Carbamazepine-Induced Cardiovascular Abnormalities in Chick Embryos

ABSTRACT  Carbamazepine dissolved in propylene glycol was administered to chick embryos in order to determine its teratogenicity in the cardiovascular system. A single dose of 3, 5, 7, or 10 mg was administered at 72 hours of incubation (Hamburger-Hamilton stage 18). On day 10 of incubation, embryos were removed and examined for cardiovascular abnormalities. Cardiovascular abnormalities were noted in 37.8%, 54.8%, 76.9%, and 88.0% of live embryos in groups treated with 3, 5, 7, and 10 mg, respectively. Our experiment represented a statistically significant increase of cardiovascular abnormalities and showed a significant dose-dependent increase. Infundibular ventricular septa1 defect was the primary cardiac anomaly observed in this study. A high percentage of this anomaly was accompanied by hypoplastic right 6th aortic arch artery and/or persistent left 4th aortic arch artery. A small number of double outlet right ventricle was found.     

Maldevelopment of Early Chick Embryos Induced by NonThermogenic Dose Radio Frequency Radiation at 428 MHz for the First 48 Hours

ABSTRACT Exposure of developing chick embryos to non-thermogenic dose of 428 MHz radio frequency (RF) have been reported to cause embryo lethality, teratogenicity and delayed hatching (Saito et al., 1991). To elucidate the mechanisms of such adverse biological effects, developing chick embryos were exposed to 428 MHz RF at 5.5 mW/cm2 for the first 48 hrs of incubation. Ten fertilized eggs were used in each experiment; exposure and sham-exposure were alternatively repeated 10 times. Embryos were examined on viability, then excised, fixed in alcohol and examined morphologically on the developing status. Some embryos were subjected to histological study. In the exposed group, embryos were alive but the development was severely delayed. The average number of somites was 10.5±2.8 SD in the exposed group and 13.1 ± 2.3 in the control, respectively. Embryos with less than 10 somites were about 27% in the exposed group. The munimum number of somites was 3 in the exposed group and 7 in the control. Developmental delay was about 6 to 16 hrs in terms of Hamburger-Hamilton stage. Two cases of duplication anomalies were detected at positions in the incubator with severely affected corresponded to those with high embryo lethality in our previous study. Histological observations suggested developmental delay might not be due to direct cytotoxicity but to the slower cell proliferation and/or to disturbances of cell-cell interaction, migration and orientation. The possibility that non-thermogenic RF electromagnetic field may affect early embryogenesis indirectly through physico-chemical modifications of metal-containing proteins are discussesd.     

Conotruncal Anomalies Induced in Chick Embryos by 2 MeV Neutron Radiation

Radiation of 2 MeV neutrons was used to induce conotruncal anomalies experimentally in chick. White leghorn eggs were exposed to a single dose of neutrons ranging from 50 to 250 rads at various stages of the development. Cardiovascular anomalies were found in 209 (40%) of 526 treated embryos; conotruncal anomalies (81/209 or 39%), simple VSD (56/209 or 27%), isolated aortic arch anomalies (69/209 or 33%) and others (3/209 or 1%). The conotruncal anomalies were induced at considerably high incidences by exposures during the 3rd day of incubation and the highest incidence was 74% in the cases malformed by 220 rads. The types of conotruncal anomalies observed were as follows: VSD with pulmonary overriding (52 cases), VSD with aortic overriding (11 cases), DORV (10 cases), truncus arteriosus (6 cases) and complete TGA (2 cases). Sixty (74%) of these cases had aortic hypoplasia, constituting coarctation or interruption complex similar to that seen in man. It is generally thought that the experimental production of complete TGA in chick appears to be impossible when utilizing ordinary teratogenic means. However, neutron radiation could induce this peculiar anomaly in chick.     

鸡胚神经管缺陷脊髓病理与组织化学研究

目的 鸡胚内注射甲氨喋呤（ＭＴＸ）,制作鸡神经管缺陷动物模型。利用该模型,进一步研究观察病变的病理变化及组织化学改变。方法 选用上海农科院“莱杭”鸡受蛋６６校,在孵化期第４、５天,注射ＭＴＸ,计量为：０．０１ｍｇ／ｋｇ及０．０２ｍｇ／ｋｇ。孵化３周后,选取病变鸡,采用ＮＡＤＰＨ－黄麦组织化学染色,测定变脊髓神经元ＮＯＳ含量;电镜观察病变脊髓神经元内线粒体结构变化。结果 ＮＡＤＰＨ－黄递酶组织化学染     

Analysis of Cardiac Loop Formation in Avian Embryos with Spontaneous Heart Malformations

Abstract Embryos with heart tube malformations on the 2nd and 3rd day of incubation were selected to support the hypothesis that the heart tube rotates and bends to the right due to the stronger tension generated on the right side of the heart primordium than that on the left side.
In 4 embryos, lateral endothelial heart tubes did not fuse at the midline, and each heart tube looped independently. It is suggested that each lateral heart tube generates tension, and can bend to its own side. In 8 conjoined twins in which 2 embryos shared a head and each embryo extended in opposite directions, lateral endothelial heart tubes did not fuse within the embryo on the ventral side, but fused between the sister embryos lateral to the embryos. Such heart tubes bent to the left. Since the heart tubes fused between the sister embryos, the heart primordium on the right side for each embryo occupied the left side of the fused heart tube. Thus in this case our hypothesis that the right-side-derived heart tube generates stronger tension for bending is valid. Heart tubes of 5 other parallel twins also supported our hypothesis.     

Morphological Analysis of Neural Tube Defects in Non-obese Diabetic (NOD) Mouse Embryos

Neural tube defects (NTDs) were demonstrated to occur at a high rate (29.4%) in non-obese diabetic (NOD) mouse embryos on day 13 of gestation. Macro-scopically, three different forms of NTDs were observed: the combined form of exen-cephaly and myeloschisis, the pure form of exencephaly, and that of myeloschisis. The neural walls of the open tube were everted bilaterally. It was microscopically demonstrated that NTDs were composed of not only the everted neural walls but also voluminous mesenchymal tissue adjacent to the everted neural walls. The everted neural wall had three-layered structure made up of outer, intermediate, and inner zones. The morphological findings of the intermediate and inner zones were similar to those of mantle and marginal layers in the normally closed neural tube. However, the outer zone, which corresponded to the ependymal layer in the normal neural tube, had characteristic findings. Namely, the cells were small, round and uniform in shape. Almost no mitotic figures were observed in this zone, and electron microscopic investigation revealed few cytoplasmic organelles. Of 9 NOD mouse embryos with NTDs, 2 exhibited duplicated notochords. In one of these two embryos, an aberrant tubal structure was formed of neural tissue. The plausible causes of NTDs in NOD mouse embryos were discussed based on these findings.     

Brain lactate in preterm and growth–retarded neonates

Glucose is the predominant cerebral energy source under physiological conditions, although other substrates may support cerebral metabolism. The present study was undertaken to determine if lactate is present in the immature human brain, and if so, whether or not concentrations of lactate differ between small–for–gestational–age and appropriate–for–gestational–age infants. Thirty stable, healthy infants with normal brains were investigated. As the only nutrient, all received milk enterally prior to the investigation, which was carried out without sedation. Mean gestational age was 35 completed weeks (range 28–41 weeks) and mean birth weight was 2170g (range 855–4100 g). Proton nuclear magnetic resonance spectra from the striatal region were obtained while the infants were sleeping quietly. Lactate was present in all 10 preterm small–for–gestational–age and 10 of 13 preterm appropriate–for–gestational–age infants, and the concentration was inversely related to postmenstrual age ( p < 0.002). In addition, lactate increased with the degree of growth retardation ( p < 0.01). At present the significance of lactate is unclear. Lactate may be produced locally or in peripheral tissues, and may support brain metabolism.     

������԰�������MRI ��ϼ����񾭷������

脑白质损伤(white matter damage,WMD)是指胎龄24～35周的早产未成熟儿,由于血管损伤或炎症反应等多种因素导致的大脑白质损伤。受累部分主要分布于脑室旁白质,包括深层脑白质的局灶坏死和中央脑白质的弥漫性病变。     

Functional Damage in the Developing Brain Induced by Maternal Environmental Agents: Ethanol, Tobacco and Low-Copper Level

To evaluate tests for behavioral teratology in animals, brain dysfunction caused by maternal environmental agents is compared both epidemiologically and experimentally. Ethanol: The features of CNS involvement in human FAS (fetal alcohol syndrome) and FAE (fetal alcohol effects) are developmental delay and intellectual impairment. One of the most vulnerable structures in the rat fetus exposed to ethanol in utero is the synaptic formation in the hippocampus. What test for brain dysfunctions, such as deficits in learning, inhibition and attention, is there? Tobacco: Thirty-three percent of human FTS (fetal tobacco syndrome) cases have CNS involvement, which is characterized by developmental delay, and behavioral problems such as a short attention span and hyperactivity. As to the concomitant effects of ethanol and tobacco on human offspring, CNS involvement appeared to be most specific for alcohol exposure, but was also observed slightly with smoking without drinking. How can the effects of concomitant substances be discriminated in an animal test? Low-copper level in brain: Related to the development of their offspring, abnormal movements in brindled mutant mouse heterozygotes are observed. These findings may be influenced by both copper and oxygen radical metabolism. The teratogenic effects of triethylene tetramine dihydrochloride, a chelating drug for copper on the fetal mouse brain are noted both grossly and microscopically. How can the abnormal CNS development in relation to a certain biochemical mechanism be detected by means of an animal test? In conclusion, to examine behavioral teratology in animals, specificity and accuracy should be considered in comparison with in humans.     

The Effect of MCT Oil Supplement in Very Low Birth Weight Infants, with Evaluation by the 13C-Labeled MCT Breath Test

We studied the efficacy of medium-chain triglyceride (MCT) as an energy source in premature infants. Infants who were given 3 g/kg/day of MCT oil gained body weight better than the control group in spite of a smaller water intake. This is advantageous to premature infants who need water restriction due to patent ductus arteriosus (PDA), bronchopulmo nary dysplasia (BPD), etc. We also proved that MCT oil is rapidly absorbed and digested, by means of the ¹³C-trioctanoin breath test.     

Bis(dicholroacetyl)diamine-induced Craniofacial Anomalies in Jcl: ICR and A/J Mice

Abstract Craniofacial anomalies induced by bis(dichloroacetyl)diamine (bisdiamine) were studied in two strains of mice, Jcl:ICR and A/J. Bisdiamine was given by oral intubation at a dose of 3,200 mg/kg/day at days 7.5 and 8.5, 8.5 and 9.5, 9.5 and 10.5 or 10.5 and 11.5 of pregnancy (VP = day 0). A/J was more susceptible to embryolethal effects of bisdiamine and had a longer sensitive period to teratogenic effects of bisdiamine. The most susceptible period for craniofacial anomalies induced by bisdiamine in A/J was one day later than that in Jcl:ICR. In both strains, median facial anomalies, cleft palate, protuberance(s) on the forehead and open eyelids were commonly induced craniofacial anomalies. Median facial anomalies were more frequent and also more severe in Jcl:ICR, while lateral cleft lip was observed only in A/J.
Strain differences for embryolethality and types and frequencies of craniofacial anomalies are discussed on the basis of genetic homozygosity, craniofacial development and embryonic face shape immediately before the fusion of the nasal prominences. Neural crest cells are thought to be the target of bisdiamine.     

Invasive bacterial diarrhea in Bangalore

Diarrheal diseases studied in 379 children below five years of age during the period January to December 1983 were classified as “invasive” or “secretory” in relation to the etiological agents. The common invasive agents were shigellae, salmonellae andCampylobacter jejuni and they contributed to a larger percentage in all age-groups except in the 7–12 months, when secretory diarrhea due to rotavirus etiology was predominant.Salmonelly typhimurium was most commonly isolated in infants below one year, while shigellae were the most common enteropathogens in the preschool age group.C. jejuni was infrequent. Common Shigella serotypes wereSh. dysenteriae type I and different serotypes ofSh. flexneri having multidrug resistance. While the resistance pattern ofSh. dysenteriae type I was CST Cot, forSh. flexneri it was ACST or ACST Cot and forS. typhimurium it was ACSTNK Cot. Drug resistance was not seen inC. jejuni. The study has highlighted the problem of invasive diarhea and the significant role played by shigellae and salmonellae in the etiology of diarrheal diseases in and around Bangalore.