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Biomedical subjects

M A Castro

Publications and source records attributed to M A Castro.

At least 19 recordsLinked to original sources
PubMed2003

NMR study of n-dodecane adsorbed on graphite.

In this brief contribution we demonstrate that 1H and 2H NMR spectroscopy can be an effective method of investigating adsorption from liquids at the solid-liquid interface. The method is illustrated here with the adsorption of a simple alkane adsorbed on graphite, in particular the system n-dodecane and graphite at coverages of 1 and 5 monolayers. Static single-pulse proton nuclear magnetic resonance and static quadrupolar echo deuterium nuclear magnetic resonance spectra were recorded for both coverages. The experimental NMR results presented here show features clearly consistent with earlier calorimetric and neutron scattering work and demonstrate the formation of solid adsorbed layers that coexist with the bulk adsorbate with both isotopes. This ability to probe both deuterated and protonated materials simultaneously illustrates that this experimental approach can be readily extended to investigate the adsorption behaviour of multicomponent mixtures.

Adsorption↗
PubMed2003

[Influence of different pharmacological agents in the ex vivo proliferation of mesothelial cells obtained from the peritoneal effluent of patients treated with peritoneal dialysis].

UNLABELLED: Mesothelial cells (MC) are the first peritoneal membrane barrier in contact with dialysate. The aim of this study was to analyze the in vitro capacity of different pharmacological agents to modify the ex vivo proliferation of MC obtained from the peritoneal effluent of patients treated with peritoneal dialysis (PD). MATERIAL AND METHODS: Thirty cultures of MC taken from nocturnal peritoneal effluent were performed. After identification, MC are subcultured in 24 multi-well plates, adding the different exogenous agents. Proliferative capacity and cell morphology were estimated on day 16th of culture. The agents evaluated were insulin, IGF-1, tamoxifen, labetalol, carvedilol, enalapril and losartan. RESULTS: Insulin shows a dose-dependent effect on MC growth, with a limit that is stimulated by the addition of fetal bovine serum (FBS). Concentrations higher than 100 micrograms/ml, are not associated with further growth, even with cell damage. In contrast, the wide range of IGF-1 dose used did not affect to MC proliferation. Tamoxifen causes negative effects on MC growth just a very high doses, not resembling doses in clinical practice. Labetalol does not modify MC proliferation used under therapeutic calculated range. However, concentrations higher than 40 micrograms/ml showed a negative influence on growth, behaving as lethal doses that over 100 micrograms/ml. The addition of FBS attenuates this effect. These effects were very similar to that caused by carvedilol addition. Enalapril and losartan act as antiproliferative agents for MC. This effect is potentiated with angiotensin II, reaching lethal concentrations increasing the dose. In conclusion, mesothelial cell growth ex vivo taken from nocturnal peritoneal effluent on PD patients is an useful tool to explore the effects of any pharmacological agent on the biology of the cell of the peritoneum. The agents used had any influence in the proliferation capacity of mesothelial cells.

Ascitic Fluid↗
PubMed2001

Gastric necrosis and perforation as a complication of splenectomy. Case report and related references.

Necrosis of the stomach after isolated splenectomy with the formation of gastrocutaneous fistula is a rare event that occurs in less than 1% of splenectomies. It is more frequent when the removal of the spleen is done because of hematological diseases. Its mortality index can reach 60% and its pathogenesis is controversial, as it may be attributed both to direct trauma of the gastric wall and to ischemic phenomena. Although the stomach may exhibit exuberant arterial blood irrigation, anatomical variations can cause a predisposition towards the appearance of potentially ischemic areas, especially after ligation of the short gastric vessels around the major curvature of the stomach. Once this is diagnosed in the immediate postoperative period, it becomes imperative to reoperate. The surgical procedure will depend on the conditions of the peritoneal cavity and patient's clinic status. The objective of this study was to report on the case of a patient submitted to splenectomy because of closed abdominal traumatism, who then presented peritonitis and percutaneous gastric fistula in the post-operative period. During the second operation, perforations were identified in anterior gastric wall where there had been signs of vascular stress. The lesion was sutured after revival of its borders, and the patient had good evolution. Prompt diagnosis and immediate treatment of this unusual complication are needed to reduce its high mortality rate.

Adolescent↗
PubMed2001

New selective cytotoxic diterpenylquinones and diterpenylhydroquinones.

A new series of diterpenylquinone/hydroquinones has been prepared by Diels-Alder cycloaddition between three labdanic diterpenoids (myrceocommunic acid, methyl myrceocommunate, and myrceocommunyl acetate) and p-benzoquinone or 1,4-naphthoquinone. Influences of the quinone/hydroquinone fragment and other structural features, such as the different functionalities in the terpenic core, are considered in relation to the cytotoxicity toward neoplastic cells and the selectivity of these diterpenylnaphthoquinones/hydroquinones and anthraquinones. Several compounds showed IC50 values under the micromolar level, and four of these derivatives were evaluated at the NCI screening panel. The results showed an important selectivity toward renal cancer lines, identifying these compounds as a very promising group of antineoplastics.

Animals↗
PubMed2001

Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non-small cell lung carcinoma cell lines.

In the present study, we examined the relationship between cell phenotype and cell survival of three human non-small cell lung carcinoma cell lines (A549, NCI-H596 and NCI-H520). Cells in exponential growth at various densities were incubated for 24 h at 37 degrees C in a 5% CO2 humidified atmosphere and then exposed to UV radiation for 1 min (256 nm, 40 W, source-to-target distance 100 cm). After two days the surviving cells were quantified by sulforhodamine beta staining and DNA fragmentation assay. The differences in UV sensitivity at 60 x 10(3) cells/cm2 among the cell lines were not related to the proliferative state of the cells but to the extent of intercellular contact. In contrast to A549 and NCI-H596, irradiated NCI-H520 cells presented lower DNA fragmentation and an aggregated cell culture phenotype even prior to confluence, suggesting that a contact-effect mechanism provides further protection against UV radiation.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Effect of bicarbonate/lactate peritoneal dialysis solutions on human mesothelial cell proliferation ex vivo.

Peritoneal membrane suffers structural and functional changes over time on peritoneal dialysis (PD)--in part, owing to the dialysis solutions currently used. Low pH seems to be an important element associated with solution bioincompatibility. Bicarbonate-containing fluids open new perspectives on this issue. The present study compared the effects of bicarbonate/lactate (Bic/Lac) solution (25 mmol/L bicarbonate, 15 mmol/L lactate) and lactate (Lac) solution (40 mmol/L lactate) on mesothelial cell (MC) growth in culture. Eight stable PD patients were asked to collect peritoneal effluent from an 8-hour dwell on two separate days, within an interval shorter than one week. For the first dwell, Lac solution was infused; for the second dwell, Bic/Lac solution was instilled. Human MCs were isolated from the effluent, seeded in 25-cm2 tissue culture flasks, and grown ex vivo. Morphology of the cells was also evaluated. In all effluents, MCs were present in mean amounts of 26,939 +/- 21,267 cells (Bic/Lac) and 25,986 +/- 15,286 cells [Lac, p = nonsignificant (NS)]. Morphology of the MCs was similar with both solutions (87.5% typical). After initial culture, MCs from 6 patients using Bic/Lac (75%) and 3 patients using Lac (37.5%) reached confluence. At this time, the number of MCs from the 3 patients who showed MC growth with both solutions was slightly higher with Bic/Lac-buffered fluid (Lac: 1,154,125 +/- 213,333 cells; Bic/Lac: 1,198,291 +/- 806,713 cells). To summarize: 3 patients showed MC growth under both solutions; 3 patients showed MC growth only under Bic/Lac solution; and 2 patients showed no MC growth at all. After cells were seeded in 24-well plates, the MC growth curve was performed in 4 cases of Bic/Lac solution use and in 3 cases of Lac solution use. Although no significant differences were observed between the solutions, the final number of MCs obtained was higher with Bic/Lac solution use. In conclusion, MCs released into peritoneal effluent under bicarbonate/lactate-buffered peritoneal dialysis solution are associated with a greater ex vivo proliferation capacity than those released under lactate solution in the same patient. This finding may demonstrate better biocompatibility for Bic/Lac solution.

Bicarbonates↗
PubMed2000

New antineoplastic prenylhydroquinones. Synthesis and evaluation.

Several prenylhydroquinones have been prepared through Diels-Alder condensation, further functionalized or degraded chemically and then evaluated for their cytotoxic activity against some neoplastic cultured cell lines. A number of them have shown IC50 values under the microM level.

Antineoplastic Agents↗
PubMed2000

Antitumor properties of podophyllotoxin and related compounds.

The lignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, lignans, and especially cyclolignans, have been the objective of numerous studies focused to prepare better and safer anticancer drugs. The mechanism by which podophyllotoxin blocks cell division is related to its inhibition of microtubule assembly in the mitotic apparatus. However, etoposide and teniposide were shown not to be inhibitors of microtubule assembly which suggested that their antitumor properties were due to another mechanism of action, via their interaction with DNA and inhibition of DNA topoisomerase II. Other podophyllotoxin derivatives has also been reported which retained or even improved the cytotoxic activity, but these were weak inhibitors of topoisomerase II in vitro; the data revealed that such analogs exhibit a different, as yet unknown, mechanism of action. The main deficiency of these compounds is their cytotoxicity for normal cells and hence side effects derived from their lack of selectivity against tumoral cells. In this regard it is necessary to investigate and prepare new more potent and less toxic analogs, that is, with better therapeutic indices. It is well accepted from structure-activity studies in this field that the trans-lactones are more potent as antineoplastics than the cis-lactones. Not only the configuration of the D ring is an important factor for high cytotoxic activity, but also a quasi-axial arrangement of the E ring is necessary. On this basis, studies on lignans have been addressed to modify the lactone moiety and prepare analogs with heteroatoms at different positions of the cyclolignan skeleton. Our group has been working during the last few years on chemical transformations of podophyllotoxin and analogs and we have prepared a large number of cyclolignan derivatives some of which display potent antiviral, immunosuppressive and cytotoxic activities. We have reported several new cytotoxic agents with nitrogen atoms at C-7 or C-9 or at both C-7 and C-9: imine derivatives, oxime derivatives, pyrazoline-, pyrazo- and isoxazoline-fused cyclolignans. At present, we are preparing mainly new compounds by modifications of the A and E cyclolignan-rings. They are being tested on cultures of different tumoral cell lines (P-388 murine leukemia, A-549 human lung carcinoma, HT-29 human colon carcinoma and MEL-28 human melanoma) and some of them have shown an interesting and selective cytotoxicity.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Effect of mode of delivery in nulliparous women on neonatal intracranial injury.

BACKGROUND: Infants delivered by vacuum extraction or other operative techniques may be more likely to sustain major injuries than those delivered spontaneously, but the extent of the risk is unknown. METHODS: From a California data base, we identified 583,340 live-born singleton infants born to nulliparous women between 1992 and 1994 and weighing between 2500 and 4000 g. One third of the infants were delivered by operative techniques. We evaluated the relation between the mode of delivery and morbidity in the infants. RESULTS: Intracranial hemorrhage occurred in 1 of 860 infants delivered by vacuum extraction, 1 of 664 delivered with the use of forceps, 1 of 907 delivered by cesarean section during labor, 1 of 2750 delivered by cesarean section with no labor, and 1 of 1900 delivered spontaneously. As compared with the infants delivered spontaneously, those delivered by vacuum extraction had a significantly higher rate of subdural or cerebral hemorrhage (odds ratio, 2.7; 95 percent confidence interval, 1.9 to 3.9), as did the infants delivered with the use of forceps (odds ratio, 3.4; 95 percent confidence interval, 1.9 to 5.9) or cesarean section during labor (odds ratio, 2.5; 95 percent confidence interval, 1.8 to 3.4), but the rate of subdural or cerebral hemorrhage associated with vacuum extraction did not differ significantly from that associated with forceps use (odds ratio for the comparison with vacuum extraction, 1.2; 95 percent confidence interval, 0.7 to 2.2) or cesarean section during labor (odds ratio, 0.9; 95 percent confidence interval, 0.6 to 1.4). CONCLUSIONS: The rate of intracranial hemorrhage is higher among infants delivered by vacuum extraction, forceps, or cesarean section during labor than among infants delivered spontaneously, but the rate among infants delivered by cesarean section before labor is not higher, suggesting that the common risk factor for hemorrhage is abnormal labor.

Birth Injuries↗
PubMed1999

Phenotype modulation of cellular UV-sensitivity.

Mammalian cell shape is critically important to cell differentiation, apoptosis, cell division, and growth arrest. In the present study we examined the relationship among cell density, cell phenotype (which include shape and coupling) and cell survival using the human A549, H596 and H520 non-small cell lung carcinoma lines. Thus, cells from monolayers, aggregated and suspended cultures at different densities were exposed to UV-radiation and both the density and the phenotype of the cells induce shifts in cellular growth rate. Except in suspended cultures, we observed a UV-sensitivity closely related to the proliferative status of the cells. The variability of the cellular response to UV were investigated taking into account the shape and the coupling potential of the cell lines, suggesting that an intercellular-contact mechanism provides further protection against UV-radiation damage.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

CD2 and CD3 associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells.

In T lymphocytes, the CD2 and CD5 glycoproteins are believed to be involved in the regulation of signals elicited by the TCR/CD3 complex. Here we show that CD2 and CD3 independently associate with CD5 in human PBMC and Jurkat cells. CD5 coprecipitates with CD2 in CD3-deficient cells and, conversely, coprecipitates with CD3 in cells devoid of CD2. In unstimulated CD2+ CD3+ Jurkat cells, CD5 associates equivalently with CD2 and CD3 and is as efficiently phosphorylated in CD2 as in CD3 immune complexes. However, upon activation the involvement of CD5 is the opposite in the CD2 and CD3 pathways. CD5 becomes rapidly tyrosine phosphorylated after CD3 stimulation, but is dephosphorylated upon CD2 cross-linking. These opposing effects correlate with the decrease in the activity of the SH2 domain-containing protein phosphatase 1 (SHP-1) following CD3 activation vs an enhanced activity of the phosphatase after CD2 triggering. The failure of CD5 to become phosphorylated on tyrosine residues in the CD2 pathway has no parallel with the lack of use of zeta-chains in CD2 signaling; contrasting with comparable levels of association of CD2 or CD3 with CD5, zeta associates with CD2 only residually and is nevertheless slightly phosphorylated after CD2 stimulation. The modulation of CD5 phosphorylation may thus represent a level of regulation controlled by CD2 in signal transduction mechanisms in human T lymphocytes.

Antibodies, Monoclonal↗
PubMed1999

Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases.

OBJECTIVE: We sought to describe our experience with the clinical diagnosis, management, and course of patients with acute fatty liver of pregnancy. STUDY DESIGN: Twenty-eight cases of acute fatty liver of pregnancy at the Los Angeles County and University of Southern California Medical Center from 1982 to June 1997 were identified, and presenting symptoms, clinical course, laboratory values, maternal complications, and neonatal outcomes were studied. RESULTS: The incidence of acute fatty liver of pregnancy was 1 in 6659 births. There were no maternal deaths. Initial presentation was at an average of 37 weeks of gestation with a characteristic prodrome of malaise, nausea, vomiting, and abdominal pain. No patient was admitted with the diagnosis of acute fatty liver of pregnancy. The condition was diagnosed most commonly on the second hospital day after laboratory results indicated coagulopathy, renal insufficiency, and liver function abnormalities. One patient underwent liver biopsy at cesarean delivery. Radiologic studies did not aid with the diagnosis. Twenty-one patients were admitted in spontaneous labor, and 16 labors were complicated by abnormal fetal heart rate patterns or meconium. There was 1 stillbirth and 1 neonatal death as a result of perinatal asphyxia. Maternal morbidity consisted of hypoglycemia, infection, renal insufficiency, coagulopathy, encephalopathy, and wound complications. All patients had evidence of disseminated intravascular coagulopathy with profoundly decreased antithrombin levels. All patients recovered normal liver function post partum. CONCLUSIONS: Reversible peripartum liver failure may be diagnosed and managed on the basis of clinical and laboratory criteria. With adequate support, these patients may have full recovery of hepatic function.

Acute Disease↗
PubMed1998

Mapping of MCP-1 functional domains by peptide analysis and site-directed mutagenesis.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the beta chemokine family which acts through specific seven transmembrane receptors to recruit monocytes, basophils, and T lymphocytes to sites of inflammation. To identify regions of the human MCP-1 protein which are important for its biological activity, we have synthesized domain-specific peptides and tested their ability to antagonize MCP-1 binding and chemotaxis in THP-1 cells. We have found that an intercysteine first loop peptide encompassing amino acids 13-35 inhibits MCP-1 binding and chemotactic activity, while peptides representing the amino-terminus (amino acids 1-10), second loop (amino acids 37-51), and carboxy-terminus (amino acids 56-71) of MCP-1 have no effect. In addition, we have found that cyclization of the first loop peptide by disulfide linkage and blocking the C-terminus of the peptide by amidation increases the activity of this peptide to block MCP-1 binding and chemotaxis. In order to specifically identify amino acid residues within the first loop that are crucial for MCP-1 functional activity, we have substituted alanine for tyrosine (Y13A) or arginine (R18A) in MCP-1 recombinant proteins. While baculovirus produced wild type and R18A MCP-1 proteins are indistinguishable in their ability to induce THP-1 chemotaxis and show modest effects in binding activity compared to commercially available recombinant MCP-1 protein, the Y13A point mutation causes a dramatic loss in function. The identification of functional domains of MCP-1 will assist in the design of MCP-1 receptor antagonists which may be clinically beneficial in a number of inflammatory diseases.

Amino Acid Sequence↗