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Biomedical subjects

I Valencia

Publications and source records attributed to I Valencia.

At least 19 recordsLinked to original sources

[The role played by calcium in neuronal injury following neonatal hypoxia or convulsions].

AIM: Calcium plays a complex and pivotal role both in neuronal development and function, and in hypoxia/ ischemia-induced cell death. In this paper, we review current concepts of calcium function emphasizing the neonatal period. DEVELOPMENT: Calcium enters the neuron through glutamate receptors (NMDA and AMPA) located on the neuronal membrane. After hypoxia or seizures, there is a conformational change of the receptors, with increased flow of calcium into the cytoplasm. Cytoplasmatic calcium triggers activation of several free-radical generation pathways, including the nitric oxide pathway, with a deleterious effect upon the neuron. Calcium then enters the neuronal nucleus, through specific receptors on the nuclear membrane. In our experience, hypoxia and neonatal seizures create nuclear membrane dysfunction, increasing the nitric-oxide-dependent flow of calcium into the nucleus. Nuclear calcium increase is critical for genetic transcription, pro-apoptotic gene activation and a cascade of biochemical and molecular events that lead to an increase of caspases and apoptotic neuronal death. CONCLUSIONS: Calcium has a crucial role in neuronal damage after neonatal hypoxia or seizures. A better knowledge of the pathogenic mechanisms that lead to neuronal damage after neonatal hypoxia or seizures will assist in future development of efficacious neuroprotective therapies.

Calcium↗

[Cerebrovascular disorders in preterm neonates].

AIM: To review the etiology, pathogenesis, clinical manifestations, diagnosis and treatment of cerebrovascular disorders (CVD) in preterm neonates. DEVELOPMENT: The germinal matrix-intraventricular hemorrhage (GM-IVH) is the most frequent intracranial hemorrhage. The pathogenesis includes intravascular, vascular and extravascular factors. The neuropathologic lesion is the hemorrhage within the subependymal GM. There are four degrees of severity. Clinical manifestations include three syndromes: catastrophic, saltatory and silent. Treatment is prophylactic. Periventricular hemorrhagic infarct is of venous origin, might be associated to GM-IVH and is difficult to differentiate from periventricular leukomalacia (PVL). Cerebellar hemorrhage frequency increases with decreasing gestational age. It may be asymptomatic or manifest with a non-specific neurologic picture. PVL is the most important ischemic lesion. Its pathogenesis includes anatomic, physiologic, maturational, biochemical, infectious and immunologic factors. The neuropathologic lesion is focal necrosis in the terminal distribution of the long penetrating arteries. Treatment is prophylactic. Other ischemic lesions are ischemic arterial infarct, cerebellar infarct, telencephalic leukoencephalopathy and pontosubicular necrosis. CVD diagnostic tests include cerebral ultrasound, computed tomography, magnetic resonance imaging and spectroscopy and electroencephalogram. Mortality of some CVD is high and some others are associated with a high risk of cerebral palsy and cognitive deficits. CONCLUSION: CVD are common in preterm neonates and represent an important cause of neurologic disease in the child.

Brain Ischemia↗

Growth kinetics of progenitor cell-enriched hematopoietic cell populations in long-term liquid cultures under continuous removal of mature cells.

BACKGROUND: During long-term culture of primitive hematopoietic cells large numbers of mature cells are generated that, on the one hand, consume nutrients and cytokines present in the medium and, on the other hand, may produce or elicit the production of soluble factors that limit the growth of primitive cells. Thus it is possible that under standard culture conditions hematopoietic stem and progenitor cells are unable to display their true proliferation and expansion potentials. METHODS: Hematopoietic cell populations, enriched for CD34+ cells, were obtained from both umbilical cord blood (UCB) and mobilized peripheral blood (MPB), and cultured in cytokine-supplemented liquid culture, under continuous removal of mature cells by means of weekly re-selection of primitive, lineage-negative (Lin-) cells. Proliferation and expansion capacities of such cells were determined weekly for a 42-day culture period. RESULTS: As expected, based on our previous studies in standard liquid cultures, throughout the culture period there was a continuous decrease in the proportion of progenitor cells; however, after every re-selection on days 7, 14 and 21, there was a significant enrichment for both CD34+ cells and colony-forming cells (CFC). As a result of such an enrichment, the cumulative increase in the numbers of total cells and CFC in cultures with two, three or four selections was significantly higher than the increments observed in standard cultures, in which only a single selection was performed on day 0. Cultures of UCB cells showed consistently higher levels of both total cells and CFC than cultures of MPB cells. DISCUSSION: Taken together, these results indicate that continuous removal of mature cells from liquid cultures of primitive progenitors results in higher increments in the levels of both total cells and CFC.

Adolescent↗

Relapse of herpes encephalitis after acyclovir therapy: report of two new cases and review of the literature.

Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.

Acyclovir↗

Vagus nerve stimulation in pediatric epilepsy: a review.

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.

Adolescent↗

Effects of psychological techniques on bruxism in children with primary teeth.

Four main causes of bruxism have been studied - high anxiety level, malocclusion, temporomandibular disorders (TMD) and oral habits. Effective dental treatment for this problem is unknown in children with primary teeth, although, high prevalence has been reported. The aim of this study was to investigate the effectiveness of psychological techniques in children with bruxism. A total of 33 children, 3-6 years of age with normal occlusal features, without oral habits, rate in the Conners' parent rating scales (CPRS) and more than 0.75% in Conners' teacher rating scales (CTRS), and one or more temporomandibular joint (TMJ) disorders registered in the Bernal and Tsamtsouris examination, were selected from 188 children. Two psychological techniques, 'directed muscular relaxation' and 'competence reaction', were applied for 6 months. The results were analysed with a Wilcoxon rank sum test. All patients reduced their anxiety level and TMJ disorders, with statistical significance (P < 0.05). The psychological techniques were effective in the reduction of signs of bruxism in children with primary teeth.

Anxiety↗

Lead induces endothelium- and Ca2+-independent contraction in rat aortic rings.

The contractile effect of lead on rat aortic rings was examined. Lead (0.1-3.1 mM) elicited concentration-dependent but endothelium-independent contractions, which were unaffected by prazosin (1 microM). The contractile effects of lead were similar when the aortic rings were bathed either in the absence or presence of external Ca2+. Lanthanum (1 mM) but not verapamil (I pM) inhibited the lead contractions; hence non-L-calcium channels are involved in such effect. In addition, lead induced contractions on aortic rings incubated in Ca2+-free EGTA-containing solution for 70 min., an experimental condition in which intracellular Ca2+-stores are depleted. Finally, the contractile effect of lead was not modified by calphostin C (an inhibitor of protein kinase C). In conclusion, the present results suggest that in rat aorta, the lead-induced contraction is independent of extra- and intracellular calcium stores. In addition, the effect of lead is independent of either catecholamines or protein kinase C. It is likely that in rat aorta, lead enters into the smooth muscle cells through non-L-calcium channels, and when acting like calcium on the contractile machinery it produces contraction. The differences observed between our results and those obtained by other authors may indicate that the mechanism of the contractile effect of lead varies among the different blood vessels.

Animals↗

Auditory evoked responses to similar words with phonemic difference: comparison between children with good and poor reading scores.

Our previous study demonstrated a physiologic deficit in two-tone discrimination in poor readers. This was specific to the left parietal area suggesting that poor readers handled rapid tones differently. The current paper extends this finding in the same population, demonstrating that poor readers also have difficulty with phonemic discrimination. Long latency auditory evoked potentials (AEP) were formed using a phonemic discrimination task in a group of children with reading disabilities and controls. Measuring peak-to-peak amplitude of the waveforms, we found reduced N1-P2 amplitude in the Poor Reader group. Using the t-statistic significance probability map (SPM) technique, we also found a group difference, maximal over the mid-parietal area, from 584 msec to 626 msec after the stimulus onset. This difference was due to a lower amplitude on the Poor Reader group. We hypothesized that this late difference constitutes a P3 response and that the Poor Reader group generated smaller P3 waves. These auditory evoked response (AER) data support a discrimination deficit for close phonemes in the Poor Reader group as they had smaller N1-P2 absolute amplitude and developed smaller P3 waves. Based on these data we should be able to differentiate between Good and Poor readers based on long latency potentials created from phonemic stimuli.

Acoustic Stimulation↗

Auditory evoked response data reduction by PCA: development of variables sensitive to reading disability.

Long latency auditory evoked responses (AER) were formed on 232 healthy normal and learning impaired subjects to tone pairs of 50 msec inter-stimulus interval (TALAER) and also to the words "tight" and "tyke" (TTAER). Both evoked potential (EP) type have been used to demonstrate differences between good readers (WIAT Basic Reading score > 115, N = 42) and poor readers (Reading score < 85, N = 42). A largely automated, hands off approach was used to reduce artifact contamination, to develop canonical measures for discriminating good from poor readers, and to predict reading scores across the entire population including intermediate (average) readers. Eye and muscle artifact were diminished by multiple regression. Substantial EP data reduction was enabled by an unrestricted use of Principal Components Analysis (PCA). For each EP type, 40 factors encompassed 70-80% of initial variance, a meaningful data reduction of about 90:1. Factor interpretation was enhanced by mapping of the factor loadings. By discriminant analysis, resulting factors predicted reading group membership with over 80% jackknifed and also split--half replication accuracy. By multiple regression, they produced a canonical variate correlating significantly (p < 0.001) with the Basic Reading score (r = 0.39). The TTAER factors were more useful than the TALAER factors. The relevance of rapid auditory processing and phonemic discrimination measurements to dyslexia is discussed.

Brain Mapping↗

Postoperative pressure-induced alopecia: report of a case and discussion of the role of apoptosis in non-scarring alopecia.

We report a case of postoperative pressure induced alopecia in a 21-year-old black female after multiple intraoperative procedures. The histopathology is distinctive and demonstrated features in common with trichotillomania and alopecia areata, including the presence of pigment casts, catagen follicles, melanophages and apoptotic bodies. External hair manipulation is considered the primary event in the etiology of pigment casts, however, our present case demonstrated numerous pigment casts despite a complete lack of evidence of external hair manipulation. We performed pattern analysis and in situ end-labeling in 19 cases of non-scarring alopecia. Pigment casts were seen in postoperative alopecia (1 case), alopecia areata (1 case) and trichotillomania (5 cases). These forms of alopecia have in common the sudden termination of the anagen phase of the hair cycle. When the anagen portion of the hair cycle is prematurely disrupted hairs enter into catagen. Pigment casts may represent a non-specific reaction pattern of follicles that are suddenly transformed from anagen to catagen. We therefore propose that hair manipulation is not uniquely responsible for the formation of pigment casts. The primary pathophysiology resulting in the formation of pigment casts more correctly reflects the sudden termination of the anagen phase of the hair cycle.

Adult↗

Kinetics of hematopoiesis in Dexter-type long-term cultures established from human umbilical cord blood cells.

In the present study, we have established Dexter-type long-term cultures (D-LTC) from human umbilical cord blood (UCB) and followed the kinetics of different hematopoietic progenitor cells (HPCs)--including multipotent (colony forming unit [CFU]-Mixture), erythroid (CFU-erythroid, BFU-E), and myeloid (CFU-granulocyte, CFU-macrophage, CFU-granulocyte/marcophage) progenitors as well as of morphologically recognizable erythroid, myeloid and lymphoid cells--during a nine-week culture period. D-LTC were also established from adult bone marrow (BM) as controls. On day 0, both UCB and BM showed similar total numbers of HPCs (about 310/10(5) cells), however, UCB showed a higher proportion of primitive HPCs (i.e., CFU-Mixture, CFU-granulocyte/macrophage and BFU-E). A poor adherent cell layer, consisting almost exclusively of macrophages, was developed in UCB D-LTC and this correlated with a continuous decline in HPC numbers throughout the culture period. In contrast, adherent cell numbers in BM D-LTC, including fibroblasts and macrophages, were two- to fourfold higher than in UCB cultures, and the numbers of HPCs were also significantly higher, reaching plateau levels between weeks 6 and 9. In both types of cultures, erythroid and multipotent progenitors declined relatively fast, reaching undetectable levels after five weeks of culture. Myeloid progenitors, on the other hand, were sustained longer (always at higher levels in BM cultures) and were still detected by week 9. Among myeloid progenitors, a shift towards the predominance of macrophage HPCs was observed, both in UCB and BM D-LTC, and this correlated with an increase in the proportion of mature monocytes and macrophages. Taken together, our results indicate that myeloid progenitor cell growth is deficient in UCB D-LTC and suggest that this is due to the impaired development of an adherent cell layer, unable to provide the factors and conditions required for their growth. Interestingly, throughout the culture period the total numbers of multipotent and erythroid progenitors were similar both in UCB and BM cultures regardless of the number and types of adherent cells present; this suggests that the stroma developed in D-LTC is not sufficient for the proliferation of these progenitor cells.

Bone Marrow Cells↗

alpha-Methylnoradrenaline-induced contractions in rat aorta are mediated via alpha 1D-adrenoceptors.

The subtype(t) of alpha-adrenoceptor-mediating contractions to alpha-methynoradrenaline in the rat aorta has been investigated by using alpha-adrenoceptor-selective competitive antagonists and the alpha 1-adrenoceptor selective agonist, phenylephrine, for comparison. alpha-Methylnoradrenaline and phenylephrine elicited concentration-dependent contractions in the endothelium-denuded and endothelium-intact aortic rings with similar potencies and maximal effects. alpha-Methylnoradrenaline- and phenylephrine-induced contractions in endothelium-denuded aortic rings were competitively antagonized by prazosin (pA2 = 9.38 and 9.13; respectively) and rauwolscine (pA2 = 7.19 and 6.60, respectively). This confirms that there is an alpha 1- and a non alpha 2-adrenoceptor response to alpha-methylnoradrenaline in the rat aorta. The subtype selective alpha 1D-adrenoceptor antagonist, BMY 7378, was found to antagonize contractions to alpha-methylnoradrenaline and phenylephrine competitively in endothelium-denuded and endothelium-intact aortic rings. The pA2 values of BMY 7378 against alpha-methylnoradrenaline (8.39 and 8.41; endothelium-intact and endothelium-denuded, respectively) and phenylephrine (8.64 and 8.76; endothelium-intact and endothelium-denuded, respectively), are consistent with its published functional potency and clonal alpha 1D-adrenoceptor binding affinity. In addition, contractions to alpha-methylnoradrenaline and phenylephrine in endothelium-denuded aortic rings, were potently inhibited by WB 4101 with pA2 values of 9.75 and 9.25, respectively. The high pA2 values for WB 4101 indicate that the alpha 1B-adrenoceptor subtype does not seem to participate in alpha-methylnoradrenaline (and phenylephrine) induced contractions in this artery. These results suggest that the alpha 1D-subtype plays a determining role in rat aorta contractions induced by alpha-methylnoradrenaline.

Adrenergic alpha-Agonists↗

Effects of thiopental on endothelium-dependent responses in rat aorta.

Effects of pretreatment with thiopental on endothelium-dependent vasodilator responses elicited by drugs in rat aortic rings were investigated. The vasodilators employed were acetylcholine and histamine (endothelium- and receptor-dependent), A23187 (endothelium-dependent but receptor-independent) and sodium nitroprusside (endothelium-independent); they were tested 15 or 60 min after aortic preparations were exposed during 15 min to thiopental. Pretreatment with the barbiturate reversibly inhibited relaxation elicited by either acetylcholine and histamine, but a high concentration of the anesthetic was needed (3.1 mg/ml). On the contrary, thiopental did not modify the relaxation elicited by sodium nitroprusside or A23187. In addition, the barbiturate inhibited basal and acetylcholine-stimulated production of nitrites (an indicator of nitric oxide output) in aortic rings. In conclusion, thiopental inhibited the endothelium-dependent relaxation elicited by either acetylcholine or histamine. Although the barbiturate also inhibited nitric oxide production, the reduction in the relaxant response provoked by it does not seem to be the result of direct guanylate cyclase or nitric oxide synthase alterations, since thiopental did not modify the effect of sodium nitroprusside or A23187. Disturbances elicited by thiopental on endothelial receptors or on signal transduction elements may indirectly provoke nitric oxide synthase inhibition.

Animals↗