PubMed Health⌕ Search

Biomedical subjects

A I Hernández

Publications and source records attributed to A I Hernández.

12 recordsLinked to original sources

Thymidine phosphorylase is noncompetitively inhibited by 5'-O-trityl-inosine (KIN59) and related compounds.

We found that 5'-O-trityl-inosine (KIN59) inhibits recombinant bacterial (E. coli) and human thymidine phosphorylase (TPase) with an IC50 of 44 microM and 67 microM, respectively. In contrast to previously described TPase inhibitors, KIN59 does not compete with thymidine (dThd) at the pyrimidine nucleoside-binding site or with inorganic phosphate (Pi) at the phosphate-binding site of the enzyme. These findings are strongly suggestive for the presence of an allosteric binding site at the enzyme. TPase is identical to the angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF). As such, PD-ECGF stimulates angiogenesis in the chick chorioallantoic membrane (CAM) assay. This angiogenic response was completely inhibited by KIN59. Inosine did not inhibit the enzyme or the angiogenic effect of TPase, confirming that the 5'-O-trityl group in KIN59 is essential for the observed effect. Our observations indicate that allosteric sites in TPase may regulate its biological activity.

Allosteric Site↗

Evaluation of real-time QRS detection algorithms in variable contexts.

A method is presented to evaluate the detection performance of real-time QRS detection algorithms to propose a strategy for the adaptive selection of ORS detectors, in variable signal contexts. Signal contexts are defined as different combinations of QRS morphologies and clinical noise. Four QRS detectors are compared in these contexts by means of a multivariate analysis. This evaluation strategy is general and can be easily extended to a larger number of detectors. A set of morphology contexts, corresponding to eight QRS morphologies (normal, PVC, premature atrial beat, paced beat, LBBB, fusion, RBBB, junctional premature beat), was extracted from 17 standard ECG records. For each morphology context, the set of extracted beats, ranging from 30 to 23000, was resampled to generate 50 realisations of 20 concatenated beats. These realisations were then used as input to the QRS detectors, without noise, and with three different types of additive clinical noise (electrode motion artifact, muscle artifact, baseline wander) at three signal-to-noise ratios (5 dB, -5 dB, -15 dB). Performance was assessed by the number of errors, which reflected both false alarms and missed beats. The results show that the evaluated detectors are indeed complementary. For example, the Pan-Tompkins detector is the best in most contexts but the Okada detector generates fewer errors in the presence of electrode motion artifact. These results will be particularly useful to the development of a real-time system that will be able to choose the best ORS detector according to the current context.

Algorithms↗

[Therapeutic efficacy of GM-CSF in pulmonary alveolar proteinosis].

Pulmonary alveolar proteinosis is a rare disease characterized by the deposit of lipid-rich proteinaceous material in alveolar spaces. The only effective treatment known to date has been periodic alveolar lavage, a technique that is laborious and requires that the patient be under general anesthesia, with selective endotracheal-bronchial intubation. Complications are not unknown. Progress in our understandint of the pathogenesis of pulmonary alveolar proteinosis has shown it to be related to changes it to be related to changes in alveolar macrophagocytic capability. We describe a patient in whom 8 weeks of subdermal GM-CSF treatment led to significant clinical, radiologic and lung function improvement.

Adult↗

Increased cAMP immunostaining in cerebral vessels in Alzheimer's disease.

Increasing evidence suggests that up-regulation of the cAMP-second messenger system is implicated in Alzheimer's disease neurodegeneration. Since previous studies reported an increased level of cAMP in microvessels of Alzheimer's patients compared with those from non-demented elderly controls, we have carried out an immunohistochemical study to compare cAMP immunostaining in brain vessels from patients with dementia and neuropathological criteria of Alzheimer's disease (n=5) with those of age-matched patients (n=10). We have also included a control group of adult patients (n=5) to evaluate the role of aging separate from the effects of dementia. Our results demonstrated an increased cAMP immunostaining in cerebral cortical and meningeal vessels from Alzheimer's patients compared to nondemented elderly and adult controls. Vascular cAMP immunostaining was mainly observed in frontal and temporal cortex, the hippocampus being the region that showed the more intense and widespread vascular cAMP immunostaining. We also observed a conspicuous vascular beta-amyloid immunostaining specifically in those vessels that showed the highest cAMP immunostaining. We suggest that increased vascular cAMP immunostaining is mainly localised in the selectively vulnerable targets of neurodegeneration that characterise AD. Moreover, the co-immunolocalisation of cAMP and beta-amyloid protein in cerebral vessels of patients with AD suggests a possible role of cAMP up-regulation in the accumulation of those amyloidogenic peptides.

Aged↗

Real-time ECG transmission via Internet for nonclinical applications.

Telemedicine is producing a great impact in the monitoring of patients located in remote nonclinical environments such as homes, elder communities, gymnasiums, schools, remote military bases, ships, and the like. A number of applications, ranging from data collection, to chronic patient surveillance, and even to the control of therapeutic procedures, are being implemented in many parts of the world. As part of this growing trend, this paper discusses the problems in electrocardiogram (ECG) real-time data acquisition, transmission, and visualization over the Internet. ECG signals are transmitted in real time from a patient in a remote nonclinical environment to the specialist in a hospital or clinic using the current capabilities and availability of the Internet. A prototype system is composed of a portable data acquisition and preprocessing module connected to the computer in the remote site via its RS-232 port, a Java-based client-server platform, and software modules to handle communication protocols between data acquisition module and the patient's personal computer, and to handle client-server communication. The purpose of the system is the provision of extended monitoring for patients under drug therapy after infarction, data collection in some particular cases, remote consultation, and low-cost ECG monitoring for the elderly.

Aged↗

N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria.

Mitochondrial oxidative damage is implicated in brain aging and in age-related neurodegenerative diseases. Since N-acetylcysteine (NAC) has recently been shown to prevent apoptotic death in neuronal cells and protect synaptic mitochondria proteins from oxidative damage in aged mice, we have investigated whether dietary administration of this thiolic antioxidant retards age-related memory loss. At 48 weeks of age, a control female OF-1 mice group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of NAC. After 23 weeks of this diet, the NAC had partially restored the memory deficit associated with aging in mice. Moreover, the lipid peroxide and protein carbonyl contents of the synaptic mitochondria were significantly decreased in the NAC-supplemented animals in comparison with their age-matched controls. The antioxidant properties and probable action on mitochondrial bioenergetic ability in the synaptic terminals may explain, at least partially, the beneficial action of NAC administration.

Acetylcysteine↗

Overview of CARMEM: a new dynamic quantitative cardiac model for ECG monitoring and its adaptation to observed signals.

Different approaches have been proposed in order to achieve knowledge integration for coronary care monitoring applications, usually in the form of expert systems. The clinical impact of these expert systems, which are based only on "shallow" knowledge, has not been remarkable due to the difficulties associated with the construction and maintenance of a complete knowledge base. Model-based systems represent an alternative to these problems because they allow efficient integration of the "deep" knowledge on the underlying physiological phenomena being monitored. In this work, a brief review of existing model-based systems for cardiac rhythm interpretation is presented, followed by the description of a new system for Cardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM). Fundamental characteristics of CARMEM are presented; in particular, its ability to provide online parameter adaptation to simulate complex rhythms and to match observed ECG signals. The proposed model can be useful for the explanation of the origin of cardiac arrhythmias and contribute towards their robust characterization in the context of coronary care units.

Artificial Intelligence↗

Hypothesis: can N-acetylcysteine be beneficial in Parkinson's disease?

Based on the finding of decreased mitochondrial complex I activity in the substantia nigra of patients with Parkinson's disease, we propose that the consequent reduction of ATP synthesis and increased generation of reactive oxygen species may be a possible cause of nigrostriatal cell death. Since sulfhydryl groups are essential in oxidative phosphorylation, thiolic antioxidants may contribute to the preservation of these proteins against oxidative damage. In the present paper, we hypothesize that treatment with a sulfur-containing antioxidant such as N-acetylcysteine may provide a new neuroprotective therapeutic strategy for Parkinson's disease.

Acetylcysteine↗

Multisensor fusion for atrial and ventricular activity detection in coronary care monitoring.

Information management for critical care monitoring is still a very difficult task. Medical staff is often overwhelmed by the amount of data provided by the increased number of specific monitoring devices and instrumentation, and the lack of an effective automated system. Specifically, a basic task such as arrhythmia detection still produce an important amount of undesirable alarms, due in part to the mechanistic approach of current monitoring systems. In this work, multisensor and multisource data fusion schemes to improve atrial and ventricular activity detection in critical care environments are presented. Applications of these schemes are quantitatively evaluated and compared with current methods, showing the potential advantages of data fusion techniques for event detection in noise corrupted signals.

Coronary Care Units↗

N-acetylcysteine protects against age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated the effect of a thiolic antioxidant on protein carbonyl content in synaptic mitochondria from female OF-1 mice. At 48 weeks of age, a control group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of N-acetylcysteine. A 24-week treatment resulted in a significant decrease in protein carbonyl content in synaptic mitochondria of the N-acetylcysteine-treated animals as compared to age-matched controls.

Acetylcysteine↗

Age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated their contents in synaptic mitochondria from five age groups of mice. Protein carbonyl content in synaptic mitochondria showed a significant positive correlation with age (r = 0.95, P = 0.01). A linear inverse relationship was observed between protein carbonyl content and complex IV/complex I ratio (which was used as an index of imbalance between mitochondrial respiratory complexes) in synaptic mitochondria in the five age groups (r = -0.99, P < 0.001). We suggest that age-related accumulation of oxidized proteins in synaptic mitochondria may be the result of an age-dependent increase in reactive oxygen species generation because of a disarrangement of mitochondrial oxidative phosphorylation.

Aging↗

[Epithelial hepatoblastomas in the adult].

Hepatoblastoma is the most frequent primary malignant liver neoplasm in childhood; in adults it is extremely rare and only 27 cases have been published. The prognosis of this neoplasm is poor because it is usually discovered late. Surgery, chemotherapy and liver transplantation have been tried with poor results. We present two adult patients who were diagnosed with an epithelial hepatoblastoma. The pathogenesis, histologic features and current management is reviewed.

Adult↗