Avaliação da deformação miocárdica pela ecocardiografia feature tracking em gatos com defeito perimembranoso do septo ventricular / Evaluation of myocardial deformation by the ecocardiography feature tracking in cats with perimembranosous defect of the septo ventricular

O desenvolvimento de novas ferramentas, como a ecocardiografia bidimensional feature tracking (2D-FTI), permite diagnosticar, de forma precoce, se há disfunção miocárdica em doenças cardíacas, inclusive as congênitas. O defeito septal ventricular (DSV) é a alteração congênita mais observada em felinos, no entanto pouco se sabe sobre a disfunção cardíaca nessa cardiopatia, especialmente em animais assintomáticos. O objetivo deste estudo foi avaliar, por meio do 2D-FTI, a deformação miocárdica ventricular esquerda pela mensuração dos índices ecocardiográficos strain (St) e strain rate (StR) radial, circunferencial e longitudinal, em gatos saudáveis e com DSV. Foram avaliados 12 gatos saudáveis e seis gatos com DSV para obtenção de St e StR em diversos segmentos miocárdicos. No sentido longitudinal, houve diferença estatística (P<0,05) para os segmentos septal basal, mediano e apical epicárdicos (P=0,0017; P<0,0001; P=0,0288), lateral mediano epicárdico (P=0,0327), septal mediano endocárdico (P=0,0035), lateral mediano endocárdico (P=0,0461), St epicárdico (P=0,0250) e St global (P=0,0382). Também houve diferença no segmento lateral mediano circunferencial endocárdico (P=0,0248), lateral mediano radial (St: P=0,0409; StR: P=0,0166) e posterior mediano radial (P=0,0369). O estudo evidenciou que, mesmo em animais assintomáticos com DSV, há redução na deformação miocárdica ventricular principalmente no sentido longitudinal, demonstrando maior vulnerabilidade dessas fibras.(AU)

The development of new tools, such as two-dimensional feature tracking (2D-FTI), allows early diagnosis of myocardial dysfunction in heart diseases including congenital heart disease. The ventricular septal defect (VSD) is the most frequently observed congenital abnormality in cats, however, little is known about cardiac dysfunction, especially in asymptomatic animals. The objective of this study was to evaluate the left ventricular myocardial deformation through 2D-FTI by the measurement of the radial, circumferential and longitudinal echocardiographic strain (St) and strain rate (StR) indices. Twelve healthy cats and six cats with VSD were evaluated to obtain St and StR in several myocardial segments. In the longitudinal direction, there was a statistical difference (P<0.05) for the epimyocardial basal septal, mid-septal, apical septal (P=0.0017; P<0.0001; P=0.0288), epimyocardial mid-lateral (P=0.0327), endomyocardial mid-septal (P=0.0035), endomyocardial mid-lateral (P=0.0461), St epimyocardial (P=0.0250) and St global (P=0.0382). There was also difference in the circumferential endomyocardial mid-lateral segment (P=0.0248), radial mid-lateral (St: P=0.0409; StR: P=0.0166) and radial mid-posterior (P=0.0369). The study showed that even in asymptomatic animals with VSD there is a reduction in ventricular myocardial deformation mainly in the longitudinal direction, demonstrating the fragility of these fibers.(AU)

Cetuximab has an inhibitory effect on cell motility in SCC-4 oral squamous cell carcinoma cell line.

Cetuximab is a chimeric monoclonal antibody that acts as a competitive antagonist, by binding to EGFR. This cell signalling pathways regulates tumor progression. The oral squamous cell carcinoma undergoes to regional spreading and distant metastasis. This study aimed to evaluate the effect of treatment with Cetuximab on cell migration and invasion in OSCC cells, by using the SCC-4 cell line. Cell migration and cell invasion assay were performed and actin cytoskeleton of control and treated with Cetuximab cells were evaluated. Differences were considered significant when p<0.05.Cetuximab inhibited the migration of SCC-4 cells at three concentrations: 1 µg/mL, 50 µg/mL and 100 µg/mL (p<0.0001) in a dose-dependent manner. The number of SCC-4 treated cells with 1 µg/mL that migrated through the membrane was statistically different from 50 µg/mL (p<0.001) and 100 µg/mL (p<0.0001), and between 50 µg/mL and 100 µg/mL (p<0.01). Cetuximab 50 µg/mL inhibited cell invasion through the MatrigelTM compared with SCC-4 control cells (p<0.01). Cetuximab 50 µg/mL affected the organization of the actin cytoskeleton. Cetuximab has an inhibitory effect on actin cytoskeleton organization, cell migration and invasion, suggesting that Cetuximab treatment can be important to avoid oral squamous cell carcinoma metastasis.

Development of a new amplification-refractory mutation system for detection of a single nucleotide polymorphism linked to drug resistance in Ancylostoma caninum.

Single nucleotide polymorphisms at codons 167, 198, and 200 in the ß-tubulin isotype 1 gene have been associated with benz-imidazole resistance. Until now, the only mutation observed in Ancy-lostoma caninum was at codon 200 of this gene. However, the standard-ized methodologies used to detect mutations in this species are faulty. The objective of this study was to standardize a molecular technique based on amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) for detecting the mutation at codon 200 in the A. caninum ß-tubulin isotype 1 gene. Controls were synthesized both for the absence of the mutation, using conventional PCR, and for the presence of the mutation, using the Megaprimer-PCR technique. After standardization of the ARMS-PCR using the controls, the technique was validated through an analysis of 75 A. caninum DNA samples, fol-lowed by sequencing. The results revealed that the developed technique has high sensitivity, specificity, and reproducibility, which allow its ap-plication in the field.

Two-flap palatoplasty for treatment of oronasal fistula by trauma sequel.

The oronasal fistula is a chronic communication between the oral and nasal cavity that often affects patients with cleft palate. However, others uncommon causes of oronasal fistula are associated with facial traumas, infections and neoplasias. In this report we present a case of oronasal fistula as consequence of facial trauma that was treated by two flaps technique for palatoplasty. In this sense, we discussed treatment indications, surgical technique and patient prognostic of a relatively simple option that can provide a definitive repair with minimal morbidity.

Thyroidectomy: post-operative care and common complications.

Any surgical procedure involves risks. Thyroid surgery can cause potentially fatal complications during the early post-operative phase. It is essential that nurses have the knowledge and skills to detect early signs and symptoms of potential complications and take appropriate action. Early detection and rapid response are key to maintaining patient safety and minimising harm.

Peripheral neuropathy and neurological disorders in an unselected Brazilian population-based cohort of IBD patients.

BACKGROUND: Several neurological disorders have been described in inflammatory bowel disease (IBD) patients, but their exact frequency is unknown. METHODS: We prospectively studied the prevalence of neurological disorders (especially peripheral neuropathy) in a group of 82 patients with Crohn's disease (CD, n = 31) or ulcerative colitis (UC, n = 51) from 2 Brazilian tertiary care university clinics and followed them through a period of at least 1 year. All patients were interviewed and had complete neurological evaluations. RESULTS: Large-fiber sensory or sensorimotor polyneuropathy (PN) was observed in 16.1% of the CD and 19.6% of the UC patients. PN was usually mild, predominantly symmetric, and distal with axonal involvement. One patient had demyelinating PN at the diagnosis of CD. Mild carpal tunnel syndrome was common in female UC patients. Sensory symptoms without electromyography abnormalities, suggestive of small-fiber neuropathy or subclinical myelopathy, affected 29% and 11.8%, respectively. After excluding other known etiological or contributory factors for PN, 13.4% of the IBD patients had otherwise unexplained large-fiber or small-fiber PN (7.3% with large-fiber SM PN). Nondebilitating headache was the most common neurological complaint. Three patients had ischemic strokes, 5 were epileptic, and 1 transient chorea. CONCLUSIONS: Neurological disorders, especially PN, are common in our Brazilian cohort of IBD patients. They are diverse, multifactorial, and more common in women. Despite the mild phenotype in most cases, attention should be given by the general practitioner and gastroenterologist since they are frequently undiagnosed. Further studies are necessary to confirm these findings in populations with different genetic and nutritional backgrounds.

Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC).

The insulin-regulated glucose transporter (GLUT4) translocates to the plasma membrane in response to insulin in order to facilitate the postprandial uptake of glucose into fat and muscle cells. While early insulin receptor signaling steps leading to this translocation are well defined, the integration of signaling and regulation of GLUT4 traffic remains elusive. Several lines of evidence suggest an important role for the actin cytoskeleton and for protein-protein interactions in regulating GLUT4 localization by insulin. Here, we applied stable isotope labeling by amino acids in cell culture (SILAC) to identify proteins that interact with GLUT4 in an insulin-regulated manner. Myc-tagged GLUT4 (GLUT4myc) stably expressed in L6 myotubes was immunoprecipitated via the myc epitope from total membranes isolated from basal and insulin-stimulated cells grown in medium containing normal isotopic abundance leucine or deuterated leucine, respectively. Proteins coprecipitating with GLUT4myc were analyzed by liquid chromatography/ tandem mass spectrometry. Of 603 proteins quantified, 36 displayed an insulin-dependent change of their interaction with GLUT4myc of more than 1.5-fold in either direction. Several cytoskeleton-related proteins were elevated in immunoprecipates from insulin-treated cells, whereas components of the ubiquitin-proteasome degradation system were generally reduced. Proteins participating in vesicle traffic also displayed insulin-regulated association. Of cytoskeleton-related proteins, alpha-actinin-4 recovery in GLUT4 immunoprecipitates rose in response to insulin 2.1 +/- 0.5-fold by SILAC and 2.9 +/- 0.8-fold by immunoblotting. Insulin caused GLUT4 and alpha-actinin-4 co-localization as revealed by confocal immunofluorescence microscopy. We conclude that insulin elicits changes in interactions between diverse proteins and GLUT4, and that cytoskeletal proteins, notably alpha-actinin-4, associate with the transporter, potentially to facilitate its routing to the plasma membrane.

Studies on a heterologous complex formed by human butyrylcholinesterase.

An electrophoretic band with butyrylcholinesterase activity was detected in 71 CHE2 C5+ and 378 CHE2 C5- individuals and was named C4/5 in view of its similar mobility to either C4 or C5, depending on the pH of the agar gel used. The present data suggest that C4/5 is a heterologous complex of butyrylcholinesterase. Although the C4/5 band may have the same mobility as C5, depending on the conditions of electrophoresis, our hypothesis is that these two bands result from the association of BChE with different molecules.

GLUT4 activation: thoughts on possible mechanisms.

A family of facilitative glucose transporters or GLUTs mediates glucose uptake by cells and tissues. The glucose transporter isoform GLUT4, which is the predominant isoform expressed in mature muscle and fat tissues, is primarily responsible for the increase in glucose uptake in response to insulin stimulation. Recent work in our laboratory suggests that there are two divergent responses initiated by insulin stimulation. The first response involves the recruitment of GLUT4 transporters from intracellular reserves and their subsequent insertion into the plasma membrane. The second pathway results in an increase in the intrinsic activity of the transporters. This review will discuss evidence supporting the divergence of the two pathways regulating glucose uptake and, in particular, evidence for the increased intrinsic activity of GLUT4 in response to insulin stimulation. Inhibitors of p38 mitogen-activated protein kinase (MAPK) affected only the arm leading to the insulin-stimulated activation of GLUT4. This implicates p38 MAPK involvement in the regulation of this pathway. There is further evidence that p38 MAPK is itself recruited to the plasma membrane. The role of the phosphorylation state of the glucose transporter in response to insulin stimulation has been studied and indicates that, contrary to what might be predicted, there is actually a decrease in its phosphorylation at the plasma membrane in response to insulin. The relationship of this change to glucose uptake remains to be established. Other possible mechanisms regulating GLUT4 activity include binding of (+) or (-) modulators of its function.

Activation of the glucose transporter GLUT4 by insulin.

The transport of glucose into cells and tissues is a highly regulated process, mediated by a family of facilitative glucose transporters (GLUTs). Insulin-stimulated glucose uptake is primarily mediated by the transporter isoform GLUT4, which is predominantly expressed in mature skeletal muscle and fat tissues. Our recent work suggests that two separate pathways are initiated in response to insulin: (i) to recruit transporters to the cell surface from intracellular pools and (ii) to increase the intrinsic activity of the transporters. These pathways are differentially inhibited by wortmannin, demonstrating that the two pathways do not operate in series. Conversely, inhibitors of p38 mitogen-activated protein kinase (MAPK) imply that p38 MAPK is involved only in the regulation of the pathway leading to the insulin-stimulated activation of GLUT4. This review discusses the evidence for the divergence of GLUT4 translocation and activity and proposed mechanisms for the regulation of GLUT4.

[Germ-cell tumors of the testis]. / Tumores germinativos do testículo.

Testis tumours constitute only 1% of all male tumours, but are the commonest neoplasia from 20 to 35 years of age. Their relative rarity, the shyness of patients and doctors, and the fact that tumours in general are not common in young adults, all contribute to frequent delays in diagnosis. Fantastic therapeutic advances have been made in the last decades, making long term survival achievable in more than 90% of patients. Nevertheless, the delays in diagnosis lead to an increase in treatment associated morbidity. In this article, the authors present the main aspects of etiopathogenesis, histopathology, diagnosis and treatment of testis tumours.