ABSTRACT 2-(2′-hydroxy-3′,5′-di-tert-butylphenyl)benzotriazole (HDBB) is an ultraviolet absorber used in plastic resin products, such as building materials and automobile components. In oral repeated dose toxicity studies using 5- or 6-week-old rats, this chemical induced hepatic histopathological changes, such as hypertrophy accompanied with eosinophilic granular changes and focal necrosis of hepatocytes, and male rats showed nearly 25 times higher susceptibility to the toxic effects than females. Castration at approximately 4 weeks of age markedly reduced the sex-related variation in HDBB toxicity, but some difference, less than five times, remained between male and female castrated rats. Following oral HDBB administration to male and female juvenile rats from postnatal days 4–21, such gender-related difference in toxic susceptibility was not detected; therefore, it is speculated that the determinants of susceptibility to HDBB toxicity are differentiated between sexes after weaning. In young rats given HDBB, there was no gender-related difference in plasma HDBB concentration, and no metabolites were detected in the plasma of either sex. HDBB induced lauric acid 12-hydroxylase activity in the liver and this change was more pronounced in males than in females. These findings indicate that HDBB could show hepatic peroxisome proliferation activity, and the difference in the susceptibility of male and female rats to this effect might lead to marked gender-related differences in toxicity.
ABSTRACT Interleukin (IL)-15 interacts with components of the IL-2 receptor (R) and exhibits T cell-stimulating activity similar to that of IL-2. In addition, IL-15 is widely expressed in many cell types and tissues, including the central nervous system. We provide evidence of a novel role of IL-15 in olfactory neurogenesis. Both IL-15 and IL-15Rα were expressed in neuronal precursor cells of the developing olfactory epithelium in mice. Adult IL-15Rα knockout mice had fewer mature olfactory neurons and proliferating cells than wild-type. Our results suggest that IL-15 plays an important role in regulating cell proliferation in olfactory neurogenesis.
ABSTRACT This is a prospective observational study on the profile of central nervous system (CNS) anomalies in a neurosurgical unit in Ikeja, Nigeria. All cases of CNS anomalies seen by the authors in 1 year, January to December 2005, were analyzed. Descriptive variables include some demographics of the patients and their parents; profiles of CNS anomalies, cranial or spinal, neural tube defects (NTD) or others; presence of associated anomalies; and rate of surgical correction of these anomalies. Sixty-one cases were recorded, approximately 64% of our total pediatric neurosurgical output. Forty-one cases were males, 20 females, with a male to female ratio of approximately 2 to 1. The age at presentation ranged from 2 days to 60 months (mean 5.6 months) and the majority of the parents were young (the mean ages of the fathers and mothers were 35 years and 28 years, respectively), and low income earners (70%). The cases comprised cranial (61%) and spinal (39%) anomalies, or 54% of NTD versus others. The cranial lesions were mainly congenital primary hydrocephalus in 44% of cases, encephalocele in 28%, and microcephaly in 17%. The spinal lesions were spinal dysraphism in more than 90%; all in the lumbosacral region. Seventy percent of the NTD had associated cranial or other system anomalies, mainly secondary hydrocephalus in 65%. The surgical correction rate of all of these cases was 38%. NTD were significantly more likely to present early, be associated with other anomalies and undergo surgical correction in this series (P < 0.001). CNS congenital anomalies are under-reported in Nigeria and other developing countries. A call is made for the establishment of nationwide efforts to fully clarify the epidemiology of this silent epidemic.
ABSTRACT We previously found newborns exhibiting syndactyly of both fore- and hindlimbs in a litter from a pair of Sprague Dawley rats. Continuous breeding of the parental animals yielded pups with the same anomaly in following litters, suggesting that the syndactyly was genetic in origin. In the present study, as all the syndactylous pups died on postnatal day 0, we conducted genetic analyses using 30 phenotypically normal female progeny and the sire. The females were subjected to caesarean section on day 20 of gestation and the fetuses were examined for the phenotypes. The results of the mating experiments suggest that the mutant phenotype is caused by a single autosomal recessive gene at a homozygous condition. As homozygous mutants are lethal at the neonatal stage, the mutant gene was named syndactyly lethal, gene symbol syl. The mutant rats have multiple abnormalities, such as syndactyly, micrognathia, fused/absent/small lung lobes, absent kidney and ureter, small spleen, small uterus, fused phalanges, sternoschisis, absent/detached rib, and splitting/fused/absent/small thoracic vertebra, some of which must be the cause of death on postnatal day 0. This mutant is considered to be useful for investigating the mechanisms and/or pathogenesis of syndactyly, as well as the accompanying malformations.
ABSTRACT Estrogens cause embryonic lethality and the disturbance of early placental development in mice. Diethylstilbestrol (DES) at 1, 10, or 100 µg/kg was orally administered to Institute of Cancer Research mice on gestational days (GD) 4 through 8, and the uterus and placenta were examined histopathologically on GD 9. Decidua of DES-treated mice showed insufficient development, and the uterine lumen at the implantation site did not effectively minimize. The trophoblast giant cell layer was not separated from the uterine lumen by the decidua capsularis, and hemorrhage from the denuded trophoblast giant cell layer into the uterine lumen was noted at the peripheral part of the decidua basalis. The results of the present study suggest that decidual hypoplasia and subsequent placental hemorrhage causes fetal death due to the administration of DES during the early stage of pregnancy.
ABSTRACT A 22-year-old pregnant woman noticed a rapid increase of abdominal growth, uterine tenderness and irregular contraction, for which she hospitalized at 25 weeks of gestation. An ultrasound examination demonstrated a single fetus with normal anatomy and massive hydramnios. Serial therapeutic amniocentesis was performed for relief of maternal symptoms and indomethacin compress was initiated. Both the maternal and amniotic fluid IgM were positive for cytomegalovirus (CMV). Maternal compress indomethacin was discontinued at 32 weeks. Cesarean section was performed due to fetal distress at 34 weeks of gestation. A female infant was delivered and the neonatal examination was within normal limits with urine culture positive for CMV. At 1 year of age the child was developing normally with normal hearing and no clinical sequelae of intrauterine CMV infection. We postulate that serial and large volume reduction of amniotic fluid by amniocentesis and compress indomethacin in our case interrupted the natural course and provided sufficient time for the fetus to recover from the acute phase of viral infection.
ABSTRACT Complete third branchial arch anomalies are rare and have been described only in case reports, affecting mainly children and typically presenting as a cervical inflammatory process. Anomalies of the third and fourth branchial apparatus, though rare, usually present as sinuses/incomplete fistulas of pyriform sinus or recurrent suppurative thyroiditis. A 6-year-old girl presented with a small opening on the left side of her anterior neck, which had been present since birth and was associated with recurrent infection. She had no history of incision and drainage of swelling. Computed tomography with contrast injection into the cervical opening revealed a fistulous tract extending from the cervical neck skin to the pyriform fossa. Complete excision of the fistulous tract and left hemithyroidectomy were performed. There was no recurrence at 22 months of follow-up.