First record of Anopheles minimus C and significant decrease of An. minimus A in central Vietnam

Before August 1998, in the Khanh Phu commune (central Vietnam), Anopheles minimus s.l. individuals were identified as species A and showed the typical species A wing form. After a significant decrease over the 3 years 1999-2001, an increase in 2002 of An. minimus s.l. possessing a different wing pattern was observed. To determine the specific status of the An. minimus species collected in 2002 and to follow changes in the species composition, an allele-specific polymerase chain reaction was applied to samples collected from 1993 to 2002. This study reports the first record of An. minimus C in central Vietnam and, since 1998, a significant reduction of An. minimus A that coincided with the wide use of permethrin-treated bednets. This change in anopheline composition may have important consequences on malaria transmission. This work shows that the geographic distribution of malaria vectors in southeast Asia is only partially known and highlights the importance of species identification for understanding changes in the vector composition as a result of selective vector control.     

Dysfunctional C8β Chain in Patients with C8 Deficiency

Two sera from unrelated individuals, each lacking C8 activity, were examined by Western blot analysis. Using antisera raised against whole C8, the two sera are shown to lack the C8 beta chain, indicating a C8 beta deficiency, which is frequently observed in cases of dysfunctional C8. In contrast, by means of a specific anti-C8-beta antiserum, a C8 beta-like polypeptide chain of apparently identical molecular weight compared to normal C8 beta was detected. Digestion of normal and dysfunctional C8 beta with Staphylococcus aureus V8 protease revealed distinct differences in the enzymatic digestion pattern. We conclude that the dysfunction in the C8 protein in these two patients resides in the dysfunctional C8 beta chain, and that this form of C8 deficiency is distinct from C8 deficiencies previously reported, in which one or both C8 subunits are lacking.     

A novel graph-based similarity measure for 2D chemical structures

In this paper, we propose a graph-based method to measure the similarity between chemical compounds described by 2D form. Our main idea is to measure the similarity between two compounds based on edges, nodes, and connectivity of their common subgraphs. We applied the proposed similarity measure in combination with a clustering method to more than eleven thousand compounds in the chemical compound database KEGG/LIGAND and discovered that compound clusters with highly similar structure compounds that share common names, take part in the same pathways, and have the same requirement of enzymes in reactions. Furthermore, we discovered the surprising sameness between pathway modules identified by clusters of similar structure compounds and that identified by genomic contexts, namely, operon structures of enzyme genes.     

Dorsal hippocampus NMDA receptors differentially mediate trace and contextual fear conditioning

The dorsal hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 microg/microl; 0.5 microl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories.     

Withdrawal syndrome from gamma-hydroxybutyric acid (GHB) and 1,4-butanediol (1,4-BD) in Sardinian alcohol-preferring rats

Gamma-hydroxybutyric acid (GHB) and its precursors, 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), are recreational drugs widely abused in the US, Europe and Australasia. A severe withdrawal syndrome from GHB, 1,4-BD and GBL has been increasingly documented over the last years, necessitating the development of a reliable animal model for investigations of potential therapeutic approaches. The present study describes the induction and occurrence of audiogenic seizures as a sign of withdrawal from GHB and 1,4-BD in selectively bred Sardinian alcohol-preferring (sP) rats, treated with escalating doses of GHB (1.5-3.5 g/kg, twice daily; i.g.) or 1,4-BD (500-1000 mg/kg, twice daily; i.g.) for 9 consecutive days. Acute administration of the selective GABA(B) receptor antagonist, SCH 50911, dramatically increased seizure occurrence. We propose that the inherent sensitivity of sP rats to different GHB-associated responses may have contributed to the unraveling of a phenomenon which was otherwise not recognizable in other rat strains.     

Antimicrobial azaphilones from the fungus Hypoxylon multiforme

Four new azaphilones named multiformins A - D together with a known compound 4 : 5:4':5'-tetrahydroxy-1 : 1'-binaphthyl were isolated from the methanolic stromatal extract of the xylariaceous ascomycete Hypoxylon multiforme. Their absolute structures were characterised by 2D-NMR, UV, IR, mass and CD spectroscopy. Multiformins A - D showed strong and apparently non-selective antimicrobial activity.     

Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo.

PURPOSE: The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has multiple antitumor effects against a variety of human cancers. EXPERIMENTAL DESIGN: We treated several anaplastic and papillary thyroid cancer cell lines with SAHA to determine if it could inhibit the growth of these cells in vitro and in vivo. RESULTS: SAHA effectively inhibited 50% clonal growth of the anaplastic thyroid cancer cell lines, ARO and FRO, and the papillary thyroid cancer cell line, BHP 7-13, at 1.3x10(-7) to 5x10(-7) mol/L, doses that are achievable in patients. In concert with growth inhibition, SAHA down-regulated the expression of cyclin D1 and up-regulated levels of p21WAF1. Annexin V and cleavage of poly(ADP)ribose polymerase were both increased by exposure of the thyroid cancer cells to SAHA. Expression of the death receptor 5 (DR5) gene was also increased by SAHA, but the combination of the DR5 ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with SAHA had little effect compared with SAHA alone. Of note, the combination of paclitaxel, doxorubicin, or paraplatin with SAHA enhanced cell killing of the thyroid cancer cells. In addition, murine studies showed that SAHA administered daily by i.p. injection at 100 mg/kg inhibited the growth of human thyroid tumor cells. CONCLUSION: Our data indicate that SAHA is a plausible adjuvant therapy for thyroid cancers.     

Vasopeptidase Inhibition Peri- and Post-MI in Zucker Insulin Resistant Rats: Effect on MI Size,Arrhythmias, Remodeling,Function and Fetal Gene Expression

Summary Mortality peri-myocardial infarction (MI) is increased with insulin resistance. As the vasopeptidase inhibitor (VPI) omapatrilat improves insulin sensitivity, it may be beneficial peri-MI in Zucker Insulin Resistant rats (ZIR). ZIR rats (n = 228) received omapatrilat 10 mg/kg/day, 7 days pre-MI, to 38 days post-MI, or control. Twenty-four protocol (n = 72): a subgroup of rats received the kinin receptor antagonist icatibant. Ambulatory ECG recordings, and MI size were evaluated. Thirty-eight-day protocol (n = 156): left ventricular (LV) remodeling, cardiac hemodynamics, morphology, infarct size, and RT-PCR for GLUT-4 and fetal genes were measured. Omapatrilat improved post-MI survival 24 h (62% vs 38%, P = 0.0007) which was maintained 38 days. There was a kinin-induced reduction of ventricular arrhythmias and there appeared to be a kinin-independent reduction in MI size (23.5 ± 2.4% vs 17.0 ± 2.2%, P = 0.053) for 24-h post-MI. Omapatrilat reduced but did not prevent LV dilatation, dysfunction, and fetal gene expression 38 days post-MI. Omapatrilat did not prevent reduced cardiac GLUT-4 expression. In ZIR rats, mortality post-MI is reduced by omapatrilat, due and a kinin-dependent reduction in ventricular arrhythmias and possibly a kinin-independent reduction in MI size. Ventricular dilatation, dysfunction, and fetal gene expression are variably attenuated but not prevented.