Failure of a synthetic vaccine to protect Aotus lemurinus against asexual blood stages of Plasmodium falciparum.

The hybrid synthetic protein SPf(66), which contains small fragments of the 83-kD, 55-kD, 35-kD, and circumsporozoite antigens of Plasmodium falciparum, was studied to determine its protective capacity against malaria infection in Aotus lemurinus monkeys. Two groups of six monkeys each were immunized six times with this polymer, which was mixed with either Freund's adjuvant or aluminum hydroxide. Two groups of five animals each were used as controls and immunized with saline solution mixed with the same adjuvants. Neither antipeptide nor antimalarial antibodies developed after the six immunization doses. Regardless of this fact, the monkeys were challenged intravenously with 10(5) P. falciparum blood stage parasites, and the resultant parasitemia was followed daily on blood smears. Only one monkey from each of the groups immunized using Freund's adjuvant (both experimental and control) was protected. In those immunized using aluminum hydroxide, one animal was protected in the experimental group, but none were protected in the control group. Anti-parasite antibodies developed during the infection, but did not correlate with protection and failed to recognize SPf(66) peptide in an enzyme-linked immunosorbent assay. Immunization with the polymer did not boost natural antibodies present in two of the monkeys before the experiment. Low levels of gamma-interferon were produced in some animals, but were not correlated with protection.     

Impact of overlapping drug-eluting stents in patients undergoing percutaneous coronary intervention.

BACKGROUND: Sirolimus-eluting stent (SES) implantation for the treatment of single coronary lesions is proven to be effective and durable. However, the safety and efficacy of overlapping SES for the treatment of long lesions have not been well established. Objectives: We conducted a retrospective analysis to compare the clinical outcomes of overlapping versus nonoverlapping SES. METHODS: Fifty-five patients who received overlapping SES were compared with 39 patients who received nonoverlapping SES. RESULTS: The baseline clinical and angiographic characteristics were balanced between the two study groups. The in-hospital complications were similar between groups, except that non-Q-wave myocardial infarction was significantly higher in the Overlapping SES group when compared with the Nonoverlapping SES group (23.6% vs. 7.7%, P = 0.04). This higher rate of myonecrosis is due to periprocedural side branch compromises, including side branch narrowing, occlusion, and flow reduction. At 30 days and 6 months follow-up, all clinical outcomes were similar between the study groups. In addition, the event-free survival rate was similar between groups (P = 0.87). CONCLUSIONS: The implantation of overlapping SES for the treatment of long, native coronary lesions is feasible and effective but is associated with an increased rate of periprocedural myonecrosis. This phenomenon is caused primarily by side branch compromises, but does not have any adverse impact on late clinical events.     

Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis

Background  

The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 μg. 100 g^-1. day^-1). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe³⁺ into free Fe²⁺, contributing to oxidative damage.     

Development of a Competitive Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against the 3B Protein of Foot-and-Mouth Disease Virus

Foot-and-mouth disease (FMD) is one of the most highly contagious and economically devastating diseases, and it severely constrains the international trade of animals. Vaccination against FMD is a key element in the control of FMD. However, vaccination of susceptible animals raises critical issues, such as the differentiation of infected animals from vaccinated animals. The current study developed a reliable and rapid test to detect antibodies against the conserved, nonstructural proteins (NSPs) of the FMD virus (FMDV) to distinguish infected animals from vaccinated animals. A monoclonal antibody (MAb) against the FMDV NSP 3B was produced. A competitive enzyme-linked immunosorbent assay (cELISA) for FMDV/NSP antibody detection was developed using a recombinant 3ABC protein as the antigen and the 3B-specific MAb. Sera collected from naive, FMDV experimentally infected, vaccinated carrier, and noncarrier animals were tested using the 3B cELISA. The diagnostic specificity was 99.4% for naive animals (cattle, pigs, and sheep) and 99.7% for vaccinated noncarrier animals. The diagnostic sensitivity was 100% for experimentally inoculated animals and 64% for vaccinated carrier animals. The performance of this 3B cELISA was compared to that of four commercial ELISA kits using a panel of serum samples established by the World Reference Laboratory for FMD at The Pirbright Institute, Pirbright, United Kingdom. The diagnostic sensitivity of the 3B cELISA for the panel of FMDV/NSP-positive bovine serum samples was 94%, which was comparable to or better than that of the commercially available NSP antibody detection kits. This 3B cELISA is a simple, reliable test to detect antibodies against FMDV nonstructural proteins.     

Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling

Rat alveolar epithelial cells (AEC) in primary culture transdifferentiate from a type II (AT2) toward a type I (AT1) cell-like phenotype, a process that can be both prevented and reversed by keratinocyte growth factor (KGF). Microarray analysis revealed that these effects of KGF are associated with up-regulation of key molecules in the mitogen-activated protein kinase (MAPK) pathway. To further explore the role of three key MAPK (i.e., extracellular signal-related kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] and p38) in mediating effects of KGF on AEC phenotype, primary rat AEC cultivated in minimal defined serum-free medium (MDSF) were treated with KGF (10 ng/ml) from Day 4 for intervals up to 48 hours. Exposure to KGF activated all three MAPK, JNK, ERK1/2, and p38. Inhibition of JNK, but not of ERK1/2 or p38, abrogated the ability of KGF to maintain the AT2 cell phenotype, as evidenced by loss of expression of lamellar membrane protein (p180) and increased reactivity with the AT1 cell-specific monoclonal antibody VIIIB2 by Day 6 in culture. Overexpression of JNKK2, upstream kinase of JNK, increased activation of endogenous c-Jun in association with increased expression of p180 and abrogation of AQP5, suggesting that activation of c-Jun promotes retention of the AT2 cell phenotype. These results indicate that retention of the AT2 cell phenotype by KGF involves c-Jun and suggest that activation of c-Jun kinase may be an important determinant of maintenance of AT2 cell phenotype.     

Genetic interactions of KIR and G1M immunoglobulin allotypes differ in obese from non-obese individuals with type 2 diabetes

We analyzed the natural killer cell immunoglobulin-like receptor (KIR) genes and immunoglobulin allotypes in the development of type 2 diabetes (T2D) based on body mass index (BMI) measurements (obese vs. non-obese) in Puerto Rican Americans. Genetic interactions between the KIR haplotype A homozygotes (HAH) and its fraction containing two inhibitory receptors 2DL3 and 2DL1 and the activating receptor 2DS4 with immunoglobulin allotypes were studied. We found a significant association between the HAH and T2D (p=0.002; OR=7.97) and its interaction with the immunoglobulin allotype z: GM f/f (-) (p=<0.0001; OR, not determined) only in non-obese individuals. This association were due to the interactions between the 2DL3/2DL3, 2DL1/2DL1, and 2DS4 fragment with GM f/f (-) in T2D patients (p=0.0017; OR=3.45). Analysis based on BMI demonstrated associations in both obese (p=0.037; OR=2.43; 95% CI=0.97-6.31) and non-obese individuals (p=<0.0001; OR=8.38; 95% CI=2.49-29.31). By contrast, the interaction of the GM allotype f/f (-) with the HAH fragment was associated with T2D only in non-obese individuals (p=<0.0001; OR=18.2; 95% CI=3.71-113.4). As expected, interaction of both HAH and its fragment with HLA-C group's ligands were significant. We used informative short tandem repeats (STRs) that distinguish major populations to determine genetic admixture and found that there was no genetic stratification in our cohort. Our findings are consistent with the possibility of an autoimmune and/or innateimmune component in the pathogenesis of T2D: NK receptors with chronic inflammation in obese and genetic interactions with G1M allotype in T2D non-obese possibly mediating autoimmunity.