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Biomedical subjects

C Peña

Publications and source records attributed to C Peña.

At least 37 records · Page 2Linked to original sources
PubMed2001

[3H]dizocilpine binding to N-methyl-D-aspartate (NMDA) receptor is modulated by an endogenous Na+, K+-ATPase inhibitor. Comparison with ouabain.

An endogenous Na+, K+-ATPase inhibitor termed endobain E has been isolated from rat brain which shares several biological properties with ouabain. This cardiac glycoside possesses neurotoxic properties attributable to Na+, K+-ATPase inhibition, which leads to NMDA receptor activation, thus supporting the concept that Na+/K+ gradient impairment has a critical impact on such receptor function. To evaluate potential direct effects of endobain E and ouabain on NMDA receptors, we assayed [3H]dizocilpine binding employing a system which excludes ionic gradient participation. Brain membranes thoroughly washed and stored as pellets ('non-resuspended' membranes) or after resuspension in sucrose ('resuspended' membranes) were employed. Membrane samples were incubated with 4 or 10 nM ligand with or without added endobain E or ouabain, in the presence of different glutamate plus glycine combinations, with or without spermidine. [3H]dizocilpine basal binding and Na+, K+- and Mg2+-ATPase activities proved very similar in 'non-resuspended' or 'resuspended' membranes. Endobain E decreased [3H]dizocilpine binding to 'resuspended' membranes in a concentration-dependent manner, attaining roughly 50% binding inhibition with the highest endobain E concentration assayed. Among tested conditions, only in 'resuspended' membranes, with 4 nM ligand and with 1x10(-8) M glutamate plus 1x10(-5) M glycine, was [3H]dizocilpine binding enhanced roughly +24% by ouabain (1 mM). After Triton X-100 membrane treatment, which drastically reduces Na+, K+-ATPase activity, the effect of ouabain on binding was lost whereas that of endobain E remained unaltered. Results indicate that not only membrane preparation but also treatment and storage are crucial to observe direct endobain E and ouabain effects on NMDA receptor, which are not attributable to changes in Na+, K+-ATPase activity or to Na+/K+ equilibrium alteration.

Animals↗
PubMed2001

An endogenous Na+, K+-ATPase inhibitor enhances phosphoinositide hydrolysis in neonatal but not in adult rat brain cortex.

The effect of an endogenous Na+, K+-ATPase inhibitor, termed endobain E, on phosphoinositide hydrolysis was studied in rat brain cortical prisms and compared with that of ouabain. As already shown for ouabain, a transient effect was obtained with endobain E; maximal accumulation of inositol phosphates induced by endobain E was 604 +/- 138% and 186 +/- 48% of basal values in neonatal and adult rats, respectively. The concentration-response plot for the interaction between endobain E and phosphoinositide turnover differed from that of ouabain, thus suggesting the involvement of distinct mechanisms. In the presence of endobain E plus ouabain at saturating concentrations, no additive effect was recorded, suggesting that both substances share at least a common step in their activation mechanism of inositol phosphates metabolism or that they enhance phosphatidylinositol 4,5-biphosphate breakdown from the same membrane precursor pool, until its exhaustion. Experiments with benzamil, a potent blocker of Na+/Ca2+ exchanger, showed that it partially and dose-dependently inhibited endobain E effect. These results indicate that the endogenous Na+, K+-ATPase inhibitor endobain E, like ouabain, is able to stimulate phosphoinositide turnover transiently during postnatal brain development.

Aging↗
PubMed2001

Olmsted syndrome.

Olmsted syndrome is an uncommon inherited disorder of keratinization that presents mutilating palmoplantar keratoderma, perioral hyperkeratosis, leukokeratosis and alopecia. We report a case of this rare syndrome diagnosed in a 48-year-old woman and confirms the existence of a generalized abnormality in keratin expression. Immunoreactivity in our case suggests an abnormal expression of keratins 5 and 14 similar to the observed in other hyperproliferative disorders.

Abnormalities, Multiple↗
PubMed2001

An outbreak of hospital-acquired Klebsiella pneumoniae bacteraemia, including strains producing extended-spectrum beta-lactamase.

This study describes the clinical outcome of an outbreak of extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) bacteraemia. Ninety-two episodes of hospital-acquired K. pneumoniae bacteraemia were studied, 49 ESBL-KP and 43 non-ESBL-KP, from May 1993 to June 1995. Of these, 44 (90%) episodes of ESBL-KP vs. 20 (46%) episodes of non-ESBL-KP occurred in intensive care unit (ICU) patients. The incidence of K. pneumoniae bacteraemia (mainly due to ESBL-KP) increased in the ICU during the outbreak. A significant association was found between intravascular catheter-related bacteraemia and isolation of ESBL-KP [27 (56%) in the ESBL-KP group vs. 13 (30%) in the non-ESBL-KP group;P= 0.01]. The worst prognostic features were identified as age > 65 years (P= 0.02), septic shock (P< 0.001) and secondary bacteraemia (P= 0.04). High rates of resistance to beta-lactam/beta-lactamase inhibitors observed in our ESBL-KP isolates, as well as variable activity of aminoglycosides, restricts the empirical use of these antibiotics. Carbapenems should be the treatment of choice since they are uniformly active against these strains. Our study shows that ESBL-KP bacteraemia occurring in an epidemic ICU setting is mainly catheter-related. We did not find ESBL strains to be associated with a significantly poor outcome.

Age Distribution↗
PubMed2001

Reconstruction of ocular surface with heterologous limbal epithelium and amniotic membrane in a rabbit model.

PURPOSE: To report in vivo reconstruction of the ocular surface using amniotic membrane and heterologous transplants of epithelial limbal cells in rabbits with chemical burns. METHODS: After severe damage to the ocular surface with n-heptanol and keratectomy, 15 rabbits developed total limbal deficiency with conjunctival epithelialization, vascularization, and chronic inflammation. One month later, a complete keratectomy was performed in all eyes: 12 received additional transplantation of human amniotic membrane and heterologous limbal epithelial cells in a double amniotic membrane layer, 2 received amniotic membrane only, and 1 control eye received no procedure. RESULTS: After 1 month of follow-up, corneas in eight of the operated eyes presented minimal vascularization, without signs of rejection. Corneal surface reconstruction was demonstrated with the growth of new corneal-like epithelial phenotype and integration of amniotic membrane to the basal corneal surface. A superficial amniotic membrane (with the amnion side up as a dressing) peeled off after 7 to 10 days. The epithelialization with heterologous limbal epithelial cells was evident underneath. The other four operated eyes were followed for 6 months; the ocular surface was also stable with a corneal-like epithelial phenotype. CONCLUSION: Simultaneous transplantation of amniotic membrane and heterologous limbal epithelial cells in severe ocular surface disorders could restore ocular surface and may be useful in patients with severe bilateral limbal epithelial loss, giving new perspectives for the treatment of severe ocular surface disorders.

Amnion↗
PubMed2001

[Medicine versus surgery: the treatment of eye diseases in the works of Abulcasis and Avenzoar].

Although they start from generically distinct positions-- from the standpoint of a surgeon in the case of Abulcasis (11th Century), and from that of a physician in the case of Abenzoar (12th Century) - we attempt to show that the latter made an important, documented and unsuspected contribution to the surgical therapy of diseases of the eye. Naturally, Abenzoar discusses the surgical approach after first recommending other pharmacological and dietary remedies. To this end, we studied the chapters dedicated to the diseases of the eye in Kitāb al-tasrīf li man 'aŷiza an al-ta 'līf: The Book of the arrangement [of medical science] for those who are unaware of it by Abulcasis, and in Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr. The Book of the Simplification of Medication and Diet by Abenzoar. In support of our hypothesis, we make some observations on the introduction and use of the cataract removal technique in al-Andalus.

Arab World↗
PubMed2000

Influence of dissolved oxygen tension and agitation speed on alginate production and its molecular weight in cultures of Azotobacter vinelandii*

The alginate production by Azotobacter vinelandii, as well as the molecular weight of the polymer, are strongly influenced by the dissolved oxygen tension (DOT) and stirring speed of the culture. Under high DOT (5% of air saturation), the bacteria produced more alginate (4.5 g/l) than that obtained at low (0.5%) oxygen tension (1.0 g/l) in cultures conducted at 300 rpm. On the other hand, under constant DOT (3%), the higher the stirring speed (from 300 to 700 rev./min), the higher the specific growth rate and the alginate production rate. However, low agitation speed (300 rev./min) lead the culture to produce a polymer of high molecular weight (680 000 g/g mol) whereas a low molecular weight (352 000 g/g mol) alginate was isolated from cultures conducted at high (700 rev./min) stirring speed. At 700 rev./min, the MMW increased to a plateau between 1 and 3% DOT and then decreased to a minimum of 0.11 x 10(6) g/g mol at 7%. Microscopic observations revealed the presence of cell aggregates (one order of magnitude larger than individual cells) when the culture was conducted at 300 rev./min. Oxygen gradients occurring within the aggregates could be responsible of this phenomenon. At high agitation rate, the MMW of the alginate dropped towards the end of the culture in all conditions evaluated. Alginase activity was detected, which would be responsible for this phenomenon.

Journal Article↗
PubMed2000

Early morphologic alterations in trophically deprived neuronal death in vitro occur without alterations in cytoplasmic Ca(2+).

Morphologic and functional parameters altered during neuronal death were investigated in chick ciliary ganglion (CG) neurons in vitro isolated from embryonic day 8 (E8, stage 34). Neurons were separated from nonneuronal cells to investigate their inherent cell death program and were cultured with or without trophic support (choroid, iris, pigment epithelium) from their appropriate target tissue. The cell death process was characterized with investigations focused on the earliest events at the onset of commitment to cell death at 11 hours after plating. Initial morphologic changes in the process of cell death were cytoplasmic; swelling, dendritic retraction, blebbing, vacuolization, which are all characteristics of necrosis. Later, nuclear chromatin condensation occurred, a characteristic of apoptosis. An increase in membrane permeability was measured earlier at 8 hours. During these alterations (associated with the initiation of cell death) single cell analysis was performed to evaluate mobile Ca(2+) changes in the same trophically deprived neurons during the course of the death process; Ca(2+) levels remained at 50 nM. Transient Ca(2+) entry was buffered in control and deprived cells at 13 hours but with different parameters. During the execution stage of death mobile Ca(2+) levels were variable. In this final stage of cell death, neurons demonstrated nuclear damage, cytosol disintegration, or morphology sharing both characteristics. These observations define embryonic CG cell death in vitro as neither purely apoptotic nor necrotic but a form of that exhibits features of both. These results also demonstrate a disassociation of changes in cytosolic Ca(2+) from both CG neuronal survival and trophically deprived cell death in vitro.

Animals↗
PubMed2000

Population-based surveillance for bacterial meningitis in the Dominican Republic: implications for control by vaccination.

Quantifying the local burden of disease is an important step towards the introduction of new vaccines, such as Haemophilus influenzae type b (Hib) conjugate vaccine. We adapted a generic protocol developed by the World Health Organization for population-based surveillance of bacterial meningitis. All hospitals that admit paediatric patients with meningitis in the National District, Dominican Republic were included in the system and standard laboratory methods were used. The system identified 111 cases of confirmed bacterial meningitis. Hib was the leading cause of bacterial meningitis, followed by group B streptococcus, S. pneumoniae, and N. meningitidis. Unlike hospital-based case series, this population-based system was able to calculate incidence rates. The incidence of Hib meningitis was 13 cases per 100,000 children < 5 years old. The data from this study were used by the Ministry of Health to support the introduction of routine Hib vaccination and will be used to monitor its effectiveness.

Child, Preschool↗
PubMed2000

Angiotensin-(1-7) does not affect norepinephrine neuronal uptake or catabolism in rat hypothalamus and atria.

1. Since we previously reported that angiotensin-(1-7) [Ang-(1-7)] increases or inhibits norepinephrine (NE) release in rat atria or hypothalamus, respectively, the present work was undertaken to investigate the effect of the heptapeptide on NE neuronal uptake and metabolism in atria and hypothalamus isolated from rats. 2. Ang II (1-10 microM) caused a decrease in neuronal NE uptake in both atria and hypothalami isolated from rats. On the contrary, tissues incubated with [3H]NE in the presence of 0.1-10 microM Ang-(1-7) showed no modification in [3H]NE content with respect to the control group, suggesting that the heptapeptide did not modify [3H]NE neuronal uptake. 3. To study the effect of the heptapeptide on NE catabolism, monoamine-oxidase (MAO) and catechol-O-methyltransferase (COMT) activities were determined. Pretreatment of the tissue with Ang-(1-7) (0.1-1.0 microM) showed a tendency to diminish MAO activity in rat atria, while no significant changes were observed in hypothalamic MAO activity. Moreover, the heptapeptide (0.1-1.0 microM) did not affect central COMT activity with respect to the control group. 4. Present results allow us to conclude that Ang-(1-7) interacts with noradrenergic neurotransmission by increasing or inhibiting NE release at the peripheral and central levels, respectively, without affecting either the neurotransmitter neuronal uptake or catabolism.

Angiotensin I↗
PubMed2000

Kinetics of Na+, K+-ATPase inhibition by an endogenous modulator (II-A).

We have previously reported the isolation by gel filtration and anionic exchange HPLC of two brain Na+, K+-ATPase inhibitors, II-A and II-E, and kinetics of enzyme interaction with the latter. In the present study we evaluated the kinetics of synaptosomal membrane Na+, K+-ATPase with II-A and found that inhibitory activity was independent of ATP (2-8 mM), Na+ (3.1-100 mM), or K+ (2.5-40 mM) concentration. Hanes-Woolf plots showed that II-A decreases Vmax in all cases; KM value decreased for ATP but remained unaltered for Na+ and K+, indicating respectively uncompetitive and noncompetitive interaction. However, II-A became a stimulator at 0.3 mM K+ concentration. It is postulated that brain endogenous factor II-A may behave as a sodium pump modulator at the synaptic region, an action which depends on K+ concentration.

Adenosine Triphosphate↗
PubMed2000

Congenital multiple clustered dermatofibroma.

Multiple clustered dermatofibroma (MCD) is a rare tumour which usually appears during the first and second decades of life. We report a man in whom the MCD was congenital, although during the first few years of his second decade it extended to involve a broad zone on the left hip, gluteal region and upper thigh.

Adolescent↗
PubMed2000

Suitable experimental conditions are required to characterize interferon-alpha2b synthetic peptides.

The binding and antiproliferative activities of synthetic peptides 29-35 and 122-139 of interferon-alpha2b, both of which contain a cysteine residue in their sequences, were studied in the presence or absence of a dissociation medium containing mainly urea, dithiothreitol and 2-mercaptoethanol. Although interferon-alpha2b peptides either did not modify or slightly increased 125I-labelled interferon-alpha2b specific binding to WISH cell-membrane receptors in the absence of dissociation medium, significant binding inhibition was obtained when both peptides were assayed in dissociation medium. Furthermore, also in the presence of dissociating agents, the two fragments inhibited cell growth in a concentration-dependent manner, the 122-139 sequence being more effective than the 29-35 sequence. No additive effect on interferon binding and cell proliferation was observed when both peptides were added simultaneously. Results obtained after submitting peptide 122-139 to gel filtration or PAGE under different experimental conditions showed the presence of dimers and/or noncovalent aggregates arising from intermolecular disulfide bridges or hydrophobic interactions. Thus, our results indicated that peptide effects on 125I-labelled interferon-alpha2b binding and WISH cell proliferation were clearly manifested when the amount of monomeric species increased, showing that suitable experimental conditions should be used to study peptide behavior. The ability of both peptides to effectively trigger an interferon-specific biological action, such as cell growth inhibition, strongly suggested that 29-35 and 122-139 interferon-alpha2b fragments constitute the conformational epitope or mimotope that interacts with the cytokine-specific receptor.

Binding Sites↗
PubMed2000

Angiotensin-(1-7) reduces norepinephrine release through a nitric oxide mechanism in rat hypothalamus.

Angiotensin (Ang)-(1-7) elicits a facilitatory presynaptic effect on peripheral noradrenergic neurotransmission, and because biological responses to the heptapeptide on occasion are tissue specific, the present investigation was undertaken to study its action on noradrenergic neurotransmission at the central level. In rat hypothalamus labeled with [(3)H]-norepinephrine, 100 to 600 nmol/L Ang-(1-7) diminished norepinephrine released by 25 mmol/L KCl. This effect was blocked by the selective angiotensin type 2 receptor antagonist PD 123319 (1 micromol/L) and by the specific Ang-(1-7) receptor antagonist ([D-Ala(7)]Ang-(1-7) (1 micromol/L) but not by losartan (10 nmol/L to 1 micromol/L), a selective angiotensin type 1 receptor antagonist. The inhibitory effect on noradrenergic neurotransmission caused by Ang-(1-7) was prevented by 10 micromol/L N(omega)-nitro-L-arginine methylester, an inhibitor of nitric oxide synthase activity, and was restored by 100 micromol/L L-arginine, precursor of nitric oxide synthesis. Methylene blue (10 micromol/L), an inhibitor of guanylate cyclase considered as the target of nitric oxide action, as well as Hoe 140 (10 micromol/L), a bradykinin B(2)-receptor antagonist, prevented the inhibitory effect of the heptapeptide on neuronal norepinephrine release, whereas no modification was observed in the presence of 0.1 to 10 micromol/L indomethacin, a cyclooxygenase inhibitor. Our results indicate that Ang-(1-7) has a tissue-specific neuromodulatory effect on noradrenergic neurotransmission, being inhibitory at the central nervous system by a nitric oxide-dependent mechanism that involves angiotensin type 2 receptors and local bradykinin production.

Angiotensin I↗
PubMed2000

Systemic lupus erythematosus presenting with a reticular erythematous mucinosis-like condition.

We report the case of a woman with clinical and histopathological features of reticular erythematous mucinosis syndrome (REM) who six years later developed diagnostic criteria for systemic lupus erythematosus (SLE). Two biopsies performed at the same area initially showed mucin dermal deposits and further development of characteristic dermo-epidermal changes of lupus erythematosus. Our findings suggest that SLE may present with an REM-like condition.

Adult↗
PubMed1999

Angiotensin-(1-7) binds at the type 1 angiotensin II receptors in rat renal cortex.

Significant angiotensin (Ang) (1-7) production occurs in kidney and effects on renal function have been observed. The present study was undertaken to investigate binding characteristics of the heptapeptide to Ang II receptors present in rat renal cortex. [125I]-Ang II binding to rat glomeruli membranes was analyzed in the presence of increasing concentrations of Ang II, Ang-(1-7), DUP 753 and PD 123319. Linearity of the Scatchard plot of the [125I]-Ang II specific binding to rat glomeruli membranes indicated a single population of receptors, with a Kd value of 0.7 +/- 0.1 nM and a Bmax of 198 +/- 0.04 fmol/mg protein. DUP 753, an specific AT1 receptor antagonist, totally displaced the specific binding of [125I]-radiolabelled hormone with a Ki of 15.8 +/- 0.9 nM, while no changes were observed in the presence of the selective AT2 receptor antagonist, PD 123319. The specific [125I]-Ang II binding to rat glomerular membranes was displaced by Ang-(1-7) with high affinity (Ki = 8.0 +/- 3.2 nM). We conclude that radioligand binding assays in the presence of selective Ang II antagonists DUP 753 and PD 123319 suggest the unique presence of AT1, receptors in rat glomeruli and a possible role in the control of the biological renal effects of Ang-(1-7).

Angiotensin I↗