Characterization of Le(x), Le(y) and A Le(y) antigen determinants in KDN-containing O-linked glycan chains from Pleurodeles waltlii jelly coat eggs.

Novel acidic oligosaccharides were isolated in large amounts by reductive alkaline treatment of the jelly coat of Pleurodeles waltlii (Michah) eggs. The oligosaccharides were found to contain the newly described KDN as acidic monosaccharide and possess either the Le(x), Le(y) and A Le(y) antigenic determinants. Occurrence of Le(x) and Le(y) determinants previously recognized as tumor-associated antigen (TAA) demonstrates that mucins of lower animals may represent a rich and easily available source for preparing TAA. Moreover, it reinforces the hypothesis according to which TAA are evolution markers.     

Platinum complexes of p- and m-aminobenzamidine. Synthesis, characterization, and cytotoxic activity.

Four platinum(II) aminobenzamidine complexes have been prepared and characterized by IR and 1H and 13C NMR spectroscopy, and tested for their ability to interact with the nicked and closed circular forms of the pUC8 plasmid DNA. The results show that the complexes of formula [Pt(LH)2Cl2]2X have a cis- geometry with an amino-Pt bonding, where L is either p- or m-aminobenzamidine and where 2X is 2Cl- or PtCl4(2-). It was observed that these complexes significantly alter the electrophoretic mobility of nicked and closed circular forms of DNA and that the alteration in electrophoretic mobility due to Pt(II)-p-aminobenzamidine binding is higher than that due to Pt(II)-m-aminobenzamidine. No difference in mobility was observed whether the DNA interacted with complexes having as counteranion Cl- or PtCl4(2-). The synthesized compounds were, in addition, assayed for antitumor activity in vitro against colon (CX-1), lung (LX-1), and mammary (MX-1) human tumor cells. The results show that these complexes inhibited the multiplication of the tumor cells and that they show higher specificity for lung cells.     

Salicylate as an in vivo free radical trap: studies on ischemic insult to the rat intestine.

Ischemia of rat intestine was induced in vivo by occlusion of the superior mesenteric artery (SMA) for 15 min. Sodium salicylate, 100 mg/kg, given IP, 30 min prior to the ischemic event served as a specific trap for hydroxyl radicals. Portions of the bowel were sequentially isolated and removed--2 min prior to ischemia, 2 min prior to declamping of the SMA, and 10 min following reperfusion. The bowel segments were homogenized in 3% TCA. The homogenate was centrifuged and filtrated through a 0.22 mu filter. The hydroxylation products of salicylate, dihydroxybenzoic acid (DHBA) derivatives, were isolated, identified, and quantified by HPLC coupled with electrochemical detection (ECD). The level of 2,5-DHBA (M +/- SE, ng/g tissue) in the preischemic bowel (N = 21) was 241.8 +/- 10.0. In the ischemic specimen the level of 2,5-DHBA increased significantly to 313.3 +/- 15.5 (p = 0.0129), and remained unchanged in the reperfusion period (322.8 +/- 15.5). The histological examination correlated well with these levels: mild villi damage in the ischemic period with no further exacerbation during the reperfusion period. This study in an in vivo animal model of intestinal ischemia-reperfusion provides direct evidence for the involvement of free radicals during the ischemic insult.     

Chloride-dependent restoration of coupling by oligomycin in rat liver mitochondria.

In rat liver mitochondria suspended in KC1 medium, oligomycin interfered with the effect of uncouplers on energy conservation. It antagonized the effect of uncouplers that are weak acids (2,4-dinitrophenol etc.), but enhanced that of the lipid-penetrating cation NN-dimethyl-N'N'-dibenzylammonium. Oligomycin caused none of the above effects when Br- or NO-/3 was substituted for C1- as the major anionic species in the assay medium. The concentration of oligomycin that exerted the above-mentioned effects was lower than that necessary for the inhibition of energy transfer, but was in the range that induced C1- permeation through the cristae membrane. The possible connexion between the effect of oligomycin on C1- permeation and its interference with the action of uncouplers is discussed.     

GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens.     

Inequality as a Powerful Predictor of Infant and Maternal Mortality around the World

Background

Maternal and infant mortality are highly devastating, yet, in many cases, preventable events for a community. The human development of a country is a strong predictor of maternal and infant mortality, reflecting the importance of socioeconomic factors in determinants of health. Previous research has shown that the Human Development Index (HDI) predicts infant mortality rate (IMR) and the maternal mortality ratio (MMR). Inequality has also been shown to be associated with worse health in certain populations. The main purpose of the present study was to determine the correlation and predictive power of the Inequality Adjusted Human Development Index (IHDI) as a measure of inequality with the Infant Mortality Rate (IMR), Maternal Mortality Rate (MMR), Early Neonatal Mortality Rate (ENMR), Late Neonatal Mortality Rate (LNMR), and the Post Neonatal Mortality Rate (PNMR).

Methods and Findings

Data for the present study were downloaded from two sources: infant and maternal mortality data were downloaded from the Global Burden of Disease 2013 Cause of Death Database and the Human Development Index (HDI) and Inequality-Adjusted Human Development Index (IHDI) data were downloaded from the United Nations Development Program (UNDP). Pearson correlation coefficients were estimated, following logarithmic transformations to the data, to examine the relationship between HDI and IHDI with MMR, IMR, ENMR, LNMR, and PNMR. Steiger’s Z test for the equality of two dependent correlations was utilized in order to determine whether the HDI or IHDI was more strongly associated with the outcome variables. Lastly, we constructed OLS regression models in order to determine the predictive power of the HDI and IHDI in terms of the MMR, IMR, ENMR, LNMR, and PNMR.Maternal and infant mortality were both strongly and negatively correlated with both HDI and IHDI; however, Steiger’s Z test for the equality of two dependent correlations revealed that IHDI was more strongly correlated than HDI with MMR (Z = 4.897, p < 0.001), IMR (Z = 2.524, p = 0.012), ENMR (Z = 2.936, p = 0.003), LNMR (Z = 2.272, p = 0.023), and PNMR (Z = 2.277, p = 0.023). Furthermore, side-by-side OLS regression models revealed that, when IHDI was used as the predictor variable instead of HDI, the R ² value was 0.053 higher for MMR, 0.025 higher for IMR, 0.038 higher for ENMR, 0.029 higher for LNMR, and 0.026 higher for PNMR.

Conclusions

Even when both the HDI and the IHDI correlate with the infant and maternal mortality rates, the IHDI is a better predictor for these two health indicators. Therefore, these results add more evidence that inequality is playing an important role in determining the health status of various populations in the world and more efforts should be put into programs to fight inequality.