Differential effects of organotin compounds on voltage-gated potassium currents in lymphocytes and neuroblastoma cells

BACKGROUND AND AIMS OF THE STUDY: There is no consensus over how to describe forward flow through valves in the mitral position. There are three main candidate hydraulic formulae; resistance, the Gorlin formula and the continuity equation. However, virtually no work has been performed to validate resistance and the continuity equation for valves in the mitral position. The aim of this study, therefore, was to compare the three formulae against an independent standard provided by directly observed orifice areas. MATERIALS AND METHODS: Five bioprosthetic valves with orifice areas between 0.14 cm2 and 2.33 cm2 were studied in a pulse simulator at up to 20 different stroke volume/rate combinations using quasi-physiologic flow curves. Orifice areas were measured using a video camera, pressure difference using strain gauge transducers and Doppler signals using a 1.9 MHz Pedoff probe with a Vingmed SD50 system. RESULTS: The Gorlin ratio (flow/square root of mean delta P) had a direct curvilinear relationship with the orifice area (log(y) = 0.31 + 0.36x; r = 0.94, SEE 0.08 cm2, p < 0.0001). Resistance (mean delta P/flow) had an indirect curvilinear relationship (log(y) = 0.19 - 0.55x, r = -0.93, SEE 0.13 cm2, p < 0.0001). The continuity equation was directly related to observed orifice area although with high scatter (y = 1.13 + 0.79x; r = 0.90, SEE 0.23 cm2, p < 0.0001). Although both the Gorlin ratio and resistance changed with flow, there was also a tendency for observed orifice areas to increase with flow. Empirical effective orifice areas calculated using the regression equations closely resembled observed orifice areas and agreement was reasonable, with 95% limits of -0.33 cm2 to +0.33 cm2 (Gorlin), -0.41 cm2 to +0.42 cm2 (resistance) and -0.40 cm2 to +0.48 cm2 (continuity). CONCLUSION: In conclusion, no single formula adequately predicted all observed orifice areas although resistance and the Gorlin formula gave useful predictions after empirical correction.     

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content

The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl2; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of organotin compounds on trout hemoglobins

Histamine is present in the gastrointestinal tract, and is an important mediator in gastrointestinal type I hypersensitivity reactions. The effect of histamine on ion transport in "stripped" porcine jejunal preparations was investigated. Histamine caused a transient increase in short-circuit current (SCC), which seemed to be concentration dependent. A maximum response was obtained at 0.1 mM. The histamine response was attenuated (44.8%) by the neuronal conduction blocker, tetrodotoxin (TTX), indicating that enteric neurotransmitters are involved. The neurokinin-1 antagonist, CP 99,994, did not alter the response to histamine (0.1 mM). Thus, tachykinins acting at NK-1 receptors do not seem to be involved in the histamine response.     

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. III. Alterations in B-cell function and viability

The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCl2 (0-1000 ng) and MeHgCl2 (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in B-cell proliferation in the presence or absence of monocytes. MeHgCl was approximately 10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize IgM and IgG. Analysis of the expression of activation markers indicated that CD69, an early marker of cell activation, was not effected by mercury. In comparison, B-cell expression of the low affinity IgE receptor and the transferrin receptor were significantly reduced. Of particular interest, cells activated by mitogen for 48 hr became refractory to the immunotoxic effects of mercury. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death.     

Immunotoxic effects of TCDD and toxic equivalency factors

This paper first summarizes the studies indicating that the immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), notably atrophy of the thymus and suppression of the thymus-dependent immunity, are mediated by binding to a soluble cytosolic protein, the aryl hydrocarbon (Ah) or TCDD receptor, present in the thymus in the epithelial cells. On the basis of a common receptor-mediated mechanism of toxic action, the relative (immuno)toxicity of individual PCDDs and PCDFs can be expressed relative to TCDD (i.e., toxic equivalents). Next, studies on TCDD-induced immunosuppression and impaired host resistance, and lowest observed effects levels of TCDD resulting in immune alterations, are summarized. Immune investigations performed in man are discussed and it is concluded that, for risk assessment purposes, further studies are necessary to determine the sensitivity of the human immune system to TCDD. For this purpose, a recent study is summarized in which the sensitivity of the human thymus to TCDD is investigated in so-called severe combined immunodeficient (SCID) mice in which human thymus grafts were transplanted. This study indicates that the human thymus and the Wistar rat thymus display a similar sensitivity to TCDD.     

Role of hydrophobic and hydrophilic interactions of organotin and organolead compounds with model lipid membranes

1. The stomach hormone gastrin and the intestinal hormone cholecystokinin (CCK) share a common C-terminal pentapeptide sequence but have different biological roles. Gastrin is the major stimulant of gastric acid secretion and has a growth stimulatory effect on the secretory part of the stomach. The physiological roles of CCK are the stimulation of pancreatic secretion and the contraction of the gall-bladder. 2. Several classes of receptors have been defined for peptides of the gastrin/CCK family. The CCKA receptor on pancreatic acini has a greater affinity for sulfated CCK than for gastrin, while the gastrin/CCKB receptor in gastric mucosa and brain has similar affinities for both gastrin and CCK. Potent and selective antagonists have been developed for both receptor classes. 3. The structures of the CCKA and gastrin/CCKB receptors have been deduced from the nucleotide sequences of cloned cDNA. The receptors, which both belong to the family with seven transmembrane segments, control secretion via similar signalling mechanisms. Occupation of either receptor leads to activation of phospholipase C, with resultant increases in intracellular levels of inositol triphosphate and Ca2+. Mitogenic signalling pathways are also being defined. 4. Recent studies have questioned the previous assumption that gastrin precursors are inactive. Glycine-extended gastrin17 has been shown to stimulate mitogenesis in some cell lines and may also have an autocrine role in the growth of colonic cancers. The receptors involved, which are clearly distinct in binding properties from the CCKA and gastrin/CCKB receptors, have not yet been cloned. Specific antagonists for the novel receptors will be required to define their function in further detail.     

Induction of apoptosis by organotin compounds in vitro: neuronal protection with antisense oligonucleotides directed against stannin

Immortalized cell lines and primary neuronal cultures were used to characterize the selective toxicity of trimethyltin (TMT),triethyltin (TET) and tributyltin (TBT). TBT and TET were cytotoxic at similar concentrations in the immortalized cell lines tested; the 50% toxic concentration (TC50) was 1 to 11 microM. In contrast, immortalized cell lines varied considerably in their sensitivity to TMT, with sensitive cell lines (neuroblastomas, T-, B-cell lines) showing TC50 values of 2 to 8 microM, whereas insensitive cells (NIH-3T3 fibroblast, HTB-14 glioma, TC-7 kidney cells) had TC 50 values > 100 microM. Primary neuronal cell cultures were very sensitive to organotins (TC50 values, 1-10nM), and showed patterns of selective toxicity with respect to neuronal and glial cells. Because organotin toxicity evolves over 24 to 48 hr. we determined whether these compounds induced apoptosis in primary cultures. TMT increased (P < .05) the fraction of apoptotic cells 6 and 12 hr after treatment with TMT at TC50 concentrations. Prior studies suggested that a protein, stannin, was localized in cells sensitive to organotins. Stannin was expressed in several TMT-sensitive cell lines (PC12, T, B cells) and in primary neurons in culture. Stannin was absent in the resistant HTB-14 glioma cell line. The role of stannin in mediating TMT toxicity in primary cultures was investigated by blocking stannin expression with specific antisense oligonucleotides. Treatment of primary cultures with antisense oligonucleotides for 48 hr before and during TMT treatment significantly protected neurons from the neurotoxic and apoptotic effects of TMT. This effect was not observed with scrambled oligonucleotide controls. Thus, TMT may induce apoptosis in sensitive cells, which is partly mediated by stannin. Based on the available data we conclude that stannin expression is necessary, but not sufficient for TMT toxicity.     

TFA-MOD制备YBCO带材工艺研究进展

由于第二代高温超导带材YBa2Cu3O7-z(简称YBCO)具有较高的不可逆磁场,可以在较高的温度和外加磁场下应用,是近年来高温超导材料研究的热点之一.采用三氟乙酸.金属有机沉积(trofluoroacetic acid-metal organic deposition,TFA-MOD)法制备第二代高温超导YBCO带材由于不需要真空系统,成本低,沉积速率快而广受关注.综述了TFA-MOD制备YBCO带材的工艺最新进展,并对TFA-MOD制备的YBCO带材性能进行了讨论.     

铋系银包套高温超导多芯带材的显微组织结构

采用粉末装管法制备了Ｍ２７（２７芯）,Ｍ１９（１９芯）六种铋系银包套高温超导多芯带材,利用标准四引线测量其电学性能临界温度（Ｔｃ）和临界电流密度（Ｊｃ）,利用高分辨电子显微镜,配有能谱仪的透射电子显微镜和扫描电子显微镜研究其显微组织结构。     

Polyol-Mediated Synthesis and Photoluminescent Properties of LaPO4： Eu^3＋ Nanoparticles

Eu^3＋-doped LaPO4 nanoparticles were prepared by polyol method and characterized by X-ray diffraction （XRD）, field emission scanning electron microscopy （FE-SEM）, thermogravimetry-differential thermal analysis （TG-DTA）, Uv-vis diffuse reflectance spectra （DRS）, photoluminescence （PL） spectra and lifetime measurement. The results of XRD indicate that the as-prepared nanoparticles are crystallized well at 160 ℃ and assigned to the monoclinic monazite-structure of LaPO4 phase. The obtained LaPO4：Eu^3＋ nanoparticles are spherical with narrow size distribution and the average size of 25 nm.     

The effects of digitalis-like compounds on rat lenses

We examined the effects of several opioids that vary in intrinsic efficacy at the mu-opioid receptor alone and in combination with morphine in a rat warm water tail withdrawal procedure using 50 degrees C and 52 degrees C water (i.e., low- and high-stimulus intensities). Morphine, levorphanol, dezocine, and buprenorphine produced dose-dependent increases in antinociception using both stimulus intensities. Butorphanol produced maximal levels of antinociception at the low, but not at the high, stimulus intensity, whereas nalbuphine failed to produce antinociception at either stimulus intensity. For cases in which butorphanol and nalbuphine failed to produce antinociception alone, these opioids dose-dependently antagonized the effects of morphine. When levorphanol, dezocine, and buprenorphine were combined with morphine, there was a dose-dependent enhancement of morphine's effects. Similar effects were obtained at the low-stimulus intensity when butorphanol was administered with morphine. In most cases, the effects of these combinations could be predicted by summating the effects of the drugs when administered alone. These results indicate that the level of antinociception produced by an opioid is dependent on the intrinsic efficacy of the drug and the stimulus intensity. Furthermore, the level of antinociception produced by the opioid, not necessarily the opioids' intrinsic efficacy, determines the type of interaction among opioids. Implications: Compared with high-efficacy opioids, lower efficacy opioids produce lower levels of pain relief, especially in situations of moderate to severe pain. When opioids are given in combination, the effects can only be predicted on the basis of the antinociception obtained when the drugs are administered alone.     

TFA-MOD技术制备YBCO涂层导体影响因素研究

采用三氟乙酸盐-金属有机物沉积法(trifluoroacetic acid-metall organic deposition,TFA-MOD)制备YB-CO带材,不需要真空系统,成本低,是近年来制备YBCO涂层导体研究的热点之一.对采用TFA-MOD技术制备YBCO涂层导体中的工艺做了较为系统的介绍,包括制备前驱物溶液、涂敷、低温烧结、高温烧结等环节,分析了加热温度,升温速率,水分压等参数的影响.并且讨论了如何从工艺环节提高YBCO涂层导体的性能.     

铋系银包套高温超导多芯带材的微观结构观察

采用粉末装管法制备了Ｍ２７（２７芯），Ｍ１９（１９芯）两种铋系银包套高温超导多芯带材。将样品制成平面及断面试样。利用配有能谱的ＪＥＭ２０００ＦＸ型透射电子显微镜对其进行了形貌观察和成分分析，确定了相组成。利用ＪＳＭ８４０型扫描电子显微镜对多芯带材进行了低倍观察以确定其多芯带材的均匀性和生长结合的完整性。     

In vitro effects of boron-containing compounds upon glioblastoma cells

Meningococcemia and disseminated intravascular coagulation (DIC) have a known association, and they have been identified as a rare cause of osteonecrosis in children. To our knowledge, we report only the second case of an adult with DIC and Neisseria meningitidis infection whose condition was subsequently diagnosed as osteonecrosis. We also review the world medical literature that pertains to osteonecrosis as a sequelae of meningococcal infection associated with DIC.     

Comparative antibacterial and antifungal effects of some phenolic compounds

The antimicrobial potential of eight phenolic compounds isolated from olive cake was tested against the growth of Escherichia coli, Klebsiella pneumoniae, Bacillus cereus, Aspergillus flavus and Aspergillus parasiticus. The phenolic compounds included p-hydroxy benzoic, vanillic, caffeic, protocatechuic, syringic, and p-coumaric acids, oleuropein and quercetin. Caffeic and protocatechuic acids (0.3 mg/ml) inhibited the growth of E. coli and K. pneumoniae. The same compounds apart from syringic acid (0.5 mg/ml) completely inhibited the growth of B. cereus. Oleuropein, and p-hydroxy benzoic, vanillic and p-coumaric acids (0.4 mg/ml) completely inhibited the growth of E. coli, K. pneumoniae and B. cereus. Vanillic and caffeic acids (0.2 mg/ml) completely inhibited the growth and aflatoxin production by both A. flavus and A. parasiticus, whereas the complete inhibition of the moulds was attained with 0.3 mg/ml p-hydroxy benzoic, protocatechuic, syringic, and p-coumaric acids and quercetin.