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Biomedical subjects

F Peña

Publications and source records attributed to F Peña.

At least 19 recordsLinked to original sources

Absence of enteroviral RNA in hearts explanted from patients with dilated cardiomyopathy.

BACKGROUND: The role of enterovirus infection in the pathogenesis of dilated cardiomyopathy (DCM) remains unclear. The objective of this study was to determine the prevalence of enterovirus in hearts explanted from patients with DCM and to compare it with enterovirus prevalence in hearts explanted from patients with other etiologies and in healthy donor hearts. METHODS: A total of 138 cardiac samples were analyzed, 70 from heart donors and 68 from transplant recipients (22 with DCM). A highly sensitive enterovirus-specific nested RT-PCR was used to test for enterovirus. RESULTS: All tests were negative except for one positive result that was attributed to carryover because sequencing of the amplification product showed it to be identical to the positive control. CONCLUSIONS: In this study the sample of explanted hearts nested RT-PCR showed no evidence of the presence of enteroviral RNA. This suggests that if enterovirus had a role in the genesis of DCM, it does not require or lead to the persistence of the virus in myocardial tissue.

Adolescent↗

Neurotoxic and synaptic effects of okadaic acid, an inhibitor of protein phosphatases.

Protein phosphorylation and dephosphorylation reactions, catalyzed by kinases and phosphatases, are involved in the regulation of a wide variety of physiological processes. In the nervous system, such reactions seem to modulate the function of several proteins crucial in synaptic transmission, including voltage-gated and ligand-gated channels, neurotransmitter release, and neurotransmitter transporters. On the other hand, hyperphosphorylation of certain cytoskeletal proteins or receptors may lead to neuronal death. In the present work we review the neurotoxic effect of okadaic acid (OKA), a potent and specific inhibitor of the serine/threonine protein phosphatases 1 and 2A, as well as its action on synaptic function. We analyze recent findings demonstrating that the microinjection of OKA in rat hippocampus induces neuronal stress, hyperexcitation and neurodegeneration, and discuss their possible relationships to alterations of protein phosphorylation-dephosphorylation observed in Alzheimer's disease brain. These results suggest that protein hyperphosphorylation due to inhibition of phosphatases in vivo induces neuronal stress and subsequent neurodegeneration.

Animals↗

Relationships among seizures, extracellular amino acid changes, and neurodegeneration induced by 4-aminopyridine in rat hippocampus: a microdialysis and electroencephalographic study.

4-Aminopyridine is a powerful convulsant that induces the release of neurotransmitters, including glutamate. We report the effect of intrahippocampal administration of 4-aminopyridine at six different concentrations through microdialysis probes on EEG activity and on concentrations of extracellular amino acids and correlate this effect with histological changes in the hippocampus. 4-Aminopyridine induced in a concentration-dependent manner intense and frequent epileptic discharges in both the hippocampus and the cerebral cortex. The three highest concentrations used induced also a dose-dependent enhancement of extracellular glutamate, aspartate, and GABA levels and profound hippocampal damage. Neurodegenerative changes occurred in CA1, CA3, and CA4 subfields, whereas CA2 was spared. In contrast, microdialysis administration of a depolarizing K+ concentration and of tetraethylammonium resulted in increased amino acid levels but no epileptic activity and no or moderate neuronal damage. These results suggest that seizure activity induced by 4-aminopyridine is due to a combined action of excitatory amino acid release and direct stimulation of neuronal firing, whereas neuronal death is related to the increased glutamate release but is independent of seizure activity. In addition, it is concluded that the glutamate release-inducing effect of 4-aminopyridine results in excitotoxicity because it occurs at the level of nerve endings, thus permitting the interaction of glutamate with its postsynaptic receptors, which is probably not the case after K+ depolarization.

4-Aminopyridine↗

Beekeeper' arthropathy.

OBJECTIVE: To describe the clinical, analytical, and radiological features of an observed arthropathy affecting beekeepers. METHODS: Prospective study of 34 patients (32 male, 2 female), mean age 42 years (range 16 to 66 years), evaluated for the presence of acute or chronic arthritis related to beekeeping. All patients were working and living in the same village, Fuenlabrada de los Montes (1300 habitants), where there is a census of 180 beekeepers. An epidemiologic inquiry reported that > 50% of them reported episodes of arthritis on the hands during the month of August, at the time of honey collection. RESULTS: Acute arthritis was observed in 10 patients. Pain, tenderness, joint swelling, and warmth were present in most cases. Chronic arthropathy was noted in 32 patients. Tenderness was present in 16 cases, synovial thickening in 12, limited joint mobility in 8, bony swelling in 15, and joint deformities in 13 patients. Radiological study showed periarticular soft tissue swelling, bone sclerosis, periostitis, bony erosions, subchondral cysts, geodes, osteophytes, and joint narrowing. CONCLUSION: Beekeepers have joint disease apparently related to bee stings. Etiopathogenesis is unknown. Mechanical trauma, venom compounds, infection, and foreign body synovitis are factors that are thought to influence the pathogenesis of this syndrome. We designate the condition "beekeepers' arthropathy," and consider it an occupational disorder.

Adolescent↗

Study on the possible involvement of protein kinases in the modulation of brain presynaptic sodium channels; comparison with calcium channels.

A possible modulatory role of kinases on voltage sensitive Na+ channels of presynaptic brain nerve endings was investigated by testing the effect of several kinase activators and inhibitors on the elevation of [Nai] induced by veratridine in mouse brain synaptosomes loaded with a selective Na+ indicator dye. Veratridine (20 microM) increases the basal [Nai] level (20 mM) more than twofold. This increase is independent of external Ca2+, but abolished by tetrodotoxin (1 microM). Activation of cAMP dependent protein kinase with forskolin or cAMP analogs, or of protein kinase C with diacylglycerol did not affect the veratridine-induced elevation in [Nai]. Drugs reported to inhibit calmodulin-dependent events, as well as the regulatory domain of protein kinase C, were potent and effective inhibitors of the increase in [Nai] induced by veratridine, as well as other veratridine induced responses, namely elevation of [Cai] (monitored with the Ca2+ indicator dye fura-2) and neurotransmitter (GABA) release. Drugs that inhibit kinases by binding to the catalytic site were ineffective, however, as was the phosphatase inhibitor, okadaic acid. A selective inhibitor of Ca2+ and calmodulin dependent protein kinase II also did not affect the elevation of [Nai] induced by veratridine, but markedly diminished the elevation of [Cai] induced by depolarization either with veratridine or with high K+ (15 and 30 mM). On the basis of these results it is concluded that, the dramatic inhibition exerted by some of the drugs tested on the elevation of [Nai] induced by veratridine is not due to their effects on kinases, but to a possible interaction of these compounds with an intracellular site of the Na+ channel. On the other hand, while Ca2+ and calmodulin dependent protein kinase II is unable to modulate brain presynaptic voltage sensitive Na+ channels, it facilitates the activation of brain presynaptic voltage sensitive Ca2+ channels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Fixation strength of interference screw fixation in bovine, young human, and elderly human cadaver knees: influence of insertion torque, tunnel-bone block gap, and interference.

A failure analysis of interference screw fixation was performed to test the hypothesis that bovine and/or elderly human cadavers are appropriate models for bone-patellar tendon-bone anterior cruciate ligament (ACL) reconstruction fixation studies. Failure mode is an important criterion for validating experimental models. The bovine, young human, and elderly human failure loads were 799 +/- 261 N, 655 +/- 186 N, and 382 +/- 118 N, respectively, and the failure modes were 75%, 69%, and 30% tissue failures, respectively. The similarities between the bovine and young human models in failure loads and failure modes indicate that bovine models are appropriate for ACL reconstruction fixation studies. The statistically significant differences between the young human and elderly human models in failure loads and failure modes indicate that elderly human cadavers are not an appropriate model for ACL reconstruction fixation studies. The differences in failure modes are consistent with previous studies using elderly human cadavers in which the predominant failure mode was bone block pullout. The tissue failures observed in the bovine and young human models contradict previous studies suggesting fixation strength is the weakest link in bone-patellar tendon-bone ACL reconstruction. Results of linear regression modeling showed statistically significant correlations between insertion torque and failure load (R2 = 0.44, P < 0.0001) and interference (defined as the screw outer thread diameter minus the tunnel-bone block gap) and insertion torque (R2 = 0.18, P = 0.003) when data from all models was combined. Results for the bovine model multiple regression showed a statistically significant regression of insertion torque (linear) and interference (quadritic) versus failure load (R2 = 0.56, P = 0.02). Regression slopes for screw diameter (P = 0.52) and gap size (P = 1.00) were not statistically significant. These results indicate that insertion torque and interference are independent predictors of failure load and should be included in future interference screw studies in addition to bone block dimensions, tunnel size, gap size, and screw diameter. Clinicians may consider using insertion torque and interference as indicators of postoperative graft fixation regarding rehabilitation decisions.

Adult↗

Hering-Breüer reflexes in high-altitude infants.

1. Pulmonary ventilation was found to be similar in high-altitude and low-altitude newborn infants, but the breathing pattern was deeper and slower at high altitude (Mortola, J.P., Frappell, P.B., Frappell, D.E., Villena-Cabrera, N., Villena-Cabrera, M., Peña, F., Am Rev Respir Dis 1992, 46: 1206-9). We questioned the contribution of vagal reflexes to these differences in breathing pattern. 2. Measurements were performed on high-altitude (La Paz, Bolivia, 3600-4050 m, inspired O2 pressure approximately 92 mmHg, n = 34) and low-altitude infants (Santa Cruz, Bolivia, 400 m, PIO2 approximately 141 mmHg, n = 26). The strength of the Hering-Breüer inspiratory inhibitory reflex was estimated from the inspiratory time during a respiratory effort against airways closed at end-expiration (Tloccl). The strength of the Hering-Breüer expiratory facilitatory reflex was estimated from the expiratory duration when airways were occluded during expiration (TEoccl). 3. Tloccl was significantly longer than the open-airways TI at both low and high altitude, but significantly more so (approximately 14%) at high altitude. TEoccl was longer than open-airways TE in both groups of infants, but significantly less so at high altitude, whether TEoccl was compared between occlusions of similar tidal volume (on average, TEoccl at high altitude was 79% of that at low altitude) or similar airway pressure (87%). 4. The results suggest that at high altitude the contribution of the phasic volume-dependent vagal input to the inspiratory off-switch threshold is higher, and that the tonic vagal expiratory facilitation is lower, than at low altitude, presumably because of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude↗

Ventilation and gaseous metabolism in infants born at high altitude, and their responses to hyperoxia.

Hyperventilation and decreased metabolic rate are commonly observed in newborns during acute hypoxia; whether these responses are also present during sustained hypoxia is not known. We asked whether infants at high altitude had higher ventilation and lower metabolism than lowlanders. Ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) were measured in newborn (< 1 day old) full-term infants in La Paz (altitude 3,800 m; inspired oxygen pressure [PIO2], 92 mm Hg) and in Santa Cruz (altitude, 400 m; PIO2, 141 mm Hg), Bolivia. Each group consisted of 30 infants selected to have similar body weight. The mothers, Amerindians and mestizos, were born in the corresponding cities or at equivalent altitudes. Despite the lower inspired oxygen concentration in La Paz (0.107 ml STPD O2/ml BTPS air) than in Santa Cruz (0.164), neither VE nor VO2 or VCO2 differed between the two groups. The breathing pattern was deeper and slower at high altitude. From the values of VE and VO2 it was calculated that high-altitude infants extracted more O2 (+62%) from the inspired air than did the lowlanders. When given pure O2 to breathe, both groups of infants similarly increased VE and gaseous metabolism; even during hyperoxia, however, the ventilatory O2 extraction was higher (+50%) in the highlanders. We conclude that, contrary to what is observed in acute hypoxia, infants at high altitude maintain metabolic rate with no major alterations in VE. The ability to use a greater fraction of the inspired O2 at high altitude probably results from functional and structural alterations stimulated by fetal hypoxia.

Altitude↗

Tracheobronchomegaly associated with interstitial pulmonary fibrosis.

Tracheobronchomegaly (TBM) is the syndrome of enlarged trachea and main bronchi associated with recurrent and chronic respiratory tract infections. A 42-year-old man with TBM and diffuse interstitial pulmonary fibrosis is described. The possible relationship between the two entities is discussed and the etiology, pathogenesis, clinical manifestations, prognosis and treatment of TBM are reviewed.

Adult↗

Compliance of the respiratory system in infants born at high altitude.

Populations living at high altitude are known to have a number of distinctive physiologic traits, including an increase in lung volume and compliance. We asked whether the factors that result in the increased compliance of high altitude natives were sufficiently expressed in utero that an increase in respiratory system compliance (Crs) could be detected at birth. Measurements were performed at about 1 day after birth on 34 infants born in La Paz, Bolivia (3,600 m, Pb about 495 mm Hg) and 36 born in Santa Cruz (400 m, Pb about 735 mm Hg). All infants were full-term and healthy, with body weights of at least 2,700 g. We measured Crs from expirations within the tidal volume range by the multiple occlusion method. Breathing pattern was measured from the spirometric record, and an index of chest wall distortion was obtained from the ratio of volume and abdominal displacement during spontaneous breathing and relaxations against closed airways. Rib cage and abdomen dimensions did not differ between the two groups. Crs values in Santa Cruz were similar to those previously obtained in Montreal and in other Caucasian infant populations at low altitudes. Crs was 33% and Crs/kg 37% greater (p less than 0.001) in the high altitude group, which included equal numbers of Amerindians and Mestizos of European ancestry. Dynamic elevation of the end-expiratory level was similar in both groups. Ventilation/kg and the distortion ratio were slightly yet significantly higher in the high altitude infants, suggesting an increased ventilatory drive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Effects of captivity on glucose tolerance in dogs.

Captivity decreased tolerance to glucose and increased blood serotonin levels in 6 normal dogs investigated. Return to freedom brought normalization in the glucose tolerance test and reverted blood serotonin to control levels.

Animals↗