However, the NOS inhibitors possess multiple non-specific actions

However, the NOS inhibitors possess multiple non-specific actions, including antagonism of muscarinic

acetylcholine Selleck GSK1210151A receptors (13), generation of superoxide anions (14), inhibition of cytochrome c reduction (15), and inhibition of endothelium-independent relaxation induced by amiloride or cAMP (16). We also reported that vascular lesion formation caused by long-term treatment with L-NAME or L-NMMA is not mediated by the simple inhibition of eNOS in mice, and that activation of the tissue renin-angiotensin system and increased oxidative stress are involved in the long-term vascular effects of the L-arginine analogues in an NO-independent manner (17) and (18). The roles of NO derived from whole NOSs have also been investigated in studies with mice that lack selleck chemicals each NOS isoform. However, although the single eNOS null mice manifest accumulation of cardiovascular risk factors that mimic human metabolic syndrome (19), and although it is well established that eNOS exerts

anti-arteriosclerotic effects (20), (21), (22), (23), (24) and (25), the single eNOS null mice do not spontaneously develop arteriosclerotic/atherosclerotic vascular lesion formation (26). This inconsistency could be due to a compensatory mechanism by other NOSs that are not genetically disrupted (27). Indeed, in the singly eNOS-/- mice, up-regulation of vascular nNOS expression has been indicated (28) and (29). Furthermore, we revealed that NOS activity and NOx (nitrite plus nitrate) production are fairly well preserved in that genotype (30). Thus, the authentic roles of endogenous NO derived from entire NOSs still remain to be fully elucidated. To address this important issue, we successfully developed mice in which all three NOS genes are completely disrupted (30). The expression and activity of NOSs are totally Ketanserin absent in the triple n/i/eNOSs null mice before and after

administration of lipopolysaccharide. While the triple NOSs null mice were viable and appeared normal, their survival and fertility rates were markedly reduced as compared with wild-type mice. The triple NOSs null mice exhibited phenotypes in the cardiovascular, metabolic, renal, respiratory, and bone systems. These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons we learned from experiments with our triple mutant model. The triple NOSs null mice were significantly hypertensive as compared with the wild-type mice (30). The degree of hypertension in the triple NOSs null mice was similar to that in the eNOS null and eNOS gene-disrupted double NOSs null mice (Fig. 1A).

Studies were also excluded if the participants had rheumatic dise

Studies were also excluded if the participants had rheumatic disease, cancer, or trauma. The two reviewers were not blinded with respect to authors, journals, and results. Potentially eligible studies were retrieved in full text for further evaluation against the criteria. When an eligible study was identified, its reference list was checked for other potentially eligible studies. When eligible studies were identified, the same reviewers extracted data regarding the study design, the characteristics of the participants,

details of the prognostic and outcome measures, and the duration of follow-up. The reviewers also extracted odds ratios or hazard ratios and their 95% CIs, or data that could be converted into these statistics. The two reviewers discussed any disagreements, seeking the advice buy Decitabine of the other reviewers (WPK, CPvdS) if necessary to reach consensus. Design • Prospective cohort studies Participants • Adults aged 18 to 65 years Predictor • Expectations regarding recovery from low back pain, measured within 12

weeks from onset of the pain Outcome measure • Continued absence from usual work at a given time point greater than 12 weeks from onset of the pain Analyses • Odds ratios or hazard ratios expressing the increased risk of the outcome due to the predictor Quality: Two reviewers (JMH, MHGdeG) used the checklist of the Agency for Healthcare Research and Quality (AHRQ) to appraise the methodological Osimertinib quality of the included studies. The AHRQ checklist consists of nine items, which are presented in Table 1. When calculating the overall AHRQ score, studies that meet all nine criteria are given a score of 1, indicating the highest quality. The score for other studies is calculated by adding 1 for each criterion that

is not met. Therefore, low scores reflect high quality, whereas high scores reflect low quality and major weaknesses. Criteria 1 to 3 and 8 assess external validity, criteria 4 to 7 internal validity, and criterion 9 assesses the statistical method. Scores less than 4 indicate a low risk of bias, scores of 4 to 6 indicate a medium risk of bias, and scores of 7 and above indicate a high risk of bias. Consensus was again reached by discussion or by intervention of a third reviewer where necessary. Participants: The age Cediranib (AZD2171) and gender of participants were recorded for each study. The time since onset of the low back pain was also recorded. Data were extracted from each study regarding the recovery expectations of the participants. Outcome measures: The number of days absent from work in a given period or time to return to work were recorded as outcome measures. Use of time absent from usual work as an outcome measure has a relatively low risk of bias ( Ostelo and de Vet, 2005). Odds ratios (ORs) computed from logistic regression were used. These derived OR values from the various studies were summarised by calculating the pooled OR using meta-analysis.

6 M sulfuric acid, 28 mM sodium phosphate and

6 M sulfuric acid, 28 mM sodium phosphate and selleck chemical 4 mM ammonium molybdate) were incubated at 95 °C for 90 min. After the mixture had cooled to room temperature, the absorbance of each solution was measured at 695 nm. The antioxidant capacity was expressed as ascorbic acid equivalent (AAE). The assessment of antioxidant activity was done through various in-vitro assays. The free radical scavenging activity of six extracts of P. tirupatiensis and l-ascorbic acid (vitamin C) was measured in terms

of hydrogen donating or radical scavenging ability using the stable radical DPPH, H2O2. Nitric acid was generated from sodium nitroprusside and measured by Griess reaction. The activity was further conformed by reducing power method. Each extracts were prepared in different concentrations ranging from 20 μg/ml to 100 μg/ml and 1 ml solution

of DPPH 0.1 mM (0.39 mg in 10 ml methanol) was added to different extracts.7 An equal volume of ethanol and DPPH was added to control. Ascorbic acid was used as standard for comparison. After 20 min of incubation in dark, absorbance was measured at 517 nm and percentage of inhibition was calculated. Inhibition(%)=Control−TestControl×100 Nitric oxide was generated from sodium nitroprusside and measured by Griess reaction.8 Sodium nitroprusside (5 mM) in PBS (phosphate buffer saline) was incubated with different concentrations (20–100 μg/ml) of the extracts, dissolved in phosphate buffer (0.25 M, pH 7.4) and the tubes were incubated at 25 °C for 5 h. Controls without PFT�� mw the test compounds, but with equivalent amounts of buffer were conducted in identical manner. After 5 h 0.5 ml

of Griess reagent (1% sulfanilamide, 2% O-phosphoric acid and Non-specific serine/threonine protein kinase 0.1% naphthylethylene diamine dihydrochloride) was added. The absorbance was measured at 546 nm. The reducing powers of nutraceutical herbs were determined according to Oyaizu.9 Each extracts were prepared in different concentrations ranging from 20 μg/ml to 100 μg/ml and 1 ml of each in distilled water were mixed with phosphate buffer (2.5 ml, 2 M, pH 6.6) and potassium ferric cyanide (2.5 ml); the mixture was incubated at 50 °C for 20 min. A portion (2.5 ml) of Trichloroacetic acid (TCA 10%) was added to the mixture, which was then centrifuged at 1500 RPM for 10 min. The upper layer of solution (2.5 ml) was mixed with distill water (2.5 ml) and FeCl3 (0.5 ml of 0.1%), and the absorbance was measured at 700 nm. Increased absorbance of the reaction mixture indicated increased reducing power. The reducing power was expressed as AAE means that reducing power of 1 mg sample is equivalent to reducing power of 1 mmol ascorbic acid.10 Each extracts were prepared in different concentrations ranging from 20 μg/ml to 100 μg/ml in phosphate buffer saline (PBS) and was incubated with 0.6 ml of 4 mM H2O2 solution prepared in PBS for 10 min. The standard ascorbic acid was used as standard and absorbance was measured at 230 nm.

17 and 18 Although the use of solid-phase extraction procedures r

17 and 18 Although the use of solid-phase extraction procedures reduces the matrix effect considerably, it increases overall time and cost of analysis. In the present method simple liquid–liquid extraction procedure, CDK inhibitor which was fast enough for high-throughput analysis, was optimized. Knowing that AT

is a member of the statins that are notoriously unstable and convert in solvents from open acid form to lactone form and vice versa, by non enzymatic reactions that are pH dependent, attempt was made to control this interconversion by adding phosphate buffer (pH 6.8). This is done before the sample extraction with the organic solvent to favour the acid form. 19, 20, 21 and 22 The good recovery of AT and EZ from plasma using the liquid–liquid extraction procedure proved that this extraction method reliably eliminated interfering material from plasma. The mean percent recovery values of AT were 94.4, 95.7 and 95.8% at low, medium and high quality control levels while that of EZ were 93.5, 95.0 and 92.6% at low, medium and high quality control levels respectively. The mean percent recovery of the IS at a concentration of 100 ng mL−1 was 90.9% with an acceptable precision (RSD < 8%). Typical MRM chromatograms obtained from different

plasma blank samples, plasma spiked AZD2281 purchase with standard AT and EZ (0.2, 4, 15 ng mL−1) and IS (100 ng mL−1), are shown in Figs. 2 and 3. Retention times of AT, EZ and the IS were 1.01, 0.97 and 0.22 min, respectively. No significant interference from endogenous peaks was observed at these retention times. Calibration curves were linear in the concentration range of 0.1–20 ng mL−1 Phosphatidylinositol diacylglycerol-lyase for

both AT and EZ. The calibration curves were fitted by weighted least-squares linear regression. The precision and accuracy of calibration samples for AT and EZ in human plasma are given in Table 2. The mean ± SD of six standard curve slopes for AT and EZ were 1.069 ± 0.018 and 0.037 ± 0.001, respectively. The coefficient of determination (R2) of the calibration curves was ≥0.999 for both analytes. The lowest limit of quantification was determined to be 0.1 ng mL−1 for both analytes with a signal to noise ratio of 5.8 and 7.1 for AT and EZ respectively ( Fig. 2). The intra- and inter-day precision and accuracy of three quality control concentrations (0.2, 4, 15 ng mL−1) are summarized in Table 3. For AT intra- and inter-day RSDs were less than 5.60 and 8.24%, respectively, whereas intra-day accuracy ranged from 94.80 to 97.78% with a mean of 95.9% and inter-day accuracy ranged from 93.6 to 96.10% with a mean of 95.2%. For EZ intra- and inter-day RSD was less than 4.73 and 7.13%, respectively. Intra-day accuracy ranged from 92.3 to 96.8% with a mean of 94.1% and inter-day accuracy ranged from 92.0 to 97.2% with a mean of 94.3%. The ability to dilute samples with concentrations above the upper limit of quantification could be made with accuracy of 93.

Bacterial strains used in this study are obtained from King Georg

Bacterial strains used in this study are obtained from King George Hospital, Visakhapatnam, A.P, India. Pure strains were isolated and maintained on nutrient agar slants for bioassays. Reference strain ATCC 43300 is obtained from Himedia laboratories, Mumbai and used as a positive control. The minimum inhibitory concentrations were determined by using agar dilution Protein Tyrosine Kinase inhibitor method, following the standard protocol of the European committee for antimicrobial susceptibility testing (EUCAST-2000). The methods implemented in the present study helped to find

out the least MIC exhibited by crude plant extract combined with antibiotics and is further useful in the study of its phytocomponents. Around 30 nocosomial isolates collected from the health care workers of King George Hospital,

Visakhapatnam and isolated for pure strains of S. aureus. Resistant and Sensitive isolates were determined by treating the pure isolates with different concentrations PLX4032 datasheet of stock methicillin 1 mg/ml. MIC values for clinical as well as reference strains was observed ( Table 1). The strains are tested with other antibiotics ( Fig. 2) and MIC’s of the synergistic combination of antibiotics and plant extracts were determined. The minimum inhibitory concentrations of the synergistic combinations of antibiotics and plant extracts are shown in (Table 2), (Fig. 1). There is a half fold drop of MIC observed with the tested combinations. The combination of Plumbago extract with various antibiotics yielded low MIC’s compared to P. granatum, Ocimum and Vitis seed. S. aureus, when tested with plant extracts, yielded low MIC found values for Plumbago compared to P. granatum, Ocimum and Vitis seed. This may be attributed due to the presence of plumbagin and

naphthoquinones which showed interesting biological activity. 9, 10 and 11 Obviously irrespective of the class of antibiotic used, there is half fold drop in the MIC values, when a combination of antibiotics and extracts were tested against S. aureus. 12 This could be referred that the crude extracts have many different phytochemicals, 9 which inhibit S. aureus by different mechanisms. This double attack of both the agents on different target sites of the bacteria could theoretically lead to either an additive or synergistic effect. 13 Combined antibiotic therapy has been shown ( Fig. 1) to delay the emergence of bacterial resistance and produce desirable synergistic effects. The results were consistent with previous invitro studies, which reported synergistic effects with significant reduction in MIC’s of the antibiotics due to combination of different antimicrobial agents with crude plant extracts against Staphylococcus aureus strains. 14, 13, 15 and 12 Natural products had proven medicinal importance in Ayurvedic and Homeopathy. Large amounts of natural products are required to fight MDR organisms.

Current recommendations

for available rotavirus vaccines

Current recommendations

for available rotavirus vaccines require that the first dose of vaccine be administered before 15 weeks of age Selleck 3Methyladenine when background rates of intussusception are low [17]. As children in many high mortality countries receive their routine immunizations late, many children would not receive rotavirus vaccine if countries adhere to the strict age at administration guidelines [18]. In a recent analysis of Demographic and Health Survey data [49], the median coverage for the first dose of diphtheria, tetanus, and pertussis (DTP) vaccines in 45 developing countries was 57% by 12 weeks of age, rising to 80% by 5 months of age. For the third dose, coverage was 27% and 65% by 5 and 12 months, respectively. In a study that focused on children <5 years of age in 117 low and low-middle income countries where 98% of the global rotavirus mortality occurs, initiating rotavirus immunization before 12 weeks of age would prevent 127,992 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events [18]. Administration of the first dose to infants up to 1 year of age would prevent an additional 32,490 rotavirus-associated deaths (total = 160,481) while potentially

resulting in an additional 1226 intussusception deaths (total = 2332). This scenario analysis suggested that restricting the first dose of rotavirus vaccines to infants see more aged <12 weeks in developing countries where delays in vaccination are common would exclude a substantial proportion of infants from receiving these vaccines. These data should be reanalyzed to examine the risk and benefits of immunizing children up to 15 weeks of age. Further research is needed to examine whether strict adherence to age at administration guidelines should be maintained. Data regarding the risk and benefits of expanding the age of administration have been communicated

to GACVS and SAGE but this information also needs to be shared with GAVI so that messaging regarding age at administration can be incorporated into the country application process. As rotavirus vaccines currently should be administered found within strict age windows, these guidelines can also be used to strengthen the on-time delivery of all vaccines by reiterating to providers and parents the importance of on-time vaccination for all routine immunizations, including rotavirus vaccine (Table 1). Numerous countries in the PAHO region have introduced rotavirus vaccine into their routine immunization programs. Review of data from these countries will identify the number of children who receive the vaccine outside the recommended age window and the number who did not receive rotavirus vaccine because they presented for immunizations outside the recommended age window.

, 2003, Segev et al , 2006, Zeck and Masland, 2007, Farrow and Ma

, 2003, Segev et al., 2006, Zeck and Masland, 2007, Farrow and Masland, 2011 and Marre et al., 2012), in particular for extracellular recordings where the morphologies of the recorded neurons are not available. Similarly relevant as the question how ganglion cells integrate visual signals over their receptive field centers is the question how they pool signals in their receptive field surrounds and how center signals and surround signals are combined. PI3K Inhibitor Library concentration Evidence for nonlinear interactions between center and surround comes from the finding that

the surround appears to act in a divisive fashion rather than in a linear, subtractive way (Merwine et al., 1995). Furthermore, it was observed that the effect of surround inhibition strongly differs for On-type and Off-type responses

of On–Off ganglion cells in the frog retina, pointing towards further intricate receptive field structure (Barlow, 1953). As discussed above, stimulus integration in the surround is an BAY 73-4506 in vivo important component for specific ganglion cell types, in particular object-motion-sensitive cells and W3 cells. More generally, it may be interesting to see whether stimulus integration in the surround allows similar classifications as for the linear or nonlinear integration over the receptive field center. The models that have been used to describe nonlinear spatial integration in center and surround have been inspired by retinal anatomy, typically using bipolar cells as subunits, assumed to cover the receptive field of the ganglion cell in some regular fashion. Two recent

methodological advances ought to provide opportunities to bring this substrate for nonlinear integration in closer alignment with the actual circuitry. First, large-scale reconstructions at the electron-microscope-level can provide circuit diagrams for individual cells after they have been physiologically characterized (Helmstaedter et al., 2008, Briggman et al., 2011 and Denk et al., 2012). This may help relate the spatial STK38 sub-structure of receptive fields to actual circuit elements on a single-cell basis. Second, physiological mappings of receptive fields at very high spatial resolution have shown that it is possible to identify the locations and identities of individual cone photoreceptors that provided signals for a measured ganglion cell (Field et al., 2010). It is conceivable that this can lay the foundation for detailed assessments of nonlinear transformations in the transmission from cones to ganglion cells, for example, by measuring iso-response stimuli when activating pairs of individual cones. The focus of this review has been on spatial integration. Yet, different nonlinear effects also occur in temporal integration by retinal ganglion cells.

Finally, the interactions of salts with mineral nutrition may res

Finally, the interactions of salts with mineral nutrition may result in nutrient imbalances and deficiencies.1 The consequence of all these ultimately leads to inhibition of growth and development, reduction in photosynthesis, respiration, and protein synthesis and disturbs nucleic acid metabolism in wheat.2, 3, 4 and 5 Plants are exposed to many types of environmental stress. Among these stresses, osmotic stress, in particular, due to drought and salinity is the vital problem that limits plant growth and crop productivity in agriculture.6 Salt

acts as a toxic substance that restricts plant growth the most. It is estimated that salinity affects at least 20% learn more of world’s arable land and more than 40% of irrigated land to various degrees.7 Hence there is an increasing need for salt tolerance in plants. So we need to find out the prominent role in plant salt tolerance Ibrutinib mw by organic

compounds such as proline.8 Based on their capacity to grow on high salt medium, plants are traditionally classified as glycophytes or halophytes. Most plants, including the majority of crop species, are glycophytes and cannot tolerate high salinity. For glycophytes, salinity imposes ionic stress, osmotic stress, and secondary stresses such as nutritional disorders and oxidative stress. Sodium toxicity represents the major ionic stress associated with high salinity.7 For cells that successfully adapt to cellular disturbances, especially water stress, three generalizations have emerged. First, during short-term water loss cells often

restore volume with inorganic ions as osmolytes while up-regulating stress (“heat-shock”) proteins,9, 10 and 11 possibly indicating disturbances in protein structures. Second, under long-term water stress, organic osmolytes replace ions for volume regulation, while stress proteins decline. High levels of inorganic ions appear to be incompatible with long-term normal protein function, as perhaps are stress proteins, which may provide no protection against osmotic stress.12 and 13 Third, these solutes are limited to a few chemical types.14 Compatible osmolytes are potent osmoprotectants that play a role in counteracting the effects of osmotic stress. Osmolyte compatibility is proposed to result from the absence of osmolyte interactions with substrates and over cofactors, and the non-perturbing or favorable effects of osmolytes on macromolecular solvent interactions. The compatible solutes may be classified into two categories: one is nitrogen-containing compounds such as proline and other amino acids, quaternary ammonium compounds and polyamines and the other is hydroxy compounds, such as sucrose, polyhydric alcohols and oligosaccharides. Proline (Pro) is one of the most common compatible osmolytes in water-stressed plants.6 Proline accumulation in dehydrated plant tissues was first reported by Kemble and Mac Pherson (1954) in wilted ryegrass.

, 2009) Madrigal et al (2001) also reported that complexes I–II

, 2009). Madrigal et al. (2001) also reported that complexes I–III and II–III of mitochondrial respiratory chain were inhibited in rat brain after chronic stress (immobilization for six hours over 21 days). Additionally, Ben-Shachar and Karry (2008) demonstrated reductions in

mRNA and protein of complex I see more subunits NDUFV1, NDUFV2 and NADUFS1 in the postmortem cerebellum from patients with depression. Hroudova and Fisar (2010) using an in vitro study from pig brain, demonstrated that the complex I, II and IV activity decreased with antidepressants and mood stabilizers, suggesting in this study that antidepressants generally act as inhibitors of electron transport chain. Our findings selleck inhibitor also showed an inhibitory effect on the activity of complex I, but contrarily to this, lamotrigine and imipramine increased the activities of complexes II, II-III and IV, suggesting

that the increase in the complexes II, II-III and IV activity may be related, at least in part to compensating the decrease of complex I activity. Such, the effects of lamotrigine and imipramine on the mitochondrial respiratory chain could be positive, taking into account that there is impairment in energy metabolism related to depression (Ben-Shachar and Karry, 2008, Rezin et al., 2009 and Madrigal et al., 2001). A balance between cell death and cell proliferation must be maintained to ensure the health of every human being. Recent findings indicate that approximately one-half of all major human diseases are a first consequence of abnormal apoptosis (Reed, 2002). Neurodegeneration mediated by apoptosis can be initiated by Bax translocation from the cytosol to the mitochondria, where it affects

membrane permeability and permits cytochrome c release and subsequent activation of caspases ( Yang et al., 1995 and Ghribi et al., 2001). Inappropriate apoptosis can cause autoimmune and neurodegenerative disorders, as well as heart disease, while resistance to apoptosis can promote cancer and impede the effectiveness of cancer therapeutics. Our results demonstrate that imipramine and lamotrigine decreased the Bcl-2 expression in the prefrontal cortex, amygdala and hippocampus in the acute and chronic treatments. Peng et al. (2008) showed that 3 μM imipramine treatment significantly up-regulated the mRNA and protein expression and Bcl-2 in day-7 imipramine-treated neural stem cells (NSCs). Huang et al. (2007) also showed that desipramine increased the Bcl-2 expression in day 3 DP-treated NSCs. Another study demonstrated that by the fourteenth day, (but not acute treatment with citalopram), imipramine and amitriptyline in mice had significantly elevated the hippocampal Bcl-2 protein expression as compared to vehicle treated animals.

0513) (Supplementary Table 1) Anti-HPV-18 GMTs were still lower

0513) (Supplementary Table 1). Anti-HPV-18 GMTs were still lower than control even when different adjuvant systems were used, though the 3-dose AS01 vaccine elicited the best anti-HPV-18 response out of the various tetravalent vaccine formulations tested. Anti-HPV-16 and -18 GMTs were significantly lower one month after the last vaccine dose when 2 doses (M0,3 or M0,6) of the AS01 formulation were administered,

compared with 3 doses of the same AS01 formulation. The results obtained for neutralizing antibodies measured by PBNA in a subset of subjects (Supplementary Fig. 1) were generally in line with those from ELISA testing, although numbers of subjects evaluated were small. In TETRA-051 (Fig. 2A), there was a significant impact of the HPV-31/45 dose on anti-HPV-31 and -45 GMTs. For groups with a 20 μg dose of HPV-31 and -45 L1 GABA cancer VLPs (groups B, D and F combined), the estimated anti-HPV-31 GMT one month after the last vaccine dose was approximately 1.4-fold higher than for groups with a 10 μg dose (groups A, C and E combined) (12,667 [10,907, 14,711] versus 9173 [7867, 10,696] EU/mL; p = 0.0033) and the estimated anti-HPV-45 GMT was approximately 1.3-fold higher (7214

[6237, 8345] versus 5638 [4855, 6548] EU/mL; p = 0.0209). All tetravalent vaccine selleck chemicals llc formulations elicited anti-HPV-31 and anti-HPV-45 GMTs that were at least 44-fold higher and 38-fold higher, respectively, than those associated with natural infection (i.e., 183.5 EU/mL for anti-HPV-31 and 139.0 EU/mL for anti-HPV-45) [20]. In NG-001 (Supplementary Table 1), in women who were initially seronegative and HPV DNA negative for the corresponding HPV type, anti-HPV-33 GMTs were significantly higher one month after

the last vaccine dose for ADP ribosylation factor the 3-dose AS01 vaccine (21,505 [17,842, 25,920] LU/mL) compared with AS02 (12,963 [10,846, 15,493] LU/mL, p = 0.0001) or AS04 (7102 [5869, 8595] LU/mL, p < 0.0001), with half the HPV-33/58 VLP content of the AS04 tetravalent formulation. Anti-HPV-58 GMTs were also significantly higher for the 3-dose tetravalent vaccine adjuvanted with AS01 (10,897 [9090, 13,064] LU/mL) compared with AS02 (6925 [5805, 8261] LU/mL, p = 0.0006) or AS04 (5524 [4556, 6698] LU/mL, p < 0.0001), with half the HPV-33/58 VLP content of the AS04 tetravalent formulation. For the AS01 formulation, anti-HPV-33 and -58 GMTs were significantly lower one month after the last vaccine dose when 2 doses (M0,3 or M0,6) were administered, compared with 3 doses. In Study NG-001, all tetravalent vaccine formulations produced cross-reacting anti-HPV-31, anti-HPV-45 and anti-HPV-52 GMTs which were at least 4-fold, 7-fold and 3-fold higher, respectively, than those associated with natural infection (i.e., 61.6 LU/mL for anti-HPV-31, 28.7 LU/mL for anti-HPV-45 and 54.