VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors

The aim of this study was to investigate the expression of vascular endothelial growth factor type C (VEGF-C) in oral squamous cell carcinoma (OSCC) cell lines through norepinephrine-induced activation of beta-adrenergic receptors. Human OSCC cell lines (SCC-9 and SCC-25) expressing beta-adrenergic receptors were stimulated with different concentrations of norepinephrine (0.1, 1, and 10 μM) and 1 μM of propranolol, and analyzed after 1, 6, and 24 h. VEGF-C gene expression and VEGF-C production in the cell supernatant were evaluated by real-time PCR and by ELISA, respectively. The results showed that beta-adrenergic receptor stimulation by different concentrations of norepinephrine or blocking by propranolol did not markedly alter VEGF-C expression by SCC-9 and SCC-25 cells. VEGF-C protein levels produced by oral malignant cell lines after stimulation with different norepinephrine concentrations or blocking with propranolol was statistically similar (p > 0.05) to those of the control group (nonstimulated OSCC cell lines). Our findings suggest that stimulation of beta-adrenergic receptors by means of norepinephrine does not seem to modulate the VEGF-C expression in OSCC cell lines. These findings reinforce the need for further studies in order to understand the responsiveness of oral cancer to beta-adrenergic receptor stimulation or blockage, especially with regard to VEGF-C production. © 2012 International Society of Oncology and BioMarkers (ISOBM).

Effects of unilateral decortication on β-adrenergic receptors in the remaining cortex and in the hypothalamus of female rats

Many experiments have been performed to evaluate the physiological role of catecholaminergic mechanisms of gonadotropin release. The purpose of the present study was to determine the concentration of β-adrenoreceptors in the remaining (right) cerebral cortex and in right and left hypothalamic halves of hemi-decorticated female rats which exhibited elevated plasma gonadotropin levels as observed previously. The density of β-receptors was measured using a high-affinity β-adrenergic ligand, iodocyanopindolol (ICYP). Scatchard estimates were obtained for maximum binding (B(max) fmol/mg of tissues) from pooled cerebral cortical and hypothalamic tissue of animals under several experimental conditions after hemi-decortication and sham operation. There was an increase in β-adrenoreceptor density in the remaining (right) cerebral cortex at all times examined in hemi-decorticate in comparison with the sham-operated animals (7 days, +10.9%; 21 days, +8.4%; 90 days, +22%; and 90 days plus ovariectomy, +34.8%). The number of β-adrenoreceptors in the right hypothalamic half in hemi-decorticates decreased at 21 days (-42.20%) and then increased at 90 days (+76.63%) and 90 days plus ovariectomy (+51.75%) when compared with the left hypothalamic half. At the same time there were no significant changes in the sham-operated animals when comparing the receptor density in the right and left hypothalamic halves, respectively. Thus, our results suggest a direct adrenergic pathway by which the left cortex can influence the right cortex and a crossed pathway to the contralateral hypothalamus changing adrenergic activity which can alter the β-adrenergic receptor binding capacity in the hypothalamus.

Effect of adrenergic stimulation of the amygdaloid complex on water intake

The effect of noradrenaline, isoproterenol, phentolamine and propranolol, injected into the basolateral nuclei of the amygdala on water intake, was investigated in male Holtzman rats. The injection of noradrenaline (40 nmol) into the amygdaloid complex (AC) of satiated rats produced no change in water intake (0.05 ± 0.03 ml/1 hour). The injection of isoproterenol (40 nmol) produced an increase in water intake in sedated rats (1.93 ± 0.23 ml/1 hour). Noradrenaline injected into the AC produced a decrease in water intake in deprived rats (0.40 ± 0.19 ml/1 hour). The injection of isoproterenol into the AC of deprived rats produced no change in water intake in comparison with control (11.65 ± 1.02 and 10.92 ± 0.88 ml/1 hour, respectively). When compared with control values, phentolamine injected prior to noradrenaline blocked the inhibitory effect of noradrenaline on water intake in deprived rats (10.40 ± 1.31 ml/1 hour). Propranolol blocked the effect of isoproterenol in satiated rats (0.85 ± 0.49 ml/1 hour) and also blocked the water intake induced by deprivation (0.53 ± 0.38 ml/1 hour). In satiated and deprived animals the injection of phentolamine before hexamethonium blocked the inhibitory effect of hexamethonium on water intake. In satiated animals, when hexamethonium was injected alone, water intake was 0.39 ± 0.25 ml/1 hour and when hexamethonium was injected with phentolamine, water intake was 1.04 ± 0.3 ml/1 hour. In deprived animals, hexamethonium alone blocked water intake (0.40 ± 0.17 ml/1 hour) and when injected with phentolamine it elicited an intake of 9.7 ± 1.8 ml/1 hour. these results clearly demonstrate the participation of catecholaminergic receptors of the AC in the regulation of water intake.

Influência do sistema nervoso simpático na periodontite induzida e em glândula salivar de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome

Purpose: To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS).Methods: This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05) in PATIENTS.Results: BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26-3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15-9.40, p<0.001).Conclusions: After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.

Effects of age on aerobic capacity in heart failure patients under beta-blocker therapy: Possible impact in clinical decision-making?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of an acute β-adrenergic blockade on the blood glucose response during lactate minimum test

The aim of this study was to determine the relationship between blood lactate and glucose during an incremental test after exercise induced lactic acidosis, under normal and acute β-adrenergic blockade. Eight fit males (cyclists or triathletes) performed a protocol to determine the intensity corresponding to the individual equilibrium point between lactate entry and removal from the blood (incremental test after exercise induced lactic acidosis), determined from the blood lactate (Lacmin) and glucose (Glucmin) response. This protocol was performed twice in a double-blind randomized order by ingesting either propranolol (80 mg) or a placebo (dextrose), 120 min prior to the test. The blood lactate and glucose concentration obtained 7 minutes after anaerobic exercise (Wingate test) was significantly lower (p<0.01) with the acute β-adrenergic blockade (9.1±1.5 mM; 3.9±0.1 mM), respectively than in the placebo condition (12.4±1.8 mM; 5.0±0.1 mM). There was no difference (p>0.05) between the exercise intensity determined by Lacmin (212.1±17.4 W) and Glucmin (218.2±22.1 W) during exercise performed without acute β-adrenergic blockade. The exercise intensity at Lacmin was lowered (p<0.05) from 212.1±17.4 to 181.0±15.6 W and heart rate at Lacmin was reduced (p<0.01) from 161.2±8.4 to 129.3±6.2 beats min-1 as a result of the blockade. It was not possible to determine the exercise intensity corresponding to Glucmin with β-adrenergic blockade, since the blood glucose concentration presented a continuous decrease during the incremental test. We concluded that the similar pattern response of blood lactate and glucose during an incremental test after exercise induced lactic acidosis, is not present during β-adrenergic blockade suggesting that, at least in part, this behavior depends upon adrenergic stimulation.

Redução da mortalidade após implementação de condutas consensuais em pacientes com infarto agudo do miocárdio

OBJETIVO: Comparar a mortalidade em 30 dias com a utilização de determinados grupos de medicamentos por pacientes, entre 1992-1997, quando não se dispunham de condutas consensuais para tratamento do infarto agudo do miocárdio, e de 2000-2002, após a padronização dessas condutas em nosso serviço. MÉTODOS: Avaliados, retrospectivamente, no 1º e 2º períodos, 172 e 143 pacientes respectivamente, admitidos com diagnóstico de infarto agudo do miocárdio: foram realizados os testes estatísticos: c² para comparar proporções, teste t de Student e o de Mann-Whitney para comparação de médias ou medianas. RESULTADOS: A análise não mostrou diferença em relação aos homens, brancos e a idade média de 61 anos, nos dois períodos. Com relação aos fatores de risco clássicos, foi observada diferença apenas na incidência de dislipidemia (17 e 29%) e, quanto à estratégia terapêutica, aumento significativo do uso de: trombolíticos (39 e 61,5%), ácido acetilsalicílico (70,9 e 96,5%), betabloqueadores (34,8 e 67,8%), inibidor da enzima conversora da angiotensina (45,9 e 74,8%), nitratos (61 e 85,3%) e a redução significativa de bloqueadores de cálcio (16,8 e 5,3%), antiarrítmicos (29,1 e 9,7%) e diuréticos (50,6 e 26,6%). O uso de inotrópicos não diferiu entre os períodos (29,6 e 32,1%). A mortalidade em 30 dias apresentou redução estatisticamente significante de 22,7 para 10,5%. CONCLUSÃO: A implementação das condutas consensuais para o tratamento do infarto agudo do miocárdio foi acompanhada por significante redução da taxa de mortalidade em 30 dias.

Clinical Profile, Predictors of Mortality, and Treatment of Patients after Myocardial Infarction, in an Academic Medical Center Hospital

OBJECTIVE: To evaluate clinical profiles, predictors of 30-day mortality, and the adherence to international recommendations for the treatment of myocardial infarction in an academic medical center hospital. METHODS: We retrospectively studied 172 patients with acute myocardial infarction, admitted in the intensive care unit from January 1992 to December 1997. RESULTS: Most patients were male (68%), white (97%), and over 60 years old (59%). The main risk factor for coronary atherosclerotic disease was systemic blood hypertension (63%). Among all the variables studied, reperfusion therapy, smoking, hypertension, cardiogenic shock, and age were the predictors of 30-day mortality. Most commonly used medications were: acetylsalicylic acid (71%), nitrates (61%), diuretics (51%), angiotensin-converting enzyme inhibitors (46%), thrombolytic therapy (39%), and beta-blockers (35%). CONCLUSION: The absence of reperfusion therapy, smoking status, hypertension, cardiogenic shock, and advanced age are predictors of 30-day mortality in patients with acute myocardial infarction. In addition, some medications that are undoubtedly beneficial have been under-used after acute myocardial infarction.

Insuficiência cardíaca com fração de ejeção normal

A insuficiência cardíaca com fração de ejeção normal (ICFEN) é uma síndrome complexa que vem sendo largamente estudada, desde a última década. É causada por disfunção ventricular diastólica evidenciada por métodos complementares, como estudo hemodinâmico ou ecocardiograma, na presença de fração de ejeção preservada. Acomete preferencialmente indivíduos mais idosos e com comorbidades, como hipertensão arterial sistêmica, insuficiência coronariana e obesidade. Os mecanismos fisiopatológicos são complexos e multifatoriais, envolvendo a rigidez passiva do miocárdio, a geometria ventricular, a força de contenção do pericárdio e a interação entre os ventrículos. Os objetivos principais do tratamento são reduzir a congestão venosa pulmonar, a frequência cardíaca e controlar as comorbidades. Ainda não há evidências fortes de que o uso de medicações específicas, como inibidores de enzima de conversão ou betabloqueadores, interfiram na mortalidade. Os fatores de pior prognóstico incluem a idade avançada, presença de disfunção renal, diabete, classe funcional III e IV (NYHA) e estágio avançado de disfunção diastólica, com padrão restritivo ao enchimento ventricular. Outro aspecto que vem ganhando espaço na literatura é o questionamento do papel da disfunção sistólica nos quadros de ICFEN. Todos esses aspectos são abordados detalhadamente na presente revisão.

Disfunção miocárdica e alterações no trânsito de cálcio intracelular em ratos obesos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Protective effects of carvedilol on systemic vascular damage induced by angiotensin II: Organ-specific effects independent of antihypertensive effects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of topical levobunolol or fixed combination of dorzolamide-timolol or association of dorzolamide-levobunolol on intraocular pressure, pupil size, and heart rate in healthy cats

Estudaram-se e compararam-se os efeitos do levobunolol, da combinação fixa de dorzolamida 2%-timolol 0,5% e da associação de dorzolamida 2% com levobunolol 0,5% sobre a pressão intra-ocular (PIO), o diâmetro pupilar (DP), a freqüência cardíaca (FC) e a hiperemia conjuntival em 18 gatos saudáveis. PIO, DP, FC e hiperemia conjuntival foram aferidos diariamente, em três horários distintos (9h, 14h e 18h). Três grupos foram formados (n=6) e um olho de cada animal recebeu, aleatoriamente, uma gota de levobunolol (L), ou a combinação comercial à base de dorzolamida-timolol (DT), ou a associação de dorzolamida com levobunolol (DL). Parâmetros basais foram aferidos no primeiro dia (dia 0). Nos quatro dias consecutivos, os fármacos foram instilados às 8h e 20h e os parâmetros aferidos nos mesmos horários. Todos os parâmetros decresceram significativamente em relação aos valores basais (P<0,001) e não se observou hiperemia conjuntival. O levobunolol reduziu significativamente a PIO, o DP e a FC e o foi o fármaco que mais reduziu a FC. Não se observou efeito sinérgico na redução da PIO quando a dorzolamida foi adicionada ao levobulol.