Acute effect of 17 beta-estradiol and lithium on ovariectomized rat brain biogenic amines metabolism

The effect of 17 beta-estradiol (E2) on the response of dopamine (DA) and serotonin (5-HT) to acute lithium in the brains of ovariectomized rats was investigated. An E2 injection (100 ng/s.c.) to ovariectomized rats did not change striatal DA levels, whereas the levels of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), increased 30 min later; concentrations of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), also remained unchanged. In the frontal cortex, DA, 5-HT, HVA and 5-HIAA levels remained unchanged after the E2 injection, whereas DOPAC levels and DOPAC/DA and HVA/DA ratios increased 30 min later. Injection of LiCl (10 mEq) decreased striatal DA levels, increased DOPAC levels and slightly decreased HVA levels; by contrast, frontal cortex DA and HVA levels increased but DOPAC levels were unchanged. A biphasic response of striatal 5-HT levels occurred, increasing shortly after injection of LiCl, followed by a decrease; 5-HIAA levels, however, increased. In the frontal cortex, injection of rats with LiCl led to a gradual increase in 5-HT levels, whereas 5-HIAA concentrations decreased. In the presence of E2, LiCl effected a greater decrease in striatal DA than injection of LiCl alone, advanced the DOPAC peak by 30 min and increased HVA levels; E2 had less effect on the 5-HT response to LiCl, except the decreases in 5-HT and 5-HIAA at 60 min were greater. Furthermore, in the striatum, the increased DA turnover caused by LiCl, estimated by the DOPAC/DA and HVA/DA ratios, was advanced in rats treated with E2. In the presence of E2, LiCl slightly increased frontal cortex DA, DOPAC and HVA levels compared with treatment with LiCl alone, whereas DOPAC levels decreased in rats treated with LiCl + E2 compared with levels in E2-treated rats. Generally, higher levels of 5-HT and 5-HIAA were measured in the frontal cortices of rats treated with LiCl + Ex compared with rats injected with LiCl. These results indicate that E2 potentiates the acute effect of lithium on striatal and frontal cortex DA and 5-HT levels and metabolism, suggesting a role of the hormonal state on this drug response.     

Evaluation of the Nuclisens HIV-1 QT assay for quantitation of human immunodeficiency virus type 1 RNA levels in plasma

Nuclisens HIV-1 QT is a new version of the NASBA HIV-1 QT assay for quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in plasma. The specificity of this assay was 100% in one laboratory and 99%-with nonrepeatability of the initial false positive-in another. The test was linear between 2.0 and 6.0 log RNA copies per ml. According to the input HIV-1 RNA concentration, accuracy varied from -0.11 to +0.10 log RNA copy per ml and precision varied from 0.66 to 0.14 log RNA copy per ml. Reproducibility decreased when the HIV-1 RNA level was near the lower limit of quantitation of the test. HIV-1 RNA could be quantitated by Nuclisens HIV-1 QT in 36% (laboratory 1) and 24% (laboratory 2) of clinical samples with HIV-1 RNA levels lower than the lower limit of quantitation by NASBA HIV-1 QT. Nuclisens HIV-1 QT was not suitable for measurement of RNA from clade G and group O HIV-1 strains.     

Stiffness of trabecular bone of the tibial plateau in patients with rheumatoid arthritis of the knee

Stiffness of subchondral proximal tibial trabecular bone is a factor in the stability of prostheses implanted into that bone. The stiffness of trabecular bone in osteoarthritis (OA) has been documented. Trabecular bone in rheumatoid arthritis (RA) is osteopenic in numerous sites and morphologically abnormal in the proximal tibia. Reliable data on proximal tibial bone in RA are lacking, although 1 study failed to identify abnormalities. The purposes of this study were (1) to document the stiffness of the proximal tibial cancellous bone in patients with RA, (2) to determine the effect of angular deformity on bone stiffness in rheumatoid patients, and (3) to compare RA stiffness values with those in published reports for OA. Fifteen tibial plateau were obtained from patients with RA during surgery. Each plateau was horizontally seated in a mold and covered with cement. The plateau was divided into 6 regions, which were used to facilitate comparison between specimens and the existing literature. Indentation tests were conducted with a 4-mm-diameter cylindrical indentor controlled by an MTS machine. The indentor descended at a rate of 2 mm/min to a maximum depth of 1.0 mm; load and displacement data were digitally recorded. Stiffness was calculated from the slope of the linear region of the curve using best-fit linear regression. Where varus deformity was present, stiffness in the medial plateau was higher overall than for the other compartment; whereas in the case of valgus deformity, stiffness of the lateral side was significantly higher (P < .05 for each observation). In comparison to older normal specimens, both the medial compartment of the varus RA specimens (P < .01) and the posterolateral compartment of the valgus RA specimens (P < .01) had significantly lower stiffness. Comparison with OA specimens showed that in varus RA, the posteromedial region had significantly lower stiffness than in varus OA at the same site (P < .01). In valgus RA, the lateral region had significantly lower stiffness than in valgus OA at the same site (P < .01). The mean stiffness ratio of the valgus RA was significantly (P < .01) altered from normal, and for the varus RA, it was significantly (P < .01) different from normal posteriorly. The stiffness ratios for the varus RA were significantly (P < .01) different from those for varus OA; there was no difference between valgus RA and valgus OA. It is concluded that RA affected bone has significantly lower stiffness than normal and osteoarthritic bone. The loaded plateau is stiffer than the unloaded plateau in angular deformity, but is still less stiff than normal bone and osteoarthritic plateaus with corresponding deformities.     

Contributions to the Ohmic Drop in the Electrolysis of ZnCl2 in a Molten Chloride Electrolyte

The electrowinning of zinc from zinc chloride with a molten chloride electrolyte was investigated. The electrolysis of zinc chloride shows ohmic limitations. The energy consumption is to a large extent determined by the anodic reaction, the evolution of chlorine. The chlorine gas plume was visualised in a see-through furnace and images were analysed to determine the plume angle. This parameter serves as an input parameter for a model to determine the ohmic contributions of the electrolyte, the plume and a layer of chlorine bubbles sticking to the anode, as well as the plume velocity. The results indicate that the major contribution (60%) to the ohmic drop is due to a stagnant layer of bubbles growing and sticking to the anode, thereby decreasing the effective anode area by coverage. The plume velocity influences coverage characteristics to some extent, which influences the ohmic drop.     

Desflurane-mediated sympathetic activation occurs in humans despite preventing hypotension and baroreceptor unloading

BACKGROUND: Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation. METHODS: Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 microg) and phenylephrine (150 microg) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level. RESULTS: The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups. CONCLUSIONS: The increase in basal levels of SNA with increasing concentrations of desflurane persisted despite "fixing" BP and thus is probably not due to hypotension and unloading of the baroreceptors. Further, the preservation of reflex increases in SNA to nitroprusside during desflurane indicates that desflurane preserves one component of the baroreflex in humans when BP is "fixed."     

Staphylococcal enterotoxin B primes cytokine secretion and lytic activity in response to native bacterial antigens

Superantigens stimulate T-lymphocyte proliferation and cytokine production, but the effects of superantigen exposure on cell function within a complex, highly regulated immune response remain to be determined. In this study, we demonstrate that superantigen exposure significantly alters the murine host response to bacterial antigens in an in vitro coculture system. Two days after exposure to the superantigen staphylococcal enterotoxin B, splenocytes cultured with Streptococcus mutans produced significantly greater amounts of gamma interferon (IFN-gamma) and interleukin-12 than did sham-injected controls. The majority of IFN-gamma production appeared to be CD8(+) T-cell derived since depletion of this cell type dramatically reduced the levels of IFN-gamma. To study host cell damage that may occur following superantigen exposure, we analyzed cytotoxicity to "bystander" fibroblast cells cultured with splenocytes in the presence of bacterial antigens. Prior host exposure to staphylococcal enterotoxin B significantly enhanced fibroblast cytotoxicity in the presence of bacteria. Neutralization of IFN-gamma decreased the amount of cytotoxicity observed. However, a greater reduction was evident when splenocyte-bacterium cocultures were separated from the bystander cell monolayer via a permeable membrane support. Increased cytotoxicity appears to be primarily dependent upon cell-cell contact. Collectively, these data indicate that overproduction of inflammatory cytokines may alter the activity of cytotoxic immune cells. Superantigen exposure exacerbates cytokine production and lytic cell activity when immune cells encounter bacteria in vitro and comparable activities could possibly occur in vivo.     

The lactulose breath hydrogen test and small intestinal bacterial overgrowth

OBJECTIVES: To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations. METHODS: Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined. RESULTS: Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose. CONCLUSIONS: Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.     

Legal issues in sharing the benefits of biodiversity prospecting

The National Cancer Institute (NCI) is the US Government's principal agency for research on the prevention, diagnosis and treatment of cancer. A critical component of the Institute's mission is the identification and development of new and promising treatments for cancer and AIDS. For many years these efforts have included a program to investigate natural products for potential new therapeutic agents. In 1986, with the advent of new screening techniques, the National Cancer Institute stepped up its exploration of natural products and began world-wide collections of plants in tropical and subtropical regions. In recognition of the principles of the Biodiversity Treaty, NCI appreciates that continued access to the natural products of these countries depends on the Institute's ability to recognize the contributions of these source countries and their indigenous peoples, and to provide them adequate incentives to conserve their natural resources for the purposes of drug discovery. Accomplishing this goal presented several legal issues for the National Cancer Institute. As an agency of the US government, the NCI has an adjunct statutory mission to facilitate the transfer of technology developed through the Institute's programs into the private sector for further development and commercialization, and NCI operates under a national policy to use the patent system to transfer Federally supported research to the private domestic sector. Reliance on patent law may limit the Institute's ability to recognize the rights of source countries and their indigenous people and provide compensation for their contributions. However, other legal instruments, such as contracts, can serve as interim measures to provide compensation to source countries and indigenous populations. The National Cancer Institute's Letter of Collection agreement (LOC, formerly the "Letter of Intent'), is an example of an alternative means that "fills-in the gaps' created by patent law and through which source countries may share in the benefits of natural product development.     

A formally specified ontology management API as a registry for ubiquitous computing systems

Recently, several standards have emerged for ontology markup languages that can be used to formalize all kinds of knowledge. However, there are no widely accepted standards yet that define APIs to manage ontological data. Processing ontological information still suffers from the heterogeneity imposed by the plethora of available ontology management systems. Moreover, ubiquitous computing environments usually comprise software components written in a variety of different programming languages, which makes it particularly difficult to establish a common ontology management API with programming language agnostic semantics. We implemented an ontological Knowledge Base Server, which can expose the functionality of arbitrary off-the-shelf ontology management systems via a formally specified and well defined API. A case study was carried out in order to demonstrate the feasibility of our approach to use a formally specified ontology management API to implement a registry for ubiquitous computing systems.