DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.

We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism.     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

Anti-inflammatory,analgesic, antipyretic and related properties of meloxicam,a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs.With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenaninduced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration.Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain.In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeastinduced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid.Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm.Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam.The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen.     

Development of a diagnostic PCR assay targeting the Mn-dependent superoxide dismutase gene (sodA) for identification of Streptococcus gallolyticus

A PCR-based assay to identify Streptococcus gallolyticus has been developed. The assay uses an oligonucleotide primer pair targeting a partial sequence of the manganese-dependent superoxide dismutase gene (sodA). The assay distinguished members of the S. gallolyticus group from other, closely related taxa successfully by yielding a 408-bp specific amplicon.     

Lectin-mediated enhancement of dengue virus infection in a mouse macrophage cell line Mk1

Summary Treatment of a mouse macrophage cell line Mk1 with pokeweed mitogen (PWM) either before or during but not after virus inoculation resulted in an enhancement of dengue virus (DV) infection. The infection enhancement was primarily due to an increase in the number of DV-infected cells but not to increased virus production in a cell. These results suggested that PWM treatment mediated increased DV binding and/or penetration to Mk1 cells, thereby resulting in the infection enhancement.N-acetylglucosamine (GlucNAc) did not suppress PWM-mediated enhancement of DV infection when added to Mk1 cells after PWM treatment was done, although GlucNAc clearly suppressed the effect of PWM when added simultaneously with PWM. The results implied the possibility that the PWM-mediated increase in viral binding/penetration was not due to a cross-linking by PWM between DV and a cell-surface receptor, but due to another mechanism, presumably exposure of a masked DV receptor(s). The DV receptor, unidentified as yet, involved in the PWM-mediated infection enhancement appeared to have no relation with IgG Fc receptors that are known to be involved in antibody-mediated enhancement of DV infection.     

Dipole-tracing of 'awareness' attenuating the cortical components of somatosensory evoked potentials

Using the dipole-tracing method, the source generators of N18, P22 and P40 of the somatosensory evoked potential (SEP) were estimated as the equivalent dipole. After voluntary action of the thumb flexion, no changes were observed in N18 or P40, but the amplitude of P22 was suppressed. The after-effects of intention accompanied by a voluntary action or the subject's awareness that electrical stimulation will be given after the voluntary action were treated as 'awareness'. By subtracting the pure SEP from SEP during 'awareness', it was found that the equivalent dipole of 'awareness' of P22 was located at the same region of pure P22, but the vector was of opposite orientation. 'Awareness' attenuated the perceptive potential of SEP like P22 generated in the cortex.     

An invasion-independent pathway of blood-borne metastasis: a new murine mammary tumor model

It is generally believed that active invasion by cancer cells is essential to the metastatic process. In this report, we describe a murine mammary tumor (MCH66) model of metastasis that does not require invasion into the vascular wall of both the primary tumor and the target organ, in this case, the lung. The process involves intravasation of tumor nests surrounded by sinusoidal blood vessels, followed by intravascular tumor growth in the lung, without penetration of the vascular wall during the process. Comparative studies using a nonmetastatic MCH66 clone (MCH66C8) and another highly invasive metastatic cell line (MCH416) suggested that high angiogenic activity and sinusoidal remodeling of tumor blood vessels were prerequisites for MCH66 metastasis. Differential cDNA analysis identified several genes that were overexpressed by MCH66, including genes for the angiogenesis factor pleiotrophin, and extracellular matrix-associated molecules that may modulate the microenvironment toward neovascularization. Our analyses suggest that tumor angiogenesis plays a role in the induction of invasion-independent metastasis. This model should prove useful in screening and development of new therapeutic agents for cancer metastasis.     

Alveolar soft part sarcoma of the uterine cervix

A rare case of an alveolar soft part sarcoma of the uterine cervix in an 8 year old girl is presented. The patient was admitted because of genital bleeding lasting for 7 months. A polypoid tumor, 2times1.5 cm in diameter, was found in her external uterine os and was surgically resected. Microscopically, the tumor consisted of a uniform sheet of tumor cells in the cytoplasm which contained granules and which were stained with periodic acid-Schiff, both before and after the diastase digestion. Alveolar arrangement of the tumor cells was manifested with reticulin silver impregnation. Dense, membrane bound granules were evident at an ultrastructural level in the cytoplasm of the tumor cells. An immunohistochemical examination demonstrated a positive reaction for anti-desmin, anti-myoglobin, anti-HHF35 and anti-neuron specific enolase in the cytoplasm.     

Immunohistochemical study of tyrosine-hydroxylase-positive cells and fibers in the chicken spinal cord.

Tyrosine hydroxylase (TH)-positive cells and fibers were examined by immunohistochemistry in the chick spinal cord. TH-positive cells, which were located in laminae I, V and X, were most frequently found in the rostral part of the cervical spinal cord, with fewer cells being found in more caudal levels of the spinal cord. TH-positive cells located in lamina X, which were bipolar in shape, were mainly found in regions lateral as well as just ventral to the central canal. They had processes reaching to the central canal. The terminals of these cerebrospinal-fluid-contacting cells were oval in shape, and were most frequently found at the ventral wall of the central canal. There were dense clusters of TH-positive fibers in lamina X. A meshwork-like structure of TH-positive fibers was found over the lateral wall of the central canal. A high density of TH-positive fibers was also found in the medial part of laminae V-VII. In lamina IX, small numbers of TH-positive fibers were observed in the lateral motor column of the brachial spinal cord, and in the medial and lateral motor columns of the lumbosacral spinal cord. However, within the medial motor column of the brachial spinal cord TH-positive fibers were densely distributed around somal as well as dendritic profiles. Similar to our previous observations on serotoninergic fibers. TH-positive fibers were also differentially distributed in the ventral horn of the chicken spinal cord: a high density of TH-positive fibers was localized to specific regions of the spinal motor nucleus.