Saponins are amphiphilic substances consisting of a hydrophobic backbone with one or two hydrophilic sugar units. Recently it was shown that saponinum album (SA) from Gypsophila paniculata L. enhanced cytotoxicity of a saporin-based chimeric toxin (up to 385,000-fold) as well as the toxicity of saporin (up to 100,000-fold) with N-glycosidase activity. Previously we have shown that toxicity of other N-glycosidases such as ricin A-chain, nigrin b, and toxins such as diphtheria toxin or microcystin-LR was not enhanced by SA. This points to a specific SA-dependent mechanism of toxicity enhancement on saporin and saporin-based toxins. Although the cytotoxicity enhancing effect was observed in up to 10 different cell lines, nothing is known about the kinetic of SA under cell culture conditions. Therefore SA was titrated, and the uptake respective liberation profile of SA was investigated in ECV-304 cells. Treatment of cells with [(3)H]-SA leads to an immediate uptake of saponin molecules. After cells were saturated with [(3)H]-SA, a first equilibrium (first eq.) was reached. The first eq. was disturbed by washing until a second equilibrium was reached between the activity observed within cells and that seen in the supernatant. After a further extensive washing, a small portion of saponin molecules remained durable associated with the cell. This portion was sufficient to induce a drastic toxicity enhancement on saporin indicating a long-lasting sensitization of cells against the toxin.

Response surface methodology (RSM) was used to optimize microencapsulation yield (MY) using three independent variables; the ratio of coating material to core material (w/w, X1), the emulsifier concentration (%, v/v, X2), and the CaCl2 concentration (%, w/v, X3). In the preparation of sodium alginate (SA) microcapsule, the regression model equation for the MY was predicted as follows; MY(%) = 56.02 + 3.64X2 + 3.18X1X2 - 3.74X2(2). The optimal conditions for the SA microcapsule were obtained at the [SA]/[alpha-TP] ratio of 6.6:3.4 (w/w), [emulsifier] of 1.35% (v/v), and [CaCl2] of 4.3% (w/v), and the predicted MY in this condition was of 57.2%. In vitro alpha-TP releasing test of the SA-based microcapsules was performed. The SA microcapsule released 28.8% of alpha-TP when exposed in the simulated gastric fluid (SGF, pH 1.2) for 24 h. In the simulated intestinal fluid (SIF, pH 7.4), the amount of released alpha-TP (81.5%) was significantly greater than that in the SGF. The duration time required for releasing 50 (T50%) and 70% (T70%) of alpha-TP from the SA-microcapsule were calculated to be 3.8 and 12.3 h, respectively. From these results, it was suggested that SA microcapsule would be structurally resistant against acidic environment, and it would rapidly release core material under mild alkali condition.

A liver transplant was performed on a 4-year-old female in liver failure caused by hereditary tyrosinaemia, with hepatocellular carcinoma following a negative evaluation for metastases. However, serum alpha-fetoprotein levels never returned to normal after the surgery. Urinary succinylacetone (SA) was detected in her urine prior to transplantation despite strict adherence to a low-tyrosine diet. Other patients with severe liver disease awaiting liver transplantation do not excrete SA in the urine. She continued to excrete SA during the postoperative period despite normal liver functions. Oral tyrosine loading resulted in significant elevation of SA excretion. Possible explanations for this observation and clinical and therapeutic relevance are discussed.

A genomic clone encoding a serine proteinase inhibitor II, designated as TPI-2, was isolated from tomato (Lycopersicon esculentum Mill.) seedling. It consisted of a 990 bp upstream regulatory region and a 680 bp transcription region containing an intron. As shown by northern hybridization, mechanical injury activated its expression in roots, stems and leaves, and so did exogenous hormones jasmonic acid (JA) and alpha-Linolenic acid (LA), though abscisic acid (ABA) and NaCl failed to induce its expression. Salicylic acid (SA) was found to inhibit the inducing effect of LA but not those of mechanical injury and JA. As demonstrated experimentally, TPI-2 could be expressed effectively in tobacco cells and the protein products showed insecticidal activity.

Introduction. Emergence of MRSA infections among previously healthy persons in community settings (without exposure to health care facilities) has been noted recently. MRSA infections are now classified as health care-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) infections. Its colonization is an important risk factor for subsequent MRSA infection. Aims and Objectives. The aim was to screen patients and health care workers for staphylococcal carriage, identify risk factors for MRSA colonization, and determine the sensitivity pattern. Materials and Methods. A total of 200 subjects were screened for nasal carriage after obtaining verbal consent. These were both healthy subjects attending various outpatient departments and health care workers. Specimens were collected from the anterior nares using premoistened sterile cotton swabs and inoculated onto blood agar and mannitol salt agar and incubated at 37°C for 24-48 h. Results. Staphylococcus aureus colonisation was found to be 12% (n = 24). MRSA was identified in 5% (n = 10) which represents 41.66% of SA. A total of 10 strains of MRSA were isolated from 200 subjects, giving an overall positivity rate of 5%. Discussion. Staphylococcal colonization was found to be 12% (MRSA 5%). Fluoroquinolone resistance was remarkable whereas all strains were sensitive to vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin.

Phospholipase C-beta (PLC-beta) isozymes (EC 3.1.4.11) hydrolyze the membrane phospholipid phosphatidylinositol-4,5-bisphosphate to generate intracellular second messenger signaling molecules inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) in response to receptor activation and other cellular stimuli. PLCbeta1 and PLCbeta3 isozymes were previously demonstrated to bind the calcium-sensitive molecule calmodulin [McCullar JS, Larsen SA, Millimaki RA, Filtz TM. Calmodulin is a phospholipase C-{beta} interacting protein. J Biol Chem 2003;278(36):33708-13]. We have now shown through fluorescence anisotropy that calmodulin/PLCbeta3 affinities increase with increasing calcium in a physiologically relevant concentration range. The bimolecular affinity constants for calmodulin interaction with PLCbeta1 or PLCbeta3 were estimated as 260 and 200 nM, respectively, from fluorescence anisotropy data. There was no effect of calmodulin on basal or G alpha q-stimulated catalytic activity for either isozyme. However, the interaction between calmodulin and PLCbeta3 leads to potentiation of activation by the G-protein beta gamma dimer in an in vitro assay. 1321N1 cells treated with calmodulin inhibitors concurrent with and post-stimulation of muscarinic receptors significantly reduced [3H]PIP hydrolysis. Together these data are suggestive of cooperative role for calmodulin in the G-protein beta gamma dimer-stimulated activity of PLCbeta3.

1. The aim of this study was to investigate constrictor <em>alpha</em>-adrenoceptors in three isolated blood vessels of the pig, the thoracic aorta (TA), the splenic artery (<em>SA</em>) and marginal ear vein (MEV) and then compare the functional response with the densities of <em>alpha</em> 1- and <em>alpha</em> 2-adrenoceptor binding sites in these and several other porcine vascular tissues, palmar common digital artery (PCDA), palmar lateral vein (PLV) and ear artery (EA). 2. Noradrenaline (NA), phenylephrine (PE) and UK14304 (all at 0.03-10 microM) elicited concentration-dependent contractions in the TA and MEV, with a rank order of potency of UK14304>> NA>> PE. UK14304 produced maximal responses which were 58% (TA) and 65% (MEV) of that of NA. In the <em>SA</em>, UK14304 and PE produced maximal responses which were less than 10% and 50% of the NA-induced maximal response respectively, with an order of potency of NA>> PE. In the <em>SA</em>, NA-induced contractions were competitively antagonized by prazosin (pA2 = 8.60 +/- 0.15). Further, rauwolscine (1-10 microM) antagonized NA-induced contractions with an apparent pKB of 6.09 +/- 0.11 (n = 6), indicating an action at <em>alpha</em> 1-adrenoceptors. The combination of the two antagonists at concentrations selective for <em>alpha</em> 1- (0.1 microM) and <em>alpha</em> 2-adrenoceptors (1 microM) had no greater effect than either antagonist alone. This suggests that the <em>SA</em> expresses only post-junctional <em>alpha</em> 1-adrenoceptors. 3. In the TA, prazosin produced non-parallel shifts in the NA-induced CRC and this was also observed with rauwolscine, where reductions in the maximal responses were also observed. In the MEV, prazosin was largely inactive in antagonizing NA-induced contractions. In both these vessels a combination of these two antagonists had a greater effect than either alone, indicating the presence of functional <em>alpha</em> 1- and <em>alpha</em> 2-adrenoceptors. The post-junctional <em>alpha</em> 2-adrenoceptors in all of these vessels were resistant to prazosin, suggesting the <em>alpha</em> 2-adrenoceptor to be of the <em>alpha</em> 2A/2D subtype. The expression of functional <em>alpha</em> 2-adrenoceptors was MEV>> TA>> PLV>> PCDA>> <em>SA</em>. 4. In radioligand binding studies using TA P2 pellet membranes, [3H]-prazosin and [3H]-RX821002 ([1,4-[6,7(n)-3H] benzodioxan-2-methoxy-2-yl)-2-imidazole) labelled different high affinity sites, and in competition studies using identical membranes corynanthine displaced [3H]-prazosin with 10 fold higher affinity than rauwolscine, indicating that [3H]-prazosin was selectively binding to <em>alpha</em> 1-adrenoceptor sites. Further, rauwolscine displaced [3H]-RX821002 with approximately 100 fold greater affinity compared to corynanthine, which is indicative of selective <em>alpha</em>2-adrenoceptor binding.5. Separation of the P2 pellet into plasma membrane and mitochondrial fractions was carried out using a differential sucrose density gradient. [3H]-prazosin and [3H]-RX821002 binding sites were found in both the plasma membrane and mitochondrial fractions.6. In saturation studies all tissues produced single site saturation curves with no difference in the Kd(range 0.13-0.20nM) of the <em>alpha</em>1-adrenoceptor sites for [3H]-prazosin. However, there was considerable variation in Bmax of <em>alpha</em> 1-adrenoceptor sites; the highest density was found in the TA (397.9 =/- 52.7 fmol mg-1, n = 4), followed by the PCDA (256.7 +/- 22.7 fmol mg-1, n = 4), the PLV and <em>SA</em> having approximately equal density (143.6 +/- 3.9 and 159.1 +/- 7.0 fmol mg-1 respectively, n = 4 for both), followed bythe EA (91.3 +/- 10.5 fmol mg-1, n = 3) and the MEV had the lowest density (48.9 +/- 11.4 fmol mg-1,n = 3).7. In saturation studies using [3H]-RX821002, all tissues produced single site saturation curves with no differences in the Kd values (range 1.31 +/- 2.16 nM) but the highest densities were found in the TA and MEV (545.3 +/- 36.2 and 531.0 +/- 40.9 fmol mg-1 respectively), followed by the PLV (418.4 +/- 39.4 fmol mg-1), then the EA (266.3 +/- 40.0 fmol mg-1), and low densities of [3H]-RX821002 binding being found in the PCDA and <em>SA</em> (155.9 +/- 18.1 and 117.5 +/- 19.3 fmol mg-1 respectively).8. The pattern of binding site distribution for <em>alpha</em> l- and <em>alpha</em> 2-adrenoceptors is in reasonable agreement with functional studies carried out in these porcine vascular tissues; the TA has the highest densities of <em>alpha</em> 1-and <em>alpha</em>2-adrenoceptors; in the <em>SA</em> and PCDA there is a predominance (although small) of <em>alpha</em> l-adrenoceptor binding sites, the reverse of which is observed both in the PLV and MEV (i.e. greater density of <em>alpha</em>2-adrenoceptor sites). Thus, it would appear that <em>alpha</em> 1- and <em>alpha</em>2-adrenoceptor densities play a role in the expression of functional responses via these receptor subtypes; although it is interesting to note that the <em>SA</em> did have a small density of <em>alpha</em> 2-adrenoceptor binding sites, no functional response was observed after <em>alpha</em>2-adrenoceptor activation.

This study examines the reliability and convergent validity of the Work/School Abuse Scale (W/SAS), a measure of the ways that abusive men interfere with women's participation in education and employment. Results indicate good reliability as measured by coefficient alpha and significant correlations with both a revised version of the Conflict Tactics Scale and the Psychological Abuse Index. The W/SAS is a useful measure of the ways in which physical force and other means of interfering with women's lives isolate them from activities that might provide income, social contacts, and a sense of accomplishment. It may also be used to examine whether changes in welfare policies affect levels of physical force and nonviolent interference in women's employment and education, as suggested by the Family Violence Option to the 1996 revisions in federal welfare policies.

Pasteurella multocida Sa, a bacterial strain isolated from mangrove sediment by enrichment technique, was capable of transforming dimethyl terephthalate (DMT). Biodegradation of DMT was shown to take place as a series of sequential steps involving the hydrolysis of two ester linkages between the carboxyl groups of the terephthalate and the methyl side-chain initially to produce mono-methyl terephthalate (MMT) and then terephthalic acid (TA), respectively. However, with ethanol as the carrying solvent, there was a formation of one metabolite previously not observed. The two metabolites were characterized by high performance-liquid chromatography-electron ionization mass spectrometry as MMT and mono-ethyl terephthalate (MET), suggesting the existence of an alternative biochemical pathway in the degradation of DMT by P. multocida Sa. Since the presence of MMT and ethanol in culture inoculated with P. multocida Sa was prerequisites for the formation of MET, biologically mediated trans-esterification was proposed as a mechanism for the novel biochemical process observed.

In this study, three cationic polyrotaxanes composed of multiple oligoethylenimine-grafted alpha-cyclodextrin rings threaded on a poly(ethylene oxide) chain have been synthesized and characterized, and investigated for gene delivery. All three cationic polyrotaxanes could efficiently compact pDNA into small nanoparticles, with diameters ranging from 100 to 200 nm. In both BHK-21 and MES-SA cell lines, the transfection efficiency mediated by the cationic polyrotaxanes were comparable or even higher than that of branched polyethylenimine (PEI) with a molecular weight of 25 kDa, which is one of the most efficient gene-delivery vectors to date. Moreover, the cationic polyrotaxanes showed much lower cytotoxicity than branched PEI (25 kDa). Hence, these cationic poly rotaxanes have high potentials as new carriers for gene delivery.

Previous studies have revealed that interferon-alpha (IFN-alpha) suppresses the B cell responses stimulated with Staphylococcus aureus (SA) + IL-2 in the complete absence of monocytes but enhances the responses of B cells contaminated with monocytes. The current studies therefore examined in detail the combined effects of IFN-alpha and monocytes on the B cell responses induced by SA + IL-2. Monocytes overcome the suppressive effects of IFN-alpha on the IgM production induced by SA + IL-2. Thus, in the presence of monocytes, IFN-alpha enhanced the IgM production by B cells stimulated with SA + IL-2. IFN-alpha still enhanced the IgM production induced by SA + IL-2 in the presence of monocytes and indomethacin. The IFN-alpha-mediated suppression of B cell responsiveness was not overcome by addition of factors generated from SA-activated monocytes, or any of IL-1 beta, IL-6, and TNF-alpha. Of note, the IFN-alpha-mediated suppression of B cell responsiveness was overcome only when B cells and monocytes were allowed to contact with each other. This reversal of the IFN-alpha-mediated suppression of B cell function was not blocked by any of the mAb to CD11a, CD18, CD54, or monomorphic determinants of HLA-DR. These results indicate that IFN-alpha enhances the B cell responses induced by SA + IL-2 through direct interactions between monocytes and B cells that do not involve lymphocyte-function-associated-1 molecules, intercellular adhesion molecule-1, or HLA-DR antigens. Thus, the data demonstrate the presence of unique direct interactions between B cells and monocytes that regulate human B cell responsiveness.

South Africa (SA), a country in which all three commercially important asbestos minerals have been mined and milled, has retained proven cases of mesothelioma linked with environmental exposure to asbestos. This study illustrates the importance of fiber type in the occurrence of environmental mesothelioma. Four studies have reviewed the source of occupational or environmental asbestos exposure in 504 histologically proven cases of mesothelioma in South Africa. One hundred and eighteen cases (23%) were thought to be related to environmental exposure to asbestos. In the vast majority of these cases, exposure was linked to crocidolite mining activities in the Northern Cape Province. Two cases were thought to have occurred in relation to amosite and Transvaal crocidolite exposure in the Limpopo Province. In the balance of cases there was some uncertainty. No cases were reported with exposure to South African chrysotile. Consequently, in the vast majority of cases of mesothelioma, environmental exposure to asbestos occurred in the Northern Cape Province, in proximity to mines, mills and dumps where crocidolite was processed. Crocidolite appears to be far more mesotheliomagenic than amosite, and chrysotile has not been implicated in the disease. This is true for both occupationally and environmentally exposed individuals.

alpha-Bisabolol (BISA) is a sesquiterpene alcohol found in the oils of chamomile (Matricaria chamomilla) and other plants. BISA has been widely used in dermatological and cosmetic formulations. This study was undertaken to investigate the mutagenicity and antimutagenicity of BISA in the Salmonella/microsome assay. Mutagenicity of BISA was evaluated with TA100, TA98, TA97a and TA1535 Salmonella typhimurium strains, without and with addition of S9 mixture. No increase in the number of his+ revertant colonies over the negative (solvent) control values was observed with any of the four tester strains. In the antimutagenicity assays, BISA was tested up to the highest nontoxic dose (i.e. 50 and 150 microg/plate, with and without S9 mix, respectively) against direct-acting (sodium azide, SA; 4-nitroquinoline-N-oxide, 4-NQNO; 2-nitrofluorene, 2-NF; and nitro-o-phenylenediamine, NPD) as well as indirect-acting (cyclophosphamide, CP; benzo[a]pyrene, B[a]P; aflatoxin B1, AFB1; 2-aminoanthracene, 2-AA; and 2-aminofluorene, 2-AF) mutagens. BISA did not alter mutagenic activity of SA and of NPD, and showed only a weak inhibitory effect on the mutagenicity induced by 4-NQNO and 2-NF. The mutagenic effects of AFB1, CP, B[a]P, 2-AA and 2-AF, on the other hand, were all markedly and dose-dependently reduced by BISA. It was also found that BISA inhibited pentoxyresorufin-o-depentylase (PROD, IC50 2.76 microM) and ethoxyresorufin-o-deethylase (EROD, 33.67 microM), which are markers for cytochromes CYP2B1 and 1A1 in rat liver microsomes. Since CYP2B1 converts AFB1 and CP into mutagenic metabolites, and CYP1A1 activates B[a]P, 2-AA and 2-AF, results suggest that BISA-induced antimutagenicity could be mediated by an inhibitory effect on the metabolic activation of these promutagens.

The availability of Met in metabolizable protein (MP) of a wide range of diets for dairy cows is low. During late pregnancy and early lactation, in particular, suboptimal Met in MP limits its use for mammary and liver metabolism and also for the synthesis of S-adenosylmethionine, which is essential for many biological processes, including DNA methylation. The latter is an epigenetic modification involved in the regulation of gene expression, hence, tissue function. Thirty-nine Holstein cows were fed throughout the peripartal period (-21 d to 30 d in milk) a basal control (CON) diet (n=14) with no Met supplementation, CON plus MetaSmart (MS; Adisseo NA, Alpharetta, GA; n=12), or CON plus Smartamine M (SM; Adisseo NA; n=13). The total mixed ration dry matter for the close-up and lactation diets was measured weekly, then the Met supplements were adjusted daily and top-dressed over the total mixed ration at a rate of 0.19 (MS) or 0.07% (SM) on a dry matter basis. Liver tissue was collected on -10, 7, and 21 d for global DNA and peroxisome proliferator-activated receptor alpha (PPARα) promoter region-specific methylation. Several PPARα target and putative target genes associated with carnitine synthesis and uptake, fatty acid metabolism, hepatokines, and carbohydrate metabolism were also studied. Data were analyzed using PROC MIXED of SAS (SAS Institute Inc., Cary, NC) with the preplanned contrast CON versus SM + MS. Global hepatic DNA methylation on d 21 postpartum was lower in Met-supplemented cows than CON. However, of 2 primers used encompassing 4 to 12 CpG sites in the promoter region of bovine PPARA, greater methylation occurred in the region encompassing -1,538 to -1,418 from the transcription start site in cows supplemented with Met. Overall expression of PPARA was greater in Met-supplemented cows than CON. Concomitantly, PPARA-target genes, such as ANGPTL4, FGF21, and PCK1, were also upregulated overall by Met supplementation. The upregulation of PPARα target genes indicates that supplemental Met, likely through the synthesis of S-adenosylmethionine, activated PPARA-regulated signaling pathways. Upregulation of hepatic PPARA has been associated with improved lipid metabolism and immune function, both of which were reported in companion publications from this study. In turn, those positive effects resulted in improved postpartal health and performance. Further research is needed to study more closely the mechanistic connections between global DNA and promoter region-specific PPARA methylation with PPARA expression and functional outcomes in liver.

The mechanism by which parathyroid hormone-related protein (PTH-RP) stimulates bone resorption is not known. Like certain other resorbing agents it may act to release bone-resorbing cytokines from the osteoblast. To examine this hypothesis, we used serum-free conditioned media (CM) from SAOS II cells incubated with 10(-8) M h(1-74) PTH-RP for 48 h. Treated CM contained substantially more bone-resorbing activity (BRA) in the fetal-rat long-bone assay than CM from untreated cells (2.17 +/- 0.21 vs 1.38 +/- 0.16 fold stimulation over basal [f]; p less than 0.05]. After centrifugation and dialysis, 1 liter of treated CM contained a total BRA of 7102 ngeq b(1-34) PTH with a specific activity (SA) of 447 ngeq b(1-34) PTH/mg protein. Treated CM did not stimulate the ROS assay and the cytokines PGE2, TGF-alpha, EGF, GM-CSF and IL-1 were present in low concentrations. The BRA was heat sensitive. Ultrafiltration revealed that 97% of the BRA was in a 3-30 kD fraction. Further purification was achieved by sequential reverse phase HPLC and size exclusion-HPLC (SE-HPLC). A single fraction containing BRA from SE-HPLC was purified 277-fold to a SA of 123,810 ngeq b(1-34) PTH/mg protein and had an apparent MW of 9 kD. SDS-PAGE revealed 4 bands in this SE-HPLC fraction with 1 band at 9 kD unique to that fraction. PTH-RP may cause bone resorption in part by stimulating the release of a 9 kD protein from osteoblasts which is responsible for activating osteoclasts.

A preliminary study of the antitumor effect of partially purified human interferon alpha (IFN-alpha) and low-level direct current (DC) was carried out using a murine subcutaneous SA-1 experimental tumor model. Tumor-bearing animals were treated with 5 x 10(4) IU IFN-alpha peritumorally, or with 0.6 mA DC current for 15 minutes daily, for 6 consecutive days. Antitumor effect was manifested 2 days after the beginning of each treatment modality. Combined treatment with DC current applied immediately after IFN-alpha application was more effective than IFN-alpha treatment alone (P less than 0.005), but not significantly better than DC current treatment (P less than 0.5). The results indicate that the combined treatment with IFN-alpha and DC current can be effective in tumor therapy; however, further work is required to determine optimal scheduling.

BACKGROUND

Fatigue is highly prevalent among doctors worldwide. However, no research has been done to examine the associations of emotional intelligence (EI) and emotional labor strategy with fatigue among Chinese doctors. This study aimed to examine whether or not emotional labor strategy mediates the association between EI and fatigue in this occupational group.

METHODS

A cross-sectional study was conducted in Shenyang from March to April 2014. A set of self-administered questionnaires was distributed to 950 doctors, including Chalder Fatigue Scale (CFS), Wong and Law Emotional Intelligence Scale (WLEIS) and a 14-item emotional labor scale. Complete responses were obtained from 740 (77.9%) participants. Hierarchical linear regression was performed to examine the associations of EI and emotional labor strategies (surface acting, SA; deep acting, DA; natural acting, NA) with fatigue. Asymptotic and resampling strategies were used to examine the mediating roles of emotional labor strategies.

RESULTS

The mean score of fatigue was 8.02 (SD = 3.39). After adjusting for age, gender, marital status, job rank, monthly income, weekly working time, shift and department, EI was negatively associated with fatigue (β = - 0.270, P < 0.001). SA was positively associated with fatigue (β = 0.168, P < 0.001), whereas NA was negatively associated with fatigue (β = - 0.105, P = 0.004); however, DA was not significantly associated with fatigue (β = 0.034, P = 0.381). Thus, SA (a × b = - 0.026, BCa 95% CI: - 0.050, - 0.011) and NA (a × b = - 0.024, BCa 95% CI: - 0.046, - 0.006) significantly mediated the association between EI and fatigue, respectively.

CONCLUSIONS

There was a high level of fatigue among Chinese doctors. EI could indirectly reduce fatigue partially through modifying SA and NA strategies, respectively. EI intervention, education and training in emotional labor should be carried out to cope with fatigue.

OBJECTIVE

Tumor necrosis factor-alpha (TNF-alpha) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-alpha gene polymorphism with pulmonary tuberculosis (TB) among patients with coal worker's pneumoconiosis (CWP).

METHODS

A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-alpha gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP). Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher's exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplicative model with combined OR. All data were analyzed using SAS version 8.2 software.

RESULTS

No significant difference in frequency of the TNF-alpha-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls (chi2 = 5.44, P = 0.07). But difference in frequency of the TNF-alpha-308 A allele was identified between them (chi2 = 5.14, P = 0.02). No significant difference in frequencies of the TNF-alpha-238 genotype and allele (P = 0.23 and P = 0.09, respectively) was found between cases and controls either, with combined (GG and AA) OR of 3.96 (95% confidence interval of 1.30-12.09) at the -308 locus of the TNF-alpha gene, as compared to combination of the TNF-alpha-238 GG and TNF-alpha-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-alpha-238 GG and TNF-alpha-308 GA genotypes was 1.98 (95% CI of 1.06-3.71) for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-alpha-308 GG genotype and body mass index (OR = 4.92), as well as an interaction between the TNF-alpha-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-alpha-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated.

CONCLUSIONS

TNF-alpha-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-alpha-238 A allele was otherwise.

We report the first account of a comparative analysis of the binding affinities of nine FDA-approved drugs against subtype B as well as the South African subtype C HIV PR (C-SA). A standardized protocol was used to generate the inhibitor/C-SA PR complexes with the relative positions of the inhibitors taken from the corresponding X-ray structures for subtype B complexes. The dynamics and stability of these complexes were investigated using molecular dynamics calculations. Average relative binding free energies for these inhibitors were calculated from the molecular dynamics simulation using the molecular mechanics generalized Born surface area method. The calculated energies followed a similar trend to the reported experimental binding free energies. Postdynamic hydrogen bonding and electrostatic interaction analysis of the inhibitors with both subtypes reveal similar interactions. Most inhibitors show slightly weaker binding affinities for C-SA PR. Molecular dynamics studies demonstrated increased flap movement for C-SA PR, which can perhaps explain the weaker affinities. This study serves as a standardized platform for optimizing the design of future more potent HIV C-SA PR inhibitors.

A novel simultaneous measurement method for alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in human sera by time-resolved fluoroimmunoassay (TR-FIA) is described. The proposed approach combines the use of europium-labeled anti-AFP antibody for AFP TR-FIA and biotinylated anti-CEA antibody complexed to samarium-labeled streptavidin for CEA TR-FIA. A 96-well microtiter plate coated with a mixture of anti-AFP and anti-CEA monoclonal antibodies was used for the assay. After it was reacted with a solution containing AFP and CEA, a mixture of anti-AFP antibody labeled with BHHCT-Eu(3+) and biotinylated anti-CEA antibody was added. The AFP concentration was determined by measuring the solid-phase fluorescence of the europium-labeled anti-AFP antibody at 615 nm. Then a BHHCT-Sm(3+)-labeled streptavidin-bovine serum albumin conjugate (SA-BSA) was added to react with the biotinylated anti-CEA antibody. After the reaction, the unreacted SA-BSA was washed out, and a 0.1 M NaOH solution containing 1.0 x 10(-5) M TOPO and 0.05% SDS was added to dissociate the samarium-labeled SA-BSA in the immune complex on the surface of the well into the solution. The CEA concentration was determined by measuring the solution fluorescence of 643 nm from the samarium-labeled SA-BSA. The present method gives detection limits of 0.07 ng/ml for AFP and 0.3 ng/ml for CEA. The coefficient variations of the method are less than 7%, and the recoveries are in the range of 90-110% for serum samples. The AFP and CEA concentrations in 27 human serum samples were determined by the present method as well as by single assay for comparison. A good correlation was obtained with the correlation coefficients of 0.990 for AFP and 0.973 for CEA.

BACKGROUND

Anti-inflammatory activities of medicinal plants have largely been attributed to their content of sesquiterpene lactones (SLs). SLs are predominantly found in the sunflower family Asteraceae and have been isolated from many plants of this family, particularly Centaurea. The anti-inflammatory activities of extract of Centaurea ainetensis, a Lebanese endemic plant, and the isolated active molecule were assessed for their potential ant-inflammatory activities.

METHODS

Plant extract from Centaurea ainetensis, and the isolated active ingredient Salograviolide A (SA), a sesquiterpene lactones guaianolide, were used for the study. Western blotting and electrophoretic mobility shift assays were used to test the effects of the plant extract and SA on interleukin-1 (IL-1) induced increase in cyclooxygenase-2 (COX-2) levels and in nuclear factor-kappaB (NF-kappaB) translocation in an intestinal epithelial cell (IEC) of inflammation. Their effects on inflammation score and cytokine levels were also studied in an iodoacetoamide-induced rat model of inflammation.

RESULTS

Plant extract and SA were shown to reverse the effects observed by IL-1 on COX-2 levels and NF-kappaB translocation in IEC. SA decreased the level of inflammatory cytokines and the level of inflammation in the animal model.

CONCLUSIONS

These findings suggest that SA may be useful in the development of natural therapies for inflammatory diseases.

A novel cellulolytic bacterium, strain S23(T), was isolated from the rhizosphere of the pine trees in Daejeon, Republic of Korea. This isolate was Gram-positive, strictly aerobic, rod-shaped, catalase-negative, oxidase-positive, motile by means of peritrichous flagella, and tested positive for alkaline phosphatase, esterase lipase, leucine arylamidase, alpha-galactosidase, and beta-galactosidase activities. The DNA G+C content was 49.5 mol%. The main cellular fatty acids were anteiso-C(15:0) (51.9%), iso-C(16:0) (14.7%), and iso-C(15:0) (13.2%). The major isoprenoid quinone was menaquinone 7 (MK-7). Diagnostic diamino acid in the cell-wall pepti-doglycan was meso-diaminopimelic acid. Comparative 16S rRNA gene sequence analysis showed that this strain clustered with Paenibacillus species. The 16S rRNA gene sequence similarity values between S23(T) and other Paenibacillus species were between 89.9% and 95.9%, and S23(T) was most closely related to Paenibacillus tarimensis SA-7-6(T). On the basis of phylogenetic and phenotypic properties of strain S23(T), the isolate is considered as a novel species belonging to the genus Paenibacillus. Therefore, the name, Paenibacillus pinihumi sp. nov., is proposed for the rhizosphere isolate; the type strain is S23(T) (=KCTC 13695(T) =KACC 14199(T) =JCM 16419(T)).

Osteoarthritis (OA) is a degenerative joint disease frequently seen in the elderly population. Sinapic acid (SA), a commonly found phenolic acid, has been pharmacologically evaluated for its anti-inflammation effects in various studies. To explore its potential therapeutic role for OA, rat chondrocytes were treated with IL-1β (10 ng/ml) with different concentrations of SA in vitro. Our study revealed that SA could inhibit the IL-1β-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Consistent with these findings, the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (Cox)-2 could also be downregulated by SA. Moreover, SA could also suppress the IL-1β-induced expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) in chondrocytes. Furthermore, our data found that SA could suppress the IL-1β-induced mitogen-activated protein kinase (MAPK) pathway activation. In general, this paper elucidates that sinapic acid inhibits the IL-1β-induced inflammation via MAPK pathways and may be a good agent for the treatment of OA.

Tellurium (Te) exhibits many intriguing properties including thermoelectricity, photoelectricity, piezoelectricity, and photoconductivity, and is widely used in detectors, sensors, transistors, and energy devices. Herein, ultrathin two-dimensional (2D) Te nanosheets were fabricated using a facile and cost-effective liquid-phase exfoliation method. Mixing the as-prepared 2D Te nanosheets with polyvinylpyrrolidone (PVP) provided a uniform 2D Te/PVP membrane. The 2D Te/PVP membrane exhibited excellent mechanical properties, thermal properties, and stability. The nonlinear optical properties of the membrane were characterized over the spectral range of 800 to 1550 nm using open-aperture Z-scan technology. A large nonlinear absorption coefficient of about 10-1 cm GW-1 over the whole tested wavelength range demonstrated the efficient broadband saturable absorptivity of the 2D Te/PVP membrane. Using the 2D Te/PVP membrane as a saturable absorber (SA), a highly stable femtosecond laser with a pulse duration of 829 fs in the communication band was obtained. This work highlights the promise of 2D Te/PVP membranes in ultrafast photonics and Te as a new 2D material for use in photonic devices such as all-optical modulators, switches, and thresholds.