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Biomedical subjects

Antonio Moreno

Publications and source records attributed to Antonio Moreno.

11 recordsLinked to original sources

Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension.

To report two unrelated patients with a new phenotype of nonketotic hyperglycinemia associated with idiopathic pulmonary hypertension. Clinical findings included rapidly progressive neurological deterioration with onset in the first year of life characterized by developmental regression without seizures or electroencephalogram abnormalities during follow-up. Both patients died before the age of 18 months. Glycine cleavage system deficiency was confirmed by enzymatic studies in frozen liver. Molecular analysis in the related genes showed no pathogenic mutation. Radiological and pathological findings were consistent with progressive vacuolating encephalopathy. Our patients with biochemical and enzymatic parameters consistent with atypical nonketotic hyperglycinemia. The clinical and radiological evolution, as progressive vacuolating leukoencephalopathy and the association with pulmonary hypertension constitute a previously unrecognized variant.

Disease Progression↗

Novel human neuropeptide Y Y5 receptor antagonists for the treatment of obesity. Synthesis and biological evaluation of pyridine hydrazide derivatives.

A series of new pyridine hydrazide derivatives with high and selective antagonist activity at the human neuropeptide Y Y5 receptor were developed. Introduction of electron-withdrawing groups into the arylsulfonamide rest, together with the 3-pyridyl analogue in the hydrazide moiety, led to a significant improvement of potency and solubility, affording trans-N-(4-[N'-(pyridine-3-carbonyl)hydrazino-carbonyl]cyclohexylmethyl)-2,4-dichloro-benzenesulfonamide (14), which binds to the hY5 receptor with an IC50 value of 7.44 nmol/L.

Anti-Obesity Agents↗

Synthesis and evaluation of new hydrazide derivatives as neuropeptide Y Y5 receptor antagonists for the treatment of obesity.

NPY is the most potent orexigenic agent known to man, with NPY Y1 and NPY Y5 being the receptor subtypes that are most likely responsible for centrally-mediated NPY-induced feeding responses. Based on the aforementioned, novel hydrazide derivatives were prepared for the purpose of searching new NPY Y5 receptor antagonists. Many of the compounds exhibited nanomolar binding affinity for this receptor, affording trans-N-(4-[N'-(3,4-dichlorophenyl)hydrazinocarbonyl]cyclohexylmethyl)-4-fluorobenzenesulfonamide, which showed the best activity (IC(50)=0.43nM).

Animals↗

Synthesis of new thiophene and benzo[b]thiophene hydrazide derivatives as human NPY Y(5) antagonists.

Neuropeptide Y is one of the most potent appetite stimulating hormones known. Novel thiophene and benzo[b]thiophene hydrazide derivatives were synthetized and evaluated biologically as NPY Y(1) and Y(5) receptor subtype antagonists. They were found to have nanomolar binding affinities for human NPY Y(5) receptor, obtaining the lead compound, trans-N-4-[N'-(thiophene-2-carbonyl)hydrazinocarbonyl]cyclohexylmethyl-4-bromobenzenesulfonamide, which binds with a 7.70 nM IC(50) to the hY(5) receptor.

Animals↗

Synthesis and evaluation of new arylsulfonamidomethylcyclohexyl derivatives as human neuropeptide Y Y5 receptor antagonists for the treatment of obesity.

NPY is the most potent orexigenic peptide identified up to now. Stimulation of food intake is measured by the Y(1) and Y(5) receptor subtypes. In this study, the synthesis and evaluation of new arylsulfonamidomethylcyclohexyl derivatives are described as potential selective antagonists of the human NPY Y(5) receptor. The SAR of these series was examined and the amide derivatives were the compounds that showed the best activities. trans-N-(4-[(Quinolin-3-yl)aminocarbonyl]cyclohexylmethyl)-2,4-dichlorobenzenesulfonamide (42) bound to the human neuropeptide Y Y(5) receptor with a 2 nM IC(50).

Animals↗

Tracking methicillin-resistant Staphylococcus aureus clones during a 5-year period (1998 to 2002) in a Spanish hospital.

Three hundred seventy-five consecutive methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates recovered between 1998 and 2002 at the Nuestra Señora de Candelaria University Hospital in Tenerife, Spain, were analyzed by molecular fingerprinting techniques to determine MRSA clonal types and their prevalence over time. After determining antibiotic susceptibility, we used SmaI-digested genomic DNA separated by pulsed-field gel electrophoresis (PFGE) to characterize MRSA isolates and to establish PFGE types. Additionally, several selected isolates representative of each major PFGE type were tested by multilocus sequence typing (MLST) and by a multiplex PCR method capable of identifying the structural type of the staphylococcal cassette chromosome mec (SCCmec), generating the corresponding sequence type (ST)-SCCmec types. Results of PFGE, supported by those of MLST and SCCmec typing, allowed us to identify six MRSA clones within the five major PFGE types and document temporal shifts in the prevalence of these MRSA clones from 1998 to 2002. Four of the clones were the pandemic "Iberian" (designated ST247-MRSA-IA), EMRSA-15 (ST22-MRSA-IV), EMRSA-16 (ST36-MRSA-II), and the so-called pediatric (ST5-MRSA-IV) clones, while the other two (ST125-MRSA-IVA and ST146-MRSA-IVA) clones could be derived from the pediatric one. The most striking temporal shift in the dominance of MRSA clones was the replacement of the multidrug-resistant and highly epidemic Iberian clone by the so-called British EMRSA-16 clone during the 5-year surveillance period. Our results are in accordance with previously stated findings showing the worldwide hospital dominance of relatively few pandemic and presumably virulent MRSA clones. We report for the first time the detection in Spain of the British EMRSA-15 and pediatric clones, as well as the abrupt replacement of the Iberian by the EMRSA-16 as the major MRSA clone.

Anti-Bacterial Agents↗

[Clinical and neuroradiographic correlates in eclampsia].

Brain computed tomography, magnetic resonance imaging and magnetic resonance angiography were performed in five eclamptic patients. Three of them had HELLP syndrome. The findings on the imaging studies showed bilateral lesions affecting regions of the brain, such as cortico-subcortical either posterior and anterior circulation territories, white matter, talamic or mesencephalic-protuberancial areas. No vasospasm in middle size arteries were observed with magnetic resonance angiography. Although visual disturbance and occipital lobe involvement were correlated, no other mentioned lesions had clinical manifestations.

Adult↗

Are quinolone-resistant uropathogenic Escherichia coli less virulent?

The prevalence of hemolysin, type 1 fimbriae, P fimbriae, cytotoxic necrotizing factor-1 (CNF-1), aerobactin, and autotransporter toxin (sat) was analyzed by polymerase chain reaction and phenotypic assays of 42 epidemiologically unrelated Escherichia coli strains causing acute pyelonephritis in women (21 nalidixic acid-susceptible and 21 nalidixic acid-resistant strains) and 58 E. coli strains causing cystitis in women (29 nalidixic acid-susceptible and 29 nalidixic acid-resistant strains). Hemolysin and CNF-1 were less prevalent (P<.05) in nalidixic acid-resistant than in nalidixic acid-susceptible E. coli strains from patients with either pyelonephritis (14.3% vs. 52.4%) or cystitis (0% vs. 31.0%). Among E. coli strains causing cystitis, type 1 fimbriae expression was less prevalent (P<.05) in the nalidixic acid-resistant group (55.2%) than in the nalidixic acid-susceptible group (86.2%). None of the nalidixic acid-resistant and 20.7% of the nalidixic acid-susceptible strains causing cystitis showed the proteolytic toxin Sat (P<.05). These results suggest that resistance to quinolones may be associated with a decrease in the presence or the expression of some virulence factors in uropathogenic E. coli.

Anti-Infective Agents↗

Low prevalence of vancomycin-resistant enterococci in clinical samples from hospitalized patients of the Canary Islands, Spain.

Over the last decade vancomycin-resistant enterococci (VRE) have emerged as nosocomial pathogens. The aim of this study was to determine the prevalence of VRE in clinical samples from hospitalized patients in the Canary Islands. From April to November 2000, 437 enterococci were isolated from patients hospitalized at the four main health care centers in those islands. Identification to the species level was performed with the GPS-TA (Vitek 1) or the Wider I system. A PCR assay was used to determine the genotype of glycopeptide resistance ( vanA, vanB, vanC1, and vanC2/C3 genes). Only three (0.7%) VRE were detected: one vanA Enterococcus faecalis, and two vanC1 Enterococcus gallinarum. To our knowledge, this is the first VRE study carried out in the Canary Islands hospitals, and the results showed a low prevalence of VRE.

Enterococcus↗

Aluminum ions induce DNA synthesis but not cell proliferation in human fibroblasts in vitro.

The effect in vitro of aluminum (Al) ions on DNA synthesis and human dermal fibroblast proliferation using [Al] concentrations from 1.85 to 74 microM and incubation periods of 1, 2, 3, 4, and 5 d was assessed. The lowest concentration of Al that exerted a slight positive, although not significant, effect on DNA synthesis was 1.85 microM, after d 3 or 5 of incubation. The stimulating action of Al was more evident and statistically significant from concentrations of 3.7 microM and 2 d exposure onward. This Al-induced effect on [3H] thymidine incorporation into DNA increased in a time-dependent manner as [Al] in the culture medium rose, provoking increments of up to 322% above the control at [Al] 74 microM and 5 d incubation. In contrast, Al salts moderately increased fibroblast division in a continuous manner only from 7.4 to 74 microM after 3 d of incubation. Although significant overall, the minimal and inconstant mitogenic activity of Al differs greatly from and is not parallel to DNA synthesis, which is not clearly related to exposure times or Al concentrations. Abnormalities in Al-induced cellular metabolic processes described herein and their influence on the cell cycle may constitute a toxicity mechanism for human tissues, leading to disease development. Further studies are required to determine whether these findings can be extrapolated to in vivo situations.

Adolescent↗