Biomedical subjects

A Castro

Publications and source records attributed to A Castro.

At least 127 records · Page 7Linked to original sources

PubMed2001

CoMFA of benzyl derivatives of 2,1,3-benzo and benzothieno[3,2-alpha]thiadiazine 2,2-dioxides: clues for the design of phosphodiesterase 7 inhibitors.

A CoMFA study of benzo- and benzothienothiadiazines derivatives as phosphodiesterase 7 inhibitors has been carried out in order to determine the factors required for the activity of these compounds and also for the selectivity versus other phosphodiesterase isoenzymes. This methodology is employed to gain clues on the design of new fused thiadiazines with improved activity and selectivity on phosphodiesterase 7. Using the information achieved from the three CoMFA models, new structures have been designed in silico and their inhibitory activity on phosphodiesterase 7 was predicted.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

c-Mos and cyclin B/cdc2 connections during Xenopus oocyte maturation.

Fully-grown G2 arrested Xenopus oocytes can be induced to enter and progress into meiotic cell cycle by progesterone stimulation. This process is termed oocyte maturation. An early response to progesterone is the synthesis of the onco-protein c-Mos, defined as the candidate initiator of Xenopus oocyte maturation, which triggers the MAPK cascade, MPF activation and promotes CSF activity. Here we review our current knowledge on the synthesis, activation and functions of c-Mos in connection with MPF activation during maturation. We also discuss our recent results concerning the dispensability of cyclin B degradation in meiosis I-meiosis II transition and the stabilization of c-Mos through its direct phosphorylation by cyclin B/cdc2.

Anaphase-Promoting Complex-Cyclosome↗

PubMed2001

[Acute myocardial infarction in nocturnal paroxysmal hemoglobinuria].

The case of a 62-year-old diabetic and smoker male who was under study in another hospital due to anemia, thrombopenia and hematuria of several months of evolution is presented. The patient was admitted to the coronary unit for an acute extensive transmural myocardial infarction and treated with t-PA. A few hours later the patient presented hematuric urine, a decrease in hemoglobin and platelets and acute renal insufficiency. Hematologic study confirmed the diagnosis of paroxystic nocturnal hemoglobinuria. The evolution of the patient was poor despite intensive medical treatment requiring hemodialysis. The patient presented cardiac tamponade and died. The role of hematologic disease in acute myocardial infarction and the treatment and evolution of the coronary syndrome in the context of the disease are discussed.

Hemoglobinuria, Paroxysmal↗

PubMed2001

[Progress in the knowledge on endothelial dysfunction and its application in clinical practice].

The endothelium plays a crucial role in the maintenance of vascular homeostasis; endothelial cells produce a series of molecules that determine vascular tone and modulate the interactions between the arterial wall components and the circulating blood. Endothelial dysfunction (ED) thus results in significantly impaired physiological responses that often lead to atheroma formation. Recent studies suggest that endothelial dysfunction as assessed invasively during coronary angiography is a prognostic marker. Recently, a non-invasive ultrasound technique has been developed which may allow screening of ED in both patients and healthy subjects. This article reviews current knowledge regarding non-invasive assessment of endothelial dysfunction and proposes potential uses of a promising ultrasound technique.

Cardiovascular Physiological Phenomena↗

PubMed2001

[Hormone replacement therapy in ischemic heart disease prevention in women. Arguments against].

Hormone replacement therapy is one of the most difficult issues women and their doctors face. Epidemiological studies have consistently found that women using hormone replacement therapy are at a substantially lower risk of developing coronary heart disease. Observational data are supported by findings demonstrating that hormone replacement therapy improves several risk factors o coronary heart disease, specially the favourable changes in lipid profile. However, no study has clearly established hormones help prevent heart disease. In women without heart disease, the benefits of hormone replacement therapy are unclear. However, recent clinical trials have sown that the use of hormone replacement therapy does not provide cardiovascular benefits in women with established heart disease.

Adult↗

PubMed2001

[When chromosomal dynamics control cell division].

In most tumor cells a chromosomal instability leads to an abnormal chromosome number (aneuploidy). The mitotic checkpoint is essential for ensuring accurate chromosome segregation by allowing mitotic delay in response to a spindle defect. This checkpoint delays the onset of anaphase until all the chromosomes are correctly aligned on the mitotic spindle. When unattached kinetochores are present, the metaphase/anaphase transition is not allowed and the time available for chromosome-microtubule capture increases. Genes required for this delay were first identified in Saccharomyces cerevisiae (the MAD, BUB and MPS1 genes) and subsequently, homologs have been identified in higher eucaryotes showing that the spindle checkpoint pathway is highly conserved. The checkpoint functions by preventing an ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC) from ubiquitinylating proteins whose destruction is required for anaphase onset.

Aneuploidy↗

PubMed2001

The APC is dispensable for first meiotic anaphase in Xenopus oocytes.

Here we show that segregation of homologous chromosomes and that of sister chromatids are differentially regulated in Xenopus and possibly in other higher eukaryotes. Upon hormonal stimulation, Xenopus oocytes microinjected with antibodies against the anaphase-promoting complex (APC) activator Fizzy or the APC core subunit Cdc27, or with the checkpoint protein Mad2, a destruction-box peptide or methylated ubiquitin, readily progress through the first meiotic cell cycle and arrest at second meiotic metaphase. However, they fail to segregate sister chromatids and remain arrested at second meiotic metaphase when electrically stimulated or when treated with ionophore A34187, two treatments that mimic fertilization and readily induce chromatid segregation in control oocytes. Thus, APC is required for second meiotic anaphase but not for first meiotic anaphase.

Anaphase↗

PubMed2001

Radiofrequency catheter ablation of idiopathic left ventricular outflow tract tachycardia: utility of intracardiac echocardiography.

INTRODUCTION: The site of origin of idiopathic ventricular tachycardia (VT) arising from the left ventricular outflow tract (LVOT) may be closely related to the aortic valve leaflets, and radiofrequency (RF) delivery potentially can damage them. Intracardiac echocardiography (ICE) can identify accurately the ablation electrode and anatomic landmarks, and contact with the endocardium can be easily assessed. The aim of this study was to define the utility and the accuracy of ICE in guiding RF ablation of idiopathic VT of the LVOT. METHODS AND RESULTS: Five consecutive patients (all men; mean age 20.4 years, range 16 to 25) symptomatic for idiopathic VT underwent RF ablation. A 9-French, in-sheath catheter with a 9-MHz ultrasound transducer was inserted through the femoral vein and positioned in the His-bundle region or right ventricular outflow tract to provide a clear view of the aortic root. Local earliest ventricular activation during tachycardia and pace mapping were used to identify the ablation site. Idiopathic VT was ablated successfully in all patients using a median of two RF pulses, delivered during tachycardia. High-resolution images of the aortic valve and ablation electrode were achievable in all cases. Direct vision of ablation electrode-endocardial contact in the outflow tract was assessed easily in all patients. CONCLUSION: Idiopathic VT of the LVOT can be treated successfully with RF ablation. ICE can accurately guide catheter ablation and identify anatomic landmarks, endocardial contact, and ablation electrode movement.

Adolescent↗

PubMed2001

Cyclin B/cdc2 induces c-Mos stability by direct phosphorylation in Xenopus oocytes.

The c-Mos proto-oncogene product plays an essential role during meiotic divisions in vertebrate eggs. In Xenopus, it is required for progression of oocyte maturation and meiotic arrest of unfertilized eggs. Its degradation after fertilization is essential to early embryogenesis. In this study we investigated the mechanisms involved in c-Mos degradation. We present in vivo evidence for ubiquitin-dependent degradation of c-Mos in activated eggs. We found that c-Mos degradation is not directly dependent on the anaphase-promoting factor activator Fizzy/cdc20 but requires cyclin degradation. We demonstrate that cyclin B/cdc2 controls in vivo c-Mos phosphorylation and stabilization. Moreover, we show that cyclin B/cdc2 is capable of directly phosphorylating c-Mos in vitro, inducing a similar mobility shift to the one observed in vivo. Tryptic phosphopeptide analysis revealed a practically identical in vivo and in vitro phosphopeptide map and allowed identification of serine-3 as the largely preferential phosphorylation site as previously described (Freeman et al., 1992). Altogether, these results demonstrate that, in vivo, stability of c-Mos is directly regulated by cyclin B/cdc2 kinase activity.

Animals↗

PubMed2001

Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome.

CDK9 paired with cyclin T1 forms the human P-TEFb complex and stimulates productive transcription through phosphorylation of the RNA polymerase II C-terminal domain. Here we report that CDK9 is ubiquitinated and degraded by the proteasome whereas cyclin T1 is stable. SCF(SKP2) was recruited to CDK9/cyclin T1 via cyclin T1 in an interaction requiring its PEST domain. CDK9 ubiquitination was modulated by cyclin T1 and p45(SKP2). CDK9 accumulated in p45(SKP2-/-) cells, and its expression during the cell cycle was periodic. The transcriptional activity of CDK9/cyclin T1 on the class II major histocompatibility complex promoter could be regulated by CDK9 degradation in vivo. We propose a novel mechanism whereby recruitment of SCF(SKP2) is mediated by cyclin T1 while ubiquitination occurs exclusively on CDK9.

Anaphase-Promoting Complex-Cyclosome↗

PubMed2001

Anti-HIV-1 activity of benzothiadiazine dioxide.

Antiviral assays carried out on the potent benzothiadiazine dioxide (BTD) human cytomegalovirus (HCMV) inhibitors have led us to find marginal but selective anti-HIV-1 activity. Specific pharmacological studies, such as time of addition experiments and assays on specific viral strains with mutations on its reverse transcriptase, have indicated that BTD compounds act as non-nucleoside reverse transcriptase inhibitors. Theoretical calculations showed a butterfly conformation for the active derivatives that are compatible with their mechanism of action. Therefore, BTD derivatives can be considered as potential lead compounds for the treatment of opportunistic HCMV infections in immunocompromised individuals such as AIDS patients.

Antiviral Agents↗

PubMed2001

Morphologic capillary changes and manifestations of connective tissue diseases in patients with primary biliary cirrhosis.

The objective of this study was to investigate the presence of nailfold capillary abnormalities and extrahepatic signs of connective tissue disease in patients with primary biliary cirrhosis (PBC), as compared to patients with other chronic liver diseases. We evaluated 22 patients with PBC and 15 patients with other chronic liver diseases as a control group. Nailfold capillaroscopy was performed by two observers blinded to clinical findings using a Wild M3 stereomicroscope with an Intralux 5000 Volpi cold light lamp. We detected nailfold capillary abnormalities in 20 out of 22 (91%) PBC patients. Twelve of these 20 patients (54%) showed capillary alterations characteristic of systemic sclerosis. In the control group only two out of 15 patients (13%) presented alterations and in both cases they were a non-specific type. The presence of nailfold capillary abnormalities was significantly greater in PBC patients than in the control group (P < 0.001). Eleven out of the 22 PBC patients (50%) had extrahepatic signs of connective tissue disease and most of them were related to systemic sclerosis; patients with other chronic liver diseases did not present rheumatic manifestations (P < 0.001). In PBC patients there was a significant association between systemic sclerosis capillary pattern and rheumatic manifestations (P < 0.03). The high prevalence of nailfold capillary abnormalities characteristic of systemic sclerosis in patients with PBC and the correlation with sclerodermal manifestations suggests that this capillaroscopic finding could be a useful indicator to investigate rheumatic manifestations in these patients.

Adult↗

PubMed2001

Peripheral and dual binding site acetylcholinesterase inhibitors: implications in treatment of Alzheimer's disease.

Recently advances in understanding the molecular basis of Alzheimer's disease have led to the consideration of the relationship between cholinergic inhibitors and amyloid deposition as a new hypothesis for the future rational design of effective anti-Alzheimer drugs. In the present review, the non-cholinergic functions of acetylcholinesterase (AChE) and the therapeutic potential of peripheral and dual binding site AChE inhibitors in delaying the neurodegenerative process will be discussed.

Acetylcholinesterase↗

PubMed2001

Facilitation of atrioventricular reentrant tachycardia by iatrogenic right bundle branch block.

The present case report describes the diagnosis of a concealed bypass tract in the right lateral wall revealed by electrophysiologic evaluation performed in a patient with rare palpitations. A iatrogenic right bundle branch block (RBBB) caused the occurrence of an incessant atrioventricular reentrant tachycardia. The disappearance of the RBBB determined a very difficult induction of the tachycardia that, when induced, showed a shorter cycle length and ventriculoatrial interval than those observed during RBBB tachycardia. The presence of a RBBB ipsilateral to the right free wall accessory pathway provided a critical delay within the circuit thus allowing the bypass tract to recover excitability. This relevant delay also allows the sinus beat to initiate and stabilize the tachycardia thus rendering it incessant.

Adult↗

PubMed2001

[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].

BACKGROUND: Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. OBJECTIVE: Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. DESIGN: Prospective study. PATIENTS: One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. RESULTS: Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. CONCLUSION: These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

Aged↗

PubMed2001

Echocardiographic patterns and prognosis in heart failure.

BACKGROUND: There are many variables with prognostic value in patients with heart failure (HF). Those related to left ventricular function are among the most important. Recently, the evaluation of the patterns of ventricular filling by pulsed Doppler echocardiography has been studied as a variable with prognostic value. OBJECTIVES: To evaluate the prognostic value of echocardiography variables (diastolic and systolic) in patients with HF. These variables were analysed in respect to hospital admission for cardiovascular reasons or death. MATERIAL AND METHODS: We evaluated 157 consecutive patients with HF and included 110 patients who were in sinus rhythm. The mean age was 68.2 +/- 0.9 years. HF was ischemic in 52.7%. Patients underwent echocardiography examination within the week of reference. The patients were grouped according to left ventricular (LV) systolic dysfunction (LV ejection fraction < 40%). We also classified patients in two groups according to the presence of a restrictive pattern in diastolic transmitral flow profile. Finally, we classified all patients in four groups according to their systolic function and diastolic pattern: Group I--systolic dysfunction and restrictive ventricular filling pattern. Group II--systolic dysfunction without restrictive ventricular filling pattern. Group III--without systolic dysfunction with restrictive ventricular filling pattern. Group IV--without systolic dysfunction without restrictive ventricular filling pattern. The events were death or hospital admission. The mean follow up time was 625 +/- 55 days. We did a statistical analysis and for all tests a p value < 0.05 was considered statistically significant. RESULTS: We found impaired LV systolic function (systolic HF) in 73.6% and restrictive ventricular filling pattern in 45.5%. During the follow-up 41.8% died or were admitted to hospital. Patients with systolic HF had lower admission free survival rate. Patients with restrictive ventricular filling pattern had lower admission free survival rate than those without. Group I had lower admission free survival rate than Group II and Group IV. Group IV had a higher admission free survival than all other Groups. CONCLUSIONS: These results support and expand previous observations that diastolic function variables, such as the pattern of ventricular filling (namely the restrictive) have independent prognostic value in patients with HF.

Aged↗

PubMed2000

Measurement of J/psi and psi(2S) polarization in pp collisions at sqrt[s] = 1.8 TeV.

We have measured the polarization of J/psi and psi(2S) mesons produced in pp collisions at sqrt[s] = 1.8 TeV, using data collected at the Collider Detector at Fermilab during 1992-1995. The polarization of promptly produced J/psi [psi(2S)] mesons is isolated from those produced in B-hadron decay, and measured over the kinematic range 4 [5.5]<P(T)<20 GeV/c and |y|<0.6. For P(T) greater than or approximately equal 12 GeV/c we do not observe significant polarization in the prompt component.

Journal Article↗

PubMed2000

Entamoeba sp. (Sarcomastigophora: Endamoebidae) from ostriches (Struthio camelus) (Aves: Struthionidae).

The first case of Entamoeba of the 1-nucleate mature cyst group in birds is described. Trophozoites and cysts of Entamoeba have been found in ostriches (Struthio camelus) from farms located all over Spain. The cysts are large (13.47microm mean diameter); they possess one nucleus when mature, with a large endosome and peripheral chromatine arranged in small granules; chromatoid bodies, when present, are large and elongated. Trophozoites are large (19. 88microm mean diameter), with a clear differentiation between ecto- and endoplasm, this containing numerous vacuoles; the nucleus is large and diffuse. The characteristics of this amoeba resembles but do not completely fulfill those of E. suis and E. chattoni; also, these species are from mammals.

Animal Husbandry↗