温病湿热证病理造型及实验研究

本文介绍利用多因素,包括模拟湿热气候环境,过食肥甘及内毒素感染等综合复制的家兔温病湿热证动物模型的方法,造型动物出现诸如发热、纳呆、不欲饮水、便软烂或溏、嗜睡懒动、舌苔白腻等表现,与临床所见该证的主要症状体征和病理变化相符合,中药反证也提供了支持的佐证;实验进而发现模型动物造型后6小时及10小时的血浆内毒素水平较单纯用内毒素致热的发热对照组为高(p<0.05),提示温热造型动物内毒素廓清较为缓慢。可见,本实验将为以后研究温病湿热证提供较为理想的动物病理模型。     

Post-translational processing of thyrotropin-releasing hormone precursor in rat brain: identification of 3 novel peptides derived from pro TRH

The sequence of rat hypothalamic pro-thyrotropin releasing hormone, deduced by sequencing of cDNA, in addition to 5 TRH progenitor genitor sequences contains leader, trailer and 4 intervening sequences separated by paired basic amino acid sequences. We have developed radioimmunoassays to synthetic peptides corresponding to portions of these cryptic proTRH sequences and have used these assays to identify and partially characterize proTRH peptides, distinct from TRH, in extracts of rat brain. Two of these peptides correspond closely in size to one intervening sequence and the car☐y-terminal sequence of proTRH. Three other peptides correspond to the intact amino-terminal leader sequence and two peptides formed by a further cleavage of the leader sequence at an internal paired basic amino acid sequence.     

Central effects of systemic lidocaine mediated by glycine spinal receptors: an iontophoretic study in the rat spinal cord

The objective of this investigation was to demonstrate the possible interactions of systemic lidocaine (lido) with inhibitory receptors in the spinal cord. In the lumbar dorsal horn of anesthetized and curarized rats, 60 physiologically identified, wide dynamic range (WDR) neurons, were recorded extracellularly. Glutamate, glycine and its selective antagonist, strychnine, were iontophoretically applied onto the neurons either singularly or concurrently. The effects of systemic lido on the drug-induced frequency changes and the interaction with the glycine receptors, using strychnine as a probe, were studied. It was consistently found that (i) lido (3–4 mg/kg) inhibited the excitatory responses to iontophoretic glutamate, (ii) this inhibition was significantly antagonized by concurrent iontophoretic strychnine, (iii) iontophoretic glycine induced comparable glutamate inhibition that was reversed by strychnine. In contrast, no effect on glutamate-induced excitations was observed when lido was applied by micropressure or a different local anesthetic was systemically administered. The results suggest that central inhibitory effects of lido could by mediated by spinal strychnine-sensitive glycine receptors, activated by lido itself or possibly by its glycine residue-bearing metabolites.     

Spectrophotometric investigation of complex formation of an oxime PAM-4Cl with palladium(II) and its analytical application

The colour reaction of 4-hydroxyiminomethyl-1-methylpyridinium chloride (PAM-4Cl) and palladium(II) chloride has been investigated. The optimum reaction conditions, spectral characteristics, conditional stability constant and composition of the yellow water-soluble complex have been established. A new spectrophotometric method is proposed for the microdetermination of PAM-4Cl.     

脾虚和肾虚雌性大鼠生育能力的实验观察

为系统观察脾虚和肾虚雌性ＳＤ大鼠的生育能力，将大鼠随机分为：脾虚组、脾虚复健组、肾虚组、肾虚复健组、正常组。脾虚组和肾虚组分别按常规方法用利血平和羟基脲制成脾虚模型和肾虚模型。虚证动物模型出现与人类相似的症状：动情周期紊乱，甚至消失；生殖器官萎缩；血清卵泡刺激素（ＦＳＨ）、雌二醇（Ｅ２）水平下降；子宫腺体数目减少，卵巢次级和成熟卵泡数减少，生育能力下降。而肾虚大鼠上述变化更显著。用四群子喂饲脾虚模     

Correlation between the intensity of cytomegalovirus infection and the amount of perivasculitis in aortic allografts

Abstract  We previously demonstrated that cytomegalovirus (CMV) infection enhanced perivascular inflammation in rat aortic allografts. In this study, we investigated the relationship between the CMV infection load and the magnitude of perivasculitis (chronic rejection) in aortic transplants. Rats received or-thotopic abdominal aortic grafts, different degrees of total body irradiation (TBI) for immunosuppres-sion and CMV inoculation. The spleens of the rats receiving 5 Gy of TBI contained more infectious virus and viral antigens than those of rats receiving 3 Gy of TBI or no TBI. Although the number of inflammatory cells infiltrating the perivascular area was decreased after TBI, CMV infection resulted in increased perivasculitis in rats that received 5 Gy of TBI as compared to non-infected animals. This virus-induced effect was characterized predominantly by an increased T-cell infiltration, including CD4 and CD8 T-cells. It is concluded that an enhanced systemic CMV infection during severe immunosuppressive therapy can accelerate the development of chronic rejection, which seems to be mediated mainly by T-cells.     

Ontogenetic Development of 5-HT1D Receptors in Human Brain: An Autoradiographic Study

The pattern of pre- and postnatal appearance of 5-HT_1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [¹²⁵I]GTI (serotonin O -carboxymethyl-glycyl-[¹²⁵I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT_1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [¹²⁵I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT_1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT_1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT_1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period.     

The value of serial determination of MEGX and hyaluronic acid early after orthotopic liver transplantation

Abstract. Post-transplant assessment of early graft function has become an essential part of monitoring, especially when deciding on retransplantation. If primary non-function is indicated, retransplantation is inevitable; early graft dysfunction may be related to subsequent complications. In a prospective study in 84 patients after orthotopic liver transplantation (OLT) we measured aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), bilirubin (BIL), prothrombin time, MEGX formation, hyaluronic acid (HA) and soluble interleukin-2 receptor (sIL-2R) concentrations during the first 2 postoperative weeks; graft outcome was followed over 4 months. The aim of this study was to determine whether graft survival could be predicted by such variables early after OLT. Compared with patients with stable graft function (n= 25), patients with post-transplant icteric cholestasis (n= 30) exhibited no difference in graft survival, despite a decrease in MEGX formation to a nadir median of 12 μgL^-1 on day 10. Patients with rejection (n= 8) and septicaemia (n= 6) showed a marked decrease in MEGX values and an increase in HA and sIL-2R concentrations between postoperative days 3 and 7. Patients with primary non-function (PNF; n= 5) were characterized by strongly reduced MEGX formation (median 4 μgL) and increased HA values (median 2300 μgL^-1) on day 3 after OLT. A total of 24/84 grafts were lost within 120 days. In a survival analysis using the Cox proportional hazards regression, HA and MEGX values on day 1 were the only independent variables entering the model that showed an adequate prognostic sensitivity. At cut-off points of 22 μgL^-1 (MEGX) and 730 μgL^-1 (HA) the combined use of these parameters in a parallel approach yielded a sensitivity of 58% with a corresponding specificity of 95% for 120-day graft survival. These findings suggest that the inclusion of MEGX and HA in postoperative monitoring of OLT patients may be helpful in the early prediction of graft survival.     

Photodynamic therapy of tumours: value of quantum chemical procedures for characterization of new drugs. Prediction of the electronic structure of zinc(II) phthalocyanine with special emphasis on triplet state excitation energies

Zinc(II) phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy in a variety of animal tumours. The photophysical properties of zinc(II) phthalocyanine have been studied in detail and compared to those of Photofrin, the only sensitizing agent approved so far for phase III/IV clinical trials. Since the efficacy of photodynamic therapy intrinsically depends on the spectroscopic features of the sensitizer, quantum chemical methods have proven to be an efficient means for optimizing chemical structures. As will be shown, a simple modification of the time-honoured INDO model of Pople allows a prediction of the singlet and triplet state properties of molecules of the size of zinc(II) phthalocyanine with an rms error of ≤ 1000 cm⁻¹.     

Quantitative evidence of peripheral conversion of angiotensin within the human leg: effects of local angiotensin-I administration and angiotensin-converting enzyme inhibition on regional blood flow and angiotensin-II balance across the leg

Summary The renin-angiotensin system relevantly contributes to the maintenance of systemic vascular tone and there is experimental evidence that large amounts of angiotensin-converting enzyme (ACE) are present in peripheral vascular tissues, including resistance vessels. To determine and quantify peripheral vascular conversion of angiotensin-I (ANG-I) to angiotensin-II (ANG-II) across the human leg, the response of regional blood flow to local regional intra-arterial infusion of ANG-I and changes in associated ANG-I1 balance were evaluated during ANG-I infusion and following additional ACE inhibition. Ten sodium-loaded healthy men were enrolled in the study. Following cannulation of both femoral arteries and the right femoral vein, leg blood flow was determined (indocyanine-green dye-dilution method) at baseline conditions and during constant intra-arterial infusion of haemodynamically ineffective doses of ANG-I as well as following concomitant intra-arterial administration of low doses of the non-sulfhydril ACE inhibitor cilazapril. From the transfemoral arterio-venous differences in ANG-II plasma concentrations and the corresponding regional blood (plasma) flow, the ANG-II balance across the leg was calculated. Systemic blood pressure did not change throughout the trial, indicating that no major systemic effects were present during ANG-I infusion or concomitant ACE inhibition. Moreover, arterial ANG-II plasma concentrations were not significantly changed by ANG-I infusion. Leg blood flow decreased to below baseline values following ANG-I infusion, increasing again then in a dose-dependent manner during concomitant cilazapril administration. The calculated baseline ANG-II balance across the leg revealed a net extraction in 6 out of 10 subjects and a net ANG-II formation in 4. Following ANG-I, a shift towards net ANG-II formation or decrease in extraction was seen in 8 subjects, while 2 had no change in ANG-II balance.During concomitant ACE inhibition, ANG-II balance was again shifted towards net extraction or reduced formation. Our results confirm that, in man, considerable regional arterio-venous differences in ANG-II plasma concentrations are present, resulting in either net transfemoral extraction or net formation of the peptide. It is suggested that systemic vascular conversion of circulating ANG-I might contribute to the maintenance of peripheral vasuclar tone in man. Send offprint requests to S. Gasic at the above address