广东省中山市头癣现状及其病原体分离结果分析

目的:了解广东省中山地区头癣现状及其病原体分布、流行情况。方法:对107例镜检阳性病发进行真菌培养、鉴定和临床分析。结果:107例患者中白癣81例(占75.7％),脓癣24例(22.4％),黑癣2例(1.9％),未发现黄癣。107例病发分离出5种共101个菌株,其中犬小孢子菌90株(占89.1％),须癣毛癣菌5株(4.9％),红色毛癣菌3株(2.79％),断发毛癣菌2株(1.98％),紫色毛癣菌1株(0.99％)。结论:广东省中山地区头癣种类以白癣为主,脓癣次之,黑癣少见,黄癣基本消失,流行的病原菌以亲动物性的犬小孢子菌占绝对多数。发病年龄以1岁～15岁的少年儿童为主,成年人少见。     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

Synthesis of 4‐[18F]fluoroiodobenzene and its application in sonogashira cross‐coupling reactions

The first application of a Sonogashira cross‐coupling reaction in ¹⁸F chemistry has been developed. The reaction was exemplified by the cross‐coupling of terminal alkynes (ethynylcyclopentyl carbinol 6 , 17α‐ethynyl‐3,17β‐estradiol 7 and 17α‐ethynyl‐3‐methoxy‐3,17β‐estradiol 8 ) with 4‐[¹⁸F]fluoroiodobenzene. 4,4′‐Diiododiaryliodonium salts were used as precursors for the synthesis of 4‐[¹⁸F]fluoroiodobenzene, enabling the convenient access to 4‐[¹⁸F]fluoroiodobenzene in 13–70% yield using conventional heating or microwave activation. The Sonogashira cross‐coupling of 4‐[¹⁸F]fluoroiodobenzene with terminal alkynes gave the corresponding 4‐[¹⁸F]fluorophenylethynyl‐substituted compounds [¹⁸F]‐9 , [¹⁸F]‐10 and [¹⁸F]‐13 in yields up to 88% within 20 min of starting from 4‐[¹⁸F]fluoroiodobenzene. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of JTT‐501 and its metabolite JTP‐20604 labelled with 13C

JTT‐501 specifically labelled with ¹³C was obtained via a four‐step synthesis at an isotopic enrichment level of 99% and in 14% overall chemical yield starting from 4‐hydroxy‐[ring‐U‐¹³C₆]benzaldehyde (3) . The hydrogenation of [¹³C₆]JTT‐501 over Pd/C gave [¹³C₆]JTP‐20604 in 90% chemical yield. Copyright © 2003 John Wiley & Sons, Ltd.     

MR Lymphography with a Lymphotropic T1-Type MR Contrast Agent: Gd-DTPA-PGM

A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T¹-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6–12 μmol Gd/kg. Tumor-lymph node contrast increased from 0.0 ± 1.2 precontrast to 19.2 ± 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60°) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.     

Dye coupling between dorsal raphe neurones

Neurones in the dorsal raphe nucleus (DRN) were impaled and filled with biocytin in coronal slices of midbrain taken from young adult rats. The electrophysiological properties and gross morphology of the cells were similar to those reported previously for serotonergic neurones in the DRN. Of 27 cases in which filled neurones were recovered in histological material, almost half (48%) showed labelling of two or three cells, although only one cell had been recorded from. Coupled cells were identified as close or distantly coupled, depending on the distance from the soma of the presumed impaled cell (23.5±15 m, n=7 and 150±26.5 m, n=10 respectively). Whereas close-coupled cells may have been artefactually coupled by the penetrating electrode, coupling between distant cells is most likely to be a result of transfer of biocytin through gap junctions. Camera lucida reconstructions of pairs of labelled cells revealed extensive overlap of dendritic fields and numerous crossings between dendrites. When examined at high magnification under a light microscope, many of the crossing dendrites were found to travel in different focal planes. Nevertheless, for each pair of cells, at least one point of close apposition was observed between dendrites or between the axon and a dendrite of the presumed impaled and coupled cell. The incidence of dye coupling between neurones in the DRN may reflect a relatively high level of electrotonic coupling between the neurones. This form of coupling may be important in determining the synchronous nature of firing of neurones in the DRN.     

The role of intracellular calcium stores in motilin induced contractions of the longitudinal muscle of the rabbit duodenum

Summary The contraction of longitudinal muscle strips of the rabbit duodenum in response to motilin and acetylcholine was investigated in normal and high K⁺-solutions in the presence and absence of external calcium, in order to demonstrate the existence of pharmaco-mechanical coupling for motilin and to examine whether the peptide mobilizes calcium from an intracellular store. In depolarized smooth muscle (140 mM K⁺), motilin (3.2×10⁹ –1×10^–7 M) and acetylcholine (1×10^–5 M) were still capable of causing a considerable, transient, concentration-dependent contraction in the presence of Ca²⁺. The extra-contraction to motilin was not blocked by tetrodotoxin (1 g/ml) nor by atropine (10^–7 M), but acetylcholine (10^–5 M) was blocked by atropine. Verapamil (10^–7 M) could selectively block the K⁺ contraction without affecting the extra agonist contraction. Nitroprusside was ineffective up to 10^–4 M in high K⁺-solutions, but in normal Hepes-buffer it caused a concentration-dependent rightward shift of the concentration-response curve of motilin and acetylcholine contractions. In a calcium-depleted medium, high K⁺-depolarized muscle strips were still responsive to motilin and acetylcholine, but higher concentrations (10^–6 M) were needed than in the presence of calcium and the contractions reached only 57 +- 11% and 74 +- 9% respectively of the maximal contraction in 1.2 mM Ca²⁺ containing solutions. The response to motilin (10^–6 M) was not only smaller than that to acetylcholine (10^–5 M), it also faded more rapidly with time. The response to one agonist could not be repeated except by using a higher concentration of the same or the other agonist, and the magnitude of this second response depended upon the dose used in the first one. We conclude that pharmaco-mechanical coupling exists for motilin and that this peptide is able to elicit contractions by mobilization of calcium from an intracellular store. This store overlaps with the one used by acetylcholine. Our experiments also reinforce the hypothesis that in the rabbit motilin exerts a direct action upon smooth muscle cells.     

Development of an ELISA for detection of an organophosphorus compound using monoclonal antibodies

This paper describes a specific and highly sensitive ELISA system using monoclonal antibodies in order to assay an organophosphorus compound. The soman derivative methyl phosphonic acid, p-aminophenyl 1,2,2,-trimethyl-propyl diester (MATP) served as model substance. In order to obtain antibody-producing hybridomas BALB/c mice were immunized with MATP linked onto human serum albumin (HSA). The spleen cells of immunized mice were fused with syngenic plasmacytomas of the non-producer-line X63Ag8.653 with the aid of polyethylene glycol. To eliminate undesirable cross-reaction, common screening procedures were modified by directly coating the ELISA plates with hapten. Five out of 15 positive cell-lines were cloned by limiting dilution and further propagated. The respective immunoglobulin class and subclass of the obtained monoclonal antibodies was determined. Four of which were identified as IgG₁, the other as IgG_2a. After enrichment of antibodies in ascites and their isolation by protein A-sepharose, the affinity of various monoclonal antibodies was estimated in competitive inhibition enzyme immunoassay (CIEIA) by measuring the IC₅₀ rates of free MATP. The rates were found to lie between 2.5 × 10^–6 mol/l and 4.3 × 10^–4 mol/l MATP. The IC₁₀ rate for detectable MATP concentration was 5.4 × 10^–7 mol/l MATP. Test duration was 280 min. The reactivity of the monoclonal antibodies with structurally related substances was used to check their specificity. Cross-reaction turned out to be negative. In order to develop a direct competitive ELISA, MATP was linked to horse radish peroxidase (HRPO) by adding a spacer. This helped to reduce total duration to 40 min. The detection level was further reduced to 1.3 × 10^–7 mol/l MATP (corresponding to 975 pg/25 l test-buffer) using the monoclonal antibody F71D7. Likewise, MATP was detected in goat serum, chicken serum, rabbit serum, milk and company's water in concentrations between 2.1 × 10^–7 mol/l (IC₁₀, company's water) and 4.9 × 10^–8 mol/l (IC₁₀, milk).     

Role of nitric oxide in skeletal muscle: synthesis,distribution and functional importance

Over the last two decades, nitric oxide (NO) has been established as a novel mediator of biological processes, ranging from vascular control to long-term memory, from tissue inflammation to penile erection. This paper reviews recent research which shows that NO and its derivatives also are synthesized within skeletal muscle and that NO derivatives influence various aspects of muscle function. Individual muscle fibres express one or both of the constitutive NO synthase (NOS) isoforms. Type I (neuronal) NOS is localized to the sarcolemma of fast fibres; type III (endothelial) NOS is associated with mitochondria. Isolated skeletal muscle produces NO at low rates under resting conditions and at higher rates during repetitive contraction. NO appears to mediate cell–cell interactions in muscle, including vasodilation and inhibition of leucocyte adhesion. NO also acts directly on muscle fibres to alter cell function. Muscle metabolism appears to be NO-sensitive at several sites, including glucose uptake, glycolysis, mitochondrial oxygen consumption and creatine kinase activity. NO also modulates muscle contraction, inhibiting force output by altering excitation–contraction coupling. The mechanisms of NO action are likely to include direct effects on redox-sensitive regulatory proteins, interaction with endogenous reactive oxygen species, and activation of second messengers such as cyclic guanosine monophosphate (cGMP). In conclusion, research published over the past few years makes it clear that skeletal muscle produces NO and that endogenous NO modulates muscle function. Much remains to be learned, however, about the physiological importance of NO actions and about their underlying mechanisms.