Preoperative supplementation with a carbohydrate mixture decreases organ dysfunction-associated risk factors.

BACKGROUND & AIMS: Recently, both asymmetrical dimethylarginine and IL-6 have been suggested to be associated with the induction and severity of single and multiple organ dysfunction. The aims of the present study were to elucidate if these factors were increased in an ischemia reperfusion (IR) model and whether pre-operative carbohydrate supplementation can reduce the risk factors along with the IR injury. METHODS: One group of male Wistar rats was fasted for 16 h (water ad libitum) prior to clamping the superior mesenteric artery (IR fasted n=14). A second group had ad libitum access to a carbohydrate solution prior to clamping (IR fasted CHO group n=11). Sham-fasted animals, which only received laparotomy and no clamping, served as controls (n=4). RESULTS: Plasma urea and ALAT activity were both increased in the IR fasted animals when compared to the sham rats (P=0.007 and P<0.02, respectively). Furthermore, it was shown that IR fasted rats had increased ADMA and IL-6 concentration in plasma when compared to sham animals (P<0.02). Moreover, the GSH level in lung was significantly decreased in the IR fasted animals (P=0.014). IR CHO supplemented showed no significant increase of ALAT activity and decrease of lung GSH. Furthermore, significantly lower plasma urea, ADMA and IL-6 concentration was seen in the IR CHO supplemented group when compared to the IR fasted rats (P=0.028, P<0.01 and P<0.02, respectively). The liver glycogen concentration in IR fasted rats was 48% of that IR rats supplemented the carbohydrate mixture. CONCLUSION: The present rat intestinal ischemia reperfusion model not only induces organ injury indicated by the classical parameters such as plasma urea and ALAT activity, but also increased plasma IL-6 and ADMA and decreased lung GSH concentration in IR fasted rats. Pre-operative supplementation with the carbohydrate mixture significantly lowered the plasma urea, IL-6 and ADMA concentrations and maintained lung GSH concentration. This indicates that pre-operative carbohydrate supplementation reduces post-operative organ injury.

Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine.

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (> or =4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were cross-reactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

Antibody avidity and immunoglobulin G isotype distribution following immunization with a monovalent meningococcal B outer membrane vesicle vaccine.

The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.

Prevention of meningococcal serogroup B infections in children: a protein-based vaccine induces immunologic memory.

Immunologic memory against meningococci was studied in 177 children (100 children were 10-11 years old and 77 were 5-6 years old) 2.5 years after vaccination with hexavalent meningococcal outer membrane vesicle (OMV) vaccine or hepatitis B (HepB) vaccine. Children were revaccinated with monovalent P1.7(h),4 meningococcal OMV vaccine. Serum bactericidal antibodies (SBAs) were measured before revaccination and after 4-6 weeks. A minimum 4-fold increase in SBAs against serosubtype P1.7(h),4 was detected in 48.5% of the children after hexavalent meningococcal vaccine and in 8.9% after HepB vaccine. Of the initial responders given hexavalent meningococcal vaccine, 78% had > or =4-fold increase in SBAs against strain P1.4. Thus, immunologic memory is present in toddlers and school-aged children previously given 3 hexavalent meningococcal vaccinations. Booster vaccination with monovalent P1.7(h),4 meningococcal OMV vaccine induces a significant increase in SBAs against serosubtype P1.7(h),4 and cross-reactivity against other serosubtypes in the hexavalent vaccine.