LHRH-A对孕中期大鼠抗妊娠作用的研究

本文观察了[D-Ala⁶,Pro⁹-Ethylamide¹⁰]-LHRH(LHRH-A)对孕中期大鼠的抗妊娠作用。结果显示:在孕9～11d sc 200μg/d LHRH-A,血浆孕酮水平自第二次给药后明显下降(P<0.05),给药大鼠均流产终止妊娠;LHRH-A的抗妊娠作用可被醋酸甲地孕酮所拮抗;LHRH-A对体外培养的假孕大鼠和孕d 9大鼠黄体细胞分泌孕酮有明显的直接抑制作用。     

Synaptic 5'-nucleotidase is transient and indicative of climbing fiber plasticity during the postnatal development of rat cerebellum

The transient appearance of 5'-nucleotidase, an adenosine-producing ecto-enzyme, was studied during specific stages of postnatal synaptogenesis in the rat cerebellum. For ultrastructural detection of 5'-nucleotidase activity, an enzyme-cytochemical technique was used. Between postnatal days 4 and 6, enzymatic reaction product was present in the synaptic clefts of climbing fibers containing the perisomatic spines, apical cones and emerging dendrites of Purkinje cells (CF-PC synapses). Labeled parallel fiber synapses were observed on dendritic shafts of cerebellar interneurons. At postnatal days 9 and 12, enzyme-positive parallel fiber terminals were in addition numerous on the spines of peripheral Purkinje branchlets, and gradually disappeared thereafter. Between postnatal days 8 and 15, labeling of perisomatic CF-PC contacts persisted. In contrast, climbing fiber synapses on Purkinje dendrites were only occasionally labeled. Between postnatal days 18 and 21, synaptic reaction product was restricted to mossy fibers. At the same time, association of 5'-nucleotidase with glial profiles was prominent throughout the cerebellar layers. In adult cerebellum (from 24 days onwards) all synapses were devoid of enzymatic activity. Throughout development, basket, stellate and Golgi cell synapses were devoid of enzymatic activity. We conclude that 5'-nucleotidase is present in excitatory cerebellar synapses during part of their generation period. The transient nature of this phenomenon suggests that 5'-nucleotidase may serve as a novel, cytochemical marker for a specific state of synaptic maturation, and in particular for climbing fiber plasticity. A role of 5'-nucleotidase in purinergic neuromodulation and cellular contact formation could be significant in these processes.     

Suramin inhibits gonadotropin action in rat testis: implications for treatment of advanced prostate cancer.

Suramin is being evaluated for the treatment of metastatic prostate cancer based on its inhibition of growth factor action. In addition, suramin may inhibit the endocrine control of androgen production, which was explored herein. Adult Sprague-Dawley rats were injected (i.p.) daily with varying doses of suramin. At a cumulative dose of 200 mg., suramin significantly depressed serum testosterone (p less than 0.05), and follicle stimulating hormone (p less than 0.002) levels. In vitro studies showed that suramin-mediated suppression of androgen production might be secondary to inhibition of gonadotropin action. In MA-10 cell cultures, suramin inhibited a maximum stimulatory dose of human chorionic gonadotropin with an ED50 of 4.4 microM. Studies in rat Sertoli cell cultures showed that follicle stimulating hormone action was also inhibited by suramin, with an ED50 of 8.6 microM. Using receptor binding assays with calf testis membrane, we showed that suramin inhibited 125I-hFSH binding to receptor in a dose dependent fashion with an ED50 of 10.4 microM; comparable to the ED50 of suramin inhibition of follicle stimulating hormone action in Sertoli cell culture cells. Thus the mechanism of suramin's suppression of androgen production may involve multiple sites of action, including inhibition of gonadotropin binding to its receptor and suppression of pituitary gonadotropin levels in serum. This inhibition of androgen production may be useful in the treatment of advanced prostate cancer.     

Instrument effects on smoothness discrimination.

Dental and dental hygiene faculty must select instruments to be used for root surface evaluation during scaling and root planing procedures. Because little information has been reported comparing the effectiveness of various instruments for this task, selection is based on subjective opinions. This study examined differences in the ability of 30 experienced and 32 inexperienced dental hygiene clinicians to differentiate degrees of surface smoothness using five different dental instruments. The relative smoothness test consisted of a set of ten paired abrasive strips of different or the same grit size. Repeated measures ANOVA revealed significance for both main effects, instrument used and experience level. All subjects made more correct assessments with the Williams probe, 3A explorer and Moffitt-MD probe than with the #17 explorer. There was no significant difference between the 3CH explorer and the other four instruments. Experienced clinicians scored significantly higher than students on the relative smoothness test. Instrument selection could affect the end products achieved by clinicians, as well as affecting validity and reliability of current clinical evaluation mechanisms.     

Heterogeneity of congenital primary hypothyroidism: the importance of thyroid scintigraphy

Current newborn screening programs in California and most of the U.S. depend for diagnosis of congenital primary hypothyroidism on demonstrating an elevated thyrotropin (TSH) level in infants with the lowest 5% to 10% of thyroxine (T4) levels by filter-paper bloodspot test. The diagnosis of primary congenital hypothyroidism based on low T4 with high TSH fails to distinguish between transient hypothyroidism, ectopic or hypoplastic thyroid, athyrosis, dyshormonogenesis, and transient hyperthyrotropinemia. We screened 166,300 newborn infants for primary congenital hypothyroidism for 6.5 years and confirmed the diagnosis in 46 cases; none of these patients had a goiter. Thyroid scintigraphy was performed in 40 with technetium-99m (Tc-99m) in the first eight cases tested and iodine-123 (I-123) in 29 of the last 32 cases. Fifteen infants were athyroid and seven had ectopic or hypoplastic glands; in 18 the thyroid gland appeared normal (present, normal location). Congenital hypothyroidism represents a spectrum of diseases from transient underactivity to complete absence of the thyroid gland. We recommend that, before starting treatment, a specific anatomic and functional diagnosis be confirmed by thyroid scintigraphy and other thyroid function tests.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Cytochemical Redistribution of 5'-Nucleotidase in the Developing Cat Visual Cortex

The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol. , 296 , 379 – 392, 1990). Using an enzyme-cytochemical technique, we now investigate the developmental redistribution of 5'-nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5'-nucleotidase at synapses parallels the time-course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse-bound 5'-nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme.