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Biomedical subjects

A C Nunes

Publications and source records attributed to A C Nunes.

9 recordsLinked to original sources

Complement resistance of Leishmania amazonensis promastigotes is independent of parasite proteases and lysis of sensitive forms is not due to natural antibodies in normal human serum.

Leishmania amazonensis promastigotes cultivated in vitro differentiate from complement-sensitive to complement-resistant forms. In order to determine the possible involvement of parasite proteases in this process, L. amazonensis promastigotes were collected daily and their proteolytic enzyme patterns analyzed using polacrylamide gels copolymerized with gelatin. Although promastigotes at different growth stages showed differences in protease patterns, these changes did not correlate with their susceptibility to complement. The major protease of promastigotes, gp63, was expressed at the same level throughout culture, regardless of the complement resistance of the promastigotes. Furthermore, inhibitors specific for the classes of proteases found in L. amazonensis promastigotes did not interfere with the complement-mediated killing of promastigotes. We also investigated the binding of natural antibodies to promastigotes. at different stages of growth using ELISA. Although complement-sensitive promastigotes bound significantly more antibodies from fresh normal human serum than complement-resistant promastigotes, equivalent amounts of C3 were detected on their surfaces following complement activation. Moreover, serum depleted of anti-Leishmania antibodies was an efficient in killing promastigotes and the intact serum. These data suggest that the resistance of L. amazonensis to complement killing involves strategies other than that of the regulated expression of endogenous proteases capable of inactivating complement components, or the differential ability to bind natural antibodies that might interfere with complement deposition on the parasite surface.

Animals

[Clinical trial with isradipine in the treatment of mild and moderate arterial hypertension].

A short-term trial of isradipine was conducted in order to assess its effectiveness and tolerability in the treatment of mild to moderate HT. The study took place in general practice on 2702 patients, aged 18 to 70, with diastolic BP (dBP) from 95 to 114 mmHg. It included a pretreatment phase of up to four weeks out of antihypertensive drugs and on placebo and a twelve week treatment phase on isradipine 2.5 mg or 5.0 mg/day. After treatment with isradipine sBP fell from 168.0 to 148.1 and dBP from 102.7 to 86.7 mmHg. The majority of patients (89.6%) had a fall in dBP over 10 mmHg; 86.2% had normal dBP (= less than 90 mmHg) in the end. Adverse effects were referred by 2.8% of the patients. Satisfaction with the drug reached 90% among patients and physicians. Thus, isradipine proved effective and very well tolerated and may deserve a place as first line treatment for hypertension.

Adult

Some focusing techniques and their application to low-angle neutron scattering.

Both imaging and simple converging collimator systems can provide a focused neutron beam. Each system has been tested and appears suitable for exploitation. Imaging systems employing bent multilayer monochromators can be made simply by elastically bending a flat multilayer. The periodic spacing of the multilayer can be made to match that of the sample. The converging Soller slit provides a purely geometric means of prouducing a focused beam. Wavelength spread and distribution across the beam can be controlled separately. Soller-slit technology is further advanced than that of multilayers. The experiments sketched above demonstrate that converging or focused neutron beams suitable for low-angle scattering work can be produced with existing technology. Focusing incurs little or no loss of intensity and does not seriously distort the resolution function of a low-angel instrument. It permits a small spectrometer to make use of both advanced detector technology and large samples and thus to approach the capability of a much larger machine.

Neutrons

The analyzer in neutron protein crystallography.

The use of a pyrolytic graphite analyzer is shown to contribute to the cleanliness of a neutron protein crystallographic study. If neutrons of approximately 1.5-A wavelength are used, higher orders are reduced by nearly an order of magnitude, and background (arising largely from incoherent inelastic neutron-proton scattering) is reduced by nearly a factor of five. These advantages are gained at the expense of approximately 50% of measured integrated intensity and a distortion of integrated intensity with scattering angle. Because background scatter is generally large compared with peak reflectivity of a protein, the large background reduction by the analyzer more than compensates for reduced peak intensity to improve the statistics of most peak reflectivity measurements. The luminance function distortion of intensity data is not large, produces a slight smearing of atomic scattering density, and can be calculated and adjusted for in the data.

Crystallography

Neutron diffraction analysis of myoglobin: structure of the carbon monoxide derivative.

The locations of hydrogen and deuterium atoms and water molecules have been investigated in carbon monoxide myoglobin using neutron diffraction, and the results are compared with earlier work on metmyoglobin. Parallel real space refinements on the two molecules show relatively few changes, but do show the carbon monoxide molecule with the iron atom moving into the heme plane.

Carbon Monoxide