Epidemiology of measles virus outbreaks in Catalonia: importance of immunization in the elimination era

Eradicating measles represents a major public health achievement, yet outbreaks still occur in territories where endemic measles virus (MV) had been eliminated. In Catalonia from the year 2000 cases have occurred as isolated cases or small outbreaks, both linked to imported cases up to the end of 2006 when a large outbreak started out affecting mainly children ≤15m. In consequence, immunization schedule was amended lowering first dose to 12m. Again new MV importations from neighboring countries triggered another outbreak on November 2010 with a different age distribution sparing small children from infection. Differences in incidence (IR), rate ratio (RR) and 95% CI and hospitalization rate (HR) by age group were determined. Statistic z was used for comparing proportions. Total number of confirmed cases was 305 vs 381 in 2006; mean age 20 yrs (SD 14.8yrs; 3m -51yrs) vs 15m (SD13.1yrs; 1m-50yrs). Highest proportion of cases was set in ≥25yrs (47%) vs 24.2% in 2006 (p<0.001). Difference in IR for ≤ 15m was statistically significant (49/100,000 vs 278.2/100,000; RR:3.9; 95%CI 2.9-5.4) and in HR 30.2% vs 15.7% (p<0.001). The change of the month of administration of the first dose proved successful. Given the current epidemiological situation, continued awareness and efforts to reach young adult population are needed to stop the spread of the virus.

Non conventional biological treatment based on Trametes versicolor for the elimination of recalcitrant anticancer drugs in hospital wastewater

This work presents a study about the elimination of anticancer drugs, a group of pollutants considered recalcitrant during conventional activated sludge wastewater treatment, using a biological treatment based on the fungus Trametes versicolor. A 10-L fluidized bed bioreactor inoculated with this fungus was set up in order to evaluate the removal of 10 selected anticancer drugs in real hospital wastewater. Almost all the tested anticancer drugs were completely removed from the wastewater at the end of the batch experiment (8 d) with the exception of Ifosfamide and Tamoxifen. These two recalcitrant compounds, together with Cyclophosphamide, were selected for further studies to test their degradability by T. versicolor under optimal growth conditions. Cyclophosphamide and Ifosfamide were inalterable during batch experiments both at high and low concentration, whereas Tamoxifen exhibited a decrease in its concentration along the treatment. Two positional isomers of a hydroxylated form of Tamoxifen were identified during this experiment using a high resolution mass spectrometry based on ultra-high performance chromatography coupled to an Orbitrap detector (LTQ-Velos Orbitrap). Finally the identified transformation products of Tamoxifen were monitored in the bioreactor run with real hospital wastewater

Elimination of dyes from aqueous solutions using iron oxides and chitosan as adsorbents: a comparative study

This work investigates the adsorption of Alizarin, Eriochrome Blue Black R and Fluorescein using chitosan, goethite and magnetite as adsorbents. For Alizarin, the best adsorbent is chitosan with a Langmuir parameter of 15.8 mmol dye/g adsorbent. For Eriochrome Blue Black R only 1.94 mmol dye/g chitosan is adsorbed. Langmuir parameters for the Alizarin adsorption on both iron oxides display one or two orders of magnitude lower than for chitosan and two orders of magnitude lower in the case of Eriochrome Blue Black R. Fluorescein does not adsorb in appreciable amounts on chitosan and it presents the lower affinity on the iron oxides.

Temperature-dependent benzoic acid elimination mechanisms in pyrolysis of (-)-cocaine

The thermal elimination of benzoic acid from (-)-cocaine is shown to be temperature-dependent. In the temperature range of 200-500 °C only a trans-elimination is observed leading to methylecgonidine. Above ca. 500 °C a second mechanism, the cis-elimination, comes up yielding a novel alkaloid methylisoecgonidine which has been characterized by means of mass spectrometry. At 600 °C the cis-elimination predominates. The trans-elimination is postulated a two-step process consisting of a 1,7- and a 1,5-hydrogen shift. The chemistry of cocaine base smoking is explained using the theory of chemical activation.

Lethal weapons : novel approaches for receptor-targeted cancer cell elimination

The currently used forms of cancer therapy are associated with drug resistance and toxicity to healthy tissues. Thus, more efficient methods are needed for cancer-specific induction of growth arrest and programmed cell death, also known as apoptosis. Therapeutic forms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are investigated in clinical trials due to the capability of TRAIL to trigger apoptosis specifically in cancer cells by activation of cell surface death receptors. Many tumors, however, have acquired resistance to TRAIL-induced apoptosis and sensitizing drugs for combinatorial treatments are, therefore, in high demand. This study demonstrates that lignans, natural polyphenols enriched in seeds and cereal, have a remarkable sensitizing effect on TRAIL-induced cell death at non-toxic lignan concentrations. In TRAIL-resistant and androgen-dependent prostate cancer cells we observe that lignans repress receptor tyrosine kinase (RTK) activity and downregulate cell survival signaling via the Akt pathway, which leads to increased TRAIL sensitivity. A structure-activity relationship analysis reveals that the γ-butyrolactone ring of the dibenzylbutyrolactone lignans is essential for the rapidly reversible TRAIL-sensitizing activity of these compounds. Furthermore, the lignan nortrachelogenin (NTG) is identified as the most efficient of the 27 tested lignans and norlignans in sensitization of androgen-deprived prostate cancer cells to TRAIL-induced apoptosis. While this combinatorial anticancer approach may leave normal cells unharmed, several efficient cancer drugs are too toxic, insoluble or unstable to be used in systemic therapy. To enable use of such drugs and to protect normal cells from cytotoxic effects, cancer-targeted drug delivery vehicles of nanometer scale have recently been generated. The newly developed nanoparticle system that we tested in vitro for cancer cell targeting combines the efficient drug-loading capacity of mesoporous silica to the versatile particle surface functionalization of hyperbranched poly(ethylene imine), PEI. The mesoporous hybrid silica nanoparticles (MSNs) were functionalized with folic acid to promote targeted internalization by folate receptor overexpressing cancer cells. The presented results demonstrate that the developed carrier system can be employed in vitro for cancer selective delivery of adsorbed or covalently conjugated molecules and furthermore, for selective induction of apoptotic cell death in folate receptor expressing cancer cells. The tested carrier system displays potential for simultaneous delivery of several anticancer agents specifically to cancer cells also in vivo.

Chromosomal abnormalities in couples with recurrent first trimester abortions

PURPOSE: To investigate the prevalence of chromosomal abnormalities in couples with two or more recurrent first trimester miscarriages of unknown cause. METHODS: The study was conducted on 151 women and 94 partners who had an obstetrical history of two or more consecutive first trimester abortions (1-12 weeks of gestation). The controls were 100 healthy women without a history of pregnancy loss. Chromosomal analysis was performed on peripheral blood lymphocytes cultured for 72 hours, using Trypsin-Giemsa (GTG) banding. In all cases, at least 30 metaphases were analyzed and 2 karyotypes were prepared, using light microscopy. The statistical analysis was performed using the Student t-test for normally distributed data and the Mann-Whitney test for non-parametric data. The Kruskal-Wallis test or Analysis of Variance was used to compare the mean values between three or more groups. The software used was Statistical Package for the Social Sciences (SPSS), version 17.0. RESULTS: The frequency of chromosomal abnormalities in women with recurrent miscarriages was 7.3%, including 4.7% with X-chromosome mosaicism, 2% with reciprocal translocations and 0.6% with Robertsonian translocations. A total of 2.1% of the partners of women with recurrent miscarriages had chromosomal abnormalities, including 1% with X-chromosome mosaicism and 1% with inversions. Among the controls, 1% had mosaicism. CONCLUSION: An association between chromosomal abnormalities and recurrent miscarriage in the first trimester of pregnancy (OR=7.7; 95%CI 1.2--170.5) was observed in the present study. Etiologic identification of genetic factors represents important clinical information for genetic counseling and orientation of the couple about the risk for future pregnancies and decreases the number of investigations needed to elucidate the possible causes of miscarriages.

Elimination of the tremorgenic toxin of Ipomoea asarifolia by milk

With the aim to determine if the tremorgenic toxin of Ipomoea asarifolia is eliminated in milk, three groups of Swiss female mice received, immediately after giving birth until weaning, a ration containing 20% or 30% of dry I. asarifolia. All the offspring of the females that received 20% or 30% I. asarifolia showed tremors 2-4 days after birth. The offspring of the females that received 20% I. asarifolia recovered 4-7 days after weaning. The offspring of the females that received 30% of the plant in the ration died while showing tremors before weaning or up to two days after weaning. It is concluded that the tremorgenic compound of I. asarifolia or its toxic metabolites are eliminated in milk, and that lactating mice may be used as a model for the determination of the toxic compound(s) in this plant.

Chromosomal evolution and comparative gene mapping in the Drosophila repleta species group

A review of our recent work on the cromosomal evolution of the Drosophila repleta species group is presented. Most studies have focused on the buzzatii species complex, a monophyletic set of 12 species which inhabit the deserts of South America and the West Indies. A statistical analysis of the length and breakpoint distribution of the 86 paracentric inversions observed in this complex has shown that inversion length is a selected trait. Rare inversions are usually small while evolutionary successful inversions, fixed and polymorphic, are predominantly of medium size. There is also a negative correlation between length and number of inversions per species. Finally, the distribution of inversion breakpoints along chromosome 2 is non-random, with chromosomal regions which accumulate up to 8 breakpoints (putative "hot spots"). Comparative gene mapping has also been used to investigate the molecular organization and evolution of chromosomes. Using in situ hybridization, 26 genes have been precisely located on the salivary gland chromosomes of D. repleta and D. buzzatii; another nine have been tentatively identified. The results are fully consistent with the currently accepted chromosomal homologies between D. repleta and D. melanogaster, and no evidence for reciprocal translocations or pericentric inversions has been found. The comparison of the gene map of D. repleta chromosome 2 with that of the homologous chromosome 3R of D. melanogaster shows an extensive reorganization via paracentric inversions and allows to estimate an evolution rate of ~1 inversion fixed per million years for this chromosome

Chromosomal polymorphism in urban populations of Drosophila paulistorum

Drosophila paulistorum populations colonizing the urban area of Porto Alegre, southern Brazil, were studied with the objective of characterizing their chromosomal polymorphism in this new environment. Despite being geographically and ecologically marginal and the fact that the colonization of the urban area seems to be a recent event, the populations showed a large number of inversions on all chromosome arms. Differences regarding inversion frequencies and percentage of heterozygosis were found when we compared the samples with respect to geographical, microenvironmental and temporal aspects. Such differences, however, could be attributed to both selective and stochastic factors

High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients

Abnormal riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinson's disease (PD), while the classical determinants of homocysteine levels (B6, folic acid, and B12) were usually within normal limits. In contrast, only 3 of 10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status. The data for 12 patients who did not complete 6 months of therapy or did not comply with the proposed treatment paradigm were excluded from analysis. Nineteen PD patients (8 males and 11 females, mean age ± SD = 66.2 ± 8.6 years; 3, 3, 2, 5, and 6 patients in Hoehn and Yahr stages I to V) received riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet. After 1 month the riboflavin status of the patients was normalized from 106.4 ± 34.9 to 179.2 ± 23 ng/ml (N = 9). Motor capacity was measured by a modification of the scoring system of Hoehn and Yahr, which reports motor capacity as percent. All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed. The data show that the proposed treatment improves the clinical condition of PD patients. Riboflavin-sensitive mechanisms involved in PD may include glutathione depletion, cumulative mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. More studies are required to identify the mechanisms involved.

Intrinsic bent DNA sites in the chromosomal replication origin of Xylella fastidiosa 9a5c

The features of the nucleotide sequences in both replication and promoter regions have been investigated in many organisms. Intrinsically bent DNA sites associated with transcription have been described in several prokaryotic organisms. The aim of the present study was to investigate intrinsic bent DNA sites in the segment that holds the chromosomal replication origin, oriC, of Xylella fastidiosa 9a5c. Electrophoretic behavior analyses, as well as in silico analyses of both the 2-D projection and helical parameters, were performed. The chromosomal segment analyzed contains the initial sequence of the rpmH gene, an intergenic region, the dnaA gene, the oriC sequence, and the 5' partial sequence of the dnaN gene. The analysis revealed fragments with reduced electrophoretic mobility, which indicates the presence of curved DNA segments. The analysis of the helical parameter ENDS ratio revealed three bent DNA sites (b1, b2, and b3) located in the rpmH-dnaA intergenic region, the dnaA gene, and the oriC 5' end, respectively. The chromosomal segment of X. fastidiosa analyzed here is rich in phased AT tracts and in CAnT motifs. The 2-D projection indicated a segment whose structure was determined by the cumulative effect of all bent DNA sites. Further, the in silico analysis of the three different bacterial oriC sequences indicated similar negative roll and twist >34.00° values. The DnaA box sequences, and other motifs in them, may be associated with the intrinsic DNA curvature.

Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome

Myelodysplastic syndrome (MDS) patients with a normal karyotype constitute a heterogeneous group from a biological standpoint and their outcome is often unpredictable. Interphase fluorescence in situ hybridization (I-FISH) studies could increase the rate of detection of abnormalities, but previous reports in the literature have been contradictory. We performed I-FISH and conventional karyotyping (G-banding) on 50 MDS patients at diagnosis, after 6 and 12 months or at any time if a transformation to acute myeloid leukemia (AML) was detected. Applying a probe-panel targeting the centromere of chromosomes 7 and 8, 5q31, 5p15.2 and 7q31, we observed one case with 5q deletion not identified by G-banding. I-FISH at 6 and 12 months confirmed the karyotype results. Eight cases transformed to AML during follow-up, but no hidden clone was detected by I-FISH in any of them. The inclusion of I-FISH during follow-up of MDS resulted in a small improvement in abnormality detection when compared with conventional G-banding.

Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.