透镜对豚鼠眼屈光不正和眼轴的作用

观察凹透镜和凸透镜对豚鼠眼球生长和屈光变化的影响，建立透镜诱导型屈光不正动物模型。方法：3～4周龄有色豚鼠47只，随机分成7组，右眼分别戴不同度数的凸或凹透镜，其左眼作为对照眼，戴镜前和戴镜后第11天分别测量其眼轴长度、屈光度，观察其变化。结果：戴镜后第11天与戴镜前相比，戴+4.00?D、+8.00?D组的豚鼠眼分别增加了+1.46?D与+1.58?D的相对远视（P＜0.05）；戴-4.00?D、-8.00?D、-15.00?D组的豚鼠分别增加了-2.92?D、-3.17?D、-3.10?D的相对近视（P＜0.01）；而戴0.00?D、-2.00?D组的豚鼠的屈光度差异无统计学意义（P＞0.05）。7组豚鼠的眼轴长度在实验眼和对照眼之间差异无统计学意义（P＞0.05）。结论：豚鼠眼球生长发育受透镜影响，可被用来建立一种简单经济的屈光不正动物模型。     

A novel brain receptor is expressed in a distinct population of olfactory sensory neurons

Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor-expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules.     

Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale

Oxytocin probably plays a role as a neurotransmitter/neuromodulator in the hippocampus of the rat. Oxytocin binding sites are present in the subiculum and CA1 region and oxytocin can excite a class of CA1 nonpyramidal neurons. In the present work we characterized the effect of oxytocin on hippocampal synaptic transmission. Whole-cell recordings were obtained from pyramidal neurons, in conditions of nearly symmetrical chloride concentrations. The selective oxytocin receptor agonist, [Thr4,Gly7]-oxytocin (TGOT), caused an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in virtually all neurons. These peptide-enhanced IPSCs were blocked by bicuculline, but not by strychnine, and reversed near 0 mV, indicating that they were mediated by gamma-aminobutyric acid (GABA)A receptors. On average, TGOT caused a nearly threefold increase in the frequency and almost a doubling in the amplitude of spontaneous IPSCs. TGOT did not influence the frequency and the amplitude of miniature IPSCs or spontaneous excitatory postsynaptic currents (EPSCs), and had no effect on evoked IPSCs. The peptide did not affect the basic membrane properties of pyramidal neurons or their GABA sensitivity. Thus, TGOT facilitated inhibitory transmission by exerting an excitatory action on the soma and/or dendrites of GABAergic interneurons. Extracellular recordings were performed in interneurons located in various hippocampal strata. Their sensitivity to TGOT was compared to that of substance P (SP). Interneurons in stratum pyramidale were excited both by TGOT and by SP. By contrast, stratum radiatum interneurons responded to SP but not to TGOT. In stratum oriens, half of the interneurons responded to SP, but only a minority to TGOT. Thus, oxytocin-responsive interneurons appear to be preferentially located in close vicinity of pyramidal neurons.     

Heme oxygenase1 (HSP-32) is induced in myelin-phagocytosing Schwann cells of injured sciatic nerves in the rat

Schwann cells participate in myelin phagocytosis in the early stage of Wallerian degeneration, prior to the recruitment of macrophages. This is the first report that Schwann cells induce heme oxygenase-1 (HO-1), a 32-kDa heat shock protein, only when they have transformed into myelin-phagocytosing cells from myelinating cells (days 2-3) immediately after crush injury of rat sciatic nerves. Double immunofluorescent labelling for HO-1 and transferrin receptors revealed that HO-1-immunoreactive Schwann cells also expressed transferrin receptors suggesting activation of iron metabolism. The transient induction of HO-1 in Schwann cells may contribute to the adaptive function in an altered environment when the cells have lost contact with axons, and may play a crucial role in the ensuing regeneration.     

Recovery from a recurrent major depressive episode

Episode-related factors and antidepressant treatment adequacy may be important determinants of recovery from a major depressive episode (MDE). We compared recovered and nonrecovered patients on baseline sociodemographic, clinical and episode-related measurements. Twenty-five inpatients with recurrent major depressive disorder diagnosed by SADS-L participated in this naturalistic, prospective, longitudinal study. Recovery, which was defined as a sustained return to non-depressed status lasting > or = 8 consecutive weeks, was assessed at 6- and 12-month follow-up with the Streamlined Longitudinal Interval Continuation Evaluation (SLICE). Thirteen (52%) patients met recovery criteria. The cumulative proportion remaining depressed for at least 52 weeks was 42.5%. Recovered patients had shorter episodes preceding the index hospitalization (P = .01). Despite adequate antidepressant pharmacotherapy, the length of the current episode remains the most important correlate of recovery from MDE recurrence. Our small sample size and the uncontrolled nature of treatment may limit the generalizability of these findings.     

Pre and postnatal diagnosis of fetus‐in‐fetu

Differentiation of abdominal masses detected on prenatal ultrasound is difficult and requires careful characterization of the mass and precise localization. Differentiation is required in order to distinguish benign from potentially malignant conditions. We describe a case of fetus‐in‐fetu with pre and postnatal imaging.     

Novel estrogen receptor ligands and their structure–activity relationship evaluated by scintillation proximity assay for high‐throughput screening

The estrogen receptor (ER) is an important drug target with allosteric characteristics that binds orthotopic hormones and other ligands. A recently developed scintillation proximity (SPA)‐based assay for high‐throughput screening (HTS) of compound libraries was used to identify novel estrogen receptor ligands that might have ER subtype selective binding activity. Radioligand binding was determined in a multi‐detector scintillation counter designed for microtitration plates. Equilibrium binding experiments and kinetic competition tests were performed with [³H]‐estradiol and human ERα and ERβ receptors. A library of 6,000 structurally diverse compounds was screened. From this, several novel ligands were identified that showed pronounced subtype‐selective differences in ligand binding for ERα and ERβ. The observed equilibrium dissociation constant (K_d) for the binding of [³H]estradiol to ERα and ERβ receptors were approximately 0.25 and 0.64 nM, respectively. When 17β‐estradiol, raloxifene and daidzein were tested for binding affinity to ERα in a competition assay, the IC₅₀ values were 0.34, 1.31, and 75.6 nM, respectively. When tested for binding affinity to ERβ, the IC₅₀ values were 1.05, 11.4, and 10.6 nM, respectively. The results obtained show that the methodology is valid in comparison to previously published data regarding estradiol and other standard compounds (raloxifene and daidzein) binding characteristics of estrogen receptors. The assay is also well suited to applied research as a tool in HTS of compound libraries in the search of ER ligands. Several novel active compounds were identified and selected as potent ER subtype ligands. Drug Dev Res 64:203–212, 2005. © 2005 Wiley‐Liss, Inc.     

Inhibition of cell cycle and induction of apoptosis by 2‐oxoheksyl isothiocyanate and alyssin in cell lines carrying various inherited BRCA1 mutations

An important aspect of the chemopreventive activity of isothiocyanates (ITC) is their ability to induce cell growth inhibition and apoptosis. In this study, the effect of two sulforaphane analogues, 2‐oxoheksyl isothiocyanate and alyssin, on lymphoblastoid cells, derived from people carrying four different germ‐line mutations in BRCA1 gene, was tested and compared to the effect on wild type cells. The mutations studied were: C61G; 3819del5; 4153delA, and 5382INSC. Changes in cell viability and density after 2‐oxoheksyl isothiocyanate and alyssin treatment were evaluated, as well as cell cycle progression, mitochondrial membrane potential changes, and phosphatidylserine externalization. Both isothiocyanates were shown to reduce cell viability and density in all cell lines tested, as well as the change in cell cycle phase's distribution. The response of cells to two ITC tested was various, as well as mutation type‐modulated. We found that change of cellular maintenance by chemopreventive agents can be modulated by single allele BRCA1 mutation. Drug Dev. Res. 65:84–92, 2005. © 2005 Wiley‐Liss, Inc.     

Synthesis of deuterium labelled 2‐bromobenzylamine by directed ortho‐metalation chemistry

Directed ortho‐metalation (DoM) strategy has been applied for the development of a short procedure for the regiospecific synthesis of [phenyl‐²H₄]‐2‐bromo‐benzylamine 6 starting from commercially available [phenyl‐²H₅]‐benzoyl chloride 1 . A strong isotope effect was observed during the ortho‐substitution. Copyright © 2005 John Wiley & Sons, Ltd.     

On the 99mTc‐labeling of isoniazid with different 99mTc cores

Recent advances in the chemistry of radiolabeling with ^99mTc such as use of the ^99mTc tricarbonyl and ^99mTc–HYNIC cores have revived interest in ^99mTc‐labeling of small biomolecules and further investigation as potential radiopharmaceuticals. Isoniazid, a drug commonly used for treatment of tuberculosis, has been chosen for the present study. Three distinct strategies were utilized to radiolabel isoniazid with ^99mTc. In the direct labeling protocol, the hydrazino amide functional group of isoniazid was used for ^99mTc‐labeling in the HYNIC sense using tricine and EDDA as co‐ligands. The other strategies of ^99mTc‐labeling involved the derivatization of isoniazid to its N, N‐diacetic acid derivative, which in turn was either used as a tridentate ligand for labeling with the [^99mTc(CO)₃(H₂O)₃]⁺ synthon or directly labeled by the conventional route wherein ^99mTc is in the +3 oxidation state. The complexes prepared in >95% yields were characterized by paper chromatography, thin layer chromatography and HPLC. Comparison of the three approaches showed that maximum specific activity and stability was obtained in the ^99mTc–isoniazid derivative synthesized via the tricarbonyl method. However, in vitro cell‐binding studies indicated that none of the ^99mTc–isoniazid complexes prepared had any appreciable uptake in Mycobacterium tuberculosis. Copyright © 2005 John Wiley & Sons, Ltd.