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Biomedical subjects

A A Almeida

Publications and source records attributed to A A Almeida.

12 recordsLinked to original sources

Determination of memantine in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of memantine (I) in human plasma is presented. Sample preparation consisted of the addition of amantadine (II) as internal standard (IS), liquid-liquid extraction in basic conditions using a mixture of diethyl ether-chloroform (7:3, v/v) as extracting solvent, followed by centrifugation, solvent evaporation and sample reconstitution in methanol. Both I and II (internal standard) were analyzed using a C18 column and a mobile phase composed of methanol-water-formic acid (80:20:0.1, v/v/v). Eluted compounds were monitored using positive mode electrospray (ES) tandem mass spectrometry. The analyses were carried out by selected reaction monitoring (SRM) using the parent to daughter combinations of m/z 180>163 (memantine) and m/z 152>135 (amantadine). The peak areas from the analyte and IS were used for quantification of I. The achieved limit of quantification (LOQ) was 0.1 ng/mL; the assay exhibited a linear dynamic range of 0.1-50.0 ng/mL with a determination coefficient (r2) of at least 0.98. Validation results on linearity, specificity, accuracy, precision and stability, as well as on application to the analysis of samples taken up to 320 h after oral administration of 20mg (two 10mg capsules) of I in healthy volunteers demonstrated the applicability to bioequivalence studies.

Antiparkinson Agents↗

Developmental lead exposure in rats: is a behavioral sequel extended at F2 generation?

Lead toxicity was studied in rats exposed from conception until weaning and assessed by monitoring offspring behavior in both the open field and elevated plus maze and by determining tissue lead in an assessment schedule extended to first (F1) and second (F2) generations. Dams utilized for the F1 generation were submitted to 750 ppm of lead (acetate) in drinking water during pregnancy and lactation. For F1 pups, behavioral alterations were not detected in the elevated plus maze, while in the open field, spontaneous locomotor activity as well as time of both grooming and rearing increased, while freezing time decreased in 30- and 90-day-old rats. Lead content was higher in tissues of 1- and 30-day-old pups. However, in 90-day-old rats, lead was detected only in the femur. F2 generation was lead-free but still presented alterations in both locomotor activity and grooming in 30- and 90-day-old pups. It appears that developmental lead exposure may cause behavioral effects during the developmental stage of the F1 generation, which remains throughout the animal's adult life as a sequel, regardless of lead accumulation, and is extended to the F2 generation of rats.

Animals↗

Haemodynamics and left ventricular mass regression: a comparison of the stentless, stented and mechanical aortic valve replacement.

OBJECTIVE: Our objective was to compare the degree of change in hemodynamics and left ventricular mass (LVM) regression after aortic valve replacement (AVR) with stentless, stented and mechanical valves. METHODS: Patients greater than 59 years of age had AVR for aortic stenosis with the stentless xenograft (Cryolife-O'Brien, CLOB), stented xenograft (Carpentier-Edwards, C-E) or mechanical valve (ATS). One-hundred and forty-two patients received stentless, 40 stented, and 69 mechanical valves (mean age 74 +/- 6 vs. 72 +/- 7 and 67 +/- 6 years, respectively). Serial echocardiography was performed. RESULTS: The left ventricular outflow tract diameter was similar pre-operatively in the stentless versus the stented versus the mechanical groups (2.2 +/- 0.4 vs. 2.3 +/- 0.2 vs. 2.2 +/- 0.3 cm; P, n.s). The effective orifice area was larger immediately post-operatively in the stentless versus the stented or the mechanical group (2.4 +/- 0.4 vs. 2.0 +/- 0.6 vs. 2.0 +/- 0.7 cm2, P = 0.0001 for both comparisons). The peak aortic gradient at 6 months was significantly less in the stentless versus the stented and mechanical groups (15 +/- 7 vs. 25 +/- 9 vs. 22 +/- 9 mmHg, P < 0.0001). LVM regressed over 6 months in all subgroups: stentless 272 +/- 64 g vs. 220 +/- 72 g, P = 0.0001, stented 257 +/- 58 vs. 230 +/- 74 g, P = 0.02, and mechanical 267 +/- 95 vs. 204 +/- 54 g, P = 0.003. The reduction in LVM was greater in the stentless versus the stented (P = 0.05) but similar to the mechanical group. CONCLUSIONS: AVR with the stentless xenograft results in superior hemodynamics compared to the stented and mechanical valve replacements. AVR in all three groups leads to a significant regression of left ventricular hypertrophy within 6 months. However the reduction in LVM is greater in subjects with stentless and mechanical valves, which may have prognostic significance.

Aged↗

Minimally invasive aortic valve replacement via hemi-sternotomy: a preliminary report.

OBJECTIVE: Aortic valve replacement has been approached by standard sternotomy. We described a technique of aortic valve replacement where the aortic valve is exposed through a hemi-sternotomy. Good exposure is obtained for aortic valve surgery with standard aortic and right atrial cannulation to establish cardiopulmonary bypass (CPB). METHODS: From October 1996 to April 1997, 19 consecutive aortic valve replacements (AVR) via hemi-sternotomy were performed by one surgeon. The results were collected and analysed prospectively. Results are expressed as mean +/- standard deviation. Nineteen patients (13 male, 6 female) had AVR with this approach. Two cases were redo AVR. The mean age was 58+/-15 years. The New York Heart Association (NYHA) class was 2.8+/-0.7. RESULTS: Aortic cross clamp time was 54+/-13 min. One of six patients requiring defibrillation after reperfusion needed conversion to full sternotomy. Four patients were extubated at the conclusion of surgery. One patient died 4 h postoperatively from low cardiac output. All patients had normal valvular function demonstrated on postoperative transoesophageal echocardiography. There were no neurological events. CONCLUSIONS: Minimally invasive aortic valve replacement can be safely performed via hemi-sternotomy with standard equipment. Less surgical trauma to the sternum has the potential benefit of less pain and shorter intensive care and hospital stay.

Aortic Valve↗

Pharmacological properties of a new kinin-potentiating peptide generated from human serum proteins.

A kinin-potentiating peptide (KPP) generated from human plasma proteins on trypsin incubation was partially purified by ultrafiltration and ion-exchange chromatography and was characterized through some of its pharmacological properties. KPP itself was devoid of any action but it potentiated the guinea-pig ileum contractions elicited by several kinins, including an analog resistant to angiotensin-converting enzyme (ACE). In contrast, contractions induced by angiotensin II, histamine, acetylcholine, barium chloride and substance P were not potentiated. Not only did KPP have high specificity towards kinins, but its action started immediately and induced kinin potentiation in a dose-dependent and reversible manner. Furthermore KPP potentiated the bradykinin contracting effects on the rat uterus, a preparation with very poor ACE activity, and on guinea-pig ileum previously incubated with 1.10-phenanthroline, a metal chelator able to inhibit ACE and kininase I activities and with phosphoramidon, a specific inhibitor of neutral endopeptidase (NEP). The results suggest that the potentiating effect of KPP is due to a mechanism different from the inhibition of kinin metabolism by ACE, NEP and kininase I.

Blood Proteins↗

Characterization of a new kinin potentiating peptide obtained from human plasma proteins.

Partially purified kinin potentiating peptide (KPP) obtained from kininogen-depleted human plasma inhibited lung angiotensin converting enzyme in vitro and potentiated guinea-pig ileum contractions induced by bradykinin (BK), Lys-BK, Met-Lys-BK, Ile-Ser-BK, and Lys-Lys-BK. Contractions evoked by angiotensin II, histamine, acetylcholine, and barium chloride were not potentiated. KPP also potentiated kinin-induced contractions of rat uterus and of guinea-pig ileum pre-incubated with 1,10-phenanthroline. It is suggested that KPP potentiation is due, at least in part, to a direct effect on kinin receptor(s).

Animals↗