AdGFP served as a positive control and showed that 90% of the cel

AdGFP served as a positive control and showed that 90% of the cells were transduced by this adenovector and expressed the GFP transgene following infection at an MOI of 200 pu/cell. These data support the previous finding that DAF anchor is more efficient to attach antigen to the cell membrane than the native MSP142 anchor in mammalian cells. We next evaluated the immunogenicity of adenovectors expressing the various forms of MSP142 in mice. We observed robust T cell responses 2 weeks after a single immunization for each of the MSP142 expressing adenovectors (Fig. 7a). A second immunization of MSP142 adenovector 6 weeks later did not increase MSP142-specific IFN-γ

responses relative to the 2-week time point (although responses induced by DSA and DS-GM constructs appear buy GDC-0199 to be sustained longer in animals that received two doses). The various MSP142 adenovectors differed in their capacity to induce Selleckchem JQ1 MSP142-specific antibody responses in mice. MSP142-specific antibodies were observed in mice after immunization

with a single administration of either AdMSP142-DS or AdMSP142-DSA, but not after one or two doses of AdMSP142-DS-GM or AdMSP142-IC. Interestingly, a second dose of either AdMSP142-DS or AdMSP142-DSA boosted MSP142-specific antibody responses by about 10-fold relative to a single administration of adenovector (Fig. 7b). Adenovector-induced antibody responses were also evaluated in rabbits following two immunizations at an 8-week interval. MSP142-IC was not included in this analysis as it was a poor inducer of antibody responses in the murine studies. The ELISA data with rabbit sera were similar to those from the murine studies. Specifically, the DS and DSA constructs induced the highest responses and

the glycosylation mutant DS-GM induced weak MSP1-specific serum antibody (Fig. 7c). The ability of the MSP142 adenovectors to induce functional antibodies, capable of inhibiting the invasion of erythrocytes by blood stage forms of P. falciparum, was evaluated using GIA. High titers of functional antibodies were induced in rabbits by the adenovectors expressing MSP142. Approximately 60% inhibition was achieved in the standard assay using 2.5 mg/ml of purified IgG from PD184352 (CI-1040) immunized rabbits. The DS and DSA versions of MSP142 induced equally high levels of functional antibodies by GIA ( Fig. 8a) and total antibody by ELISA ( Fig. 8b). We observed similar results using diluted antibody ( Fig. 8c and d). AdMSP142-DS and AdMSP142-DSA performed comparably inducing statistically significant increases in GIA relative to AdNull and AdMSP142-GM (p = 0.0005). There is considerable enthusiasm for the evaluation of adenovirus-based vectors as a gene delivery platform for vaccines. This is driven by findings from different laboratories that adenovectors induce robust and protective T cell responses in multiple animal models of infectious diseases [20], [21], [22], [23] and [24].

Les cas de vascularites à ANCA (anticorps anticytoplasme des poly

Les cas de vascularites à ANCA (anticorps anticytoplasme des polynucléaires neutrophiles) sont très rares. Ils s’observent surtout en cas de traitement prolongé par un dérivé du thiouracile. La présence d’ANCA a été constatée chez

un tiers à deux tiers des sujets soumis à un traitement au long cours par le PTU. S’il est important de préciser que la présence d’ANCA n’est pas nécessairement liée à l’apparition de signes cliniques de vascularite, leur survenue constitue cependant un facteur de prédiction du risque d’angéite. Dès lors, le recours à une autre thérapeutique doit être envisagé. Les ANCA ont été observés aussi mais plus rarement sous thiamazole, et même chez les basedowiens avant tout traitement. Il n’y a pas d’étude randomisée qui ait définitivement établi la supériorité d’un antithyroïdien en termes d’efficacité, de coût ou de tolérance. Toutefois, il est manifeste que l’activité antithyroïdienne des imidazolines est plus forte. Chez l’enfant, il est déconseillé d’utiliser en première intention les dérivés du thiouracile, du fait de rares cas d’hépatite cytolytique sévère, constatés surtout lors de l’utilisation de PTU

à forte dose. Celles-ci ont conduit à des insuffisances hépatiques définitives, nécessitant une greffe hépatique. Dans les hyperthyroïdies sévères et celles liées aux surcharges iodées (hyperthyroïdies de type 1), l’utilisation préférentielle de PTU a été suggérée SP600125 mw du fait de sa capacité à réduire essentiellement la désiodation de T4 en Adenosine T3. Dans ces situations, il faut tenir compte toutefois des altérations

de la désiodation déjà présentes, du fait de la sévérité de l’état général, de l’utilisation éventuelle de la corticothérapie ou du propranolol, ou lorsque l’hyperthyroïdie s’est constituée sous amiodarone ; de plus, la nécessité de fortes doses d’antithyroïdiens légitime aussi l’utilisation possible des présentations disponibles de thiamazole ou de carbimazole. L’utilisation préférentielle du PTU est recommandée lors de l’initiation des grossesses chez les femmes atteintes de maladie de Basedow soumises à un antithyroïdien. En effet, les aplasies du cuir chevelu, les embryopathies des ATS (omphalocèle, atrésies choanales ou œsophagiennes, malformations diaphragmatique, cardiaque…) n’ont été décrites que sous imidazolines, même si elles ont pu survenir en l’absence de traitement, et chez les sujets indemnes de pathologie thyroïdienne. En revanche, leur survenue n’a pratiquement jamais été rapportée sous dérivés du thiouracile, ce qui légitime l’utilisation du Propylex® si l’initiation d’une grossesse sous ATS est programmée, ou possible (en l’absence de contraception efficace).

In these HPV types, the role of the wound healing response in dri

In these HPV types, the role of the wound healing response in driving the initial proliferation of the infected cell(s) may well be critical [103], with signalling from the local microenvironment influencing viral gene expression [104] and/or protein functions. In the case of the high-risk types that cause neoplasia, there is a clear role of the viral E6 and E7 proteins in driving cell proliferation in the basal and parabasal DNA Damage inhibitor cell

layers, especially at cervical sites where neoplasia can occur [3]. It is also clear that there are many functional differences between the high and low-risk E6 and E7 proteins (see Fig. 4A and [105]), and that these contribute, along with differences in promoter activity and patterns of gene expression, to the different HPV-associated pathologies seen in vivo. Indeed, recent studies have suggested that the deregulation of E6/E7 expression, even in the absence of genome integration,

is a critical event in determining neoplastic grade [106], which is classified according to the extent to which basal-like cells extend into suprabasal epithelial layers [107]. The E6/E7-mediated proliferation 3-MA in vivo of the basal and parabasal cells following infection by the high-risk HPV types facilitates an expansion in lesion size, which is thought in part to be linked to specific functions of the high-risk E6 and E7 proteins (Fig. 4A). Functional differences between the high- and low-risk E7 proteins centre to a large extent on their differential ability to associate with members of the Retinoblastoma (Rb) protein (pRb) family, with the high-risk E7 proteins being able to bind and degrade both p105 and p107, which control cell cycle entry in the basal layer, as well as p130, which is involved in cell cycle re-entry in the upper epithelial layers ([48] and [108] and Figure 4 and Figure 5). The low-risk E7 proteins generally appear to have a lower affinity for p105 out and p107 than the high-risk types, but can associate with and degrade p130 in order to create a replication-competent environment in

the mid-epithelial layers that is suitable for genome amplification [105] and [109] (Fig. 5). An unfortunate characteristic of the high-risk E7 proteins however is their ability to stimulate host genome instability, particularly through deregulation of the centrosome cycle in the proliferating basal cells [110], [111], [112], [113], [114] and [115]. The PDZ–domain-binding motif, which is located at the C-terminus of all the high-risk E6 proteins, provides another key difference between high- and low-risk PVs. High-risk E6 proteins are able to interact with a several PDZ targets through this motif, many of which are involved in the regulation of cell polarity, cell proliferation and cell signalling [116] and [117].

However, the antibodies induced during natural hRSV infection fai

However, the antibodies induced during natural hRSV infection fail to prevent recurrent infections throughout life, indicating that also the efficacy of vaccine-induced neutralizing antibodies may be limited [7] and [11]. Controversy

also exists concerning the precise role of the T cell compartment in pneumovirus-induced disease [12] and [13]. Several studies have shown that although T cells are essential in eradicating established infections [14], they also are important mediators of hRSV-induced immunopathology buy LGK-974 [15], [16], [17], [18] and [19]. In murine models, especially Th2 skewing of the CD4+ T-cell lineage after immunization with FI-RSV or hRSV-G protein encoding recombinant Vaccinia virus vectors have been shown to lead to enhanced disease following subsequent hRSV infection [12], [13] and [20]. Induction of CD8+ T-cell responses, on the other hand, inhibited vaccine-enhanced pulmonary disease [21], [22] and [23]. Thus, despite the notion that T cells play a role in pneumovirus-induced immunopathology, these studies suggest that vaccines designed to induce antipneumoviral CD8+ T cell responses may offer an alternative to vaccines targeting the humoral response. Pneumoviruses display a narrow host range and several species-specific variants

have been described [1], adapted for evasion of defense mechanisms in their specific hosts [24] and [25]. Therefore, instead of hRSV, its mouse-adapted variant PVM is increasingly

used to study pneumovirus-specific immune responses and immunopathogenesis in mouse models. PVM and hRSV display a marked genetic learn more similarity and use similar evasion strategies [26], [27] and [28]. Intranasal (i.n.) administration of a low PVM inoculum results in effective replication and severe respiratory disease in mice, with several hallmarks similar to severe hRSV disease in humans, including severe pulmonary inflammation, edema, and influx oxyclozanide of granulocytes [29]. Although extensively studied during hRSV infections in mouse models, only limited studies evaluated T cells in PVM infected mice [30] and [31]. Frey et al. showed that, like in hRSV-infection, T-cells are essential for viral elimination in PVM-infected mice, but are also important mediators of infection-associated pathology [31]. This observation raises the question of whether a pneumovirus-vaccine that targets CD8+ T cell responses would be safe. In this study, we used the PVM mouse model of respiratory infection to determine whether pre-existing virus-specific CD8+ T-cells may provide protection against pneumovirus-induced disease. PVM strain J3666 was passaged in mice to retain full pathogenicity and hRSV strain A2 was grown in BSC-1 cells and concentrated as described [32]. For both viruses, plaque assays on BSC-1 cells were performed to determine viral titers. Influenza strains A/HK/x31 (H3N2) and A/PR/8/34 (H1N1) were grown as described [33].

Losartan potassium microcapsule from a batch was taken at random

Losartan potassium microcapsule from a batch was taken at random and was crushed to a fine powder. The powdered material was transferred into a 100 ml volumetric flask and 70 ml of 6.8 pH phosphate buffer was added to it. It was shaken occasionally for about 30 min and the volume was made up to 100 ml by adding 6.8 pH phosphate buffer. About 10 ml of the solution from the volumetric flask was taken and centrifuged. The supernatant solution from the centrifuge tube was collected and again filtered by using Millipore

filter. Then the filtrate was subsequently diluted and the absorbance was measured at 254 nm. This test was repeated six times (N = 6) for each batch of microcapsules. Based on the dissolution studies performed on all the microcapsules, some of the optimized formulation were selected and further investigation by SEM analysis, DSC and FTIR spectral studies. Dissolution rate studies for each batch of microcapsules were performed in a calibrated 8 station dissolution

test apparatus (LABINDIA DS 8000), equipped with paddles (USP apparatus II method) employing 900 ml of 6.8 pH phosphate buffer as dissolution medium.11 Samples were withdrawn at regular intervals up to 16 h. Fresh volume of the medium was replaced with the withdrawn volume to maintain constant volume throughout the experiment. Samples withdrawn were suitably diluted with same dissolution medium and the amount of drug released was estimated by ELICO double beam spectrophotometer at 254 nm find more based on the various dissolution parameters were calculated with the following, first order, Higuchi and Koresmeyer Peppa’s equation respectively. The dissolution profiles of various microcapsules were shown as Fig. 1. The dissolution parameters evaluated were given in Table 3. The samples were coated with a thin gold layer by sputter coater unit (SPI, Sputter, USA). Then, the SEM photographs were taken by a scanning electron microscope (scanning electron microscope JSM-6390, Japan) operated at an accelerated

voltage of 5 KV. A differential scanning calorimeter (DSC 60, Shimadzu) was used to obtain the DSC curves of LP by solvent evaporation. About 10 mg of sample was weighed in a standard open aluminium pans, were scanned from 20 to 300 °C, at a heating rate of 10 °C/min while being purged with dry nitrogen. until I.R spectral studies were carried out on some selected microcapsules by using BRUKER FTIR. These studies on microcapsules were performed before they are subjected to dissolution studies to check the structural variation if any arised between the drug and excipients used. In the present investigation losartan potassium microcapsules were prepared by solvent evaporation technique. Eudragit S100 was used as controlled release coating polymeric material for the preparation of microcapsules. Methanol and acetone at 1:1 ratio was used as solvent for dissolving Eudragit S100 and losartan potassium.

This effect may be due to a depletion of enzymes, as previously d

This effect may be due to a depletion of enzymes, as previously described by Obay et al. (2008) and Silva et al. (2009), in brain tissues treated with PTZ. Organic grape juice attenuates this decrease in the activities of SOD and CAT, as previously shown for erdosteine (Ilhan et al., 2005), ghrelin (Obay et al., 2008) and isopulegol (Silva

et al., 2009) treatments in rats. In contrast, conventional juice was not able to block the modulation of enzymes induced by PTZ. While other studies are needed, it is possible that this effect could be due the reduced polyphenol (Table 2) and ascorbic acid (Table 1) content buy Bioactive Compound Library of the conventional grape juice. Organic juice also showed higher concentrations of catechin, cyanidin, epicatechin, malvidin diglycoside, procyanidin B1 and resveratrol compared to conventional juice (Table 2). Phenolic compounds are secondary metabolites that are produced and accumulated in plant tissues. Organic farming is currently practiced worldwide and does not use pesticides Selleck ISRIB or synthetic fertilizers. As pesticides are not used, plants are more susceptible to the actions of phytopathogens, and this susceptibility causes the plant to produce higher amounts of polyphenols

as a means of defending itself (Dani et al., 2007 and Soleas et al., 1997). It has been demonstrated that seizures induced by PTZ produce chances in nitric oxide metabolism (Naziroglu et al., 2009). The generation of nitric oxide results in lipid peroxidation, which may also induce epileptic activity by the direct inactivation of glutamine synthase, thereby permitting an abnormal buildup of the major excitatory neurotransmitter glutamate (Dillioglugil et al., 2010, Militão et al., 2010 and Tomé et al., 2010). In all tissues,

both organic and conventional grape juices were able to attenuate the increase in nitric oxide content induced by PTZ. Fossariinae Similar results were observed for rats treated with lipoic acid (Militão et al., 2010) and α-tocopherol (Tomé et al., 2010) in a pilocarpine model of epilepsy. Nitric oxide could react with superoxide, generating the potent tissue-damaging moiety peroxynitrite, which has a high affinity for sulfhydryl groups and thus inactivates several key sulfhydryl-bearing enzymes (Katzung, 2004). This effect is probably the reason that sulfhydryl proteins are reduced in the PTZ group. In contrast, in all tissues assayed, the treatment with either organic or conventional grape juice protected sulfhydryl groups from the oxidation induced by PTZ (Table 3, Table 4 and Table 5). We did not observe differences in the results obtained from the different tissues assayed. The hippocampus is part of the limbic system, and it is important for learning and memory (Hansen and Koeppen, 2002). In addition, the hippocampus is a structure that is involved in the expression and propagation of seizures (Bear and Lothman, 1993).

This permitted a comparison between two groups: participants with

This permitted a comparison between two groups: participants with (n = 33) or without shoulder pain (n = 61). Several factors were observed to differ between those with or without pain (Table 1). Those with pain tended to be younger, took longer to be admitted to rehabilitation after their

stroke, and had lower Motor Assessment Scale (Carr et al 1985) scores for the arm. They also tended to have limited passive range of shoulder motion, shoulder subluxation, impaired sensation, and altered muscle tone. For this study, altered muscle tone included both hypotonia and hypertonia (Carr and Shepherd 1998). In contrast, no differences were observed for several variables including the presence of inattention, communication impairment, or area and side of stroke (Table 1). The BMS-777607 in vivo four predictors selected for inclusion in logistic regression were Motor Assessment Scale Upper Arm item, passive range of shoulder flexion, subluxation, and altered sensation. These were selected from the 10 variables that differentiated between people with and without pain (Table 1) for several reasons. The predictors focused on primary and secondary impairments

following the stroke rather than those relating to hospital processes (eg, days between onset and admission to rehabilitation). When two similar variables were moderately related, only one variable was selected. For instance, the Motor Assessment Scale Upper Arm item was selected over the Hand item as it was considered more relevant to the shoulder. Passive range of shoulder flexion was chosen over external rotation as it was Bortezomib ic50 considered easier to measure clinically given the reliance upon retrospective data. Although Nicks and colleagues (2007) suggested that less than 160 degrees shoulder flexion was a predictor for post-stroke shoulder pain, we used ≤ 150 degrees as a predictor due to the distribution

of shoulder ranges observed. Altered tone was not selected as a predictor as it related to several variables including Motor Assessment Scale scores, subluxation and shoulder range of motion. Logistic regression using the four predictors identified shoulder pain as reliably associated with two predictors: Motor Assessment Scale Upper Arm item and passive range of shoulder flexion (Box 1). These findings indicate Rolziracetam that the odds of experiencing shoulder pain are, on average, 14% greater for people with ≥150 degrees passive shoulder flexion relative to those with ≥ 150 degrees. The average odds of shoulder pain increase by 64% for each unit lower on the Motor Assessment Scale Upper Arm item (ie, a score of 5 has a 64% greater chance of shoulder pain than a score of 6). Based on the prediction equation, the mean odds and probabilities for experiencing shoulder pain are estimated for the range of people with stroke admitted to rehabilitation (Table 2). Regression coefficients of predictors Constant = 3.73 PROM shoulder flexion = −1.

The concentration of test inhibitor required for 50% reduction in

The concentration of test inhibitor required for 50% reduction in the measured isozyme activity (IC50) was estimated using GrapPad Prism® software. Samples for in vitro biotransformation Selleck E7080 were obtained following incubation

of DNDI-VL-2098 (10 μM) with microsomes in presence of cofactors, and with hepatocytes for up to 120 min as described for metabolic stability. Samples for in vivo biotransformation were oral PK blood samples at 4, 6 and 8 h post dose from mouse (50 mg/kg), rat (500 mg/kg) and dog (50 mg/kg). All samples were precipitated with acetonitrile, vortex-mixed and centrifuged (1700g, 10 min) and the supernatants were analyzed for Phase I and Phase II metabolites. All in vivo and in vitro samples were analyzed

for DNDI-VL-2098 and internal standard (DNDI-VL-2075, a structural analog) content using a high performance liquid chromatography (HPLC, Shimadzu Prominence, Japan) tandem mass spectrometric (API4000, Applied Biosystems, USA) method. Positive-ion electron spray ionization mode was used and MRM transitions of 360.20/175.00 for DNDI-VL-2098 and 370.20/241.20 for DNDI-VL-2075 (5 μg/mL) were monitored. An isocratic HPLC method with a 4 min run time was employed for analysis. The mobile phase comprised 5 mM ammonium formate and acetonitrile 20:80 (v/v) with 0.05% formic acid and the flow rate was 0.6 mL/min. Separation was achieved using Kromasil® C8 column (4.6 × 50 mm, 5 μ, Chromatographie Service, USA) maintained at 40 °C employing an injection volume of 10 μL for in vivo samples and 5 μL for in vitro samples. In preliminary studies, DNDI-VL-2098 showed some instability in plasma from different species. Acidification of blood samples from dosed animals with enough an equal volume of 0.1 M HCl resolved the issue, as bench-top stability of greater than 5 h was achieved; therefore all concentrations were determined in blood. Blood samples were extracted using liquid–liquid extraction (LLE) with methyl tert-butyl ether (MTBE). A 50 μL aliquot of

blood, internal standard (20 μL) and potassium dihydrogen phosphate buffer (100 mM, 50 μL) and 1.25 mL of MTBE were vortex mixed and then centrifuged at 2500g for 5 min. A 1 mL aliquot of supernatant was evaporated under flow of nitrogen gas at 50 °C until dryness, and the residue was reconstituted with 200 μL of mobile phase before analysis. The lower limit of quantification (LLOQ) was 5 ng/mL and the assay was linear over a 1000-fold concentration range. All samples were processed along with calibration curve and quality control samples. An acceptance criterion of ±15% was used for all calibration curve (CC), and quality control (QC) standards except for LLOQ sample where ±20% was the acceptance criteria. Samples were processed by protein precipitation with acetonitrile for all assays except the blood to plasma concentration ratio assay where LLE using MTBE was employed.

, 1993) A Do > 1 indicates

, 1993). A Do > 1 indicates GSK-3 beta phosphorylation that the complete dose cannot

dissolve in 250 mL of medium while a Do < 1 indicates that the dose is soluble in this volume. None of the studied compounds obtained an increase in Sapp due to ethanol in FaSSGF that was high enough to cause a shift in Do when the highest prescribed dose was used for the calculation. Cinnarizine was completely soluble in both FaSSGF and FaSSGF20%Ethanol while all other compounds were not. If this analysis were to be performed using a normal tablet strength rather than the highest prescribed dose, all weak bases in this study would have been soluble in all the media. A normal dose for felodipine (2.5 mg) gave rise to a Do shift from above 1 in FaSSGF to below 1 after addition of 20% ethanol. Compared to our previous study on ethanol effects on Sapp in intestinal media 20% ethanol in FaSSIF did induce a Do shift using the max doses of felodipine and indoprofen. These Do shifts in FaSSIF were the result of a moderate increase in Sapp due to 20% ethanol, with a 2- and 3-fold increase respectively for these compounds. Due to high dose and/or low initial Sapp in FaSSIF, no Do shift occurred as result of 20% ethanol for dipyridamole (19-fold increase), griseofulvin (8-fold), progesterone (7-fold) indomethacin and tolfenamic acid (3-fold). see more As the intestinal Sapp of terfenadine and

cinnarizine did not increase with the addition of ethanol, neither was

there any shift in Do for these compound in the simulated intestinal fluid ( Fagerberg et al., 2012). The computational simulations with GI-Sim revealed that although the solubility of indomethacin and indoprofen was increased with the addition of 20% ethanol in the gastric and duodenal compartments, the effects on absorption Levetiracetam were small as the compounds were absorbed rapidly and completely in the fasted state. The small observed increase in Cmax is likely to be negligible. The decrease in Tmax could indicate a potential reduction in onset due to ethanol. This assumes however that no other parameters except the concentrations in the stomach and intestine affect the absorption and the resulting plasma concentration. The absorption of tolfenamic acid and the two basic compounds terfenadine and cinnarizine was also more or less unaffected by the simulated concomitant ethanol intake. For the latter two the absorption was reduced slightly due to a lower Sapp in duodenal media (FaSSIF with 20% ethanol) as a result of suppressed ionization caused by the ethanol. Dipyridamole is completely charged at the gastric pH but only slightly so at the intestinal pH where its Sapp is effectively increased by the addition of ethanol. This results in a higher extent and rate of absorption predicted by the simulations.

We observed a RIR (95% CI) of 1 09 (1 03, 1 15) for females versu

We observed a RIR (95% CI) of 1.09 (1.03, 1.15) for females versus males, which is similar to the result of our non-restricted analysis (Table 3). We then further restricted the event definition to include Epigenetics Compound Library only specific types of adverse events

that would be expected following MMR vaccine. The four event types included, based on ICD-10 codes, were: fever, rash, febrile convulsions and viral enanthema [13] and [10]. The results of this restricted analysis showed a much larger RIR for females versus males of 1.23 (95% CI 0.99, 1.51) p = 0.06, which did not achieve nominal statistical significance due to the loss of events with the restricted event definition ( Table 4). Higher relative incidences in girls compared to CT99021 chemical structure boys were exhibited for each of the four event types, though none achieved nominal

statistical significance. We demonstrated that females had an increased risk of ER visits and/or hospitalizations during a specified ‘at risk’ period, immediately following the 12-month vaccination but not 2-, 4- and 6-month vaccinations. The increased risk associated with female sex translates to 192 excess events in females as compared to males, for every 100,000 infants vaccinated. As previously noted, the vaccine routinely administered at 12 months of age in Ontario during the entire period of study was MMR. A meningococcal disease (type C) vaccine was added to Ontario’s publicly-funded immunization schedule in September 2004. The time period

for increase in ER visits or hospitalizations following 12-month vaccination is consistent with the next known risk period following MMR vaccination [11], [13] and [18]. Our observations could either be explained by gender differences – the socially constructed distinction between the sexes, or by sex differences – the physiological differences between males and females. If gender differences accounted for our observation, one explanation would be that parents respond differently to similar adverse reactions between boys and girls, and are more likely to seek medical care for girls. Our analysis cannot find evidence to support or refute this hypothesis, although we may have expected lower acuity of presentation in girls if this were the case. In contrast, it is recognized in the medical literature that important physiological differences exist between males and females that govern their responses to infections and vaccines [19], [20], [21] and [22]. For example, estrogen can potentiate antibody responses to antigens, while both progesterone and androgens tend to have immunoregulatory or immunosuppressive actions [20], [22] and [23]. Sex differences in immune responses to measles vaccines have certainly been observed both in terms of immunogenicity [21] and [24] and short-term reactogenicity of both the live-attenuated rubella [1] and both high- and standard-titer measles vaccines [4], [25] and [26].