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Biomedical subjects

A Montero

Publications and source records attributed to A Montero.

At least 37 records · Page 2Linked to original sources
PubMed2000

A novel approach for the virtual screening and rational design of anticancer compounds.

A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% of compounds in an external prediction set with only 1.43% of false actives and 7. 14% of false inactives. The model developed is then used in a simulation of a virtual search for Ras FTase inhibitors; 87% of the Ras FTase inhibitors used in this simulated search were correctly classified, thus indicating the ability of the TOSS-MODE model of finding lead compounds with novel structures and mechanism of action. Finally, a series of carbonucleosides was designed, and the compounds were classified as active/inactive anticancer compounds by using the model developed here. From the compounds so-designed, 20 were synthesized and evaluated experimentally for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (Molt4/C8 and CEM/0); 80% of these compounds were well-classified, as active or inactive, and only two pairs of isomeric compounds were false actives. The chloropurine derivatives were the most active compounds, especially compounds 6c, d.

Alkyl and Aryl Transferases↗
PubMed2000

Candida infection of cerebrospinal fluid shunt devices: report of two cases and review of the literature.

Use of CSF shunt devices is a common practice in neurosurgery, and infection of the shunt is the most frequent complication. In spite of the fact that bacteria are the most widely implicated pathogens, reports of fungal infections, especially due to Candida sp., have increased in recent years. Their reported frequency ranges between 6% and 17%. Many factors have been implicated in the pathogenesis of Candida meningitis, such as broad spectrum antibiotics used in the treatment of a bacterial meningitis, steroids and indwelling bladder and intravenous catheters. The treatment of Candida meningitis still consists of systemic antifungal agents and removal of the shunt.

Adolescent↗
PubMed2000

Nutritional status of young female elite gymnasts.

The purpose of this study was to evaluate the nutritional status of a group of 10 young female elite gymnasts aged 13-17 years, who do a physical exercise of 48 h/wk. Assessment included dietary intake for 7 days, body mass index, ideal body weight, and skinfold thickness. In addition, the number of total leukocytes, total lymphocytes and lymphocyte subsets CD2, CD3, CD4, CD8, CD19 and CD56 were counted. The results were compared with a control group consisting of 50 volunteer students doing less than 12 h/wk of physical exercise, who were matched by sex, age, and sociocultural level. The total weekly calorie intake was lower in gymnasts than in controls; gymnasts showed a higher calorie intake from dietary protein together with a lower calorie intake from lipid and carbohydrate sources in comparison with controls. All the anthropometric parameters, except height which was not different in the two groups, were lower in gymnasts than in controls. The lymphocyte and leukocyte counts were also lower in gymnasts in relation to controls, except CD19 and CD56 subsets which were similar in both groups. It is suggested that gymnasts are at risk of malnutrition, which when compounded with intense physical exercise could lead to immunosuppression in these athletes.

Adolescent↗
PubMed2000

F(2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type I diabetes.

BACKGROUND: The recently discovered arachidonic acid derivatives, isoprostanes, are increased in pathological conditions associated with oxidative stress, such as diabetes. No role has yet been described for isoprostanes during the development of diabetic nephropathy. Cell culture in high ambient glucose has been used as a model in elucidating cellular mechanisms underlying diabetic nephropathy. Among the growth factors involved in the effect of high glucose, transforming growth factor-beta (TGF-beta) has been described as playing a key role in the development of nephropathy. METHODS: Streptozotocin-induced diabetic rats were supplemented in their diet with the antioxidant vitamin E (1000 U/kg diet). Blood and urine samples were taken to determine renal function and isoprostane concentration, as determined by gas chromatography/mass spectrometry. Glomerular mesangial and endothelial cells were cultured in high ambient glucose to determine the synthesis of isoprostanes and the role of isoprostanes in high glucose-induced synthesis of TGF-beta. RESULTS: Streptozotocin-induced diabetic rats had marked increases in plasma levels and urinary excretion rates of F(2)-isoprostanes. Dietary supplementation with vitamin E normalized (plasma) and reduced (urine) isoprostane levels and, surprisingly, improved proteinuria and blood urea nitrogen (BUN) levels. High ambient glucose increased F(2)-isoprostane synthesis in glomerular endothelial and mesangial cells in culture. Incubation of glomerular cells with F(2)-isoprostanes stimulated the production of TGF-beta. CONCLUSIONS: Increased F(2)-isoprostane synthesis during diabetes appears to be responsible in part for the increase in renal TGF-beta, a well-known mediator of diabetic nephropathy.

Animals↗
PubMed2000

Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii.

Beginning in 1992, a sustained outbreak of multiresistant Acinetobacter baumannii infections was noted in our 1,000-bed hospital in Barcelona, Spain, resulting in considerable overuse of imipenem, to which the organisms were uniformly susceptible. In January 1997, carbapenem-resistant (CR) A. baumannii strains emerged and rapidly disseminated in the intensive care units (ICUs), prompting us to conduct a prospective investigation. It was an 18-month longitudinal intervention study aimed at the identification of the clinical and microbiological epidemiology of the outbreak and its response to a multicomponent infection control strategy. From January 1997 to June 1998, clinical samples from 153 (8%) of 1,836 consecutive ICU patients were found to contain CR A. baumannii. Isolates were verified to be A. baumannii by restriction analysis of the 16S-23S ribosomal genes and the intergenic spacer region. Molecular typing by repetitive extragenic palindromic sequence-based PCR and pulsed-field gel electrophoresis showed that the emergence of carbapenem resistance was not by the selection of resistant mutants but was by the introduction of two new epidemic clones that were different from those responsible for the endemic. Multivariate regression analysis selected those patients with previous carriage of CR A. baumannii (relative risk [RR], 35.3; 95% confidence interval [CI], 7.2 to 173.1), those patients who had previously received therapy with carbapenems (RR, 4.6; 95% CI, 1.3 to 15.6), or those who were admitted into a ward with a high density of patients infected with CR A. baumannii (RR, 1.7; 95% CI, 1.2 to 2.5) to be at a significantly greater risk for the development of clinical colonization or infection with CR A. baumannii strains. In accordance, a combined infection control strategy was designed and implemented, including the sequential closure of all ICUs for decontamination, strict compliance with cross-transmission prevention protocols, and a program that restricted the use of carbapenem. Subsequently, a sharp reduction in the incidence rates of infection or colonization with A. baumannii, whether resistant or susceptible to carbapenems, was shown, although an alarming dominance of the carbapenem-resistant clones was shown at the end of the study.

Acinetobacter↗
PubMed2000

Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation.

Basic fibroblast growth factor (FGF-2), an important modulator of cartilage and bone growth and differentiation, is expressed and regulated in osteoblastic cells. To investigate the role of FGF-2 in bone, we examined mice with a disruption of the Fgf2 gene. Measurement of trabecular bone architecture of the femoral metaphysis of Fgf2(+/+) and Fgf2(-/-) adult mice by micro-CT revealed that the platelike trabecular structures were markedly reduced and many of the connecting rods of trabecular bone were lost in the Fgf2(-/-) mice. Dynamic histomorphometry confirmed a significant decrease in trabecular bone volume, mineral apposition, and bone formation rates. In addition, there was a profound decreased mineralization of bone marrow stromal cultures from Fgf2(-/-) mice. This study provides strong evidence that FGF-2 helps determine bone mass as well as bone formation.

Alkaline Phosphatase↗
PubMed2000

[Perfusion SPECT with (99m)Tc-HMPAO in type I diabetics with no background of central neurologic symptoms. A study of activation with acetazolamide].

OBJECTIVE: This study aimed to assess if activation with acetazolamide increases the diagnostic capacity of baseline SPECT with (99m)Tc-HMPAO in the study of brain perfusion in type I diabetic patients with no history of neurological symptoms. MATERIAL AND METHODS: A baseline SPECT was carried out in 11 diabetes mellitus type I patients with no neurological symptoms with 555 MBq of (99m)Tc-HMPAO; 1 g of acetazolamide was administered during the examination and a second SPECT was obtained 20' later with the same methodology used in the baseline SPECT. The images were visually analyzed. The post-acetazolamide studies were analyzed with (CBS) and without (WBS) baseline image subtraction and both methods were compared. RESULTS: The baseline SPECT showed 48 hypoperfused cortical areas. The post-acetazolamide SPECT analyzed without baseline image subtraction detected 14 new hypoperfused areas and those analyzed with it detected 26 areas. 69% of the baseline hypoperfused areas were hyporeactive in the WBS analysis and 54% in the CBS analysis. CONCLUSION: The perfusion SPECT with acetazolamide improves the diagnostic capacity of the baseline perfusion (99m)Tc-HMPAO SPECT, and makes it possible to classify the abnormalities as metabolic or vascular, with a preference for the post-acetazolamide CBS imaging analysis.

Acetazolamide↗
PubMed2000

[Hyperprolactinemia is a frequent finding in HIV infection but does not correlate with viral burden].

Although many authors have reported the finding of hyperprolactinemia during the course of HIV infection, the circumstances determining the rise of prolactin (PRL) concentrations in serum are poorly understood. To analyze the relationships between serum PRL and other clinical variables in HIV-infected patients, 46 HIV-infected patients and 17 seronegative controls were studied. Serum PRL concentrations were significantly higher in the HIV-infected group (p = 0.022). Furthermore, Serum PRL and serum IgG correlated positively (Rs = 0.42; p = 0.05, Spearman-Rank). On the contrary, serum PRL concentrations did not correlate with the plasmic viral burden (Rs 0.039; p = 0.841), Our data confirm that hyperprolactinemia is a frequent finding during the course of HIV infection, and that serum PRL are independent of viral replication kinetics. Considering that a positive correlation was found between serum PRL and immunoglobulins, it is possible that serum PRL might increase in response to non specific immunological activation, or even in response to immunological activation at the onset of infections.

Adult↗
PubMed2000

[Immunological properties of prolactin].

A profound bi-directional interaction exists between the hormone prolactin and the immune system. Even the name "hormone" seems to be inadequate, since prolactin is clearly a growth factor and in fact it functions as an immune co-mitogenic cytokine using autocrine, paracrine and obviously endocrine mechanisms. Prolactin (PRL) stimulates lymphocyte proliferation in response to antigen and mitogens. In addition, prolactin is locally secreted by immune cells, and the pituitary production of prolactin is partially under the control of pro-inflammatory cytokines. These reciprocal influences imply the presence of specific receptors for prolactin in many immune cells, such as lymphocytes and other accessory cells. The PRL-binding to its receptor stimulates the synthesis and secretion of lymphocyte cytokines. In addition, it is a growth factor essential for at least one lymphoid cell line. The PRL-corresponding mRNA has been demonstrated in the cytoplasm of mitogen-stimulated lymphocytes, and the secretion of PRL has been well documented in lymphoid cells. Moreover, PRL acts on NK cells to induce their differentiation to prolactin-activated killer cells (PAK cells) in a dose-dependent way (activation at physiological concentrations, and cytotoxicity inhibition at tenfold higher concentrations). PRL also shows a well known capacity to induce IFN-gamma and IL-2 synthesis, suggesting their participation in the genesis of Th1-responses. These PRL immunological properties strongly support PRL as a cytokine. PRL involvement in both the normal immune response and in many pathological conditions raises important considerations regarding potential diagnostic and therapeutic applications.

Animals↗
PubMed1999

Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis.

The human 15-lipoxygenase (15-LO) gene was transfected into rat kidneys in vivo via intra-renal arterial injection. Three days later, acute (passive) or accelerated forms of antiglomerular basement membrane antibody-mediated glomerulonephritis were induced in transfected and nontransfected or sham-transfected controls. Studies of glomerular functions (filtration and protein excretion) and ex vivo glomerular leukotriene B(4) biosynthesis at 3 hr, and up to 4 days, after induction of nephritis revealed preservation or normalization of these parameters in transfected kidneys that expressed human 15-LO mRNA and mature protein, but not in contralateral control kidneys or sham-transfected animals. The results provide in vivo-derived data supporting a direct anti-inflammatory role for 15-LO during immune-mediated tissue injury.

Animals↗
PubMed1999

Löfgren's syndrome revisited: a study of 186 patients.

PURPOSE: To evaluate the clinical features, the results of noninvasive tests and biopsies, and the outcome of patients with Löfgren's syndrome. SUBJECTS AND METHODS: Patients diagnosed as having Löfgren's syndrome at a university hospital in Barcelona, Spain, from 1974 to 1996, were prospectively followed. Löfgren's syndrome was defined as the association of erythema nodosum or periarticular ankle inflammation with unilateral or bilateral hilar or right paratracheal lymphadenopathy. RESULTS: Löfgren's syndrome was diagnosed in 186 patients. The mean age was 37 +/- 11 years, and 157 (85%) were women. In 91 patients (49%), symptoms started during the spring (P < 0.0001). Erythema nodosum, periarticular ankle inflammation, or both were present at onset in 173 patients (93%). At the time of diagnosis, 161 patients (87%) had no respiratory symptoms; 151 (81%) had stage I abnormalities on chest radiograph, 29 (16%) stage II, and 6 (3%) stage 0. Five percent of patients had decreased forced vital capacity, and 15% had decreased carbon monoxide diffusing capacity. Extrathoracic involvement was infrequent. Serum angiotensin-converting enzyme levels were increased in 50% of patients. Gallium-67 scans showed hilar uptake in all the studied patients, but it yielded useful additional diagnostic information only in those with normal chest radiographs or with unilateral hilar lymphadenopathy. The diagnosis was proven with biopsy results in 63% of patients. None of the patients without histologic confirmation were subsequently found to have a diagnosis other than sarcoidosis. In the 133 patients who were followed for a mean of almost 5 years, 11 (8%) continued to have active disease, and 8 (6%) had several recurrences between 18 months and 20 years after a complete resolution. A normal serum angiotensin-converting enzyme level at diagnosis was associated with disease resolution without recurrence. CONCLUSION: Löfgren's syndrome is usually a self-limiting form of sarcoidosis. Histologic confirmation is not necessary in typical cases. In a small number of patients, the disease may remain active or recur long after its onset, although usually with mild organ dysfunction.

Adolescent↗
PubMed1999

Free-radical-generated F2-isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells.

BACKGROUND: Free-radical-generated F2-isoprostane stimulates DNA synthesis and endothelin-1 (ET-1) expression on endothelial cells. 8-Iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a member of the recently discovered family of prostanoids, the F2-isoprostanes, produced in vivo by cyclooxygenase-independent, free-radical-catalyzed lipid peroxidation. The goal of our study is to establish the effect of isoprostane on ET-1 production by endothelial cells, as well to determine the receptors responsible for these effects. METHODS: The proliferative effect of isoprostanes was measured as an increase of viable cell number and [3H]-thymidine uptake. ET-1 gene expression and protein synthesis were determined by Northern blot and radioimmunoassay, respectively. We also determined inositol 1,4,5-trisphosphate synthesis. Thromboxane A2 (TXA2) receptor antagonist SQ29,548 was used to establish the role of TXA2 receptor in isoprostane effect, as well as to determine the type of receptors involved in these effects. RESULTS: Our results show that physiological concentrations of 8-iso-PGF2alpha stimulated cell proliferation, DNA synthesis, and ET-1 mRNA and protein expression in bovine aortic endothelial cells (BAECs). The proliferative effect was partially abolished by treatment with anti-endothelin antibody. 8-Iso-PGF2alpha also increased inositol 1, 4,5-trisphosphate formation in these cells. These effects were partially inhibited by SQ29,548. In competitive binding assays, two binding sites were recognized on BAECs with dissociation constants (Kd) and binding site densities at equilibrium similar to those previously described in smooth muscle cells and likely represent [3H]-8-iso-PGF2alpha binding to its own receptor (high-affinity binding site) and cross-recognition of the TXA2 receptor (low-affinity binding site). CONCLUSION: These studies expand the potential scope of the pathophysiologic significance of F2-isoprostanes, released during oxidant injury, to include alteration of endothelial cell biology.

Animals↗