body weight gain in the groups treated with CLM. No deaths occurred in any of the groups. 2. ERG measured at the day after the final application of the drug was no remarkable difference between the CLM treated and control rats. 3. No statistic difference of histopathological alterations of eye ball was observed in any treated groups. 4. Toxicological influence of the CLM on the funduscopy of rabbits and beagle dogs was not observed. In consequence, CLM has no toxicological influences and specific effects on visual organs under these experimental conditions.
•New all-cellulose and all-wood composites were prepared by a simple process using ionic liquid.•The SEM analysis revealed that the lignocellulosic fibers and matrix combined together.•Both the ...composites had equal or higher crystallinity compared with the starting biomass.•Tensile strength and moduli of the all-cellulose composites increased with the pressure of hot press.•The all-wood composite showed a superior tensile modulus over 6GPa.
After cotton fabric (CF) and hinoki lumber (HL) were dipped in 1-butyl-3-methylimidazolium chloride (BMIMCl) at 100°C, the BMIMCl-impregnated CF and HL were hot-pressed to give CF-BMIMCl and HL-BMIMCl composites, respectively. The BMIMCl contained in the composites was removed by Soxhlet extraction, and subsequently annealed to produce all-cellulose and all-wood composites (CF-A and HL-A). The SEM analyses revealed that cellulose fibers combined together for CF-A and the surface of HL-A became smooth, respectively. The XRD measurements indicated that the crystallinity index of cellulose component decreased by the hot press, increased by the extraction, and further increased by the annealing for both the composites. The tensile modulus of CF-A increased with increasing pressure of hot-press. Although tensile strength of HL-A was a little lower than that of original HL, tensile modulus of the former was much higher than that of the latter.
Double-stranded DNA (dsDNA) derived from pathogen- or host-damaged cells triggers innate immune responses when exposed to cytoplasm. However, the machinery underlying the primary recognition of ...intracellular dsDNA is obscure. Here we show that the DNA damage sensor, meiotic recombination 11 homolog A (MRE11), serves as a cytosolic sensor for dsDNA. Cells with a mutation of MRE11 gene derived from a patient with ataxia-telangiectasia–like disorder, and cells in which Mre11 was knocked down, had defects in dsDNA-induced type I IFN production. MRE11 physically interacted with dsDNA in the cytoplasm and was required for activation of stimulator of IFN genes (STING) and IRF3. RAD50, a binding protein to MRE11, was also required for dsDNA responses, whereas NBS1, another binding protein to MRE11, was dispensable. Collectively, our results suggest that the MRE11–RAD50 complex plays important roles in recognition of dsDNA and initiation of STING-dependent signaling, in addition to its role in DNA-damage responses.
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