Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.     

Rice varieties with similar amylose content differ in starch digestibility and glycemic response in humans

Three high-amylose rice varieties, IR42, IR36, and IR62, with similar chemical composition including amylose content (26.7-27.0%), were cooked under the same conditions and tested for in vitro digestibility as well as blood glucose and insulin responses in healthy human volunteers. The starch-digestion rate and the glycemic and insulin responses were the highest in IR42, followed by IR36 and, then IR62. The differences were not due to unabsorbed carbohydrate but were related to their physicochemical properties, such as gelatinization temperature, minimum cooking time, amylograph consistency, and volume expansion upon cooking. When the three varieties were cooked for their minimum cooking time, they had the same degree of gelatinization and their starch-digestion rates and glycemic responses were similar. We conclude that amylose content alone is not a good predictor of starch-digestion rate or glycemic response. Rice varieties with similar high-amylose contents can differ in physicochemical (gelatinization) properties and this, in turn, can influence starch digestibility and blood glucose response.     

1,2,3-triazolo[4,5-f]quinolines. II. Preparation and antimicrobial evaluation of 6-ethyl-6,9-dihydro-1(2)(3)-R-1(2) (3)H-triazolo [4,5-f]quinolin-9-one-8-carboxylic acids as anti-infectives of the urinary tract (1)

Some 6-ethyl-1(2)(3)-R-1(2)(3)H-triazolo[4,5-f]quinolin-9-one-8-carboxy lic acids were prepared as novel analogues of oxolinic acid in order to evaluate the effect on antibacterial activity of the isosteric replacement of the dioxolic moiety with the triazole ring substituted in position 1 or 2. In vitro tests showed a good and selective activity against Escherichia coli (MIC 12.5 micrograms/ml) of compound (XVI).     

Hantaviruses in Central South America: phylogenetic analysis of the S segment from HPS cases in Paraná, Brazil

We sequenced the complete S segments of hantaviruses detected from 12 HPS patients living in southern of Brazil. Samples were obtained from patients diagnosed in different years, in distinct areas, and with a broad spectrum of clinical signs. Despite these differences, all the S proteins of hantavirus from Paraná were identical, except for one amino acid substitution. Phylogenetic analyses of the complete S segment nucleotide and amino acid sequences indicated that hantaviruses from Paraná form a distinct clade from those circulating in South and North America. Other hantaviruses from Brazil were not placed in the same clade. The Oligoryzomys nigripes-associated strains ITA37 and ITA38 from Paraguay were found to belong to the same clade as the hantaviruses from Paraná. Paraguay and Paraná state are located at the same latitude and some ecosystems are similar in both places. The geographic position and common rodent hosts could explain this phylogenetic relationship.     

Anatomic study of the tricuspid valve in children

We performed an anatomic study of the right atrioventricular valve in children under one year of age using a conservative method of dissection of the heart valve. The main aspects studied were the number of cusps and their morphometric characteristics, such as the width of the base and the depth of the cusps. Other parameters studied were the number of papillary muscles, number of tendinous cords, and diameter of the fibrous ring and the last one were divided in three regions, anterior, posterior and septal for localization of cusps. Our results showed that the number of cusps varied from two to four. Three cusps was the commonest finding and the fourth cusp, if present, was classified as anterolateral in location. The anterior and septal cusps had bases bigger than those of the posterior and anterolateral cusps; the septal cusp was deeper than the others; and the number of tendinous cords was greater for the anterior and septal cusps than for the posterior and anterolateral cusps. In addition, the posterior region showed great variability: in 35.7% it was occupied by undeveloped valve tissue and the posterior valve in these cases was located anteriorly.     

Cysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitors

Cysteine-proteinases from parasitic protozoa have been recently characterized as factors of virulence and pathogenicity in several human and veterinary diseases. In Chagas' disease, the chronic infection caused by Trypanosoma cruzi, structure-functional studies on cysteine proteases were thus far limited to the parasite's major isoform, a cathepsin L-like lysosomal protease designated as cruzipain, cruzain or GP57/51. Encoded by a large gene family, cruzipain is efficiently targeted by synthetic inhibitors, which prevent parasite intracellular growth and differentiation. We have previously demonstrated that the multicopy cruzipain gene family includes polymorphic sequences, which could encode functionally different isoforms. We report here a comparative kinetic study between cruzain, the archetype of the cruzipain family, and an isoform, termed cruzipain 2, which is expressed preferentially by the mammalian stages of T. cruzi. Heterologous expression of the catalytic domain of cruzipain 2 in Saccharomyces cerevisae yielded an enzyme that differs markedly from cruzain with respect to pH stability, substrate specificity and sensitivity to inhibition by natural and synthetic inhibitors of cysteine proteases. We suggest that the structural-functional diversification imparted by genetic polymorphism of cruzipain genes may have contributed to T. cruzi adaptation to vertebrate hosts.     

Acute respiratory infection by human metapneumovirus in children in southern Brazil.

BACKGROUND: Human metapneumovirus (hMPV) has been described as an etiologic agent of acute respiratory infections (ARI), mainly in pediatric patients. Viral isolation is difficult and has low sensitivity, and consequently RT-PCR assays are currently used for detection. OBJECTIVES: Detect hMPV in ARI in hospitalized children in Southern Brazil; standardize a RT-PCR for routine hMPV diagnosis; validate a positive control for molecular tests; and perform phylogenetics analyses. STUDY DESIGN: Nasopharyngeal aspirates (NPA) from 156 hospitalized children were studied. A conserved region of the nucleoprotein gene was cloned, characterized and used to standardize an RT-PCR assay. Phylogenetic analyses were performed. Clinical data were obtained from medical records. RESULTS: hMPV was detected in 6.4% of the samples. Dyspnea and wheezing were frequently reported symptoms and the most common diagnoses were bronchiolitis, acute respiratory insufficiency or laryngotracheobronchitis. Nucleotide sequence alignment revealed 97.7% identity with genotype A1 of hMPV. The detection limit of hMPV genomes by RT-PCR in clinical samples was 180 copies/microL. CONCLUSION: This is the first report of the detection and genetic characterization of hMPV infections in children with lower ARI in Southern Brazil.     

A combined 2-deoxyglucose and neurophysiological study of primate somatosensory cortex

The metabolic activity pattern produced in the primary somatosensory cortex (SI) of primates by repetitive delivery of a tactile stimulus is distinctly patchy. The functional significance of these patches, however, remains obscure. This investigation sought to determine the correlation between neural and metabolic activity produced by tactile stimuli and to evaluate the relationship, if any, between the neural activity and metabolic patches evoked by similar stimuli. Experiments were undertaken in which extracellular microelectrode recordings were carried out in animals that subsequently underwent a 2-deoxyglucose (2DG) study. Three types of relations were identified. First, the receptive fields (RF) and modality properties of neurons sampled in locations at which patches of metabolic label were found matched the "place" and "modal" properties of the stimulus used to produce 2DG labeling. Second, in cortical locations where the RF and modality properties of the sampled neurons differed from either the place or modal properties of the stimulus used to evoke the 2DG label, no above-background increases in metabolic labeling were found. Finally, in some cortical locations at which the receptive field and modality properties of the neurons matched those of the 2-deoxyglucose mapping stimulus, no above-background increases in metabolic labeling were found. This outcome leads us to suggest that moment-to-moment changes in neural responsivity, which might remain undetected by conventional receptive field mapping methods, contribute to the patchy pattern of metabolic activity visualized by the 2-deoxyglucose method.     

Mechanism of the selective toxicity of amphotericin B incorporated into liposomes

Previously, it has been shown that incorporation of the membrane channel-forming polyene antibiotic, amphotericin B (AMB), into liposomes composed of dimyristoyl phosphatidylcholine/dimyristoyl phosphatidylglycerol (7:3 ratio) results in reduced drug toxicity to animals with full retention of therapeutic activity against systemic fungal infections. In this report we explore the cellular and biochemical bases of the enhanced therapeutic index of liposomal amphotericin B (L-AMB). AMB and L-AMB are equally potent and both promptly induce rapid cation efflux from Candida albicans cells. By contrast, AMB, but not L-AMB, induces cation efflux and cell lysis in mammalian erythrocytes, demonstrating the selectivity of L-AMB at the cellular level. The characteristics of the lipid of the erythrocyte membrane seem to be the most important determinant of cellular sensitivity, since AMB, but not L-AMB, induces cation release from large unilamellar liposomes composed of red cell membrane lipids, thus paralleling the observations on intact cells. The ability of L-AMB to induce cation release and cause toxicity to erythrocytes, however, can be modulated by changing the lipid composition of the liposome carrier. Thus, AMB-containing liposomes composed of phospholipids with saturated acyl chains are nontoxic, whereas AMB liposomes composed of phospholipids containing unsaturated acyl chains are almost as toxic as AMB itself. The acyl chain composition rather than the head group composition seems most important, although substitution of anionic phosphatidylglycerols for phosphatidylcholines contributes somewhat to the protective effect. Analysis of several types of liposomes containing AMB at concentrations up to 5 mol %, using electron paramagnetic resonance and freeze fracture electron microscopy, shows that the drug is incorporated in the lipid bilayer but produces only modest disruptive effects on bilayer structure. Current results are interpreted in terms of a selective transfer of AMB from "donor" liposomes to "target" cell membranes. The transfer process probably occurs by diffusion of AMB through the solvent but is regulated by the physical properties of both donor and target membranes.