Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients

Background. Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU. Aim. This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients. Results. We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin-1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET-1 plasma concentrations. Conclusions. These results strongly suggest that the elevation in ET-1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients.     

Synergistic effect of deoxyspergualin (DSP) and cyclosporin A (CsA) in the prevention of spontaneous autoimmune diabetes in BB rats

Dose-dependent side effects are frequently observed with immunosuppressive drugs of potential relevance for the immunotherapy of insulin-dependent diabetes mellitus (IDDM), such as CsA and DSP. If CsA and DSP acted synergistically in vivo, their combined use would allow using each compound at lower doses than those required when each drug is given in monotherapy. Consequently, dose-dependent side effects could be reduced and the therapeutic activity maintained or even enforced. Toward this end we studied the effects of combined treatment with CsA and DSP on the course of IDDM in the diabetes-prone (DP)-BB rat. The results show that two ‘low’ doses of CsA (2mg/kg) and DSP (1mg/kg) that are clinically ineffective in suppressing IDDM development in BB rats when administered alone under a prolonged prophylactic regimen (30–105 days old), may successfully prevent, but not cure, the disease when given contemporaneously under the same experimental conditions. The combined treatment was well tolerated, and no side effects were noticed. These data suggest that the combined use of CsA and DSP may deserve consideration for its possible application in the prevention/treatment of human IDDM and other autoimmune diseases.     

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis

Background An increased nutnber of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. Oiyective To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. Methods We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in II subjects with chronic bronchitis examined during an exacerbation. The findings were compared wilh those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells ftryptase), and T-lymphocytes (CD3) in the submucosa. Results As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of ehronic bronchitis (P < 0.001). whereas the number of I L-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No diflerences were observed in the number of tnast cells and T-lymphocytes between the four groups of subjects examined. Conciusions This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of ehronic bronchitis, but only in asthma is it associated with an increased expression of I L-5 protein in the bronchial tnucosa.     

肾上腺髓质素对豚鼠心室肌细胞L-型钙通道的作用及其信号转导机制

目的: 研究肾上腺髓质素( adrenomedullin, ADM)抑制豚鼠心室肌细胞L-型钙通道的信号转导机制。方法: 应用全细胞膜片钳技术,记录应用ADM(1-100 nmol·L^-1)前后L-型钙电流(I_Ca,L),以及分别记录应用ADM特异性受体拮抗剂ADM_22-52(100 nmol·L^-1)+ADM(100 nmol·L^-1)、蛋白激酶A (PKA) 特异性拮抗剂H-89(10 μmol·L^-1) + ADM(100 nmol·L^-1)、蛋白激酶C (PKC) 特异性拮抗剂PKC_19-36(10 μmol·L^-1)+ADM(100 nmol·L^-1)、PKC特异性激动剂PMA(1 μmol·L^-1)前后I_Ca,L。结果: ADM(1-100 nmol·L^-1)浓度依赖性地抑制豚鼠心室肌细胞I_Ca,L,并可被ADM_22-52(100 nmol·L^-1)完全阻断;H-89(10 μmol·L^-1)对ADM抑制I_Ca,L的作用无影响。PKC_19-36(10 μmol·L^-1)可完全阻断ADM 对I_Ca,L的抑制效应,且PMA(1 μmol·L^-1)可模拟ADM 对I_Ca,L的抑制效应。结论: ADM作用于特异性ADM受体可浓度依赖性地抑制豚鼠心室肌细胞I_Ca,L,此作用有可能与PKC激活相关。     

表皮生长因子影响肿瘤患者舌苔变化的分子机制研究

目的 研究表皮生长因子（EGF）对食管癌细胞Eca-109细胞周期及表皮生长因子受体（EGF－R）表达的影响，探讨EGF促进肿瘤患者舌苔增厚的分子机制。方法 应用流式细胞术，检测EGF－R的表达和细胞周期。结果 EGF能明显促进Eca-109细胞膜上EGF－R的表达，使细胞增殖活性大大增强。结论EGF有是通过促进EGF－R的表达影响舌苔形成。     

外伤性视神经损伤后视神经及视网膜形态的动态观察

目的:了解外伤性视神经损伤后的病理变化、溃变特点与时相间的关系。方法:参照Allen脊髓损伤法,造成视神经眶尖段间接600gcm力冲击、挤压伤。伤后对视神经和视网膜行形态学动态观察。结果:①伤后48h,视神经轻度肿胀和空泡反应;1周时损伤处视神经出现溃变,神经胶质细胞增生,视网膜神经节细胞(retinalganglioncells,RGCs)形态改变不明显;2周时神经纤维轴束间空泡样改变,局灶性坏死,RGCs核固缩和细胞数量减少。术后3月,视神经损伤部位直径缩小,形成胶质疤痕,RGCs数量明显减少,核固缩细胞增多。②RGCs数量于术后48h、1周、2周、1月和3月分别比正常对照组低3.35%、13.23%、19.74%、23.20%、29.28%。③视网膜细胞在48h内出现凋亡。结论:本实验模型可造成明确的视神经和视网膜损伤,神经元的损伤程度从节细胞、中间神经元、感光细胞的次序依次递减。视网膜和视神经损伤的严重程度与时间呈相关性。RGCs数量在48h至1周时下降速率最快。     

A synthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis

The heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10±7kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp 10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroES is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co-chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant-induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES nor the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N-terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased litres to both hsp10 and hsp65: hsp10-treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co-chaperonin in pathophysiological situations.     

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.     

The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen

The differentiation of the urinogenital system and the appendicular skeleton in vertebrates is under the control of Hox genes. The common control of digit and gonad differentiation raises the possibility that patterns of digit formation may relate to spermatogenesis and hormonal concentrations. This work was concerned with the ratio between the length of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in right and left hands has a sexually dimorphic pattern; in males mean 2D:4D = 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal length. The dimorphism is present from at least age 2 years and 2D:4D is probably established in utero; (ii) high 2D:4D ratio in right hands was associated with germ cell failure in men (P = 0.04); (iii) sperm number was negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men testosterone concentrations were negatively related to right hand 2D:4D and in women and men LH (right hand), oestrogen (right and left hands) and prolactin (right hand) concentrations were positively correlated with 2D:4D ratio and (v) 2D:4D ratio in right hands remained positively related to luteinizing hormone and oestrogen after controlling for sex, age, height and weight.      

糖尿病大鼠心肌NF-κB、iNOS、COX-2表达的研究

目的：观察核因子-κＢ（ＮＦ-κＢ）、诱导型一氧化氮合酶（iNOS）以及环氧化酶-2（COX-2）3种炎症因子在糖尿病大鼠心肌组织的表达。方法:30只SD大鼠随机分为正常对照组和糖尿病组，糖尿病组大鼠按60 mg/kg的剂量1次性腹腔注射链脲菌素。实验于24周末结束，观察2组大鼠的体重、平均血糖浓度、心重指数。并取心肌组织石蜡切片分别行NF-κＢ、iNOS和COX-2免疫组化染色。同时用凝胶电泳迁移率（EMSA）的方法测定心肌组织ＮＦ-κＢ活性。结果:(1)糖尿病大鼠心肌组织ＮＦ-κＢ阳性表达细胞明显多于对照组；（2）EMSA方法显示，糖尿病大鼠心肌组织ＮＦ-κＢ表达强度明显高于对照组；（3）对照组大鼠心肌组织未见iNOS的表达，糖尿病大鼠见明显iNOS的表达；（4）对照组大鼠心肌组织偶见COX-2的表达，糖尿病大鼠见明显COX-2的表达。结论:NF-κＢ、iNOS和COX-2在糖尿病大鼠心肌组织中表达活性明显增强。