Experimental studies of thermal therapy for severe nonvariceal bleeding in dogs

Background: There are several methods of achieving endoscopic hemostasis for nonvariceal hemorrhage, including use of a heater probe, bipolar electrocoagulation, use of a Gold probe, and injection therapy with epinephrine or ethyl alcohol. However, due to clinical variations, clinical studies comparing thermal with injection therapy have yielded conflicting results. Therefore, we used a canine model of acute bleeding from gastric serosal vessels to examine the efficacy of the heater probe and the Gold probe in achieving hemostasis and to compare the injurious effects of these methods with injection therapy. Methods: Seven mongrel dogs were used in the study. Four were assigned to acute experiments in which transected blood vessels were allowed to bleed profusely. Two dogs of this group were treated with either a large or small Gold probe, while the other two were treated with either a large or small heater probe. In the other three dogs, we tested the chronic effects of the heater probe, the Gold probe, and injection therapy with dilute epinephrine. Results: Complete hemostasis was achieved for all four dogs in the acute experiments. Dogs treated with either a large or small heater probe had coagulation necrosis that extended to the serosa and muscularis but not to the mucosa. The large Gold probe had similar results, but the small Gold probe caused tissue damage to the serosa, muscularis, submucosa, and mucosa at several of the application sites. Both probes caused scarring of the gastric wall. In the chronic experiments, we found that the Gold probe caused larger mucosal ulcers than the heater probe. All ulcers healed in 3 weeks. The epinephrine injection caused localized swelling and discoloration, but after 1 week the tissue returned to normal. Conclusions: Both the heater probe and the Gold probe are effective in achieving hemostasis in a canine model of nonvariceal hemorrhage, and both methods are superior to injection therapy. For active bleeding ulcers, we currently recommend a combination therapy, using first injection therapy and then a heater or Gold probe. However, clinicians should be aware of the potential for tissue damage. Received: 31 July 1998/Accepted: 22 March 1999     

Colocalization of peptide hormones in neuroendocrine cells of human fetal and newborn lungs: An electron microscopic study

This study investigated the colocalization of the peptide hormones bombesin or calcitonin with calcitonin gene related peptide (CGRP) in neuroendocrine cells (NE) in the lungs of human fetuses of varying gestational ages and in the lungs of newborn infants who died with acute or chronic lung disease in the first weeks or months after birth. Double immunolabeling of dense core granules for these peptides was also studied in this same patient population. On-grid double gold immunolabeling was carried out on 29 subjects using anti-bombesin and anti-CGRP and on 22 subjects using anti-calcitonin and anti-CGRP as primary antibodies, the secondary antibodies being labeled with different-size gold spheres. Colocalization of both bombesin and calcitonin with CGRP was demonstrated, not only in the same NE cell, but also on the same dense core granule. Colocalization was rarely found in normal fetuses, and most frequently found in newborn infants with acute lung disease, usually hyaline membrane disease (HMD), or with the development of chronic lung disease in the first weeks or months after birth. Double labeling of the same dense core granules might imply action of peptides in concert, or perhaps one peptide acting in a paracrine role (e.g., on bronchial or bronchiolar smooth muscle) and the second peptide acting in an autocrine fashion on the parent cell (e.g., in the regulation of granule production or release). © 1993 Wiley-Liss, Inc.     

Self-reactive anti-class II T helper type 2 cell lines derived from gold salt-injected rats trigger B cell polyclonal activation and transfer autoimmunity in CD8-depleted normal syngeneic recipients

Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex-type glomerulonephritis in the context of a polyclonal B cell activation that was suspected to be due to the emergence of anti-self major histocompatibility complex (MHC) class II T cells. In the present study, six anti-self MHC class II T cell lines have been derived from six gold salttreated rats by repeated stimulations with normal syngeneic MHC class II-bearing cells. The T cell lines proliferated in the presence of self MHC class II-positive B cell-enriched or B cell-depleted cells and the proliferation was inhibited by preincubating stimulator cells with an anti-IA monoclonal antibody. The T cell lines produced interleukin (IL)-4 only or IL-4 and some interferon (IFN)-γ and could, therefore, be considered as T helper type 2 (Th2) and Th0 cells, respectively. They triggered normal syngeneic B cells to produce in vitro IgE, anti-DNA, anti-laminin and anti-2,4-6-trinitrophenol antibodies through, at least in part, cognate interactions. More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than the one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in serum IgE concentration and the production of anti-DNA and anti-laminin antibodies. In addition, all recipients displayed an autoimmune glomerulonephritis due to anti-laminin antibodies, granular IgG deposits in the interstitium, in the vessel walls and along the tubular basement membranes and a severe tubulointerstitial nephritis with marked mononuclear cell infiltration. An anti-ovalbumin T cell line that produced IL-4 and low amounts of IFN-γ was used as a control and did not induce autoimmunity. These results demonstrate for the first time the ability of autoreactive Th2 as well as Th0 cell lines to induce antibody-mediated autoimmunity. They also show that CD8⁺ cells play a crucial role in the control of such autoreactive cells. Finally, this work suggests that Th2 cells could initiate cell-mediated reactions either directly or indirectly.     

Evaluation of a method for weighing small tissue samples: Investigations into freezing and evaporation

Summary A method for weighing very small wet tissue samples with a view to estimating percentage water is described, involving the use of gold foil buckets weighed on an electrobalance. A comparison of precision of this method and that of an existing method is presented. The effect on percentage water of freezing the tissue has been investigated. The rate of evaporation of water from tissue in unsealed containers has been estimated and a relationship shown with the weight of the tissue. The rate of evaporation can be minimized by folding correctly.     

Effects of bipiperidyl mustard (BPM) lesions on insulin hypoglycemic convulsions

Systemic gold thioglucose (GTG) is well known to produce hyperphagia, resulting in obesity, and histological damage focused relatively selectively in the ventromedial hypothalamus (VMH). Although structurally very different, bipiperidyl mustard (BPM) produces apparently similar effects. However, a proposed mechanism for concentration and hence localization of GTG toxicity depends on its structural similarity to glucose, binding it to glucoreceptors and focusing the cytotoxicity of the gold thio-portion. We recently showed that GTG treatment also produces an early decrease and a later increase in sensitivity to insulin hypoglycemic convulsions. We report here that BPM also produces a similar biphasic change in sensitivity to insulin hypoglucemic convulsions. For both, the differences are in the brain's convulsive response to hypoglycemia, rather than in the degree of hypoglycemia in response to insulin. Thus, GTG and BPM cytotoxic lesions appear similar in this regard as well. BPM is another way of producing a relatively discrete brain lesion which alters the brain's functional adjustment to hypoglycemia. The significance of this control center and its relationship to the control(s) of feeding and systemic metabolism are discussed.     

Bronchiolar disease associated with gold compounds administration in a patient with rheumatoid arthritis

We report the case of a female patient with rheumatoid arthritis (RA) treated with gold sodium thiomalate and auranofin who developed bronchopulmonary involvement. Chest X-ray films showed diffuse mottled infiltrates and bronchial wall thickness in both lungs. Computed tomography revealed opacities along the thickening of the bronchovascular bundles. The pathologic findings were indistinguishable from those of diffuse panbronchiolitis. After discontinuation of gold compounds and initiation of steroid administration, her subjective symptoms immediately subsided. We conclude that our patient, who had suffered from chronic sinusitis and had a predisposition to bronchiolar disease, had bronchiolar disease induced by gold compounds.     

胶体金在临床检验诊断中的研究进展

胶体金是一种广泛应用于纳米诊断的纳米材料,具有较大的比表面积,独特的物理特征,良好的生物相容性和化学稳定性。对胶体金进行特定的修饰可赋予其新的功能。本文主要对其在临床检验诊断中的研究进展作一综述。     

黄金散治疗经漏组方的临床疗效

目的：探讨黄金散治疗经漏的临床疗效,并分析其药理作用。方法将本院诊治的76例经漏患者按照患者知情自愿原则分为观察组（39例）与对照组（37例）,对照组采用西药黄体酮注射液联合米非司酮口服治疗,观察组采用黄金散7.5 g餐前温水送服,疗程均为3个月,比较两组患者治疗后的疗效,临床症状的改善情况。结果观察组治疗后痊愈18例,显效14例,有效5例,无效2例,对照组治疗后痊愈7例,显效13例,有效3例,无效14例,观察组疗效显著优于对照组,观察组治疗总有效率显著高于对照组（94.9％vs 62.2％）;观察组治疗后的腰骶部疼痛（12.8％ vs 35.1％）、夜眠困难（5.1％vs 21.6％）、白带异常（7.7％ vs 24.3％）比例显著低于对照组（ P＜0.05）。结论黄金散治疗经漏疗效可靠,有效率高,可有效改善临床症状。     

Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles

Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV. Pfs25 has a complex tertiary structure characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it has been rather difficult to obtain Pfs25 as a homogenous product in native conformation in any heterologous expression system. Recently, we have reported expression of codon-harmonized recombinant Pfs25 in Escherichia coli (CHrPfs25) and which elicited highly potent malaria transmission-blocking antibodies in mice. In the current study, we investigated CHrPfs25 along with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity. The results revealed that CHrPfs25 delivered with various gold nanoparticles elicited strong transmission blocking antibodies and suggested that gold nanoparticles based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens.     

Effects of nanoparticle size and gestational age on maternal biodistribution and toxicity of gold nanoparticles in pregnant mice

Gold nanoparticles (GNPs) have considerable applications in biomedicine, such as in bio-sensing, bio-imaging, drug delivery and photothermal therapeutics. However, currently there are limited information regarding the impact of pregnancy on their biodistribution, elimination and toxicity. In this study, we investigated the biodistribution and potential toxic effects of different-sized GNPs (1.5, 4.5, 13, 30 and 70 nm in diameter) in non-pregnant and pregnant mice at different gestational ages (E5.5, 7.5, 9.5, 11.5 and 13.5). 5 h after intravenous injection, GNPs exhibited size-dependent biodistribution profiles; however, regardless of size, no significant biodistribution changes were observed between non-pregnant and pregnant mice. Kinetic studies showed that 4.5 nm GNPs were primarily excreted through urine within 5 h, whereas 30 nm GNPs had a more prolonged blood circulation time. No apparent toxic effects (e.g., increased mortality, altered behavior, reduced animal weight, abnormal organ morphology or reduced pregnancy duration) were observed with different-sized GNPs in pregnant mice. However, treatment with 30 nm GNPs induced mild emphysema-like changes in lungs of pregnant mice. These results indicated that the maternal biodistribution patterns of GNPs in pregnant mice depended on particle size, but not gestational age; organ-specific adverse effects may arise with treatment with some GNPs according to their size.