Evaluation of chromosomal abnormalities by cIg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

Effects of a cyanobacterial extract containing-anatoxin-a(s) on the cardiac rhythm of Leurolestes circunvagans

This work presents the effects of an anatoxin-a(s)-containing extract on a cockroach semi-isolated heart preparation and the results supporting the extract s biological activity on acetylcholinesterase (purified from ell). The presence of the toxin in cyanobacterial strains Anabaena spiroides (ITEP-024, ITEP-025 and ITEP-026) isolated from the Tapacurá reservoir in Pernambuco, Brazil, was confirmed by means of liquid chromatography coupled to an ion-trap mass spectrometer. The anticholinesterase activity was assessed biochemically by the Ellman test and was confirmed by measuring the cockroach s heart rate. The concentration of the extract containing the tested anatoxin-a(s) (antx-a(s)) (10, 16 and 100 μg.μL-1) inhibited the eel acetylcholinesterase (AChE) by more than 90%. The cockroach cardiac frequency increased by a maximum of about 20% within 29 min after the addition of 2.5x10³ μg of extract containing antxa (s).g-1 bw (n=9, p<0.05). Our results strongly indicate that antx-a(s) is capable of exerting biological effects on cockroach, indicating that more research might be conducted to determine its role in the environment, especially on insects.

Adaptação e validação do Cardiac Patients Learnings Needs Inventory para pacientes brasileiros

OBJETIVOS: Adaptar culturalmente o Cardiac Patients'Leaning Needs Inventory para uso no Brasil e testar sua confiabilidade (consistência interna e estabilidade) em pacientes brasileiros com doença arterial coronariana. MÉTODOS: Participaram do estudo 65 pacientes com infarto agudo do miocárdio, internados em um hospital público do interior do Estado de São Paulo. Para a coleta dos dados, foram utilizados um instrumento para caracterização sociodemográfica e a versão em português do Cardiac Patients Leaning Needs Inventory. A consistência interna foi estimada com base no alfa de Cronbach. A estabilidade foi medida apoiada no teste-reteste e calculada pelo teste t de Student. O nível de significância adotado foi 0,05. RESULTADOS: Identificou-se consistência interna alta (0,96 na primeira medida e 0,78 na segunda). O domínio que apresentou melhor consistência interna foi Fatores de Risco (α= 0,91). CONCLUSÃO: A versão adaptada manteve as equivalências conceituais, semânticas e idiomáticas da versão original e apresentou confiabilidade e estabilidade adequadas.

Nuclear abnormalities in erythrocytes and morphometric indexes in the catfish Cathorops spixii (Ariidae) from different sites on the southeastern Brazilian coast

Nuclear abnormalities in erythrocytes (NAE) were taken as biomarkers in the catfish Cathorops spixii (Ariidae) sampled in an estuary little affected by human activity (Cananéia) and in three regions (Santos Channel: SC, Santos Bay: SB and São Vicente Channel: SVC) of the Santos-São Vicente estuary impacted by various anthropogenic activities. Increases in NAE were observed in fish from SC and SVC sampled in the summer period as compared with specimens from the Cananéia estuary. These results suggest the presence of genotoxic compounds in these regions. However, the absence of significant differences in micronuclei frequency reflects slight mutagenic effects in these individuals. It is possible that the lower NAE frequency in specimens from SB might be associated with the greater remobilization and dilution of chemicals in this region. The low frequency of NAE in C. spixii from the Cananéia estuary is in accordance with the slight anthropogenic influence in this system, and may be suggestive of the absence of genotoxic and mutagenic effects in these organisms.

Cardiac markers: profile in rats experimentally infected with Toxocara canis

The aim of this study was to evaluate the profile of the enzymes creatine kinase (CK), creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) in Wistar rats infected with 250 (GI, n = 24) or 1000 (GII, n = 24) Toxocara canis eggs. Animals were evaluated on days 7, 15, 30, 60, 120 and 180 post-infection (DPI). Only the GI rats showed an increase in CK and CK-MB, at 15 and 30 DPI, respectively. Anti-Toxocara spp. antibodies were detected by ELISA in infected animals. Despite of the presence of eosinophilic infiltrate in the heart of three infected animals, none larva was recovered from the organ neither by acid digestion nor by Baermann procedure. Eosinophilia was observed in both groups but there was no significant difference in the eosinophil counts between GI and GII (p = 0.2239). It is possible to consider that cardiac lesion is an eventual finding in murine model for toxocariasis.

Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing ventilator-associated pneumonia after cardiac surgery: an observational study

Abstract Background The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery. Methods This was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1. Results Thirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29). Conclusion Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.

Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction

BACKGROUND: Ischemia and reperfusion (IR) injury remains a major cause of morbidity and mortality and multiple molecular and cellular pathways have been implicated in this injury. We determined whether acute inhibition of excessive mitochondrial fission at the onset of reperfusion improves mitochondrial dysfunction and cardiac contractility postmyocardial infarction in rats. METHODS AND RESULTS: We used a selective inhibitor of the fission machinery, P110, which we have recently designed. P110 treatment inhibited the interaction of fission proteins Fis1/Drp1, decreased mitochondrial fission, and improved bioenergetics in three different rat models of IR, including primary cardiomyocytes, ex vivo heart model, and an in vivo myocardial infarction model. Drp1 transiently bound to the mitochondria following IR injury and P110 treatment blocked this Drp1 mitochondrial association. Compared with control treatment, P110 (1 μmol/L) decreased infarct size by 28 ± 2% and increased adenosine triphosphate levels by 70+1% after IR relative to control IR in the ex vivo model. Intraperitoneal injection of P110 (0.5 mg/kg) at the onset of reperfusion in an in vivo model resulted in improved mitochondrial oxygen consumption by 68% when measured 3 weeks after ischemic injury, improved cardiac fractional shortening by 35%, reduced mitochondrial H2O2 uncoupling state by 70%, and improved overall mitochondrial functions. CONCLUSIONS: Together, we show that excessive mitochondrial fission at reperfusion contributes to long-term cardiac dysfunction in rats and that acute inhibition of excessive mitochondrial fission at the onset of reperfusion is sufficient to result in long-term benefits as evidenced by inhibiting cardiac dysfunction 3 weeks after acute myocardial infarction.

MiRNA-208a and miRNA-208b are triggered in thyroid hormone-induced cardiac hypertrophy - role of type 1 Angiotensin II receptor (AT1R) on miRNA-208a/α-MHC modulation

Hyperthyroidism promotes cardiac hypertrophy and the Angiotensin type 1 receptor (AT1R) has been demonstrated to mediate part of this response. Recent studies have uncovered a potentially important role for the microRNAs (miRNAs) in the control of diverse aspects of cardiac function. Then, the objective of the present study was to investigate the action promoted by hyperthyroidism on β-MHC/miR-208b expression and on α-MHC/miR-208a expression, as well as the possible contribution of the AT1R in this event. The findings of this study confirmed that AT1R is a key mediator of the cardiac hypertrophy induced by hyperthyroidism. Additionally, we demonstrated that like β-MHC, miR-208b was down-regulated in the hyperthyroid group. Similarly, like the expression of its host gene, α-MHC, miR-208a expression was up-regulated in response to hyperthyroidism. Finally, our data suggest for the first time that AT1R mediates the hyperthyroidism-induced increase on cardiac miRNA-208a/α-MHC levels, while does not influence on the reduction of miRNA-208b/β-MHC levels.

Subcutaneous Tissue Thickness is an Independent Predictor of Image Noise in Cardiac CT

Background: Few data on the definition of simple robust parameters to predict image noise in cardiac computed tomography (CT) exist. Objectives: To evaluate the value of a simple measure of subcutaneous tissue as a predictor of image noise in cardiac CT. Methods: 86 patients underwent prospective ECG-gated coronary computed tomographic angiography (CTA) and coronary calcium scoring (CAC) with 120 kV and 150 mA. The image quality was objectively measured by the image noise in the aorta in the cardiac CTA, and low noise was defined as noise < 30HU. The chest anteroposterior diameter and lateral width, the image noise in the aorta and the skin-sternum (SS) thickness were measured as predictors of cardiac CTA noise. The association of the predictors and image noise was performed by using Pearson correlation. Results: The mean radiation dose was 3.5 ± 1.5 mSv. The mean image noise in CT was 36.3 ± 8.5 HU, and the mean image noise in non-contrast scan was 17.7 ± 4.4 HU. All predictors were independently associated with cardiac CTA noise. The best predictors were SS thickness, with a correlation of 0.70 (p < 0.001), and noise in the non-contrast images, with a correlation of 0.73 (p < 0.001). When evaluating the ability to predict low image noise, the areas under the ROC curve for the non-contrast noise and for the SS thickness were 0.837 and 0.864, respectively. Conclusion: Both SS thickness and CAC noise are simple accurate predictors of cardiac CTA image noise. Those parameters can be incorporated in standard CT protocols to adequately adjust radiation exposure.

M-protein is down-regulated in cardiac hypertrophy driven by thyroid hormone in rats

Although it is well known that the thyroid hormone (T3) is an important positive regulator of cardiac function over a short term and that it also promotes deleterious effects over a long term, the molecular mechanisms for such effects are not yet well understood. Because most alterations in cardiac function are associated with changes in sarcomeric machinery, the present work was undertaken to find novel sarcomeric hot spots driven by T3 in the heart. A microarray analysis indicated that the M-band is a major hot spot, and the structural sarcomeric gene coding for the M-protein is severely down-regulated by T3. Real-time quantitative PCR-based measurements confirmed that T3 (1, 5, 50, and 100 physiological doses for 2 days) sharply decreased the M-protein gene and protein expression in vivo in a dose-dependent manner. Furthermore, the M-protein gene expression was elevated 3.4-fold in hypothyroid rats. Accordingly, T3 was able to rapidly and strongly reduce the M-protein gene expression in neonatal cardiomyocytes. Deletions at the M-protein promoter and bioinformatics approach suggested an area responsive to T3, which was confirmed by chromatin immunoprecipitation assay. Functional assays in cultured neonatal cardiomyocytes revealed that depletion of M-protein (by small interfering RNA) drives a severe decrease in speed of contraction. Interestingly, mRNA and protein levels of other M-band components, myomesin and embryonic-heart myomesin, were not altered by T3. We concluded that the M-protein expression is strongly and rapidly repressed by T3 in cardiomyocytes, which represents an important aspect for the basis of T3-dependent sarcomeric deleterious effects in the heart.

Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer

[EN] To determine central and peripheral hemodynamic responses to upright leg cycling exercise, nine physically active men underwent measurements of arterial blood pressure and gases, as well as femoral and subclavian vein blood flows and gases during incremental exercise to exhaustion (Wmax). Cardiac output (CO) and leg blood flow (BF) increased in parallel with exercise intensity. In contrast, arm BF remained at 0.8 l/min during submaximal exercise, increasing to 1.2 +/- 0.2 l/min at maximal exercise (P < 0.05) when arm O(2) extraction reached 73 +/- 3%. The leg received a greater percentage of the CO with exercise intensity, reaching a value close to 70% at 64% of Wmax, which was maintained until exhaustion. The percentage of CO perfusing the trunk decreased with exercise intensity to 21% at Wmax, i.e., to approximately 5.5 l/min. For a given local Vo(2), leg vascular conductance (VC) was five- to sixfold higher than arm VC, despite marked hemoglobin deoxygenation in the subclavian vein. At peak exercise, arm VC was not significantly different than at rest. Leg Vo(2) represented approximately 84% of the whole body Vo(2) at intensities ranging from 38 to 100% of Wmax. Arm Vo(2) contributed between 7 and 10% to the whole body Vo(2). From 20 to 100% of Wmax, the trunk Vo(2) (including the gluteus muscles) represented between 14 and 15% of the whole body Vo(2). In summary, vasoconstrictor signals efficiently oppose the vasodilatory metabolites in the arms, suggesting that during whole body exercise in the upright position blood flow is differentially regulated in the upper and lower extremities.

Plasma volume expansion does not increase maximal cardiac output or VO2 max in lowlanders acclimatized to altitude

[EN] With altitude acclimatization, blood hemoglobin concentration increases while plasma volume (PV) and maximal cardiac output (Qmax) decrease. This investigation aimed to determine whether reduction of Qmax at altitude is due to low circulating blood volume (BV). Eight Danish lowlanders (3 females, 5 males: age 24.0 +/- 0.6 yr; mean +/- SE) performed submaximal and maximal exercise on a cycle ergometer after 9 wk at 5,260 m altitude (Mt. Chacaltaya, Bolivia). This was done first with BV resulting from acclimatization (BV = 5.40 +/- 0.39 liters) and again 2-4 days later, 1 h after PV expansion with 1 liter of 6% dextran 70 (BV = 6.32 +/- 0.34 liters). PV expansion had no effect on Qmax, maximal O2 consumption (VO2), and exercise capacity. Despite maximal systemic O2 transport being reduced 19% due to hemodilution after PV expansion, whole body VO2 was maintained by greater systemic O2 extraction (P < 0.05). Leg blood flow was elevated (P < 0.05) in hypervolemic conditions, which compensated for hemodilution resulting in similar leg O2 delivery and leg VO2 during exercise regardless of PV. Pulmonary ventilation, gas exchange, and acid-base balance were essentially unaffected by PV expansion. Sea level Qmax and exercise capacity were restored with hyperoxia at altitude independently of BV. Low BV is not a primary cause for reduction of Qmax at altitude when acclimatized. Furthermore, hemodilution caused by PV expansion at altitude is compensated for by increased systemic O2 extraction with similar peak muscular O2 delivery, such that maximal exercise capacity is unaffected.