IntroductionOver 80% of stroke deaths occur in low-income and middle-income regions of the world. Identification of predictors of mortality is vital so that prompt therapeutic measures could be instituted to improve outcome. Previous studies have identified factors such as stroke severity, stroke type, older age, impairment of consciousness and hyperglycaemia as predictors of mortality for acute stroke but mortality remain high among patients hospitalized for acute stroke. The study objective was to determine the association between admission serum albumin levels and short-term outcome following acute ischaemic stroke in Nigerians.MethodsConsecutive first-ever acute ischaemic stroke patients were prospectively enrolled between February 2009 and May 2010. Stroke severity at presentation was determined using National Institute of Heath Stroke Score (NIHSS). Admission serum chemistry including albumin, were measured. Patients were then followed up for 30 days and outcome measures applied at the end of the study were 30-day mortality and functional outcome using the Modified Rankin Scale (MRS) and graded as favourable(MRS 0-3) or unfavourable(MRS 4-6). Relationship between serum albumin and stroke outcome was determined.Results75 acute stroke cases were studied. Mean age was 57.68 ± 12.4 years. Outcome was favourable in 48% while 30-day case fatality was 17.3%. The mean age (61.13 years) of those with poor outcome was significantly higher than those with favourable outcome. Mean serum albumin (3.03g/dL) of those with favourable outcome was also significantly higher than (2.08g/dL) of those with unfavourable outcome (p=0.0001). Patients that died had significantly lower serum albumin (1.66g/dl) than survivors (p=0.0001).Receiver operating characteristics curve for optimal cut off point of serum albumin to predict survival or death within 30 days revealed area under the cure (AUC) of 0.870, p-value 0.0001, 95% C/I=0.759-0.982. Serum albumin of 1.55g /dL has sensitivity of 100% and specificity of 61.5%. NIHSS and serum albumin were predictors of poor outcome using multiple regression.ConclusionLow admission serum albumin was an independent determinant of poor outcome.

Recombinant Plasmodium falciparum merozoite surface protein 3 (PfMSP3F) and a 24-kDa fragment from its N terminus (MSP3N) that includes the essential conserved domain, which elicits the maximum antibody (Ab)-dependent cellular inhibition (ADCI), were expressed as soluble proteins in Escherichia coli. Both proteins were found to be stable in both soluble and lyophilized forms. Immunization with MSP3F and MSP3N formulated separately with two human-compatible adjuvants, aluminum hydroxide (Alhydrogel) and Montanide ISA 720, produced significant antibody responses in mice and rabbits. Polyclonal Abs against both antigens recognized native MSP3 in the parasite lysate. These two Abs also recognized two synthetic peptides, previously characterized to possess B cell epitopes from the N-terminal region. Antibody depletion assay showed that most of the IgG response is directed toward the N-terminal region of the full protein. Anti-MSP3F and anti-MSP3N rabbit antibodies did not inhibit merozoite invasion or intraerythrocytic development but significantly reduced parasitemia in the presence of human monocytes. The ADCI demonstrated by anti-MSP3N antibodies was comparable to that exhibited by anti-MSP3F antibodies (both generated in rabbit). These results suggest that the N-terminal fragment of MSP3 can be considered a vaccine candidate that can form part of a multigenic vaccine against malaria.

Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process engaging proteins on the merozoite surface and those contained and sequentially released from the apical organelles (micronemes and rhoptries). Fundamental to invasion is the formation of a moving junction (MJ), a region of close apposition of the merozoite and the RBC plasma membranes, through which the merozoite draws itself before settling into a newly formed parasitophorous vacuole (PV). SURFIN4.2 was identified at the surface of the parasitized RBCs (pRBCs) but was also found apically associated with the merozoite. Using antibodies against the N-terminus of the protein we show the presence of SURFIN4.2 in the neck of the rhoptries, its secretion into the PV and shedding into the culture supernatant upon schizont rupture. Using immunoprecipitation followed by mass spectrometry we describe here a novel protein complex we have named SURGE where SURFIN4.2 forms interacts with the rhoptry neck protein 4 (RON4) and the Glutamate Rich Protein (GLURP). The N-terminal cysteine-rich–domain (CRD) of SURFIN4.2 mediates binding to the RBC membrane and its interaction with RON4 suggests its involvement in the contact between the merozoite apex and the RBC at the MJ. Supporting this suggestion, we also found that polyclonal antibodies to the extracellular domain (including the CRD) of SURFIN4.2 partially inhibit merozoite invasion. We propose that the formation of the SURGE complex participates in the establishment of parasite infection within the PV and the RBCs.

Background: Plasmodium falciparum merozoite surface protein 3 (MSP3) oligomerizes and binds heme. Results: MSP3 forms amyloid-like structures that bind ϳ35 heme molecules, and these filamentous structures are also present on the surface of merozoites. Conclusion: Amyloid formation by MSP3 is related to heme binding. Significance: The presence of MSP3 fibrils on merozoite surface and significant heme binding suggest its functional role during erythrocytic stages of P. falciparum.

Synthesis of a 80-member library of novel pyrano[4,3-b]quinolines in solution-phase is reported. The key intermediate, 4-iodopyrano[4,3-b]quinolines were synthesized by the electrophilic iodocyclization of corresponding ortho-alkynyl aldehydes in good to excellent yields under mild reaction conditions. Subsequently a diverse set of libraries was generated by employing palladium-catalyzed Suzuki-Miyaura, Heck, and Sonogashira coupling reactions on 4-iodopyrano[4,3-b]quinolines. In this way, a series of structurally different and biologically interesting molecules were obtained. Some of the selected compounds were screened against 3D7 strains of Plasmodium falciparum for antimalarial activity. Suzuki coupling products 6{3} and 6{21} and Heck coupling product 8{12} exhibit promising antimalarial activity.