Protein-based nanodevices for therapeutic applications

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Patterned CNT-PDMS nanocomposites for flexible pressure sensors

This paper reports the fabrication process and characterization of a flexible pressure sensor based on polydimethylsiloxane (PDMS) and multi-walled carbon nanotubes (CNT-PDMS). The proposed approach relies on patterned CNT-PDMS nanocomposite strain gauges fabricated with SU-8 microstructures (with the micropatterns) in a low‑cost and simple fabrication process. This nanocomposite polymer is mounted over a PDMS membrane, which, in turn, lies on top of a PDMS diaphragm like structure. This configuration enables the PDMS membrane to bend when pressure is applied, thereby affecting the nanocomposite strain gauges, effectively changing their electrical resistance. Carbon nanotubes have several advantages such as excellent mechanical properties, high electrical conductivity and thermal stability. Furthermore, the measurement range of the proposed sensor can be adapted according to the application by varying the CNTs content and geometry of microstructure. In addition, the sensor’s biocompatibility, low cost and simple fabrication makes it very appealing for biomechanical strain sensing. The sensor’s sensitivity was about 0.073%ΔR/mmHg.

Flexible gastrointestinal motility pressure sensors based on aluminum thin-film strain-gauge arrays

This paper reports on an innovative approach to measuring intraluminal pressure in the upper gastrointestinal (GI) tract, especially monitoring GI motility and peristaltic movements. The proposed approach relies on thin-film aluminum strain gauges deposited on top of a Kapton membrane, which in turn lies on top of an SU-8 diaphragm-like structure. This structure enables the Kapton membrane to bend when pressure is applied, thereby affecting the strain gauges and effectively changing their electrical resistance. The sensor, with an area of 3.4 mm2, is fabricated using photolithography and standard microfabrication techniques (wet etching). It features a linear response (R2 = 0.9987) and an overall sensitivity of 2.6 mV mmHg−1. Additionally, its topology allows a high integration capability. The strain gauges’ responses to pressure were studied and the fabrication process optimized to achieve high sensitivity, linearity, and reproducibility. The sequential acquisition of the different signals is carried out by a microcontroller, with a 10-bit ADC and a sample rate of 250 Hz. The pressure signals are then presented in a user-friendly interface, developed using the Integrated Development Environment software, QtCreator IDE, for better visualization by physicians.

An epidemiological study determining blood pressure in a Portuguese cohort: the Guimaraes/Vizela study

Surveying the evolution of blood pressure (BP) levels and hypertension (HTN) prevalence is important. A stringent strategy was utilized in a population cohort study. The BP was measured at two visits at least 3 months apart, and the results were analyzed using the following two methods: the Surveillance method (three BP measurements were performed in one visit, and the results were compared with those published previously for the identical method) and the Clinical method (three measurements per visit for two visits, and the concordant results in both visits were used to determine the BP classification). A total of 2542 subjects completed the evaluation. Using the Clinical method, an average systolic/diastolic BP value of 129.8/76.8?mm?Hg was obtained, and the prevalence of HTN was 31.6%. Of the hypertensive patients, 74.3% were aware of his/her condition; 69.1% were treated and 40.8% of those treated had adequate BP control. A total of 24.7% of subjects changed his/her BP classification between visits, and 13.7% misreported HTN. Using the Surveillance method, we determined that the average global SBP has been maintained, with HTN prevalence increasing in this region, drifting from reported trends nationally and worldwide. There has been improvement in the proportion of treated and controlled subjects; however, the Surveillance method overestimated the HTN prevalence and underestimated the proportion of treated and controlled subjects. The BP levels were higher than observed worldwide in high-cardiovascular (CV) risk countries as well as higher than the minimum risk exposure level for developing CV disease.

The positive effect on ketamine as a priming adjuvant in antidepressant treatment.

Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.

Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room

OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP) in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3%) complained of high BP, and 61 (76.3%) received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%). One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5%) were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits). Currently, the therapeutic approach is not recommended, even in specialized clinics.

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

Coronary artery disease, microalbuminuria and lipid profile in patients with non-insulin dependent diabetes mellitus

PURPOSE: To determine the frequency of coronary artery disease, microalbuminuria and the relation to lipid profile disorders, blood pressure and clinical and metabolic features. METHODS: Fifty-five type 2 diabetic patients (32 females, 23 males), aged 59.9±9 years and with known diabetes duration of 11±7.3 years were studied. Coronary artery disease (CAD) was defined as a positive history of myocardial infarction, typical angina, myocardial revascularization or a positive stress testing. Microalbuminuria was defined when two out of three overnight urine samples had a urinary albumin excretion ranging 20 - 200µg/min. RESULTS: CAD was present in 24 patients (43,6%). High blood pressure (HBP) present in 32 patients (58.2%) and was more frequent in CAD group (p=0.05) HBP. Increased the risk of CAD 3.7 times (CI[1.14-12]). Microalbuminuria was present in 25 patients (45.5%) and tended to associate with higher systolic blood pressure (SBP) (p = 0.06), presence of hypertension (p = 0.06) and know diabetes duration (p = 0.08). In the stepwise multiple logistic regression the systolic blood pressure was the only variable that influenced UAE (r = 0.39, r² = 0.14, p = 0.01). The h ypertensive patients had higher cholesterol levels (p = 0.04). CONCLUSION: In our sample the frequency of microalbuminuria, hypertension, hypercholesterolemia and CHD was high. Since diabetes is an independent risk factor for cardiovascular disease, the association of others risk factors suggest the need for an intensive therapeutic intervention in primary and in secundary prevention.

Influence of the elevation of the left ventricular diastolic pressure on the values of the first temporal derivative of the ventricular pressure (dP/dt)

PURPOSE: To assess the effects of the elevation of the left ventricular end-diastolic pressure (LVEDP) on the value of the 1st temporal derivative of the ventricular pressure (dP/dt). METHODS: Nineteen anesthetized dogs were studied. The dogs were mechanically ventilated and underwent thoracotomy with parasympathetic nervous system block. The LVEDP was controlled with the use of a perfusion circuit connected to the left atrium and adjusted to the height of a reservoir. The elevation of the LVEDP was achieved by a sudden increase in the height of a reservoir filled with blood. Continuous recordings of the electrocardiogram, the aortic and ventricular pressures and the dP/dt were performed. RESULTS: Elevation of the LVEDP did not result in any variation of the heart rate (167±16.0bpm, before the procedure; 167±15.5bpm, after the procedure). All the other variables assessed, including systolic blood pressure (128±18.3mmHg and 150±21.5mmHg), diastolic blood pressure (98±16.9mmHg and 115±19.8mmHg), LVEDP (5.5±2.49 and 9.3±3.60mmHg), and dP/dt (4,855 ± 1,082 mmHg/s and 5,149±1,242mmHg/s) showed significant increases following the expansion of the ventricular cavity. Although the elevation of the dP/dt was statistically significant, 6 dogs curiously showed a decrease in the values of dP/dt. CONCLUSION: Sudden elevation of the LVEDP resulted in increased values of dP/dt; however, in some dogs, this response was not uniform.

Doppler echocardiographic evaluation of HIV-positive patients in different stages of the disease

OBJETIVE: To evaluate by Doppler echocardiography (DE) early abnormalities of ventricular function in HIV-positive patients, as well as other cardiac abnormalities that can be detected by this method, with special emphasis on mitral valve flow. METHODS: 84 HIV- positive patients, 59 with CD4 cell count >500/mm³ (Group A) and 25 with CD4 cell count <500/mm³ (Group B), were analyzed. CD4 cells were counted and matched with structural data and systolic and diastolic function of the left ventricle (LV), as analyzed by DE. The results were compared with those obtained in 47 healthy individuals (Group C). RESULTS: 8% of patients in Group B had mild pericardial effusion; 31.5% showed decreased systolic function of the LV, and 12% had moderate mitral regurgitation. A wave velocity from the mitral inflow was different among the 3 groups, being higher in Group B, where the deceleration time of the E wave of the mitral inflow and the E/A ratio were significantly lower with a normal value of the isovolumic relaxation time (IVRT). CONCLUSION: HIV-positive patients with a CD4 cell count >500/mm³ had no abnormalities by DE. Patients with a more advanced infection (those with a CD4 cell count <500/mm³), had a significantly abnormal LV systolic function and a higher incidence of pericardial effusion and mitral regurgitation. Mitral valve inflow by Doppler did not indicate diastolic dysfunction.

Laboratory assessment of the hypertensive individual. Value of the main guidelines for high blood pressure

OBJECTIVE: To determine if abnormal laboratory findings are more common in individuals with hypertension and in those with other risk factors, such as obesity, smoking and alcohol ingestion. METHODS: A study was carried out in the general outpatient clinics of a university hospital (145 individuals without previous diagnosis of hypertension) and the following variables were assessed: high blood pressure (as defined by the VI Joint National Committee on Prevention, Detection and Treatment of High Blood Pressure - VI JNC), obesity [calculated using body mass index (BMI)], tobacco use, and alcoholic ingestion. The laboratory examinations consisted of the following tests: hemogram, glycemia, uric acid, potassium, total/HDL-fraction cholesterol, triglycerides, calcium and creatinine. RESULTS: High blood pressure was not associated with a higher number of abnormal laboratory tests. Hypertensive individuals with a BMI > or = 25kg/m² or normotensive obese individuals, however, had a higher frequency of diabetes (12X), hypertriglyceridemia (3X), and hypercholesterolemia (2X), as compared with hypertensive individuals with BMI <25kg/m² and preobese/normal weight normotensive individuals. CONCLUSION: High blood pressure is not associated with a higher frequency of abnormal laboratory tests. The association of high blood pressure and obesity, however, increases the detection of diabetes and dyslipidemias.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE: To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS: 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52±14 years). The average duration of the siesta was 118±58 minutes. RESULTS: (average ± standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138±16/85±11 vs 139±16/86±11 mmHg, p<0.05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION: The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.

Avaliação da toxicidade das águas do rio Cubatão (Norte) - Joinville, SC, com base em ensaios ecotoxicológicos com Daphnia magna

Dissertação de mestrado em Ecologia