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Biomedical subjects

A Ortiz

Publications and source records attributed to A Ortiz.

At least 91 records · Page 5Linked to original sources
PubMed1999

The Fas ligand/Fas system in renal injury.

The FasL-Fas system regulates renal cell apoptosis, as well as the immune and inflammatory responses. Evidence that FasL and Fas participate in renal injury may be summarized along modified Koch's postulates (Table 1): (i) FasL is expressed by renal cells and during renal injury, (ii) activation of the Fas receptor promotes apoptosis of cultured renal cells, (iii) Fas agonists induce glomerular injury but they may also decrease renal injury by limiting injurious immunological responses, (iv) mice with disrupted FasL/Fas systems are protected from tubular cell injury during ischaemia reperfusion, although they develop autoimmune glomerulonephritis if other genetic predisposing factors are present. FasL/Fas must be considered a new target for therapeutic intervention in renal injury. Therapeutic modulation of Fas should aim not only at protecting intrinsic glomerular or tubular epithelial cells from death, but also at modulating the immune, inflammatory, and fibrogenic responses. Possible therapeutic interventions include Fas agonists, soluble Fas receptors, or other antagonists, and targetting of Fas to undesired cells, such as fibroblasts, in order to decrease their numbers in a physiological manner through apoptosis. Any therapeutic attempt should carefully take into account the possible effects of interference with Fas in other 1833 cell systems. Given the complexities of the FasL/Fas system, further studies are warranted.

Animals↗
PubMed1999

Reading with a head-mounted video magnifier.

PURPOSE: This study compared the effectiveness of a head-mounted video magnifier, low-vision enhancement system (LVES), with closed-circuit TV (CCTV) and large print as a device or means of improving reading performance in people with low vision. METHODS: The reading performance of ten low-vision participants was assessed in two ways: (1) By measuring reading speed as a function of print size with LVES and without LVES, and (2) by comparing reading speed and comprehension of news articles using the LVES vs. a popular non-head-mounted video magnifier, the CCTV. RESULTS: Maximum reading speeds with LVES matched the maximum reading speeds with unaided vision attained by enlarging print. The critical print size (the smallest print size that could be read at maximum reading speed) improved significantly for all participants using LVES compared with unaided vision. When comparing reading performance using LVES and CCTV, we found that reading speed and comprehension for the two conditions were equivalent. The two low-vision participants with lowest acuities (20/640 and 20/960) could not read the 10-point newspaper articles with LVES, even with an 8 D auxiliary reading lens that permitted a very close reading distance. CONCLUSIONS: Head-mounted video magnifiers, such as LVES, can support good low-vision reading performance, but the restricted range of magnification may limit the usefulness of the device as a reading magnifier for people with very low acuity.

Adult↗
PubMed1999

Molecular mechanism of the intestinal biotin transport process.

Previous studies have characterized different aspects of the cellular/membrane mechanism and regulation of the intestinal uptake process of the water-soluble vitamin biotin. Little, however, is known about the molecular mechanisms of the uptake process. In this study, we have identified a cDNA from rat small intestine that appears to be involved in biotin transport. The open reading frame of this cloned cDNA consisted of 1,905 bases and was identical to that identified for the vitamin transporter in placental tissue. Significant heterogeneity, however, was found in the 5' untranslated region of this clone, with three distinct variants (II, III, IV) being identified in the small intestine; the placental variant (variant I), however, was not present in the small gut. Variant II was found to be the predominant form expressed in the rat small and large intestines. Functional identity of the cloned intestinal cDNA was confirmed by stable expression in COS-7 cells, which showed a four- to fivefold increase in biotin uptake in transfected COS-7 cells compared with controls. The induced biotin uptake in transfected COS-7 cells was found to be 1) Na(+) dependent, 2) saturable as a function of concentration with an apparent K(m) of 8. 77 microM and a V(max) of 779.7 pmol. mg protein(-1). 3 min(-1), and 3) inhibited by unlabeled biotin and pantothenic acid and their structural analogs. The distribution of complementary mRNA transcripts of the cloned cDNA along the vertical and longitudinal axes of the intestinal tract was also determined. Results of this study describe the molecular characteristics of the intestinal biotin absorption process and report the identification of a cDNA that encodes a Na(+)-dependent biotin uptake carrier that appears to exist in the form of multiple variants.

5' Untranslated Regions↗
PubMed1999

Transport of thiamine in human intestine: mechanism and regulation in intestinal epithelial cell model Caco-2.

The present study examined the intestinal uptake of thiamine (vitamin B(1)) using the human-derived intestinal epithelial cells Caco-2 as an in vitro model system. Thiamine uptake was found to be 1) temperature and energy dependent and occurred with minimal metabolic alteration; 2) pH sensitive; 3) Na(+) independent; 4) saturable as a function of concentration with an apparent Michaelis-Menten constant of 3.18 +/- 0.56 microM and maximal velocity of 13.37 +/- 0.94 pmol. mg protein(-1). 3 min(-1); 5) inhibited by the thiamine structural analogs amprolium and oxythiamine, but not by unrelated organic cations tetraethylammonium, N-methylnicotinamide, and choline; and 6) inhibited in a competitive manner by amiloride with an inhibition constant of 0.2 mM. The role of specific protein kinase-mediated pathways in the regulation of thiamine uptake by Caco-2 cells was also examined using specific modulators of these pathways. The results showed possible involvement of a Ca(2+)/calmodulin (CaM)-mediated pathway in the regulation of thiamine uptake. No role for protein kinase C- and protein tyrosine kinase-mediated pathways in the regulation of thiamine uptake was evident. These results demonstrate the involvement of a carrier-mediated system for thiamine uptake by Caco-2 intestinal epithelial cells. This system is Na(+) independent and is different from the transport systems of organic cations. Furthermore, a CaM-mediated pathway appears to play a role in regulating thiamine uptake in these cells.

Biological Transport↗
PubMed1998

3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.

Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to induce apoptosis in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis of VSMCs, cultured rat VSMCs were treated with increasing doses of atorvastatin in the presence of FBS as a survival factor. The presence of apoptosis was evaluated by morphological criteria, annexin V binding, and DNA fragmentation and quantified as the proportion of hypodiploid cells by flow cytometry. Atorvastatin induced apoptosis in a dose-dependent manner, an effect also seen with simvastatin and lovastatin, but not with the hydrophilic drug pravastatin. The proapoptotic effect of statins was seen only when the inhibition of acetate incorporation into sterols was >95% and was fully reversed by mevalonate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate but not by isopentenyl adenosine, ubiquinone, or squalene, suggesting a role for prenylated proteins in the regulation of VSMC apoptosis. To further assess the role of protein prenylation, VSMCs were exposed to the prenyl transferase inhibitors perillic acid and manumycin A. Both agents induced VSMC apoptosis as evaluated by the above-mentioned criteria. Finally, VSMC treatment with lipophilic statins was associated with decreased prenylation of p21-Rho B, further supporting the role of protein prenylation inhibition in statin-induced VSMC apoptosis. The present data suggest that interference with protein prenylation by HMG-CoA reductase inhibitors or other agents may provide new strategies for the prevention of neointimal thickening.

Animals↗
PubMed1998

2,5-Diamino-p-benzoquinone Derivatives as Photosystem I Electron Acceptors: Synthesis and Electrochemical and Physicochemical Properties.

A series of 2,5-diamino-p-benzoquinone derivatives have been prepared and their physicochemical properties studied. The sensitivity of their photoreduction potential to 3-(3,4-dichlorophenyl)-1,1-dimethylurea, 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, and KCN, as well as the photosystem I (PSI) activity, suggests that the reduction of 2,5-diamino-p-benzoquinone derivatives in the illuminated thylakoid is at the primary electron acceptor of PSI and it is reversible. The half-wave potentials of these compounds to their corresponding radical anions in an aprotic medium such as acetonitrile were found to be comparable with the midpoint potential values of the electron transport carriers at the reducing site of PSI. The strong reductant produced by PSI is really more accessible to the strong lipophilic electron acceptor. These lipophilic p-benzoquinone derivatives can reach the carriers inside the thylakoid membrane more easily than the ionic electron acceptor. The accepting electron properties of these compounds at PSI are similar to those of the bipyridinium herbicides.

Journal Article↗
PubMed1998

Riboflavin uptake by the human-derived liver cells Hep G2: mechanism and regulation.

The water-soluble vitamin riboflavin (RF) plays a critical role in many metabolic reactions, and thus, is essential for normal cellular functions and growth. The liver plays a central role in normal RF metabolism and is the site of maximal utilization of the vitamin. The mechanism of liver uptake of RF has been studied in animals, but no information is available describing the mechanism of the vitamin uptake in the human situation and its cellular regulation. In this study, we used the human-derived liver cells Hep G2 as an in vitro model system to address these issues. Uptake of RF by Hep G2 cells was found to be temperature- and energy-dependent but Na+-independent in nature. Uptake seemed to involve a carrier-mediated process as indicated by the saturation as a function of substrate concentration (apparent Km 0.41 +/- 0.08 microM), and by the ability of the structural analogs lumiflavin and lumichrome to inhibit the uptake process [inhibition constant (K) of 1.84 and 6.32 microM, respectively]. RF uptake was energy dependent, and was inhibited by the -SH group blocker p-chloromercuriphenylsulfonate (p-CMPS) (Ki of 0.10 mM). Specific modulators of intracellular protein kinase A (PKA)-, protein kinase C (PKC)-, and protein tyrosine kinase (PTK)-mediated pathways did not affect RF uptake by Hep G2 cells. On the other hand, specific inhibitors of Ca2+/calmodulin-mediated pathway significantly inhibited the uptake process; this effect seemed to be mediated through a decrease in the Vmax of the substrate uptake process. Maintaining Hep G2 cells in a RF-deficient growth medium was associated with a significant up-regulation in the substrate uptake; this effect was specific for RF and was mediated mainly by means of an increase in the Vmax of the uptake process. These results describe, for the first time, the mechanism and cellular regulation of RF uptake by a human-derived liver cellular preparation, and shows the involvement of a carrier-mediated system in the uptake process. Furthermore, the uptake process seems to be regulated by an intracellular Ca2+/calmodulin-mediated pathway and by extracellular substrate levels.

Antiemetics↗
PubMed1998

Dissimilar protection of tocopherol isomers against membrane hydrolysis by phospholipase A2.

Porcine pancreatic phospholipase A2 (PLA2) hydrolyses phosphatidylcholine when in the lamellar state as well as in the micellar state. We have found that alpha-tocopherol, the most active form of vitamin E, is able to inhibit PLA2 activity only toward lamellar fluid membranes, thus protecting phospholipids toward this lytic enzyme. This compound decreases both the initial rate and the extent of hydrolysis. The inhibition is of the non-competitive type and the evidence strongly suggests that it is due to an effect of alpha-tocopherol on the substrate, i.e. the membrane, and not on the enzyme itself. Other tocopherols, such as the isomers beta-, gamma- and delta-tocopherol also display PLA2 inhibition but consecutively to a lower extent. The grade of inhibition of PLA2 activity by tocopherols correlates well with their biological activity and with their location in the bilayer as shown by fluorescence quenching. Cholesterol does not inhibit PLA2 activity at concentrations even higher than those of tocopherols, indicating that the effect of tocopherols is not due to alteration of membrane fluidity. The possible mechanisms underlying the different behaviour of tocopherol isomers as PLA2 inhibitors are discussed considering its biological significance as membrane stabilizers, suggesting biological actions of compounds with vitamin E activity other than their classical roles as antioxidants.

Animals↗
PubMed1998

Proliferative effect of insulin on cultured smooth muscle cells from rat mesenteric resistance vessels.

The present study evaluates the growth promoting effect of insulin on the proliferative activity of cells from rat mesenteric arteries in culture in order to test the hypothesis that insulin may play a pathogenetic role in the hypertrophy of resistance vessels. The proliferative effect of insulin was studied in cultured vascular smooth muscle cells (SMC) obtained from two functionally different rat vessels: mesenteric arteries and aorta. Growth characteristics (cell number and growth rate) of mesenteric and aortic cells were determined after a quiescent period and followed-up for 24, 72, and 120 h after the addition of insulin. At all studied time intervals, aortic SMC exhibited a significatively higher cell number and specific growth rate than did mesenteric SMC. Aortic SMC also displayed a greater proliferation than did mesenteric SMC in the presence of 10% fetal calf serum (FCS). At a physiological concentration of 100 microU/mL, the proliferative effect of insulin, after a quiescent period, was seen only in aortic SMC, at 72 and 120 h. Higher insulin concentration (500 microU/mL) increased significantly the cell number in SMC of both arteries. The proliferative effect was significant at all studied periods for aortic SMC; however, in mesenteric SMC, insulin increased the cell number only at 72 and 120 h. The proliferative effect of insulin was observed on SMC obtained from functionally different arteries such as aorta and mesenteric, being greater in the former. The different behavior of these SMC in the presence not only of insulin, but also of 10% FCS, provides further evidence for the existence of intervascular heterogeneity. The mild stimulatory effect of insulin in vitro may contribute in this way to the vascular hypertrophy of pathological entities exhibiting hyperinsulinemia.

Animals↗
PubMed1998

Protamine inhibits angiogenesis and growth of C6 rat glioma; a synergistic effect when combined with carmustine.

Protamine inhibits angiogenesis and blocks endothelial, fibroblast and platelet growth factors. Human and experimental gliomas spread and grow in response to both paracrine and autocrine release of these factors. Our objective was to study the effect of protamine administration on cell proliferation, angiogenesis and tumoral growth of C6 glioma. Additionally, we compared the antitumoral effect of protamine with that of another inhibitor of angiogenesis, suramin, and investigated a potential synergistic antitumoral action of low doses of protamine combined with the antineoplastic carmustine. C6 glioma cells were implanted subcutaneously in Wistar rats. A highly malignant glioma developed in 80% of animals; when the tumour reached a diameter of 1.5 cm, either protamine, suramin, carmustine or protamine plus carmustine were administered in various doses. Tumour parameters were measured and compared between groups. In a dose-dependent manner, protamine reduced tumour volume (P < 0.001), mitotic index (P < 0.05), vascular density (P < 0.05) and cell viability (P < 0.005) of C6 glioma. An ultrastructural study demonstrated membranous inclusions in the cytoplasm of 28% of tumoral and endothelial cells of tumours from animals treated with protamine. The inhibition of tumoral growth produced by moderate doses of protamine was similar to that produced by toxic doses of suramin. The combination of protamine and carmustine had a synergistic curtailing effect on tumoral growth (P < 0.001). Our results indicate that protamine is an effective agent against glioblastoma; in non-toxic doses it could potentiate the antineoplastic effect of nitrosoureas for the treatment of glial tumours.

Animals↗
PubMed1998

Clinical features and investigations in patients with columnar-lined oesophagus.

BACKGROUND: It is unclear why some patients with a columnar-lined oesophagus present with intestinal metaplasia and others do not. The physiopathological and clinical implications of the length of the metaplastic segment are also controversial. The aim of the study was to determine whether the length of the metaplasia and the presence of intestinal epithelium are related to the clinical, manometric and pHmetric data in patients with columnar-lined oesophagus. METHODS: A comparison of clinical, endoscopic, pathological, manometric and pHmetric data was made between patients with columnar-lined oesophagus of 3-5 cm (n=31) and those with a metaplastic segment of 5 cm or more (n=28); the same comparison was made between patients who had specialized intestinal metaplasia (n=37) and those who did not (n=22). RESULTS: No significant difference was found in any of the variables studied except for associated inflammatory lesions above the columnar epithelium which were more frequent in patients with a shorter metaplastic segment (P < 0.05). CONCLUSION: Neither the length of the metaplastic segment nor the presence of intestinal metaplasia was related to a more evolved gastro-oesophageal reflux disease, a poorer oesophageal clearing function or higher acid reflux rates.

Adult↗
PubMed1998

Role of cytokines in the response to erythropoietin in hemodialysis patients.

BACKGROUND: Cytokines are regulatory factors of erythropoiesis, especially in pathologic conditions. Even though a relevant role for a deranged cytokine production in the pathogenesis of dialysis anemia has been suggested, no data are available that analyze the role of cytokines in the key therapeutic issue of the needs of erythropoietin. The aim of the present study in hemodialysis patients was, therefore, to examine the relationship between the dose of recombinant human erythropoietin (EPO) and the production of cytokines by peripheral blood mononuclear cells (PBMC). METHODS: After the exclusion of subjects with major active causes of EPO resistance, data from 34 hemodialysis patients were available for analysis. Cytokine levels were measured in the supernatants of stimulated [with bacterial lipopolysaccharide and interferon gamma (IFN-gamma)] and unstimulated PBMC. Mean yearly values of hematocrit, hemoglobin, transferrin saturation, ferritin, parathormone (PTH) and aluminum levels and EPO doses (U/kg/week) were calculated. For analysis, the 34 patients were divided according to their cutoff requirements for EPO: patients with requirements of EPO > or = 60 U/kg/week (group A1, 26 subjects) versus EPO < 60 U/kg/week (group B1, 8 subjects) and patients with requirements of EPO > or = 100 U/kg/week (group A2, 18 subjects) versus <100 U/kg/week (group B2, 16 subjects). RESULTS: A significant direct correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) production values and EPO doses was found (P = 0.039 and P = 0.02 respectively). On the other hand, there was a significantly negative correlation between interleukin-12 (IL-12) production values and EPO doses (P = 0.029). Patients of groups A1 and A2 had spontaneously higher tumor necrosis factor-alpha (TNF-alpha) and lower IL-12 and IFNgamma production compared to patients from groups B1 and B2. CONCLUSIONS: Our data disclose a previously undescribed pattern of cytokine alteration that is relevant to determine increased needs of EPO in hemodialysis patients. The present results have potential applicability in designing strategies to improve EPO resistance.

Aged↗
PubMed1998

Cyclosporine A induces apoptosis in murine tubular epithelial cells: role of caspases.

BACKGROUND: The pathogenesis of cyclosporine A (CsA) nephrotoxicity has not been completely elucidated. METHODS: The ability of CsA to induce apoptosis in cultured murine tubular epithelial cells and its regulation by the cell microenvironment and inhibitors of caspases were studied. RESULTS: This study found that CsA induces apoptotic death in murine proximal tubular epithelial MCT cells in a dose- (0.1 to 15 micrograms/ml) and time-dependent (24 to 72 hr) manner. Death caused by CsA is additive to apoptosis induced by deprivation of the survival factors present in serum. Primary cultures of murine tubular epithelial cells are also sensitive to CsA-induced apoptosis. Peptide inhibitors of caspases such as zVAD-fmk (which inhibits caspases 8 and 9) and DEVD-CHO (which inhibits caspase 3 and related caspases) prevented CsA-induced apoptosis in MCT cells, although zVAD-fmk was effective at lower concentrations. CONCLUSION: These data suggest that tubular cell apoptosis mediated by caspases may play a role in CsA nephrotoxicity and that the microenvironment modulates resistance to CsA lethality as low local levels of survival factors may potentiate nephrotoxicity. Caspases my be new therapeutic targets in the management of nephrotoxic injury.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Composition and antibacterial activity of the essential oils of Helichrysum rupestre and H. ambiguum growing in the Balearic Islands (Part III)

The chemical compositions of the essential oils obtained from the aerial parts of Helichrysum rupestre and H. ambiguum were analysed by GC and GC/MS. From the forty-five identified constituents representing 90.21% and 93.90% of the two oils, respectively, manoyl oxide, dodecanal, nonanal, p-cymene, alpha-pinene, and 2,4,6-tris(1,1-dimethylethyl)benzoic acid, were found to be the major components. Furthermore, the oils were tested against six Gram (+/-) bacteria and it was found that one of them exhibited significant antibacterial activity.

Anti-Bacterial Agents↗