Further evidence for a biological role of anti-estrogen-binding sites in mediating the growth inhibitory action of diphenylmethane derivatives

Several diphenylmethane derivatives have been synthesized with variable affinities for Anti-estrogen Binding Sites (ABS) but not for the estrogen receptor. Using these molecules as probes it is shown that their binding affinities for ABS correlate with their abilities to inhibit the growth of MCF-7 human breast cancer cells. In contrast they have no influence on the proliferation of tamoxifen-resistant variant cells (RTx6) in which ABS are undetectable. These data support the conclusion that ABS has a functional role in the anti-proliferative effect of triphenylethylene anti-estrogens and structurally related compounds.     

Flow‐injection chemiluminescence determination of haemoglobin in the blood

In this study, a sensitive and simple flow‐injection chemiluminescence (CL) method was developed for the quantitative analysis of haemoglobin. The method is based on the ability of haemoglobin to enhance the CL signal generated by a H₂O₂–K₄Fe(CN)₆–fluorescein alkaline system enhanced by CdTe quantum dots. Under the optimized conditions, haemoglobin can be detected in concentration range 7.35 × 10^–9–2.5 × 10^–6 mol/L, with a detection limit (3σ) of 1.8 × 10^–9 mol/L and a relative standard deviation (RSD; for 5 × 10^–7 mol/L haemoglobin) of 2.06% (n = 11). The present CL method was successfully applied for the determination of haemoglobin in three kinds of blood samples taken from an infant, an adult man, an adult woman and two reference samples. Compared with previous reports, the CL method described in this work is simple and rapid, with high sensitivity. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficiency,genotypic variability,and cellular origin of primary and secondary somatic embryogenesis of <Emphasis Type="Italic">Theobroma cacao</Emphasis> L.

Summary The development of efficient tissue culture systems for cacao holds the potential to contribute to the improvement of this tropical erop by providing a rapid and efficient vegetative propagation system for multiplication of elite genotypes. It may also find application in facilitation of germplasm movement across quarantine borders, enhancement of germplasm conservation via cryo-preservation, and development of genetic transformation systems. Somatic embryogenesis using floral tissue explants was previously the only tissue culture procedure for regeneration of cacao. We report the development of a secondary embryogenesis system utilizing primary somatic embryo cotyledon explants, which results in up to a 30-fold increase in somatic embryo production compared to primary somatic embryogenesis. The influence of genotype on the efficiency of the system was evaluated. To understand the cellular origins and developmental pathways operative in this system, we investigated the morphological changes occurring over time using light and scanning electron microscopy. While primary embryos arise from clusters of cells forming embryonic nodules, secondary embryos arise predominantly from the division of single cells, in a pathway reminiscent of zygotic embryogenesis. These results have important significance to the application of tissue culture to cacao improvement programs.     

A surface acoustic wave sensor functionalized with a polypyrrole molecularly imprinted polymer for selective dopamine detection

A surface acoustic wave sensor operating at 104 MHz and functionalized with a polypyrrole molecularly imprinted polymer has been designed for selective detection of dopamine (DA). Optimization of pyrrole/DA ratio, polymerization and immersion times permitted to obtain a highly selective sensor, which has a sensitivity of 0.55°/mM (≈550 Hz/mM) and a detection limit of ≈ 10 nM. Morphology and related roughness parameters of molecularly imprinted polymer surfaces, before and after extraction of DA, as well as that of the non imprinted polymer were characterized by atomic force microscopy. The developed chemosensor selectively recognized dopamine over the structurally similar compound 4‐hydroxyphenethylamine (referred as tyramine), or ascorbic acid,which co‐exists with DA in body fluids at a much higher concentration. Selectivity tests were also carried out with dihydroxybenzene, for which an unexpected phase variation of order of 75% of the DA one was observed. Quantum chemical calculations, based on the density functional theory, were carried out to determine the nature of interactions between each analyte and the PPy matrix and the DA imprinted PPy polypyrrole sensing layer in order to account for the important phase variation observed during dihydroxybenzene injection. Copyright © 2015 John Wiley & Sons, Ltd.     

HIV-2 Integrase Variation in Integrase Inhibitor-Na?ve Adults in Senegal,West Africa

Background

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods

We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results

No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion

Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients.     

Emergence of epidemic Neisseria meningitidis serogroup X meningitis in Togo and Burkina Faso

Serogroup X meningococci (NmX) historically have caused sporadic and clustered meningitis cases in sub-Saharan Africa. To study recent NmX epidemiology, we analyzed data from population-based, sentinel and passive surveillance, and outbreak investigations of bacterial meningitis in Togo and Burkina Faso during 2006-2010. Cerebrospinal fluid specimens were analyzed by PCR. In Togo during 2006-2009, NmX accounted for 16% of the 702 confirmed bacterial meningitis cases. Kozah district experienced an NmX outbreak in March 2007 with an NmX seasonal cumulative incidence of 33/100,000. In Burkina Faso during 2007-2010, NmX accounted for 7% of the 778 confirmed bacterial meningitis cases, with an increase from 2009 to 2010 (4% to 35% of all confirmed cases, respectively). In 2010, NmX epidemics occurred in northern and central regions of Burkina Faso; the highest district cumulative incidence of NmX was estimated as 130/100,000 during March-April. Although limited to a few districts, we have documented NmX meningitis epidemics occurring with a seasonal incidence previously only reported in the meningitis belt for NmW135 and NmA, which argues for development of an NmX vaccine.     

B cell analysis of ethnic groups in Mali with differential susceptibility to malaria

ABSTRACT: BACKGROUND: Several studies indicate that people of the Fulani ethnic group are less susceptible to malaria compared to those of other ethnic groups living sympatrically in Africa, including the Dogon ethnic group. Although the mechanisms of this protection remain unclear, the Fulani are known to have higher levels of Plasmodium falciparum-specific antibodies of all Ig classes as compared to the Dogon. However, the proportions of B cell subsets in the Fulani and Dogon that may account for differences in the levels of Ig have not been characterized. METHODS: In this cross-sectional study, venous blood was collected from asymptomatic Fulani (n=25) and Dogon (n=25) adults in Mali during the malaria season, and from P. falciparum-naive adults in the U.S. (n=8). At the time of the blood collection, P. falciparum infection was detected by blood-smear in 16% of the Fulani and 40% of the Dogon volunteers. Thawed lymphocytes were analysed by flow cytometry to quantify B cell subsets, including immature and naive B cells; plasma cells; and classical, activated, and atypical memory B cells (MBCs). RESULTS: The overall distribution of B cell subsets was similar between Fulani and Dogon adults, although the percentage of activated MBCs was higher in the Fulani group (Fulani: 11.07% [95% CI: 9.317 - 12.82]; Dogon: 8.31% [95% CI: 6.378 - 10.23]; P=0.016). The percentage of atypical MBCs was similar between Fulani and Dogon adults (Fulani: 28.3% [95% CI: 22.73 - 34.88]; Dogon: 29.3% [95% CI: 25.06 - 33.55], but higher than U.S. adults (U.S.: 3.0% [95% CI: -0.21 - 6.164]; P<0.001). Plasmodium falciparum infection was associated with a higher percentage of plasma cells among Fulani (Fulani infected: 3.3% [95% CI: 1.788 - 4.744]; Fulani uninfected: 1.71% [95% CI: 1.33 - 2.08]; P=0.011), but not Dogon adults. CONCLUSION: These data show that the malaria-resistant Fulani have a higher percentage of activated MBCs compared to the Dogon, and that P. falciparum infection is associated with a higher percentage of plasma cells in the Fulani compared to the Dogon, findings that may account for the higher levels of P. falciparum antibodies in the Fulani.     

Pneumococci in the African Meningitis Belt: Meningitis Incidence and Carriage Prevalence in Children and Adults

Background

The development of optimal vaccination strategies for pneumococcal conjugate vaccines requires serotype-specific data on disease incidence and carriage prevalence. This information is lacking for the African meningitis belt.

Methods

We conducted hospital-based surveillance of acute bacterial meningitis in an urban and rural population of Burkina Faso during 2007–09. Cerebrospinal fluid was evaluated by polymerase chain reaction for species and serotype. In 2008, nasopharyngeal swabs were obtained from a representative population sample (1 month to 39 years; N = 519) and additional oropharyngeal swabs from 145 participants. Swabs were evaluated by culture.

Results

Annual pneumococcal meningitis incidence rates were highest among <6-month-old (58/100,000) and 15- to 19-year-old persons (15/100,000). Annual serotype 1 incidence was around 5/100,000 in all age groups. Pneumococcal carriage prevalence in nasopharyngeal swabs was 63% among <5-year-old children and 22% among ≥5-year-old persons, but adding oropharyngeal to nasopharyngeal swabs increased the estimated carriage prevalence by 60%. Serotype 1 showed high propensity for invasive disease, particularly among persons aged ≥5 years.

Conclusions

Serotype 1 causes the majority of cases with a relatively constant age-specific incidence. Pneumococcal carriage is common in all age groups including adults. Vaccination programs in this region may need to include older target age groups for optimal impact on disease burden.     

Statins (HMG-coenzyme A reductase inhibitors)-biomimetic membrane binding mechanism investigated by molecular chromatography

Many studies have demonstrated that the statin beneficial effects on cardiovascular diseases like coronary are linked to their hypocholesterolemic properties. These lipid-lowering drugs are the first-line pharmacologic therapy for hypercholesterolemia. In this paper, the interaction of a series of statin molecules STCOOH (pravastatin (prava), mevastatin (meva), simvastatin (simva) and fluvastatin (fluva)) with a phosphatidylcholine monolayer immobilized on to porous silica particles has been studied using a biochromatographic approach (molecular chromatography). The immobilized artificial membrane (IAM) provided a biophysical model system to study the binding of the statin molecules to a lipid membrane. For all the test statin molecules, linear retention plots were observed at all temperatures. An analysis of the thermodynamics (i.e., enthalpy (DeltaH(0)), entropy (DeltaS(0)*)) of the interaction of the statin molecules with the immobilized monolayer was also carried out. The DeltaH(0) and DeltaS(0)* values were negative due to van der Waals interactions and hydrogen bonding between the statin molecules with the polar head groups of the phospholipid monolayer (polar retention effect). The statin elution order was: Prava相似文献