The efficacy of amoxicillin sodium against streptococcosis in cultured olive flounder Paralichthys olivaceus and its pharmacokinetics.

The efficacy of amoxicillin sodium for controlling field and experimental Streptococcus iniae and S. parauberis infections in olive flounder (Paralichthys olivaceus) was evaluated after a single intramuscular administration. Furthermore, the minimal inhibitory concentrations (MIC) against 21 Streptococcus strains were determined. In addition, the pharmacokinetics and residue depletion in olive flounder were investigated. Single intramuscular doses of amoxicillin sodium at 20, 40, 80, and 160 mg/kg b.w. fish significantly reduced cumulative mortality rates to 18.8-31.3% (P < 0.05) for S. iniae and to 5.0-15.0% (P < 0.01) for S. parauberis, whereas the S. iniae- and S. parauberis-infected positive control groups showed cumulative mortality rates of 68.8% and 60.0%, respectively. In a S. parauberis outbreak, amoxicillin sodium reduced the cumulative mortality rate to 7.5% and 4.8% at 20 and 40 mg/kg b.w. fish, respectively, whereas that of the untreated control group was 35.2%. Peak plasma concentrations (Cmax ) following a single intramuscular dose of 40 and 80 mg/kg b.w. fish were 62.64 (Tmax , 1.59 h) and 87.61 (Tmax , 3.02 h) µg/mL, respectively, with large AUC0-t /MIC and Cmax /MIC ratios, and sufficient T > MIC (time for maintaining plasma drug concentration greater than MICs) for S. iniae and S. parauberis. The estimated withdrawal period of amoxicillin sodium from muscle of olive flounder was about 8 days at 40 mg/kg b.w. fish (at 22 ± 1 °C). These results demonstrated a single intramuscular administration of amoxicillin sodium to be effective against streptococcosis in olive flounder.

Six new Phytophthora species from ITS Clade 7a including two sexually functional heterothallic hybrid species detected in natural ecosystems in Taiwan.

During a survey of Phytophthora diversity in natural ecosystems in Taiwan six new species were detected. Multigene phylogeny based on the nuclear ITS, ß-tubulin and HSP90 and the mitochondrial cox1 and NADH1 gene sequences demonstrated that they belong to ITS Clade 7a with P. europaea, P. uniformis, P. rubi and P. cambivora being their closest relatives. All six new species differed from each other and from related species by a unique combination of morphological characters, the breeding system, cardinal temperatures and growth rates. Four homothallic species, P. attenuata, P. flexuosa, P. formosa and P. intricata, were isolated from rhizosphere soil of healthy forests of Fagus hayatae, Quercus glandulifera, Q. tarokoensis, Castanopsis carlesii, Chamaecyparis formosensis and Araucaria cunninghamii. Two heterothallic species, P. xheterohybrida and P. xincrassata, were exclusively detected in three forest streams. All P. xincrassata isolates belonged to the A2 mating type while isolates of P. xheterohybrida represented both mating types with oospore abortion rates according to Mendelian ratios (4-33 %). Multiple heterozygous positions in their ITS, ß-tubulin and HSP90 gene sequences indicate that P. xheterohybrida, P. xincrassata and P. cambivora are interspecific hybrids. Consequently, P. cambivora is re-described as P. xcambivora without nomenclatural act. Pathogenicity trials on seedlings of Castanea sativa, Fagus sylvatica and Q. suber indicate that all six new species might pose a potential threat to European forests.

Low pathogenicity of flounder iridovirus (FLIV) and the absence of cross-protection between FLIV and rock bream iridovirus.

The genus Megalocytivirus is known to infect a wide range of cultured marine fish. In this study, we examined the pathogenicity of FLIV (Megalocytivirus from olive flounder, genotype III) and RBIV (Megalocytivirus from rock bream, genotype I) to their homologous and heterologous host species. Olive flounder (7.5 ± 1.3 cm) injected with FLIV [major capsid protein (MCP) gene copies, 6.8 × 103 -6.5 × 106 /fish] at 24 °C did not die until 90 days post-infection (dpi). The average virus replication in the spleen peaked (1.27 × 106 /fish) at 20 dpi. Rock bream (6.5 ± 1.5 cm) injected with FLIV (8.8 × 105 and 6.5 × 106 /fish of MCP copies) showed no mortality until 50 dpi. The rock bream that survived after FLIV infection were rechallenged with RBIV at 50 dpi had 100% mortality, showing that there is no cross-protection between FLIV and RBIV. Temperature shifting (26 °C and 20 °C at 12 h intervals) did not cause FLIV-specific mortality into olive flounder, but higher virus copies were observed in the fish exposed to higher stocking density. This study demonstrates that FLIV and RBIV have different antigenic and pathogenic characteristics and that FLIV has low pathogenicity to olive flounder.

Effects of water temperature on mortality in Megalocytivirus-infected rock bream Oplegnathus fasciatus (Temminck et Schlegel) and development of protective immunity.

Rock bream iridovirus (RBIV) causes huge losses, especially in rock bream Oplegnathus fasciatus. Rock bream injected with RBIV and held at 29, 26, 23 or 20 °C had 100% mortality. Conversely, all infected fish held at 17 °C survived even after the temperature was progressively increased to 26 °C at 100 dpi. Rock bream exposed to virus and held for 2, 4 and 7 days at 23/26 °C before the temperature was reduced to 17 °C had mortality rates of 26.6/73.2%, 66.6/100% and 93.4/100%, respectively, through 100 dpi. When surviving fish had the water temperature increased from 17 to 26 °C at 100 dpi, they did not exhibit signs of disease and had low virus copy numbers (below 10(3)). To investigate the development of a protective immune, rock bream were infected with RBIV and held at 23 °C before shifting the water temperature to 17 °C at 4 dpi. All injected fish survived until 120 dpi. While 100% of the previously unexposed fish died, 80.2% of the previously infected fish survived. When the survivors were rechallenged again at 160 dpi, no further mortality occurred. The high survival rate of fish following rechallenge with RBIV indicates that protective immunity was established in the surviving rock bream.

Resveratrol prevents development of eosinophilic rhinosinusitis with nasal polyps in a mouse model.

BACKGROUND: Since the recent establishment of a murine model of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), both the development of new drugs for treatment or prevention of eosinophilic CRSwNP and elucidation of their pathogenesis have been feasible. We investigated the therapeutic effects of resveratrol on CRSwNP and its mechanism of action using a murine model. METHODS: After induction of eosinophilic CRSwNP, the therapeutic effects of resveratrol were tested and compared with those of triamcinolone acetonide. Histopathologic changes were evaluated using hematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and Masson's trichrome stain for collagen. The expression levels of the interleukin (IL)-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were assessed by quantitative real-time PCR. Cyclooxygense-2 and 5-lipoxygense levels were evaluated by immunohistochemical staining and Western blot analysis. RESULTS: The degree of eosinophilic infiltration and subepithelial fibrosis was significantly decreased by administration of high-dose resveratrol, the potency of which was similar to that of triamcinolone acetonide. The expression levels of the IL-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were significantly decreased by administration of low- or high-dose resveratrol. The production of 5-lipoxygenase was strongly inhibited by high-dose resveratrol. CONCLUSIONS: Resveratrol may be useful for the prevention of eosinophilic CRSwNP. A key mechanism of its action is believed to be its anti-inflammatory effect, particularly on eosinophils, by inhibiting the lipoxygenase pathway.

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD. METHOD: Twenty unmedicated patients with OCD and 20 age-, sex-, and IQ-matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task. RESULTS: Compared with controls, patients with OCD showed increased ventral striatal activation in the no-loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no-gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation. CONCLUSION: These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.

Uterine müllerian adenosarcoma with sarcomatous overgrowth and lung metastasis in a 25-year-old woman.

Uterine müllerian adenosarcoma with sarcomatous overgrowth (MASO), uncommon in premenopausal women, is a rare variant of uterine adenosarcomas characterized by a sarcomatous portion constituting >25% of the tumor. Uterine MASO often appears as a benign, protruding cervical polyp. However, in contrast to typical müllerian adenosarcomas (MAs), MASO is a highly aggressive tumor, frequently associated with a fatal outcome. Though very rare in premenopausal women, because of the high aggressiveness and malignant potential, uterine MASO should be considered, even in women of a young age with benign-appearing polypoid masses, and treated aggressively at the time of initial diagnosis without delay. We present herein a case of uterine MASO in a 25-year-old woman with lung metastasis who was lost to follow-up for one month after the initial diagnosis had been established.

Towards better understanding of the contributions of overwork and glucotoxicity to the beta-cell inadequacy of type 2 diabetes.

Type 2 diabetes (T2D) is characterized by reduction of beta-cell mass and dysfunctional insulin secretion. Understanding beta-cell phenotype changes as T2D progresses should help explain these abnormalities. The normal phenotype should differ from the state of overwork when beta-cells compensate for insulin resistance to keep glucose levels normal. When only mild hyperglycaemia develops, beta-cells are subjected to glucotoxicity. As hyperglycaemia becomes more severe, so does glucotoxicity. beta-Cells in all four of these situations should have separate phenotypes. When assessing phenotype with gene expression, isolated islets have artefacts resulting from the trauma of isolation and hypoxia of islet cores. An advantage comes from laser capture microdissection (LCM), which obtains beta-cell-rich tissue from pancreatic frozen sections. Valuable data can be obtained from animal models, but the real goal is human beta-cells. Our experience with LCM and gene arrays on frozen pancreatic sections from cadaver donors with T2D and controls is described. Although valuable data was obtained, we predict that the approach of taking fresh samples at the time of surgery is an even greater opportunity to markedly advance our understanding of how beta-cell phenotype evolves as T2D develops and progresses.

The pressure effect on magnetism in CeTe(1.82).

We report the pressure effect of the normal-state transport and magnetic properties of CeTe(1.82) up to 9 kbar. We found that the applied pressure increases the Kondo temperature (T(K)(*)∼170 K), which is associated with the two-dimensional motion of carriers confined within the Te plane. Both the short-range ferromagnetic ordering temperature (T(SRF)∼6 K) and the long-range antiferromagnetic transition temperature (T(N)∼4.3 K) are slightly increased with pressure. We suggest that the application of pressure enhances coupling between the 4f and conduction electrons. While applying the magnetic field, a large magnetoresistance is observed in the vicinity of T(SRF), which is analogous to that at ambient pressure.

Small cell carcinoma of the uterine cervix: clinicopathologic study of 20 cases in a single center.

PURPOSE: To investigate clinicopathologic findings of patients with small cell carcinoma of the uterine cervix (SCCUC), and evaluate their prognosis. METHODS: We retrospectively reviewed the medical records of 20 patients with histologically confirmed SCCUC treated between October 1996 and December 2004 at Asan Medical Center, Korea. The review included demographic data, pathologic findings, treatments, and outcomes. RESULTS: Of 1,358 invasive cervical carcinoma, the incidence of SCCUC was 1.5%. Median age was 45.5 years. The clinical stages were Ib in 11, IIa in two, IIb in one, IIIa in one, IIIb in one, IVa in three and IVb in one. Fourteen patients underwent radical hysterectomy. Ten patients are alive and nine show no evidence of disease. Median overall survival was 77.0 months and 5-year overall survival rate was 50%. There was significant difference in overall survival with FIGO stage and tumor mass size. CONCLUSION: Advanced FIGO stage and tumor mass size are poor prognostic factors for overall survival in patients with SCCUC. Even though SCCUC is a highly aggressive neoplasm, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients.

Field-driven domain wall motion under a bias current in the creep and flow regimes in Pt/[CoSiB/Pt]N nanowires.

The dynamics of magnetic domain wall (DW) in perpendicular magnetic anisotropy Pt/[CoSiB/Pt]N nanowires was studied by measuring the DW velocity under a magnetic field (H) and an electric current (J) in two extreme regimes of DW creep and flow. Two important findings are addressed. One is that the field-driven DW velocity increases with increasing N in the flow regime, whereas the trend is inverted in the creep regime. The other is that the sign of spin current-induced effective field is gradually reversed with increasing N in both DW creep and flow regimes. To reveal the underlying mechanism of new findings, we performed further experiment and micromagnetic simulation, from which we found that the observed phenomena can be explained by the combined effect of the DW anisotropy, Dzyaloshinskii-Moriya interaction, spin-Hall effect, and spin-transfer torques. Our results shed light on the mechanism of DW dynamics in novel amorphous PMA nanowires, so that this work may open a path to utilize the amorphous PMA in emerging DW-based spintronic devices.

Negative regulation of the androgen receptor gene promoter by NFI and an adjacently located multiprotein-binding site.

The upstream promoter of the rat androgen receptor (AR) gene contains a strong negative regulatory region located at the -388 to -340 nucleotide position. The distal part (-388/-373) of this regulatory region binds NFI, a ubiquitous transcription factor, while the proximal portion (-372/-340) contains an overlapping binding site for two nuclear proteins. This composite regulatory region (-388/-340) was initially defined by deoxyribonuclease I footprinting as the continuous stretch of a nuclease-protected site. NFI specificity of the distal portion (-388/-373) of the footprint was established through cross-competition in electrophoretic mobility shift assay (EMSA) using the well characterized NFI element of the adenovirus major late promoter and by immunoreactivity to the NFI antibody. EMSA with oligonucleotide duplexes corresponding to the proximal domain (-372/-340) indicated multiple retarded bands with at least two major DNA-protein complexes. Further analysis with truncated oligonucleotide duplexes showed that these two major proteins bind to this domain in an overlapping manner. Within this overlapping area, the position spanning -359 to -347 is essential for the formation of either of these two complexes. Substitution of four G with T residues in the overlapping area totally abolished all protein binding at the downstream -372/-340 site. Point mutations that abolish specific binding at either the NFI or immediately downstream multiprotein-binding site caused about a 10-fold increase in AR promoter activity in transfected HepG2 cells. Double mutation involving both the NFI and proximal overlapping protein-binding sites failed to cause any additional increase in promoter function. From these results we conclude that the AR promoter contains a composite negative regulatory region at -388/-340, and the repressor function may involve a coordinate interaction between NFI and at least two other nuclear factors.

The evolutionary tangle of aging, sex, and reproduction and an experimental approach to its molecular dissection.

Exchange of genetic materials by two individual members of the same species is considered to be the origin of primitive sex. During evolution, this primitive form of molecular sex has been transformed into a complex biological function involving specialized sexual structures and multiple hormonal interactions. Development and maintenance of these reproductive structures are also dependent on hormones and hormone receptors. Furthermore, reproductive specialization in higher forms of life has led to customized species-specific rates of aging and life-span potentials that are commensurate with the reproductive needs of the particular type of organism. Because of this reproductive imposition on aging of the organism, temporal regulation of the hormone response is a significant component of the genetics of aging. We have observed a marked age-dependent alteration in the hepatic expression of the rat androgen receptor (rAR) gene. Among the large number of transcription factors that control the rAR gene, at least three appear to participate in its age-dependent regulation. Two of these are positively acting and yet/to be characterized transcription factors, while the third is a negative regulator the nuclear factor kappa B (NF-kappa B). NF-kappa B is the major trans-regulator for genes involved in the immune response, inflammation, and oxidative stress. Involvement of NF-kB in the modulation of both oxidative stress and sex function provides the first example of a common molecular link between sex and aging.

Regulation of androgen action by receptor gene inhibition.

Regulated functions of hormonal agents play a critical role in health and disease. Target cell responsiveness to a hormonal signal is a product of both cellular concentrations of the hormone ligand and the corresponding receptor protein. The major thrust of the drug design for treatment of endocrine-related problems, so far, has been directed to ligand derivatives. In certain cases, receptor regulation through antigene technology has much to offer with improvements in both target cell and hormonal specificity. Three different antigene approaches are currently being explored. The first approach is to inhibit the expression of the receptor gene by disrupting the DNA protein interaction at critical cis-elements by short triple helix-forming oligonucleotides. The second approach is to sequester and inactivate the receptor mRNA by the antisense mRNA produced in the target tissue directed by a heterologous tissue-specific promoter. The third approach is the tissue-specific expression of a catalytic ribozyme that binds to the specific receptor mRNA and selectively degrades it before its translation into the protein. In this study, we have characterized the promoter of the rat androgen receptor, and by progressive deletion from its 5' end have identified two critical cis-regulatory elements, one at the -960 to -940 region and the other at the -554 to -574 positions. The former is an activator while the latter is an inhibitor domain. The inhibitory domain is the binding site for the nuclear factor kappa B (NF-kappa B) and more specifically, the p50/p50 homodimer of this transcription factor family. We have also provided correlative data to show that under normal physiological conditions, the NF-kappa B functions as an antiandrogen during the age-dependent desensitization of the liver. In addition to the naturally functioning antiandrogenic influence of NF-kappa B, we have designed an artificial antiandrogenic agent, a triplex-forming oligonucleotide (TFO) directed to the -960/-940 activator domain of the rat androgen receptor gene promoter. This oligonucleotide at a TFO-to-promoter ratio of 500 is able to cause about 60% inhibition of rAR promoter function in transfected COS-1 cells. These results clearly demonstrate the feasibility of the antigene approach for effective inhibition of steroid hormone action.

Use of polyurethane with sustained release dexamethasone in delayed adjustable strabismus surgery.

AIM: To determine the effect of polyurethane film with sustained release dexamethasone (SRD) in delayed adjustable strabismus surgery. METHODS: A prospective, masked observer, controlled study was performed in rabbits. Thirty four rabbit eyes were divided into three groups. After recession of the superior rectus muscle (SRM), polyurethane film with or without SRD, or balanced salt solution was applied beneath and over SRM in the polyurethane-dexamethasone group (group P-D), polyurethane group (group P), and the control group (group C), respectively. Delayed adjustment was performed once on each SRM at 4 and 6 weeks postoperatively by a masked observer. The possible length to adjust and the necessary force required for the adjustment, as well as the degree of any adhesions, were also evaluated. RESULTS: In the control group, adjustment was impossible in all of the eyes at 4 and 6 weeks postoperatively. In group P-D, adjustment was possible in 11 out of 11 eyes (11/11) 4 weeks postoperatively and in 10/11 eyes 6 weeks postoperatively. In group P, adjustment was possible in 9/11 eyes 4 weeks postoperatively and in 10/12 eyes 6 weeks postoperatively. CONCLUSIONS: Use of polyurethane film with and without SRD could delay adjustment in most eyes for up to 6 weeks postoperatively. Polyurethane is helpful for delaying adjustment in rabbit eyes until 6 weeks postoperatively without the need for frequent topical instillation of steroids.

Synthesis and biological activity of novel 3-(2-propenyl)-cephalosporins. II. Preparation of prodrugs.

Three prodrug esters (2a approximately 2c) of 3-(2-propenyl)cephem (1a) have been prepared and their oral absorption was determined in rats and mice. While pivaloyloxymethyl ester (2a) did not improve the oral absorption of the parent cephem 1a, [(1-methyl)ethoxycarbonyloxy]ethyl ester (2b) and (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester (2c) improved oral absorption by a factor of five.

Synthesis and pharmacokinetic profile of 3-methoxymethyl cephalosporin prodrugs.

Preparation and biological activity of prodrug-type 3-methoxymethyl cephalosporins were described. From the mixtures, R- and S-prodrugs were separated and their absolute configurations were determined, and also their bioavailability was investigated.

Corticotropin-releasing hormone enhances the invasiveness and migration of Ishikawa cells, possibly by increasing matrix metalloproteinase-2 and matrix metalloproteinase-9.

Corticotropin-releasing hormone (CRH), synthesized in the hypothalamus, is also produced at several extrahypothalamic sites and in normal endometrial cells. CRH exerts antiproliferative activity on oestrogen-dependent tumour cell lines (Ishikawa cells and breast cancer cells) via the CRH receptor-1. This study investigated the potential role of CRH as a factor affecting endometrial migration and invasion in Ishikawa cells, and the possible mechanisms involved in this process. Increasing concentrations of CRH (1, 10 and 100 nM) significantly reduced the proliferation of Ishikawa cells but increased the invasiveness these cells compared with the control group. All three concentrations of CRH significantly increased matrix metalloproteinase (MMP)-2 and MMP-9 levels in Ishikawa cells. In conclusion, CRH inhibited the growth of Ishikawa cells but enhanced their invasiveness, possibly by increasing MMP-2 and MMP-9 levels. These findings suggest that CRH might induce invasion and migration by upregulating MMP-2 and MMP-9 in endometrial cancer.