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Biomedical subjects

M Ortiz

Publications and source records attributed to M Ortiz.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Amiodarone absorption and elimination after oral and intravenous administration in healthy individuals].

We studied amiodarone absorption and disposal in eight male healthy subjects aged 21 +/- 1 years old and weighting 69.8 +/- 7.1 kg. An intravenous dose of 5 mg/kg and an oral dose of 600 mg of amiodarone were administered. Amiodarone concentrations were measured by HPLC and calculations were performed using a compartment model independent pharmacokinetic analysis program. After oral administration a Cmax of 1.17 +/- 0.3 mg/ml was achieved at 3.25 +/- 0.46 h (tmax). Absolute bioavailability ranged from 50.4 to 87.8% (68.6 +/- 12.6%). Compared to previous reports, the variability of this parameter is similar and the mean value is one of the highest informed. After intravenous administration, Amiodarone had a half life of 7.53 +/- 0.96 h, a total body clearance of 4.25 +/- 0.73 ml/kg/min and a distribution volume of 2.99 +/- 0.71 l/kg. Except the later figure, which is in the inferior range, all other parameters are within previously reported values. It is concluded that amiodarone absorption and disposal values found in Chilean subjects are similar to those reported abroad.

Administration, Oral↗
PubMed1995

Peribulbar anaesthesia: the role of local anaesthetic volumes and Thiomucase in motor block and intraocular pressure.

Peribulbar anaesthesia is a useful regional anaesthesia and akinesia technique for eye surgery. We studied changes in muscular akinesia and intraocular pressure under peribulbar anaesthesia caused by different volumes of 0.75% bupivacaine with or without the addition of Thiomucase (chondroitin sulphatase) in patients undergoing cataract surgery. A total of 120 patients were randomly allocated into four groups: group 1, bupivacaine 5 mL; group 2, bupivacaine 5 mL plus Thiomucase 10 U mL-1; group 3, bupivacaine 9 mL; group 4, bupivacaine 9 mL plus Thiomucase 10 U mL-1. We assessed: (1) akinesia according to mobility in the four quadrants of the eyeball and the palpebral opening using a scoring system between 0 (total akinesia) and 10 (full movement); and (2) intraocular pressure before, immediately after and 15 min after peribulbar anaesthesia. A significantly better motor blockade was observed in groups 2, 3 and 4 than in group 1 (P < 0.05). Thiomucase increased the quality of motor blockade in group 2, but not in group 4. Intraocular pressure increased by 5-10 mmHg in comparison with baseline values and, after 15 min application of Honan's balloon, decreased by 8-10 mmHg in comparison with baseline values, with no significant differences between groups. Thiomucase can improve the motor block if a lower volume of local anaesthetic is used. The administration of 5 or 9 mL volumes or the addition of Thiomucase decreases the the intraocular pressure in a similar way.

Aged↗
PubMed1994

Transforming growth factor beta 1, insulin and prostaglandin E1 enhance prostaglandin F2 alpha mitogenic action in Swiss 3T3 cells via separate events.

Transforming growth factor beta 1 (TGF beta 1) had no mitogenic effect in Swiss 3T3 cells, but could increase prostaglandin F2 alpha (PGF2 alpha)-induced DNA synthesis. Insulin, but not prostaglandin E1 (PGE1), further enhanced PGF2 alpha action at low TGF beta 1 concentrations. TGF beta 1 also acted concertedly with the protein kinase C (PKC) activator 1-oleoyl-2-acetylglycerol to induce mitogenesis. Thus, it appears that TGF beta 1 and insulin act via separate signals, while TGF beta 1 and PGE1 might share a common pathway not involving TGF beta 1-mediated prostaglandin synthesis. These results suggest that TGF beta 1 might elicit various signalling mechanisms to enhance PGF2 alpha-triggered events.

3T3 Cells↗
PubMed1994

Distinct and overlapping direct effects of macrophage inflammatory protein-1 alpha and transforming growth factor beta on hematopoietic progenitor/stem cell growth.

Both transforming growth factor beta (TGF beta) and macrophage inflammatory protein 1 alpha (MIP-1 alpha) have been shown to be multifunctional regulators of hematopoiesis that can either inhibit or enhance the growth of hematopoietic progenitor cells (HPC). We report here the spectrum of activities of these two cytokines on different hematopoietic progenitor and stem cell populations, and whether these effects are direct or indirect. MIP-1 alpha enhances interleukin-3 (IL-3)/and granulocyte-macrophage colony-stimulating factor (GM-CSF)/induced colony formation of normal bone marrow progenitor cells (BMC) and lineage-negative (Lin-) progenitors, but has no effect on G-CSF or CSF-1/induced colony formation. Similarly, TGF beta enhances GM-CSF/induced colony formation of normal BMC and Lin- progenitors. In contrast, TGF beta inhibits IL-3/ and CSF-1/induced colony formation of Lin- progenitors. The effects of MIP-1 alpha and TGF beta on the growth of Lin- progenitors were direct and correlate with colony formation in soft agar. Separation of the Lin- cells into Thy-1 and Thy-1lo subsets showed that the growth of Thy-1lo Lin- cells is directly inhibited by MIP-1 alpha and TGF beta regardless of the cytokine used to stimulate growth (IL-3), GM-CSF, or CSF-1). In contrast, two other stem cell populations (0% to 15% Höechst 33342/Rhodamine 123 [Hö/Rh123] and Lin-Sca-1+ cells) were markedly inhibited by TGF beta and unaffected by MIP-1 alpha. Furthermore, MIP-1 alpha has no effect on high proliferative potential colony-forming cells 1 or 2 (HPP-CFC/1 or /2) colony formation in vitro, whereas TGF beta inhibits both HPP-CFC/1 and HPP-CFC/2. Thus, MIP-1 alpha and TGF beta are direct bidirectional regulators of HPC growth, whose effects are dependent on other growth factors present as well as the maturational state of the HPC assayed. The spectrum of their inhibitory and enhancing activities shows overlapping yet distinct effects.

Animals↗
PubMed1994

Interleukin-1 (IL-1) directly and indirectly promotes hematopoietic cell growth through type I IL-1 receptor.

Interleukin-1 (IL-1) has been shown to stimulate hematopoietic progenitor cell growth both in vitro and in vivo. Although IL-1 alone lacks the ability to promote hematopoietic progenitor growth in vitro, it is a potent synergistic factor in combination with other colony-stimulating factors (CSFs). Because it was unknown whether type I (p80), type II (p68), or other IL-1-binding proteins mediated the synergistic effects of IL-1 on purified progenitor cells, we used the difference in immunoreactivity between type I and type II IL-1 receptor (IL-1R) to better assess the role of these receptors in hematopoietic progenitor growth. Therefore, the synergistic effects of IL-1 alpha on IL-3-, CSF-1-, and granulocyte macrophage (GM)-CSF-induced progenitor growth, both in CFU-c and single-cell assays, were determined in the presence of monoclonal antibodies (MoAbs) 35F5 and 4E2 that block the binding of IL-1 alpha to type I and type II IL-1R, respectively. The synergistic effect of IL-1 alpha on IL-3 responsive Lin- and Lin(-)-Thy-1+ progenitors was indirectly mediated and could be inhibited by MoAb 35F5. In contrast, IL-1 alpha directly synergized with CSF-1 and GM-CSF to promote progenitor cell growth. The direct synergistic effect of IL-1 alpha on CSF-1-induced progenitor growth was observed in all progenitor populations examined (Lin-, Lin-Thy-1+, and Lin-Thy-1-) and was inhibited by MoAb 35F5. However, the direct synergistic effect of IL-1 alpha on GM-CSF-responsive progenitors. Lin- and Lin-Thy-1+, was partially inhibited by MoAb 35F5. In contrast, the MoAb antitype II IL-1R (MoAb 4E2) could not inhibit the direct synergistic effects of IL-1 alpha on CSF-1- or GM-CSF-induced progenitor growth. Thus, IL-1 alpha directly and indirectly stimulates the growth and differentiation of purified progenitors through the type I IL-1R but not the type II IL-1R.

Animals↗
PubMed1994

Regional changes in amino acid levels of the neonate rat brain during anoxia and recovery.

The aim of this study was to compare the changes in amino acids (alanine, aspartate, GABA, glutamate, glutamine, glycine, serine taurine) that are produced in different regions of the neonate brain (telencephalon, diencephalon cerebellum, brain stem) following a survivable period of anoxia and after the re-establishment of air respiration. Anoxia provoked different responses in the different regions. The changes during the anoxic period were as follows. In the brain stem there was a decrease in aspartate, in the telencephalon there was a significant increase in GABA and alanine and a decrease in aspartate, in the diencephalon, glutamate and GABA increased, and in the cerebellum, glycine and alanine levels were enhanced. The changes during recovery were even more dissimilar. Here the greatest shifts were seen in the brain stem with increases in glutamine, GABA, aspartate, glycine, serine, alanine, and taurine. In the telemcephalon glutamate fell and alanine increased, in the diencephalon GABA increased, and in the cerebellum, glutamate fell while glycine and alanine increased. In none of the major brain regions did the pattern of changes in neurotransmitters correspond to that seen in anoxic tolerant species.

Amino Acids↗
PubMed1994

PCR analysis of the cryI insecticidal crystal family genes from Bacillus thuringiensis.

A method allowing rapid and accurate identification of different subgroups within the insecticidal crystal CryI protein-producing family of Bacillus thuringiensis strains was established by using PCR technology. Thirteen highly homologous primers specific to regions within genes encoding seven different subgroups of B. thuringiensis CryI proteins were described. Differentiation among these strains was determined on the basis of the electrophoretic patterns of PCR products. B. thuringiensis strains, isolated from soil samples, were analyzed by PCR technology. Small amounts of bacterial lysates were assayed in two reaction mixtures containing six to eight primers. This method can be applied to rapidly detect the subgroups of CryI proteins that correspond with toxicity to various lepidopteran insects.

Bacillus thuringiensis↗
PubMed1994

Immunodetection of the ribosomal transcription factor UBF at the nucleolus organizer regions of fish cells.

A human autoimmune serum to nucleolus organizer regions (NORs) has been used to localize these structures at the light microscopic level in carp and trout tissue culture cells. In interphase cells, the immunofluorescence pattern indicates that the NORs autoantigens are contained exclusively within the nucleolus of carp epithelial (EPC) and trout gonad (RTG) cells. This fluorescence is punctuate rather than uniform, and presumably represents transcriptional complexes of ribosomal DNA. During mitosis, the autoantigens are detected by immunofluorescence microscopy at the chromosomal nucleolus organizer regions of condensed chromosomes, indicating that a considerable quantity of the molecule(s) remains bound to the ribosomal RNA genes. The major nucleolus autoantigen, defined in mammals as the upstream ribosomal binding factor (UBF), has been identified on immunoblots as a 90 kDa protein in extracts from fish cell lines and tissues. Thus, NORs appear to function as nucleation centers for ribosomal RNA together with a complex set of well-conserved protein factors, such as UBF. Our results suggest evolutionary conservation from fish to mammals with respect to ribosomal RNA biosynthesis driven by RNA polymerase I.

Animals↗
PubMed1994

The growth response of Lin-Thy-1+ hematopoietic progenitors to cytokines is determined by the balance between synergy of multiple stimulators and negative cooperation of multiple inhibitors.

The present studies investigated the balance of positive and negative growth signals in direct regulation of hematopoiesis. Interleukin-3 (IL-3) combined with Steel factor (SLF) optimally stimulated proliferation of Lin-Thy-1+ murine bone marrow progenitors in single-cell assays, and that proliferation was inhibited more than 90% by transforming growth factor-beta 1 (TGF-beta 1). Colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1, or IL-6 as a third stimulatory growth factor was incapable of counteracting the TGF-beta 1-mediated inhibition of IL-3-plus-SLF-stimulated growth, while G-CSF slightly enhanced the number of TGF-beta 1-resistant clones. As a fourth factor, only IL-1 could partially overcome the TGF-beta 1-induced growth inhibition. While the presence of a cocktail of five additional stimulatory growth factors did not enhanced the frequency of single Lin-Thy-1+ progenitors proliferating in response to IL-3 plus SLF, the number of responding progenitors in the presence of TGF-beta 1 was enhanced nine-fold. Furthermore, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not macrophage inflammatory protein-1 alpha (MIP-1 alpha), cooperated with TGF-beta 1 to reverse the proliferative effects of multiple stimulatory cytokines, resulting in 76% inhibition. Thus, the direct effects of single inhibitory factors on hematopoietic progenitor cell growth can be reversed by multiple stimulatory growth factors, and negative growth factors can directly cooperate to suppress progenitor cell growth stimulated by multiple positive-acting factors.

Animals↗
PubMed1994

Distinct and direct synergistic effects of IL-1 and IL-6 on proliferation and differentiation of primitive murine hematopoietic progenitor cells in vitro.

While interleukin-1 (IL-1) and IL-6 have been demonstrated to synergize with colony-stimulating factors (CSFs) and stem cell factor (SCF) to stimulate myeloid colony formation of primitive hematopoietic progenitor cells, it has not yet been established whether these effects are directly mediated. In the present study, direct effects of IL-1 and IL-6 were examined on primitive Lin-Sca-1+ murine bone-marrow progenitor cells that were cultured and plated individually. IL-1 and IL-6 showed not only overlapping, but also distinct, patterns of direct synergy. While IL-1 or IL-6 had no proliferative effects as single growth factors, IL-1, in combination with granulocyte-macrophage CSF (GM-CSF), IL-3, CSF-1, and SCF, but not granulocyte-CSF (G-CSF), enhanced the cloning frequency of Lin-Sca-1+ progenitors three- to five-fold, whereas IL-6 increased the cloning frequency in response to all four CSFs and SCF two- to seven-fold. In all cases, the size of the colonies observed were increased as well. Furthermore, the combined action of IL-1 and IL-6 resulted in additive or synergistic enhancement of CSF- and SCF-stimulated colony formation of Lin-Sca-1+ high proliferative potential colony-forming cells (HPP-CFCs). Finally, IL-6, but not IL-1, enhanced the number of immature blast cells observed in CSF- and SCF-stimulated cultures.

Animals↗
PubMed1993

Interaction between the C-terminal peptides of tubulin and tubulin S detected with the fluorescent probe 4',6-diamidino-2-phenylindole.

The digestion of tubulin with subtilisin and the reassociation of the digestion products was followed by means of the fluorescent probe 4',6-diamidino-2-phenylindole (DAPI). The fluorescence spectra of DAPI bound to chicken brain tubulin and to the main products of tubulin digested with subtilisin-agarose (tubulin S and C-terminal peptides) were analyzed. The corrected emission spectrum of DAPI in the presence of tubulin showed an enhancement of fluorescence intensity with a maximum at 452 nm. The digestion reaction was followed by the diminution of the area of DAPI-tubulin emission spectra, which showed biphasic pseudo-first-order kinetics. The values for the rate constants were 1.2 x 10(-2) min-1 and 3.5 x 10(-2) min-1 for the alpha and beta subunits, respectively, and were similar to those determined from the undigested subunits using polyacrylamide gel electrophoresis. Tubulin S and the C-terminal peptides were purified by means of a Bio-Gel P-60 column. The C-terminal peptides obtained from this column were analyzed by urea-sodium dodecyl sulfate polyacrylamide gel electrophoresis, and an apparent molecular weight around 3000 was determined. The corrected emission spectrum of DAPI in the presence of tubulin S showed a maximum shifted to 460 nm and a lower enhancement of fluorescence than the emission spectrum of the DAPI-tubulin complex. Titration of purified tubulin S with the C-terminal peptides of tubulin showed, after the addition of DAPI, an increase in the fluorescence intensity at 460 nm with a saturation function dependent on the concentration of peptides added. On the other hand, the emission spectrum of DAPI in the presence of the C-terminal peptides was unchanged from that of free DAPI in the solution. From these results we propose that the DAPI binding site is located on tubulin S and that the C-terminal peptides interact with tubulin S after digestion with subtilisin.

Fluorescent Dyes↗
PubMed1992

Anti-muscarinic activity of a family of C11N5 compounds isolated from Agelas sponges.

In a search for potential target sites for C11N5 compounds obtained from marine sponges of the genus Agelas we evaluated their interaction with muscarinic acetylcholine receptors from rat brain membranes. In competition experiments with 3H-QNB these compounds displayed the following rank order of potency: sceptrin greater than oroidin greater than or equal to dibromosceptrin greater than or equal to clathrodin. Sceptrin (50 microM) was shown to be a competitive inhibitor of 3H-QNB binding as revealed by Scatchard analysis. The results demonstrate the ability of these compounds to interact with multiple target molecules in the micromolar range.

Alkaloids↗
PubMed1992

[Determination of plasma concentration of amiodarone and desethylamiodarone with high pressure liquid chromatography. Preliminary experience].

A simple specific and sensitive high pressure liquid chromatography method (HPLC) to measure amiodarone and desethylamiodarone is described. The plasma sample is deproteinized with acetonitrile and a 50 ul aliquote run in the HPLC system with reverse phase column (C-18). Methanol-ammonium hydroxide is used to separate and spectrophotometric measurements are read at 254 nm.95% of the drug present in plasma is extracted with this method, with a sensitivity of 0.03 ug/ml and a day to day variation under 3%. Preliminary measurements were analyzed in 14 subjects receiving amiodarone for treatment of supraventricular arrhythmia. With a mean dose of 267 +/- 116 (SD) mg/day, plasma levels of 1.3 +/- 0.6 ug.ml for amiodarone and 0.9 +/- 0.5 mg/ml for desethylamiodarone were obtained.

Adult↗
PubMed1991

Monoclonal antibody with specificity to a conserved epitope in the C-terminal domain of histone H1 variants.

A monoclonal type M-immunoglobulin (IgM) was generated in mice against a nuclease-urea extract of HeLa metaphase chromosomes. This antibody stains metaphase chromosomes from a variety of mammalian cultured cell types by indirect immunofluorescence. Antibody 12C7 reacts by western transfer technique with histone H1 in all the cell lines tested. The antibody cross-reacts with H1, and H1(0) in human cells. Proteolytic digestions of H1 suggest that the epitope is localized in the carboxy-terminal domain of the histone H1 molecule. Digestion with trypsin demonstrates that the antibody 12C7 does not react with the globular domain of histone H1. The C-terminal domain of H1 subtypes therefore seems to have a conserved determinant which does exist in H1, H1(0), and probably in H5. This antibody has applications in studying the role of that domain of H1 in processes like chromosome condensation and variations in chromatin structure which influence gene expression.

Antibodies, Monoclonal↗
PubMed1991

Heparin-induced hyperkalemia: a prospective study.

Heparin is frequently used for the prophylaxis and treatment of deep venous thromboembolism and it induces hypoaldosteronism leading to hyperkalemia, an uncommon adverse effect. In an intensive prospective drug monitoring study, 154 inpatients at the Internal Medicine Unit of Hospital Sotero del Río, Santiago, Chile, received heparin in the period between March and November 1990. Mean age of the patients was 65.8 +/- 12.9 years and 56.5% were female. Twenty-one (13.6%) patients developed heparin-induced adverse reactions. Thirteen events were hyperkalemia, 7 ecchymoses and 1 hematuria. The monitoring team and attending physicians have agreed to classify 9 heparin-induced hyperkalemia cases as probable and the other 4 as possible. No adverse reaction was fatal but 8 of the patients had severe hyperkalemia. Almost all reactions were dose-related. Hyperkalemia was more frequent in patients with diabetes mellitus, metabolic acidosis and long-term heparin therapy. The frequency of hyperkalemia did not correlate with age, sex, renal impairment or with previous use of anti-inflammatory drugs, heparin or aspirin.

Adolescent↗
PubMed1991

[Myocardial contraction and ventricular function in normal subjects evaluated with isotopic ventriculography and phase analysis].

Normal heart contraction was studied in 20 healthy subjects (14 males and 6 female, mean age 33 years). Rest radioventriculography and phase analysis were used. Ejection fraction was 66 +/- 7% for the LV and 53 +/- 7% for the RV (p < 0.0001). Peak filling rates in the first third of diastole were 1.6 +/- 0.6 EDV/sec for the LV and 0.7 +/- 0.3 EDV/sec for RV (p < 0.0001). Time to peak filling rate normalized for heart rate was 180 +/- 52 ms for the LV and 203 +/- 60 ms for the RV (p = 0.05). Filling fractions were 23 +/- 10% and 9 +/- 3%, respectively (p < 0.0001). Segmental motility was normal in all subjects. Phase analysis revealed faster emptying of the left atrium with phase angles of 171 +/- 13 degrees in the LA and 185 +/- 12 degrees in the RA (p = 0.00007). This difference may be related to faster diastolic events in the left ventricle. Phase angles for the LV and RV were -8.75 +/- 3 and -9.44 +/- 5 degrees, respectively (NS). We conclude that activation occurs earlier in the left atrium, proceeds through the septum and then synchronically over both ventricles.

Adolescent↗