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Biomedical subjects

V Castro

Publications and source records attributed to V Castro.

At least 19 recordsLinked to original sources
PubMed2005

Hyoid and laryngeal chondrosarcomas have different clinicopathologic features.

Hyoid chondrosarcomas (CSs) are uncommon cervical tumours with different features compared to laryngeal CSs. Herein we report a hyoid CS in a 36-year-old male and review the literature. Only eight cases of hyoid CS have been reported to date. We have found important differences between hyoid and laryngeal CSs in terms of the age at presentation, gender, clinical symptoms, time before diagnosis, histologic findings and tumour size.

Adult↗
PubMed2005

Core-shell CdS/Cd(OH)2 quantum dots: synthesis and bioconjugation to target red cells antigens.

We report a new and efficient methodology of labelling red blood cells, in order to investigate the expression of anti-A antigen, employing luminescent semiconductor nanocrystals. Highly luminescent and stable core-shell cadmium sulphide/cadmium hydroxide [CdS/CdS(OH)2] colloidal particles were obtained in the nanometre size range. The surface of these particles was characterized by using a monoclonal anti-A antibody via a one-step glutaraldehyde cross-linking procedure, followed by conjugation of the particles to red cells of blood groups A+, and O+. Laser scanning confocal microscopy images indicated that after conjugation for 30 min, A+ and erythrocytes presented different patterns of dual bright emission whereas the O+ group cells showed no emission. We suggest that this labelling procedure may be applied as a quantitative tool to investigate the distribution and expression of alloantigen in red blood cells.

Alloys↗
PubMed2004

Polymorphism of the human platelet antigen-5 system is a risk factor for occlusive vascular complications in patients with sickle cell anemia.

BACKGROUND: Polymorphisms of platelet membrane glycoproteins such as human platelet antigen (HPA)-1b, HPA-2b, the -5T/C Kozak sequence and C807T have been described as risk factors for vascular disease. Vaso-occlusion episodes are a common feature of sickle cell anaemia (SCA), leading to complications such as stroke, acute chest syndrome, avascular head femur necrosis and priapism. Complex interactions are involved in vaso-occlusion, and activated platelets may play an important role. These data raised the question of whether platelet polymorphisms could be implicated in occlusive vascular complications (OVC) of SCA. MATERIALS AND METHODS: In this study, 97 patients with SCA were analysed in two groups: 34 patients presenting with OVC (SCA-VC) and 63 without these complications (SCA-N). The distribution of the HPA-1, -2 and -5 systems, as well as C807T dimorphism and -5T/C Kozak sequence alleles, was evaluated using DNA-based methods. RESULTS: Patients of the SCA-VC group showed a higher frequency of the HPA-5b allele (0.324) compared with those of the SCA-N group (0.111) (chi2 = 13.19, P = 0.0002). None of the other polymorphisms, isolated or associated as haplotypes, demonstrated any correlation with the development of OVC in these patients. CONCLUSIONS: The findings of this study suggest that the HPA-5b allele is a genetic risk factor for the development of OVC in patients with SCA. This allele could be explored as a target for the development of new therapeutic approaches.

Adolescent↗
PubMed2004

Hydration of ds-DNA and ss-DNA by neutron quasielastic scattering.

Quasielastic neutron scattering measurements were performed in hydrated samples of ds-DNA and ss-DNA. The samples were hydrated in a high relative humidity atmosphere, and their final water content was 0.559 g H(2)O/g ds-DNA and 0.434 g H(2)O/g ss-DNA. The measurements were performed at 8 and 5.2 A for the ds-DNA sample, and at 5.2 A for the ss-DNA sample. The temperature was in both cases 298 K. Analysis of the obtained data indicates that in the ds-DNA sample we can distinguish two types of protons-those belonging to water molecules strongly attached to the ds-DNA surface and another fraction belonging to water that diffuses isotropically in a sphere of radius 2.8 A, with a local diffusion coefficient of 2.2 x 10(-5) cm(2) s(-1). For ss-DNA, on the other hand, no indication was found of motionally restricted or confined water. Further, the fraction of protons strongly attached to the ds-DNA surface corresponds to 0.16 g H(2)O/g ds-DNA, which equals the amount of water that is released by ds-DNA upon thermal denaturation, as studied by one of us (G.M.) by differential scanning calorimetry. This value also equals the difference between the critical hydration values of ds-DNA and ss-DNA, also determined by DSC. These results represent, thus, a completely independent measurement of water characteristics and behavior in ds- and ss-DNA at critical hydration values, and therefore substantiate the previous suggestions/conclusions of the results obtained by calorimetry.

DNA↗
PubMed2003

Severe immune haemolysis in a group A recipient of a group O red blood cell unit.

Haemolysis caused by passive ABO antibodies is a rare transfusional complication. We report a case of severe haemolytic reaction in a 38-year-old man (blood group A) with lymphoma who had received one red blood cell (RBC) unit group O. After transfusion of 270 mL, the patient experienced fever, dyspnoea, chills and back pain. On the following morning he was icteric and pale. Haptoglobin was inferior to 5.8 mgdL(-1), haemoglobin was not increased and lactate dehydrogenase was elevated. Haemolysis was evident on observation of the patient's post-transfusion samples. The recipient's red cells developed a positive direct antiglobulin test and Lui elution showed anti-A coated the cells. Fresh donor serum had an anti-A titre of 1024, which was not reduced by treating the serum with dithiothreitol. Donor isoagglutinin screening has been determined by microplate automated analyser and showed titre higher than 100. Physicians should be aware of the risk of haemolysis associated with ABO-passive antibodies. There is generally no agreement justifying the isoagglutinin investigation prior to transfusion. However, automated quantitative isoagglutinin determination could be part of the modern donor testing process, mainly in blood banks where identical ABO group units (platelets or phenotyped RBCs) are not available owing to limited supply.

ABO Blood-Group System↗
PubMed2002

Sesquiterpene lactones as inhibitors of human neutrophil elastase.

Human neutrophil elastase (HNE) is a serine protease that has been implicated in the abnormal turnover of connective tissue proteins and has been described as an important pathogenic factor in several inflammatory diseases such as rheumatoid arthritis or cystic fibrosis. Here we investigated 17 sesquiterpene lactones (SLs) for their ability to inhibit human neutrophil elastase in an in vitro assay. Podachaenin was the most active compound with an IC(50) value of 7 microM. SLs do not covalently bind to the amino acids of the catalytic triad, thus differing from other elastase inhibitors with a lactone moiety. In contrast to most other biological activities of SLs HNE inhibition is not mediated by alpha,beta-unsaturated carbonyl functions. Ligand binding calculations using the X-ray structure of HNE and the program FlexX revealed structural elements which are a prerequisite for their inhibitory activity.

Enzyme Inhibitors↗
PubMed2001

Inhibition of inflammatory cytokine production and lymphocyte proliferation by structurally different sesquiterpene lactones correlates with their effect on activation of NF-kappaB.

Many sesquiterpene lactones (Sls) are known to possess anti-inflammatory activities. To gain further insight into their structure-activity relationships and the molecular mechanism of action, four germacranolide sesquiterpene lactones which differ in the skeleton and the number of reactive centers (4beta,15-epoxy-miller-9E-enolide (1), 15-acetoxy-eremantholide B (2), a mixture of 15-(isovaleroyl)/15-(2-methyl-butyryl)-2alpha-acetoxy-miguanin (3), and 15-(2-hydroxy)-isobutyryloxy-micrantholide (4)) were investigated for their effect on production of proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-6, and tumor necrosis factor-alpha [TNF-alpha]) as well as proliferation of concanavalin A (Con A) and lipopolysaccharide (LPS)-stimulated mouse lymphocytes. Compounds 1 and 3 which possess an alpha-methylene-gamma-lactone function and a conjugated carbonyl group induced a half-maximal inhibition of cytokine synthesis in adherent mouse peritoneal exudate cells at micromolar concentrations (IC(50) 0.69-1.70 microM), while compound 4 which contains only an alpha-methylene-gamma-lactone residue was less active (IC(50) > or 38 microM). Interestingly, compound 2, which carries only a conjugated keto group, displayed a potency similar to those of the bifunctional compounds 1 and 3. All four Sls suppressed proliferation of murine lymphocyte at IC(50) concentrations between 0.22 and 5.03 microM. The rank order of potency was 1 = 2 > 3 > 4. Generally, the growth of LPS-stimulated cells was more strongly influenced than those of Con A-activated lymphocytes. This effect was particularly pronounced with 4. Inhibitory concentrations correlated well with those necessary for inhibition of the transcription factor nuclear factor kappaB (NF-kappaB) observed in a previous investigation. Therefore, it can be assumed that NF-kappaB may be involved in the suppressive effect of Sls on cytokine production and lymphocyte proliferation.

Animals↗
PubMed2001

Cysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones.

Sesquiterpene lactones (SLs) have potent anti-inflammatory properties. We have shown previously that they exert this effect in part by inhibiting activation of the transcription factor NF-kappaB, a central regulator of the immune response. We have proposed a molecular mechanism for this inhibition based on computer molecular modeling data. In this model, SLs directly alkylate the p65 subunit of NF-kappaB, thereby inhibiting DNA binding. Nevertheless, an experimental evidence for the proposed mechanism was lacking. Moreover, based on experiments using the SL parthenolide, an alternative mode of action has been proposed by other authors in which SLs inhibit IkappaB-alpha degradation. Here we report the construction of p65/NF-kappaB point mutants that lack the cysteine residues alkylated by SLs in our model. In contrast to wild type p65, DNA-binding of the Cys(38) --> Ser and Cys(38,120) --> Ser mutants is no longer inhibited by SLs. In addition, we provide evidence that parthenolide uses a similar mechanism to other SLs in inhibiting NF-kappaB. Contrary to previous reports, we show that parthenolide, like other SLs, inhibits NF-kappaB most probably by alkylating p65 at Cys(38). Although a slight inhibition of IkappaB degradation was detected for all SLs, the amount of remaining IkappaB was too low to explain the observed NF-kappaB inhibition.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

3-Desoxyanthocyanidins from Arrabidaea chica.

The new 3-desoxyanthocyanidins 6,7,3'-trihydroxy-5,4'-dimethoxy-flavylium and 6,7,3',4'-tetrahydroxy-5-methoxy-flavylium and the known 6,7-dihydroxy-5,4'-dimethoxy-flavylium (Carajurin) were isolated by bioguided fractionation from the leaves of Arrabidaea chica, with transcription factor NF-kappaB as target. The structure of Carajurone was revised to be 6,7,4'-trihydroxy-5-methoxy-flavylium. Additionally, the flavone acacetin was found. All structures were mainly established on the basis of MS- and NMR data (1H, 1H-1H COSY and partly 13C, GHMQCR and GHSQCR). Carajurin, which failed to give a positive result in the DPPH TLC assay completely inhibited NF-kappaB, but not NF-AT at a 500 microM concentration.

Anti-Inflammatory Agents↗
PubMed2001

[Symptomatic xanthograuloma of the lateral ventricle].

Xanthogranulomas of the choroid plexus in the lateral ventricle are usually asymptomatic lesions found incidentally at autopsy. Symptomatic cases are rare. We present the case of a 30-year-old woman with a xanthogranuloma of the right lateral ventricle who showed intracranial hypertension and visual disturbance. Plain T1-weighted magnetic resonance images disclosed a isointense right temporal lesion in the ventricular horn which showed decreased signal intensity on T2-weighted images and massive enhancement on T1-weighted images after gadolinium injection. She was operated on through a right temporal craniotomy with total excision. We review the literature and discuss radiological findings on MRI.

Brain Diseases↗
PubMed2001

Complications of the mandibular sagittal split ramus osteotomy associated with the presence or absence of third molars.

PURPOSE: This study compared the number of unfavorable fractures after sagittal split osteotomies (SSOs) of the mandible when third molars were present or absent. PATIENTS AND METHODS: The treatment records of 262 patients (500 SSOs) were retrospectively evaluated. Group 1 consisted of 250 SSOs and concomitant removal of impacted mandibular third molars and group 2 consisted of 250 SSOs with absence of third molars. A modified SSO technique with inferior border cuts was used on all patients, and the third molars, when present, were removed after separation of the proximal and distal segments. Rigid fixation was applied using bicortical bone screws. Bone plates with monocortical screws were additionally used to secure the free bony segments of the proximal segment in cases with unfavorable fracture. RESULTS: There were 11 (2.2%) unfavorable fractures in 500 SSO procedures. The incidence of unfavorable splits was 3.2% in group 1 and 1.2 % in group 2. In group 1, all fractures occurred in teenagers, with 7 of 8 fractures extending through the extraction socket in the distal segment. Six of the 8 fractures were associated with completely impacted third molars, and 2 involved partially impacted teeth. All 3 fractures in group 2 occurred in the proximal segment. No significant difference was seen in the amount of relapse in patients with unfavorable or favorable splits. CONCLUSIONS: The occurrence of unfavorable splits is uncommon when using a modification of the SSO that includes an inferior border osteotomy. Although more unfavorable fractures occurred in teenage patients with third molars, this had no impact on the stability of the final result.

Adolescent↗
PubMed2001

Stability of maxillary advancement using rigid fixation and porous-block hydroxyapatite grafting: cleft palate versus non-cleft patients.

This study was undertaken to evaluate the stability of maxillary advancement using bone plates for skeletal stabilization and porous block hydroxyapatite (PBHA) as a bone graft substitute for interpositional grafting in cleft and non-cleft patients. The records of 74 patients (41 females, 33 males) who underwent Le Fort I maxillary advancement using rigid fixation and PBHA interpositional grafting were evaluated retrospectively. All patients also underwent simultaneous sagittal split mandibular ramus osteotomies. Patients were divided into 2 groups for study purposes: group 1 consisted of 17 cleft palate patients and group 2 consisted of 57 non-cleft patients. Each group was further subdivided into 2 subgroups based on the concurrent vertical positioning of the maxillary incisors: groups 1a and 2a, where the maxilla underwent 3 mm or more of inferior repositioning, and groups 1b and 2b, where the maxilla underwent minimal vertical change (< or = 1 mm). Presurgery, immediate postsurgery, and longest follow-up lateral cephalometric tracings were superimposed and analyzed to calculate surgical change and long-term stability of results by assessing horizontal and vertical changes at point A, incisor superius, and the mesial cusp tip of maxillary first molar. The average follow-up time in group 1 was 37.9 months (range 12 to 136) and in group 2 was 28.77 months (range 17 to 88). Average maxillary advancement at point A was: group 1a, 5.4 mm; group 1b, 5.25 mm; group 2a, 5.48 mm; group 2b, 5.46 mm. Average relapse at point A was: group 1a, -0.75 mm; group 1b, -1 mm; group 2a, -0.47 mm; group 2b, -0.48 mm. Average horizontal and/or vertical relapse at the central incisors and first molars was 1 mm or less in group 1 and less than 0.5 mm in group 2. Although there was a slightly greater relapse in group 1, no statistically significant difference was observed between the groups. Maxillary advancement with Le Fort 1 osteotomies using rigid fixation and interpositional PBHA grafting during bimaxillary surgery is a stable procedure with good predictability in cleft and non-cleft patients, regardless of the direction of vertical maxillary movement.

Adolescent↗
PubMed2000

Study of sesquiterpene lactones from Milleria quinqueflora on their anti-inflammatory activity using the transcription factor NF-kappa B as molecular target.

In Central America aerial parts of the Asteraceae Milleria quinqueflora are used in traditional medicine as a remedy for skin infections. Reinvestigation of this plant afforded thirteen sesquiterpene lactones (Sls), three of them are new. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-kappa B as molecular target. NF-kappa B is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. NF-kappa B DNA binding was inhibited at micromolar concentrations by all Sls.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Inhibition of the transcription factor NF-kappa B by sesquiterpene lactones from Podachaenium eminens.

Investigation of Podachaenium eminens afforded nine sesquiterpene lactones (Sls) from which costunolide, 7-hydroxycostunolide, santamarin as well as 3-chlorodehydroleucodin are new for this plant and 3,4-dehydro-4-dehydroxypodachaenin (= 3-costoyloxydehydroleucodin) is found for the first time in nature. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-kappa B as a molecular target. NF-kappa B is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. Except for podachaenin, all compounds completely inhibited NF-kappa B DNA binding in an electrophoretic mobility shift assay at concentrations between 5 and 200 microM without showing any cytotoxic effects. 3,4-Epoxydehydroleucodin possessing an alpha-methylene-gamma-butyrolactone and a second reactive structure element by its epoxy ring alpha,beta to a carbonyl group was most active. Although the majority of the Sls tested in this study were monofunctional only low concentrations of 50 microM were often needed for complete inhibition. Possible reasons are discussed for this result.

Asteraceae↗
PubMed1999

Inhibition of transcription factor NF-kappaB by sesquiterpene lactones: a proposed molecular mechanism of action.

Many sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. They inhibit the transcription factor NF-kappaB by selectively alkylating its p65 subunit probably by reacting with cysteine residues. Here we assayed 28 sesquiterpene lactones for their ability to inhibit NF-kappaB. The majority of the potent NF-kappaB inhibitors possess two reactive centers in form of an alpha-methylene-gamma-lactone group and an alpha,beta- or alpha,beta,gamma,delta-unsaturated carbonyl group. Based on computer molecular modelling we propose a molecular mechanism of action, which is able to explain the p65 selectivity of the SLs and the observed correlation of high activity with alkylant bifunctionality. A single bifunctional SL molecule can alkylate the cysteine residue (Cys 38) in the DNA binding loop 1 (L1) and a further cysteine (Cys 120) in the nearby E' region. This cross link alters the position of tyrosine 36 and additional amino acids in such a way that their specific interactions with the DNA become impossible. We also created a model for monofunctional SLs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Abnormal circadian rhythm and increased non-pulsatile secretion of thyrotrophin in Sheehan's syndrome.

OBJECTIVE: It has previously been shown that patients with postpartum pituitary necrosis (Sheehan's syndrome, SS) have paradoxically increased TSH levels and loss of the nocturnal TSH surge. This study sought to determine the circadian and pulsatile characteristics of TSH secretion underlying those abnormalities. DESIGN AND PATIENTS: Chronobiological and cluster analyses of 24-h TSH profiles were performed in nine SS patients (43-61 years, median = 52 years) and nine healthy female controls (33-47 years, median = 42 years). MEASUREMENTS: Serum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radioimmunoassay; TSH, GH, PRL and LH were determined by immunometric assays. RESULTS: All patients and controls showed significant circadian TSH rhythms, but the percentage amplitude was decreased (7.5% vs. 21.3%, P < 0.0001) and the acrophase was markedly displaced in SS patients, occurring between 0315 h and 1515 h in seven/nine patients and in two/nine controls (P = 0.057). Patients showed increased total 24-h TSH secretion (6054 +/- 2293 vs. 2193 +/- 340 mU/l/min, mean +/- SE, P = 0.04) due to increased non-pulsatile or tonic 24-h TSH secretion (5631 +/- 2105 vs. 1925 +/- 301 mU/l/min, P = 0.026), but no difference was detected in pulsatile secretion (424 +/- 191 vs. 268 +/- 41, P = 0.82). The contribution of non-pulsatile to total TSH secretion was also increased in SS patients (93.8% vs. 87.6%, P = 0. 002). No significant changes were found in TSH pulse frequency, amplitude, duration or interpeak interval. When cluster parameters were individually analysed in two distinctive 12-h periods corresponding to acrophase and nadir, patients showed increased non-pulsatile TSH secretion in both periods, but no differences were found in pulsatile TSH secretion, pulse frequency or amplitude. The increment of TSH secretion during the acrophase in SS patients was exclusively due to increased non-pulsatile TSH secretion, as opposed to controls who displayed significant increments in both non-pulsatile and pulsatile TSH secretions. CONCLUSIONS: Sheehan's syndrome patients have increased total TSH secretion due to increased tonic TSH secretion. A circadian TSH rhythm is still present in these patients, but shows decreased magnitude and markedly displaced acrophase.

Adult↗