Mast cells are critical mediators of vaccine-induced Helicobacter clearance in the mouse model

BACKGROUND & AIMS: Despite the proven ability of immunization to prevent Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. METHODS: We explored the cellular events associated with Helicobacter clearance from the stomach following vaccination by flow cytometry analysis and histological and molecular studies. RESULTS: Kinetic studies showed that the infection is undetectable in vaccinated mice at day 5 postbacterial challenge. Flow cytometry analysis showed that the percentages of mast cells (CD3 - CD117 + ) increased in the lymphoid cells isolated from the stomach at day 4 postchallenge in urease + cholera toxin (CT)-vaccinated mice in comparison with mice administered with CT alone (9.4% +/- 4.4% and 3.1% +/- 1%, respectively, for vaccinated and CT administered, n = 5; P < .01). Quantitative PCR analysis showed an increased messenger RNA (mRNA) expression of the mast cell proteases 1 and 2 at day 5 postchallenge in the stomach of vaccinated mice. In contrast to wild-type mice, mast cell-deficient mice (W/W v mice) were not protected from H felis colonization after vaccination. Indeed only 1 out of 12 vaccinated W/W v mice showed a negative urease test. Remarkably, vaccinated W/W v mice reconstituted with cultured bone marrow-derived mast cells recovered the ability to clear the infection after vaccination (8 out of 10 mast cell-reconstituted mice showed negative urease tests [ P < .006 as compared with wild-type mice]). CONCLUSIONS: These experiments show that mast cells are, unexpectedly, critical mediators of anti- Helicobacter vaccination.     

Is the burden of oral diseases higher in urban disadvantaged community compared to the national prevalence?

Background

The urban low income has often been assumed to have the greatest dental treatment needs compared to the general population. However, no studies have been carried out to verify these assumptions. This study was conducted to assess whether there was any difference between the treatment needs of an urban poor population as compared to the general population in order to design an intervention programme for this community.

Methods

A random sampling of living quarters (households) in the selected areas was done. 586 adults over 19 years old living in these households were clinically examined using World Health Organization (WHO) Oral Health Survey criteria 4th edition (1997).

Results

The overall prevalence of dental caries, periodontal disease, denture wearers and temporomandibular joint problems were 70.5%, 97.1%, 16.7% and 26%, respectively. The majority (80.5%) needed some form of dental treatment. The highest treatment needs were found in the oldest age group while the lowest were in the youngest group (19-29 years) (p = 0.000). The most prevalent periodontal problem was calculus; regardless of gender, ethnicity and age. Significantly more females (20.5%) wore prosthesis than males (11.1%) (p = 0.003). Prosthetic status and need significantly increased with age (p = 0.000). About one in four adults had Temporo-Mandibular Joint (TMJ) problems. Overall, it was surprising to note that the oral disease burden related to caries, prosthetic status and treatment need were lower in this population as compared to the national average (NOHSA, 2010). However, their periodontal disease status and treatment needs were higher compared to the national average indicating a poor oral hygiene standard.

Conclusions

The evidence does not show that the overall oral disease burden and treatment needs in this urban disadvantaged adult population as higher than the national average, except for periodontal disease. The older age groups and elderly were identified as the most in need for oral health intervention and promotion. An integrated health intervention programme through a multisectoral common risk factor approach in collaboration with the Faculties of Medicine, Dentistry and other agencies is needed for the identified target group.

     

India’s first successful intestinal transplant: The road traveled and the lessons learnt

Intestinal transplant is a therapeutic challenge not just surgically but also logistically because of the multidisciplinary expertise and resources required. A large proportion of patients who undergo massive bowel resection and develop intestinal failure have poor outcome, because of inability to sustain long-term parenteral nutrition and limited availability of intestinal and multi-visceral transplantation facilities. We report the first successful isolated intestinal transplant from India.     

Development of Solid Dispersion by Hot Melt Extrusion Using Mixtures of Polyoxylglycerides With Polymers as Carriers for Increasing Dissolution Rate of a Poorly Soluble Drug Model

Various polyoxylglycerides have been researched extensively in the development of solid dispersions (SDs) for bioavailability enhancement of poorly water-soluble drugs. However, because of their low melting points (40°C-60°C), SDs produced are usually soft and semisolid. The objective of present study was to prepare SDs of a Biopharmaceutical Classification System class II drug, carvedilol, in mixtures of stearoyl polyoxylglycerides (Acconon^® C-50; m.p. ～50°C) with polymers by hot melt extrusion to obtain free-flowing powder upon grinding. Miscibility of carvedilol with Kollidon^® VA64, hydroxypropyl methylcellulose acetate succinate, and Klucel^? EXF was first evaluated by film casting, and Kollidon^® VA64 was selected for further study. SDs containing 5%-20% carvedilol, 0%-20% Acconon^® C-50, and the remaining Kollidon^® VA64 were prepared for hot melt extrusion. SDs were characterized by differential scanning calorimetry and powder X-ray diffraction analysis, and dissolution tests were conducted in 250 mL of pH 6.8 phosphate buffer by filling powders in capsules. Carvedilol was miscible with all polymers tested up to 50% and remained amorphous in SDs. The drug release from formulations containing 20% carvedilol and 0, 5%, 10%, and 20% Acconon^® C-50 were 30%, 30%, 70%, and 90%, respectively, in 60 min. SDs containing carvedilol and Acconon^® C-50, up to 20% each, as well as Kollidon^® VA64, were physically stable after 3 months of storage at 25°C/60% relative humidity.     

The effect of timing of maternal tetanus,diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels – A prospective study

Background

The Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27–36 weeks.

Aim

To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn.

Methods

This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n = 61).

Results

The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks (n = 21) compared with 31–36 weeks (n = 30) and >36 weeks (n = 7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29–87.30) vs. 8.69 IU/mL (95% CI, 3.66–20.63) and 21.12 IU/mL (95% CI, 7.93–56.22), p < 0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks compared with 31–36 weeks and >36 weeks, 225.86 IU/mL (95% CI, 182.34–279.76) vs. 178.31 IU/mL (95% CI, 134.59–237.03) and 138.03 IU/mL (95% CI, 97.61–195.16), p < 0.02, respectively.

Conclusions

Immunization of pregnant women with Tdap between 27–30⁺⁶ weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.     

Evaluation of immune responses to an oral typhoid vaccine,Ty21a,in children from 2 to 5 years of age in Bangladesh

Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years.     

Sample size calculation in cost‐effectiveness cluster randomized trials: optimal and maximin approaches

In this paper, the optimal sample sizes at the cluster and person levels for each of two treatment arms are obtained for cluster randomized trials where the cost‐effectiveness of treatments on a continuous scale is studied. The optimal sample sizes maximize the efficiency or power for a given budget or minimize the budget for a given efficiency or power. Optimal sample sizes require information on the intra‐cluster correlations (ICCs) for effects and costs, the correlations between costs and effects at individual and cluster levels, the ratio of the variance of effects translated into costs to the variance of the costs (the variance ratio), sampling and measuring costs, and the budget. When planning, a study information on the model parameters usually is not available. To overcome this local optimality problem, the current paper also presents maximin sample sizes. The maximin sample sizes turn out to be rather robust against misspecifying the correlation between costs and effects at the cluster and individual levels but may lose much efficiency when misspecifying the variance ratio. The robustness of the maximin sample sizes against misspecifying the ICCs depends on the variance ratio. The maximin sample sizes are robust under misspecification of the ICC for costs for realistic values of the variance ratio greater than one but not robust under misspecification of the ICC for effects. Finally, we show how to calculate optimal or maximin sample sizes that yield sufficient power for a test on the cost‐effectiveness of an intervention. Copyright © 2014 John Wiley & Sons, Ltd.     

Heart Fields: Spatial Polarity and Temporal Dynamics

In chick and mouse, heart fields undergo dynamic morphological spatiotemporal changes during heart tube formation. Here, the dynamic change in spatial polarity of such fields is discussed and a new perspective on the heart fields is proposed. The heart progenitor cells delaminate through the primitive streak and migrate in a semicircular trajectory craniolaterally forming the bilateral heart fields as part of the splanchnic mesoderm. They switch their polarity from anteroposterior to mediolateral. The anterior intestinal portal posterior descent inverts the newly formed heart field mediolateral polarity into lateromedial by 125° bending. The heart fields revert back to their original anteroposterior polarity and fuse at the midline forming a semi heart tube by completing their half circle movement. Several names and roles were assigned to different portions of the heart fields: posterior versus anterior, first versus second, and primary versus secondary heart field. The posterior and anterior heart fields define basically physical fields that form the inflow–outflow axis of the heart tube. The first and second heart fields are, in contrast, temporal fields of differentiating cardiomyocytes expressing myosin light chain 2a and undifferentiated and proliferating precardiac mesoderm expressing Isl1 gene, respectively. The two markers present a complementary pattern and are expressed transiently in all myocardial lineages. Thus, Isl1 is not restricted to a portion of the heart field or one of the two heart lineages as has been often assumed. Anat Rec, 297:175–182, 2014. © 2013 Wiley Periodicals, Inc.