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Biomedical subjects

A Cano

Publications and source records attributed to A Cano.

At least 19 recordsLinked to original sources
PubMed2006

Snail silencing effectively suppresses tumour growth and invasiveness.

The transcription factor Snail has been recently proposed as an important mediator of tumour invasion because of its role in downregulation of E-cadherin and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led to the consideration of Snail as a potential therapeutic target to block tumour progression. In this report, we provide evidence for this hypothesis. We show that silencing of Snail by stable RNA interference in MDCK-Snail cells induces a complete mesenchymal to epithelial transition (MET), associated to the upregulation of E-cadherin, downregulation of mesenchymal markers and inhibition of invasion. More importantly, stable interference of endogenous Snail in two independent carcinoma cell lines leads to a dramatic reduction of in vivo tumour growth, accompanied by increased tumour differentiation and a significant decrease in the expression of MMP-9 and angiogenic markers and invasiveness. These results indicate that use of RNA interference can be an effective tool for blocking Snail function, opening the way for its application in new antiinvasive therapies.

Animals↗
PubMed2006

Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice.

BACKGROUND: Within the last few years, much evidence has been presented on the involvement of the immune system in certain types of bone loss, such as activated T cells in rheumatoid arthritis and in periodontitis. Estrogen deficiency induces bone loss; however, how this deficiency affects the immune system has not been sufficiently studied. METHODS: To evaluate the effects of estrogen withdrawal on the status and functionality of the immune system, mice were ovariectomized or sham-operated, and 5 weeks after surgery, when osteopenia had developed, several parameters were analysed in spleen and in bone marrow. We analysed bone turnover, cell phenotype by flow cytometry, cell function by cell proliferation assays, and the expression of several genes related to the process. RESULTS: Five weeks after ovariectomy, augmented osteoclastogenesis persisted in the bone marrow. In addition, the ovariectomized mice had more B-cells and CD3+ T-cells expressing the receptor activator of NF-kappaB ligand (CD3+/RANKL+). The ovariectomized mice had lower serum alkaline phosphatase activity, a normal amount of T cells, lower percentages of CD11b+ and CD51+ cells in the bone marrow, and a lower serum interferon-gamma level compared with sham-operated controls. CONCLUSIONS: The data suggest that, 5 weeks after ovariectomy, bone turnover remains imbalanced, with increased osteoclastogenesis and a decreased rate of bone formation. Moreover, there is an increase in B-cell formation, with normal and decreased percentages of T cells and myelomonocytic cells (CD11b+), respectively, in the bone marrow. Decreased serum interferon-gamma levels could be involved in the increased osteoclastogenesis found in the present work.

Alkaline Phosphatase↗
PubMed2006

New potential therapeutic targets to combat epithelial tumor invasion.

Metastasis is the deadly face of epithelial tumors. The studies performed in the last decade have shed considerable light on the processes involved in the metastatic cascade. In particular, much effort has focused on defining the molecular changes that govern the conversion from an epithelial to a mesenchymal cell, a process known as epithelial-mesenchymal transition (EMT). The process of EMT is considered a fundamental event in the metastatic cascade (i.e. during invasion and/or intravasation) and several molecules involved in EMT have been described, including epithelial markers, transcription factors, as well as extracellular proteins and growth factors. In this green series article, we will focus our attention on the new molecules described in the recent years that appear to influence EMT and that are therefore relevant to epithelial carcinogenesis. Furthermore, we will try to explain how these molecules collaborate with the tumor microenvironment to trigger metastasis. Recent advances in our understanding of this process is generating a wide range of molecules that could be potentially considered as new therapeutic targets for drug design to block metastatic spreading.

Antineoplastic Agents↗
PubMed2006

Cyclooxygenases regulation by estradiol on endothelium.

Estrogen and hormone replacement therapies are being tested to prevent the incidence of cardiovascular disease in postmenopausal women. In spite of the evidence from several epidemiological studies suggesting that estrogens protect against atherosclerosis and associated diseases, controversy exists. Moreover, it is important to develop synthetic compounds that achieve the beneficial effects of estrogens on the cardiovascular system while minimizing such undesirable effects on other tissues as the increased risk of endometrial and breast cancer. Some drugs that modulate estrogen function in a tissue-specific manner (Selective Estrogen Receptor Modulators; SERMs) have been discovered and are currently being used in clinical practice. An example of these is raloxifene. Clinical and experimental data support the consideration of endothelium as a target for estradiol and other sexual hormones. Among other actions, estradiol has been implicated in the control of prostacyclin production through cyclooxygenases (COX) regulation in endothelial cells. Prostacyclins are powerful vasodilators and potent inhibitors of platelet aggregation which are produced from free arachidonic acid through the catalytic activity of two COX: COX-1 and COX-2. Together, these COX represent the main control mechanism for prostacyclin production. Although several non-specific COX inhibitors have been available for decades (aspirin, indomethacin, ibuprofen), COX-2 selective inhibitors have been commercialized only within the last few years, thus making it possible to increase the study and treatment of different disorders. This review will discuss clinical and experimental data that document the endothelial effects of estradiol and SERMs on prostacyclin production and COX regulation, their vascular consequences, and their possible interactions with COX inhibitors.

Animals↗
PubMed2005

Immune response to Neospora caninum in naturally infected heifers and heifers vaccinated with inactivated antigen during the second trimester of gestation.

The objective of this study was to compare the immune response to Neospora caninum in naturally infected heifers and heifers inoculated with a killed whole N. caninum tachyzoite preparation during the second trimester of gestation. Nine Holstein heifers were used in this study; three naturally infected heifers were born from seropositive dams, and six seronegative heifers were born from seronegative dams. Four seronegative heifers were subcutaneously vaccinated with a killed whole N. caninum tachyzoite preparation at weeks 13, 15 and 17 of gestation. A killed whole N. caninum tachyzoite preparation containing 45 mg of protein/5 ml dose was formulated with 70% of mineral oil adjuvant (13% consisting of Arlacel C, 85% Marcol 52 and 2% Tween-80). Similarly, two seronegative heifers (negative controls) were inoculated with mock-infected bovine monocytes in oil adjuvant. Humoral immune responses were tested by using an indirect fluorescent antibody test (IFAT) and an indirect enzyme-linked immunosorbent assay (ELISA) for detecting isotype specific antibodies. Cellular immune responses were assessed by lymphocyte proliferation test (LPT) and IFN-gamma production. N. caninum-specific antibody responses increased in immunized cattle by week 15 of gestation (mean reciprocal antibody titers 450+/-252), peaked at week 23 (mean 16,000+/-6400). Maximum antibody response in naturally infected heifers was observed at week 19 of gestation (mean: 3467+/-2810). Mean serum IFAT titers were significantly higher in immunized heifers compared with those in naturally infected heifers from weeks 17 to 25 (P < 0.05). Analysis of isotype specific antibodies in naturally infected heifers revealed a predominant IgG1 response in one heifer and a predominant IgG2 response in the other two. Similar titers of IgG1 and IgG2 occurred in immunized heifers. Control heifers remained seronegative throughout the study by IFAT and ELISA. Significant antigen-specific proliferation responses were only detected in naturally infected heifers in week 19 of gestation. Peripheral mononuclear blood cells (PMBC) from immunized animals produced IFN-gamma in similar concentrations to those of infected animals (P > 0.05). No abortion was seen in any experimental group; however, one calf from a vaccinated heifer died due to dystocia. All calves from vaccinated and control heifers were seronegative by IFAT at 6 months of age; in contrast, calves born from naturally infected heifers remained seropositive with titers > or = 200. Killed vaccine induced similar immune responses to those found in chronically, naturally infected cattle which did not abort; however, different immune pathways may be followed in vaccinated and natural infected heifers with differences in degree of protective immunity.

Animals↗
PubMed2005

Progestogens stimulate prostacyclin production by human endothelial cells.

BACKGROUND: The effects of progestogens on endothelial physiology are poorly studied. Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase (COX) in endothelium. We examined the effects of two clinically used progestogens, progesterone and medroxyprogesterone acetate (MPA), on prostacyclin production by cultured human umbilical vein endothelial cells (HUVEC) and the possible role of progesterone receptors and both COX enzymes. METHODS: Cells were exposed to 1-100 nmol/l of either progesterone or MPA and prostacyclin production was measured in culture medium. RESULTS: Both progestogens significantly increased prostacyclin release in a time- and dose-dependent manner, being higher than control after 24 h. Progesterone and MPA, both at 10 nmol/l, increased mRNA expression and protein content of both COX. All these effects were mediated through progesterone receptor activation, since they were abolished by treatment of cells with the progesterone receptor antagonist RU-486. Selective inhibitors of COX-1 and -2 (SC-560 and NS-398 respectively) reduced basal prostacyclin release, and eliminated increased production in response to progestogens. In combination with estradiol, progestogens had an additive effect without eliminating estradiol-induced prostacyclin production. CONCLUSIONS: Our results support the hypothesis that progesterone and MPA increased HUVEC prostacyclin production in a progesterone receptor-dependent manner, by enhancing COX-1 and COX-2 expression and activities.

Cells, Cultured↗
PubMed2005

[Cytochrome c oxydase-deficient Leigh syndrome with homozygous mutation in SURF1 gene].

Leigh syndrome is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Mutations in SURF1 gene have been identified in patients with cytochrome c oxidase deficiency. We report a homozygous splice site deletion [516-2_516-1delAG] in a young girl presenting with cytochrome c oxidase-deficient Leigh syndrome. Identification of molecular defect is indispensable for genetic counselling and prenatal diagnosis.

Cytochrome-c Oxidase Deficiency↗
PubMed2005

[Advantages and characteristics of the laparoscopic approach in the elderly].

Both the age of the population and anesthetic and surgical techniques are advancing. Currently, 40% of surgical activity is performed in patients older than 65 years, who present a higher surgical risk than younger patients. The aim of treatment in the elderly is to provide the best possible quality of life, even though this represents a surgical challenge because of associated comorbidity and reduced cardiopulmonary reserve. From the moment at which laparotomy becomes an increased stress in the elderly, laparoscopic surgery can be particularly advantageous in this population. Therefore, minimally invasive surgery may have a greater impact in these individuals than in younger patients in reducing postoperative pain, cardiorespiratory complications, hospital stay, and recovery time before resuming physical activity. The recent advances in anesthesia, together with improved patient selection and perioperative cardiac care, and the general adoption of minimally invasive access have enabled more complex gastrointestinal procedures to be performed in the elderly. The factors that could influence the development of this type of approach in the elderly, as well as the precautions that should be taken, should be further analyzed.

Aged↗
PubMed2004

Explanation of the glasslike anomaly in the low-temperature specific heat of incommensurate phases.

An explanation of the glasslike anomaly observed in the low-temperature specific heat of incommensurate phases is proposed. The key point of this explanation is to properly account for the phason damping when computing the thermodynamic magnitudes. The low-temperature specific heat of the incommensurate phases is discussed within three possible scenarios for the phason dynamics: no phason gap, static phason gap, and a phason gap of dynamical origin. Existing NMR and inelastic scattering data indicate that these scenarios are possible in biphenyl, blue bronze K(0.30)MoO(3), and bis (4-chlorophenyl) sulfone respectively. Estimates of the corresponding low-temperature specific heat are in reasonable agreement with the experiments.

Journal Article↗
PubMed2004

[Oxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure].

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also called hypersensitivity reaction, is a severe idiosyncratic reaction to drugs, especially to anti-epileptic drugs. Clinical features associate cutaneous eruption, fever, multiple peripheral ganglions, and potentially life-threatening damage of one or more organs. DRESS syndrome is well described in adults treated with aromatic anti-epileptic drugs, such as phenytoin, phenobarbital, and carbamazepine, but also with other drugs. The new anti-epileptic drugs, such as oxcarbazepine also induce various cutaneous eruptions, but with less report of DRESS syndrome. In children, DRESS syndrome is rare and probably underdiagnosed. We report on the case of a 11-year-old girl hospitalised with an acute severe hepatitis revealing an oxcarbazepine-induced DRESS syndrome.

Acute Kidney Injury↗
PubMed2004

Effect of delayed breeding on the reproductive performance of female mice.

The aim of the present study was to determine, in the mouse, whether maintaining females as virgins until an advanced reproductive age was associated with decreased reproductive performance and reproductive lifespan compared with females of the same age that were first mated with males at an earlier reproductive age. Randomly selected virgin hybrid (C57BL/6JIco female x CBA/JIco male) female mice were housed individually with a randomly selected 12- to 14-week-old hybrid male either at the age of 28 weeks (normal breeding group; n = 20) or 51 weeks (delayed breeding group; n = 23) for the rest of their reproductive life. Females were checked once daily to determine the day of parturition and to record the litter size and gender of pups at birth for each consecutive litter. At weaning, offspring were weighed and killed. Delayed breeding was associated with smaller litter sizes, both at birth and at weaning, a higher bodyweight of pups at weaning, a higher percentage of litters with at least one newborn pup cannibalised, earlier cessation of female reproductive life and a higher mortality rate of dams during the breeding period. These results show that delayed breeding in the mouse is associated with decreased reproductive performance and a shorter reproductive lifespan compared with females bred at an earlier reproductive age.

Age Factors↗
PubMed2004

A role for Id in the regulation of TGF-beta-induced epithelial-mesenchymal transdifferentiation.

Epithelial-mesenchymal transdifferentiation (EMT) is a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors. EMT can be induced by transforming growth factor (TGF)-beta in mouse NMuMG mammary epithelial cells. Here, we demonstrate a central role of helix-loop-helix factors, E2A and inhibitor of differentiation (Id) proteins, in TGF-beta-induced EMT. Epithelial cells ectopically expressing E2A adopt a fibroblastic phenotype and acquire migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Id proteins interacted with E2A proteins and antagonized E2A-dependent suppression of the E-cadherin promoter. Levels of Id proteins were dramatically decreased by TGF-beta. Moreover, NMuMG cells overexpressed Id2 showed partial resistance to TGF-beta-induced EMT. Id proteins thus inhibit the action of E2A proteins on the expression of E-cadherin, but after TGF-beta stimulation, E2A proteins are present in molar excess of the Id proteins, thus over-riding their inhibitory function and leading to EMT.

Animals↗
PubMed2003

Bone turnover markers and PTH levels in surgical versus natural menopause.

In order to assess similarities and differences in women that suffer surgical versus natural menopause, a series of bone, clinical, and biochemical parameters was assayed in a clinical sample of 35 women with surgical menopause and 112 women with natural menopause. Biochemical parameters included hormones [parathyroid hormone (PTH) and the sex steroids estradiol and testosterone] and several markers of bone turnover measured in urine (N-telopeptide and calcium/creatinine ratio) or serum (osteocalcin, total alkaline phosphatase, total and ionic calcium, phosphate, and magnesium). In addition to type of menopause, women were divided by years since menopause (ysm </= 2 or >2). To detect differences and relationships between variables, ANOVA, ANCOVA, and linear regression analyses were used. Only N-telopeptide, one resorption marker, was significantly affected by the variable years since menopause </=2 or >2 ( P <0.01), but not by type of menopause. The age-corrected level of PTH was significantly decreased in the surgical menopause group ( P < 0.05). In conclusion, type of menopause did not impose significant differences in bone turnover markers. PTH, one powerful resorption hormone, was diminished in surgical menopause.

Absorptiometry, Photon↗
PubMed2002

Oral administration of pharmacological doses of vitamins C and E reduces reproductive fitness and impairs the ovarian and uterine functions of female mice.

This study aims to ascertain whether oral administration of pharmacological doses of Vitamins C and E has any detrimental effect on reproductive fitness of female mice. We fed hybrid female mice from the first day of weaning a standard diet supplemented or not supplemented with pharmacological doses of Vitamins C and E. At the age of 28 weeks, we individually caged females with a male for the rest of their reproductive life. We performed a series of mating experiments to ascertain the number of oocytes ovulated and the potential for embryo development in vitro to the blastocyst stage and in vivo to Day 12 of gestation. The antioxidant diet decreased the frequency of litters, litter size, total number of offspring born and survival of male pups to weaning. This effect was associated with lower number of corpora lutea in the left ovary, decreased percentage of viable fetuses, and higher number of fetal resorptions in the left uterine horn when compared to the control group. The strategy of supplementing the diet with antioxidant vitamins to prevent the age associated decrease in reproductive potential should not be implemented in human beings until a safe and efficient diet is designed.

Animals↗
PubMed2002

Effect of dietary supplementation with a mixture of Vitamins C and E on fertilization of tertiary butyl hydroperoxide-treated oocytes and parthenogenetic activation in the mouse.

The present study aims to analyze the effect of dietary supplementation with a mixture of Vitamins C and E on fertilization and later development of tertiary butyl hydroperoxide (tBH)-treated mouse oocytes and on parthenogenetic activation of freshly ovulated mouse oocytes. We fed hybrid mice a standard diet supplemented or not supplemented with Vitamins C and E from the first day of weaning until the age of 12 weeks. We noted no significant effect of diet on fertilization rate, percentage of total and hatching blastocysts, total number of cells, mitotic index and percentage of apoptotic nuclei at 120 h post-insemination of oocytes incubated for 15 min in the presence of 0, 1, 5 and 10 microM tBH. Furthermore, diet did not affect the percentage of activated oocytes after treatment with Ca2+ ionophore, acid Tyrode's solution or ethanol. The percentage of parthenogenetically activated oocytes that progressed to the pronuclear stage was significantly higher in the antioxidant group. Oocytes from antioxidant females exhibited a significantly lower mitogen-activated protein kinase (MAPK) activity than oocytes from control females. We detected no significant differences between groups in M-phase-promoting factor (MPF) activity. These results show that oral administration of antioxidants decreases MAPK activity and increases the probability of reaching the pronuclear stage after parthenogenetic activation.

Animals↗
PubMed2002

Superoxide scavenging by polyphenols: effect of conjugation and dimerization.

The superoxide anion scavenging capacity of two flavonols (quercetin and kaempferol) and some of their conjugates (quercetin-3-rhamnoglucoside, quercetin-3-sophoroside, quercetin-3-sulphate, quercetin-3-glucuronide, kaempferol-3-sophoroside, kaempferol-3-glucuronide) and of several hydroxycinnamic acids (caffeic acid, ferulic acid, 5-5 diferulic acid, 8-O-4 diferulic acid and 8-8 diferulic acid) were studied. Superoxide anions were generated non-enzymatically in a phenazine methosulphate-NADH system and assayed by reduction of nitro-blue tetrazolium. Among the flavonols examined, the most effective scavengers of superoxide anions were the sophoroside, glucuronide and rhamnoglucoside conjugates. Conversely, quercetin-3-sulphate and the flavonol aglycones, exhibited some pro-oxidant activity at the range of concentrations tested (0.5-10 microM). These results show that conjugation has a marked effect on the scavenging capacity of flavonols and that the type of conjugate at the 3-position determines the final superoxide scavenging capacity. Caffeic acid and ferulic acid showed no effect on the generation of superoxide anions by phenazine methosulphate-NADH. However, dimerization of ferulic acid enhanced the superoxide scavenging capacity of this hydroxycinnamic acid, but this depended on the type of linkage between the monomers. The order, from highest to lowest, of superoxide radical scavenging capacity for the dimers of ferulic acid was: 5-5-diferulic acid > 8-O-4-diferulic acid > 8-8-diferulic acid.

Dimerization↗
PubMed2001

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause.

OBJECTIVE: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). METHODS: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). RESULTS: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels were found in the apo E2/E3 group (P<0.0001). After HRT, women with phenotype E3/E4 showed higher levels of TC and TC/HDL-C ratio (P<0.0001 and P<0.006, respectively). The apo E2/E3 phenotype group showed increased levels of TG (P<0.0001). In the multivariant analysis the changes of TG after HRT were related to the type of treatment used (P<0.001), age (P=0.05) and the apo E phenotype (E2/E3). CONCLUSION: Women with phenotype E2/E3 have higher plasma TG levels and show a significant post HRT increase compared with the other phenotypes. Other factors with a lower impact on TG levels are age and progestagen association.

Administration, Cutaneous↗