Relationship between maternal and newborn endothelial function and oxidative stress.

OBJECTIVE: To evaluate the Relationship between maternal and newborn endothelial function and oxidative stress. METHODS: Forty-three pregnant women and their offspring were evaluated. As markers of endothelial function, the flow-mediated dilation (FMD) was measured in pregnant women in the second and third trimesters, and nitric oxide (NO) was quantified in the endothelial cells of the umbilical cord vein. Malondialdehyde (MDA), as a marker of oxidative stress, was measured in the maternal plasma (second and third trimesters) and plasma from umbilical cord blood. Gestational age and birth weight were recorded. Correlations between variables were estimated, and adjustments were made for specific gestational week of measurement, gestational age at birth, and complications during pregnancy and/or at delivery. RESULTS: Maternal FMD at second trimester correlated positively with newborn MDA, although with marginal significance (P = 0.090). The change in maternal FMD was positively correlated with newborn NO (P = 0.039), although adjustment for gestational age and specific week of gestation attenuated this relationship (P = 0.070). Maternal MDA at second trimester correlated positively with newborn MDA independently of gestational age at birth, specific week of gestation of the measurement, and having complications during pregnancy or at delivery (P = 0.032). After adjustments, the change in maternal MDA correlated with newborn MDA but marginally (P = 0.077). CONCLUSION: Study findings suggest that under physiological conditions, enhanced endothelial function and/or oxidative stress in the mother may impact on normal fetal development. Future studies are recommended, employing larger sample sizes, a more extensive set of markers of oxidative stress, and comparisons of complicated versus normal pregnancies.

Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct.

BACKGROUND: The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in parasite invasion of host cells. The protein amino (N-terminal) flank has a cleavage region (region I), essential for proteolytic processing prior to parasite invasion of liver cells. METHODS: We have developed a 131-mer long synthetic polypeptide (LSP) named PvNR1R2 that includes the N-terminal flank and the two natural repeat variant regions known as VK210 and VK247. We studied the natural immune response to this region in human sera from different malaria-endemic areas and its immunogenicity in mice. RESULTS: PvNR1R2 was more frequently recognized by sera from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong antibody responses in both C3H and CB6F1 mice strains. Antibodies from immunized mice as well as affinity-purified human IgG reacted with native protein by IFA test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of sporozoite invasion (ISI) of hepatoma cell lines. CONCLUSIONS: These results encourage further studies in non-human primates to confirm the elicitation of sporozoite invasion blocking antibodies, to assess cell mediated immune responses and the protective efficacy of this polypeptide.

Neurodegenerative diversity in human cortical contusion: histological analysis of tissue derived from decompressive craniectomy.

The principal aim in the management of patients with cerebral contusion (CC) following severe traumatic brain injury (TBI) is the prevention, amelioration, and treatment of secondary neuronal dysfunction and pathology. Distinguishing between irreversibly damaged and surviving tissue could have considerable therapeutic and prognostic implications for patients. To characterize structurally the neuronal compartment of the contused region in samples derived from patients who suffered severe TBI and were subjected to decompressive craniectomy, we used NeuN, a neuronal marker. We determined that NeuN "patches", sectors with loss of NeuN immunoreactivity (NeuN-IR), represented 25% of the area among the analyzed cases. We also found a 67% decrease in NeuN levels via Western blot. Tissue adjoining patches of NeuN-IR were considered "preserved" due to the apparent normal density of neurons and conservation of the six cortical layers. Nevertheless, these sectors retained only 39% of their neurons with the classical pattern described for normal NeuN-IR. Using Fluorojade we identified a 16-fold increase in density of moribund neurons in "preserved" sectors when compared to controls. Additionally these abnormalities were enhanced 5-fold in "patches" of NeuN-IR when compared to preserved regions. Therefore, NeuN/Fluorojade abnormalities are indicative of different cell fates characteristic of CC tissue. This analysis addressed exclusively the neuronal compartment and provides new insights into the degenerative state of neurons in the contused region that is likely to contribute to clinical outcome and differentiate TBI from ischemia.