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Biomedical subjects

M Chacon

Publications and source records attributed to M Chacon.

12 recordsLinked to original sources
PubMed2004

Neural network modelling of dynamic cerebral autoregulation: assessment and comparison with established methods.

A time lagged recurrent neural network (TLRN) was implemented to model the dynamic relationship between arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) and its performance was compared to classical linear model such as transfer function analysis, Aaslid's dynamic autoregulation model, and the Wiener-Laguerre moving average filter. A simple linear regression was also tested as a naive estimator. In 16 normal subjects, CBFV was continuously recorded with Doppler ultrasound and ABP with the Finapres device during six repeated thigh cuff manoeuvres. Using mean beat-to-beat values of ABP as input and CBFV as output, the performance of each method was assessed by the model's predicted velocity correlation coefficient and normalized mean square error (MSE). Cross-validation was performed using three thigh cuff manoeuvres for the training data set and the other three for the validation set. The four methods studied performed significantly better than the zero-order naive estimator. The TLRN performed better than transfer function analysis, but was not significantly different from the time-domain techniques, despite showing the minimum predictive MSE. CBFV step responses could be extracted from the TLRN showing the presence of non-linear behaviour both in terms of amplitude and directionality.

Adaptation, Physiological↗
PubMed2002

Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone.

A number of signaling molecules have been implicated in the acute response to hypoxia/ischemia in the adult brain. In contrast, the reaction to chronic hypoxemia is largely unexplored. We used a protocol of chronic hypoxia in rat pups during the first three postnatal weeks, encompassing the period of cellular plasticity in the cerebral cortex. We find that the levels of fibroblast growth factor 1 (FGF1) and FGF2, two members of the FGF family, increase after 2 weeks of chronic hypoxia. In contrast, members of the neurotrophin family are unaffected. FGF2 is normally expressed in the nucleus of mature, glial fibrillary acidic protein (GFAP)-containing astrocytes. Under hypoxia, most FGF2-containing cells do not express detectable levels of GFAP, suggesting that chronic low O(2) induces their transformation into more immature glial phenotypes. Remarkably, hypoxia promotes the appearance of radial glia throughout the sub-ventricular and ependymal zones. Most of these cells express vimentin and brain lipid binding protein. A subset of these radial glial cells expresses FGF receptor 1, and are in close contact with FGF2-positive cells in the sub-ventricular zone. Thus, FGF receptor signaling in radial glia may foster cell genesis after chronic hypoxic damage. From the results of this study we suggest that after the chronic exposure to low levels of oxygen during development, the expression of radial glia increases in the forebrain periventricular region. We envision that astroglia, which are the direct descendants of radial glia, are reverting back to immature glial cells. Alternatively, hypoxia hinders the normal maturation of radial glia into GFAP-expressing astrocytes. Interestingly, hypoxia increases the levels of expression of FGF2, a factor that is essential for neuronal development. Furthermore, chronic hypoxia up-regulated FGF2's major receptor in the periventricular region. Because radial glia have been suggested to play a key role in neurogenesis and cell migration, our data suggests that hypoxia-induced FGF signaling in radial glia may represent part of a conserved program capable of regenerating neurons in the brain after injury.

Animals↗
PubMed2001

Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis.

Pulmonary arteries of patients with severe pulmonary hypertension (SPH) presenting in an idiopathic form (primary PH-PPH) or associated with congenital heart malformations or collagen vascular diseases show plexiform lesions. It is postulated that in lungs with SPH, endothelial cells in plexiform lesions express genes encoding for proteins involved in angiogenesis, in particular, vascular endothelial growth factor (VEGF) and those involved in VEGF receptor-2 (VEGFR-2) signalling. On immunohistochemistry and in situ hybridization, endothelial cells in the plexiform lesions expressed VEGF mRNA and protein and overexpressed the mRNA and protein of VEGFR-2, and the transcription factor subunits HIF-1alpha and HIF-1beta of hypoxia inducible factor, which are responsible for the hypoxia-dependent induction of VEGF. When compared with normal lungs, SPH lungs showed decreased expression of the kinases PI3 kinase and src, which, together with Akt, relay the signal transduction downstream of VEGFR-2. Because markers of angiogenesis are expressed in plexiform lesions in SPH, it is proposed that these lesions may form by a process of disordered angiogenesis.

Aryl Hydrocarbon Receptor Nuclear Translocator↗
PubMed1996

Application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement.

Cyclosporin A (CyA) is a good candidate for incorporation in colloidal carriers such as nanoparticles (NP) that would diminish the adverse effects associated with its use under conventional pharmaceutical dosage forms and improve bioavailability after oral administration. In this study a composite rotational experimental design was used to evaluate the joint influence of five formulation variables: temperature of the aqueous phase, needle gauge, volume of the organic phase, and the amounts of polymer and surfactant on the micromeritic characteristics of the CyA-loaded NP obtained by the method of Fessi et al. The percentage of drug encapsulated in the NP was also evaluated for each formulation, and the yield, which was expressed as the ratio between the experimentally measured quantity of drug in the formulation and the theoretical content, was determined because CyA undergoes surface absorption. Potential variables such as stirring speed (500 rpm), final drug concentration (100 micrograms/mL), or injection rates (GRi = 0.379 mL/s) were maintained constant. The ANOVA corresponding to the experimental design showed that the amounts of polymer and surfactant, and the diameter of the needle used in the preparation of NP, significantly affected the percentage of entrapped drug (I2 = 0.8916). The mean particle size was significantly affected by all the formulation variables tested except for the amount of surfactant dissolved in the external aqueous phase (r2 = 0.9518). Neither the yield (mean value of 99.61%) nor the size distribution parameters (polydispersity and coefficient of variation) presented good correlation coefficients for the equations obtained, although some variables showed statistical significance. A second study was carried out to investigate the effects on the drug-loaded NP characteristics of varying the global injection rates (GRi) for the organic phase into the aqueous medium. The results showed a dramatic decrease in both particle size and drug incorporation in the carrier as the rate of mixing increased. From the results of both the experimental design and the second study, a theoretical model for nanoparticle formation is proposed that considers the most significant variables, and an empirical relationship to predict mean particle size is presented. Thus, particle size can be controlled by the injection rates (GRi), the needle gauge, and the polymer concentration.

Cyclosporine↗
PubMed1986

Thyroid hormone actions on a cholinergic neuroblastoma cell line (S-20Y).

Thyroid hormone (T3) has a multiplicity of effects on the developing nervous system. We have investigated T3 action using a cholinergic neuroblastoma cell line (S-20Y) as a model. S-20Y contains a nuclear receptor for T3 with binding properties similar to those of other T3 target tissues. In addition, these cells can carry out 5'-deiodination, which is necessary to produce active thyroid hormone in vivo. The enzyme involved in this process appears to be a type I deiodinase, based on its reaction kinetics and its susceptibility to inhibition by propylthiouracil. S-20Y cells maintained in T3-depleted medium showed decreased choline acetyltransferase (ChAT) activity. ChAT activity was restored to the control level in a dose-dependent manner by T3 repletion. Neither cell density nor viability was influenced by the hypothyroid state. The presence of a T3 receptor and the enzyme activity for T3 production, together with an effect of T3 on ChAT activity, demonstrate that S-20Y cells are a target for T3 action and suggest that these cells represent an excellent model system for studies of T3 effects on nervous tissues.

Animals↗
PubMed1985

Fibre-type specificity and effect of thyroid hormone on glucose 6-phosphate dehydrogenase activity in normal and denervated skeletal muscles of the rat.

Glucose-6-phosphate dehydrogenase activity increases following denervation of rat skeletal muscle. The specificity of this effect to muscle fibre type was studied. Basal activity of the dehydrogenase was higher in soleus, a muscle composed predominantly of type I fibres, than in extensor digitorum longus, a muscle composed predominantly of type IIa and b fibres. The enzymatic activity of the soleus was also greater than that of the red (RQ) and white (WQ) portions of quadriceps muscle (predominantly type IIa and type IIb fibres, respectively). Following denervation, glucose-6-phosphate dehydrogenase increased in extensor digitorum longus and RQ, but not in WQ or the soleus. Following chronic treatment of rats with 3,3',5-triiodothyronine, which converts type I muscle fibres to type II, the dehydrogenase activity increased in both denervated soleus and extensor digitorum longus. It is concluded that the effect of denervation on glucose-6-phosphate dehydrogenase activity is selective for type IIa (fast oxidative-glycolytic) muscle fibres.

Animals↗
PubMed1984

Stimulatory effects of follicle-stimulating hormone and luteinizing hormone upon secretion of progesterone and inhibin activity by cultured infant human ovarian granulosa cells.

Ovarian tissue obtained from three human infants (60, 120, and 210 days of age) was separated into cell types and cultured. Granulosa cells from two of three subjects were viable and grew in culture. The cells had the potential to secrete low levels of progesterone and responded to luteinizing hormone and follicle-stimulating hormone added in culture with greatly enhanced ability to secrete progesterone. Granulosa cells could also secrete inhibin activity in culture and responded to luteinizing hormone and follicle-stimulating hormone with enhanced inhibin secretion. The granulosa cells also had the potential to secrete estrogen in the presence of testosterone. Serum levels of gonadotropin in the human infant are elevated for a period between 1 and 4 months; yet only follicular growth, not luteinization, occurs. It can be concluded that infant human granulosa cells, like adult human granulosa cells, have the potential of responding in vitro to gonadotropin.

Androstenedione↗
PubMed1984

Follicular fluid inhibin activity and steroid levels in ovarian tissue obtained at autopsy from human infants from 18 to 200 days of age.

The ovaries of 25 human infants from 18 to 200 days of age were obtained at autopsy, and their follicular fluid was subjected to measurement of inhibin activity, estrogen, progesterone, androstenedione, and testosterone. Significant inhibin activity was present in all samples of follicular fluid (charcoal-treated) (138 +/- 19 U/10 microliter follicular fluid; 10,545 +/- 2758 U/ovary). There was a tendency for greater inhibin activity, follicular volume, and estrogen in infants from 18 to 59 days than in older infants. There was a significant positive correlation between follicular fluid volume, estrogen, and androstenedione, compared with follicular fluid inhibin content per ovary. It is possible that elevated serum follicle-stimulating hormone and luteinizing hormone observed early in life stimulates follicle growth, inhibin, and estrogen production. As a result of elevated inhibin and estrogen, the gonadotropins may be inhibited, which may cause a decline in follicular activity after 4 to 6 months.

Age Factors↗
PubMed1981

Selective carnitine palmitoyltransferase deficiency in fibroblasts from a patient with muscle CPT deficiency.

A 13-year-old boy developed cramps and myoglobinuria following exertion. Mitochondrial preparations from a skeletal muscle biopsy were deficient in carnitine palmitoyltransferase (CPT) activity when assayed by the hydroxamate and kinetic assays. The patient's fibroblasts were also deficient when assayed by the hydroxamate and kinetic assays, but not when tested by the DTNB (5,5'-dithiobis-[nitrobenzoic acid]) method. This disparity probably indicates a specific deficiency in fibroblasts of one of the two carnitine palmitoyltransferases, presumably CPT II.

Acyltransferases↗
PubMedDate not supplied

The effect of chronic ethanol feeding on ornithine decarboxylase activity and liver regeneration.

The effects of ethanol on liver regeneration are poorly understood. Acute and chronic exposure to ethanol have been found to exert opposite effects on the induction of ornithine decarboxylase, the rate-limiting enzyme for polyamine biosynthesis. Polyamines are necessary for DNA synthesis and liver regeneration after chemical or surgical liver injury. Short-term exposure to ethanol, which inhibits ornithine decarboxylase has been shown to inhibit DNA synthesis and liver regeneration, whereas more chronic exposure to ethanol increases ornithine decarboxylase activity and therefore could conceivably stimulate DNA synthesis and regeneration. To explore this later possibility, the effects of chronic ethanol consumption on ornithine decarboxylase activity, DNA synthesis and liver regeneration were studied in rats after sham laparotomy and partial hepatectomy. Chronic ethanol feeding failed to inhibit the induction of ornithine decarboxylase that occurred after partial hepatectomy and yet significantly inhibited posthepatectomy DNA synthesis and restitution of liver mass. These data suggest that the induction of hepatic polyamine biosynthesis is dissociated from DNA synthesis and liver regeneration after chronic consumption of ethanol.

Alcohol Drinking↗
PubMedDate not supplied

Muscular structural changes following fadenoperation.

The authors describe the macroscopic, histological, and ultrastructural findings observed in an experimental animal model of the fadenoperation . Grossly, muscular fibrosis and musculo-scleral adhesions were well established after the second postoperative month. Histologic findings demonstrated the development of a granulomatous, foreign body reaction around the musculo-scleral fixation suture, collagenization of the muscle tissue from the first postoperative month and degenerative phenomena in the muscle fibers. Electron transmission microscopic study showed atrophy and angulation with distortion of the myofibrillar matrix, along with alteration of the Z bands of muscle fibers, mitochondrial alteration, and dilatation of the sarcotubular system. All these experimental findings suggest the relative irreversible effects of the fadenoperation after the early postoperative period and for the first time, demonstrated that this surgical technique alters the muscle structure.

Animals↗