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Biomedical subjects

A Almeida

Publications and source records attributed to A Almeida.

At least 73 records · Page 4Linked to original sources
PubMed1996

Fuel utilization by early newborn brain is preserved under congenital hypothyroidism in the rat.

Mental retardation associated with hypothyroidism may be caused by impairment of brain ketone body-metabolizing enzymes during the suckling period. However, much evidence suggests that, immediately after delivery, lactate, instead of ketone bodies or glucose, may be the best substrate for the brain. In this work, we have studied the effect of experimentally induced congenital hypothyroidism on the rate of lactate, glucose, and 3-hydroxybutyrate utilization in early neonatal brain slices. Methimazole (MMI) administration to the mothers caused a 5.4- and 1.7-fold decrease in neonatal plasma concentrations of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3), respectively. Propylthiouracil (PTU) administration to the mothers caused a 7.3- and > 2-fold decrease in plasma T4 and T3 concentrations, respectively. MMI-induced hypothyroidism did not significantly modify the rate of lactate, glucose, or 3-hydroxybutyrate oxidation to CO2 and their incorporation into lipids by the neonatal brain. However, PTU-induced hypothyroidism decreased the rate of lactate and glucose oxidation to CO2 and their incorporation into lipids by 17% (p < 0.05). 3-Hydroxybutyrate utilization was not modified by this treatment. Separation by HPLC of the lipids revealed that PTU-mediated inhibition of lipid synthesis from lactate and glucose may be accounted for by specific inhibition of the rate of sterol synthesis (15%, p < 0.05), whereas the rate of phospholipid synthesis was unaffected. These results suggest that the early newborn may develop mechanisms aimed at avoiding the possible brain damage caused by the inhibition of lipid synthesis brought about by mild neonatal hypothyroidism.

3-Hydroxybutyric Acid↗
PubMed1996

Massive lower gastrointestinal bleeding from cecal lymphoid polyp in renal transplant recipient.

A 25-year-old renal transplant recipient receiving anticoagulant therapy for renal vein thrombosis, presented with massive lower gastrointestinal bleeding. Superior mesenteric angiogram revealed active bleeding in the cecum. Colonoscopy revealed a sessile ulcerated polyp in the cecum with satellite polyps. The polyps were fulgurated with Nd:YAG laser. Colonoscopy later revealed a remnant of the polyp, which was excised. The histopathology revealed a lymphoid polyp.

Adult↗
PubMed1995

Projection sites of superficial or deep dorsal horn in the dorsal reticular nucleus.

The termination sites in the medullary dorsal reticular nucleus (DRt) of axons arising from superficial or deep dorsal horn cells were analysed by anterograde tracing with biotinylated dextran (BD). Following BD injections in spinal laminae I-III or in these laminae plus the dorsal funiculus, labelled fibres and boutons were located in the dorsal most ipsilateral portion of the DRt. Injections covering laminae III-V or laminae I-V resulted in bilateral labelling of the ventral DRt and ipsilateral labelling of the dorsal DRt. These findings, together with previous data concerning the origin of DRt projections to the superficial or deep dorsal horn, suggest the occurrence of reciprocal anatomical loops connecting the dorsal or the ventral areas of both regions.

Animals↗
PubMed1995

Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions.

A modified comparative genomic hybridization (mCGH) technique was used to identify and map amplified DNA sequences in six homogeneously staining regions (hsr) from three primary breast carcinomas. Five different chromosomal regions and bands were identified as sites of amplification: 8p1, 17q21.1, 17q23 (two cases), 19q13.3, and 20q13.3. The mCGH site located on 17q21.1 was demonstrated to correspond to a 50-100-fold amplification of ERBB2. Further in situ hybridization experiments were used to confirm the mCGH results and to characterize the organization of the amplified sequences within the hsr. In five of six instances, two or more chromosomal regions were found amplified in the same hsr. In the tumor with the less modified karyotype, the two hsr comprised DNA sequences from three different chromosomes and showed different patterns of amplification. In the tumor with the most rearranged karyotype, the hsr-carrying chromosomes were formed by the translocation and amplification of sequences from three or four different chromosomal sites. This illustrates the complexity of the amplification process in breast cancers.

Breast Neoplasms↗
PubMed1995

Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia.

In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min-1 (mitochondria and synaptosomes) and complex II-III activities decreased at blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels.

Animals↗
PubMed1995

Effect of reperfusion following cerebral ischaemia on the activity of the mitochondrial respiratory chain in the gerbil brain.

The effect of reperfusion following 30 min of cerebral ischaemia on brain mitochondrial respiratory chain activity has been studied in the gerbil. The state 3 respiration rates with both FAD- and NAD-linked substrates were reduced after ischaemia. After 5 min of reperfusion, state 3 respiration with FAD-linked substrates was restored, but levels of NAD-linked substrates did not return to control values until 30 min of reperfusion. By 120 min of reperfusion state 3 respiration decreased relative to control values with all substrates studied. Measurement of the individual respiratory chain complexes showed that complex I, complex II-III, and complex V activities were reduced after ischaemia. By 5 min of reperfusion complex II-III activity was restored, but the activities of complexes I and V did not return to control values until 30 min of reperfusion. In contrast, complex IV activity was unaffected by ischaemia or 5 and 30 min of reperfusion but was significantly reduced after 120 min of reperfusion, possibly owing to free radical production and lipid peroxidation.

Animals↗
PubMed1995

Effect of ethanol consumption on adult rat liver mitochondrial populations analyzed by flow cytometry.

In the present study, the effects of administering ethanol to adult male rats on the distribution of the low fluorescence population (LFP) and high fluorescence population (HFP), and the rhodamine-123 fluorescence intensity of these groups of mitochondria are analyzed by flow cytometry. Our results show that ethanol administration to adult male rats induces a redistribution of the HFP and LFP mitochondrial populations leading to an increase of the less functional HFP mitochondria. In addition, ethanol induced an increase in the mean intensity of green fluorescence of the HFP that is probably related to an increased number of rhodamine-123 binding sites per mitochondria resulting from mitochondria enlargement.

Alcoholism↗
PubMed1995

Postnatal development of the complexes of the electron transport chain in synaptic mitochondria from rat brain.

The postnatal development of the complexes of the electron transport chain in mitochondria isolated from rat brain synaptosomes was investigated. Synaptosomal brain mitochondria were isolated from rats aged 10-60 days, and the activities of mitochondrial complex I, complex II-III, complex IV and complex V were measured. There was a significant increase in the activity of II-III from day 10 to day 15 and complex IV from day 10 to day 21, thereafter the activities of complexes I-III and IV did not change significantly. The activity of complex I did not change significantly during the period 10-60 days post partum. In synaptic mitochondria, complex V activity was higher than in non-synaptic mitochondria, whereas the activity of complex I was lower than in non-synaptic mitochondria. These data show that the complexes of the respiratory chain within synaptic mitochondria have activities different from those of non-synaptic mitochondria and may have major implications for the relative susceptibility of mitochondria in different brain cell types to neurotoxins such as MPP+, hypoxic/ischaemic damage and oxidative stress.

Acetylcholinesterase↗
PubMed1995

Hypothyroidism prevents postnatal changes in rat liver mitochondrial populations defined by rhodamine-123 staining.

The effect of hypothyroidism on the percentages of low fluorescence population (LFP) and high fluorescence population (HFP) rhodamine-123-stained mitochondria, respiratory parameters, and ATPase activity were studied in liver mitochondria from early newborn rats. Hypothyroidism prevented the decrease in the percentage of HFP and the subsequent increase in LFP that occurs immediately after birth. This effect coincides with the impairment of mitochondrial respiratory function, as shown by the low respiratory control ratio and the low activity of F0,F1-ATPase found in hypothyroid newborns. All of these changes were reversed by the administration of thyroid hormones. ATP in vitro promotes the conversion of HFP into LFP and increases the respiratory control ratio in hypothyroid newborns, although this effect was not observed after thyroid hormone treatment. The effect of thyroid hormones on both the postnatal changes in mitochondrial populations and in F0,F1-ATPase activity was prevented by cycloheximide, but not by streptomycin. Thus, the observed effects of thyroid hormones on neonatal mitochondria must be accomplished by the induction of the synthesis of some nuclei-coded protein, possibly involved in F0,F1-ATPase assembly.

Adenosine Triphosphate↗
PubMed1995

Induced alterations in calcium uptake rate in normoxic rate proximal tubules.

This study is well-oxygenated, freshly isolated rat proximal tubules (RPT), examined the effects of several drugs that alter the transmembrane K+ and Na+ gradients across cell membranes, including valinomycin (VAL), amphotericin B (AMPHO), and ouabain (OUAB). The effects of high extracellular potassium chloride (KCl) concentrations (45 mM) and low extracellular sodium concentration (100mM) were also studied. After 10 min of drug exposure Ca2+ uptake rate (nmol/mg/min) increased from 2.7 to 3.8 with VAL (p < .02), from 2.9 to 3.7 with AMPHO (p < .05), from 3.6 to 4.1 with OUAB (p < .05), and from 3.2 to 4.8 with 45 mM KCl (p < .001). Ca2+ uptake rate was sustained at these high levels at 20 min in all treated RPT except those exposed to OUAB. LDH release averaged less than 15% in control tubules and did not increase significantly except in RPT treated with VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p < .001). Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7 nmol/mg in control to 2.0 +/- 0.3 nmol/mg in VAL, p < .001). Treatment with verapamil reduced Ca2+ uptake rates at 10 min in VAL-treated RPT (from 3.8 to 3.1, p < .02, in AMPHO-treated RPT (from 3.8 to 3.1 p < .001), in OUAB-treated tubules (from 4.0 to 3.4, p < .01), and in KCl-treated RPT (from 3.7 to 3.2, p < .01). These results indicate that acute changes in the transmembrane ion gradient in RPT are accompanied by increased Ca2+ uptake rates. Ca2+ uptake rates are also increased during O2 deprivation in RPT, a situation in which the transmembrane ion gradient is likewise altered. The increased Ca2+ uptake rate observed in the present study and during hypoxia may have a common basis, that is, altered transmembrane ion gradients or some function thereof.

Adenosine Triphosphate↗
PubMed1994

Postnatal changes in rhodamine-123 stained mitochondrial populations are sensitive to protein synthesis inhibitors but mimicked in vitro by ATP.

The incubation of term fetus mitochondria with ATP mimicked in vitro the increase in the respiratory control index and in the percentage of the rhodamine-123-low fluorescence population that occurred in vivo immediately after birth, suggesting that both phenomena are closely associated. The administration of streptomycin inhibited the increase in the percentage of the low fluorescence population that occurred immediately after birth, while the administration of cycloheximide even reversed these changes. These results suggest that the in vivo interconversion between mitochondrial forms depends on both cytosolic and mitochondrial protein synthesis.

Adenosine Diphosphate↗
PubMed1994

Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique.

A modified comparative genomic hybridization (mCGH) technique was applied to a series of 17 primary breast carcinomas in which cytogenetic study (CG) demonstrated the presence of homogeneously staining region(s), suggesting the occurrence of DNA amplification. mCGH demonstrated recurrent amplifications of the whole chromosome arms 8q (9 times) and 1q (7 times) and of DNA loci in the following bands: 11q13 (6 times), 9p13 and 17q21.1 (4 times), 1q21.1 and 16p11.2 (3 times), and 8q22, 8q24.1, 10q22, 15q26, 17q23, and 20q13.3 (twice). Amplification of whole chromosome arms is likely to have resulted from unbalanced translocations or isochromosomes, whereas amplifications of smaller chromosomal segments probably arose through real DNA amplification processes. In all tumors but one, more than one amplified locus was detected. The fact that many chromosomal sites were involved suggests that the process of amplification is complex and that many genes are potential targets.

Breast Neoplasms↗
PubMed1994

Postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria.

The postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria were investigated. Nonsynaptosomal brain mitochondria were isolated from rats aged 1-60 days, and the activities of mitochondrial complexes I, II-III, IV, V and citrate synthase were measured. There was a significant increase in the activity of complex I from postnatal day 1 to day 21, and in the activities of complex II-III, complex IV and citrate synthase from postnatal day 1 to day 60. In contrast, the activity of complex V increased significantly between postnatal day 1 and day 10 where it attained adult levels. These data are consistent with the increasing demand for mitochondrial ATP production as the brain develops and as aerobic glycolysis becomes the major pathway for energy production.

Adenosine Triphosphate↗