Effects of pineal indoles on ovarian response to gonadotropin-induced ovulation in mice

Summary Ovulation was induced in immature mice by injections of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) spaced 48 hours apart. The mice were divided into six groups: one group received intraperitoneal injections of normal saline, another group received alcoholic saline which was used as the vehicle of pineal indoles, and the remaining groups received respectively hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptamine (MTA) and methoxytryptophol (MTP). The pineal indoles were administered 24 hours before, on the same day as, 24 hours after and 48 hours after the PMSG injection. The mice were sacrificed 24 hours after the HCG injection. The numbers of growing primary follicles, multilaminar primary follicles, Graafian follicles, preovulatory follicles and corpora lutea in the ovary were not altered by treatment with pineal indoles. However, there was an increased incidence of follicular atresia in the groups treated with MEL, MTA and MTP. The pineal indoles did not affect the number of ovulated oocytes, but there was a large number of degenerated and fragmented ovulated oocytes in the MTA- and MTP-treated groups. Treatment with MEL, MTA and MTP also resulted in lower plasma levels of estradiol-17 and progesterone.     

Cultured chinese-hamster ovary cells lack a transferable x-radiation resistance factor

We determined if we could transfer X-radiation resistance from CHO AA8 cells to their radiosensitive, mutant V3 cells by several methods. These methods include co-incubating the two cell lines for three days before irradiation, adding heavily-irradiated AA8 to V3 cells following irradiation of the latter and then co-incubating these cells for at least eight days during the colony-forming assay and lastly, adding conditioned medium from unirradiated, subconfluent AA8 cells to V3 cultures and incubating for two days before irradiation. None of these procedures enhanced the clonogenic survival of the V3 cells to a single dose of 4 Gy X-radiation. Adding heavily-irradiated V3, instead of AA8, cells did not increase the clonogenic survival of the 4 Gy-irradiated V3 cells either, indicating that there was no autocrine mode of action. Moreover, adding conditioned medium from a related CHO cell line, K1, to its own radiosensitive, mutant 5-11 and incubating for two days before irradiation did not enhance clonogenic survival of the latter to a single dose of 3 Gy X-radiation. We therefore conclude that it is unlikely that CHO cells have the X-radiation resistance factor that has been reported in some mouse melanoma cell lines by other investigators.     

Cognitive and behavioral outcome following mild traumatic head injury in children.

OBJECTIVES: To investigate outcome in children with mild traumatic head injury (THI) at 1 week and 3 months postinjury and to identify factors associated with persisting problems. DESIGN: Postconcussional symptomatology, behavior ratings, and neuropsychological test performance were examined at 1 week and 3 months postinjury. SETTING: Participants were recruited from successive presentations to emergency departments of two major hospitals. PARTICIPANTS: 130 Children with mild THI were compared with 96 children having other minor injuries as controls. RESULTS: Children with mild THI experienced headaches, dizziness, and fatigue but exhibited no cognitive impairments, relative to controls, at 1 week postinjury. By 3 months, symptoms had resolved. However, 17% of children showed significant ongoing problems. They were more likely to have a history of previous head injury, learning difficulties, neurological or psychiatric problems, or family stressors. CONCLUSIONS: Persisting problems following mild head injury in children are more common in those with previous head injury, preexisting learning difficulties, or neurological, psychiatric, or family problems. These "at-risk" children should be identified in the emergency department and monitored.     

Regulation of striatal dopamine release through 5-HT1 and 5-HT2 receptors

Dopamine (DA) release in the striatum is regulated by 5-hydroxytryptamine (5-HT, serotonin) through putative heteroreceptors. However, the effect of 5-HT is controversial. The present study investigated the effects of different 5-HT receptor ligands on DA release in the rat striatum by using in vivo microdialysis in conscious and freely moving rats. Perfusion with 5-carboxamidotryptamine, anpirtoline, pindobind-5-HT1A, and isamoltane demonstrated the involvement of 5-HT1A and 5-HT1B receptors in facilitating DA release. In contrast, 5-HT2 receptors mediated inhibition of DA efflux, as shown by experiments with DOI [R-(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and ketanserin. A 5-HT3 agonist (1-(m-chlorophenyl)-biguanide hydrochloride) did not have any effect. None of the agonists used affected DA uptake into striatal synaptosomes. Unilateral 6-hydroxydopamine lesioning of the nigrostriatal DA pathway led to a selective decrease in 5-HT2 receptors. It is concluded that there are 5-HT2 heteroreceptors at the dopaminergic terminals that mediate inhibition of DA release. Further investigation is required to clarify the localization of the 5-HT1 receptors in the striatum.     

Isolated pedunculated congenital corneal dermoid

PURPOSE: To investigate a case of isolated pedunculated congenital corneal dermoid. METHODS: Case report. RESULTS: In a 14-day-old infant, the pedunculated portion of the dermoid was removed and confirmed by histopathologic examination. No surgical complication or recurrence was encountered, and the patient is waiting for a rotational autokeratoplasty. CONCLUSIONS: Prompt treatment of such an unusual tumor is important to allow for visual rehabilitation and development.     

Discovery of novel non-peptide CCR1 receptor antagonists

Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.     

Random primed polymerase chain reaction differentiates Codonopsis pilosula from different localities

DNA fingerprints distinctive among the samples from different localities in China were successfully reproduced for the Chinese herb Dangshen, the roots of CODONOPSIS PILOSULA, (Campanulaceae). Similarity index (S.I.) analysis revealed that C. PILOSULA samples from the same province generated similar DNA fingerprints, while samples of different provinces displayed different DNA fingerprints. This method may be a general and valuable tool for locality authentication of other Chinese herbal medicinal materials.