Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme

Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40–75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan–Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11–0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19–2.66) for CRC and 1.48 (1.04–2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.     

Hydrography of Crater Lake of Isabel Island,Nayarit, México

Limnology - An observational campaign was carried out in the hypersaline Crater Lake of Isabel Island to explain the main factors of its hydrodynamics. Wind, temperature and relative humidity time...     

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose,short-term experimental model

Background

The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol.

Objectives

This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses.

Methods

Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 μg of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 μg of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE.

Results

Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses.

Conclusions

The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE.     

Risk factors for asthma and allergy associated with urban migration: background and methodology of a cross-sectional study in Afro-Ecuadorian school children in Northeastern Ecuador (Esmeraldas-SCAALA Study)

Background

This study examined the attitudes and actions of 3415 physician-recruited adults aged ≥ 16 years with asthma in eleven countries who were prescribed regular maintenance therapy with inhaled corticosteroids or inhaled corticosteroids plus long-acting β₂-agonists.

Methods

Structured interviews were conducted to assess medication use, asthma control, and patients' ability to recognise and self-manage worsening asthma.

Results

Despite being prescribed regular maintenance therapy, 74% of patients used short-acting β₂-agonists daily and 51% were classified by the Asthma Control Questionnaire as having uncontrolled asthma. Even patients with well-controlled asthma reported an average of 6 worsenings/year. The mean period from the onset to the peak symptoms of a worsening was 5.1 days. Although most patients recognised the early signs of worsenings, the most common response was to increase short-acting β₂-agonist use; inhaled corticosteroids were increased to a lesser extent at the peak of a worsening.

Conclusion

Previous studies of this nature have also reported considerable patient morbidity, but in those studies approximately three-quarters of patients were not receiving regular maintenance therapy and not all had a physician-confirmed diagnosis of asthma. This study shows that patients with asthma receiving regular maintenance therapy still have high levels of inadequately controlled asthma. The study also shows that patients recognise deteriorating asthma control and adjust their medication during episodes of worsening. However, they often adjust treatment in an inappropriate manner, which represents a window of missed opportunity.     

V gamma 1 gammadelta T cells regulate type-1/type-2 immune responses and participate in the resistance to infection and development of heart inflammation in Trypanosoma cruzi-infected BALB/c mice

Many different cell populations or lineages participate in the resistance to Trypanosoma cruzi infection. gammadelta T cells may also take part in a network of interactions that lead to control of T. cruzi infection with minimal tissue damage by controlling alphabeta T cell activation, as was previously suggested. However, the gammadelta T cell population is not homogeneous and its functions might vary, depending on T cell receptor usage or distinct stimulatory conditions. In this study, we show that the in vivo depletion of V gamma 1-bearing gammadelta T cells, prior to the infection of BALB/c mice with the Y strain of T. cruzi, induces an increased susceptibility to the infection with lower amounts of IFN-gamma being produced by conventional CD4+ or CD8+ T cells. In addition, the production of IL-4 by spleen T cells in V gamma 1-depleted mice was increased and the production of IL-10 remained unchanged. Since V gamma 1(+) gammadelta T cell depletion diminished the conversion of naive to memory/activated CD4 T cells and the production of IFN-gamma during the acute infection, these cells appear to function as helper cells for conventional CD4+ Th1 cells. Depletion of V gamma 1(+) cells also reduced the infection-induced inflammatory infiltrate in the heart and skeletal muscle. More importantly, V gamma 1(+) cells were required for up-regulation of CD40L in CD4+ and CD8+ T cells during infection. These results show that a subset of gammadelta T cells (V gamma 1(+)), which is an important component of the innate immune response, up-regulates the type 1 arm of the adaptative immune response, during T. cruzi infection.     

Some Coumarins and Triphenylethene Derivatives as Inhibitors of Human Testes Microsomal 17β-hydroxysteroid Dehydrogenase (17β-HSD Type 3): Further Studies with Tamoxifen on the Rat Testes Microsomal Enzyme

The 7-hydroxycoumarins, umbelliferone and 4-methylumbelliferone (IC 50 =1.4 and 1.9 μM, respectively) were potent inhibitors of human testes microsomal 17 β -HSD (type 3) enzyme whereas 7-methoxycoumarin, 4-hydroxycoumarin and 7-ethoxycoumarin had little or no inhibitory activity. Analogues of the weak inhibitory triphenylethenes tamoxifen and clomiphene but lacking the basic substituent, were weak inhibitors of the human microsomal enzyme. Inhibitory activity was improved by replacement of the triphenylethene structure with a triphenylmethyl (17, 52.6% inhibition) or phenylpropyl (16, 94.8%, IC 50 =42.1 μM) skeleton. Further studies on tamoxifen using rat testes microsomal 17 β -HSD showed that the inhibition was time-dependent and irreversible but not specifically mechanism-based.