Characterization and distribution of Teredinidae assemblage in an estuary in Ceará, Brazil's Northeast.

Teredinids are bivalves mollusks considered the most abundant of invertebrates group of marine wood borers performing an important role in the mangrove environment. This study aimed to characterize the Teredinidae species from the Acaraú River estuary in Ceará and analyse the relationship between the mangrove plant structure and the distribution of Teredinidae, according to gradients estuaries: vertical (flooding) and horizontal (salinity). The collection of mangrove logs with Teredinidae happened in three places within the estuary (inner, median, and upper); in each area, three transects were traced in which three plots were lined off, and a total of 40 logs were collected. Teredinidae species were found and identified: Nausitora fusticula; Neoteredo reynei; Teredo turnerae; Teredo cf. bartschi; Bankia bipennata; Bankia gouldi; Lirodus massa and Lyrodus cf. bipartitus. The Lyrodus cf. bipartitus, Bankia gouldi, and Teredo cf. bartschi species were registered for the first time in Ceará. The distribution and species richness of Teredinidae were directly related to the vertical gradient (flooding) and heterogeneity of the mangrove forest habitat. The data presented here are essential for comprehending the mechanisms responsible for the distribution patterns of the Teredinidae species in the mangrove, contributing to biodiversity conservation in Ceará coastal zones.

Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?

X-linked inhibitor of apoptosis protein (XIAP) finely tunes the balance between survival and death to control homeostasis. XIAP is found aberrantly expressed in cancer, which has been shown to promote resistance to therapy-induced apoptosis and confer poor outcome. Despite its predominant cytoplasmic localization in human tissues, growing evidence implicates the expression of XIAP in other subcellular compartments in sustaining cancer hallmarks. Herein, we review our current knowledge on the prognostic role of XIAP localization and discuss molecular mechanisms underlying differential biological functions played in each compartment. The comprehension of XIAP subcellular shuttling and functional dynamics might provide the rationale for future anticancer therapeutics.

Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo.

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430-450 nm in the ultraviolet-visible (UV-Vis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FT-IR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm-1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.

Genomic variation at the MDR1 promoter and P-glycoprotein expression and activity in AML patients.

Sequence variation at the proximal MDR1 promoter of 72 patients with acute myeloid leukemia (AML) was investigated and its association with P-glycoprotein (Pgp) expression and activity using flow cytometry were analyzed. Two variants were found: -129T/C and a non-described A/T substitution at position +68 of intron 1 in one patient. Three different genotypes were identified for single nucleotide polymorphism (SNP) -129T/C: 60 patients TT, 11 individuals TC, and 1 CC. No significant association was found between SNP variants and Pgp activity and expression, at protein level. Our data also suggested that an evaluation of MDR1 promoter polymorphisms is of uncertain prognostic value.

Rosai-Dorfman disease: a report of eight cases in a tertiary care center and a review of the literature.

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats.

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150-180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Occurrence of Neospora caninum and Toxoplasma gondii DNA in brain tissue from hoary foxes (Pseudalopex vetulus) in Brazil.

The hoary fox (Pseudalopex vetulus) is a wild canid native to Brazil and is commonly found in the semiarid northeastern area living in contact with cattle. The main purpose of this study was to investigate the presence of Neospora caninum and Toxoplasma gondii DNA in hoary foxes, in the state of Paraíba, Brazil. Brain tissue samples were collected from 49 hoary foxes. From the samples, DNA extraction and the polymerase chain reaction (PCR) were performed using specific primers for N. caninum and T. gondii. The prevalences found were 14.3% (7/49) for T. gondii and 12.2% (6/49) for N. caninum. The molecular identities of the amplified products were confirmed by means of the sequencing reaction. This study demonstrated the presence of N. caninum and T. gondii DNA in free-ranging hoary foxes in Brazil for the first time, thus confirming that this species is an intermediate host.

Heparin reverses Rhodamine 123 extrusion by multidrug resistant cells.

The effect of heparin as a reversing agent of multidrug resistance (MDR) was tested on normal mononuclear cells from 24 healthy volunteers and leukaemic cells from 12 acute myeloid leukaemia, five chronic myeloid leukaemia, five acute lymphoid leukaemia and three chronic lymphoid leukaemia patients. Two cell lines were used as controls, the human erythroleukaemia K562 and its vincristine-resistant derivative K562-Lucena 1. Heparin was not cytotoxic by itself as determined using a MTT assay and cell counts. MDR modulation was assessed by Rhodamine 123 extrusion using flow-cytometry. Modulation of the resistant cell line was produced by the classical reversing agent verapamil and also by heparin, the same being observed in normal and leukaemic cells and being independent of the type of leukaemia. Our work suggests that heparin may be considered a potential MDR modulator.

Clinical approach to circumvention of multidrug resistance in refractory leukemic patients: association of cyclosporin A with etoposide.

Alternative therapy for refractory leukemic patients is being increasingly adopted. Circumvention of multidrug resistance represents a strategy that has been taken into account when conventional chemotherapy failed. In this work a group of 15 refractory, heavily pretreated, patients was enrolled in a circumvention protocol including etoposide (ETO) and cyclosporin A (CSA). All patients received etoposide prior to this schedule. Toxicity to circumvention protocol was acceptable and only one serious side-effect was observed. Two hematological clinical responses were seen, both of which were positive to P-glycoprotein immunostaining and exhibited in vitro modulation by CSA in cultures using the thymidine incorporation assay. Three out of four patients negative for P-glycoprotein achieved a minor response. Three out of six clinical failures were also negative for Pgp immunostaining one of which exhibited sinergistic effect between ETO and CSA. Our study suggests that hematological response to ETO and CSA association can be obtained in intensely pretreated leukemic patients. Several factors may affect the response such as clinical status before this therapy. Additionally, it also suggests that not all CSA effects on the combination ETO-CSA can be attributed to Pgp modulation.

Sensitivity of vincristine-sensitive K562 and vincristine-resistant K562-Lucena 1 cells to anthracyclines and reversal of multidrug resistance.

The phenomenon of multidrug resistance (MDR), that involves the efflux pump P-glycoprotein, can be reversed by a number of substances known as MDR modulators or reversing agents. In the present study we investigated the action of three anthracyclines, mitoxantrone and vincristine on short-term (72 h) cultures using 2 methods ([3H] incorporation and MTT (3-[4,5-dimethylthiasol-2-yl]-2,5-diphenyltetrazolium bromide)), on 2 cell lines: K562, a human erythroleukemia, and a vincristine-resistant subline K562-Lucena 1. Using the same culture methods plus flow cytometry analysis, the reversing potentials of cyclosporin A and verapamil were studied in both cell lines. There were differences in the sensitivity and resistance profiles of the two lines to the various drugs but daunorubicin (5 micrograms/ml) and idarubicin (0.035 micrograms/ml) were the most effective when each was used in high concentration. Cyclosporine at 200 ng/ml and verapamil at 5 micrograms/ml reversed MDR in the resistant line, and had a synergistic action with chemotherapeutic agents on the sensitive line. Again differences were demonstrable between combinations of the various drugs and reversal was only clearly shown with the method measuring cell proliferation ([3H] incorporation) but not by the method measuring metabolic activity (MTT). The efflux of rhodamine-123 mimics the functional activity of the pump and cyclosporine was a better reversing agent by this criteria. These data show that the results obtained in in vitro studies attempting to identify treatments for different types of leukemias depend to a large extent on the methods used to measure cell response.

p53 gene analysis in childhood B non-Hodgkin's lymphoma.

CONTEXT: Mutations or deletions in the tumor-suppressor gene p53 are among the commonest genetic changes found in human neoplasms including breast, lung and bowel cancers. In hematological malignancies, p53 is most often mutated in Burkitt's lymphoma, with p53 mutations present in 30 to 40% of tumor samples and in 70% of cell lines. OBJECTIVE: To analyze the p53 gene alterations in child patients with B non-Hodgkin's lymphoma. DESIGN: Descriptive study. SETTING: Tertiary oncology care center. PARTICIPANTS: The study investigated 12 patients with childhood B non-Hodgkin's lymphoma (Burkitt's lymphoma). Screening for p53 mutations was done by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of exon 5 to 8/9 of the gene. RESULTS: Abnormal polymerase chain reaction-single strand conformational polymorphism migration pattern was observed in 4 patients (33.3%), one on exon 6 and three on exon 7. Positive cases included 2 patients who died from disease. CONCLUSION: These preliminary results suggest that p53 mutations are quite frequent in children with Burkitt's lymphoma and may play a role in lymphoma genesis or disease progression.

[Clinical significance of multidrug resistance in acute leukemias]. / Importância clínica da resistência a múltiplas drogas nas leucemias agudas.

A significant number of patients with acute leukaemias fail in their treatment as a result of the development of resistance to chemotherapy. Several evidences indicate that the expression of a mdr 1 gen, which codifies for P glycoprotein (PgP), contributes to this resistance in leukaemic cells. PgP functions as an energy-dependent efflux pump transporting a variety of unrelated drugs to the outside of the cells. It is possible to modulate this efflux using a number of drugs known as multidrug resistance (MDR) reversors or modulating agents. The present paper discusses some of the methods used for detecting the MDR phenotype, although the most reliable results are the ones that take into account an association of various methods. Despite the existence of disagreements regarding which method presents the greatest sensitivity or specificity the majority of authors agrees that the MDR phenotype, in isolation, affects the prognosis of leukaemias. The, coexpression of PgP with the molecule CD34 confers the worst prognosis in acute leukaemias. The authors demonstrate using cell cultures testing chemotherapeutic agents, alone or associated to modulating agents, that this line of research may allow in the future to elaborate an individualized clinical treatment. They emphasize the necessity of integration between haematologists and basic research as this may lead to a new therapeutic option for refractory patients to conventional treatment.

Reproductive cycle and embryonic development of the gastropod Melampus coffeus (Linnaeus, 1758) (Ellobiidae) in the Brazilian Northeast.

Melampus coffeus belongs to a primitive group of pulmonate mollusks found mainly in the upper levels of the marine intertidal zone. They are common in the neotropical mangroves. Little is known about the biology of this species, particularly about its reproduction. The aim of this study was to 1) characterize the morphology and histology of M. coffeus' gonad; 2) describe the main gametogenesis events and link them to a range of maturity stages; 3) chronologically evaluate the frequency of the different maturity stages and their relation to environmental factors such as water, air and sediment temperatures, relative humidity, salinity and rainfall; and 4) characterize M. coffeus' spawning, eggs and newly hatched veliger larvae. Samples were collected monthly between February, 2007 and January, 2009 from the mangroves of Praia de Arpoeiras, Acaraú County, State of Ceará, northeastern Brazil. The characterization of the gonad development stages was carried out using routine histological techniques. The results of this study show that Melampus coffeus is a simultaneous hermaphrodite. The follicles have masculine and feminine elements, interleaved within the gonad. M. coffeus presents a well-defined synchronous reproductive cycle, showing successive maturation, release and resting periods. The average diameter of the oocytes was negatively correlated with salinity and positively correlated with rainfall. The results show that no reproductive activity occurs during periods of drought. After the dry season, the increasing rainfall levels and reduced salinity lead to the appearance of very dense populations, predominantly composed of small individuals.

Rosai-Dorfman disease: a report of eight cases in a tertiary care center and a review of the literature

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

LASSBio-881: an N-acylhydrazone transient receptor potential vanilloid subfamily type 1 antagonist orally effective against the hypernociception induced by capsaicin or partial sciatic ligation.

BACKGROUND AND PURPOSE: Compound LASSBio-881 is an orally effective antinociceptive that binds to cannabinoid receptors and is active mainly on the neurogenic component of pain models. We investigated whether transient receptor potential vanilloid subfamily type 1 (TRPV1) channels are involved in the effects of LASSBio-881. EXPERIMENTAL APPROACH: Modulation of capsaicin (CAP)- and low pH-induced currents was evaluated in TRPV1-expressing Xenopus oocytes. In vivo effects were evaluated in CAP-induced acute and inflammatory changes in nociception, as well as in partial sciatic ligation-induced thermal hypernociception. KEY RESULTS: LASSBio-881 inhibited TRPV1 currents elicited by CAP with an IC(50) of 14 microM, and inhibited proton-gated currents by 70% at 20 microM. Functional interaction with CAP was surmountable. Locally applied LASSBio-881 decreased time spent in CAP-elicited nocifensive behaviour by 30%, and given orally it reduced measures of CAP- or carrageenan-evoked thermal hypernociception by 60 and 40% respectively. In addition, LASSBio-881 decreased the paw withdrawal responses to thermal stimuli of animals with sciatic neuropathy 7-11 days after nerve ligation, at a dose of 300 micromol*kg(-1)*day(-1) p.o. At this dose, hyperthermia was not observed within 4 h following oral administration. CONCLUSIONS AND IMPLICATIONS: LASSBio-881 is a TRPV1 antagonist that apparently competes with CAP. Accordingly, LASSBio- 881 inhibited nociception in models of acute, inflammatory and neuropathic pain presumed to involve TRPV1 signalling. These in vivo actions were not hindered by hyperthermia, a common side effect of other TRPV1 antagonists. We propose that the antinociceptive properties of LASSBio-881 are due to TRPV1 antagonism, although other molecular interactions may contribute to the effects of this multi-target drug candidate.

Digestibilidade do cálcio de ingredientes para suínos, avaliada por meio de dois métodos / Calcium digestibility from feedstuffs for pigs evaluated using two methods

Determinaram-se os coeficientes de digestibilidade aparente e verdadeira do cálcio (Ca) de ingredientes para suínos por meio de dois métodos. Foram utilizados 60 suínos machos castrados, alojados em gaiolas de metabolismo e distribuídos em delineamento experimental inteiramente ao acaso, em arranjo fatorial 2 x 10 (métodos x tratamentos) e seis repetições por tratamento. Os tratamentos consistiram em oito alimentos, uma ração basal (0,072% de Ca total) e uma ração com baixo teor de Ca (0,018%). Os coeficientes de digestibilidade aparente e verdadeira do Ca foram avaliados utilizando-se simultaneamente dois métodos: coleta total de fezes e coleta de fezes com indicador fecal (cinza ácida insolúvel - CAI). Os coeficientes de digestibilidade verdadeira do Ca, obtidos pelo método de coleta total e pelo método de indicador fecal, foram, respectivamente: calcário calcítico 1, 84,80 e 87,33%; calcário calcítico 2, 84,19 e 86,32%; fosfato bicálcico, 79,36 e 84,55%; fosfato monobicálcico, 83,83 e 85,81%; calcário dolomítico, 85,65 e 87,39%; farinha de carne e ossos (40% PB), 70,00 e 68,64%; farinha de carne e ossos (50% PB), 66,92 e 68,03%; farinha de vísceras, 73,40 e 73,95%, lactato de Ca, 95,10 e 97,33%. Não houve diferença significativa (P>0,05) entre os métodos avaliados coleta total (80,14%) e indicador fecal (82,15%)...

The coefficients of apparent and true digestibility of calcium (Ca) of eight feedstuffs for pigs were determined. A total of 60 barrows were housed in metabolism cages and distributed in a completely randomized design in a factorial 2 X 10 (treatments X methods) and 6 replicates per treatment. Treatments consisted of eight feedstuffs, a basal diet (0.072% Ca) and a diet with low Ca content (0.018%). The coefficients of apparent and true digestibility of Ca were determined using two methods simultaneously: total fecal collection and fecal marker (Acid Insoluble Ash - AIA). The true digestibility coefficients of Ca, obtained by the total fecal collection and the fecal marker methods were respectively: Limestone 1, 84.80 and 87.33%; Limestone 2, 84.19% and 86.32; Dicalcium Phosphate, 79.36 and 84.55%; Monodicalcium Phosphate, 83.83 and 85.81%, Dolomitic Limestone, 87.39% and 85.65; Meat and Bone Meal (40% CP), 70.00 and 68,64%; Meat and Bone Meal (50% CP), 66.92% and 68.03; Poultry by Product Meal, 73.40 and 73.95%, Calcium Lactate, 95.10 and 97.33%. There was no significant difference (P>0.05) between the total fecal collection (80.14%) and fecal marker (82.15%) with the methods evaluated...

Pomolic acid-induced apoptosis in cells from patients with chronic myeloid leukemia exhibiting different drug resistance profile.

Pomolic acid (PA) is a pentacyclic triterpene which has been previously described as active in inhibiting the growth of K562 cell line-originated from chronic myeloid leukemia (CML) in blast crisis-and its vincristine-resistant derivative K562-Lucena1. In this work, cells from CML patients were treated with PA and the apoptotic index was compared with the multidrug resistance (MDR) profile and clinical status of the patients. Our findings show that PA 12.5 microg/ml at 24 h (p = 0.000), at 48 h (p = 0.012) and at 72 h (p = 0.005) has a potent apoptotic index in CML cells as compared to mononuclear cells from healthy donors. PA was capable to induce apoptosis in cells from CML patients exhibiting functional MDR phenotype but not in P-glycoprotein expression. In addition, PA was effective in chronic as well as in blast phase of CML. Moreover, similar apoptotic index induced by PA was observed in low, intermediate and high-risk Sokal score as well as in samples from the group of patients with clinical resistance to interferon and/or imatinib and non-treated patients. These results suggest that PA may be an effective agent for the treatment of CML.

Retinoblastoma-related geneRb2/p130 are rarely mutated in Burkitt's lymphoma from Brazil.

It has been suggested that alterations of cell cycle genes probably contribute to the pathogenesis of endemic Burkitt's lymphoma (BL) in addition to c-MYC translocation. Mutations disrupting the normal nuclear localization signal of the retinoblastoma-related gene Rb2/p130 have been documented in BL cell lines and primary tumors from endemic areas. The aim of this study was to investigate the involvement of Rb2/p130 gene in the pathogenesis of sporadic BL in Brazil. DNA samples from 26 pediatric BL tumors and two healthy blood donors were screened by PCR amplification followed by single strand conformation polymorphism analysis of exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus), where most of the point mutations in the Rb2/p130 gene were identified. No abnormal band shifts were present in the samples analyzed. We concluded that mutations in exons 19-22 of the Rb2/p130 are unlikely to be involved directly in the pathogenesis of sporadic Brazilian BL.