Correlation of plasma butyrylcholinesterase concentration with Acethylcholinesterase H353N polymorphism in the inflammatory response of Chagas disease patients.

Trypanosoma cruzi infection triggers an intense production of pro-inflammatory cytokines mediated by T helper 1 lymphocytes, inducing the anti-inflammatory reflex of acetylcholine (ACh). The ACh concentration modulation is associated to the two major esterases, the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). AChE H353N protein polymorphism is related to low Chagas chronic disease prognostic. In order to evaluate the correlation of plasmatic BuChE concentration and the presence of AChE H353N polymorphism in Chagas disease patients and healthy individuals, we studied two groups of individuals, one of 61 Chagas disease patients and another of 74 healthy individuals. Plasma concentration of BuChE was measured by the chemiluminescent method and AChE H353N polymorphism was investigated by PCR-RFLP and sequencing of the respective encoding AChE gene fragment. The BuChE concentration was statistically higher in Chagas disease patients, with no AChE genotype significant influence. AChE genotypes YT*A/YT*A, YT*A/YT*B and YT*B/YT*B, respectively, were expressed in 53 (86.88%), 7 (11.46%) and one (1.64%) chagasic patients, and in 68 (91.89%), 6 (8.10%) and none healthy individuals. BuChE activity may represent an important marker for chronic Chagas disease inflammatory process and prognostic. Lower BuChE concentration correlated with AChE YT*B allele, although without statistical power.

Efficacy and Adverse Effects of Whitening Dentifrices Compared With Other Products: A Systematic Review and Meta-analysis.

Whitening dentifrices (WDs) are widespread and accessible worldwide, claiming to whiten teeth. Therefore, this systematic review aimed to assess the extrinsic stain removal (ESR), the whitening potential, and the adverse effects of WDs. Randomized controlled trials comparing WDs with regular dentifrices (RDs) and other home-based whitening products were searched at NCBI-PubMed, Cochrane-CENTRAL, EBSCO-Host, and clinicaltrials.gov. The studies were screened and had data extracted by two independent researchers. Eligible studies presented outcomes of ESR, color change, and adverse effects, with no restriction of publication date. Data were meta-analyzed using RevMan 5.3, and the level of evidence was rated according to GRADE criteria. Eleven studies (n=1962) assessed reduction of stain area and intensity through Lobene Stain index, with a mean difference (MD) of -0.33 ([-0.41;-0.25]; p=0.00001) and -0.34 ([-0.44;-0.25]; p=0.00001), respectively. When the modified Lobene Stain index was used (six studies; n=2576), MD was -0.42 ([-0.58;-0.25]; p=0.00001) and -0.30 ([-0.39;-0.21]; p=0.00001), respectively. Mean color change through shade guide tabs (three studies; n=1322) was -1.80 ([-2.33;-1.26]; p=0.00001). All differences were in favor of the WDs, which also produced a risk of adverse effects (RR=1.74; [1.20, 2.52]; p=0.003; four studies; n=1322). The comparison of WDs with paint-on gel (two studies; n=58) yielded similar efficacy and adverse effects (p>0.05), whereas the comparison of WDs with white strips (two studies; n=87) yielded higher efficacy of the latter (p=0.00001) and similar adverse effects (p=0.52). The quality of evidence varied from low to moderate. WDs are more effective in reducing extrinsic stain and producing a whitening-like effect in teeth than RDs, although they also produce more adverse effects. Whitening efficacy of WDs is similar to paint-on gel and lower than white strips. Higher-quality evidence demands larger, well-conducted, independent studies.

Phylogeography of isolated freshwater three-spined stickleback Gasterosteus aculeatus populations in the Adriatic Sea basin.

Analyses of mitochondrial (mt) DNA and microsatellite variation were carried out to examine the relationships between 10 freshwater populations of three-spined sticklebacks Gasterosteus aculeatus along the eastern coast of the Adriatic Sea. Partial sequences of the mtDNA control region and cytochrome b gene, in addition to 15 microsatellite loci, were used to analyse populations from four isolated river catchments. Results uncovered an Adriatic lineage that was clearly divergent from the European lineage, and confirmed that the most divergent and ancient populations are located within the Adriatic lineage as compared with other European populations. Two northern Adriatic populations formed independent clades within the European mitochondrial lineage, suggesting different colonization histories of the different Adriatic populations. Nuclear marker analyses also indicated deep divergence between Adriatic and European populations, albeit with some discordance between the mtDNA phylogeny of the northern Adriatic populations, further highlighting the strong differentiation among the Adriatic populations. The southern populations within the Adriatic lineage were further organized into distinct clades corresponding to respective river catchments and sub-clades corresponding to river tributaries, reflecting a high degree of population structuring within a small geographic region, concurrent with suggestions of existence of several microrefugia within the Balkan Peninsula. The highly divergent clades and haplotypes unique to the southern Adriatic populations further suggest, in accordance with an earlier, more limited survey, that southern Adriatic populations represent an important reservoir for ancient genetic diversity of G. aculeatus.

Leucemias agudas pediátricas de inmunofenotipo inusual / Childhood acute leukemias of unusual phenotype

La mayoría de las Leucemias Agudas (LA) pediátricas pueden clasificarse como Linfoblásticas (principalmente de fenotipo B o T) o Mieloblásticas dependiendo del linaje celular de los blastos, recibiendo tratamiento específico de acuerdo a esta caracterización. La inmunotipificación de las LA se basa en la evaluación de la expresión de antígenos de superficie y/o intracitoplasmáticos de diferenciación linfoide (B o T) o mieloide (My) en los blastos, lo cual permite definir la estirpe celular y clasificar la LA de acuerdo al grado de maduración. Sin embargo, existen grupos particulares poco frecuentes de LA cuya clasificación resulta dificultosa y por eso se las denomina LA de linaje ambiguo (fenotipo mixto/indiferenciadas) y LA de linaje dendrítico. Las de fenotipo mixto son aquellas en las que los blastos expresan marcadores de más de un linaje, y las indiferenciadas aquellas que no expresan antígenos específicos para ningún linaje. Diferentes convenciones se han ido desarrollando para definir y clasificar estos fenotipos inusuales, siendo la más actualizada la propuesta por la Organización Mundial de la Salud (2008). De acuerdo a estas pautas, de 1301 casos de LA diagnosticados entre abril de 1994 y abril de 2009, 28 fueron re-clasificados como LA de linaje Ambiguo, 3 como leucemia mieloide aguda minimamente diferenciadas y 3 como LA de células dendríticas. Debido a lo infrecuente de estos casos, su caracterización resulta relevante, ya que la bibliografía presenta, en general, sólo comunicaciones esporádicas de estos fenotipos particulares. Dada la importante casuística del Hospital Garrahan y el amplio seguimiento de los pacientes, el relevamiento de estos casos inusuales permite caracterizarlos desde el inmunofenotipo, la morfología/citoquímica, la citogenética/biología molecular y evaluar su presentación clínica, evolución, respuesta al tratamiento y sobrevida libre de eventos con la finalidad de colaborar con la definición de su pronóstico y eventualmente con la elaboración de protocolos de tratamiento diferenciados para estos subgrupos de LA (AU)

The majority of childhood acute leukemias (AL) can be classified as lymphoblastic (mainly phenotype B or T) or myeloblastic, depending on the cell lineage of the blasts, requiring specific treatment according to this characterization. Immunotypification of AL is based on surface and/or intracytoplasmic antigen expression with lymhoid (B or T) or myeloide (My) blast differentiation, allowing definition of cell lineage and classification of the AL according to the grade of maturation. Nevertheless, there are rare cases of AL that are difficult to classify, denominated AL of ambiguous lineage (mixed/undifferentiated lineage) and acute dendritic cell leukemia. In AL of the mixed phenotype, the blasts express markers of more than one lineage and in undifferentiated AL, the blasts lack antigen expression of any specific lineage. Different conventions have tried to define and classify these unusual phenotypes, among which the most recent proposal of the World Health Organization (2008). According to the criteria of the latter, of 1301 cases of AL diagnosed between April 1994 and April 2009, 28 were re-classified as AL of ambiguous lineage, 3 as minimally differentiated acute myeloid leukemia, and 3 as acute dendritic cell leukemia. Characterization of these cases is important, as in the literature only sporadic reports of these rare phenotypes are found. Given the large number of patients with a long follow-up of the Garrahan Hospital, a review of these unusual cases allowed characterization from the point of view of the immunophenotype, morphology/cytochemistry, cytogenetics/molecular biology and to evaluate clinical presentation, evolution, response to treatment, and event-free survival to help define the prognosis and develop protocols for the treatment of these subgroups of AL (AU)

Occurrence of four-spined Gasterosteus aculeatus in an isolated Croatian river population.

An isolated population of the three-spined stickleback Gasterosteus aculeatus in Croatia was found to have a high incidence of specimens either having a fourth dorsal spine or showing remnants of a fourth spine. Juvenile individuals showed a 9.4% incidence of a fourth spine. The population was examined for asymmetry of the skeletal defensive complex in order to determine whether the additional spine could be the result of developmental instability, a response to predation or environmental conditions.

Primary malignant myoepithelioma of the distal femur.

A 55-year-old male presented with a 1-month history of localized pain caused by an osteolytic and destructive lesion in the right distal femur. Histologically, the tumour consisted of spindle cells intermingled with epithelioid eosinophilic cells arranged in small cords embedded in a hyalinized-to-chondromyxoid stroma. Electron microscopy and immunohistochemistry showed features of myoepithelial differentiation. RT-PCR failed to demonstrate chimeric transcripts of extraskeletal myxoid chondrosarcoma. The final diagnosis was primary malignant myoepithelioma of bone. The patient is alive with lung metastases 13 months after surgery. Primary malignant myoepithelioma of bone is an exceptionally rare neoplasm that should be considered in the differential diagnosis with the more aggressive myxoid spindle cell sarcomas.

Molecular alterations of monophasic synovial sarcoma: loss of chromosome 3p does not alter RASSF1 and MLH1 transcriptional activity.

Differential diagnosis of monophasic synovial sarcoma requires the detection of specific biological markers. In this study we evaluated the presence of molecular alterations in 15 monophasic synovial sarcomas. Multiple changes affecting chromosome arms were detected by CGH-array in all microdissected cases available, and an association between gain or loss of specific regions harbouring cancer progression-associated genes and aneuploid status was found. The most frequent alteration was loss of 3p including 3p21.3-p23 region that, however, did not involve the promoter regions of the corresponding genes, RASSF1 and MLH1. Using Real-Time PCR, mRNA levels of both resulted moderately high compared to normal tissue; however, the weak to absent protein expression suggests RASSF1 and MLH1 post-transcription deregulation. Moreover, immunohistochemical analysis revealed that both mesenchymal and epithelial antigens were present in diploid tumours. These findings confirm the genetic complexity of monophasic synovial sarcoma and underline the need to integrate different analyses for a better knowledge of this tumour, essential to investigate new diagnostic and prognostic markers.

Histochemical and ultrastructural study of an elastofibroma dorsi coexisting with a high grade spindle cell sarcoma.

Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.

Tissue and serum loss of metalloproteinase inhibitors in high grade soft tissue sarcomas.

The activity of matrix metalloproteinases (MMPs) in degrading extracellular matrix is controlled by activation of pro-enzymes and inhibition of MMP tissue inhibitors (TIMPs). To assess proteolytic cascade imbalance in malignancy progression, the enzymatic activity of MMP2 and MMP9 and the expression and serum level of their inhibitors, TIMP2 and TIMP1 respectively, was evaluated in selected patients with high-risk soft tissue sarcoma (STS). Gelatinase activity and inhibitor expression was evaluated on 69 biopsies by zymography and immunohistochemistry. TIMP1 and TIMP2 serum concentration was tested in 53 STS patients and in 56 controls using a sandwich enzyme immunoassay. Clinical and biological variables were related to clinical outcome of the patients. A significant gelatinolytic activity was seen in a high percentage of STS. TIMP expression was weak or negative in the majority of samples. The difference between disease-free (p=0.001) and overall survival (p=0.007) curves based on TIMP2 immunoreactivity was statistically significant. TIMP plasma concentration of 53 STS revealed significantly lower levels compared to those of 56 controls (p=0.0001). In conclusion, low levels of negative regulators of proteolysis may be related to tumor biological aggressiveness and used to select patients with poor prognosis to improve cure.

Elastofibroma associated with high grade leiomyosarcoma of the soft tissues: a light and ultrastructural study of one case.

Elastofibroma is a benign lesion occurring almost exclusively in the chest wall, parascapular region being the most frequent site. Rare lesions have been reported in other anatomic locations, but there are no reports about the co-existence of an elastofibroma with a malignant sarcoma. The purpose of the authors is to describe histologically and ultrastructurally the synchronous detection of an elastofibroma and a high grade leiomyosarcoma, speculating on eventual links between the two pathological states.

Sequence comparison and phylogenetic analysis of fish nodaviruses based on the coat protein gene.

We have amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced a 605-bp fragment covering the variable region of the coat protein gene of fish nodaviruses infecting European sea bass, Dicentrarchus labrax (n = 24), and shi drum, Umbrina cirrosa (n = 2), in the Mediterranean basin. Nine new isolates were identified and their sequences were combined with sequences in the literature to produce three different data sets. The first set, based on amino acid sequences, was used to verify the monophyly of fish nodaviruses. The second and third data sets, based on nucleic acids, were used to resolve the phylogenetic relationships between closely related fish nodaviruses. Phylogenetic analyses were performed according to the maximum parsimony and neighbor-joining methods. Our results support the monophyly of fish nodaviruses. Moreover, they confirm the subdivision of fish nodaviruses into four main clusters, in agreement with the previously suggested phylogeny of the genus Piscinodavirus, that was based on a smaller number of sequences and an alternative phylogenetic approach [14]. All the Mediterranean isolates were clustered in the group of the red-spotted grouper nervous necrosis virus and appear to have a restricted geographic distribution, except for one sequence-type (10 samples) that is widespread throughout the basin.

Cellular schwannoma: a benign neoplasm sometimes overdiagnosed as sarcoma.

A case of cellular schwannoma originating in the left lumbar paraspinal region is described. The diagnosis was originally made on needle biopsy material. The histological examination is usually not sufficient to correctly diagnose this benign neoplasm. Bone erosion, neurological symptoms, caused by compression of the spinal roots, together with hypercellularity, pleomorphism and an occasional increase in mitotic activity, may lead to an erroneous diagnosis of malignancy. Immunohistochemistry and ultrastructural analysis are helpful in confirming the diagnosis. The recognition of this entity avoids unnecessary overtreatment of these patients.

DNA analysis with flow cytometry and image cytometry in colorectal polyps.

Ploidy was studied with flow and image cytometry in 51 polyps removed endoscopically from 44 patients. Evaluation was carried out on frozen material in 34 cases and on material fixed in formalin and embedded in paraffin in the remaining 17. Data analysis showed a statistically significant correlation between polyp size and aneuploidy frequency (P > 0.05). No statistically significant correlation was found between aneuploidy frequency and histological type. The linear correlation study did, however, show a correlation tendency between histological type and aneuploidy (R = 0.42211).