Efficacy of curcumin therapy against Angiostrongylus cantonensis-induced eosinophilic meningitis.

Angiostrongylus cantonensis can invade the central nervous system, leading to human eosinophilic meningitis or eosinophilic meningoencephalitis. Curcumin is a natural product which has the effects of anti-inflammation, anti-oxidation and anti-carcinogensis, while the administration of curcumin has been reported to possibly relieve the symptoms of meningitis. The present study tested the potential efficacy of curcumin in A. cantonensis-induced eosinophilic meningitis of BALB/c mice. Assay indicators for the therapeutic effect included the larvicidal effect, eosinophil counts and matrix metalloproteinase-9 (MMP-9) activity in angiostrongyliasis. Eosinophils were mildly reduced in treatment groups compared with infected-untreated mice. However, there were no significant differences in larvicidal effects or MMP-9 activity. This study suggests that anti-inflammatory treatment with curcumin alone has low efficacy, but the treatment does not interfere with MMP-9 expression and is not useful for larvicidal effects. The possible reasons include low curcumin across the blood-brain barrier and also those larvae that survive stimulate MMP-9 production, which promotes blood-brain barrier damage, with leukocytes then crossing the blood-brain barrier to cause meningitis. Further studies will be required to test these possibilities.

Dynamics of supercooled water in mesoporous silica matrix MCM-48-S.

Using three different quasielastic neutron spectrometers with widely different resolutions, we have been able to study the microscopic translational and rotational dynamics of water, in a mesoporous silica matrix MCM-48-S, from T=300 K to 220 K, with a single consistent model. We formulated our fitting routine using the relaxing cage model. Thus, from the fit of the experimental data, we extracted the fraction of water bound to the surface of the pore, the characteristic relaxation times of the long-time translational and rotational decays, the stretch exponent describing the shape of the relaxation processes, and the power exponent determining the Q-dependence of the translational relaxation time. A tremendous slowing down of the rotational relaxation time, as compared to the translational one, has been observed.

Differential expression and regulation of macrophage inflammatory protein (MIP)-1alpha and MIP-2 genes by alveolar and peritoneal macrophages in LPS-hyporesponsive C3H/HeJ mice.

A point mutation in Toll-like receptor 4 (Tlr4) gene in C3H/HeJ mice underlies a defect in LPS-induced cytokine production by peritoneal macrophages (PMphi;). Whether the C-C and the C-X-C chemokines are induced differently by LPS between alveolar macrophages (AMphi;) and PMphi; in this mice remains unclear. Thus, we examined the expression and regulation of macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-2 (MIP-2) in C3H/HeJ macrophages. These results showed that the accumulation of MIP-1alpha and MIP-2 mRNA increased dose dependently in response to LPS. PMphi; responded to LPS to produce significantly higher levels of both chemokine mRNA and protein than AMphi;. In addition, both macrophages produced much more MIP-2 than MIP-1alpha by the same doses of LPS stimulation. Moreover, the chemokine production by C3H/HeN macrophages was significantly higher than that of the C3H/HeJ macrophages. IFN-gamma suppressed the LPS-induced MIP-1alpha release but enhanced the LPS-induced MIP-2 secretion in both macrophages. These results show that the chemokine production was induced and regulated differentially in AMphi; and PMphi;.

Effects of quorum sensing signal molecules on the hydrogen peroxide resistance against planktonic Pseudomonas aeruginosa.

The effects of quorum sensing signal molecules in Pseudomonas aeruginosa, N-butanoyl-L-homoserinelactone (C4-HSL) and N-(3-oxododecanoyl)-L-homoserinelactone (3-oxo-C12-HSL) on planktonic cell resistance against hydrogen peroxide were studied. In P. aeruginosa JP2 cells with the deletion of lasI and rhlI, the viable cell concentration decreased with time and was reduced by about 4 log after 2 h of 7.5 mM H2O2 treatment, while only a 2-log reduction was found for the wild type P. aeruginosa PAO1 cells. When cultured with 20% PAO1 spent medium, P. aeruginosa JP2 showed similar hydrogen peroxide resistance to that seen in P aeruginosa PAO1. Culturing with 20% JP2 spent medium or with 10 microM C4-HSL and 20 microM 3-oxo-C12-HSL did not affect P aeruginosa JP2 cell susceptibility to hydrogen peroxide. Although both 20% PAO1 and JP2 spent media reacted with H2O2 and reduced H2O2 to 50% of the strength of the original concentration, the remaining H2O2 was still sufficient to kill P. aeruginosa JP2. These results indicate that the difference in cell resistance against H2O2 between P. aeruginosa PAO1 and JP2 was related to the existence of gene products of the lasI and rhlI systems. However, adding synthetic homoserine lactones alone did not increase P. aeruginosa JP2 cell resistance to H2O2 as seen in the experiments adding PAO1 spent medium. Determination of the detailed relation between cascade regulation in P. aeruginosa and its cell resistance to H2O2 will require further investigation.

Differential expression of inducible nitric oxide synthase gene by alveolar and peritoneal macrophages in lipopolysaccharide-hyporesponsive C3H/HeJ mice.

In lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, alveolar macrophages (AMphi) produce much more tumour necrosis factor-alpha than peritoneal macrophages (PMphi) when stimulated with LPS (10 microgram/ml), but the induction of inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide (NO) in AMphi are not found. In the present study, we determined the induction of iNOS gene expression, using semi-quantitative reverse transcription-polymerase chain reaction, and the release of NO in AMphi and PMphi from C3H/HeJ and C3H/HeN mice. The results showed the induction of iNOS mRNA accumulation in a dose-dependent manner by LPS alone or in combination with interferon-gamma in both macrophages. The effects of the stimuli on iNOS gene expression and NO production were significantly higher in AMphi than in the PMphi of C3H/HeJ mice. The response of macrophages from C3H/HeN mice was similar to those from C3H/HeJ mice, but the difference of iNOS gene expression between AMphi and PMphi in C3H/HeN mice was not as striking as in C3H/HeJ mice. The results show that the iNOS gene expression and NO production were activated differently in AMphi and PMphi and suggest that the functional properties of macrophages isolated from distinct origins are different.

Single-stranded RNA molecular weight and shape determination by differential pressure capillary viscometry, sedimentation velocity, and gel electrophoresis.

Determination of the size of a population of nucleic acids can be achieved by several distinct methods. Most of these methods are cumbersome and require complicated equipment or techniques. We demonstrate here the use of a differential pressure capillary viscometer for the rapid and simple determination of RNA molecular weight. This highly sensitive viscometer allowed single viscosity determinations on dilute solutions of RNA, providing a direct measure of the intrinsic viscosity without the need to extrapolate from several concentrations. The molecular weights and conformations of the linear single-stranded RNA homopolymer poly(inosinic acid) (poly(I] and the single-stranded RNA (ssRNA) copolymer poly(cytidylic acid:uridylic acid, 12:1) (poly(C12,U], were determined. The ssRNAs were synthesized in a range of sizes (100 to 100,000 bases). They were widely polydisperse. The Mandelkern-Flory equation (1952, J. Chem. Phys. 20, 212-214), which requires both the intrinsic viscosity and sedimentation coefficient of a macromolecule, was used to calculate the molecular weights. The molecular weights determined by agarose gel electrophoresis were compared to those determined by intrinsic viscosity plus sedimentation coefficient. The correlation between the molecular weights determined by these two methods was good, at R2 greater than or equal to 0.92. The conformations of the RNAs were determined by application of the Mark-Houwink equation. The Mark-Houwink exponents for poly(I) and poly(C12,U) intrinsic viscosities were 0.90 and 0.84, respectively. When compared to other nucleic acid polymers, for which the conformations have been established by several methods, poly(I) and poly(C12,U) are rigid, extended random coils, in a low-salt buffer (15 mM).(ABSTRACT TRUNCATED AT 250 WORDS)